latest research of diabetes

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.

Give Today and Change Lives!

Featured Topics

Featured series.

A series of random questions answered by Harvard experts.

Explore the Gazette

Read the latest.

Had a bad experience meditating? You’re not alone.

Families may remove brain-injured patients from life support too soon

What to do about mental health crisis among Black males

“When my son was diagnosed [with Type 1], I knew nothing about diabetes. I changed my research focus, thinking, as any parent would, ‘What am I going to do about this?’” says Douglas Melton.

Kris Snibbe/Harvard Staff Photographer

Breakthrough within reach for diabetes scientist and patients nearest to his heart

Harvard Correspondent

100 years after discovery of insulin, replacement therapy represents ‘a new kind of medicine,’ says Stem Cell Institute co-director Douglas Melton, whose children inspired his research

When Vertex Pharmaceuticals announced last month that its investigational stem-cell-derived replacement therapy was, in conjunction with immunosuppressive therapy, helping the first patient in a Phase 1/2 clinical trial robustly reproduce his or her own fully differentiated pancreatic islet cells, the cells that produce insulin, the news was hailed as a potential breakthrough for the treatment of Type 1 diabetes. For Harvard Stem Cell Institute Co-Director and Xander University Professor Douglas Melton, whose lab pioneered the science behind the therapy, the trial marked the most recent turning point in a decades-long effort to understand and treat the disease. In a conversation with the Gazette, Melton discussed the science behind the advance, the challenges ahead, and the personal side of his research. The interview was edited for clarity and length.

Douglas Melton

GAZETTE: What is the significance of the Vertex trial?

MELTON: The first major change in the treatment of Type 1 diabetes was probably the discovery of insulin in 1920. Now it’s 100 years later and if this works, it’s going to change the medical treatment for people with diabetes. Instead of injecting insulin, patients will get cells that will be their own insulin factories. It’s a new kind of medicine.

GAZETTE: Would you walk us through the approach?

MELTON: Nearly two decades ago we had the idea that we could use embryonic stem cells to make functional pancreatic islets for diabetics. When we first started, we had to try to figure out how the islets in a person’s pancreas replenished. Blood, for example, is replenished routinely by a blood stem cell. So, if you go give blood at a blood drive, your body makes more blood. But we showed in mice that that is not true for the pancreatic islets. Once they’re removed or killed, the adult body has no capacity to make new ones.

So the first important “a-ha” moment was to demonstrate that there was no capacity in an adult to make new islets. That moved us to another source of new material: stem cells. The next important thing, after we overcame the political issues surrounding the use of embryonic stem cells, was to ask: Can we direct the differentiation of stem cells and make them become beta cells? That problem took much longer than I expected — I told my wife it would take five years, but it took closer to 15. The project benefited enormously from undergraduates, graduate students, and postdocs. None of them were here for 15 years of course, but they all worked on different steps.

GAZETTE: What role did the Harvard Stem Cell Institute play?

MELTON: This work absolutely could not have been done using conventional support from the National Institutes of Health. First of all, NIH grants came with severe restrictions and secondly, a long-term project like this doesn’t easily map to the initial grant support they give for a one- to three-year project. I am forever grateful and feel fortunate to have been at a private institution where philanthropy, through the HSCI, wasn’t just helpful, it made all the difference.

I am exceptionally grateful as well to former Harvard President Larry Summers and Steve Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute, who supported the creation of the HSCI, which was formed specifically with the idea to explore the potential of pluripotency stem cells for discovering questions about how development works, how cells are made in our body, and hopefully for finding new treatments or cures for disease. This may be one of the first examples where it’s come to fruition. At the time, the use of embryonic stem cells was quite controversial, and Steve and Larry said that this was precisely the kind of science they wanted to support.

GAZETTE: You were fundamental in starting the Department of Stem Cell and Regenerative Biology. Can you tell us about that?

MELTON: David Scadden and I helped start the department, which lives in two Schools: Harvard Medical School and the Faculty of Arts and Science. This speaks to the unusual formation and intention of the department. I’ve talked a lot about diabetes and islets, but think about all the other tissues and diseases that people suffer from. There are faculty and students in the department working on the heart, nerves, muscle, brain, and other tissues — on all aspects of how the development of a cell and a tissue affects who we are and the course of disease. The department is an exciting one because it’s exploring experimental questions such as: How do you regenerate a limb? The department was founded with the idea that not only should you ask and answer questions about nature, but that one can do so with the intention that the results lead to new treatments for disease. It is a kind of applied biology department.

GAZETTE: This pancreatic islet work was patented by Harvard and then licensed to your biotech company, Semma, which was acquired by Vertex. Can you explain how this reflects your personal connection to the research?

MELTON: Semma is named for my two children, Sam and Emma. Both are now adults, and both have Type 1 diabetes. My son was 6 months old when he was diagnosed. And that’s when I changed my research plan. And my daughter, who’s four years older than my son, became diabetic about 10 years later, when she was 14.

When my son was diagnosed, I knew nothing about diabetes and had been working on how frogs develop. I changed my research focus, thinking, as any parent would, “What am I going to do about this?” Again, I come back to the flexibility of Harvard. Nobody said, “Why are you changing your research plan?”

GAZETTE: What’s next?

MELTON: The stem-cell-derived replacement therapy cells that have been put into this first patient were provided with a class of drugs called immunosuppressants, which depress the patient’s immune system. They have to do this because these cells were not taken from that patient, and so they are not recognized as “self.” Without immunosuppressants, they would be rejected. We want to find a way to make cells by genetic engineering that are not recognized as foreign.

I think this is a solvable problem. Why? When a woman has a baby, that baby has two sets of genes. It has genes from the egg, from the mother, which would be recognized as “self,” but it also has genes from the father, which would be “non-self.” Why does the mother’s body not reject the fetus? If we can figure that out, it will help inform our thinking about what genes to change in our stem cell-derived islets so that they could go into any person. This would be relevant not just to diabetes, but to any cells you wanted to transplant for liver or even heart transplants. It could mean no longer having to worry about immunosuppression.

Share this article

You might like.

Altered states of consciousness through yoga, mindfulness more common than thought and mostly beneficial, study finds — though clinicians ill-equipped to help those who struggle

Of the survivors within one study group, more than 40% recovered at least some independence.

Symposium examines thorny, multifaceted dilemma from systemic racism in policing, healthcare to stigma attached to psychotherapy in community

Six receive honorary degrees

Harvard recognizes educator, conductor, theoretical physicist, advocate for elderly, writer, and Nobel laureate

Everything counts!

New study finds step-count and time are equally valid in reducing health risks

Bridging social distance, embracing uncertainty, fighting for equity

Student Commencement speeches to tap into themes faced by Class of 2024

Masks Strongly Recommended but Not Required in Maryland, Starting Immediately

Due to the downward trend in respiratory viruses in Maryland, masking is no longer required but remains strongly recommended in Johns Hopkins Medicine clinical locations in Maryland. Read more .

• Vaccines  
• Masking Guidelines
• Visitor Guidelines  

New Research Sheds Light on Cause of Type 2 Diabetes

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 .

Cornell Chronicle

• Architecture & Design
• Arts & Humanities
• Business, Economics & Entrepreneurship
• Computing & Information Sciences
• Energy, Environment & Sustainability
• Food & Agriculture
• Global Reach
• Health, Nutrition & Medicine
• Law, Government & Public Policy
• Life Sciences & Veterinary Medicine
• Physical Sciences & Engineering
• Social & Behavioral Sciences
• Coronavirus
• News & Events
• Public Engagement
• New York City
• Photos of the Week
• Big Red Sports
• Freedom of Expression
• Student Life
• University Statements
• Around Cornell
• All Stories
• In the News
• Expert Quotes
• Cornellians

Large-scale study reveals new genetic details of diabetes

By wynne parry weill cornell medicine.

In experiments of unprecedented scale, investigators at Weill Cornell Medicine and the National Institutes of Health have revealed new aspects of the complex genetics behind Type 2 diabetes. Through these discoveries, and by providing a template for future studies, this research furthers efforts to better understand and ultimately treat this common metabolic disease.

Previous studies have generally examined the influence of individual genes. In research described Oct. 18 in Cell Metabolism, senior co-author Shuibing Chen , the Kilts Family Professor of Surgery at Weill Cornell Medicine, working alongside senior co-author Dr. Francis Collins , a senior investigator at the Center for Precision Health Research within the National Human Genome Research Institute of the U.S. National Institutes of Health, took a more comprehensive approach. Together, they looked at the contribution of 20 genes in a single effort.

“It’s very difficult to believe all these diabetes-related genes act independently of each other,” Chen said. By using a combination of technologies, the team examined the effects of shutting each down. By comparing the consequences for cell behavior and genetics, she said, “we found some common themes.”

As with other types of diabetes, Type 2 diabetes occurs when sugar levels in the blood are too high. In Type 2 diabetes, this happens in part because specialized cells in the pancreas, known as β-cells, don’t produce enough insulin, a hormone that tells cells to take sugar out of the blood for use as an energy source. Over time, high levels of blood sugar damage tissues and cause other problems, such as heart and kidney disease. According to the United States Centers for Disease Control and Prevention, nearly 9% of adults in the United States have been diagnosed with Type 2 diabetes. 

Both genetic and environmental factors, such as obesity and chronic stress, can increase risk for it. Yet evaluating the role of the genetic contributors alone is a massive project. So far, researchers have identified more than 290 locations within the genome where changes to DNA can raise the likelihood of developing the disease. Some of these locations fall within known genes, but most are found in regions that regulate the expression of nearby genes.

For the new research, the team focused on 20 genes clearly identified as contributors. They began their investigation by using the gene editing system CRISPR-Cas9 to shut down these genes, one at a time, within 20 sets of identical stem cells. 

These stem cells had the potential to generate any kind of mature cell, but the researchers coaxed them into becoming insulin-producing β-cells. They then examined the effects of losing each gene on five traits related to insulin production and the health of β-cells. They also documented the accompanying changes in gene expression and the accessibility of DNA for expression.

To make sense of the massive amount of data they collected, the team developed their own computational models to analyze it, leading to several discoveries: By comparing the effects of all 20 mutations on β-cells, they identified four additional genes, each representing a newly discovered pathway that contributes to insulin production. They also found that, of the original 20 genes, only one, called HNF4A, contributed to all five traits, apparently by acting as a master controller that regulates the activity of other genes. In one specific example, they explained how a small variation, located in a space between genes, contributes to the risk of diabetes by interfering with HNF4A’s ability to regulate nearby genes.

Ultimately, this study and others like it hold the promise of benefiting patients, Collins said. “We need to understand all the genetic and environmental factors involved so we can do a better job of preventing diabetes, and to develop new ideas about how to effectively treat it.”

Collins and Chen note that their approach may have relevance beyond diabetes, to other common diseases, such as Alzheimer’s, Parkinson’s and Crohn’s disease, that involve many genetic factors.

The work reported in this newsroom story was supported in part by the United States’ National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and the American Diabetes Association.

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 Shuibing Chen .

Wynne Parry is a freelance writer for Weill Cornell Medicine.

Media Contact

Krystle lopez.

Get Cornell news delivered right to your inbox.

You might also like

Gallery Heading

• May 28, 2024 | Scientists May Have Discovered an Achilles Heel for Hepatitis B
• May 28, 2024 | Challenging Classical Physics: Surprising Properties of Elastic Turbulence Discovered
• May 28, 2024 | Johns Hopkins Scientists Solve 30-Year Biological Mystery of Night Blindness
• May 28, 2024 | Cutting-Edge Phage Research Promises New Solutions for Old Pathogens
• May 28, 2024 | Vanishing Without a Trace: Why Stars Mysteriously Disappear From the Night Sky

Beyond Blood Sugar Control: New Target for Curing Diabetes Unveiled

By Helmholtz Munich March 22, 2024

Targeting the inceptor receptor could lead to breakthrough treatments for diabetes by protecting beta cells and improving blood sugar control, with German research institutions leading this promising discovery. Insulin-producing beta cells in the islet of Langerhans. Credit: Helmholtz Munich | Erik Bader

Research focusing on the insulin -inhibitory receptor, known as inceptor, has revealed promising paths for protecting beta cells, providing optimism for therapy that directly addresses diabetes. A groundbreaking study involving mice with obesity caused by diet shows that eliminating inceptor improves glucose management. This finding encourages further investigation into inceptor as a potential therapeutic target for treating type 2 diabetes.

These findings, led by Helmholtz Munich in collaboration with the German Center for Diabetes Research, the Technical University of Munich, and the Ludwig-Maximilians-University Munich, drive advancements in diabetes research.

Targeting Inceptor to Combat Insulin Resistance in Beta Cells

Insulin resistance, often linked to abdominal obesity, presents a significant healthcare dilemma in our era. More importantly, the insulin resistance of beta cells contributes to their dysfunction and the transition from obesity to overt type 2 diabetes. Currently, all pharmacotherapies, including insulin supplementation, focus on managing high blood sugar levels rather than addressing the underlying cause of diabetes: beta cell failure or loss. Therefore, research into beta cell protection and regeneration is crucial and holds promising prospects for addressing the root cause of diabetes, offering potential avenues for causal treatment.

With the recent discovery of inceptor, the research group of beta cell expert Prof. Heiko Lickert has uncovered an interesting molecular target. Upregulated in diabetes, the insulin-inhibitory receptor inceptor may contribute to insulin resistance by acting as a negative regulator of this signaling pathway. Conversely, inhibiting the function of the inceptor could enhance insulin signaling – which in turn is required for overall beta cell function, survival, and compensation upon stress.

In collaboration with Prof. Timo Müller, an expert in molecular pharmacology in obesity and diabetes, the researchers explored the effects of inceptor knock-out in diet-induced obese mice. Their study aimed to determine whether inhibiting inceptor function could also enhance glucose tolerance in diet-induced obesity and insulin resistance, both critical pre-clinical stages in the progression toward diabetes. The results were now published in Nature Metabolism .

Removing Inceptor Improves Blood Sugar Levels in Obese Mice

The researchers delved into the effects of removing inceptor from all body cells in diet-induced obese mice. Interestingly, they found that mice lacking inceptor exhibited improved glucose regulation without experiencing weight loss, which was linked to increased insulin secretion in response to glucose. Next, they investigated the distribution of inceptor in the central nervous system and discovered its widespread presence in neurons. Deleting inceptor from neuronal cells also improved glucose regulation in obese mice. Ultimately, the researchers selectively removed the inceptor from the mice’s beta cells, resulting in enhanced glucose control and a slight increase in beta cell mass.

Research for Inceptor-Blocking Drugs

“Our findings support the idea that enhancing insulin sensitivity through targeting inceptor shows promise as a pharmacological intervention, especially concerning the health and function of beta cells,” says Timo Müller. Unlike intensive early-onset insulin treatments, utilizing inceptor to enhance beta cell function offers promise in alleviating the detrimental effects on blood sugar and metabolism induced by diet-induced obesity. This approach avoids the associated risks of hypoglycemia-associated unawareness and unwanted weight gain typically observed with intensive insulin therapy.

“Since inceptor is expressed on the surface of pancreatic beta cells, it becomes an accessible drug target. Currently, our laboratory is actively researching the potential of several inceptor-blocking drug classes to enhance beta cell health in pre-diabetic and diabetic mice. Looking forward, inceptor emerges as a novel and intriguing molecular target for enhancing beta cell health, not only in prediabetic obese individuals but also in patients diagnosed with type 2 diabetes,” explains Heiko Lickert.

Reference: “Global, neuronal or β cell-specific deletion of inceptor improves glucose homeostasis in male mice with diet-induced obesity” by Gerald Grandl, Gustav Collden, Jin Feng, Sreya Bhattacharya, Felix Klingelhuber, Leopold Schomann, Sara Bilekova, Ansarullah, Weiwei Xu, Fataneh Fathi Far, Monica Tost, Tim Gruber, Aimée Bastidas-Ponce, Qian Zhang, Aaron Novikoff, Arkadiusz Liskiewicz, Daniela Liskiewicz, Cristina Garcia-Caceres, Annette Feuchtinger, Matthias H. Tschöp, Natalie Krahmer, Heiko Lickert and Timo D. Müller, 28 February 2024, Nature Metabolism . DOI: 10.1038/s42255-024-00991-3

More on SciTechDaily

Quantum Breakthrough Reveals Superconductor’s Hidden Nature

Novel Molecules Discovered to Combat Asthma and COVID-Related Lung Diseases

Orbital Engineering, Yale Engineers Change Electron Trajectories

Finding and Erasing Quantum Computing Errors in Real-Time

“Glow-in-the-Dark” Proteins: The Future of Viral Disease Detection?

A black hole – a million times as bright as our sun – offers potential clue to reionization of universe.

Risk Factors for Falls in Older Americans Identified – A Growing Public Health Concern

Common Fireworks Emit Toxic Metals Into the Air – Damage Human Cells and Animal Lungs

1 comment on "beyond blood sugar control: new target for curing diabetes unveiled".

Interesting study and hopefully another tool which will apply to diabetic patients.

Leave a comment Cancel reply

Email address is optional. If provided, your email will not be published or shared.

Save my name, email, and website in this browser for the next time I comment.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Biomedicines

Current Advances in the Management of Diabetes Mellitus

Chinyere aloke.

1 Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg 2050, South Africa

2 Department of Medical Biochemistry, Alex Ekwueme Federal University Ndufu-Alike, Abakaliki PMB 1010, Nigeria

Chinedu Ogbonnia Egwu

Patrick maduabuchi aja.

3 Department of Biochemistry, Faculty of Biological Sciences, Ebonyi State University, Abakaliki PMB 53, Nigeria

Nwogo Ajuka Obasi

Jennifer chukwu.

4 John Hopkins Program on International Education in Gynaecology and Obstetrics, Abuja 900281, Nigeria

Blessing Oluebube Akumadu

Patience nkemjika ogbu, ikechukwu achilonu, associated data.

Not applicable.

Diabetes mellitus (DM) underscores a rising epidemic orchestrating critical socio-economic burden on countries globally. Different treatment options for the management of DM are evolving rapidly because the usual methods of treatment have not completely tackled the primary causes of the disease and are laden with critical adverse effects. Thus, this narrative review explores different treatment regimens in DM management and the associated challenges. A literature search for published articles on recent advances in DM management was completed with search engines including Web of Science, Pubmed/Medline, Scopus, using keywords such as DM, management of DM, and gene therapy. Our findings indicate that substantial progress has been made in DM management with promising results using different treatment regimens, including nanotechnology, gene therapy, stem cell, medical nutrition therapy, and lifestyle modification. However, a lot of challenges have been encountered using these techniques, including their optimization to ensure optimal glycemic, lipid, and blood pressure modulation to minimize complications, improvement of patients’ compliance to lifestyle and pharmacologic interventions, safety, ethical issues, as well as an effective delivery system among others. In conclusion, lifestyle management alongside pharmacological approaches and the optimization of these techniques is critical for an effective and safe clinical treatment plan.

1. Introduction

Diabetes mellitus (DM) is a long-standing, complicated, and non-transmissible endocrine ailment that is growing rapidly and has posed clinical challenges globally, often linked with threats related to complicated metabolic development in patients. It is marked by elevated glucose and lipids in the blood as well as oxidative stress, which culminate in chronic complications involving diverse organs, mainly the kidneys, eyes, nerves, and blood vessels, among others, in the body. As reported by World Health Organization (WHO), DM is an outbreak prone to high malaise and death. Globally, approximately 387 million persons are affected by this disorder and it is estimated to be more than 640 million by 2040 [ 1 ].

According to a report in 2017 by International Diabetes Federation (IDF), 425 million persons suffer from diabetes mellitus out of which more than 90 percent are adults and 352 million had impaired glucose tolerance (IGT) [ 2 ]. In individuals suffering from type II diabetes mellitus (T2DM), hyperglycemia is not the only characteristic; it also involves multiple complications such as kidney failure, blindness, heart attack, stroke, and amputations of the lower limb [ 3 ]. Mounting evidence obtained from epidemiological studies has shown that T2DM is an ailment with numerous causes associated with both polygenic and various environmental factors [ 4 ]. T2DM is thus too complicated to cure due to genetic polymorphism and other numerous risk factors.

Despite the fact that most cases are a result of obesity-linked T2DM, the annual prevalence of T1DM is on the rise [ 5 ]. It has been reported that about 10 percent of people suffering from diabetes have T1DM. However, the two forms are linked with a prolonged risk of circulatory system complexities [ 6 ] and the threat of lowered blood glucose. Ample proof suggests that normoglycemia accomplishment will mitigate the risk of complications linked with DM [ 7 ]. However, hypoglycemia occurrences limit the attainment of near normoglycemia in subjects with T1DM. Diabetic individuals who are not aware of their hypoglycemic status are vulnerable to T1DM which then limits them from the attainment of the needed glycemic control. Globally, DM health centers have several individuals with T1DM who have recurrent low blood glucose and the idea of hypoglycemic unconsciousness poses critical clinical challenges. Providentially, many favorable and interesting gain ground exist in the perspective for subjects with the problem of DM, including gene therapy, as reported by Bosch and colleagues [ 8 ].

Currently, the main therapeutic regimens for T2DM are injection of insulin-like agents and oral administration of hypoglycaemic agents. However, these agents play crucial functions in T2DM treatment but are laden with side effects [ 9 , 10 ]. Insulin has taken the centerpiece for the management of unrestrained insulin-deficient DM since its invention [ 11 ]. Admittedly, due to the severe lack of beta cells, the injection of exogenous insulin is vital for survival. Notwithstanding the advances made in comprehending the etiology, effects, and continuance of DM, including the progress made in insulin development and its analogues, ensuring tight glycaemic modulation without negative side effects such as low blood glucose and gain in weight still poses significant problems [ 7 , 12 , 13 ]. Hence, this further accentuates the importance of alternative techniques or adjuncts to insulin [ 14 ].

Consequently, this narrative review exploits different alternative therapeutic regimen for the management of two forms of DM, including nanotechnology, stem cell technology, gene therapy, medical nutrition therapy, lifestyle modification and the challenges associated with these techniques.

To identify published works on recent advances in the management of DM, the literature search for this narrative review was carried out using different search engines including Scopus, Google Scholar, Pubmed/Medline and Web of Science databases. Keywords and subject headings employed include diabetes mellitus, hyperglyceamia, management of DM, T2DM, nanotechnology in diabetes, gene therapy in DM management and current treatment, etc. The titles and abstracts of the results after the search were painstakingly screened to select eligible articles for full-text reading. Articles that were found to be eligible were retrieved and full-text screening was performed independently by three of the authors to select studies for inclusion in the final analysis. Original research and review articles published between 1993 and 2022 (in English) were included. Unpublished articles and thesis were excluded. All authors confirmed the validity of the selected papers.

3. Risk Factors of Diabetes

There are several risk factors associated with diabetes. These risk factors contribute significantly to the progression of diabetes. They include but not limited to age; weight; family history of diabetes; smoking and race/ethnicity [ 15 , 16 ] (Asiimwe et al., 2020; Noh et al., 2018). While T1DM is mostly found in the young, T2DM is an adult-related condition. The risk of T2DM increases with age which is due to the deficiency of insulin secretion which develops with age, and growing insulin resistance caused by a change in body composition [ 17 ]. Increase in body weight which leads to obesity is closely associated with diabetes in a condition termed diabesity. This is because increase in body weight leads to increased insulin resistance [ 18 ].

According to the FDA, smokers are 30 to 40% more likely to come down with T2DM than nonsmokers. Smoking can also increase insulin resistance which makes the patients require more insulin for the control of their sugar level [ 19 ]. Diabetes is hereditary. Those with the family history are advised to adhere to lifestyles that reduce the risk of developing diabetes.

4. Management of Diabetes

There are several modern approaches involved in the management of diabetes. However, early diagnosis is central to achieving any targets set in DM management [ 20 ]. Each patient is treated with the aim of achieving a particular outcome. These outcomes are set out from the first day of clinic visit to ensure an individualized approach in the management of diabetes.

4.1. Internet Intervention for Lifestyle Modification in Diabetes

Lifestyle modification is an integral part of diabetes management. It is recommended for both patients in pre-diabetic and diabetic conditions, respectively. Reduced sedentary lifestyle, increased physical activities, and healthy diets are among the recommended lifestyle modifications. The right exercise may depend on the state of the patient. The exercise helps to bring down the plasma glucose level. For a healthy diet, it is recommended that diabetic subjects take a lot of vegetables, fruits, and whole grains; choose nonfat dairy and lean meats; and limit foods that are high in sugar and fat. Other lifestyle changes include stopping smoking and reduction in alcohol intake [ 21 , 22 ]. The lifestyle changes are usually individualized.

Even though the above strategies help in the effective management of diabetes, communicating or constantly reminding the subjects to complete them could be challenging. Web or internet-based program have been deployed to improve adherence to the lifestyle changes. These web-based strategies provide a viable option for facilitating diabetes self-management [ 23 ].

4.2. Nanotechnology and Diabetes

Nanotechnology involves the use of nanoparticles (<100 nm). These nanoparticles are developed through the manipulation of individual atoms or molecules in a substance. The application of nanotechnology in medicine is termed nanomedicine. Nanomedicine involves the combination of the knowledge of nanotechnology in the application of drugs or diagnostic molecules which generally improves their ability to target specific cells or tissues. Nanotechnology in diabetes research has played several roles in improving the outcome of diabetic management in diabetics through the deployment of novel nanotechnology-based glucose measurement and insulin delivery techniques [ 24 , 25 ]. Nanotechnology employs non-invasive approaches for insulin delivery and the development of a more efficacious vaccine including cell-based and gene-based therapies for T1DM [ 24 ]. The importance of nanotechnology in diabetes includes, but is not limited to, inventive diabetes diagnosis, detection of immune cell activity and beta-cell mass, monitoring of glucose level, and non-invasive insulin delivery, etc.

Early and accurate diagnosis of a disease may be as important as the treatment of the disease itself. Prompt diagnosis may prevent dysglycaemia and reduce the time to onset of diabetes [ 26 ]. Conventional approaches have been utilized in the different diagnostic needs in diabetes, such as detection of immune destruction that precedes T1DM and/or measurement of plasma glucose levels. However, the shortcomings of the conventional approaches which include, but are not limited to, non-early detection of the disease progression necessitate the need for a novel technology that can improve the diagnostic outcome.

The mass of the beta cell is an indication of the functionality of the beta-cell in secreting insulin. The progressive loss of the beta cells precipitates T1DM [ 27 ]. Prompt detection of the stage of beta cell loss through nanotechnology can allow for the immediate application of clinical interventions for its arrest. Magnetic nanoparticles (MNPs), for instance, have distinctive physical properties qualifying them as outstanding contrast media for magnetic resonance imaging (MRI). This can enable the early detection of the stages of beta-cell loss.

Glycaemic fluctuation should be avoided during diabetic management. Individuals have treatment goals set by their physicians. Regular or daily glucose monitoring is performed to ascertain the control achieved by the treatment and the diabetes progression [ 28 ]. However, this comes with some challenges including poor compliance as a result of the regular pricking of the patients and inability to monitor glucose levels at certain times of the day (e.g., sleeping and driving times). The overall impact is irregular monitoring of the glucose level which can lead to dangerous fluctuations that may worsen diabetic complications. To circumvent this challenge, continuous glucose monitoring (CGM) systems are essential. The implantation of biosensors (e.g., amperometric sensors) subcutaneously had been used to achieve CGM for 10 days; however, this has its drawbacks including instabilities and the need for a weekly change of the implantation [ 29 , 30 ].

Nanomedicine can overcome the aforementioned obstacles in CGM. The glucose-sensing device has three key components: a detector, a transducer, and a reporter. The detector measures the glucose level while the transducer converts the measurement into an output signal. The reporter finally processes the signal into an interpretable form. For an effective measure of the glucose level, the glucose sensors are usually made of nanoparticles in nanotechnology which are made from mainly three molecules: glucose oxidase, glucose-binding proteins, and glucose-binding small molecules [ 24 , 31 ]. The coupling of these nanoparticles as transducers enables the accurate detection of glucose in a patient-friendly and rapid manner [ 31 ].

Insulin shots are the mainstay in the management of T1DM and T2DM. The conventional approach of insulin delivery involves the use of needle injections. Even though some needles have been significantly improved to be painless during delivery, the thought of needles alone could be discouraging [ 32 ]. This significantly affects the compliance of patients to insulin use. Moreover, the lingering time between the time of glucose measurement and the insulin dosing in addition to the hindrance in the absorption of insulin ensuing the conventional subcutaneous injection, do not allow for a close plasma glucose control which leads to fluctuations and times of hyperglycemia [ 24 ]. An approach that is non-invasive will be well accepted by both patients and medical practitioners to improve compliance and the overall outcome of treatment.

To overcome the recent delivery challenges faced by the conventional approaches, microcomputer closed-loop or nano pumps are being developed to ensure the timely delivery of insulin while ensuring continuous glucose monitoring. In other words, this system is built to link insulin delivery to plasma glucose concentration. This will prevent the risk of plasma glucose fluctuations [ 26 , 33 ]. Other less invasive means of insulin delivery that involve the use of nanoparticles are also being explored to facilitate insulin delivery orally, transdermally, and/or via inhalation [ 26 ].

4.3. Medical Nutrition Therapy in Diabetes

Medical nutrition therapy (MNT) is a “nutrition-based treatment provided by a registered dietitian nutritionist.” It comprises nutrition diagnosis and therapeutic and professional counseling services that aid in the management of DM. MNT is a critical aspect of diabetes education and management. Recommendations on MNT by international collaborative groups for diabetes management have attempted to reform and provide courses for adverse nutritional transition [ 34 , 35 ]. For instance, MNT has been employed for the treatment of GDM because carbohydrate (CHO) is the main causative agent as a result of its impact on glycaemia. According to the Institute of Medicine, pregnant women require a minimum of 175 g CHO per day, and low-CHO diets already in use traditionally for the treatment of GDM have proven to be safe [ 36 ]. Moreover, MNT has been reported to be critical in the management of other types of DM and as such has significantly impacted patients, especially women and newborns [ 37 ]. Primarily, MNT ensures the maintenance of euglycemia via adequacy in weight gain in pregnancy and growth of fetus while avoiding ketogenesis and metabolic acidosis. Nonetheless, MNT is yet to establish the optimal diet in terms of energy content and macronutrient distribution, quality, and amount, among others, in DM [ 37 ]. Reports have shown that the nutritional requirements for GDM patients are the same for all pregnancy cases when their carbohydrate intake is taken into special cognizance. Currently, a low-glycemic index diet has been reported to be more favorable in the management of GDM than the traditional intervention of carbohydrates restriction even though the evidence is still restrained [ 37 ]. Caloric restrictions are very vital in the management of overweight or obesity.

Reports have charged MNT with the design of signature diet strategies that will be suitable medically as well as patient focused. By this, it is hoped that practicing diabetologists and registered dieticians (RDs) will partner to furnish nutritional guidelines based on evidence for use by MNT for the prevention and management of DM and related comorbidities [ 38 ]. Indications show that MNT may be a potent, easily available, and cheap therapeutic technique and could be an essential tool for DM prevention and management [ 35 ].

4.4. Gene Therapy and Diabetes Mellitus

Gene therapy is a technique that involves remedying the symptoms of an ailment orchestrated by a defective gene via the incorporation of the exogenous normal gene. Its advantage is that a single treatment can be used to cure any type of disease and currently, gene therapy is opening up novel treatment options in different branches of medicine [ 39 ]. At present, gene manipulation is not limited to the addition of a gene but also gene modulation and editing [ 40 , 41 ]. Gene therapy can also be explained as a method of introduction of a gene or gene manipulation within a cell as a curative regimen in the treatment of disease [ 42 ]. The objective of this approach is to remedy abnormal genes that have been implicated as the causative agent in any ailment and to successfully halt the beginning of the ailment or prevent its continuation. The gene therapy approach involves three major intervention methods: (i) delivery of a new gene into the body, (ii) substitution of the abnormal gene with a working gene, and (iii) disabling the malfunction genes responsible for the ailment [ 42 , 43 ]. Gene therapy can be further classified into somatic gene therapy or germline gene therapy. While the primary target in somatic gene therapy is the somatic cells often referred to as the diseased cells, the reproductive cells are the targets in germline gene therapy. Germline therapy halts the development of the disease in subsequent generations [ 43 ]. The application of gene therapies as trends in evolving therapeutics is due to its potential for the treatment of diverse ailments including DM, autoimmune disorders, heart diseases, and cancers among others that are difficult to manage using conventional therapies [ 44 ].

T1DM is an autoimmune ailment marked by T-cell-orchestrated self-damage of the islet beta cells responsible for the secretion of insulin. Its management is problematic and complex, particularly using conventional drugs. Thus, gene therapy is partly an emerging promising therapeutic alternative in its treatment [ 45 , 46 ]. The etiology of T1DM is multifactorial involving both environmental and genetic factors akin to any other autoimmune disease. In the recent past, researchers have favourably pointed out many genes accountable for the evolution of T1DM [ 47 ]. Thus, alteration or grappling with these genes employing gene therapy techniques will probably foster better comprehensible management of the ailment or even cure T1DM.

Even though gene therapy for DM majorly centres on T1DM, many genes have been evaluated as a probable treatment for T2DM as the ailment has a compelling genetic susceptibility [ 48 ]. About 75 independent genetic loci have been identified for T2DM via genetic linked studies and different novel therapeutic targets have also been determined [ 46 ]. Genetic loci might have a huge impact on drug response in contrast to the incidence and development of diseases whose effects are limited [ 49 ]. Many genetic loci exist with prospects for T2DM gene therapy. For instance, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) is a good example. NLRP3 inhibition mitigates inflammation, guard against apoptosis of pancreatic b-cells including the prevention of development of T2DM in mice [ 50 ]. Hypothetically, all genes associated with the beginning, evolution, and deterioration of T2DM are probable targets. In Table 1 [ 51 ], the genes that modulate the homeostasis of glucose, ameliorate insulin synthesis or/and responsiveness, and improve diabetic mellitus-induced complications are abridged for simplicity.

Promising targets that can be employed for T2DM gene therapy.

Legend: HSP70 = heat shock protein 70; NLRP3 = nucleotide-binding oligomerization domain-like receptor protein 3; SGLTs = sodium-glucose co-transporters; GLUTs, glucose transporters; SIRT6=Sirtuin 6; FGFs = fibroblast growth factors; GPGRs = G protein–coupled receptors; GLP-1= glycogen-like peptide 1; ADPN = adiponectin; CTB APSL = cholera toxin B subunit and active peptide from shark liver; TGF-a = transforming growth factor-alpha; DKD = diabetic kidney disease [ 51 ].

4.5. Stem Cell Therapy in Diabetes

The conventional approaches in the management of DM do not resolve the causes of the ailment and are laden with adverse effects. Hence, there is a quest for a desirable different therapeutic regimen. The cellular-based therapeutic technique currently in use in DM management is based on the pancreas or islet-cell transplantation to revive the beta cells for insulin secretion. This approach is restricted due to a lack of donor organs. These problems lead to the exploration of the possibility of constructing beta cells using stem cells. The peculiar rebuilding potential of stem cells might be an important tool that could be used in the management of DM. Development of replenishable islets source using stem cells might avert the recent supply/demand problems in the transplantation of islet and furnish DM subjects with a prolonged source of beta cells for insulin secretion. Hence, in the management of DM, stem cell investigation has become a promising approach [ 52 ].

The stem cell DM therapy is aimed at the replacement of malfunctioning or damaged pancreatic cells by employing pluripotent or multipotent stem cells. This technique has exploited the ability of various kinds of stem cells including induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), and adult stem cells using diverse methods to produce surrogate beta cells or to bring back the physiologic role of the beta cell [ 53 ].

Advancement in technology has facilitated the development of stem cells using different kinds of tissue sources such as adipose tissue, skin, bone marrow, umbilical cord blood, periosteum, and dental pulp. In searching for promising stem cells, the first organ of choice is usually the pancreas. Studies with animal models have indicated that a small number of pancreatic tissue when made available could bring back the optimum pancreatic beta-cell mass [ 54 ]. This is sequel to the differentiated beta cells from the pancreatic duct undergoing replication and dedifferentiation culminating in the formation of pluripotent cells which in turn synthesize more beta cells. Additional study suggested that these ductal cells populations could be produced in vitro and directed to produce insulin synthesizing clusters [ 55 , 56 ].

Moreover, the haemopoietic adult stem cells such as HSCs and mesenchymal stem cells (MSCs) have the potential to transdifferentiate into so many cell lineages such as the brain, liver, and lung as well as gastrointestinal tract cells [ 57 , 58 , 59 ]. A different group of researchers experimented on the multipotent differentiation of haemapoietic progenitors to replenish the beta cell number in T1DM. It was reported that the bone marrow of mouse was differentiated ex vivo into functional beta cells [ 60 ]. Relatedly, studies using the mice model indicated that cells of the bone marrow could be amenable to the pancreas as a target and that elevated blood glucose could be normalized [ 61 ]. An experiment with autologous HSCs demonstrated an improvement in T1DM and T2DM [ 62 , 63 ]. These studies furnish potential outcomes for the usage of autologous HSCs in the management of DM.

4.6. Latest Inventions in Diabetes Management

In addition to the aforementioned innovations in the management of diabetes, several drugs are still at different stages of clinical trial for eventual use. Others are ready and have been recently introduced into the market.

4.6.1. Drugs Recently Introduced

Tirzepatide: The drug was recently approved by the FDA under the trade name mounjaro for the treatment of T2DM [ 64 ]. Tirzepatide is an injectable given under the skin once in a week which targets the receptors of hormones which play central role in the metabolism of glucose. These hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). While the GLP-1 reduces blood glucose by several mechanisms, including stimulating insulin secretion and suppressing glucagon release during hyperglycemia, GIP stimulates insulin release during hyperglycemia, but it also stimulates glucagon release during hypoglycemia.

Tirzepatide acts as agonist to their receptors [ 65 ], hence elongating their functions which results in blood glucose control. The efficacy of tirzepatide was established against a placebo, a GLP-1 receptor agonist (semaglutide) and two long-acting insulin analogs either as monotherapy or in combination with other antidiabetic agents [ 64 ]. In comparison to the placebo, it lowered the HbA1c by 11.6% and 1.5% as monotherapy and combination therapy, respectively. In comparison to other antidiabetic drugs, at the highest dose of 15 mg, it lowered the HbA1c 0.5% more than semaglutide, 0.9% more than insulin degludec and 1.0% more than insulin glargine [ 64 ]. Because of the efficacy therein and the once in a week dosing, tirzepatide provides a desirable paradigm shift in the management of T2DM.

4.6.2. Drugs in the Pipeline

Several drug candidates are at different phases of development for the management of DM. These are listed below.

LY3502970: LY3502970 is a partial agonist, biased toward G-protein activation over β-arrestin recruitment at the (GLP-1 receptor (GLP-1R). The molecule is highly potent and selective against other class B G-protein-coupled receptors (GPCRs) with a pharmacokinetic profile favorable for oral administration [ 66 ]. It is a product that is currently being developed by Eli lilly.

SCO-094: SCO-094 is a drug candidate identified by SCOHIA company which has a dual target of the receptors of GIP and GLP-1 [ 67 ]

Ladarixin (LDX): Ladarixin is an inhibitor of the interleukin-8 receptors CXCR1 and CXCR2, in new-onset T1DM [ 68 ]. It is a drug candidate developed by Dompe Farmaceutici. Short term LDX treatment of newly diagnosed patients with T1DM had no appreciable effect on preserving residual beta cell function [ 68 ].

5. Discussion of Major Findings

DM is a complex, progressive, and multifactorial metabolic disorder needing more complex treatments over time. Globally, researchers have worked assiduously in the discovery and development of novel drugs for the treatment of diabetes. There is significant progress in research into the cause and management of T1DM [ 69 ]. Mounting evidence indicates that modern insulin therapy in combination with glucose self-monitoring including blood pressure and lipid monitoring has profoundly improved the long-term prognosis of T1DM [ 70 ]. The literature indicates that regular exercise and improved diet may enhance the quality of life for diabetic subjects but in the absence of adequate exercise and diet, medications may help diabetic persons regulate their blood glucose level. Moreover, implantation of insulin producing cells could furnish the basal glucose level essential for maintaining glucose homeostasis in vivo and thus hinder long-term injury from occurring in different tissues regardless of hormone administration [ 71 ].

The attainment of the full potential of gene therapy technique could be obtained via the design of gene delivery vectors that are safe, efficient, and specific and/ or the development of a technique for engineering of cell, in which the stem cell seems to be of great importance. Thus, the establishment of a reliable, sensitive, and acutely monitored feedback system is needed for the generation of a safe and efficient vector to facilitate diabetes gene therapy for clinical trial. Probably, the curtailment of islet transplantation rejection is the first clinical technique to DM gene therapy approach. On the other hand, insulin gene therapy is carried out in concert with conventional insulin treatment culminating in tight glycemic regulation in the absence of fasting hypoglycemia in T1DM subjects, as reported in T1DM rats [ 72 ].

Physical activity and nutrition therapy could help individuals with DM achieve metabolic goals. Employing diverse lifestyle approaches might help. Regulation of metabolic parameters such blood pressure, glucose, glycated hemoglobin, lipids, and body weight including the assessment of life quality are critical in determining the level of treatment goals by lifestyle changes [ 73 ]. However, different countries have focused on DM management and its complications on the normalization of glycemic control as assessed by hemoglobin A1 or fasting blood glucose which only addresses the need of subjects who were already diabetic. Thus, it is imperative to design programs for the early detection of altered glucose metabolism and to carry out robust approaches for the normalization of this changed state. Furthermore, through robust prevention strategies, better diagnostic tests, early risk detection, and management of the risks will help mitigate the incidence of DM and reduce or prevent events associated with end-organ failure [ 73 ].

Besides glycemic control, multifactorial interventions using different treatment regimen, including nanotechnology, gene therapy, stem cell, medical nutrition therapy, and lifestyle modification have yielded significant results in ameliorating the impact of DM but not without some challenges. Regardless of the promising nature of nanotechnology and its projected ability to turn around the fortunes in diabetes management, it is still faced with some challenges. One of the major limitations is the cost. Most of the gadgets required for CGM, and insulin delivery are very expensive. This limits their use to the rich class even when diabetes cuts across different economic classes. More so, there is an increased risk of infection via the implantation of sensors and cannulas which increases inflammation and could be frightening sometimes [ 24 ].

Notwithstanding the merits linked with the gene therapy approach, there could equally be problems. For example, genes introduced employing a viral vector might provoke an immune response and aggravate the disease condition [ 74 ]. Additionally, gene therapy studies are still mostly carried out using animal models and their safety is yet to be validated in humans [ 46 ].

Currently, it is established that gene delivery technology is the primary hurdle for successful gene therapy. The prime factors for an effective gene delivery technique include efficiency, stability, specificity, safety, and convenience. Thus, the greatest obstacle in gene therapy is the method of delivery of the corrective gene to the target site safely and efficiently. There is, therefore, a requirement of desirable gene delivery technology or vector to furnish the therapeutic potential where required. The two main vectors currently employed are viral and non-viral vectors. The merit of the non-viral vector is that it has low immunity, a low financial burden, and its preparation is convenient but the major obstacles for its extensive use emanate from the inefficiency of delivery method and expression of gene transiently [ 75 ]. Contrastingly, reports show that viral vectors are more efficient in gene delivery as several of them use a distinct mechanism for DNA delivery to the cells. Viral vectors are arranged as viral particles having precisely the important modulated sequences of the virus and from which all the genes of the virus have been excised. These viruses, when prepared very well, are defective that after target cell infection, there is no probable replication or infection theoretically [ 76 ]. Viral DNA is integrated with the genome of the host cell, thereby bestowing the capability for sturdy therapeutic gene expression.

Despite the fact that viral vectors are more efficient in comparison to non-viral vectors as gene delivery systems, there are still challenges associated with them, including inflammation, cytotoxicity, and immunogenicity which are needed to be looked into during the construction of viral vector system [ 46 ].

Notwithstanding the huge and novel impacts recorded in the applicable areas of stem cell biology in the management of DM, it is still in its primitive stage. A lot of hurdles still hinder the progression of stem cell research technologically and ethically, including:

The use of ESCs is confronted with the formation of teratomas and the danger of malignancy [ 77 ], thus raising safety concerns. This makes it imperative for a thorough investigation and screening of the probable adverse effects prior to its deployment in clinical trials and human treatment.

The primary hurdle associated with transplantation is autoimmune rejection. This makes it necessary for a stable and appropriate regimen for immunosuppression. There is a need for the stabilization of current transplantation protocols with the standard testing module. The transplantation of stem cells needs a few experimental works to appraise the problems linked with the stability, durability, and the survival of the transplanted cell with appropriate vascular and neural support in the new microenvironment.

The challenges of scale-up problems arise after the optimization of the appropriate developmental procedures. The number of cells must be enough to cope with the requisite request for future research including clinical investigations. Hence, an efficient method is required for the maximization of the yield via an adjustment in the culture requirements. The stem cells’ scale-up ability is needed for future exploration for the provision of surplus transplanted cellular reserves in order to strike equilibrium between demand and usage.

As a result of where it is obtained from, the ESCs are the potential targets for the ethicists. Normally, ESCs are obtained from embryos not fertilized or used during ex vivo fertilization in hospitals. Informed consent is usually required in the procurement of these ESCs from the donor prior to the usage in clinical research. Sadly, though, in the majority of instances, there is the destruction of the embryo during the process of obtaining the cells from the embryo, and this questions the source of life and the ethical license to terminate the fetus. Adult stem cells are preferable to embryonic ones as the controversy about their usage is limited. The current advancement in technology in induced pluripotent stem cell research is to allow the use of ones’ stem cells for diverse uses [ 78 ]. The adult cells are reprogrammed in such cases to pluripotent conditions and thereafter transformed into working beta cells. This approach might eventually resolve the impasse linked with ESCs and contribute to further safety issues likely to be tackled later in the future.

6. Conclusions

DM has become a public clinical challenge that requires urgent attention and the increasing trend in its cases is suggested to continue for more decades. Currently, there is no permanent cure for DM. Many treatment regimens have shown promising results in DM management. Yet, notwithstanding the potential of these giant treatment plans, DM remains a serious challenge that may continue to threaten public health. Thus, the problems encountered in each of these approaches need to be addressed to achieve a robust, efficient, and safe clinical management plan. There is a need for optimal metabolic regulation of glucose, blood pressure, and body weight which requires proper education and support for the improvement of diet, physical activity, and reduction in body weight. To effectively and successfully manage the control of this disease, an emphasis on public policies to reinforce health care access and resources, the promotion of a patient-centred care approach, and health-promoting infrastructures at environmental level are required.

Funding Statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author Contributions

Conception and Design: C.A., C.O.E. and I.A.; Data Collection: C.A., C.O.E., P.N.O. and N.A.O.; Data Analysis and Table Creation: C.A., P.M.A., J.C. and B.O.A. Writing the Manuscript: C.A., C.O.E., P.M.A., N.A.O., J.C., B.O.A., P.N.O. and I.A.; Vetting the manuscript for intellectual content: I.A.; Approval of the manuscript for submission: All the authors. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Informed consent statement, data availability statement, conflicts of interest.

The authors declare that they have no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Breakthrough diabetes study could lead to end of regular insulin injections, researchers say

Researchers say they have made a breakthrough in the treatment of type 1 diabetes which could replace the need for regular insulin injections.

Research published by Baker Heart and Diabetes Institute scientists shows they have manipulated existing pancreatic stem cells to prompt them to produce insulin.

The study from the Melbourne researchers builds on previous work by Monash University scientists, using two existing cancer drugs. 

The research is still in its early days and the next step will be pre-clinical animal trials.

But lead researcher and Baker institute scientist, Sam El-Osta, said the potential treatment could be viable for children and adults in the future.

"What we've discovered is the ability to harness the patient's remaining pancreatic cells to influence those cells to behave like insulin-producing beta cells," Professor El-Osta told ABC Radio Melbourne.

"This could potentially modify the course of diabetes and potentially eliminate the need for round-the-clock insulin injections in some people living with type 1 diabetes."

Broadly, people with diabetes do not naturally produce enough insulin, or their bodies do not use the hormone as they should.

For many people with diabetes, it means multiple insulin injections are required daily to manage the illness.

Research could be 'holy grail'

The two cancer drugs used in the research are already approved by the US Food and Drug Administration.

Researchers said the potential treatment could be "rapid" compared to current treatment options for type 1 diabetes.

"We've been able to repurpose these drugs to determine whether we could influence the trajectory by using these small molecule inhibitors in pancreatic ductal cells," Professor El-Osta said.

"We can quickly influence insulin restoration in a number of days in a dish from tissues derived from type 1 diabetes donors, both children and adults."

Diabetes Australia estimates around 134,000 people in Australia are living with type 1 diabetes, which represents about 10 per cent of all diabetes cases.

The Baker Heart and Diabetes Institute researchers are optimistic their work could potentially help people living with insulin-dependent type 2 diabetes.

The research has been published in a Nature scientific journal, Signal Transduction and Targeted Therapy.

Chief executive of the Australian Diabetes Society and University of Melbourne associate professor, Sof Andrikopoulos, labelled the research as "remarkable". 

"For the 135,000 Australians with type 1 diabetes, this is the holy grail. This is it," he said. 

"There's a potential here that this research might lead to the cure of type 1 diabetes, at some point down the road.

"It also has the potential to make a significant improvement in type 2 diabetes."

Dr Andrikopoulos, who was not involved with the study, said the research would reduce the burden of the disease.

"This research has the potential for the body itself, to produce and secrete insulin. So you can see that you're getting rid of needles, you're getting rid of insulin pumps, you're getting rid of finger pricking, you're getting rid of continuous glucose monitors," he said.

While he was hopeful for the future, Dr Andrikopoulos warned steps towards a cure would require consistent funding for diabetes research.

• X (formerly Twitter)
• Science and Technology

A .gov website belongs to an official government organization in the United States.

A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

• Risk Factors
• Providing Care
• Living with Diabetes
• Clinical Guidance
• DSMES for Health Care Providers
• Prevent Type 2 Diabetes: Talking to Your Patients About Lifestyle Change
• Employers and Insurers
• Community-based Organizations (CBOs)
• Toolkits for Diabetes Educators and Community Health Workers
• National Diabetes Statistics Report
• Reports and Publications
• Data and Statistics
• Current Research Projects
• National Diabetes Prevention Program
• State, Local, and National Partner Diabetes Programs for Public Health
• Diabetes Self-Management Education and Support (DSMES) Toolkit

Diabetes Data and Statistics

At a glance.

Access the U.S. Diabetes Surveillance System, the National Diabetes Statistics Report, and additional resources for key diabetes data and statistics.

About the interactive U.S. Diabetes Surveillance System

Watch this brief animation to learn how to use the U.S. Diabetes Surveillance System , an interactive web tool that provides diabetes data at national, state, and county levels and by age, sex, race/ethnicity, and education.

Data and statistics FAQs‎

Get the latest data on diabetes incidence, prevalence, complications, cost, and more.

Diabetes State Burden Toolkit

Access the toolkit here .

More data resources

• Kidney Disease Surveillance System
• Vision and Eye Health Surveillance System
• Morbidity and Mortality Weekly Report

Diabetes is a chronic disease that affects how your body turns food into energy. About 1 in 10 Americans has diabetes.

For Everyone

Health care providers, public health.

Cure-Focused Diabetes Research

The Diabetes Research Institute houses teams of scientists, engineers, and clinicians with the expertise required to tackle diabetes from many angles. This integration of medicine and technology drives the vision behind the DRI strategy, a comprehensive, multidisciplinary approach to cure diabetes. The strategy builds upon decades of cure-focused research and addresses the major challenges that stand in the way of a biological cure.

A cure is within reach.

A cure would mean restoring natural insulin production and normalizing blood sugar levels without imposing other risks.

DRI clinical trials are already dramatically improving the lives of some people with type 1 diabetes who are now living insulin-free.

The Institute’s scientists are addressing the major research challenges that stand in the way of a biological cure. But continuing this research is only possible with your support.

News & Events

Visit the DRI Foundation Virtual Tour >

Tour the DRI’s facilities and meet our team in the metaverse! Learn how you can help us find a cure…

Inside Our Labs…

Hamptons Garden Gala…

Diabetes Research…

Get the latest news in your inbox.

Hear from our team.

Meet our team in the search for a cure. Hear the stories of the researchers, patients, and supporters who are helping drive our research forward.

Diabetes and Family…

Advancements and…

DRIF 50 Years…

Help our team find a cure.

Dri virtual tour.

Diabetes News

Top headlines, latest headlines.

• BCG Vaccine: Protecting Type 1 Diabetics
• Ancestral Components of Japanese People
• Neuropathy Very Common, Underdiagnosed
• Improving Preeclampsia Detection
• Cells That Can Repair Damaged Blood Vessels
• Cranberry Extracts and Health
• Genetics of Common Childhood Obesity
• Toward More Effective Gene Therapies
• Promising Experimental Type 1 Diabetes Drug
• Preventing Depression and Type 2 Diabetes

Earlier Headlines

Thursday, april 25, 2024.

• Food in Sight? The Liver Is Ready!

Tuesday, April 23, 2024

• Genetics Predict Type 2 Diabetes Risk and Disparities in Childhood Cancer Survivors
• Follow-Up 50 Years on Finds Landmark Steroid Study Remains Safe

Friday, April 19, 2024

• Shoe Technology Reduces Risk of Diabetic Foot Ulcers

Thursday, April 18, 2024

• Siblings With Unique Genetic Change Help Scientists Progress Drug Search for Type 1 Diabetes

Tuesday, April 16, 2024

• New Study Focuses on the Placenta for Clues to the Development of Gestational Diabetes

Monday, April 15, 2024

• Take It from the Rats: A Junk Food Diet Can Cause Long-Term Damage to Adolescent Brains

Friday, April 12, 2024

• Scientists Uncover a Missing Link Between Poor Diet and Higher Cancer Risk

Thursday, April 11, 2024

• This Outdated Diabetes Drug Still Has Something to Offer

Wednesday, April 10, 2024

• Does the Time of Day You Move Your Body Make a Difference to Your Health?
• Global Research Team Finds No Clear Link Between Maternal Diabetes During Pregnancy and ADHD in Children

Tuesday, April 9, 2024

• Beating Back Bitter Taste in Medicine

Thursday, April 4, 2024

• Few Newly Diagnosed Type 2 Diabetics Succeed in Losing Weight -- Weight Gain Linked to Much Higher Risk of Complications
• Study Finds Less Invasive, Safer Option for Removing Benign Pancreatic Tumors

Wednesday, April 3, 2024

• Large Language Models Respond Differently Based on User's Motivation

Tuesday, April 2, 2024

• Wound Treatment Gel Fights the Battle Against Antibacterial Resistance

Thursday, March 28, 2024

• Do Sweeteners Increase Your Appetite? New Evidence from Randomised Controlled Trial Says No
• For Younger Women, Mental Health Now May Predict Heart Health Later
• Eggs May Not Be Bad for Your Heart After All
• Clear Shift in Arterial Diseases in Diabetes
• Miscarriages Linked to Health Risks in Later Pregnancies

Wednesday, March 27, 2024

• Risk Factors for Faster Aging in the Brain Revealed in New Study
• Discovery Has Potential to Solve the Billion-Dollar Global Cost of Poorly Managed Wound Healing

Monday, March 25, 2024

• Insulin Affects the Recycling of Cellular Power Plants

Wednesday, March 20, 2024

• Metformin During Pregnancy Affects the Brain Development in Offspring Mice, Study Finds

Monday, March 18, 2024

• Kallistatin Contributes to the Beneficial Metabolic Effects of Weight Loss
• Study With Innovative Insights Into the Heterogeneity of Type 2 Diabetes
• Potential Novel Biomarkers of Coronary Heart Disease Discovered

Wednesday, March 13, 2024

• Revolutionary Chronic Wound Treatment Could Help Millions
• Milk to the Rescue for Diabetics? Cow Produces Human Insulin in Milk

Wednesday, March 6, 2024

• Study Reveals Genetic Clusters and Biological Pathways That May Explain Differences in Type 2 Diabetes Risk
• AI Can Speed Design of Health Software
• Too Little Sleep Raises Risk of Type 2 Diabetes, New Study Finds

Wednesday, February 21, 2024

• Blood Test Could Determine Diabetes Risks

Tuesday, February 20, 2024

• Red Light Can Reduce Blood Glucose Levels
• Fasting-Like Diet Lowers Risk Factors for Disease, Reduces Biological Age in Humans

Monday, February 19, 2024

• Newly Discovered Genetic Markers Help Pinpoint Diabetes Risks, Complications

Wednesday, February 14, 2024

• Gargling Away the 'bad' Bacteria in Type 2 Diabetes

Tuesday, February 13, 2024

• Type 2 Diabetes Alters the Behavior of Discs in the Vertebral Column

Thursday, February 8, 2024

• Heart Organoids Simulate Pregestational Diabetes-Induced Congenital Heart Disease
• AI Model as Diabetes Early Warning System When Driving

Tuesday, February 6, 2024

• Males Born to Obese Mothers More Likely to Suffer Health Issues as Adults

Monday, February 5, 2024

• New Weight Loss Medication May Help Lower Blood Pressure in Adults With Obesity

Thursday, February 1, 2024

• Disrupted Cellular Function Behind Type 2 Diabetes in Obesity
• Researchers Use the Eye as a Window to Study Liver Health
• Diabetes and Liver Cancer: Study Suggests New Screening Guidelines

Wednesday, January 31, 2024

• Diabetes Medication Class Tied to Lower Risk of Kidney Stones
• Researchers Uncover Potential Non-Opioid Treatment for Chronic Pain

Tuesday, January 23, 2024

• Popular Diabetes Drug May Also Reduce the Risk of Severe Liver Disease
• Few Patients Successfully Treat Their Type 2 Diabetes Through Weight Loss

Friday, January 19, 2024

• Simple and Reliable Early Prediction of Diabetes
• New Medicine Can Create a New Life for Diabetes Patients -- Without Needles

Thursday, January 18, 2024

• Role of 'hunger Hormone' Receptor in Obesity-Realted Chronic Inflammation

Wednesday, January 17, 2024

• Childhood Stress Linked to Higher Risk of High Blood Pressure, Obesity, Diabetes in Adults

Saturday, January 13, 2024

• Study Finds AI-Driven Eye Exams Increase Screening Rates for Youth With Diabetes

Thursday, January 11, 2024

• Genetically Modified Pluripotent Stem Cells May Evade Immunological Rejection After Transplantation, Study Shows

Tuesday, January 9, 2024

• How Fruit Bats Got a Sweet Tooth Without Sour Health
• Arsenic May Raise Diabetes Risk for Males

Thursday, January 4, 2024

• Study Shows Liraglutide Results in Increased Insulin Sensitivity Independent of Weight Loss
• Study Charts Possibilities for a Better Way to Diagnose Gestational Diabetes

Wednesday, January 3, 2024

• New Reasons Eating Less Fat Should Be One of Your Resolutions

Thursday, December 21, 2023

• Why People With Diabetes Are More Prone to Respiratory Risk

Tuesday, December 19, 2023

• Novel Approach Emerging for Rescuing Limbs at Risk

Friday, December 15, 2023

• US Adults Eat a Meal's Worth of Calories of Snacks in a Day

Wednesday, December 13, 2023

• Epigenetic Changes Can Cause Type 2 Diabetes

Tuesday, December 12, 2023

• Nearly 40% of Type 2 Diabetes Patients Stop Taking Their Second-Line Medication

Monday, December 11, 2023

• Tirzepatide Enhances Weight Loss With Sustained Treatment but Discontinuation Leads to Weight Regain

Friday, December 8, 2023

• New Cause of Diabetes Discovered, Offering Potential Target for New Classes of Drugs to Treat the Disease

Thursday, December 7, 2023

• Diabetes Drug May Reduce Risk for Colorectal Cancer

Monday, December 4, 2023

• Stimulating Nerves Connected to the Pancreas Regenerates Insulin-Producing Cells, Mouse Study Shows
• Macrophages 'eat' Insulin-Producing Cells to Regulate Insulin After Mice Have Given Birth

Friday, December 1, 2023

• Researchers Caution Diabetes Patients' Use of Fitness Video Games

Monday, November 27, 2023

• Stem Cell-Based Treatment Controls Blood Sugar in People With Type 1 Diabetes

Tuesday, November 21, 2023

• Novel Molecular Mechanisms in the Early Development of Diabetes Mellitus

Thursday, November 16, 2023

• Hormones Have the Potential to Treat Liver Fibrosis

Wednesday, November 15, 2023

• NHS Diabetes Prevention Programme May Have Global Impact

Monday, November 13, 2023

• Shortening Sleep Time Increases Diabetes Risk in Women
• Semaglutide Reduced Cardiovascular Events by 20% in Certain Adults

Thursday, November 9, 2023

• Drug Screen Points Toward Novel Diabetes Treatments

Tuesday, November 7, 2023

• Obesity Linked to Neurodegeneration Through Insulin Resistance

Monday, November 6, 2023

• A Step Closer to Injection-Free Diabetes Care: Innovation in Insulin-Producing Cells

Wednesday, November 1, 2023

• Repurposed Drug Offers New Potential for Managing Type 1 Diabetes
• New Research Links High Salt Consumption to Risk of Type 2 Diabetes

Tuesday, October 31, 2023

• High Insulin Levels Directly Linked to Pancreatic Cancer

Monday, October 30, 2023

• Weekly Insulin Injections Have the Potential to Be as Effective in Diabetes Management as Now-Common Daily Injection Regimes

Friday, October 27, 2023

• Intermittent Fasting Is Safe, Effective for Those With Type 2 Diabetes, Study Suggests

Tuesday, October 24, 2023

• New Technology 'game Changing' For Pregnant Women With Diabetes

Thursday, October 19, 2023

• Red Meat Consumption Associated With Increased Type 2 Diabetes Risk
• NUS Scientists Develop Innovative Magnetic Gel That Heals Diabetic Wounds Three Times Faster
• Eyes May Be the Window to Your Soul, but the Tongue Mirrors Your Health

Wednesday, October 18, 2023

• Strength Training May Reduce Health Risks of a High-Protein Diet

Wednesday, October 11, 2023

• Risk Factors for Dementia Vary by Ethnicity, Study Finds

Tuesday, October 10, 2023

• Maternal Obesity Predicts Heart Disease Risk Better Than Pregnancy Complications

Tuesday, October 3, 2023

• Pregnant Women Offered New Hope for Safe and Effective Gestational Diabetes Treatment
• Type 2 Diabetes Diagnosis at Age 30 Can Reduce Life Expectancy by Up to 14 Years

Friday, September 29, 2023

• Diabetes May Accelerate Blood Cancer Growth, Yet Survival Outcomes Differ by Race

Wednesday, September 27, 2023

• Exercise and Muscle Regulation: Implications for Diabetes and Obesity

Monday, September 25, 2023

• Wearable Devices Show Who May Need More Help Managing Diabetes

Thursday, September 21, 2023

• Compound Derived from Hops Reduces Abundance of Gut Microbe Associated With Metabolic Syndrome
• Study Shows Morning and Afternoon Slightly Better Than Evening Physical Activity for Diabetes Prevention
• LATEST NEWS
• Health & Medicine
• Diseases & Conditions
• Alzheimer's Research
• Amyotrophic Lateral Sclerosis
• Attention Deficit Disorder
• Back and Neck Pain
• Birth Defects
• Bladder Disorders
• Blood Clots
• COVID and SARS
• Cervical Cancer
• Bladder Cancer
• Multiple Myeloma
• Pancreatic Cancer
• Brain Tumor
• Colon Cancer
• Breast Cancer
• Ovarian Cancer
• Lung Cancer
• Mesothelioma
• Skin Cancer
• Prostate Cancer
• Cerebral Palsy
• Chikungunya
• Chronic Fatigue Syndrome
• Cold and Flu
• Crohn's Disease
• Cystic Fibrosis
• Dengue Fever
• Down Syndrome
• Eating Disorder Research
• Encephalitis
• Epilepsy Research
• Erectile Dysfunction
• Fibromyalgia
• Gastrointestinal Problems
• HIV and AIDS
• Headache Research
• Hearing Loss
• Heart Health
• Cholesterol
• Stroke Prevention
• Heart Disease
• Hormone Disorders
• Hypertension
• Infectious Diseases
• Insomnia Research
• Irritable Bowel Syndrome
• Kidney Disease
• Liver Disease
• Lung Disease
• Lyme Disease
• Mental Health Research
• Multiple Sclerosis Research
• Mumps, Measles, Rubella
• Muscular Dystrophy
• Osteoporosis
• Parkinson's Research
• Prostate Health
• Restless Leg Syndrome
• Sickle Cell Anemia
• Sleep Disorder Research
• Thyroid Disease
• Triglycerides
• Tuberculosis
• Medical Topics
• Accident and Trauma
• Alternative Medicine
• Birth Control
• Bone and Spine
• Chronic Illness
• Controlled Substances
• Dietary Supplements and Minerals
• Epigenetics
• Food Additives
• Foodborne Illness
• Foot Health
• Gene Therapy
• Health Policy
• Human Biology
• Immune System
• Joint Health
• Medical Imaging
• Nervous System
• Pain Control
• Personalized Medicine
• Pharmacology
• Psychology Research
• Wounds and Healing
• PHYSICAL/TECH
• ENVIRONMENT
• SOCIETY & EDUCATION
• Orchids Aid Seedlings Through Fungal Networks
• Precise Maps of the Moon's Surface
• Amazing Expertise of Scent Detection Dogs
• Getting to Grips With a Handy Extra Thumb
• H5N1 Bird Flu Transmitted from Cows to Humans
• YouTubers Cheer You Up More Than Casual Friends
• Brain Network Responsible for Stuttering
• When Should You Neuter or Spay Your Dog?
• Why Do Dyeing Poison Frogs Tap Dance?
• Cold Supply Chains for Food: Huge Savings

Trending Topics

Strange & offbeat.

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Published: 28 May 2024

Prediabetes remission for type 2 diabetes mellitus prevention

• Andreas L. Birkenfeld   ORCID: orcid.org/0000-0003-1407-9023 1 , 2 , 3 , 4 &
• Viswanathan Mohan   ORCID: orcid.org/0000-0001-5038-6210 5 , 6  

Nature Reviews Endocrinology ( 2024 ) Cite this article

3 Altmetric

Metrics details

• Medical research
• Pre-diabetes

Current guidelines for the delay and prevention of type 2 diabetes mellitus recommend for people with prediabetes to lose at least 7% of their body weight. Here, we advocate to use glycaemic remission as a goal of prevention in people with prediabetes and those who are at high risk for type 2 diabetes mellitus.

This is a preview of subscription content, access via your institution

Access options

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

24,99 € / 30 days

cancel any time

Subscribe to this journal

Receive 12 print issues and online access

195,33 € per year

only 16,28 € per issue

Buy this article

• Purchase on Springer Link
• Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Nathan, D. M. et al. Does diabetes prevention translate into reduced long-term vascular complications of diabetes? Diabetologia 62 , 1319–1328 (2019).

Article   PubMed   PubMed Central   Google Scholar  

American Diabetes Association Professional Practice Committee. prevention or delay of diabetes and associated comorbidities: standards of care in diabetes-2024. Diabetes Care 47 (Suppl 1), S43–S51 (2024).

Article   Google Scholar  

Sandforth, A. et al. Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS). Lancet Diabetes Endocrinol. 11 , 798–810 (2023).

Article   PubMed   Google Scholar  

Fritsche, A. et al. Different effects of lifestyle intervention in high- and low-risk prediabetes: results of the randomized controlled Prediabetes Lifestyle Intervention Study (PLIS). Diabetes 70 , 2785–2795 (2021).

Article   CAS   PubMed   Google Scholar  

Zhyzhneuskaya, S. V. et al. Time course of normalization of functional β-cell capacity in the diabetes remission clinical trial after weight loss in type 2 diabetes. Diabetes Care 43 , 813–820 (2020).

Tabák, A. G. et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 373 , 2215–2221 (2009).

Jumpertz von Schwartzenberg, R., Vazquez Arreola, E., Sandforth, A. et al. Role of weight loss-induced prediabetes remission in the prevention of type 2 diabetes: time to improve diabetes prevention. Diabetologia https://doi.org/10.1007/s00125-024-06178-5 (2024).

Taylor, R. Type 2 diabetes and remission: practical management guided by pathophysiology. J. Intern. Med. 289 , 754–770 (2021).

Sathish, T. et al. Effect of conventional lifestyle interventions on type 2 diabetes incidence by glucose-defined prediabetes phenotype: an individual participant data meta-analysis of randomized controlled trials. Diabetes Care 46 , 1903–1907 (2023).

Wagner, R. et al. Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes. Nat. Med. 27 , 49–57 (2021).

Download references

Acknowledgements

The authors acknowledge the members of ‘The Prediabetes Group’, who are listed in the Supplementary Information document, for their assistance with reviewing this article. A.L.B. acknowledges the support of funding from the German Federal Ministry for Education and Research (01GI0925) via the German Center for Diabetes Research (DZD e.V.).

Author information

Authors and affiliations.

German Center for Diabetes Research (DZD), Neuherberg, Germany

Andreas L. Birkenfeld

Department of Internal Medicine IV, Diabetology, Endocrinology and Nephrology, Eberhard-Karls University Tübingen, Tübingen, Germany

Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany

Department of Diabetes, Life Sciences & Medicine Cardiovascular Medicine & Sciences, King’s College London, London, UK

Madras Diabetes Research Foundation, Chennai, India

Viswanathan Mohan

Dr. Mohan’s Diabetes Specialities Centre, Chennai, India

You can also search for this author in PubMed   Google Scholar

Corresponding author

Correspondence to Andreas L. Birkenfeld .

Ethics declarations

Competing interests.

The authors declare no competing interests.

Additional information

Related links.

Diabetes mellitus: https://www.who.int/news-room/fact-sheets/detail/diabetes

World Health Organization’s global targets for noncommunicable diseases: https://www.who.int/publications/i/item/9789241506236

Supplementary information

Rights and permissions.

Reprints and permissions

About this article

Cite this article.

Birkenfeld, A.L., Mohan, V. Prediabetes remission for type 2 diabetes mellitus prevention. Nat Rev Endocrinol (2024). https://doi.org/10.1038/s41574-024-00996-8

Download citation

Published : 28 May 2024

DOI : https://doi.org/10.1038/s41574-024-00996-8

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

International study reveals surprising twist in how diabetes drugs help the heart

A randomized, placebo-controlled clinical trial led by a collaboration between Duke-NUS Medical School, National Heart Center Singapore (NHCS) and Klinikum Nürnberg, Germany, has revealed surprising new insights into how SGLT2 inhibitor drugs, originally developed for diabetes, benefit patients with heart failure.

Contrary to common assumptions, these drugs may improve cardiac outcomes and heart health without acting as diuretics.

Heart failure is a condition where the heart cannot pump enough blood to meet the body's demands, often leading to fluid build-up in tissues and congestion of the blood circulation. This congestion strains the heart and causes symptoms like breathlessness and swelling.

Reducing congestion is key to managing heart failure, as it reduces the workload of the heart and thereby eases pumping.

SGLT2 inhibitor drugs are the new blockbuster treatment for chronic heart failure because they very quickly stabilize heart function and reduce hospitalizations and patient deaths. The drugs release more glucose into the urine, and thereby have the potential to pull more fluid from the body into the urine, alleviating the congestion experienced by patients with heart disease.

Given this diuretic potential, leaflets accompanying the drugs list dehydration as a common side effect of their use.

However, results from this clinical trial, published in the Journal of the American College of Cardiology , cast doubt on the presumed diuretic action of SGLT2 inhibitors in patients with heart failure.

First author Dr. Adriana Marton, visiting senior research fellow with the Cardiovascular & Metabolic Disorders Program at Duke-NUS, who kicked-off this pilot study in Singapore, said, "Many experts who relied on the idea that SGLT2 inhibitors act as diuretic drugs raised their eyebrows when we first reported our data, showing that the body instead activates a very elegant defense mechanism that almost entirely abolishes the potential diuretic effects of these drugs."

Conducted together with NHCS in Singapore, the double-blind, randomized, placebo-controlled trial, the gold standard of clinical trials, examined the SGLT2 inhibitor dapagliflozin in patients with chronic heart failure.

As expected, the drug sharply increased urine glucose excretion. This increased concentration of glucose in urine creates an osmotic imbalance that should cause more water to be pulled into the urine and therefore increase urine volume.

But that's not what happened. Instead, the body responded by releasing more vasopressin, a brain hormone that instructs the kidneys to conserve water. This minimized any rise in urine volume and even after 24 hours, patients' urine volume remained stable despite persistent glucose excretion from dapagliflozin.

These results, which are the first to be published from this international collaborative project, contradict the prevailing theory that SGLT2 inhibitors reduce congestion through diuresis or increased urine production.

Senior author Associate Professor Jens Titze from the Cardiovascular & Metabolic Disorders Program at Duke-NUS, explained that the brain quickly compensates for potential dehydration caused by these drugs, suggesting that their benefit to patients with heart failure might be through mechanisms other than reducing fluid overload.

"It seems that the brain's internal hydration meter very quickly detects reduced hydration levels, and then forces the kidneys to further concentrate the urine to prevent body water loss. This suggests that we need to rethink our assumptions of how SGLT2 inhibitors benefit patients with heart failure, since decongestion by increased urine production doesn't seem to be the answer," said Titze.

Associate Professor David Sim, head and senior consultant from the Department of Cardiology at NHCS and a senior co-author of the study, said, "As a cardiologist caring for many patients with heart failure, I am excited by the fresh perspective this study brings and the wider benefits these drugs may confer.

"We need robust research like this to stimulate new thinking on how to optimally treat heart failure—and ideally to prevent the disease even before it occurs. Our ultimate goal is to translate these insights into better outcomes for our patients, and to support Singaporeans in living long and healthy lives without heart disease."

New non-invasive tools ready to support next phase of this research collaboration

While these drugs clearly benefit patients with heart failure or chronic kidney disease, the mechanisms responsible for these beneficial effects are still unclear. One theory is that the process of energy and water conservation induced by these drugs induces metabolic changes in the body that improve organ function.

"We think that the initial glucose and water loss caused by the SGLT2 inhibitors triggers some ancient and highly conserved evolutionary body survival signals that flip metabolic switches to improve heart and kidney function," said Titze.

"Imagine walking in the desert on limited food and water. Your body would adapt by slowing non-essential processes to conserve resources, and invest energy only in the processes you really need. We hypothesize that SGLT2 inhibitors trigger similar survival pathways that re-program cell metabolism."

In parallel to the clinical trial in Singapore, the team's collaborators in Germany have developed methods that are now available to detect activation of these ancient metabolic pathways in patients' urine.

The team will use these to uncover the actual mechanisms behind these drugs' organ-protective benefits and investigate how these changes may improve the healthspan not just of patients with heart failure but also with kidney disease, diabetes or living with other aging-related ailments.

"We are very excited because we finally have treatment options that will improve the outcomes for these chronically ill patients, but there clearly is much more to learn about how these drugs protect the kidneys and the heart, and improve longevity, " explained Dr. Marton.

Martin is also a consultant nephrologist and clinical investigator at Klinikum Nürnberg and its medical university, Paracelsus Medizinische Privatuniversität (PMU), where she is currently conducting a follow-up clinical trial in patients with chronic kidney disease.

More information: Adriana Marton et al, Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure, Journal of the American College of Cardiology (2024). DOI: 10.1016/j.jacc.2024.02.020

Provided by Duke-NUS Medical School

Advertisement

Supported by

Ozempic Cuts Risk of Chronic Kidney Disease Complications, Study Finds

A major clinical trial showed such promising results that the drug’s maker halted it early.

• Share full article

By Dani Blum

Dani Blum has reported on Ozempic and similar drugs since 2022.

Semaglutide, the compound in the blockbuster drugs Ozempic and Wegovy , dramatically reduced the risk of kidney complications, heart issues and death in people with Type 2 diabetes and chronic kidney disease in a major clinical trial, the results of which were published on Friday. The findings could transform how doctors treat some of the sickest patients with chronic kidney disease, which affects more than one in seven adults in the United States but has no cure.

“Those of us who really care about kidney patients spent our whole careers wanting something better,” said Dr. Katherine Tuttle, a professor of medicine at the University of Washington School of Medicine and an author of the study. “And this is as good as it gets.” The research was presented at a European Renal Association meeting in Stockholm on Friday and simultaneously published in The New England Journal of Medicine .

The trial, funded by Ozempic maker Novo Nordisk, was so successful that the company stopped it early . Dr. Martin Holst Lange, Novo Nordisk’s executive vice president of development, said that the company would ask the Food and Drug Administration to update Ozempic’s label to say it can also be used to reduce the progression of chronic kidney disease or complications in people with Type 2 diabetes.

Diabetes is a leading cause of chronic kidney disease, which occurs when the kidneys don’t function as well as they should. In advanced stages, the kidneys are so damaged that they cannot properly filter blood. This can cause fluid and waste to build up in the blood, which can exacerbate high blood pressure and raise the risk of heart disease and stroke, said Dr. Subramaniam Pennathur, the chief of the nephrology division at Michigan Medicine.

The study included 3,533 people with kidney disease and Type 2 diabetes, about half of whom took a weekly injection of semaglutide, and half of whom took a weekly placebo shot.

Researchers followed up with participants after a median period of around three and a half years and found that those who took semaglutide had a 24 percent lower likelihood of having a major kidney disease event, like losing at least half of their kidney function, or needing dialysis or a kidney transplant. There were 331 such events among the semaglutide group, compared with 410 in the placebo group.

People who received semaglutide were much less likely to die from cardiovascular issues, or from any cause at all, and had slower rates of kidney decline.

Kidney damage often occurs gradually, and people typically do not show symptoms until the disease is in advanced stages. Doctors try to slow the decline of kidney function with existing medications and lifestyle modifications, said Dr. Melanie Hoenig, a nephrologist at Beth Israel Deaconess Medical Center who was not involved with the study. But even with treatment, the disease can progress to the point that patients need dialysis, a treatment that removes waste and excess fluids from the blood, or kidney transplants.

The participants in the study were extremely sick — the severe complications seen in some study participants are more likely to occur in people the later stages of chronic kidney disease, said Dr. George Bakris, a professor of medicine at the University of Chicago Medicine and an author of the study. Most participants in the trial were already taking medication for chronic kidney disease.

For people with advanced kidney disease, in particular, the findings are promising. “We can help people live longer,” said Dr. Vlado Perkovic, a nephrologist and renal researcher at the University of New South Wales, Sydney, and another author of the study.

While the data shows clear benefits, even the researchers studying drugs like Ozempic aren’t sure how, exactly, they help the kidneys. One leading theory is that semaglutide may reduce inflammation, which exacerbates kidney disease.

And the results come with several caveats: Roughly two-thirds of the participants were men and around two-thirds were white — a limitation of the study, the authors noted, because chronic kidney disease disproportionately affects Black and Indigenous patients. The trial participants taking semaglutide were more likely to stop the drug because of gastrointestinal issues, which are common side effects of Ozempic.

Doctors said they wanted to know whether the drug might benefit patients who have kidney disease but not diabetes, and some also had questions about the potential long-term risks of taking semaglutide.

Still, the results are the latest data to show that semaglutide can do more than treat diabetes or drive weight loss. In March, the F.D.A. authorized Wegovy for reducing the risk of cardiovascular issues in some patients. And scientists are examining semaglutide and tirzepatide, the compound in the rival drugs Mounjaro and Zepbound, for a range of other conditions , including sleep apnea and liver disease.

If the F.D.A. approves the new use, it could drive even more demand for Ozempic, which has faced recurrent shortages .

“I think it’s a game changer,” Dr. Hoenig said, “if I can get it for my patients.”

Dani Blum is a health reporter for The Times. More about Dani Blum

A Close Look at Weight-Loss Drugs

Reduced Disease Complications: Semaglutide, the compound in Ozempic and Wegovy, dramatically reduced the risk of kidney complications , heart issues and death in people with Type 2 diabetes and chronic kidney disease in a major clinical trial.

Supplement Stores: GNC and the Vitamin Shoppe are redesigning displays and taking other steps  to appeal to people who are taking or are interested in drugs like Ozempic and Wegovy.

Senate Investigation: A Senate committee is investigating the prices that Novo Nordisk charges  for Ozempic and Wegovy, which are highly effective at treating diabetes and obesity but carry steep price tags.

A Company Remakes Itself: Novo Nordisk’s factories work nonstop turning out Ozempic and Wegovy , but the Danish company has far bigger ambitions.

Transforming a Small Danish Town: In Kalundborg, population under 17,000, Novo Nordisk is making huge investments to increase production  of Ozempic and Wegovy.