research on type 2 diabetes

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New Research Sheds Light on Cause of Type 2 Diabetes

Matthew N. Poy, Ph.D., Johns Hopkins All Children's Hospital

St. Petersburg, Fla. – September 12, 2023 – Scientists at Johns Hopkins All Children’s Hospital, along with an international team of researchers, are shedding new light on the causes of Type 2 diabetes. The new research, published in the journal Nature Communications , offers a potential strategy for developing new therapies that could restore dysfunctional pancreatic beta-cells or, perhaps, even prevent Type 2 diabetes from developing.

The new study shows that the beta-cells of Type 2 diabetes patients are deficient in a cell trafficking protein called “phosphatidylinositol transfer protein alpha” (or PITPNA), which can promote the formation of “little packages,” or intracellular granules containing insulin. These structures facilitate processing and maturation of insulin “cargo.” By restoring PITPNA in the Type 2 deficient beta-cells, production of insulin granule is restored and this reverses many of the deficiencies associated with beta-cell failure and Type 2 diabetes.

Researchers say it’s important to understand how specific genes regulate pancreatic beta-cell function, including those that mediate insulin granule production and maturation like PITPNA to provide therapeutic options for people.

Matthew Poy, Ph.D. , an associate professor of Medicine and Biological Chemistry in the Johns Hopkins University School of Medicine and leader of the Johns Hopkins All Children’s team within the Institute for Fundamental Biomedical Research , was lead researcher on the study. He adds that follow-up work is now focused on whether PITPNA can enhance the functionality of stem-cell-derived pancreatic beta-cells. Since stem cell-based therapies are still in their relatively early stages of clinical development, it appears a great deal of the potential of this approach remains untapped. Poy believes that increasing levels of PITPNA in stem cell-derived beta-cells is an approach that could enhance the ability to produce and release mature insulin prior to transplantation in diabetic subjects.

“Our dream is that increasing PITPNA could improve the efficacy and potency of beta-like stem cells,” Poy says. “This is where our research is heading, but we have to discover whether the capacity of these undifferentiated stem cells that can be converted into many different cell types can be optimized — and to what level — to be converted into healthy insulin producing beta-cells. The goal would be to find a cure for type 2 diabetes.”

Read more about this groundbreaking research.

This study was funded through grants from the Johns Hopkins All Children’s Foundation , the National Institute of Health, the Robert A. Welch Foundation, the Helmholtz Gemeinschaft , the European Foundation for the Study of Diabetes, the Swedish Science Council , the NovoNordisk Foundation and the Deutsche Forschungsgemeinschaft . About Johns Hopkins All Children’s Hospital Johns Hopkins All Children’s Hospital in St. Petersburg is a leader in children’s health care, combining a legacy of compassionate care focused solely on children since 1926 with the innovation and experience of one of the world’s leading health care systems. The 259-bed teaching hospital, stands at the forefront of discovery, leading innovative research to cure and prevent childhood diseases while training the next generation of pediatric experts. With a network of Johns Hopkins All Children’s Outpatient Care centers and collaborative care provided by All Children’s Specialty Physicians at regional hospitals, Johns Hopkins All Children’s brings care closer to home. Johns Hopkins All Children’s Hospital consistently keeps the patient and family at the center of care while continuing to expand its mission in treatment, research, education and advocacy. For more information, visit HopkinsAllChildrens.org .

Weill Cornell Medicine

New Study Reveals Promising Findings to Treat Type 2 Diabetes

A new study published in the Journal of Clinical Investigation has demonstrated that activating a pathway to promote cell division not only expanded the population of insulin-producing cells, but, surprisingly, also enhanced the cells’ function. The findings hold promise for future therapeutics that will improve the lives of individuals with type 2 diabetes—a condition that affects more than half a billion people worldwide.

Dr. Laura Alonso

“That’s reassuring because there is a long-standing belief in the field that proliferation can lead to ‘de-differentiation’ and a loss of cell function,” said study senior author Dr. Laura Alonso , chief of the division of endocrinology, diabetes and metabolism, director of the Weill Center for Metabolic Health , and the E. Hugh Luckey Distinguished Professor in Medicine at Weill Cornell Medicine. “Our result flies in the face of that dogma and suggests if we can find a way to trigger replication of the beta cells in the body, we won’t impair their ability to produce and secrete insulin.”

First author, Rachel Stamateris, also contributed to this work as an MD, PhD student at the University of Massachusetts Medical School and visiting graduate assistant in medicine at Weill Cornell Medicine.

When Beta Cells Fail

In type 2 diabetes, the body’s tissues become resistant to insulin, which means they can’t take in and use blood sugar. At the same time, insulin-producing beta cells in the pancreas fail—diminishing in number and losing their ability to function.

Dr. Alonso and her colleagues reproduced these conditions in a mouse model of diabetes that lacks IRS2, a protein that allows insulin to transmit its signal for cells to absorb blood sugar. These mice displayed insulin resistance, a seminal feature of human type 2 diabetes. “On top of that,” said Dr. Alonso, “the IRS2 protein also turns out to be critical for beta cell function and beta cell number.” So, their pool of beta cells was depleted.

The first order of business to rescue these mice: boost beta cell numbers. But how? She and her team took a closer look at the molecular machinery that controls cell proliferation. The researchers observed that in the IRS-deficient diabetic mice, beta cells failed to elevate production of cyclin D2. This protein, when partnered with a protein called CDK4, drives cell division. Previous studies had shown that mice lacking CDK4 also develop diabetes.

It seemed logical to test if boosting CDK4 activity would help increase beta cell quantity. When Dr. Alonso’s team genetically introduced an active form of CDK4 into the diabetic mice that was more available to attach to cyclin D2, the first thing they noticed was the animals’ blood sugars were restored to normal. Their beta cells were more plentiful than in the untreated, IRS2 mutant mice. But even better: “The beta cells looked amazingly healthy in the treated mice compared with the original diabetic mice, whose beta cells look terrible. Increasing the activity of CDK4 resulted in beta cells packed full of insulin,” said Dr. Alonso, who is also an endocrinologist at NewYork-Presbyterian/Weill Cornell Medical Center.

This supports the concept that beta cell mass can be expanded without compromising function.

While CDK4 is not, itself, a viable therapeutic target because its ability to stimulate proliferation could increase the risk of cancer, Dr. Alonso is confident that probing the molecular pathways that govern beta cell division and function could someday lead to a clinical breakthrough. She pointed to Ozempic, one of the most talked about new treatments for diabetes. “That medication was discovered by a scientist studying toxins in the saliva of the Gila monster,” said Dr. Alonso. “So, it’s clear that understanding how fundamental biology works can lead to real advances in treating or even preventing diabetes.”

Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, see the profile for Dr. Laura Alonso .

This study was supported by grants K08DK076562, R01DK095140, R01DK124906, and R01DK114686 from the National Institute of Diabetes and Digestive and Kidney Diseases.

Releated Links: Boosting Beta Cells to Treat Type 2 Diabetes

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Type 2 diabetes

Affiliations.

1 Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK.
2 Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
3 Family Medicine Department, Korle Bu Teaching Hospital, Accra Ghana and Community Health Department, University of Ghana Medical School, Accra, Ghana.
4 Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK. Electronic address: [email protected].
PMID: 36332637
DOI: 10.1016/S0140-6736(22)01655-5

Type 2 diabetes accounts for nearly 90% of the approximately 537 million cases of diabetes worldwide. The number affected is increasing rapidly with alarming trends in children and young adults (up to age 40 years). Early detection and proactive management are crucial for prevention and mitigation of microvascular and macrovascular complications and mortality burden. Access to novel therapies improves person-centred outcomes beyond glycaemic control. Precision medicine, including multiomics and pharmacogenomics, hold promise to enhance understanding of disease heterogeneity, leading to targeted therapies. Technology might improve outcomes, but its potential is yet to be realised. Despite advances, substantial barriers to changing the course of the epidemic remain. This Seminar offers a clinically focused review of the recent developments in type 2 diabetes care including controversies and future directions.

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Conflict of interest statement

Declaration of interests EA has received fellowship funding from AstraZeneca. SL has been a member on advisory boards or has consulted with Merck Sharp & Dohme, and NovoNordisk. He has received grant support from AstraZeneca, Merck Sharp & Dohme, and Astellas. He has also served on the speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co, Merck Sharp & Dohme, Chong Kun Dang Pharmaceutical, and Novo Nordisk. RL has received a research grant from Novo Nordisk. She has also received funds for serving on an advisory board for Sanofi and consultancy fees from Sanofi, AstraZeneca, Novo Nordisk, and Boehringer Ingelheim. DRW has received honoraria as a speaker for AstraZeneca, Sanofi-Aventis, and Lilly, and received research funding support from Novo Nordisk. MJD has acted as consultant, advisory board member, and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk, and Sanofi; an advisory board member and speaker for AstraZeneca; an advisory board member for Janssen, Lexicon, Pfizer, and ShouTi Pharma; and as a speaker for Napp Pharmaceuticals, Novartis, and Takeda Pharmaceuticals International. She has received grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca, and Janssen.

Cancer is becoming the leading cause of death in diabetes. Wang M, Sperrin M, Rutter MK, Renehan AG. Wang M, et al. Lancet. 2023 Jun 3;401(10391):1849. doi: 10.1016/S0140-6736(23)00445-2. Lancet. 2023. PMID: 37270233 No abstract available.

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Diabetes describes a group of metabolic diseases characterized by high blood sugar levels. Diabetes can be caused by the pancreas not producing insulin (type 1 diabetes) or by insulin resistance (cells do not respond to insulin; type 2 diabetes).

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Clinical Research in Type 2 Diabetes

Studies in humans aimed at the prevention, treatment, and diagnosis of Type 2 Diabetes and the mechanistic aspects of its etiology.

The Clinical Research in Type 2 Diabetes (T2D) program supports human studies across the lifespan aimed at understanding, preventing and treating T2D. This program includes clinical trials that test pharmacologic, behavioral, surgical or practice-level approaches to the treatment and/or prevention of T2D, including promoting the preservation of beta cell function. Studies may also advance the development of new surrogate markers for use in clinical trials. Studies can be designed to understand the pathophysiology of T2D, including the role of gestational diabetes and metabolic imprinting on the development of T2D, as well as factors influencing the response to treatment. The program also encompasses epidemiologic studies that improve our understanding of the natural history and pathogenesis of T2D, and the development of diagnostic criteria to distinguish type 1 and type 2 diabetes, especially in the pediatric population. The program also supports research to understand and test approaches to accelerate the translation of efficacious interventions into real-world practice and adoption; and to address health equity by reducing health disparities in the incidence and/or clinical outcomes of T2D.

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Jean M. Lawrence, Sc.D., M.P.H., MSW Type 2 diabetes risk and prevention after gestational diabetes; Studies of adults with diabetes/pre-diabetes using secondary data and observational designs, and natural experiments
Hanyu Liang, M.D., Ph.D. Hepatic Metabolism; Insulin Resistance; Type 2 Diabetes; Obesity; Bariatric Surgery
Barbara Linder, M.D., Ph.D. Type 2 diabetes in children and youth; human studies of metabolic imprinting
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Recent Advances

ADA-funded researchers use the money from their awards to conduct critical diabetes research. In time, they publish their findings in order to inform fellow scientists of their results, which ensures that others will build upon their work. Ultimately, this cycle drives advances to prevent diabetes and to help people burdened by it. In 2018 alone, ADA-funded scientists published over 200 articles related to their awards!

Identification of a new player in type 1 diabetes risk

Type 1 diabetes is caused by an autoimmune attack of insulin-producing beta-cells. While genetics and the environment are known to play important roles, the underlying factors explaining why the immune system mistakenly recognize beta-cells as foreign is not known. Now, Dr. Delong has discovered a potential explanation. He found that proteins called Hybrid Insulin Peptides (HIPs) are found on beta-cells of people with type 1 diabetes and are recognized as foreign by their immune cells. Even after diabetes onset, immune cells are still present in the blood that attack these HIPs.

Next, Dr. Delong wants to determine if HIPs can serve as a biomarker or possibly even targeted to prevent or treat type 1 diabetes. Baker, R. L., Rihanek, M., Hohenstein, A. C., Nakayama, M., Michels, A., Gottlieb, P. A., Haskins, K., & Delong, T. (2019). Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes. Diabetes , 68 (9), 1830–1840.

Understanding the biology of body-weight regulation in children

Determining the biological mechanisms regulating body-weight is important for preventing type 2 diabetes. The rise in childhood obesity has made this even more urgent. Behavioral studies have demonstrated that responses to food consumption are altered in children with obesity, but the underlying biological mechanisms are unknown. This year, Dr. Schur tested changes in brain and hormonal responses to a meal in normal-weight and obese children. Results from her study show that hormonal responses in obese children are normal following a meal, but responses within the brain are reduced. The lack of response within the brain may predispose them to overconsumption of food or difficulty with weight-loss.

With this information at hand, Dr. Schur wants to investigate how this information can be used to treat obesity in children and reduce diabetes.

Roth, C. L., Melhorn, S. J., Elfers, C. T., Scholz, K., De Leon, M. R. B., Rowland, M., Kearns, S., Aylward, E., Grabowski, T. J., Saelens, B. E., & Schur, E. A. (2019). Central Nervous System and Peripheral Hormone Responses to a Meal in Children. The Journal of Clinical Endocrinology and Metabolism , 104 (5), 1471–1483.

A novel molecule to improve continuous glucose monitoring

To create a fully automated artificial pancreas, it is critical to be able to quantify blood glucose in an accurate and stable manner. Current ways of continuously monitoring glucose are dependent on the activity of an enzyme which can change over time, meaning the potential for inaccurate readings and need for frequent replacement or calibration. Dr. Wang has developed a novel molecule that uses a different, non-enzymatic approach to continuously monitor glucose levels in the blood. This new molecule is stable over long periods of time and can be easily integrated into miniaturized systems.

Now, Dr. Wang is in the process of patenting his invention and intends to continue research on this new molecule so that it can eventually benefit people living with diabetes.

Wang, B. , Chou, K.-H., Queenan, B. N., Pennathur, S., & Bazan, G. C. (2019). Molecular Design of a New Diboronic Acid for the Electrohydrodynamic Monitoring of Glucose. Angewandte Chemie (International Ed. in English) , 58 (31), 10612–10615.

Addressing the legacy effect of diabetes

Several large clinical trials have demonstrated the importance of tight glucose control for reducing diabetes complications. However, few studies to date have tested this in the real-world, outside of a controlled clinical setting. In a study published this year, Dr. Laiteerapong found that indeed in a real-world setting, people with lower hemoglobin A1C levels after diagnosis had significantly lower vascular complications later on, a phenomenon known as the ‘legacy effect’ of glucose control. Her research noted the importance of early intervention for the best outcomes, as those with the low A1C levels just one-year after diagnosis had significantly lower vascular disease risk compared to people with higher A1C levels.

With these findings in hand, physicians and policymakers will have more material to debate and determine the best course of action for improving outcomes in people newly diagnosed with diabetes.

Laiteerapong, N. , Ham, S. A., Gao, Y., Moffet, H. H., Liu, J. Y., Huang, E. S., & Karter, A. J. (2019). The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes & Aging Study). Diabetes Care , 42 (3), 416–426.

A new way to prevent immune cells from attacking insulin-producing beta-cells

Replacing insulin-producing beta-cells that have been lost in people with type 1 diabetes is a promising strategy to restore control of glucose levels. However, because the autoimmune disease is a continuous process, replacing beta-cells results in another immune attack if immunosorbent drugs are not used, which carry significant side-effects. This year, Dr. Song reported on the potential of an immunotherapy he developed that prevents immune cells from attacking beta-cells and reduces inflammatory processes. This immunotherapy offers several potential benefits, including eliminating the need for immunosuppression, long-lasting effects, and the ability to customize the treatment to each patient.

The ability to suppress autoimmunity has implications for both prevention of type 1 diabetes and improving success rates of islet transplantation.

Haque, M., Lei, F., Xiong, X., Das, J. K., Ren, X., Fang, D., Salek-Ardakani, S., Yang, J.-M., & Song, J . (2019). Stem cell-derived tissue-associated regulatory T cells suppress the activity of pathogenic cells in autoimmune diabetes. JCI Insight , 4 (7).

A new target to improve insulin sensitivity

The hormone insulin normally acts like a ‘key’, traveling through the blood and opening the cellular ‘lock’ to enable the entry of glucose into muscle and fat cells. However, in people with type 2 diabetes, the lock on the cellular door has, in effect, been changed, meaning insulin isn’t as effective. This phenomenon is called insulin resistance. Scientists have long sought to understand what causes insulin resistance and develop therapies to enable insulin to work correctly again. This year, Dr. Summers determined an essential role for a molecule called ceramides as a driver of insulin resistance in mice. He also presented a new therapeutic strategy for lowering ceramides and reversing insulin resistance. His findings were published in one of the most prestigious scientific journals, Science .

Soon, Dr. Summers and his team will attempt to validate these findings in humans, with the ultimate goal of developing a new medication to help improve outcomes in people with diabetes.

Chaurasia, B., Tippetts, T. S., Mayoral Monibas, R., Liu, J., Li, Y., Wang, L., Wilkerson, J. L., Sweeney, C. R., Pereira, R. F., Sumida, D. H., Maschek, J. A., Cox, J. E., Kaddai, V., Lancaster, G. I., Siddique, M. M., Poss, A., Pearson, M., Satapati, S., Zhou, H., … Summers, S. A. (2019). Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science (New York, N.Y.) , 365 (6451), 386–392.

Determining the role of BPA in type 2 diabetes risk

Many synthetic chemicals have infiltrated our food system during the period in which rates of diabetes has surged. Data has suggested that one particular synthetic chemical, bisphenol A (BPA), may be associated with increased risk for developing type 2 diabetes. However, no study to date has determined whether consumption of BPA alters the progression to type 2 diabetes in humans. Results reported this year by Dr. Hagobian demonstrated that indeed when BPA is administered to humans in a controlled manner, there is an immediate, direct effect on glucose and insulin levels.

Now, Dr. Hagobian wants to conduct a larger clinical trial including exposure to BPA over a longer period of time to determine precisely how BPA influences glucose and insulin. Such results are important to ensure the removal of chemicals contributing to chronic diseases, including diabetes.

Hagobian, T. A. , Bird, A., Stanelle, S., Williams, D., Schaffner, A., & Phelan, S. (2019). Pilot Study on the Effect of Orally Administered Bisphenol A on Glucose and Insulin Response in Nonobese Adults. Journal of the Endocrine Society , 3 (3), 643–654.

Investigating the loss of postmenopausal protection from cardiovascular disease in women with type 1 diabetes

On average, women have a lower risk of developing heart disease compared to men. However, research has shown that this protection is lost in women with type 1 diabetes. The process of menopause increases rates of heart disease in women, but it is not known how menopause affects women with type 1 diabetes in regard to risk for developing heart disease. In a study published this year, Dr. Snell-Bergeon found that menopause increased risk markers for heart disease in women with type 1 diabetes more than women without diabetes.

Research has led to improved treatments and significant gains in life expectancy for people with diabetes and, as a result, many more women are reaching the age of menopause. Future research is needed to address prevention and treatment options.

Keshawarz, A., Pyle, L., Alman, A., Sassano, C., Westfeldt, E., Sippl, R., & Snell-Bergeon, J. (2019). Type 1 Diabetes Accelerates Progression of Coronary Artery Calcium Over the Menopausal Transition: The CACTI Study. Diabetes Care , 42 (12), 2315–2321.

Identification of a potential therapy for diabetic neuropathy related to type 1 and type 2 diabetes

Diabetic neuropathy is a type of nerve damage that is one of the most common complications affecting people with diabetes. For some, neuropathy can be mild, but for others, it can be painful and debilitating. Additionally, neuropathy can affect the spinal cord and the brain. Effective clinical treatments for neuropathy are currently lacking. Recently, Dr. Calcutt reported results of a new potential therapy that could bring hope to the millions of people living with diabetic neuropathy. His study found that a molecule currently in clinical trials for the treatment of depression may be valuable for diabetic neuropathy, particularly the type affecting the brain.

Because the molecule is already in clinical trials, there is the potential that it can benefit patients sooner than later.

Jolivalt, C. G., Marquez, A., Quach, D., Navarro Diaz, M. C., Anaya, C., Kifle, B., Muttalib, N., Sanchez, G., Guernsey, L., Hefferan, M., Smith, D. R., Fernyhough, P., Johe, K., & Calcutt, N. A. (2019). Amelioration of Both Central and Peripheral Neuropathy in Mouse Models of Type 1 and Type 2 Diabetes by the Neurogenic Molecule NSI-189. Diabetes , 68 (11), 2143–2154.

ADA-funded researcher studying link between ageing and type 2 diabetes

One of the most important risk factors for developing type 2 diabetes is age. As a person gets older, their risk for developing type 2 diabetes increases. Scientists want to better understand the relationship between ageing and diabetes in order to determine out how to best prevent and treat type 2 diabetes. ADA-funded researcher Rafael Arrojo e Drigo, PhD, from the Salk Institute for Biological Studies, is one of those scientists working hard to solve this puzzle.

Recently, Dr. Arrojo e Drigo published results from his research in the journal Cell Metabolism . The goal of this specific study was to use high-powered microscopes and novel cellular imaging tools to determine the ‘age’ of different cells that reside in organs that control glucose levels, including the brain, liver and pancreas. He found that, in mice, the cells that make insulin in the pancreas – called beta-cells – were a mosaic of both old and young cells. Some beta-cells appeared to be as old as the animal itself, and some were determined to be much younger, indicating they recently underwent cell division.

Insufficient insulin production by beta-cells is known to be a cause of type 2 diabetes. One reason for this is thought to be fewer numbers of functional beta-cells. Dr. Arrojo e Drigo believes that people with or at risk for diabetes may have fewer ‘young’ beta-cells, which are likely to function better than old ones. Alternatively, if we can figure out how to induce the production of younger, high-functioning beta-cells in the pancreas, it could be a potential treatment for people with diabetes.

In the near future, Dr. Arrojo e Drigo’s wants to figure out how to apply this research to humans. “The next step is to look for molecular or morphological features that would allow us to distinguish a young cell from and old cell,” Dr. Arrojo e Drigo said.

The results from this research are expected to provide a unique insight into the life-cycle of beta-cells and pave the way to novel therapeutic avenues for type 2 diabetes.

Watch a video of Dr. Arrojo e Drigo explaining his research!

Arrojo E Drigo, R. , Lev-Ram, V., Tyagi, S., Ramachandra, R., Deerinck, T., Bushong, E., … Hetzer, M. W. (2019). Age Mosaicism across Multiple Scales in Adult Tissues. Cell Metabolism , 30 (2), 343-351.e3.

Researcher identifies potential underlying cause of type 1 diabetes

Type 1 diabetes occurs when the immune system mistakenly recognizes insulin-producing beta-cells as foreign and attacks them. The result is insulin deficiency due to the destruction of the beta-cells. Thankfully, this previously life-threatening condition can be managed through glucose monitoring and insulin administration. Still, therapies designed to address the underlying immunological cause of type 1 diabetes remain unavailable.

Conventional approaches have focused on suppressing the immune system, which has serious side effects and has been mostly unsuccessful. The American Diabetes Association recently awarded a grant to Dr. Kenneth Brayman, who proposed to take a different approach. What if instead of suppressing the whole immune system, we boost regulatory aspects that already exist in the system, thereby reigning in inappropriate immune cell activation and preventing beta-cell destruction? His idea focused on a molecule called immunoglobulin M (IgM), which is responsible for limiting inflammation and regulating immune cell development.

In a paper published in the journal Diabetes , Dr. Brayman and a team of researchers reported exciting findings related to this approach. They found that supplementing IgM obtained from healthy mice into mice with type 1 diabetes selectively reduced the amount of autoreactive immune cells known to target beta-cells for destruction. Amazingly, this resulted in reversal of new-onset diabetes. Importantly, the authors of the study determined this therapy is translatable to humans. IgM isolated from healthy human donors also prevented the development of type 1 diabetes in a humanized mouse model of type 1 diabetes.

The scientists tweaked the original experiment by isolating IgM from mice prone to developing type 1 diabetes, but before it actually occurred. When mice with newly onset diabetes were supplemented with this IgM, their diabetes was not reversed. This finding suggests that in type 1 diabetes, IgM loses its capacity to serve as a regulator of immune cells, which may be contribute to the underlying cause of the disease.

Future studies will determine exactly how IgM changes its regulatory properties to enable diabetes development. Identification of the most biologically optimal IgM will facilitate transition to clinical applications of IgM as a potential therapeutic for people with type 1 diabetes. Wilson, C. S., Chhabra, P., Marshall, A. F., Morr, C. V., Stocks, B. T., Hoopes, E. M., Bonami, R.H., Poffenberger, G., Brayman, K.L. , Moore, D. J. (2018). Healthy Donor Polyclonal IgM’s Diminish B Lymphocyte Autoreactivity, Enhance Treg Generation, and Reverse T1D in NOD Mice. Diabetes .

ADA-funded researcher designs community program to help all people tackle diabetes

Diabetes self-management and support programs are important adjuncts to traditional physician directed treatment. These community-based programs aim to give people with diabetes the knowledge and skills necessary to effectively self-manage their condition. While several clinical trials have demonstrated the value of diabetes self-management programs in terms of improving glucose control and reducing health-care costs, whether this also occurs in implemented programs outside a controlled setting is unclear, particularly in socially and economically disadvantaged groups.

Lack of infrastructure and manpower are often cited as barriers to implementation of these programs in socioeconomically disadvantaged communities. ADA-funded researcher Dr. Briana Mezuk addressed this challenge in a study recently published in The Diabetes Educator . Dr. Mezuk partnered with the YMCA to evaluate the impact of the Diabetes Control Program in Richmond, Virginia. This community-academic partnership enabled both implementation and evaluation of the Diabetes Control Program in socially disadvantaged communities, who are at higher risk for developing diabetes and the complications that accompany it.

Dr. Mezuk had two primary research questions: (1) What is the geographic and demographic reach of the program? and (2) Is the program effective at improving diabetes management and health outcomes in participants? Over a 12-week study period, Dr. Mezuk found that there was broad geographic and demographic participation in the program. The program had participants from urban, suburban and rural areas, most of which came from lower-income zip codes. HbA1C, mental health and self-management behaviors all improved in people taking part in the Greater Richmond Diabetes Control Program. Results from this study demonstrate the value of diabetes self-management programs and their potential to broadly improve health outcomes in socioeconomically diverse communities. Potential exists for community-based programs to address the widespread issue of outcome disparities related to diabetes. Mezuk, B. , Thornton, W., Sealy-Jefferson, S., Montgomery, J., Smith, J., Lexima, E., … Concha, J. B. (2018). Successfully Managing Diabetes in a Community Setting: Evidence from the YMCA of Greater Richmond Diabetes Control Program. The Diabetes Educator , 44 (4), 383–394.

Using incentives to stimulate behavior changes in youth at risk for developing diabetes

Once referred to as ‘adult-onset diabetes’, incidence of type 2 diabetes is now rapidly increasing in America’s youth. Unfortunately, children often do not have the ability to understand how everyday choices impact their health. Could there be a way to change a child’s eating behaviors? Davene Wright, PhD, of Seattle Children’s Hospital was granted an Innovative Clinical or Translational Science award to determine whether using incentives, directed by parents, can improve behaviors related to diabetes risk. A study published this year in Preventive Medicine Reports outlined what incentives were most desirable and feasible to implement. A key finding was that incentives should be tied to behavior changes and not to changes in body-weight.

With this information in hand, Dr. Wright now wants to see if incentives do indeed change a child’s eating habits and risk for developing type 2 diabetes. She is also planning to test whether an incentive program can improve behavior related to diabetes management in youth with type 1 diabetes. Jacob-Files, E., Powell, J., & Wright, D. R. (2018). Exploring parent attitudes around using incentives to promote engagement in family-based weight management programs. Preventive Medicine Reports , 10 , 278–284.

Determining the genetic risk for gestational diabetes

Research has identified more than 100 genetic variants linked to risk for developing type 2 diabetes in humans. However, the extent to which these same genetic variants might affect a woman’s probability for getting gestational diabetes has not been investigated.

Pathway to Stop Diabetes ® Accelerator awardee Marie-France Hivert, MD, of Harvard University set out to answer this critical question. Dr. Hivert found that indeed genetic determinants of type 2 diabetes outside of pregnancy are also strong risk factors for gestational diabetes. This study was published in the journal Diabetes .

The implications? Because of this finding, doctors in the clinic may soon be able to identify women at risk for getting gestational diabetes and take proactive steps to prevent it. Powe, C. E., Nodzenski, M., Talbot, O., Allard, C., Briggs, C., Leya, M. V., … Hivert, M.-F. (2018). Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus. Diabetes , 67 (12), 2703–2709.

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Patient Care & Health Information
Diseases & Conditions
Type 2 diabetes

Type 2 diabetes is usually diagnosed using the glycated hemoglobin (A1C) test. This blood test indicates your average blood sugar level for the past two to three months. Results are interpreted as follows:

Below 5.7% is normal.
5.7% to 6.4% is diagnosed as prediabetes.
6.5% or higher on two separate tests indicates diabetes.

If the A1C test isn't available, or if you have certain conditions that interfere with an A1C test, your health care provider may use the following tests to diagnose diabetes:

Random blood sugar test. Blood sugar values are expressed in milligrams of sugar per deciliter ( mg/dL ) or millimoles of sugar per liter ( mmol/L ) of blood. Regardless of when you last ate, a level of 200 mg/dL (11.1 mmol/L ) or higher suggests diabetes, especially if you also have symptoms of diabetes, such as frequent urination and extreme thirst.

Fasting blood sugar test. A blood sample is taken after you haven't eaten overnight. Results are interpreted as follows:

Less than 100 mg/dL (5.6 mmol/L ) is considered healthy.
100 to 125 mg/dL (5.6 to 6.9 mmol/L ) is diagnosed as prediabetes.
126 mg/dL (7 mmol/L ) or higher on two separate tests is diagnosed as diabetes.

Oral glucose tolerance test. This test is less commonly used than the others, except during pregnancy. You'll need to not eat for a certain amount of time and then drink a sugary liquid at your health care provider's office. Blood sugar levels then are tested periodically for two hours. Results are interpreted as follows:

Less than 140 mg/dL (7.8 mmol/L ) after two hours is considered healthy.
140 to 199 mg/dL (7.8 mmol/L and 11.0 mmol/L ) is diagnosed as prediabetes.
200 mg/dL (11.1 mmol/L ) or higher after two hours suggests diabetes.

Screening. The American Diabetes Association recommends routine screening with diagnostic tests for type 2 diabetes in all adults age 35 or older and in the following groups:

People younger than 35 who are overweight or obese and have one or more risk factors associated with diabetes.
Women who have had gestational diabetes.
People who have been diagnosed with prediabetes.
Children who are overweight or obese and who have a family history of type 2 diabetes or other risk factors.

After a diagnosis

If you're diagnosed with diabetes, your health care provider may do other tests to distinguish between type 1 and type 2 diabetes because the two conditions often require different treatments.

Your health care provider will test A1C levels at least two times a year and when there are any changes in treatment. Target A1C goals vary depending on age and other factors. For most people, the American Diabetes Association recommends an A1C level below 7%.

You also receive tests to screen for complications of diabetes and other medical conditions.

More Information

Glucose tolerance test

Management of type 2 diabetes includes:

Healthy eating.
Regular exercise.
Weight loss.
Possibly, diabetes medication or insulin therapy.
Blood sugar monitoring.

These steps make it more likely that blood sugar will stay in a healthy range. And they may help to delay or prevent complications.

Healthy eating

There's no specific diabetes diet. However, it's important to center your diet around:

A regular schedule for meals and healthy snacks.
Smaller portion sizes.
More high-fiber foods, such as fruits, nonstarchy vegetables and whole grains.
Fewer refined grains, starchy vegetables and sweets.
Modest servings of low-fat dairy, low-fat meats and fish.
Healthy cooking oils, such as olive oil or canola oil.
Fewer calories.

Your health care provider may recommend seeing a registered dietitian, who can help you:

Identify healthy food choices.
Plan well-balanced, nutritional meals.
Develop new habits and address barriers to changing habits.
Monitor carbohydrate intake to keep your blood sugar levels more stable.

Physical activity

Exercise is important for losing weight or maintaining a healthy weight. It also helps with managing blood sugar. Talk to your health care provider before starting or changing your exercise program to ensure that activities are safe for you.

Aerobic exercise. Choose an aerobic exercise that you enjoy, such as walking, swimming, biking or running. Adults should aim for 30 minutes or more of moderate aerobic exercise on most days of the week, or at least 150 minutes a week.
Resistance exercise. Resistance exercise increases your strength, balance and ability to perform activities of daily living more easily. Resistance training includes weightlifting, yoga and calisthenics. Adults living with type 2 diabetes should aim for 2 to 3 sessions of resistance exercise each week.
Limit inactivity. Breaking up long periods of inactivity, such as sitting at the computer, can help control blood sugar levels. Take a few minutes to stand, walk around or do some light activity every 30 minutes.

Weight loss

Weight loss results in better control of blood sugar levels, cholesterol, triglycerides and blood pressure. If you're overweight, you may begin to see improvements in these factors after losing as little as 5% of your body weight. However, the more weight you lose, the greater the benefit to your health. In some cases, losing up to 15% of body weight may be recommended.

Your health care provider or dietitian can help you set appropriate weight-loss goals and encourage lifestyle changes to help you achieve them.

Monitoring your blood sugar

Your health care provider will advise you on how often to check your blood sugar level to make sure you remain within your target range. You may, for example, need to check it once a day and before or after exercise. If you take insulin, you may need to check your blood sugar multiple times a day.

Monitoring is usually done with a small, at-home device called a blood glucose meter, which measures the amount of sugar in a drop of blood. Keep a record of your measurements to share with your health care team.

Continuous glucose monitoring is an electronic system that records glucose levels every few minutes from a sensor placed under the skin. Information can be transmitted to a mobile device such as a phone, and the system can send alerts when levels are too high or too low.

Diabetes medications

If you can't maintain your target blood sugar level with diet and exercise, your health care provider may prescribe diabetes medications that help lower glucose levels, or your provider may suggest insulin therapy. Medicines for type 2 diabetes include the following.

Metformin (Fortamet, Glumetza, others) is generally the first medicine prescribed for type 2 diabetes. It works mainly by lowering glucose production in the liver and improving the body's sensitivity to insulin so it uses insulin more effectively.

Some people experience B-12 deficiency and may need to take supplements. Other possible side effects, which may improve over time, include:

Abdominal pain.

Sulfonylureas help the body secrete more insulin. Examples include glyburide (DiaBeta, Glynase), glipizide (Glucotrol XL) and glimepiride (Amaryl). Possible side effects include:

Low blood sugar.
Weight gain.

Glinides stimulate the pancreas to secrete more insulin. They're faster acting than sulfonylureas. But their effect in the body is shorter. Examples include repaglinide and nateglinide. Possible side effects include:

Thiazolidinediones make the body's tissues more sensitive to insulin. An example of this medicine is pioglitazone (Actos). Possible side effects include:

Risk of congestive heart failure.
Risk of bladder cancer (pioglitazone).
Risk of bone fractures.

DPP-4 inhibitors help reduce blood sugar levels but tend to have a very modest effect. Examples include sitagliptin (Januvia), saxagliptin (Onglyza) and linagliptin (Tradjenta). Possible side effects include:

Risk of pancreatitis.
Joint pain.

GLP-1 receptor agonists are injectable medications that slow digestion and help lower blood sugar levels. Their use is often associated with weight loss, and some may reduce the risk of heart attack and stroke. Examples include exenatide (Byetta, Bydureon Bcise), liraglutide (Saxenda, Victoza) and semaglutide (Rybelsus, Ozempic, Wegovy). Possible side effects include:

SGLT2 inhibitors affect the blood-filtering functions in the kidneys by blocking the return of glucose to the bloodstream. As a result, glucose is removed in the urine. These medicines may reduce the risk of heart attack and stroke in people with a high risk of those conditions. Examples include canagliflozin (Invokana), dapagliflozin (Farxiga) and empagliflozin (Jardiance). Possible side effects include:

Vaginal yeast infections.
Urinary tract infections.
Low blood pressure.
High cholesterol.
Risk of gangrene.
Risk of bone fractures (canagliflozin).
Risk of amputation (canagliflozin).

Other medicines your health care provider might prescribe in addition to diabetes medications include blood pressure and cholesterol-lowering medicines, as well as low-dose aspirin, to help prevent heart and blood vessel disease.

Insulin therapy

Some people who have type 2 diabetes need insulin therapy. In the past, insulin therapy was used as a last resort, but today it may be prescribed sooner if blood sugar targets aren't met with lifestyle changes and other medicines.

Different types of insulin vary on how quickly they begin to work and how long they have an effect. Long-acting insulin, for example, is designed to work overnight or throughout the day to keep blood sugar levels stable. Short-acting insulin generally is used at mealtime.

Your health care provider will determine what type of insulin is right for you and when you should take it. Your insulin type, dosage and schedule may change depending on how stable your blood sugar levels are. Most types of insulin are taken by injection.

Side effects of insulin include the risk of low blood sugar — a condition called hypoglycemia — diabetic ketoacidosis and high triglycerides.

Weight-loss surgery

Weight-loss surgery changes the shape and function of the digestive system. This surgery may help you lose weight and manage type 2 diabetes and other conditions related to obesity. There are several surgical procedures. All of them help people lose weight by limiting how much food they can eat. Some procedures also limit the amount of nutrients the body can absorb.

Weight-loss surgery is only one part of an overall treatment plan. Treatment also includes diet and nutritional supplement guidelines, exercise and mental health care.

Generally, weight-loss surgery may be an option for adults living with type 2 diabetes who have a body mass index (BMI) of 35 or higher. BMI is a formula that uses weight and height to estimate body fat. Depending on the severity of diabetes or the presence of other medical conditions, surgery may be an option for someone with a BMI lower than 35.

Weight-loss surgery requires a lifelong commitment to lifestyle changes. Long-term side effects may include nutritional deficiencies and osteoporosis.

People living with type 2 diabetes often need to change their treatment plan during pregnancy and follow a diet that controls carbohydrates. Many people need insulin therapy during pregnancy. They also may need to stop other treatments, such as blood pressure medicines.

There is an increased risk during pregnancy of developing a condition that affects the eyes called diabetic retinopathy. In some cases, this condition may get worse during pregnancy. If you are pregnant, visit an ophthalmologist during each trimester of your pregnancy and one year after you give birth. Or as often as your health care provider suggests.

Signs of trouble

Regularly monitoring your blood sugar levels is important to avoid severe complications. Also, be aware of symptoms that may suggest irregular blood sugar levels and the need for immediate care:

High blood sugar. This condition also is called hyperglycemia. Eating certain foods or too much food, being sick, or not taking medications at the right time can cause high blood sugar. Symptoms include:

Frequent urination.
Increased thirst.
Blurred vision.

Hyperglycemic hyperosmolar nonketotic syndrome (HHNS). This life-threatening condition includes a blood sugar reading higher than 600 mg/dL (33.3 mmol/L ). HHNS may be more likely if you have an infection, are not taking medicines as prescribed, or take certain steroids or drugs that cause frequent urination. Symptoms include:

Extreme thirst.
Drowsiness.
Dark urine.

Diabetic ketoacidosis. Diabetic ketoacidosis occurs when a lack of insulin results in the body breaking down fat for fuel rather than sugar. This results in a buildup of acids called ketones in the bloodstream. Triggers of diabetic ketoacidosis include certain illnesses, pregnancy, trauma and medicines — including the diabetes medicines called SGLT2 inhibitors.

The toxicity of the acids made by diabetic ketoacidosis can be life-threatening. In addition to the symptoms of hyperglycemia, such as frequent urination and increased thirst, ketoacidosis may cause:

Shortness of breath.
Fruity-smelling breath.

Low blood sugar. If your blood sugar level drops below your target range, it's known as low blood sugar. This condition also is called hypoglycemia. Your blood sugar level can drop for many reasons, including skipping a meal, unintentionally taking more medication than usual or being more physically active than usual. Symptoms include:

Irritability.
Heart palpitations.
Slurred speech.

If you have symptoms of low blood sugar, drink or eat something that will quickly raise your blood sugar level. Examples include fruit juice, glucose tablets, hard candy or another source of sugar. Retest your blood in 15 minutes. If levels are not at your target, eat or drink another source of sugar. Eat a meal after your blood sugar level returns to normal.

If you lose consciousness, you need to be given an emergency injection of glucagon, a hormone that stimulates the release of sugar into the blood.

Medications for type 2 diabetes
GLP-1 agonists: Diabetes drugs and weight loss
Bariatric surgery
Endoscopic sleeve gastroplasty
Gastric bypass (Roux-en-Y)

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Clinical trials

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.

Lifestyle and home remedies

Careful management of type 2 diabetes can reduce the risk of serious — even life-threatening — complications. Consider these tips:

Commit to managing your diabetes. Learn all you can about type 2 diabetes. Make healthy eating and physical activity part of your daily routine.
Work with your team. Establish a relationship with a certified diabetes education specialist, and ask your diabetes treatment team for help when you need it.
Identify yourself. Wear a necklace or bracelet that says you are living with diabetes, especially if you take insulin or other blood sugar-lowering medicine.
Schedule a yearly physical exam and regular eye exams. Your diabetes checkups aren't meant to replace regular physicals or routine eye exams.
Keep your vaccinations up to date. High blood sugar can weaken your immune system. Get a flu shot every year. Your health care provider also may recommend the pneumonia vaccine. The Centers for Disease Control and Prevention (CDC) also recommends the hepatitis B vaccination if you haven't previously received this vaccine and you're 19 to 59 years old. Talk to your health care provider about other vaccinations you may need.
Take care of your teeth. Diabetes may leave you prone to more-serious gum infections. Brush and floss your teeth regularly and schedule recommended dental exams. Contact your dentist right away if your gums bleed or look red or swollen.
Pay attention to your feet. Wash your feet daily in lukewarm water, dry them gently, especially between the toes, and moisturize them with lotion. Check your feet every day for blisters, cuts, sores, redness and swelling. Contact your health care provider if you have a sore or other foot problem that isn't healing.
Keep your blood pressure and cholesterol under control. Eating healthy foods and exercising regularly can go a long way toward controlling high blood pressure and cholesterol. Take medication as prescribed.
If you smoke or use other types of tobacco, ask your health care provider to help you quit. Smoking increases your risk of diabetes complications. Talk to your health care provider about ways to stop using tobacco.
Use alcohol sparingly. Depending on the type of drink, alcohol may lower or raise blood sugar levels. If you choose to drink alcohol, only do so with a meal. The recommendation is no more than one drink daily for women and no more than two drinks daily for men. Check your blood sugar frequently after drinking alcohol.
Make healthy sleep a priority. Many people with type 2 diabetes have sleep problems. And not getting enough sleep may make it harder to keep blood sugar levels in a healthy range. If you have trouble sleeping, talk to your health care provider about treatment options.
Caffeine: Does it affect blood sugar?

Alternative medicine

Many alternative medicine treatments claim to help people living with diabetes. According to the National Center for Complementary and Integrative Health, studies haven't provided enough evidence to recommend any alternative therapies for blood sugar management. Research has shown the following results about popular supplements for type 2 diabetes:

Chromium supplements have been shown to have few or no benefits. Large doses can result in kidney damage, muscle problems and skin reactions.
Magnesium supplements have shown benefits for blood sugar control in some but not all studies. Side effects include diarrhea and cramping. Very large doses — more than 5,000 mg a day — can be fatal.
Cinnamon, in some studies, has lowered fasting glucose levels but not A1C levels. Therefore, there's no evidence of overall improved glucose management.

Talk to your health care provider before starting a dietary supplement or natural remedy. Do not replace your prescribed diabetes medicines with alternative medicines.

Coping and support

Type 2 diabetes is a serious disease, and following your diabetes treatment plan takes commitment. To effectively manage diabetes, you may need a good support network.

Anxiety and depression are common in people living with diabetes. Talking to a counselor or therapist may help you cope with the lifestyle changes and stress that come with a type 2 diabetes diagnosis.

Support groups can be good sources of diabetes education, emotional support and helpful information, such as how to find local resources or where to find carbohydrate counts for a favorite restaurant. If you're interested, your health care provider may be able to recommend a group in your area.

You can visit the American Diabetes Association website to check out local activities and support groups for people living with type 2 diabetes. The American Diabetes Association also offers online information and online forums where you can chat with others who are living with diabetes. You also can call the organization at 800-DIABETES ( 800-342-2383 ).

Preparing for your appointment

At your annual wellness visit, your health care provider can screen for diabetes and monitor and treat conditions that increase your risk of diabetes, such as high blood pressure, high cholesterol or a high BMI .

If you are seeing your health care provider because of symptoms that may be related to diabetes, you can prepare for your appointment by being ready to answer the following questions:

When did your symptoms begin?
Does anything improve the symptoms or worsen the symptoms?
What medicines do you take regularly, including dietary supplements and herbal remedies?
What are your typical daily meals? Do you eat between meals or before bedtime?
How much alcohol do you drink?
How much daily exercise do you get?
Is there a history of diabetes in your family?

If you are diagnosed with diabetes, your health care provider may begin a treatment plan. Or you may be referred to a doctor who specializes in hormonal disorders, called an endocrinologist. Your care team also may include the following specialists:

Certified diabetes education specialist.
Foot doctor, also called a podiatrist.
Doctor who specializes in eye care, called an ophthalmologist.

Talk to your health care provider about referrals to other specialists who may be providing care.

Questions for ongoing appointments

Before any appointment with a member of your treatment team, make sure you know whether there are any restrictions, such as not eating or drinking before taking a test. Questions that you should regularly talk about with your health care provider or other members of the team include:

How often do I need to monitor my blood sugar, and what is my target range?
What changes in my diet would help me better manage my blood sugar?
What is the right dosage for prescribed medications?
When do I take the medications? Do I take them with food?
How does management of diabetes affect treatment for other conditions? How can I better coordinate treatments or care?
When do I need to make a follow-up appointment?
Under what conditions should I call you or seek emergency care?
Are there brochures or online sources you recommend?
Are there resources available if I'm having trouble paying for diabetes supplies?

What to expect from your doctor

Your health care provider is likely to ask you questions at your appointments. Those questions may include:

Do you understand your treatment plan and feel confident you can follow it?
How are you coping with diabetes?
Have you had any low blood sugar?
Do you know what to do if your blood sugar is too low or too high?
What's a typical day's diet like?
Are you exercising? If so, what type of exercise? How often?
Do you sit for long periods of time?
What challenges are you experiencing in managing your diabetes?
Professional Practice Committee: Standards of Medical Care in Diabetes — 2020. Diabetes Care. 2020; doi:10.2337/dc20-Sppc.
Diabetes mellitus. Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/diabetes-mellitus-dm. Accessed Dec. 7, 2020.
Melmed S, et al. Williams Textbook of Endocrinology. 14th ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed Dec. 3, 2020.
Diabetes overview. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/diabetes/overview/all-content. Accessed Dec. 4, 2020.
AskMayoExpert. Type 2 diabetes. Mayo Clinic; 2018.
Feldman M, et al., eds. Surgical and endoscopic treatment of obesity. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 11th ed. Elsevier; 2021. https://www.clinicalkey.com. Accessed Oct. 20, 2020.
Hypersmolar hyperglycemic state (HHS). Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/hyperosmolar-hyperglycemic-state-hhs. Accessed Dec. 11, 2020.
Diabetic ketoacidosis (DKA). Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/diabetic-ketoacidosis-dka. Accessed Dec. 11, 2020.
Hypoglycemia. Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/hypoglycemia. Accessed Dec. 11, 2020.
6 things to know about diabetes and dietary supplements. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/tips/things-to-know-about-type-diabetes-and-dietary-supplements. Accessed Dec. 11, 2020.
Type 2 diabetes and dietary supplements: What the science says. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/providers/digest/type-2-diabetes-and-dietary-supplements-science. Accessed Dec. 11, 2020.
Preventing diabetes problems. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/all-content. Accessed Dec. 3, 2020.
Schillie S, et al. Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recommendations and Reports. 2018; doi:10.15585/mmwr.rr6701a1.
Diabetes prevention: 5 tips for taking control
Hyperinsulinemia: Is it diabetes?

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Living With Diabetes

Warning signs of diabetes, types of diabetes, type 1 vs type 2 diabetes, type 1 diabetes, type 1 diabetes causes, type 1 diabetes symptoms, is there a cure for type 1 diabetes, type 2 diabetes, type 2 diabetes treatment.

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Type 2 Diabetes is a serious condition which causes higher than normal blood sugar levels. It affects people from all social, economic, and ethnic backgrounds.

It is estimated that more than 34 million Americans have diabetes, including approximately 7 million who have the disease but have not yet been diagnosed. Worldwide, it is estimated that over 463 million people are living with some form of the disease.

Diabetes mellitus (type 2 diabetes), the medical term for the condition, occurs when the body cannot make or effectively use its own insulin, a hormone produced by special cells in the pancreas called islet (eye-let) cells. Insulin is like a key that opens the door of a cell so that food, or glucose, can enter. Without insulin, this glucose builds up in the blood and leads to starvation of the body’s cells, as well as dehydration and break down of body tissue.

There are multiple forms of diabetes. Type 2 diabetes is the most common form. Approximately 90 percent of those with diabetes have type 2. Unlike type 1 diabetes, in which all the insulin-producing cells are destroyed, people with type 2 diabetes are able to produce some of their own insulin, but their bodies are unable to use this insulin to completely control blood sugar levels. This is known as insulin resistance.

Who gets type 2 diabetes?

Type 2 diabetes usually develops after the age of 35, although it can occur in younger people as well, especially if they are overweight and have a sedentary lifestyle.

Commonly referred to as “adult onset” diabetes, 80% of those with this form of diabetes are overweight and have a family history of type 2 diabetes.

Certain ethnic groups have a higher risk of developing this form of the disease, including African Americans, Hispanics and American Indians. In addition, women who had diabetes during pregnancy (gestational diabetes) are also at greater risk of developing type 2 diabetes later in life.

What are the symptoms of type 2 diabetes?

Knowing the warning signs of type 2 diabetes is helpful for early diagnosis. Symptoms can include:

Increased thirst
Increased urination
Unexplained weight loss
Extreme hunger
Extreme weakness or fatigue
Blurred vision
Infections which are slow or difficult to heal

The symptoms of type 2 diabetes usually happen over time, unlike the symptoms of type 1 diabetes which are sudden and often too severe to overlook. That’s why many people mistakenly overlook the warning signs of type 2, and often think the symptoms are signs of other conditions, such as aging, overworking, or hot weather. Because these symptoms are often ignored, it is estimated that more than seven million people in the United States have diabetes and are not aware of it.

Individuals who have undiagnosed or untreated diabetes for several years may develop some complications, such as nerve damage, pain or numbness in their hands and feet, or changes in their eyes or kidneys. People who are over 35, overweight, have a family history of diabetes, or who belong to a high-risk group should be checked at least once a year to detect diabetes at its earliest stages.

What is the treatment for type 2 diabetes?

The treatment for type 2 diabetes focuses on improving the person’s ability to more effectively use the insulin his/her own body produces to normalize blood sugar levels. A treatment program including diet, exercise, and weight loss will help decrease insulin resistance and, in turn, lower blood sugar levels. If blood sugar levels are still high, there are many medications which can help to either stimulate more insulin production in the pancreas or help the body better use the insulin it makes. Insulin injections may be needed if these oral medications, along with diet and exercise, do not lower blood sugar levels enough.

What are the problems associated with type 2 diabetes?

New advances in research and treatment methods are helping people with type 2 diabetes live full, active and healthy lives. However, it is important to remember that diabetes is a serious, chronic condition with potential short-term and long-term complications. Frequent self-monitoring of blood sugar levels and carefully following an individualized meal and exercise program is a good course of action.

People with undiagnosed, untreated or long-term diabetes are at risk of developing complications, including nerve and blood vessel damage. These potential complications, which can affect the eyes, kidneys, limbs, heart, brain, and stomach, may occur after many years of living with diabetes. Early detection, improved medications, and new technologies may help prevent or minimize diabetes-related complications.

Can type 2 diabetes be prevented?

The key to success is in preventing pre-diabetes and type 2 diabetes. Identifying risk means asking yourself the following key questions:

Am I aged 35 years or older?
Am I overweight?
Do I have high blood pressure or cholesterol?
Do I have a family history of diabetes?
Am I African American, Hispanic, American Indian or Asian?
Do I have a history of diabetes occurring during pregnancy?
Did I deliver a baby weighing more than 9 pounds?

If you answered “yes” to any of these questions, then you should make an appointment with your physician to be screened. To lower your risk of pre-diabetes and type 2 diabetes try the following:

Look for opportunities to move more during the day
Exercise 30 minutes at least five times per week
Eat a healthy meal plan including grains, cereals, fresh fruit and vegetables, low fat dairy and lean meat
Reduce fat intake
Reduce food portions
Maintain an ideal body weight

Get more answers to your questions about type 1 diabetes, type 2 diabetes and gestational diabetes symptoms and treatments. (In Spanish: ¿Que es La Diabetes?).

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SLU Research: PTSD Is a Modifiable Risk Factor for Type 2 Diabetes, Related Adverse Outcomes

Bridjes O'Neil Communications Specialist [email protected] 314-282-5007

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ST. LOUIS — Patients with post-traumatic stress disorder (PTSD) and type 2 diabetes have worse glycemic control, increased risk of hospitalization, and poorer self-reported health compared with type 2 diabetes alone, according to a Saint Louis University study.

The study , published online Aug. 13 in JAMA Network Open , shows that treating PTSD is associated with better overall well-being and lower risk of some chronic health conditions, including type 2 diabetes.

Jeffrey Scherrer, Ph.D., professor of family and community medicine and professor of psychiatry and behavioral neuroscience at Saint Louis University School of Medicine. Scherrer is also co-director of research for SLU’s Advanced HEAlth Data Research Institute. SLU file photo.

“To our knowledge, this is the first evidence that PTSD is a modifiable risk factor, albeit a modest one, for some adverse diabetes outcomes such as microvascular complications,” said Jeffrey Scherrer, Ph.D. , professor of family and community medicine and professor of psychiatry and behavioral neuroscience at Saint Louis University School of Medicine, the paper’s senior author.

Scherrer is also co-director of research for SLU’s Advanced HEAlth Data ( AHEAD ) Research Institute, a center that addresses public health issues to improve patient health outcomes through data-driven innovation.

"This is further evidence that we should not separate mental from physical health. Treating the whole patient with comorbid PTSD and diabetes should address both conditions to optimize outcomes. Screening for and treating PTSD as part of diabetes care may lead to better clinical outcomes for both conditions," he said.

In this retrospective study, Scherrer and his co-authors collected patient data from 2011 to 2022 from the Veterans Health Administration (VHA). The data sets were comprised of 10,002 VHA patients, ages 18 to 80, with comorbid PTSD and type 2 diabetes.

Scherrer and his co-authors observed that when patients’ PTSD improved to a level where they no longer met the criteria for PTSD, that improvement was associated with an 8% reduction in risk for microvascular complications compared to those who continued to meet the criteria associated with a PTSD diagnosis. Among those ages 18-49, but not among older patients, no longer meeting PTSD criteria was linked to a significantly lower risk of insulin initiation and all-cause mortality.

PTSD is a metabolic disease related to the body’s inflammatory response. Scherrer and his co-authors found that it is possible that physiological abnormalities in the hypothalamic-pituitary-adrenal axis, changes in metabolic hormones, poor diet and a lack of exercise could explain the connection between PTSD and prediabetes and type 2 diabetes.

Other authors include Joanne Salas, of the AHEAD Research Institute, Saint Louis University School of Medicine; Wenjin Wang, of the Department of Family and Community Medicine, Saint Louis University School of Medicine; Kenneth E. Freedland, Ph.D., of the Department of Psychiatry, Washington University School of Medicine; Patrick J. Lustman, Ph.D., of the Department of Psychiatry, Washington University School of Medicine; Paula P. Schnurr, Ph.D., of the National Center for PTSD, White River Junction, Vermont, and the Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; Beth E. Cohen, M.D., of the Department of Medicine, University of California San Francisco School of Medicine and San Francisco VA Medical Center, San Francisco, California; Allan S. Jaffe, M.D. of the Department of Cardiovascular Medicine and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; Matthew J. Friedman, MD, Ph.D., of the Department of Psychiatry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.

This study was supported by grant R01HL160553 from the National Heart, Lung, and Blood Institute.

Open access
Published: 15 August 2024

Evaluation of a specialist nurse-led structured self-management training for peer supporters with type 2 diabetes mellitus with or without comorbid hypertension in Slovenia

Tina Virtič Potočnik 1 , 2 ,
Matic Mihevc 1 , 3 ,
Črt Zavrnik 1 , 3 ,
Majda Mori Lukančič 1 ,
Nina Ružić Gorenjec 1 , 4 ,
Antonija Poplas Susič 1 , 3 &
Zalika Klemenc-Ketiš 1 , 2 , 3

BMC Nursing volume 23 , Article number: 567 ( 2024 ) Cite this article

Metrics details

The training of peer supporters is critical because the success of the entire peer support intervention depends on the knowledge and experience that peer supporters can share with other patients. The objective of this study was to evaluate the pilot implementation of a specialist nurse-led self-management training programme for peer supporters with type 2 diabetes mellitus (T2DM) with or without comorbid hypertension (HTN) at the primary healthcare level in Slovenia, in terms of feasibility, acceptability, and effectiveness.

A prospective pre-post interventional pilot study was conducted in two Community Health Centres (CHC) in Slovenia from May 2021 to August 2022. Purposive sampling was employed to recruit approximately 40 eligible volunteers to become trained peer supporters. A specialist nurse-led structured training lasting 15 h over a 2-month period was delivered, comprising four group and two individual sessions. The comprehensive curriculum was based on interactive verbal and visual learning experience, utilising the Diabetes Conversation Maps™. Data were collected from medical records, by clinical measurements, and using questionnaires on sociodemographic and clinical data, the Theoretical Framework of Acceptability, knowledge of T2DM and HTN, and the Appraisal of Diabetes Scale, and evaluation forms.

Of the 36 participants, 31 became trained peer supporters (retention rate of 86.1%). Among them, 21 (67.7%) were women, with a mean age of 63.9 years (SD 8.9). The training was evaluated as satisfactory and highly acceptable. There was a significant improvement in knowledge of T2DM ( p < 0.001) and HTN ( p = 0.024) among peer supporters compared to baseline. Six months post-training, there was no significant improvement in the quality of life ( p = 0.066), but there was a significant decrease in body mass index (BMI) ( p = 0.020) from 30.4 (SD 6.2) at baseline to 29.8 (SD 6.2).

The pilot implementation of a specialist nurse-led self-management training for peer supporters was found to be feasible, acceptable, and effective (in the study group). It led to improvements in knowledge, maintained disease control, and promoted positive self-management behaviours among peer supporters, as evidenced by a decrease in their BMI over six months. The study emphasises the need for effective recruitment, training, and retention strategies.

Trial registration

The research is part of the international research project SCUBY: Scale up diabetes and hypertension care for vulnerable people in Cambodia, Slovenia and Belgium, which is registered in ISRCTN registry ( https://www.isrctn.com/ISRCTN41932064 ).

Peer Review reports

New models for comprehensive, patient-centred, integrated care have been introduced in Slovenian primary care to improve the quality of care for people with type 2 diabetes mellitus (T2DM) and hypertension (HTN) [ 1 , 2 , 3 , 4 ]. One example of an evidence-based model of such care is the Integrated Care Package [ 5 ], which encompasses elements of early detection and diagnosis, treatment in primary care, health education, self-management support by patients and caregivers, and collaboration among caregivers [ 5 , 6 ]. The integrated care provided for patients with T2DM and HTN in Slovenia is generally of high quality. However, the implementation of self-management support is only weakly developed [ 7 ]. The provision of self-management support for T2DM and HTN requires the ongoing engagement and motivation of patients, which cannot be adequately addressed by the healthcare system alone [ 8 , 9 ]. Consequently, the focus of patient-centered care should shift from healthcare institutions to the patient’s local and home environment [ 10 ]. One potential solution is the introduction of peer support by appropriately trained lay people, which would empower patients, family members and other informal caregivers in the local community [ 7 ]. This form of collaboration between peer supporters, patients, healthcare providers, and the local community is not yet established in Slovenia. Therefore, there is a necessity to investigate and implement this approach to scale-up integrated care for individuals with T2DM and HTN.

Patients are well-suited for the role of volunteer peer supporters because they can share first-hand knowledge, similar experiences and lifestyle issues with others who have the same chronic disease. As they operate within the local community, there are no demographic, language or cultural barriers between them. Peer supporters do not possess medical qualifications; rather, their role is to complement health services by providing practical assistance to individuals living with the same chronic disease. This assistance encompasses a range of activities, including offering guidance on coping with daily life, creating a supportive emotional and social environment, and providing ongoing support to assist with the lifelong needs of disease self-management [ 11 , 12 , 13 ]. Several systematic reviews have demonstrated that peer support interventions significantly improve glycaemic outcomes in adults with T2DM who receive such support [ 14 , 15 , 16 ]. A systematic review and meta-analysis on the effects of peer support interventions on other cardiovascular disease risk factors in adults with T2DM found a positive effect only on recipients’ systolic blood pressure (SBP) but not on diastolic blood pressure (DBP), cholesterol, body mass index (BMI), diet, or physical activity [ 17 ].

Training and coordinating peer supporters is crucial for the success of the peer support intervention, as it is essential that peer supporters have the knowledge and experience to effectively assist others [ 11 , 12 ]. The main problem is the lack of studies describing training models that provide comprehensive knowledge and enhance the ability of peer supporters to support self-management. The literature predominantly focuses on the peer support intervention itself and only a handful on peer supporter’s training, changes in knowledge, skills acquired [ 19 , 20 , 21 ] or impact on health outcomes [ 22 ]. There is a lack of guidelines in the methodology of training programme, including recruitment strategies, materials used, individuals delivering the training and duration of the training [ 11 , 12 , 18 , 21 , 23 , 24 ].

The primary objective of this study was to assess the feasibility and acceptability of a specialist nurse-led structured self-management training programme for peer supporters with T2DM, with or without comorbid HTN, at the primary healthcare level in Slovenia. Additionally, the study aimed to determine the improvement in peer supporters in terms of changes in their acquired knowledge about T2DM and HTN, quality of life and clinical outcomes.

Study design and settings

This was a prospective pre-post interventional pilot study conducted in two Community Health Centres (CHCs) in Slovenia. The initial criteria for the selection of the CHCs was based on the objective of ensuring both urban and rural settings. The CHC Ljubljana is situated in the largest municipality and capital city of Slovenia. It serves approximately 300,000 residents and is representative of an urban setting, contributing 38.4% of Slovenia's total GDP in 2022. In contrast, CHC Slovenj Gradec, located in the smallest municipality in Slovenia, serves an estimated population of 17,000 residents, representing a rural region. This CHC contributed 6.4% of Slovenia's total GDP in 2022 [ 25 ]. This approach considered the different cultural and social environments in urban and rural areas, and acknowledged that distinct forms of peer support are acceptable in each setting [ 26 ].

The study was nested within a larger parent study, which spanned from May 2021 to December 2023. Its objective was to develop an evidence-based model of peer support for people with T2DM, with or without comorbid HTN, at the primary healthcare level in Slovenia. The peer support intervention was a prospective, mixed-methods pilot study that commenced with the recruitment of eligible individuals with T2DM and HTN through purposive sampling, with the objective of training them as peer supporters via specialist nurse-led structured self-management training. Each trained peer supporter voluntarily shared their knowledge and experience at monthly group meetings with up to 10 people with T2DM and HTN over a three-month period in the local community. Data was collected through series of interviews, focus groups, and questionnaires to evaluate the role of peer support. This involved introducing trained peer supporters, determining the relationships between peer support and patient-reported quality of life and level of empowerment, and assessing the acceptability and feasibility of the peer support intervention [ 27 ].

The study was approved by the National Medical Ethics Committee (reference number 0120–219/2019/4, approved on 24 May 2019).

Participants and recruitment

Purposive sampling was employed to recruit eligible patients with T2DM, with or without comorbid HTN, from two CHCs by registered nurses and family medicine physicians. These patients were interested in serving as volunteer peer supporters. The purposive sampling method ensured that the recruited participants were suitable for the peer supporter role based on their responsibility, confidence, communication skills and willingness to collaborate with an educator from the CHC. It is important to note that peer supporters should be aware that they are not medical professionals and should not attempt to provide medical treatment or diagnosis. In the event that a situation arises that is beyond the scope of their knowledge and experience, it is recommended that they refer the recipient of peer support to a healthcare professional for appropriate care [ 27 ].

Inclusion criteria were as follows: i) a confirmed diagnosis of T2DM with fasting blood glucose (BG) value ≥ 7.0 mmol/l or venous plasma glucose ≥ 11.1 mmol/l two hours after glucose tolerance test or at any random opportunity, or glycated haemoglobin (HbA1c) ≥ 6.5% [ 28 ], ii) with or without comorbid HTN with a 7-day mean home BP values ≥ 135/85 mmHg or with 24-h blood pressure monitoring mean ≥ 130/80 mmHg [ 29 ], iii) for a duration of at least one year. This was deemed necessary in order to ensure that participants have had sufficient time to adapt to their diagnosis, understand their treatment regimen, and develop a baseline level of disease management.

Exclusion criteria included: type 1 diabetes or gestational diabetes, < 18 years of age and a documented diagnosis of cognitive decline obtained from the participant’s medical records. This diagnosis was based on comprehensive assessments of the individual’s clinical presentation, medical history, and relevant test results conducted by family physicians and other healthcare professionals.

Participation in the study was voluntary. All participants received an explanation of the study objectives and a participant information sheet that provided additional information. To participate in the study, it was obligatory to sign the informed consent form.

Structured self-management educational training

The self-management training was designed to empower peer supporters and equip them with comprehensive knowledge of T2DM and HTN and communication skills to provide effective peer support to other patients with T2DM, with or without comorbid HTN. The training was led by an educator with the expertise of a registered nurse with specialised knowledge in the field of health education of people with T2DM—a specialist nurse. There was ongoing consultation with the mentor-educator throughout the training, who remained their mentor while providing peer support, either in person, by telephone or by email. In addition, a specialist nurse actively promoted the awareness and value of peer support, thereby reducing the spread of misinformation and concerns about recommending it [ 11 , 17 ].

The training lasted a total of 15 h over a period of 2 months and consisted of four group sessions and two individual sessions. The training was organised in small groups of 6–10 candidates and conducted in accordance with the T2DM education [ 30 ] and treatment [ 28 ] guidelines. To ensure a consistent programme, each educator led the training based on the comprehensive curriculum (Table 1 ). To provide a comprehensive and interactive verbal and visual learning experience and to facilitate T2DM self-management through a patient-centred approach, the educators used Diabetes Conversation Maps™. Several well-established models of health behavior, such as the Biopsychosocial Model of health and illness, were considered in the development of this effective health education tool [ 31 ].

After the group sessions, participants had two individual sessions with the educator, a specialist nurse. The focus was on analysing the themes from the group session (Table 1 ), reviewing the self-monitoring diary of BG and BP, assessing the knowledge gained and discussing the aims of voluntary peer support, the role of a trained peer supporter and opportunities of organising peer group meetings, and ways of further collaboration with healthcare professionals, patients, and the local community. Throughout the training, the educator taught participants how to communicate assertively and used motivational and coaching techniques to approach volunteering and working with people. At the end of the 15-h training, each participant was given four different Conversation Maps™ and a honorary certificate of the acquired title of “trained peer supporter” and CHC ambassador at the award ceremony to ackowledge the completion of the training, and to acknowledge the participants’ efforts [ 27 ]. The study flow chart is presented in Fig. 1 .

Study flow chart (n, number; T2DM, type 2 diabetes mellitus; HTN, hypertension; CHC, Community Health Centre)

Theoretical intervention model

The theory of change underlying the intervention was based on the hypothesis that training peer supporters would influence their knowledge, perceptions, and intentions, which in turn would lead to changes in self-management behavior and ultimately improved health outcomes. This would also enable effective delivery of peer support, resulting in behavior change and health benefits among people with T2DM, with or without comorbid HTN, receiving peer support. The theory of planned behavior [ 32 ] was used to predict and explain behavior change. Our pilot study protocol is schematically presented in Fig. 2 , outlining its objectives in terms of feasibility, acceptability, and effectiveness (in the study group). The ongoing collaboration between trained peer supporters, people with T2DM, with or without comorbid HTN, caregivers in the local community, and healthcare professionals aims to make them partners in health and care.

Schematic presentation of the pilot study and the theory of change framework (HTN –hypertension; T2DM – type 2 diabetes mellitus)

Instruments and data collection

The study lasted from May 2021 to August 2022. Data were collected from medical records, clinical measurements were conducted by a registered nurse at both the pre- and post-intervention stages, and structured questionnaires were completed by the peer supporters at entry into the study (baseline) and after completing the training. At the conclusion of the training, peer supporters were invited to complete an evaluation form as the sole method to provide qualitative feedback with quotations on their overall satisfaction with the training. Variables were observed across several categories (Table 2 ).

Participants underwent anthropometric and biochemical measurements at baseline and 6 months after completing the training. Measurements were performed by a registered nurse at CHC using a validated scale and blood pressure monitor. SBP and DBP were measured as recommended in the guidelines [ 29 ]. HbA1c level and fasting BG value were determined using peripheral venous blood sampling. To assess the acceptability of the healthcare intervention Sekhon et al. developed the TFA tool (Table 3 ) [ 33 ]. Specifically, we used a 19-items TFA questionnaire (Appendix 1) developed by Timm et al. [ 34 ], which covers all 7 domains of acceptability based on the TFA tool: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy [ 33 ]. Each item is rated on a 5-point Likert scale, the score for each of the 7 domains and the total score range between 1 and 5. To assess knowledge about HTN and T2DM, we used validated Slovenian versions of the Hypertension Knowledge Test (HKT) [ 35 ] with 11 true/false questions and the first 14-item questionnaire of the Diabetes Knowledge Test (DKT) [ 36 ], the result of both is between 0 and 100%. The Appraisal of Diabetes Scale (ADS) [ 37 ] was used to assess the individual’s appraisal of T2D, which is diabetes-specific indicator of quality of life [ 38 ], consists of 28 items on a 5-point Likert scale yielding the final score between 7 and 35 where lower score is better.

Sample size elaboration

We employed purposive sampling method to recruit approximately 40 eligible individuals (30 from CHC Ljubljana and 10 from CHC Slovenj Gradec) with T2DM, with or without comorbid HTN, to become volunteer peer supporters. Each peer supporter was expected to share their knowledge and experience with around 10 patients with the same chronic condition in their local community, potentially providing support to up to 400 patients. Considering an estimated dropout rate of 20%, we anticipated that 32 peer supporters would remain, each supporting a group of 8 patients, resulting in 256 patients receiving peer support. The power analysis was done for the sample size of patients receiving peer support for the two outcomes in that larger parent study. Specifically, for the ADS score, a planned sample size of 256 patients achieves 80% power to detect a mean difference (between pre- and post-intervention) of 1.6 using two-tailed paired samples t-test, assuming the SD of differences of 9.3 (this represents the largest possible SD if the differences in ADS scores are normally distributed, given their range is at most [-28,28]) [ 27 ].

Statistical analysis

We summarised categorical variables with frequencies and percentages, and numerical variables with means and standard deviations (SD) or medians and interquartile ranges (IQR) in the case of asymmetric distributions (determined by Shapiro–Wilk normality test and visual inspection of graphs). To compare numerical variables between pre- and post-intervention, we used paired-samples t -test (together with 95% confidence interval (CI) for the mean difference) or Wilcoxon signed-rank test in the case of asymmetric distributions. A p -value of < 0.05 was considered statistically significant.

Of 36 patients (10 from CHC Slovenj Gradec and 26 from CHC Ljubljana) with T2DM, with or without comorbid HTN, recruited for the study, 31 (86.1%) attended all meetings, successfully completed the specialist nurse-led training, and became trained peer supporters. All the results are for the sample of 31 trained peer supporters.

Sociodemographic data and clinical history

The basic socio-demographic characteristics of the 31 trained peer supporters are shown in Table 4 . Among them, 21 (67.7%) were women, with a mean age of 63.9 (SD 8.9) years. They had all been treated for T2DM for a median duration of 15.0 years (IQR 5.0 – 20.5). As a comorbidity, 24 (77.4%) peer supporters had HTN. The median duration of treatment was 8.5 years (IQR 2.8 – 18.2). Of the 31 trained peer supporters, 7 (22.6%) were treated non-pharmacologically with diet and exercise, 13 (41.9%) with hypoglycaemic agents, 5 (16.1%) with a combination of hypoglycaemics and insulin, and 6 (19.3%) with insulin alone.

Acceptability of the self-management educational training

Participants rated the training as highly acceptable in all 7 domains, with median scores ranging from 4.0 to 5.0 and the lowest first quartile being 4.0 (Table 5 ). The median total score was 4.5 with IQR (4.1 – 4.7).

Peer supporters’ satisfaction with educational training

Some of the quotations from the evaluation forms highlight the satisfaction with the training: “It is fascinating how much I have learned about both diseases, even though I have been living with T2DM and HTN for years;” “I can always contact my educator by mail or phone if I have a problem;” “The training encouraged me to continue with a healthy lifestyle and to take greater control of my health;” “This programme gave me additional motivation to maintain my health and to share my experiences with others;” “I believe that the Conversation Maps are great; when I showed them at home, the words about T2DM just rolled out of my tongue.”

Knowledge about T2DM and HTN

After completing the training, knowledge of T2DM and HTN increased significantly ( p < 0.001 and p = 0.024, respectively). The mean knowledge of T2DM at baseline was 72.9% (SD 15.6%, median 79.0%, IQR (64.0% – 86.0%)), the mean difference in knowledge of T2DM was 9.4% (SD 12.9%, median 8.0%, IQR (0.0% – 14.5%)) with 95% CI for the mean difference (4.7%, 14.1%). The median knowledge of HTN at baseline was 91.0% with IQR (77.5% – 91.0%), the median difference in knowledge of HTN was 0.0% but with IQR (0.0% – 9.0%).

Quality of life

Quality of life with T2DM was not significantly better after the completed training ( p = 0.066). Participants' perceived burden of T2DM decreased from a mean score of 16.1 (SD 3.5) to 14.8 (SD 4.2) after the training (lower ADS score is better), the 95% CI for the mean difference was (-0.1, 2.7).

Clinical outcomes

The mean anthropometric and biochemical measurements at baseline and 6 months after completion of the training are shown in Table 6 . Peer supporters' weight decreased significantly ( p = 0.022) from 85.8 (SD 19.5) kg at baseline to 84.2 (SD 20.0) kg 6 months after training, and BMI decreased from 30.4 (SD 6.2) to 29.8 (SD 6.2) ( p = 0.020). Changes in fasting BG, HbA1c, SBP and DBP were not significant.

Our pilot study indicates that specialist nurse-led self-management training for peer supporters is feasible, acceptable, effective (in the study group), and highly valued by participants. The training enabled peer supporters to acquire knowledge about T2DM and HTN and equipped them with self-management skills to effectively support other people with the same chronic condition by sharing first-hand knowledge, similar experiences and lifestyle issues. Our study was unique in measuring changes in clinical measures of peer supporters in primary care settings. Peer supporters were successful in maintaining disease control and making positive changes in their self-management behaviours, as reflected in the reduction in their BMI over the six-months following the training.

The literature has not used rigorous approaches to recruit appropriate peer supporters [ 19 , 21 ]. Recruitment has mainly been done through referrals from healthcare professionals based on candidate interest in volunteering and diagnosis of T2DM as inclusion criteria [ 21 , 39 ]. In contrast to our study, some listed inclusion criteria of acceptable glycemic control (HbA1c ≤ 8.5%) [ 21 , 23 , 39 , 40 ], which could increase the retention rate and improve the chances of success [ 21 ]. We used the purposeful sampling method to ensure that recruited participants were suitable for the peer supporter role. Recruitment of peer supporters should emphasize the importance of their personal experience with the same chronic condition as people they will be supporting. This unique perspective allows them to better understand and empathize with the challenges that their support recipients are facing [ 12 ]. We believe it is important to promote this uniqueness when recruiting peer supporters, as it can help to build trust and confidence in the support programme.

There is limited data on the socio-demographic characteristics of peer supporters; most were female and had at least a high school education [ 21 , 39 , 41 , 42 ], which is consistent with the findings of our study. Most of our trained peer supporters were retired, had a longer duration of T2DM and were older than in other studies [ 21 , 39 , 43 ]. In one study, 90% of peer supporters were unemployed [ 43 ]. The Slovenian peer supporters were mainly older, disease-experienced individuals who were no longer involved in the daily stress of work. They rated the training as very acceptable. Participating in the training was effortless for them, it fitted well with their life beliefs and values, and they understood the process of the whole intervention. They felt empowered and confident in their ability to transfer the knowledge and skills they had acquired to other patients.

There are no clear recommendations on who should lead the training of peer supporters (nurse educator, multidisciplinary team, research expert, etc.) and how long the training should last (from a few hours to several months) [ 12 , 18 , 19 , 20 , 24 , 39 , 42 ]. Training programmes were mostly based on a structured curriculum [ 12 , 18 , 20 , 21 , 23 , 40 ]. Teaching methods included role-playing [ 12 , 20 , 21 , 43 ], brainstorming, group facilitation simulations [ 20 ], PowerPoint presentations [ 12 ], training booklets [ 19 , 21 ], and Conversation Maps™ [ 19 ]. We used four different Diabetes Conversation Maps™ as teaching tools, and trained peer supporters were given the same collection of four Maps™ to bring to peer support meetings after completing the training. These maps are designed to be interactive and engaging, encouraging participants to talk about the challenges of living with T2DM and HTN, to share their stories, knowledge and experiences, and to emphasise the importance of medication adherence, healthy lifestyles and regular check-ups with healthcare professionals. The maps help to create a structured and supportive environment where participants can learn from each other and feel empowered to take control of their disease management [ 31 , 44 ]. Our detailed self-management training programme (Table 1 ) makes the lesson preparation transparent and allows for replication when designing future interventions.

Consistent with the findings of our pilot study, other studies have also shown that the development of self-management educational training leads to improved knowledge of T2DM among peer supporters [ 19 , 43 ]. Six months after the training, peer supporters' weight and BMI decreased significantly compared with baseline measurements. There were no significant differences in the measurements of fasting BG, HbA1c, SBP and DBP after six months, nor were the changes that occurred clinically significant. We did not expect clinically significant changes in such a short period of time, as we believe that a longer study period is needed to detect significant changes. In addition, the peer supporters already had well-controlled clinical parameters at baseline. The results are still relevant as they show that patients were able to maintain their disease control and even improve some clinical parameters over the six-month period. Peer supporters who can model healthy behaviours and share their own experiences of disease management may be more effective in helping others to make positive changes in their own lives. To our knowledge, only Yin et al. have investigated the effects of peer support on the health of peer supporters. However, their study was conducted in hospital-based diabetes clinics and involved a multidisciplinary team to train the peer supporters, unlike our primary care setting. They found improvements in peer supporters self-care behaviours and maintenance of their glycaemic control over 4 years [ 22 ].

The actual implementation of our research depends on the willingness and motivation of individuals to provide peer support voluntarily, so a gradual decline in motivation and in some cases withdrawal can be expected [ 11 ]. We recognised the importance of acceptability in the evaluation of the healthcare interventions [ 33 ]. Participants assessed our training as highly acceptable and satisfactory. Consequently, we found that participation in the training was high and consistent, with 86.1% of patients successfully completing the training and becoming trained peer supporters. The reasons for dropping out were all external, such as changes in personal or family health status, rather than dissatisfaction with the programme or its content. The demographic and clinical characteristics of the non-completers were diverse, supporting the assertion of external reasons for dropping out (they were aged 57–77 years, with a gender split of 3 women and 2 men, 4 were retired and 1 was still working, 4 had completed secondary school and 1 university, had been managing T2DM for a range of 5–30 years, with only 2 having HTN as a comorbidity). In the study by Chan et al. 74.7% completed the training and 41.8% agreed to continue providing peer support [ 39 ]. In a study by Afshar et al., the retention rate among peer leaders ranged from 56 to 88% [ 21 ]. To overcome this problem, it is important to focus on engagement and recognition strategies, such as good communication, collaboration among stakeholders and a clear presentation of the benefits of peer support [ 11 ]. The future connection and collaboration between trained peer supporters, patients, family members, caregivers in the local community and health professionals could make them partners in health and care. Together they could achieve the ultimate goal of a comprehensive, patient-centred approach: empowering individuals to take an active role in managing their illness and achieving their health goals [ 45 ].

Strengths and limitations

Peer supporters are becoming an integral part of diabetes management. This study addresses an important gap in person-centred diabetes care by providing new insights into the feasibility and acceptability of a training programme for peer supporters. To ensure that the intervention is well organised, effective and sustained, emphasis needs to be placed on recruiting, training and retaining peer supporters for ongoing effective self-management and support of others with the same chronic condition. This can be achieved through several key strategies, including purposive sampling to select suitable candidates for the peer supporter role, the involvement of a mentor-educator to provide ongoing support and supervision, regular evaluation and monitoring of the training to identify challenges and areas for improvement, and the acknowledgement of peer supporters with honorary titles and certificates. The study provided valuable insights that could contribute to the successful implementation of peer support training interventions in diabetes care.

Our study has several limitations. Firstly, the lack of a control group of potential peer supporters who did not attend the training makes it impossible to estimate the real effectiveness of the training programme, and further research with a control group is needed. We decided not to use a control group due to our limited sources and our goal to train as many peer supporters as possible in a short period of time. Secondly, the use of the same DKT and HKT questionnaires at the beginning and the end of the two-month training means that participants already knew the questions, which could influence their actual knowledge. However, previous studies showing improved knowledge of T2DM after training [ 19 , 43 ], also repeated the same test, suggesting that question familiarity is not predictive of the second test results. Thirdly, it is not possible to measure the long-term effects as the questionnaires were only measured after the training was compiled, and clinical outcomes were only measured 6 months after the training. Fourthly, we cannot say that 15 h of training is sufficient. Therefore, a follow-up evaluation is needed to examine retention and acquisition of skills and knowledge for ongoing peer support intervention. Fifthly, in anticipation of a small sample size and difficulty in recruiting a large enough sample of participants with both T2DM and HTN who were willing to become peer supporters, we included in the pilot study all individuals with a confirmed diagnosis of T2DM, regardless of whether they had comorbid HTN. In addition, the use of purposive sampling introduces potential bias and limits the generalisability of the findings. Finally, we did not formally evaluate the teaching effectiveness or information transfer skills of the peer supporters. However, to the best of our knowledge, no studies [ 11 , 12 , 18 , 21 , 23 , 24 ] have included teaching skills in peer support training programmes, as the focus has been on practical and experiential skills that are crucial for managing their condition.

Conclusions

The structured self-management training for peer supporters, led by a specialist nurse, was found to be highly acceptable, effective (in the study group), and feasible, indicating significant potential for scaling-up integrated care for people with T2DM, with or without comorbid HTN, at the primary healthcare level in Slovenia. Trained peer supporters improved their knowledge and gained self-management skills, leading to positive changes in their behaviour, as evidenced by a decrease in their BMI over six months. The training programme enabled them to effectively support others with the same chronic condition by sharing first-hand knowledge, similar experiences, and lifestyle advice. However, further research is needed to confirm the true effectiveness of the training programme with a control group and to improve the quality of the peer support provided.

Availability of data and materials

The datasets generated and/or analyzed during the current study are not publicly available because the data is part of an unpublished dissertation but are available from the corresponding author upon reasonable request.

Abbreviations

Type 2 diabetes mellitus

Hypertension

Community Health Centres

Body mass index

Systolic blood pressure

Diastolic blood pressure

Blood glucose

Glycated haemoglobin

Appraisal of Diabetes Scale

Theoretical Framework of Acceptability

Diabetes Knowledge Test

Hypertension Knowledge Test

Standard deviation

Interquartile range

Confidence interval

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Acknowledgements

We want to thank all peer supporters who participated in this study.

The research is part of the international research project SCUBY, funded from the European Union’s Horizon 2020 programme under grant agreement number 825432. The funding is not involved in study design, data collection, analysis and interpretation of data, writing of the paper or decision to submit the article for publication.

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Tina Virtič Potočnik, Matic Mihevc, Črt Zavrnik, Majda Mori Lukančič, Nina Ružić Gorenjec, Antonija Poplas Susič & Zalika Klemenc-Ketiš

Faculty of Medicine, Department of Family Medicine, University of Maribor, Taborska 8, 2000, Maribor, Slovenia

Tina Virtič Potočnik & Zalika Klemenc-Ketiš

Faculty of Medicine, Department of Family Medicine, University of Ljubljana, Poljanski Nasip 58, 1000, Ljubljana, Slovenia

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TVP, MML, TPS, ZKK, MM and ČZ were responsible for study conception and design. MML and TVP performed the data collection. TVP and NRG contributed to the data analysis and interpretation. TV drafted the manuscript under the supervision of ZKK. To ensure the quality of the study MM, ČZ, NRG, TPS, MML and ZZK made critical revisions to the paper. All authors read and approved the final manuscript.

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Virtič Potočnik, T., Mihevc, M., Zavrnik, Č. et al. Evaluation of a specialist nurse-led structured self-management training for peer supporters with type 2 diabetes mellitus with or without comorbid hypertension in Slovenia. BMC Nurs 23 , 567 (2024). https://doi.org/10.1186/s12912-024-02239-7

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The Unexpected Superfood for Diabetes: Scientists Identify New Health Benefits of Potatoes

Nutrition sciences professor Neda Akhavan’s recent research identifies potatoes as a potential superfood for individuals with Type 2 diabetes.

New research reveals that properly prepared potatoes can offer significant health benefits, including cardiovascular improvements, for people with Type 2 diabetes, challenging their negative dietary reputation.

The potato is small enough to fit inside a person’s hand yet contains enough nutrients to whittle waistlines and lower blood sugar in adults with Type 2 diabetes. Yet, despite the fact that potatoes – particularly the skins – are packed with health-boosting nutrients, they routinely get a bad rap among dieters.

That may soon change, thanks to new research by Neda Akhavan, assistant professor in the Department of Kinesiology and Nutrition Sciences within UNLV’s School of Integrated Health Sciences . Akhavan recently presented her findings on the cardiovascular benefits of potatoes for those living with Type 2 diabetes to the Alliance for Potato Research and Education.

“I like doing research on food items that are highly stigmatized in the nutrition world,” she said. “Most people associate the potato as something that is mostly fried or has a lot of fat, and we wanted to shine a light on how a potato – when prepared properly – can be both functional and healthy.”

Putting Potatoes to the Test

Akhavan enlisted 24 participants for the study , all of whom had Type 2 diabetes that was well controlled with medication. Funded by the Alliance for Potato Research and Education, this is believed to be the first study of its kind to scientifically measure the cardiovascular benefits of potatoes for adults with diabetes.

Participants in the study group were each given a pre-prepared baked potato with the skin measured to 100g, with only 20 grams of carbohydrates, roughly enough to fit in one hand to incorporate as a snack or side with meals daily. The control group was given a similar potion of white rice with the same number of calories and carbohydrates. The study ran daily for 12 weeks, which is considered the minimum time needed to see changes in indices of glycemic control and cardiometabolic health.

Study participants were permitted to add herbs or spices to the potatoes, or up to ½ tbsp of butter, but they were advised not to fry their potato.

Key Takeaways and Recommendations

A modest decrease in fasting blood glucose levels was present for study participants who ate potatoes. Study participants also showed improvements in body composition, waist circumference, and a decrease in resting heart rate.

“The results from our study provide evidence that white potatoes can be healthfully incorporated in the diet of individuals with Type 2 diabetes when substituted for other foods with a high glycemic load, such as long-grain white rice,” Akhavan said. “Additionally, there were no harmful effects on measured health outcomes, and some cardiometabolic health benefits were shown, which aligned with what we expected to see. Therefore, diabetics should not shy away from potatoes.”

Akhavan says that just like all foods, moderation – and preparation methods – are key.

“Potatoes are a very versatile food and can be eaten with most types of cuisines, but you want to make sure to incorporate them into a well-rounded diet,” she said. “For those tight on time, consider making a large batch of baked or roasted potatoes and meal prep to last you a while. I’m not against boiling potatoes, but you want to keep as much of the potassium from the skin as you can, and you lose some of that when you boil them.”

Making the Case for Potatoes

Potatoes are the richest source of dietary potassium in Western diets, and high-potassium diets have been shown to prevent high blood pressure and Type 2 diabetes development. Additionally, potato skins contain a certain type of fiber called “resistance starch,” which has been shown to improve glucose control, lipid profiles, and satiety. Because of these added health benefits, Akhavan recommends eating potatoes with the skin.

So, the next time you want to reach for a banana, she added, reach for that potato instead.

“A lot of people are shocked to learn that a potato has a higher level of potassium than a banana,” she said. “Believe it or not, a baked potato is one of the most satiating foods consumed within the western diet. And, when it is consumed baked, it increases our ability to feel fuller throughout the day.”

Akhavan intends to expand the study in the coming months to include a larger and more diverse participant population, and incorporation of potatoes within a Mediterranean dietary pattern. She also plans to explore the role of potato consumption and its effects on dietary patterns and related health benefits.

Meeting: NUTRITION 2024

The research was funded by the Alliance for Potato Research and Education.

Making this simple dietary change could significantly reduce your risk of diabetes and cancer, concerning: drinking 100% fruit juice could increase young boys’ risk of diabetes, first-of-its-kind study: plant-based diets improve metabolic, liver, and kidney health, is intermittent fasting safe and effective for diabetics, low-frequency intermittent fasting helps fight inflammation, warning: excess consumption of eggs linked to diabetes, new research targets our second brain to fight diabetes, zero-calorie sweeteners linked to dramatic increase in diabetes and obesity, new study shows fructose alters brain genes, which can lead to disease.

Funded by the Alliance for Potato Research and Education,

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August 13, 2024

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New molecular insights into bariatric surgery's impact on obesity and type 2 diabetes

by Susann-C. Ruprecht, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

Researchers from the German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) and the German Center for Diabetes Research (DZD) have published a study in Diabetes & Metabolism that sheds light on the molecular adaptations occurring in skeletal muscle following bariatric surgery, particularly in individuals with and without type 2 diabetes.

Bariatric surgery is a widely recognized intervention for obesity management. The medical intervention alters the digestive system to limit the amount of food that can be eaten or absorbed or affect hunger via the incretin system, thereby promoting significant and sustained weight loss. Bariatric surgery is typically considered for individuals who have not achieved long-term weight loss through diet and exercise.

It is known that during the development of type 2 diabetes (T2D), epigenetic alterations (DNA methylation and hydroxymethylation) occur in skeletal muscle , a key tissue taking up glucose in response to insulin. However, it is unclear to what extent these alterations are reversible through interventions such as bariatric surgery .

Linking clinical outcomes to transcriptome and epigenome

Therefore, an interdisciplinary DZD team including the researchers Leona Kovac, Annette Schürmann and Meriem Ouni from the DIfE as well as Sabine Kahl and Michael Roden from the German Diabetes Center (DDZ) investigated the effects of surgically induced weight loss on metabolic, transcriptional, and epigenetic adaptations in skeletal muscle of obese individuals with and without T2D by using a comprehensive bioinformatic approach.

Additionally, multidimensional links between molecular and metabolic changes induced by bariatric surgery were explored. These links aimed at identifying novel prominent candidates associated with weight loss and improved muscle function.

The examined individuals were a subset of participants from the BARIA_DDZ cohort study, which closely monitors individuals through detailed metabolic characterization both before and over five years following bariatric surgery.

The study described here focused on the metabolic and molecular outcomes achieved during the first year. In total, 13 male participants with obesity (OB) and 13 participants with OB and T2D underwent an extensive anthropometric and metabolic investigation including a muscle biopsy and detection of tissue-specific insulin sensitivity before and one year after surgery.

Perturbed epigenetic flexibility

DZD researchers found distinct molecular responses in skeletal muscle following bariatric surgery between obese individuals and those with additional T2D. Before surgery, obese T2D participants exhibited higher fasting glucose and insulin levels alongside lower insulin sensitivity compared to OB. Following surgery, improvements in metabolic health were more pronounced in OB, reflected by differential gene expression patterns related to insulin signaling, intracellular signal transduction, and oxidative phosphorylation.

In contrast, obese T2D participants showed alterations only in genes associated with ribosome and spliceosome pathways, with less pronounced changes in DNA methylation, potentially linked to altered expression of one of the T2D risk genes involved in the demethylation processes.

Tailoring of individual therapies

These findings underscore the importance of understanding molecular adaptations in skeletal muscle post-bariatric surgery, particularly in individuals with type 2 diabetes. "Our study suggests that epigenetic mechanisms play a crucial role in mediating these responses and predicting the health outcome," states Dr. Ouni.

"Our future research will investigate the molecular mechanisms underlying changes in DNA hydroxymethylation and its potential function in skeletal muscle post-surgery. Furthermore, we aim to validate specific candidates identified by the bioinformatic approach as potential therapeutic targets in muscle," emphasizes Prof. Dr. Schürmann, Head of the Department of Experimental Diabetology at DIfE. In this manner, approaches for individuals with different metabolic profiles could be tailored.

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'New Era' in Insulin Possible if Research Successful

Miriam E. Tucker

August 15, 2024

A multi-institutional partnership has funded six new research projects aimed at developing novel insulin analogs that more closely mimic the action of a healthy pancreas.

The Type 1 Diabetes Grand Challenge comprises Diabetes UK, JDRF (now called "Breakthrough T1D" in the United States), and the Steve Morgan Foundation. It will provide a total of £50 million (about $64 million in US dollars) for type 1 diabetes research, including £15 million (~$19 million) for six separate projects on novel insulins to be conducted at universities in the United States, Australia, and China. Four will aim to develop glucose-responsive "smart" insulins, another one ultrafast-acting insulin, and the sixth a product combining insulin and glucagon.

"Even with the currently available modern insulins, people living with type 1 diabetes put lots of effort into managing their diabetes every day to find a good balance between acceptable glycemic control on the one hand and avoiding hypoglycemia on the other. The funded six new research projects address major shortcomings in insulin therapy," Tim Heise, MD, vice-chair of the project's Novel Insulins Scientific Advisory Panel, said in a statement from the Steve Morgan Foundation.

All six projects are currently in the preclinical stage, Heise told Medscape Medical News , noting that "the idea behind the funding program is to help the most promising research initiatives to reach the clinical stage."

Glucose-responsive, or so-called "smart" insulins, are considered the holy grail because they would become active only to prevent hyperglycemia and remain dormant otherwise, thereby not causing hypoglycemia as current insulin analogs can. The idea isn't new. In 2010, there was excitement in the type 1 diabetes community when the pharmaceutical company Merck acquired a smaller company called SmartCells that had been working on a "smart insulin" for several years. But nothing came of that.

"The challenges then and today are pretty similar. In particular, it is quite difficult to find a glucose-sensing moiety that is safe, reacts sufficiently to relatively small changes in the human body in both falling and increasing glucose, and can be produced in large quantities," Heise, lead scientist and co-founder of the diabetes contract research organization Profil, based in Neuss, Germany, told Medscape Medical News .

Several papers since have reported proof-of-concept in rodents, but there are no published data thus far in humans. However, in recent years the major insulin manufacturers Novo Nordisk , and Eli Lilly have acquired smaller companies with the aim of smart insulin development.

It will still take some time, Heise said. "The challenges are well understood, although difficult to overcome. There has been quite some progress in the development of glucose-sensing moieties including, but not limited to, nanotechnological approaches."

Applications for the newly funded projects "were thoroughly reviewed by a large panel of scientists with different areas of expertise. At the end, there was agreement in the review panel that these projects deserved further investigation, although considering their early stage, there still is a substantial risk of failure for all these projects," he told Medscape.

The development path might be a bit more straightforward for the other two projects. Ultra–fast-acting insulin is needed because the action of the current ones, Novo Nordisk's Fiasp and Eli Lilly and Company's Lyumjev, is still delayed, potentially leading to postmeal hyperglycemia if administered after or immediately prior to eating. "A truly rapid short-acting insulin might make it finally possible to progress from hybrid to fully closed loop systems, allowing a technological 'cure' for people with diabetes," Heise said in the statement.

And a protein combining insulin with glucagon could help minimize the risk for hypoglycemia, which still exists for current insulin analogs and remains "one of the major concerns associated with insulin therapy today," he noted.

Heise told Medscape Medical News that compared with "smart" insulin, development of the other two products "might be a bit faster if they succeed. But none of these approaches will make it to market in the next 5 years, and if one entered clinic within the next 2 years, that would be a huge success." Nonetheless, "these research projects, if successful, might do no less than heralding a new era in insulin therapy."

Heise is an employee of Profil, which has worked with a large number of the major diabetes industry manufacturers.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR's Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker.

Send comments and news tips to [email protected] .

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Reversing Type 2 Diabetes: A Narrative Review of the Evidence

Sarah j hallberg.

1 Virta Health, 535 Mission Street, San Francisco, CA 94105, USA; moc.htlaehatriv@einimahs

2 Indiana University Health Arnett, Lafayette, IN 47904, USA; gro.htlaehui@nubzaht

3 Indiana University School of Medicine, Indianapolis, IN 46202, USA

Victoria M Gershuni

4 Department of Surgery, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA; moc.liamg@dminuhsregairotciv

Tamara L Hazbun

Shaminie j athinarayanan.

Background: Type 2 diabetes (T2D) has long been identified as an incurable chronic disease based on traditional means of treatment. Research now exists that suggests reversal is possible through other means that have only recently been embraced in the guidelines. This narrative review examines the evidence for T2D reversal using each of the three methods, including advantages and limitations for each. Methods: A literature search was performed, and a total of 99 original articles containing information pertaining to diabetes reversal or remission were included. Results: Evidence exists that T2D reversal is achievable using bariatric surgery, low-calorie diets (LCD), or carbohydrate restriction (LC). Bariatric surgery has been recommended for the treatment of T2D since 2016 by an international diabetes consensus group. Both the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) now recommend a LC eating pattern and support the short-term use of LCD for weight loss. However, only T2D treatment, not reversal, is discussed in their guidelines. Conclusion: Given the state of evidence for T2D reversal, healthcare providers need to be educated on reversal options so they can actively engage in counseling patients who may desire this approach to their disease.

1. Introduction

According to 2017 International Diabetes Federation (IDF) statistics, there are approximately 425 million people with diabetes worldwide [ 1 ]. In the United States, there are an estimated 30.3 million adults living with diabetes, and its prevalence has been rising rapidly, with at least 1.5 million new diabetes cases diagnosed each year [ 2 ]. Diabetes is a major public health epidemic despite recent advances in both pharmaceutical and technologic treatment options.

Type 2 diabetes (T2D) has long been identified as an incurable chronic disease. The best outcome that has been expected is amelioration of diabetes symptoms or slowing its inevitable progression. Approximately 50% of T2D patients will need insulin therapy within ten years of diagnosis [ 3 ] Although in the past diabetes has been called chronic and irreversible, the paradigm is changing [ 4 , 5 ].

The recent 2016 World Health Organization (WHO) global report on diabetes added a section on diabetes reversal and acknowledged that it can be achieved through weight loss and calorie restriction [ 4 ]. “Diabetes reversal” is a term that has found its way into scientific articles and the lay press alike; “remission” has also been used. While the exact criteria are still debated, most agree that a hemoglobin A1c (HbA1c) under the diabetes threshold of 6.5% for an extended period of time without the use of glycemic control medications would qualify [ 6 ]. Excluding metformin from the glycemic control medications list, as it has indications beyond diabetes, may also be a consideration [ 7 , 8 ]. Likewise, terms such as “partial” (HbA1c <6.5 without glycemic control medications for 1 year) or “complete” (HbA1c <5.7 without glycemic control medications for 1 year) remission have been defined by an expert panel as more evidence accumulates that points to the possibility of avoiding the presumably progressive nature of T2D [ 9 ]. It is important to note that the term “cure” has not been applied to T2D, as there does exist the potential for re-occurrence, which has been well documented in the literature.

Despite the growing evidence that reversal is possible, achieving reversal is not commonly encouraged by our healthcare system. In fact, reversal is not a goal in diabetes guidelines. Specific interventions aimed at reversal all have one thing in common: they are not first-line standard of care. This is important, because there is evidence suggesting that standard of care does not lead to diabetes reversal. This raises the question of whether standard of care is really the best practice. A large study by Kaiser Permanente found a diabetes remission rate of 0.23% with standard of care [ 10 ]. The status quo approach will not reverse the health crisis of diabetes.

A significant number of studies indicate that diabetes reversal is achievable using bariatric surgery, while other approaches, such as low-calorie diets (LCD) or carbohydrate restriction (LC), have also shown effectiveness in an increasing number of studies. This review will examine each of these approaches, identifying their beneficial effects, supporting evidence, drawbacks, and degree of sustainability.

2. Materials and Methods

A literature search was performed as appropriate for narrative reviews, including electronic databases of PubMed, EMBASE, and Google Scholar from 1970 through December 2018. We reviewed English-language original and review articles found under the subject headings diabetes, bariatric surgery, metabolic surgery, very low-calorie diet, calorie restriction, low carbohydrate diet, ketogenic diet, diabetes remission, and diabetes reversal. References of the identified publications were searched for more research articles to include in this review. Selected studies were reviewed and evaluated for eligibility for inclusion in this review based on their relevance for diabetes reversal and remission. Either remission or reversal needed to be discussed in the paper or the results were consistent with these terms for inclusion. Randomized clinical trials and intervention-based studies were given emphasis for inclusion.

A total of 99 original articles containing information pertaining to diabetes reversal or remission were included in this narrative review.

3. Results and Discussion

3.1. bariatric surgery.

Bariatric surgery has long been recognized as a potential treatment for both morbid obesity and the metabolic processes that accompany it, specifically T2D. While the efficacy of T2D reversal depends on the choice of procedure, there is unilateral improvement in glycemia following operation [ 11 ], and bariatric surgery has been found to be superior to intensive T2D medical management. Accordingly, in 2016, the second Diabetes Surgery Summit (DSS-II) released recommendations, endorsed by 45 medical and scientific societies worldwide, to use bariatric surgery as a treatment for T2D (bariatric surgery is currently approved by the 2016 recommendations for adults with a body mass index (BMI) >40, or >35 kg/m 2 with obesity-related comorbidities) [ 12 ]. Of interest is the consistent finding that glycemic improvements occur rapidly, often within hours to days, and precede weight loss, which likely represents the enteroendocrine responses to altered flow of intestinal contents (i.e., bile acid signaling and changes in microbiota and their metabolome) [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ].

The most commonly performed bariatric surgeries in the United States include laparoscopic and robotic Roux-en-Y Gastric Bypass (RYGB) or Sleeve Gastrectomy (SG). While surgical treatment is based on the principles of restriction and intestinal malabsorption, evidence suggests that there are more complex mechanisms at play. Bariatric surgery has consistently been shown to dramatically and rapidly improve blood glucose [ 20 ] while allowing decreased oral hypoglycemic medications and insulin use, effectively reversing diabetes in up to 80% of patients [ 21 ] in the short term. In addition to early post-operative improvement in blood glucose and insulin sensitivity, bariatric surgery has also been shown to cause alterations in GI hormone release, including ghrelin, leptin, cholecystokinin (CCK), peptide-tyrosine-tyrosine (PYY), and glucagon-like peptide 1 (GLP-1), that may impact feeding behavior via the gut–brain axis in addition to modulating euglycemia [ 22 ]. Furthermore, microbial changes in the human gut have been linked to obesity, and surgical alterations to gastrointestinal anatomy have been associated with dramatic changes in gut microbiota populations with reversion from an “obesogenic” to a lean bacterial population [ 13 , 14 , 16 , 19 , 23 , 24 ].

Long-term outcomes from bariatric surgery depend on multiple factors, including type of surgery performed, patient comorbidities, patient readiness for lifelong dietary change, and ongoing surveillance. While bariatric surgery has been demonstrated to be safe and effective overall, it is important to recognize that it is not without risks. Each patient must weigh the risks and benefits associated with untreated morbid obesity versus those associated with surgery or effective dietary management and choose accordingly. Surgery of any type can be associated with complications leading to morbidity or mortality; the complication rates have been stated to be as high as 13% and 21% for SG and RYGB, respectively. The postoperative mortality rate is 0.28–0.34% for SG and 0.35–0.79% for RYGB; in comparison, an elective laparoscopic cholecystectomy is associated with overall complication rates of 9.29% and with a 30-day mortality rate of 0.15–0.6%, depending on the series [ 25 , 26 ]. Significant complications include anastomotic leak or hemorrhage, post-operative readmission, need for reoperation, post-operative hypoglycemia, dumping syndrome, worsening acid reflux, marginal ulceration, and micronutrient deficiencies [ 25 , 26 , 27 , 28 , 29 ].

It is important to consider that while short-duration studies have shown early resolution of comorbidities following bariatric procedures, when followed for multiple decades, there may be decreased efficacy of disease resolution and increased incidence of hospital admission long-term. Long-term reversal of T2D and true glucose homeostasis remain uncertain. Weight loss after surgery is a significant predictor of a return to euglycemia post-operatively. Multiple studies have reported initial T2D remission rates as high as 80% [ 30 , 31 ], however, long-term remission is less durable. The five-year follow-up outcomes of the SLEEVEPASS RCT found complete or partial remission of T2D in 37% of SG and 45% of RYGB patients, which is similar to other studies showing long-term T2D remission in up to a third of patients [ 32 ]. In the large prospective cohort study Longitudinal Assessment of Bariatric Surgery 2 (LABS-2), the investigators found that long-term diabetes remission after RYGB was higher than predicted by weight loss alone, which suggests that the surgery itself impacts metabolic factors that contribute to disease management [ 31 ]. Similarly, the STAMPEDE trial—an RCT that followed 150 patients with T2D who were randomized to intensive medical intervention (IMT) versus IMT plus RYGB versus IMT plus SG for diabetes resolution (defined as HbA1c <6.0%) and followed for five years—revealed increased rates of T2D resolution with RYGB (29%) and SG (23%) compared to IMT alone (5%) ( Figure 1 ). The surgery cohort also demonstrated greater weight loss and improvements in triglycerides, HDL, need for insulin, and overall quality of life [ 33 , 34 , 35 ].

An external file that holds a picture, illustration, etc.
Object name is nutrients-11-00766-g001.jpg

( A ) Mean changes of hemoglobin A1c (HbA1c) from baseline to last published date for each study retrieved to represent the three methods of reversal; ( B ) mean changes of weight from baseline to last published date for each studies retrieved to represent the three methods of reversal. Note: We chose these three studies to represent the three methods of reversal based on publication date and relevance to diabetes reversal. Note that baseline characteristics differ. Surgery trial examined by sleeve gastrectomy and Roux-en-Y gastric bypass separately and were represented as sleeve and bypass in the graph. Surgery: STAMPEDE [ 34 , 35 ]. Low-calorie diets (LCD): DIRECT [ 65 , 66 ]; carbohydrate restriction (LC): IUH [ 99 , 107 ].

Despite the likelihood of improved glycemic control, there are significant financial costs for the patient, health system, and insurance companies associated with bariatric surgery (U.S. average of $14,389) [ 36 ]. Despite the high initial cost of surgery, Pories and colleagues found that prior to surgery, patients spend over $10,000 per year on diabetes medications; after RYGB, the annual cost falls to less than $2000, which represents an $8000 cost savings at the individual level [ 30 ]. Furthermore, economic analyses show that surgery is likely to be cost-effective, especially in patients who are obese [ 37 , 38 ]. In a clinical effectiveness review of the literature that included 26 trials extracted from over 5000 references, Picot et al. found that bariatric surgery was a more effective intervention for weight loss than non-surgical options; however, there was extreme heterogeneity and questionable long-term adherence to the non-surgical interventions [ 39 ]. After surgery, metabolic syndrome improved, and there were higher rates of T2D remission compared to the non-surgical groups [ 39 ]. Further, while there were improvements in comorbidities after surgery independent of bariatric procedure, there was also an increased likelihood of adverse events. While the overall event rate remained low, major adverse events included medication intolerance, need for reoperation, infection, anastomotic leakage, and venous and thromboembolic events [ 39 ].

It is imperative to consider that one of the requirements of qualifying for bariatric surgery is demonstration of at least six months of unsuccessful attempts at weight loss using traditional dietary and exercise advice according to the 2016 Recommendations [ 12 ]. There are, however, no requirements as to what weight loss strategy is employed, which may represent a time point where dietary intervention, including low-calorie, ketogenic, or carbohydrate-restricted diets, should be utilized. At least two recent clinical trials have demonstrated safety and efficacy in pre-operative very low-carbohydrate ketogenic diets before bariatric surgery for increasing weight loss and decreasing liver volume [ 40 , 41 ].

Furthermore, despite technically adequate surgery, an alarming number of patients may still experience weight regain and/or recurrence of comorbid obesity-associated conditions. In these patients, effective strategies for dietary intervention are even more important. Approximately 10–15% of patients fail to lose adequate weight (failure defined as <50% of excess weight) or demonstrate significant weight regain after bariatric surgery without evidence of an anatomic or technical reason [ 42 ]. Additionally, in 25–35% of patients who undergo surgery, significant weight regain (defined as >15% of initial weight loss) occurs within two to five years post-operatively [ 43 ]. These patients often require further medical management with weight loss medications, further dietary and behavioral intervention, and, for some, reoperation. Reoperation can be for either revision for further weight loss (narrowing of the gastric sleeve, conversion of VSG to RYGB , and increasing the length of the roux limb) or reversal of RYGB due to health concerns, most commonly associated with malnutrition. A small cohort of patients (4%) may experience severe weight loss with significant malnutrition leading to hospitalization in over 50%, mortality rates of 18%, and need for reversal of RYGB anatomy. While the incidence of RYGB reversal is unknown, based upon a systematic review that included 100 patients spanning 1985–2015, the rate of reversal parallels the increasing rate of bariatric surgery [ 44 ].

In the short term, T2D reversal rates with surgery have been reported to be as high as 80%, with an additional 15% demonstrating partial improvement in T2D despite still requiring medication [ 17 ]. Within one week after RYGB, patients experience improved fasting hepatic insulin clearance, reduced basal de novo glucose production, and increased hepatic insulin sensitivity; by three months and one year after surgery, patients have improved beta-cell sensitivity to glucose, increased GLP-1 secretion from the gut, and improved insulin sensitivity in muscle and fat cells [ 45 ]. Over time, T2D remission rates remain high but do decline; Purnell and colleagues reported three-year remission rates of 68.7% after RYGB [ 29 ]. However, Pories published results from a 14-year prospective study with mean follow-up of 7.6 years, and found 10-year remission rates remained around 83% [ 46 ]. In a 10-year follow-up study of participants from the Swedish Obese Subjects (SOS) study that prospectively followed patients who underwent bariatric surgery, the authors reported a 72% ( n = 342) and 36% ( n = 118) recovery rate from T2D for RYGB at two years and 10 years, respectively [ 47 ].

The long-term metabolic impact and risk reduction from surgery remain high in a substantial number of patients and this route to reversal clearly has the most robust data to support its use. As evidenced by the dramatic improvements in metabolic state that precede weight loss, bariatric surgery is far more than merely a restrictive and/or malabsorptive procedure. Large shifts in bile acid signaling in the lumen of the small intestine, gut nutrient sensing, and changes in the microbiota community appear to greatly impact overall host health. Further research is ongoing using both basic and translational science models to identify the role of these various hormones and metabolites; perhaps there will be a way to one day harness the beneficial effects of bariatric surgery without the need for anatomic rearrangement.

3.2. Low-Calorie Diets (LCD)

As diabetes rates have risen to unprecedented levels [ 1 , 2 ], the number of studies examining diabetes reversal using non-surgical techniques has increased. A handful of studies have reported successful weight loss with decreased insulin resistance, plasma glucose, and medication use following a LCD. As early as 1976, Bistrian et al. [ 48 ] reported that a very low-calorie protein-sparing modified fast allowed for insulin elimination in all seven obese patients with T2D. The average time to insulin discontinuation was only 6.5 days, and the longest was 19 days. In a study by Bauman et al., a low-calorie diet of 900 kcal, including 115 g of protein, led to significant improvement in glycemic control that was mainly attributed to improvements in insulin sensitivity [ 49 ]. Furthermore, a study conducted in obese T2D patients found that a LCD and gastric bypass surgery were equally effective in achieving weight loss and improving glucose and HbA1c levels in the short term [ 50 ]. Weight loss, however, persisted in the diet-treated patients only for the first three months, indicating difficulty with long-term maintenance [ 47 ]. Similarly, other studies also reported similar pattern of early blood glucose normalization without medication use, but the improvements were not sustained long-term [ 51 , 52 , 53 ]. Likewise, the study by Wing et al., even though reported significant and greater improvements of HbA1c at 1 year in the intermittently delivered very low-calorie diet, the HbA1c improvement was not significantly different than what was reported in the patients receiving low-calorie diet (LCD) throughout the one year period [ 54 ]. Furthermore, the glycemic improvements observed at 1 year were not maintained through 2-years, even though the group with intermittent very low-calorie diet had less medication requirement than the group in the LCD arm at 2 years [ 54 ]. Lastly, micronutrient deficiencies with the use of calorie restricted diets has been shown and supplementation and monitoring for deficiencies is a consideration with their use [ 55 , 56 ].

While these previous studies were not assessing diabetes remission or reversal rate per se, they demonstrated the effectiveness of calorie restriction in achieving weight loss and improved glycemic control, which are the core goals of reversal. In 2003, the Look AHEAD trial randomized 5145 overweight or obese patients with T2D to an intervention group that received either an intensive lifestyle intervention (ILI) including calorie restriction and increased physical activity or to a control group that included diabetes support and education (DSE) [ 57 ]. Post hoc analysis of this study revealed that at one year, 11.5% of the participants in the ILI group achieved remission (partial or complete); however, remission rates subsequently decreased over time (9.2% at year two and 7.3% at year four). Nevertheless, the remission rates achieved through ILI were three to six times higher than those achieved in the DSE group. Lower baseline HbA1c, greater level of weight loss, shorter duration of T2D diagnosis, and lack of insulin use at baseline predicted higher remission rate in ILI participants [ 58 ].

Following the Look AHEAD study, other studies have evaluated a LCD for diabetes remission [ 59 , 60 , 61 ]. Most of these studies assessed remission over a short period of time in a small study sample. Bhatt et al. reported that six of the 12 individuals achieved partial remission at the end of the three-month intervention [ 61 ]. Ades et al. studied an intensive lifestyle program including calorie restriction and exercise, and reported that eight of the 10 individuals with recently diagnosed T2D achieved partial remission at six months, including one with complete remission [ 60 ]. The study ended at six months, therefore long term sustainability was not assessed. Another study assessing a one-year diabetes remission retrospectively among those undergoing 12 weeks of the intensive weight loss program “Why Wait” had a much lower remission rate of 4.5%, with 2.3% of them achieving partial remission, while another 2.3% had complete remission [ 59 ]. This study suggests that long-term maintenance of remission is a challenge. Moreover, diabetes remission was more likely reported in those who had a shorter diabetes duration, lower baseline HbA1c, and were taking fewer hypoglycemic medications [ 59 , 61 ].

An initial 2011 diabetes reversal study by Taylor and colleagues showed that a very low-calorie diet of 600 Kcal/day not only normalized glucose, HbA1c, and hepatic insulin sensitivity levels within a week, but also led to decreased hepatic and pancreatic triacylglycerol content and normalization of the insulin response within eight weeks [ 62 ]. At 12 weeks post-intervention, many of the improvements were maintained, but over a quarter of the patients had an early recurrence of diabetes. Further, average weight regain during the 12 weeks post-intervention was 20% [ 62 ]. As a follow-up to the 2011 study, the same group performed a larger and longer study with eight weeks of a very low-calorie meal replacement (624–700 kcal/day) followed by two weeks of solid food replacement and a weight maintenance program of up to six months [ 63 ]. In this study, those who achieved a fasting blood glucose of <7 mmol/L (<126 mg/dL) were categorized as responders, while others were categorized as non-responders. At six months, 40% of participants who initially responded to the intervention were still in T2D remission which was defined by achieving a fasting plasma glucose of <7mmol/L; the majority of those who remitted (60%) had a shorter diabetes duration (<4 years) [ 63 ].

These short-term studies were the foundation for a community-based cluster-randomized clinical trial called DiRECT (Diabetes Remission Clinical Trial). DiRECT enrolled a sample of 306 relatively healthy participants with T2D (people on insulin or with a diabetes duration longer than six years were excluded) [ 64 ] ( Figure 1 ). They were cluster randomized to either standard diabetes care or an intervention using low-calorie meal replacement diet (825–853 kcal/day) for three to five months, followed by stepwise food re-introduction and a long-term weight maintenance program. At one-year follow-up, 46% of patients met the study criteria of diabetes remission (HbA1c <6.5% without antiglycemic medications) [ 64 ] and at two years the remission rate was 36% [ 65 ]. The DiRECT study has extended their follow-up an additional three years to assess the long-term impact on remission.

Taken together, evidence suggests that a LCD is effective in reversing diabetes in the short term up to two years, and its effectiveness was predominantly demonstrated in those with shorter duration since diabetes diagnosis. It is important to note that a substantial level of calorie restriction is needed to generate a sufficient level of weight loss for reversing diabetes. Short-term intervention with moderate energy restriction and metformin for modest weight loss was not as effective in reversing diabetes as compared to standard diabetes care [ 66 ]. Lifestyle intervention with severe energy restriction may have some deleterious effect on the body composition and physiology, which poses a concern for long-term health [ 67 ]. Furthermore, long-term achievement of diabetes remission, adherence to the diet, and weight loss maintenance after the diet remain a challenge. Studies have also suggested that physiological and metabolic adaptation of the body in response to caloric restriction may shift energy balance and hormonal regulation of weight toward weight regain after weight loss [ 67 , 68 ]. Thus, it is crucial that future studies are directed towards assessing the long-term sustainability of diabetes remission led by LCD and feasibility of this diet on the physiological adaptation and body composition changes.

3.3. Carbohydrate-Restricted Diets (LC)

Before the discovery of insulin in 1921, low carbohydrate (LC) diets were the most frequently prescribed treatment for diabetes [ 69 , 70 ]. The paradigm shifted both with the development of exogenous insulin and later with the emergence of the low-fat diet paradigm. A diet low in fat, which by default is high in carbohydrate, became the standard recommendation in guidelines around the globe [ 71 ]. Rather than preventing elevations in glucose, the goal became maintenance of blood sugar control via the increased use of glycemic control medications, including insulin [ 72 ]. Over the last decade, clinical studies have begun to resurrect the pre-insulin LC dietary approach. In response to the new evidence on the efficacy of carbohydrate restriction, low-carbohydrate has recently been endorsed as an eating pattern by the ADA and the European Association for the Study of Diabetes (EASD) [ 5 , 73 ]. In addition, the Veterans Affairs/Department of Defense (VA/DOD) guidelines now recommend carbohydrate restriction as low as 14% of energy intake in its most recent guidelines for treatment of diabetes (VA) [ 74 ].

LC diets are based on macronutrient changes rather than a focus on calorie restriction [ 75 ]. Although the exact definition varies, a low-carbohydrate diet usually restricts total carbohydrates to less than 130 grams per day, while a very low-carbohydrate or ketogenic diet usually restricts total carbohydrates to as low as 20–30 grams per day. Protein consumption is generally unchanged from a standard ADA diet (around 20% of intake), with the remaining energy needs met by fat from either the diet or mobilized body fat stores. Carbohydrate sources are primarily non-starchy vegetables with some nuts, dairy, and limited fruit [ 75 ].

A total of 32 separate trials examining carbohydrate restriction as a treatment for T2D were found when our search was performed [ 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ]. However, for reasons that may include varied levels of carbohydrate restriction and differing levels of support given, not all studies had results that would be consistent with diabetes reversal. A number of shorter-term trials have found a significant between-group advantage of a low-carbohydrate intervention for T2D [ 80 , 84 , 92 , 97 ]. Data from longer-term trials are limited, and in some follow-up studies, the between-group advantage seen initially was lost or reduced, although it often remains significantly improved from baseline. This raises the question of long-term sustainability using this approach. Due to heterogeneity in methodology and definition of carbohydrate restriction, the ability to fully examine T2D reversal based on the existing studies is limited. Based upon a recent systematic review of LC, it appears that the greatest improvements in glycemic control and greatest medication reductions have been associated with the lowest carbohydrate intake [ 109 ]. In consideration of these limitations, it appears important to assess the level of carbohydrate restriction, support or other methods given to encourage sustainability, and length of follow-up.

A study comparing an ad libitum very low-carbohydrate (<20 g total) diet to an energy-restricted low-glycemic diet in T2D found greater reduction in HbA1c, weight, and insulin levels in the low-carbohydrate arm [ 89 ]. Additionally, 95% of participants in the low-carbohydrate arm reduced or eliminated glycemic control medications, compared to 62% in the low glycemic index arm at 24 weeks. Instruction was given in a one-time session with a dietician and included take-home materials for reference. A slightly longer study (34 weeks) trial [ 85 ] found that a very low-carbohydrate ketogenic diet intervention (20–50 g net carbs per day) resulted in HbA1c below the threshold for diabetes in 55% of the patients, compared to 0% of patients in the low-fat arm. The education sessions were all online and included behavior modification strategies and mindful eating which was aimed to address binge eating. New lessons were emailed to the patients weekly for the first 16 weeks and then every two weeks for the remainder of the study.

A small (34 participants) one-year study of an ad libitum, very low-carbohydrate diet compared to a calorie-restricted moderate carbohydrate diet found a significant reduction in HbA1c between groups favoring the low-carbohydrate arm [ 86 ]. At one year, 78% of participants who began the trial with a HbA1c above 6.5% no longer met the cutoff for the diagnosis of diabetes, no longer required any non-metformin medication, and significantly reduced or eliminated metformin. Total kilocalorie intake was not significantly different between the two groups, even with moderate carbohydrate restriction. Despite equal energy intake, the low carbohydrate group lost significantly more weight and had improved glycemic control, which indicates a potential mechanistic role for carbohydrate restriction itself. The support given was 19 classes over the 12-month period, tapering in frequency over time.

Another one-year trial [ 76 ] found significant HbA1c reduction in the subset of patients with diabetes ( n = 54) assigned to an ad libitum low-carbohydrate diet (<30 total grams per day), compared to an energy-restricted low-fat diet. These results remained significant after adjusting the model for weight loss, indicating an effect of the carbohydrate reduction itself. The support given was four weekly sessions during the first month, followed by monthly sessions for the remaining 11 months.

A metabolic ward study on 10 patients with T2D [ 96 ] found that 24-h glucose curves normalized within two weeks on a very low-carbohydrate diet (<21 g total per day). This was in addition to medication reduction and elimination including insulin and sulfonylureas After accounting for body water changes, the average weight loss during the two-week period was 1.65 kg (average of <2% total body weight which is similar to the results of bariatric surgery, where normoglycemia is seen prior to significant weight loss. Interestingly, despite the diet being ad libitum other than the carbohydrate limit, the average energy intake decreased by 1000 kcal per day. Assuming no further change in glycemic control, HbA1c would be 5.6% after eight weeks, which would represent a reduction of 23% from baseline. The fact that HbA1c reductions were greater than in other, longer-term outpatient studies may indicate that support of dietary changes is the key to longer-term success.

In our published trial providing significant support through the use of a continuous care intervention (CCI), we examined using a low-carbohydrate diet aimed at inducing nutritional ketosis in patients with T2D ( n = 262), compared with usual care T2D patients ( n = 87) [ 98 ] ( Figure 1 ). At one year, the HbA1c decreased by 1.3% in the CCI, with 60% of completers achieving a HbA1c below 6.5% without hypoglycemic medication (not including metformin). Overall, medications were significantly reduced, including complete elimination of sulfonylureas and reduction or elimination of insulin therapy in 94% of users. Most cardiovascular risk factors showed significant improvement [ 110 ]. The one-year retention rate was 83%, which indicates that a non-calorie-restricted, low-carbohydrate intervention can be sustained. Improvements were not observed in the usual care patients. The newly released two-year results of this trial [ 106 ] show sustained improvements in normoglycemia, with 54% of completers maintaining HbA1c below 6.5% without medication or only on metformin. The retention rate at two years was 74%, further supporting the sustainability of this dietary intervention for diabetes reversal. Weight loss of 10% was seen at 2-years despite no intentional caloric restriction instruction. Additionally, this trial involved participants with a much longer duration of diabetes (8.4 years on average) than other nutrition trial interventions [ 58 , 64 , 65 ] and did not exclude anyone taking exogenous insulin. As duration of T2D and insulin use have both been identified to be negative factors in predicting remission after bariatric surgery [ 111 , 112 ], the 2-year results of this trial may be even more significant.

It is interesting to note that most studies utilize ad libitum intake in the carbohydrate-restricted arm. Despite this, in studies that have tracked energy intake, spontaneous calorie restriction has occurred [ 113 , 114 ]. In many trials where energy intake has been prescribed or weight loss has been equal, an advantage has been seen in glycemic control, weight, or both in the low-carbohydrate arm [ 86 , 91 , 107 ]. A better understanding of the role that caloric intake, whether prescribed or spontaneous, plays in the overall success is important. In cases of spontaneous energy intake reduction, elucidating the specific mechanism behind this reduction would help in the overall personalization of this approach.

Multiple studies have evaluated side effects or potential complications of carbohydrate restriction. The diet has been found to be safe and well tolerated although long term hard outcome data is lacking and should be a focus of future research. A transient rise in uric acid early in very low-carbohydrate restriction without an associated increase in gout or kidney stones has been documented [ 84 , 98 , 100 ]. Blood urea nitrogen (BUN) has been found to increase and decrease in different studies without an associated change in kidney function [ 87 , 98 , 100 , 115 , 116 ]. Recently, bone mineral density has been found to be unchanged despite significant weight loss after two years of a ketogenic diet intervention in patients with T2D [ 108 ]. While most studies show an improvement or no change in LDL-C levels in patients with T2D on a low-carbohydrate diet, there have been two studies that have found an increase in LDL-C in participants with T2D [ 99 , 111 ]. In one of the studies that found an increase in calculated LDL-C, a non-significant reduction in measured ApoB lipoproteins and unchanged non-HDL cholesterol were seen. Monitoring LDL-C or a measured value of potentially atherogenic lipoproteins such as ApoB should be considered. Lastly, micronutrient deficiency has been seen with a carbohydrate restricted diet, supplementation and monitoring should be given consideration with this intervention [ 56 ].

Although the use of very low-carbohydrate diets for diabetes reversal shows promising results, the lack of longer-term follow-up studies remains a limitation. Follow up is limited to two years, and therefore longer-term studies are needed to determine the sustainability of the metabolic improvements. Determining the appropriate method of support may be a key to the overall success with disease reversal.

Additional evidence has become available in recent years suggesting that diabetes reversal is a possible alternative to consider in place of traditional diabetes treatment and management. In this paper, we provide a review of three methods that have been shown to successfully reverse type 2 diabetes. The current body of evidence suggests that bariatric surgery is the most effective method for overall efficacy and prolonged remission, even though concerns associated with surgical complications, treatment cost and complete lifestyle modification after surgery remain challenges for wide adoption of this approach. While both the LCD and LC dietary approaches are convincing for reversing diabetes in the short term (up to two years), long term maintenance of diabetes remission is still unproven. There are limited available data supporting long term maintenance of weight loss and its associated glycemic improvements in response to LCD; similarly, long-term adherence to a low carbohydrate diet will likely remain an obstacle without the development of proper patient education and optimal support for long-term behavioral change. Moreover, research in understanding the mechanism of diabetes reversibility in all three approaches and its overlapping mechanistic pathways are lacking; this is an area for future research emphasis.

There are similar identified negative predictors of remission for all three approaches. These factors include longer diabetes duration and increased severity, lower BMI, advanced age, poor glycemic control, and low C-peptide levels (indicating decreased endogenous insulin production) [ 117 ]. Further exploration into the heterogeneity of these factors will help personalize the approach, determine realistic goals for each patient, and should be considered during treatment discussions. Ongoing research into algorithm development will be helpful in this regard.

5. Conclusions

Overall, as a society we can no longer afford or tolerate the continued rising rates of diabetes. Despite many barriers within the healthcare system as a whole, providers are responsible on a daily basis for the lives of patients caught up in this unprecedented epidemic. The current standard of care may be suitable for some, but others would surely choose reversal if they understood there was a choice. The choice can only be offered if providers are not only aware that reversal is possible but have the education needed to review these options in a patient-centric discussion.

Acknowledgments

We thank James McCarter and Stephen Phinney for their edits, which greatly improved the manuscript.

Abbreviations:

C	carbohydrate restriction
DSS-II	Diabetes Surgery Summit
RYGB	Roux-en-Y Gastric Bypass
SG	Sleeve Gastrectomy
CCK	cholecystokinin
PYY	peptide-tyrosine-tyrosine
GLP-1	glucagon-like peptide 1
LABS-2	Longitudinal Assessment of Bariatric Surgery 2
LCD	low-calorie diet
IMT	intensive medical intervention
DiRECT	Diabetes Remission Clinical Trial
ASD	European Association for the Study of Diabetes
VA/DOD	Veterans Affairs/Department of Defense

Author Contributions

Conceptualization, S.J.H. and S.J.A. Investigation, S.J.H., V.M.G., T.L.H., S.J.A. Writing—original draft, S.J.H., V.M.G., S.J.A. Writing—review and editing, S.J.H., V.M.G., T.L.H., S.J.A. All authors approved of the final manuscript.

Conflicts of Interest

S.J.H. is an employee and shareholder of Virta Health, a for-profit company that provides remote diabetes care using a low-carbohydrate nutrition intervention, and serves as an advisor for Atkins Corp. V.M.G. has no conflicts of interest to declare. T.L.H. is an employee of Virta Health. S.J.A. is an employee and shareholder of Virta Health.

Higher heme iron intake linked to increased risk of type 2 diabetes

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Higher intake of heme iron, the type found in red meat and other animal products-;as opposed to non-heme iron, found mostly in plant-based foods-;was associated with a higher risk of developing type 2 diabetes (T2D) in a new study led by researchers at Harvard T.H. Chan School of Public Health. While the link between heme iron and T2D has been reported previously, the study's findings more clearly establish and explain the link.

Compared to prior studies that relied solely on epidemiological data, we integrated multiple layers of information, including epidemiological data, conventional metabolic biomarkers, and cutting-edge metabolomics. This allowed us to achieve a more comprehensive understanding of the association between iron intake and T2D risk, as well as potential metabolic pathways underlying this association." Fenglei Wang, lead author, research associate in the Department of Nutrition

The study will be published August 13 in Nature Metabolism.

The researchers assessed the link between iron and T2D using 36 years of dietary reports from 206,615 adults enrolled in the Nurses' Health Studies I and II and the Health Professionals Follow-up Study. They examined participants' intake of various forms of iron-;total, heme, non-heme, dietary (from foods), and supplemental (from supplements)-;and their T2D status, controlling for other health and lifestyle factors.

The researchers also analyzed the biological mechanisms underpinning heme iron's relationship to T2D among smaller subsets of the participants. They looked at 37,544 participants' plasma metabolic biomarkers, including those related to insulin levels, blood sugar, blood lipids, inflammation, and two biomarkers of iron metabolism. They then looked at 9,024 participants' metabolomic profiles-;plasma levels of small-molecule metabolites, which are substances derived from bodily processes such as breaking down food or chemicals.

The study found a significant association between higher heme iron intake and T2D risk. Participants in the highest intake group had a 26% higher risk of developing T2D than those in the lowest intake group. In addition, the researchers found that heme iron accounted for more than half of the T2D risk associated with unprocessed red meat and a moderate proportion of the risk for several T2D-related dietary patterns. In line with previous studies, the researchers found no significant associations between intakes of non-heme iron from diet or supplements and risk of T2D.

The study also found that higher heme iron intake was associated with blood metabolic biomarkers associated with T2D. A higher heme iron intake was associated with higher levels of biomarkers such as C-peptide, triglycerides, C-reactive protein, leptin, and markers of iron overload, as well as lower levels of beneficial biomarkers like HDL cholesterol and adiponectin.

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