A new article reviewing advances in the pathogenesis and treatment of diabetes explores the complex factors that contribute to the onset and progression of the disease, suggesting that understanding these dynamics is key to developing targeted interventions to reduce the risk of developing diabetes and manage its complications.
In an article published on July 25 in a special edition of 50He Anniversary issue of the peer-reviewed journal CellThe authors analyzed hundreds of studies that have emerged over the years and that examine the causes of type 1 (T1D) and type 2 (T2D) diabetes and new treatments for the disease. They examined the role played by genes, environmental factors, and social determinants of health, and the effect of diabetes on cardiovascular and kidney disease.
What they discovered shows that there are many advances in treatments that could stem the tide of a disease that has affected millions of people around the world and continues to grow. And some of these advances could be used to treat other disorders. But challenges remain.
“As the prevalence of diabetes continues to grow worldwide, it is important to understand the latest advances in research so that physicians can provide the best care for their patients and patients can make informed decisions that support better health outcomes,” said senior author Dr. E. Dale Abel, chair of the UCLA Department of Medicine. “This is an educational resource that integrates the latest research and trends in diabetes management, which may have implications for clinical practice as the diabetic patient population continues to grow.
“This review will be the go-to reference for clinicians and researchers and will provide a cutting-edge update on where the field currently stands and where it is headed,” Abel added.
Most people suffer from type 2 diabetes, the most important underlying causes of which are poor diet and obesity. Type 1 diabetes accounts for less than 5% of all cases. In 2021, about 529 million people worldwide had been diagnosed with diabetes, representing about 6.1% of the world’s population, or about one in 16 people. Prevalence in some regions is as high as 12.3%. Type 2 diabetes comprises about 96% of cases, with more than half due to obesity. An estimated 1.31 billion people will suffer from the disease by 2050, with prevalence rising to 16.8% in North Africa and the Middle East and 11.3% in Latin America and the Caribbean, the researchers write.
Genetics, the central nervous system and the interaction between various organs, as well as social and environmental factors such as food insecurity and air pollution, play a role in the development of diabetes.
However, some recent discoveries represent important advances toward controlling and perhaps even reversing the disease. For example, a 2019 study found that a 14-day course of the antibody teplizumab delayed the progression of type 1 diabetes from stage 1 to stage 3 by 24 months. A follow-up analysis in 2021 showed the delay could be as long as 32.5 months.
Based on these results, the U.S. Food and Drug Administration approved teplizumab as the first disease-modifying therapy for type 1 diabetes, the researchers write.
Advances in insulins with optimized pharmacokinetics, algorithm-driven subcutaneous insulin pumps, continuous glucose monitoring, and improved self-management tools have significantly improved the quality of life and outcomes for people with stage 3 type 1 diabetes.
In addition, stem cells could replace insulin-producing cells that are lost in type 1 diabetes, Abel said.
For type 2 diabetes, three classes of glucose-lowering medications (glucagon-like peptide receptor agonists (GLP1RAs), DPP-4 inhibitors, and SGLT-2 inhibitors) have been introduced over the past 20 years, allowing people to control their glucose levels without gaining weight and with a low risk of developing hypoglycemia. Personalized and precision medicine approaches are being explored to address the molecular mechanisms underlying diabetes. However, they need to prove that the benefits are clinically superior to standard care and that they are cost-effective. Furthermore, it remains to be seen whether precision approaches can be implemented in all settings around the world, including those with limited resources.
Combinations of GLP1Ras with molecules that act on other receptors, such as GIP, have shown even greater efficacy in treating diabetes. Recent studies have also shown them to be highly effective in treating obesity, certain types of heart failure and even sleep apnea, in part due to their potency in inducing weight loss and reducing inflammation. Clinical trials are currently underway to test their efficacy in treating other disorders, such as Alzheimer’s disease, Abel said.
“Advances in therapy now raise hopes for preventing or curing type 1 diabetes and treating type 2 diabetes in ways that not only improve metabolic homeostasis but also specifically reduce the risk and progression of cardiorenal disease,” the researchers write. “Finally, as we understand and develop tools to discern the underlying heterogeneity that leads to diabetes and its complications, the stage will be set to guide therapies and prevention strategies to optimize their impact, in ways that are broadly applicable across diverse populations and the availability of health care resources.”
Other co-authors include Anna Gloyn of Stanford University, Carmella Evans-Molina of Indiana University, Joshua Joseph of Ohio State University, Shivani Misra of Imperial College London, Utpal Pajvani of Columbia University, Judith Simcox of the University of Wisconsin-Madison, Katalin Susztak of the University of Pennsylvania, and Daniel Drucker of the University of Toronto.
The study authors’ research programs have been funded by the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK127236, U01DK127786, U01DK127382, R01 DK127308, R01DK133881, UC4 DK104166, P30 DK097512, UM1 DK126185, U01DK123743, U24DK098085, P30DK11607406, R01DK132403, AHRQ R01HS028822, DK103818, DK119767, R01DK133479), the National Heart, Lung, and Blood Institute(RO1DK125079, R61HL141783), American Heart Association (20SFRN35120123, 23SFRNCCS1052486, 23SFRNPCS1067039, 24FIM1266846), US Department of Veterans Affairs Merit Award (I01BX001733), Wellcome Trust (095101, 200837), Wellcome Trust Career Development Award (223024/Z/21/Z), Glenn Foundation, American Federation for Aging Research (A22068); Hatch Fellowship (WIS04000-1024796); JDRF (JDRF201309442); Canadian Institutes of Health Research (154321), a BBDC-Novo Nordisk Chair in Incretin Biology, and a Sinai Health-Novo Nordisk Endowment in Regulatory Peptides.