new research on type 2 diabetes

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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.

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These New Developments Could Make Living With Type 2 Diabetes More Manageable

E xperts often talk about the “burden” of a disease or illness. The word acts as a tidy container for all the unpleasantness people with that condition may experience—from their symptoms, to the cost of their care, to the restrictions imposed on their lifestyle, to the health complications that may arise. For people with Type 2 diabetes , this burden can be high.

Routine management of Type 2 diabetes often involves major changes to one’s diet and physical activity . And for many, especially those taking insulin to manage their blood sugar, the disease can necessitate daily blood-glucose monitoring, a process that entails pricking a finger to draw blood and then dabbing that blood onto a glucose monitor’s test strip. Doing this several times a week—month after month—can present overlapping challenges. According to a 2013 survey in the journal Diabetes Spectrum, people find finger-prick glucose monitoring to be painful, and the results can be confusing or unhelpful.

“Patients don’t want to prick their fingers, and they come in all the time and say, ‘I’m tired of this,’” says Dr. Francisco Pasquel, a diabetes specialist and associate professor of medicine at Emory University School of Medicine in Atlanta.

But relief is on the way. Continuous glucose monitors, or CGMs, are small devices-—often about the size of a quarter-—that use a small under-the-skin needle to continuously monitor blood-glucose levels. This information can be transmitted—in some cases wirelessly and automatically—to a smartphone app or other device. “You can look at glucose levels for a single point in time, but you can also look at trends in values over time,” says Dr. Roy Beck, medical director of the nonprofit Jaeb Center for Health Research in Tampa. Beck’s work has found that continuous glucose monitoring may provide a number of benefits for people with Type 2 diabetes.

These monitors are just one of several new advancements in Type 2 diabetes care and management. From connected technologies to new drug treatments, medical science is making steady and sometimes life-changing progress in the treatment of this condition. Here, experts describe some of the latest and greatest developments.

Continuous glucose monitors

People with Type 1 diabetes typically have to check their blood-sugar levels on a daily basis, or even multiple times each day. Because testing is such a big part of managing that disease, the research on continuous glucose monitors started with these patients. That work has shown that CGMs provide multiple benefits, including reduced hemoglobin A1C (HbA1c) levels, which is an important measure of healthy blood glucose. Continuous glucose monitors are now being studied in people with Type 2 diabetes, and research points to multiple benefits.

For a study published in 2021 in the Journal of the American Medical Association, Beck and his colleagues compared continuous glucose monitoring to standard finger-prick tests among people with Type 2 diabetes who were using insulin. They found that continuous monitoring was associated with a significantly greater drop in HbA1c. They also found that continuous monitoring helped people avoid risky and severe drops in blood sugar (a.k.a. hypoglycemia). “It’s pretty clear that there’s a benefit for people with Type 2 diabetes who are using insulin,” he says.

More than 90% of people with diabetes have Type 2 diabetes, and Beck says that roughly 30% of these people are using insulin. In other words, there are many people with Type 2 diabetes who stand to benefit from continuous glucose monitoring. However, use of these monitors is still mostly confined to people with Type 1 diabetes. “Use is slowly increasing in Type 2 patients, but I think it’s still too low considering this is a non-pharmacological approach”—something many people prefer because it avoids the side effects of medications—“that can help people,” he says.

Even for people with Type 2 diabetes who are not taking insulin, Beck says that continuous glucose monitoring could be helpful. “There’s a need for more studies to prove it, but it makes sense that it would likely have benefits,” he says. For example, monitoring blood sugar in real time could help people make diet or lifestyle changes that reduce their risks for long-term health complications. “Normally, blood glucose following a meal shouldn’t go above 140 [mg/dL],” he says. But based on factors like diet, meal timing, and exercise habits, someone with Type 2 diabetes may experience post-meal blood-sugar spikes that surpass 200 or even 300 mg/dL. These spikes could cause few symptoms or short-term consequences, Beck says, but over time they can contribute to the development of common diabetes-related complications such as kidney failure, heart disease, or diabetic retinopathy (an eye condition that can cause blurry vision or blindness). “The first time people use these continuous monitors, it can be a real eye-opener,” he adds. “I think they could be most helpful for self-management, and Type 2 diabetes is a disease where self-management through diet and exercise can make a huge difference.”

Other experts second this. “Patients using these devices can receive a graph of their glucose values over time, which helps them understand the effects of nutrition on glucose control, or how they could modify their exercise to make improvements,” says Dr. Ilias Spanakis, an associate professor of medicine in the division of endocrinology, diabetes, and nutrition at the University of Maryland School of Medicine.

For patients who are reliant on insulin to manage their blood glucose, combining continuous glucose monitors with insulin pumps—devices that automatically inject insulin as needed—could also lead to major improvements. “Smart algorithms that connect the two can automatically adjust glucose based on glucose values,” Spanakis says. This is already possible, and it’s likely to become much more commonplace, he adds.

For many people with diabetes, continuous glucose monitoring could provide a safer and simpler path forward.

Read More: The Link Between Type 2 Diabetes and Psychiatric Disorders

Bariatric surgery for Type 2 diabetes

Historically, bariatric (weight-loss) surgery has been used primarily to help people manage severe obesity, which the U.S. Centers for Disease Control and Prevention defines as a BMI of 40 or higher. Many people who are severely obese also have diabetes, and research has found that these surgical procedures can help reduce the burden of Type 2 diabetes or even send it into remission.

A 2018 study from researchers at the University of Oklahoma found that Roux-en-Y gastric bypass surgery, a common bariatric procedure, vastly outperformed typical medical management techniques—such as diet changes, doctor’s visits, and prescription drugs—among people with Type 2 diabetes. Surgery led to diabetes remission in roughly 28% of patients, compared with a remission rate of just 4% among the non-surgery group, according to the study results. More research has found that bariatric surgery may effectively send Type 2 diabetes into remission.

“Surgery does not just lead to weight loss, but also to an improvement in glycemic control, which happens even before the weight loss occurs,” says Emory’s Pasquel, who has published work on the benefits of bariatric surgery for people with Type 2 diabetes. Exactly how the surgery does this isn’t well understood, he says. However, bariatric surgery affects appetite, food intake, caloric absorption, and multiple neuroendocrine pathways—all of which could contribute to its beneficial actions for people with Type 2 diabetes.

In the future, Pasquel says these procedures are likely to become more commonplace even for people with Type 2 diabetes who are not severely obese.

More from TIME

New pharmaceutical drugs.

There are a lot of different diabetes drugs on the market, each with its own risks and benefits. But experts say two types are emerging as potential “game changers” when it comes to Type 2 diabetes treatment.

Glucagon-like peptide 1 (GLP-1) is a hormone released in the gut during digestion—one that plays a role in blood-sugar homeostasis. A class of drugs known as GLP-1 receptor agonists can interact with GLP-1 receptors in ways that lower appetite, slow digestion, and provide other benefits for people with Type 2 diabetes. These GLP-1 drugs aren’t new. But Pasquel says the latest versions are different in that they work on two different receptors, not one. “Recent evidence shows that activating both receptors has a remarkable impact on weight loss and glycemic control,” he says. Especially for people with Type 2 diabetes who are at high risk for heart or arterial disease, he says that these new drugs seem to be a big upgrade over previous medications.

A second category of drug has also emerged as a standout in the treatment of Type 2 diabetes. Known as sodium-glucose cotransporter-2 (SGLT-2) inhibitors, these drugs help the kidneys remove sugar from a person’s blood. Not only does this improve blood-sugar control in people with Type 2 diabetes, but it also helps protect them from heart failure and kidney disease—two common and serious complications. Pasquel says these drugs are so effective that they’re now being used in people with heart failure or kidney disease who do not have Type 2 diabetes.

Read More: The Truth About Fasting and Type 2 Diabetes

Emerging ways to think about weight loss

Experts have long understood that weight loss can help people reduce their Type 2 diabetes symptoms and risks . This recognition has led to research on a number of weight-loss diets . More research is needed, but some of the latest studies suggest that fasting plans—in particular, intermittent fasting—may be particularly beneficial for people with Type 2 diabetes.

Intermittent fasting involves cutting out calorie-containing foods and drinks for an extended period of time—anywhere from 12 hours to two days depending on the approach a person chooses. A 2019 research review in the journal Nutrients found that intermittent fasting promotes weight loss, increases insulin sensitivity, and reduces insulin levels in the blood. All of this is helpful for people with Type 2 diabetes. “Essentially, fasting is doing what we prescribe diabetes medications to do, which is to improve insulin sensitivity,” says Benjamin Horne, director of cardiovascular and genetic epidemiology at Intermountain Healthcare in Utah.

It’s not yet clear which form of intermittent fasting is best. But Horne says that time-restricted eating—a type of fasting that involves squeezing all the day’s calories into single six- or eight-hour feeding windows—is leading the pack, largely because patients are able to stick with it.

There are more new advancements in Type 2 diabetes care. The interventions described here—from continuous glucose monitors to novel drugs—are some of the most promising, but they have company. It’s safe to say that, looking ahead, more people with Type 2 diabetes will be able to effectively manage or mitigate their symptoms.

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“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.

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Type 2 Diabetes Research At-a-Glance

The ADA is committed to continuing progress in the fight against type 2 diabetes by funding research, including support for potential new treatments, a better understating of genetic factors, addressing disparities, and more. For specific examples of projects currently funded by the ADA, see below.

Greg J. Morton, PhD

University of Washington

Project: Neurocircuits regulating glucose homeostasis

“The health consequences of diabetes can be devastating, and new treatments and therapies are needed. My research career has focused on understanding how blood sugar levels are regulated and what contributes to the development of diabetes. This research will provide insights into the role of the brain in the control of blood sugar levels and has potential to facilitate the development of novel approaches to diabetes treatment.”

The problem: Type 2 diabetes (T2D) is among the most pressing and costly medical challenges confronting modern society. Even with currently available therapies, the control and management of blood sugar levels remains a challenge in T2D patients and can thereby increase the risk of diabetes-related complications. Continued progress with newer, better therapies is needed to help people with T2D.

The project: Humans have special cells, called brown fat cells, which generate heat to maintain optimal body temperature. Dr. Morton has found that these cells use large amounts of glucose to drive this heat production, thus serving as a potential way to lower blood sugar, a key goal for any diabetes treatment. Dr. Morton is working to understand what role the brain plays in turning these brown fat cells on and off.

The potential outcome: This work has the potential to fundamentally advance our understanding of how the brain regulates blood sugar levels and to identify novel targets for the treatment of T2D.

Tracey Lynn McLaughlin, MD

Stanford University

Project: Role of altered nutrient transit and incretin hormones in glucose lowering after Roux-en-Y gastric bypass surgery

“This award is very important to me personally not only because the enteroinsular axis (gut-insulin-glucose metabolism) is a new kid on the block that requires rigorous physiologic studies in humans to better understand how it contributes to glucose metabolism, but also because the subjects who develop severe hypoglycemia after gastric bypass are largely ignored in society and there is no treatment for this devastating and very dangerous condition.”

The problem: Roux-en-Y gastric bypass (RYGB) surgery is the single-most effective treatment for type 2 diabetes, with persistent remission in 85% of cases. However, the underlying ways by which the surgery improves glucose control is not yet understood, limiting the ability to potentially mimic the surgery in a non-invasive way. Furthermore, a minority of RYGB patients develop severe, disabling, and life-threatening low-blood sugar, for which there is no current treatment.

The project: Utilizing a unique and rigorous human experimental model, the proposed research will attempt to gain a better understanding on how RYGB surgery improves glucose control. Dr. McLaughlin will also test a hypothesis which she believes could play an important role in the persistent low-blood sugar that is observed in some patients post-surgery.

The potential outcome: This research has the potential to identify novel molecules that could represent targets for new antidiabetic therapies. It is also an important step to identifying people at risk for low-blood sugar following RYGB and to develop postsurgical treatment strategies.

Rebekah J. Walker, PhD

Medical College of Wisconsin

Project: Lowering the impact of food insecurity in African Americans with type 2 diabetes

“I became interested in diabetes research during my doctoral training, and since that time have become passionate about addressing social determinants of health and health disparities, specifically in individuals with diabetes. Living in one of the most racially segregated cities in the nation, the burden to address the needs of individuals at particularly high risk of poor outcomes has become important to me both personally and professionally.”

The problem: Food insecurity is defined as the inability to or limitation in accessing nutritionally adequate food and may be one way to address increased diabetes risk in high-risk populations. Food insecure individuals with diabetes have worse diabetes outcomes and have more difficulty following a healthy diet compared to those who are not food insecure.

The project: Dr. Walker’s study will gather information to improve and then will test an intervention to improve blood sugar control, dietary intake, self-care management, and quality of life in food insecure African Americans with diabetes. The intervention will include weekly culturally appropriate food boxes mailed to the participants and telephone-delivered diabetes education and skills training. It will be one of the first studies focused on the unique needs of food insecure African American populations with diabetes using culturally tailored strategies.

The potential outcome: This study has the potential to guide and improve policies impacting low-income minorities with diabetes. In addition, Dr. Walker’s study will help determine if food supplementation is important in improving diabetes outcomes beyond diabetes education alone.

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Management of type 2 diabetes in the new era

• Review Article
• Open access
• Published: 13 September 2023
• Volume 22 , pages 677–684, ( 2023 )

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• Aris Liakos   ORCID: orcid.org/0000-0003-3261-2979 1 , 2 ,
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Management of type 2 diabetes is advancing beyond glycemic control and is increasingly based on cardiovascular risk stratification. This review summarizes recent advances in the field and identifies existing knowledge gaps and areas of ongoing research.

A bibliographic search was carried out in PubMed for recently published cardiorenal outcome trials, relevant guidelines, and studies on antidiabetic agents in the pipeline.

Findings from cardiovascular outcome trials support the use of glucagon-like peptide 1 (GLP-1) receptor agonists or sodium-glucose cotransporter 2 (SGLT-2) inhibitors for patients with established cardiovascular disease or multiple risk factors, although it as yet remains uncertain whether the benefits are transferable to patients at lower absolute cardiovascular risk. Additionally, robust evidence suggests that SGLT-2 inhibitors improve clinical outcomes for people with concomitant heart failure or chronic kidney disease. Gut hormone multiagonists will likely represent another major addition to the therapeutic armamentarium for morbidly obese individuals with diabetes. Moreover, nonalcoholic fatty liver disease is a common comorbidity and several liver outcome trials are awaited with great interest. Use of insulin as first-line injectable therapy has been displaced by GLP-1 receptor agonists. Once-weekly formulations of basal insulins along with combinations with GLP-1 receptor agonists are also under development and could increase patient convenience. Technologies of glucose sensors are rapidly evolving and have the potential to reduce the burden of frequent blood glucose measurements, mainly for patients treated with intensified insulin regimens.

Management of type 2 diabetes requires a holistic approach and recent breakthroughs are expected to improve the quality of care.

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Avoid common mistakes on your manuscript.

Introduction

Maintaining normoglycemia has been the primary focus in the pharmacological management of type 2 diabetes for a very long time. Accordingly, practicing clinicians largely relied on hemoglobin A 1c (HbA 1c ) to initiate or modify antidiabetic treatment. In this context, hypoglycemia was the main limiting factor of first-generation antidiabetic agents, such as sulfonylureas and insulin. In the following years, new antihyperglycemic agents were gradually introduced in clinical practice, including the dipeptidyl-peptidase 4 (DPP-4) inhibitors, which have a safe profile in terms of hypoglycemia. Newer insulin regimens that closely mimic physiologic response, such as basal insulin degludec and glargine U-300 as well as the fast-acting insulin aspart (FIAsp) and ultra-rapid lispro (URLi) along with advances in insulin injection devices, also simplified insulin therapy while reducing the risk of hypoglycemia [ 1 , 2 ]. However, the landscape as regards management of type 2 diabetes was virtually transformed following publication of the results of a series of cardiovascular outcome trials (CVOTs), which were imposed by the drug regulators back in 2008 in response to safety concerns about rosiglitazone [ 3 ]. In 2015, EMPA-REG OUTCOME [ 4 ] was the first large randomized controlled trial of this kind that provided robust evidence of the cardiovascular benefits of empagliflozin, and soon thereafter, more CVOTs supported the cardioprotective effects of other sodium-glucose cotransporter 2 (SGLT-2) inhibitors and certain glucagon-like peptide 1 (GLP-1) receptor agonists. The salutary effects of the aforementioned drug classes on hard cardiovascular endpoints were more pronounced for patients with established cardiovascular disease (CVD) or multiple risk factors and likely extend beyond glycemic control. Hence, current management of patients with type 2 diabetes is increasingly based on stratification of cardiovascular risk and, in this regard, SGLT-2 inhibitors and GLP-1 receptor agonists are prioritized for patients at high cardiovascular risk [ 5 ]. Moreover, high-quality evidence now suggests that SGLT-2 inhibitors reduce rates of hospitalization for heart failure and ameliorate progression of diabetic kidney disease, and this is also taken into account when making treatment choices for patients with these comorbidities. Finally, rates of obesity are constantly increasing among people with diabetes and contemporary recommendations for the management of the disease has put increased emphasis on use of certain GLP-1 receptors agonists for body weight control, such as liraglutide and semaglutide as well as the recently approved dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide which is highly effective in reducing body weight [ 6 ].

In the foreseeable future, new agents that are currently under clinical development will possibly be added to the therapeutic armamentarium for type 2 diabetes. Regarding glycemic management, insulin icodec is a basal insulin analog under clinical development with prolonged duration of action that allows for once-weekly administration, thereby further reducing the complexity of insulin therapy while increasing its acceptance [ 7 ]. Uptake of technological innovations initially designed for type 1 diabetes is also increasing. Soon, traditional measures of blood glucose control such as HbA 1c may become outdated and more widespread use of the ambulatory glucose profile derived from continuous glucose monitoring will help to develop a more personalized treatment plan. Finally, nonalcoholic fatty liver disease (NAFLD) represents a significant comorbidity amongst individuals with diabetes for whom effective interventions beyond lifestyle modifications are lacking. Several randomized trials assessing the effect of antidiabetic agents such as SGLT-2 inhibitors, GLP-1, and dual GIP/GLP-1 receptor agonists on liver outcomes are underway. If the encouraging preliminary findings from these liver outcome trials (LOTs) are corroborated, targeting NAFLD will probably be upgraded as a therapeutic priority in upcoming treatment algorithms for type 2 diabetes.

This review highlights recent changes in the management of type 2 diabetes to date and outlines existing challenges and future advances that will likely address unmet needs for a chronic condition that represents a substantial burden not only for individuals but also for healthcare systems and society as a whole (Table 1 ). We conducted a PubMed search up to July 2023 for recently published cardiorenal outcome trials and evidence syntheses thereof as well as pertinent guidelines for the management of diabetes and its associated comorbidities. Moreover, we scanned pharmaceutical companies’ websites to identify candidate molecules under development that might be introduced in clinical practice in the years to come.

Mitigation of cardiovascular risk

The American Diabetes Association and the European Association for the Study of Diabetes recommend that GLP-1 receptor agonists or SGLT-2 inhibitors should be used for patients with established CVD as well as patients without established CVD but with high-risk indicators, including age ≥ 55 years plus two or more additional risk factors, such as obesity, hypertension, smoking, dyslipidemia, or albuminuria [ 5 ]. The European Society of Cardiology questions the primacy of metformin and advocates upfront treatment with a GLP-1 receptor agonist or a SGLT-2 inhibitor for patients at high or very high cardiovascular risk, such as those with established CVD, end organ damage (i.e., proteinuria, estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m 2 , left ventricular hypertrophy or retinopathy), and presence of three or more major risk factors as well as patients with diabetes duration ≥ 10 years plus any additional risk factor [ 8 ]. For these individuals, the decision to initiate a GLP-1 receptor agonist or a SGLT-2 inhibitor should be independent of background use of metformin or baseline HbA 1c [ 9 ]. Of note, GLP-1 receptor agonists appear more effective in preventing stroke and should be prioritized for patients with atherosclerotic CVD, whereas SGLT-2 inhibitors are superior in reducing heart failure hospitalizations [ 10 ].

Nevertheless, it still remains unclear whether the favorable cardiovascular effects of the aforementioned drug classes are applicable to people with type 2 diabetes at low absolute cardiovascular risk given that this population was excluded from the respective CVOTs [ 3 ]. Randomized controlled trials are needed to address the paucity of evidence about the cardioprotective effects of glucose-lowering medications for this low-risk subgroup, although fewer cardiovascular events are expected and, hence, large sample sizes will be required to effectively capture differences among antidiabetic agents. The remaining knowledge gap concerns a significant number of patients with type 2 diabetes; thus, the conduct of such complex and resource-intensive megatrials is probably less appealing to the ongoing diabetes research enterprise. Registry-based randomized trials, which rely on routinely collected healthcare data for the ascertainment of the outcome, can be proposed to rectify this issue since they allow enrollment of a large sample, which is also representative of a real-world population, at minimal cost. As opposed to observational studies, the randomization protects against the effects of unmeasured confounders and selection bias by indication [ 11 ].

To reduce incidence of vascular complications and mortality among patients with type 2 diabetes, a multifactorial approach, apart from glucose regulation, is required taking into consideration the management of hypertension and dyslipidemia [ 12 ]. Guidelines for the management of hypertension have not changed substantially in recent years; clinicians should target a systolic blood pressure (SBP) of < 130 mmHg if it can be safely attained, although not < 120 mmHg, as well as a diastolic blood pressure of < 80 mmHg, but not < 70 mmHg, and these blood pressure targets should be individualized. For older people aged > 65 years, a more moderate SBP goal of < 140 mmHg might be appropriate, whereas for patients at increased risk of a cerebrovascular event, such as those with a history of stroke, a SBP of < 130 could be considered. Renin angiotensin aldosterone system (RAAS) blockers are considered first-line antihypertensive therapy for patients with type 2 diabetes, especially in the presence of albuminuria or coronary artery disease, while treatment can be advanced with the addition of a calcium channel blocker or a thiazide like diuretic [ 8 , 12 ].

Regarding the management of dyslipidemia, low-density lipoprotein cholesterol (LDL-C) targets are constantly on the decrease. Based on the underlying cardiovascular risk, a LDL-C target of < 100 mg/dl is recommended for moderate-risk patients, whereas for patients with multiple atherosclerotic CVD factors or for secondary prevention, LDL-C levels below 70 and 55 mg/dl, respectively, should be aimed for, along with a reduction of at least 50% in LDL-C. In this regard, the majority of patients with type 2 diabetes will eventually qualify for high-intensity statin therapy, such as atorvastatin 40–80 mg or rosuvastatin 20–40 mg: if the target LDL-C level is not achieved stepwise, addition of ezetimibe followed by a proprotein convertase subtilisin/kexin type 9 inhibitor should be considered [ 13 ]. Nevertheless, real-world data consistently suggest that control of LDL-C remains decidedly suboptimal in high-risk individuals [ 14 ]. Because practicing clinicians are often reluctant to pursue very low LDL-C targets, more efforts are needed to bridge this gap between guideline recommendations and clinical care.

Management of concomitant heart failure

Heart failure is predicted to be the new epidemic of the twenty-first century. People with type 2 diabetes are at increased risk for developing heart failure, which further increases their risk of adverse outcomes, mainly severe exacerbations that require hospitalization, as well as of mortality. Several trials have documented the effectiveness of SGLT-2 inhibitors for reducing rates of worsening heart failure in individuals across the full range of ejection fraction [ 15 , 16 , 17 ]. The beneficial effects of SGLT-2 inhibitors on heart failure outcomes are mediated by osmotic diuresis and occur irrespective of the presence of diabetes, thereby expanding the indication of these agents for patients with isolated heart failure without diabetes. Guidelines for the management of heart failure from the American College of Cardiology/American Heart Association have been modified accordingly and now include strong recommendations in favor of SGLT-2 inhibitors for patients with reduced ejection fraction as well as for individuals with preserved ejection fraction, for whom effective medical therapies are, admittedly, more limited [ 18 ].

Recent findings derived from network meta-analysis suggest that GLP-1 receptor agonists probably also reduce hospital admissions for worsening heart failure [ 19 ], although, in contrast to SGLT-2 inhibitors, dedicated trials for heart failure outcomes with these agents are lacking. GLP-1 receptor agonists are increasingly being used as a component of obesity treatment, which is clearly a pressing need for patients with comorbid heart failure. However, at the same time these agonists increase heart rate and, hence, any modest clinical benefits might diminish, especially among individuals with severe left ventricular dysfunction. Patients with preserved ejection fraction who have less well-established treatment options could benefit more from weight reduction. In this regard, it might be prudent for future research on GLP-1 receptor agonists to focus primarily on this subpopulation. Indeed, results from the SUMMIT trial (NCT04847557), a study of the newly approved GIP/GLP-1 receptor agonist tirzepatide in people with heart failure with preserved ejection fraction and obesity, could offer new insights.

Prevention of diabetic kidney disease

Diabetic nephropathy affects as many as 40% of patients with type 2 diabetes and is the leading cause of end-stage kidney disease requiring renal replacement therapy. Interventions to stabilize renal function in patients with diabetic kidney disease include optimal glycemic control, more stringent blood pressure targets, and use of RAAS inhibitors as well as management of excess cardiovascular risk with an appropriate lipid-lowering regimen. Beyond RAAS blockade, based on findings from cardiorenal outcome trials patients with type 2 diabetes and an eGFR < 60 ml/min/1.73 m 2 or albuminuria defined as an albumin to creatinine ratio ≥ 30 mg/g should preferably be treated with a SGLT-2 inhibitor to reduce the risk of kidney failure [ 20 , 21 , 22 ]. Because their effect on blood glucose is modest with worsening renal function owing to the decrease in the filtered glucose load, favorable kidney outcomes with SGLT-2 inhibitors are likely related to a reduction in intraglomerular pressure and are independent of the presence of type 2 diabetes.

GLP-1 receptor agonists are considered second-line therapy for cardiovascular risk reduction in patients with type 2 diabetes and chronic kidney disease (CKD) who do not meet glycemic targets with a SGLT-2 inhibitor or for whom a SGLT-2 inhibitor is contraindicated [ 5 , 23 ]. Nevertheless, this recommendation is mainly driven by the positive effect of these agents on reducing the risk for persistent macroalbuminuria and evidence for hard renal endpoints is still lacking. In this regard, the FLOW trial (NCT03819153) is a dedicated kidney outcomes trial with semaglutide that is expected to clarify whether this once-weekly GLP-1 receptor agonist delays the progression of kidney disease [ 24 ].

Apart from glucose-lowering medications, the nonsteroidal mineralocorticoid receptor antagonist finerenone has recently received regulatory approval for people with type 2 diabetes and concomitant nephropathy with albuminuria. The FIDELIO-DKD trial showed that finerenone ameliorates progression of CKD and reduces rates of cardiovascular events [ 25 ]. All participants in this trial received background therapy with RAAS blockers, but only a small minority were treated with a SGLT-2 inhibitor. Hence, the added value of finerenone for kidney protection on top of standard of care therapy with SGLT-2 inhibitors warrants further investigation. Finally, initial promising evidence of renoprotection with endothelin receptor antagonists such as atrasentan should prompt further research to investigate the potential role of this drug class for the treatment of patients with type 2 diabetes at high renal risk [ 26 ].

Development of new GLP-1 receptor agonists

Tirzepatide is the first-in-class dual GIP/GLP-1 receptor agonist with marketing authorization for the treatment of diabetes in Europe and the USA administered once weekly by subcutaneous injection. Compared to GLP-1 receptor monoagonism, combined activation of GLP-1 and GIP appears to have a synergistic effect. In tirzepatide’s clinical development program, SURPASS, the drug was highly effective in reducing HbA 1c up to approximately 2% for the maximal approved dose of 15 mg and even outperformed other potent GLP-1 receptor agonists without increasing the risk of hypoglycemia. Moreover, tirzepatide 15 mg was associated with weight loss of up to approximately 9 kg relative to placebo and was also superior in head-to-head comparisons with dulaglutide and semaglutide. The incidence of gastrointestinal side effects was similar to that of GLP-1 receptor agonists [ 6 ]. Given the well-documented cardiovascular benefits of certain GLP-1 receptor agonists, evidence of the effect of tirzepatide on long-term, hard clinical endpoints is much anticipated. Initial meta-analytic findings from the SURPASS clinical development program are encouraging [ 27 ]. The ongoing SURPASS-CVOT trial (NCT04255433) with more than 13,000 participants, to be completed by the end of 2024, is expected to clarify the cardiovascular effects of tirzepatide compared to dulaglutide.

The continuous refinement of GLP-1 receptor agonists has led to the development of multiagonist peptides that have the potential to reshape the management of obesity and hyperglycemia. In a phase 2 trial involving adults with obesity, the GIP, GLP-1, and glucagon receptor triple agonist retatrutide induced substantial body weight reduction of 24.2% after 48 weeks of intervention [ 28 ]. Hopefully, triple peptide hormone receptor agonists could more closely mimic the effects of metabolic surgery, which, though not scalable, offers substantial weight loss benefits and could even lead to remission of diabetes.

An oral formulation of the GLP-1 receptor agonist semaglutide taken once daily has also received marketing authorization. Although less effective for weight reduction, it could offer a more attractive option for earlier initiation of GLP-1 receptor agonist therapy in patients reluctant to use injectable agents [ 29 ]. Propitiously, results from the dedicated CVOT for oral semaglutide PIONEER 6 trial suggest a positive impact on all-cause and cardiovascular mortality [ 30 ]. Finally. orforglipron is another nonpeptide GLP-1 receptor agonist for daily oral administration for which weight loss up to 14.7% among patients with obesity has been observed in a phase 2 clinical trial [ 31 ].

The “diabesity” epidemic and NAFLD

Liver steatosis, which can progress to nonalcoholic steatohepatitis (NASH) and cirrhosis, is the most common hepatic disorder in Western countries that affects as many as 70% of people with type 2 diabetes, especially those who are overweight or obese. NAFLD represents a major public health problem of growing prevalence for which licensed treatments are lacking. Several antidiabetic agents have been evaluated as candidate molecules for the management of NAFLD [ 32 ]. Pioglitazone is associated with reductions in hepatic steatosis and lobular inflammation, while the GLP-1 receptor agonists liraglutide and semaglutide, which have also received marketing authorization at higher doses for chronic weight management, might promote histologic resolution of NASH and halt the progression of fibrosis. Finally, studies using mainly magnetic resonance imaging (MRI)-based techniques for evaluation of liver fat content and fibrosis have also pointed to potential benefits with the use of several SGLT-2 inhibitors. Interestingly, reduction in liver fat content has been noted in a MRI substudy with the dual GIP/GLP-1 receptor agonist tirzepatide [ 33 ]; however, SYNERGY-NASH, a dedicated trial with liver histological endpoints (NCT04166773), will provide more specific data on hepatoprotection for this agent.

Progress in insulin therapy

Many patients with type 2 diabetes will at some point during the course of the disease need insulin. Although insulin therapy has made considerable progress over the last few years, insulin is no longer regarded as first-line injectable therapy for people with type 2 diabetes. Before initiation of insulin, use of GLP-1 receptor agonists should be considered unless contraindicated because of their comparable glycemic efficacy and their favorable profile with respect to hypoglycemia [ 34 ]. Moreover, for patients already receiving basal insulin, a GLP-1 receptor agonist should be preferred over prandial insulin. Fixed ratio combinations of basal insulin with GLP-1 receptor agonists are also commercially available that minimize the injection burden while balancing out the risk of hypoglycemia and weight gain [ 35 ]. Nevertheless, it is still imperative not to postpone insulin therapy if it is deemed appropriate for certain individuals. Clinician and patient inertia regarding initiation of insulin has long been recognized and the extent to which this phenomenon will be affected by modern perceptions as to the role of insulin in type 2 diabetes pharmacotherapy remains to be elucidated.

The added value of newer basal insulin analogs such as degludec and glargine U-300 for glycemic control has so far been negligible, their main advantages being related to the lower risk of nocturnal hypoglycemia [ 2 ]. Regarding prandial insulin, ultra-rapid acting insulin analogs including FIAsp and URLi have recently been introduced in everyday clinical practice. Theoretically, their faster onset of action could better control mealtime glucose excursions and allows for greater dosing flexibility. However, these pharmacokinetic properties have not been shown to translate into clinically relevant benefits regarding the effect on HbA 1c or incidence of hypoglycemia compared to their rapid-acting counterparts [ 1 ]. All these advancements should be put in context with the steeply rising cost of insulin in the USA and elsewhere which deters compliance and hampers optimal glycemic control. Biosimilars did not have a sizeable impact on cost savings; thus, professional diabetes associations and patient advocacy groups are calling for further reductions in insulin prices and especially out-of-pocket expenses.

Icodec and basal insulin Fc (efsitora alfa) represent novel basal insulin formulations with a pharmacokinetic profile suitable for once-weekly administration. Insulin icodec is currently being evaluated in a series of clinical trials (ONWARDS). Specifically, in a 26-week, phase 2 trial, icodec showed comparable glycemic efficacy to insulin glargine and similar rates of hypoglycemia among patients treated with metformin with or without a DPP-4 inhibitor [ 7 ]. In another 26-week, phase 3 study enrolling patients treated with basal insulin, switching to icodec was superior to insulin degludec for reducing HbA 1c , though with modest weight gain and numerically more episodes of hypoglycemia [ 36 ]. Preliminary results also suggest that basal insulin Fc is non-inferior to degludec in terms of HbA 1c lowering [ 37 ]. Although more research is needed on the optimal titration scheme, the potential introduction in clinical practice of a once-weekly basal insulin regimen could encourage insulin acceptance and improve adherence. Finally, a combination of insulin icodec with the GLP-1 receptor agonist semaglutide (icosema) intended for once-weekly administration is in the pipeline.

Continuous glucose monitoring and insulin pumps

Self-monitoring of blood glucose in type 2 diabetes has consistently failed to provide clinically meaningful benefits. Use of continuous glucose monitoring (CGM) is widespread among patients with type 1 diabetes but its place in the management of type 2 diabetes and predominantly people treated with intensified insulin regimens remains controversial. HbA 1c reductions in the order of 0.3–0.4% have been observed with CGM compared to fingerprick measurements in randomized trials enrolling patients with type 2 diabetes receiving basal insulin alone or multiple daily injections [ 38 , 39 ], but evidence of the ability to decrease risk of severe hypoglycemia is lacking. In contrast to use of HbA 1c to evaluate glycemic control, CGM additionally captures glycemic variability and hypoglycemic episodes and, in this sense, time spent in target range as well as time spent in hypoglycemic range are gradually replacing traditional measures of glycemic efficacy initially in the context of clinical research and potentially in clinical practice as well. Similarly, the effectiveness of continuous subcutaneous insulin infusion has not been convincingly demonstrated in type 2 diabetes. In a large, randomized trial (OpT2mise), patients with type 2 diabetes and inadequate glycemic control achieved a greater reduction by 0.7% in HbA 1c with insulin pump therapy compared to multiple daily injections. The daily insulin dose was also lower, but the two groups did not differ in rates of hypoglycemia [ 40 ]. Interestingly, extensive research is currently being conducted on sweat-based and other noninvasive, wearable glucose sensors. Although all the aforementioned technologies are attractive tools for the management of insulin-treated patients with type 2 diabetes, their high cost and concerns about the associated user information overload are still barriers to their wider adoption. The promise that such exciting technologies will lead to improvements in patient-oriented outcomes has not yet been realized.

Conclusions

Recent innovations, including the introduction of antidiabetic drugs with proven cardiorenal benefits, highly effective agents for inducing weight loss, and more convenient insulin regimens and glucose sensors are having a profound impact on the everyday lives of patients with type 2 diabetes. Beyond these exciting interventions, lifestyle modification and diabetes self-management education and support, which are the mainstay of a holistic diabetes care plan, should continue to be energetically promoted.

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Liakos, A., Karagiannis, T., Avgerinos, I. et al. Management of type 2 diabetes in the new era. Hormones 22 , 677–684 (2023). https://doi.org/10.1007/s42000-023-00488-w

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• Helen E. Thomas

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Overview of Clinical Trials on Type 2 Diabetes Mellitus: A Comprehensive Analysis of the ClinicalTrials.gov Database

Jianyan long.

1 Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

Ruiming Liang

Qiuyi zheng.

2 Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

3 Phase I Clinical Trial Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

4 Department of Medical Records, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

Xinwen Chen

Fenghua lai.

A better understanding of the current features of type 2 diabetes mellitus (T2DM)-related clinical trials is important for improving designs of clinical trials and identifying neglected areas of research. It was hypothesized that the trial registration policy promoted the designs of T2DM-related trials over the years. Therefore, this study aimed to present a comprehensive overview of T2DM-related clinical trials registered in the ClinicalTrials.gov database.

T2DM-related clinical trials registered in the ClinicalTrials.gov database were searched and assessed the characteristics of the relevant trials. We searched PubMed and Google Scholar for the publication statuses of the primary completed trials.

Overall, 5117 T2DM-related trials were identified for analysis. Of the interventional trials, 71.5% had a primary treatment purpose while only 8.9% were prevention or health service. There were more interventional trials registered prior to patient recruitment between 2012 and 2019 than between 2004 and 2011 (44.6% vs 19.9%, P <0.001). The period between 2012 and 2019 also had more trials that enrolled <100 participants (59.2% vs 50.9%), were single-center studies (60.7% vs 50.6%), had non-randomized allocations (11.3% vs 6.3%), were open-label (49.2% vs 45.6%), and had smaller sample sizes than the period between 2004 and 2011 (all P <0.001). The five-year cumulative publication rates after primary completion of the trials were <40%.

Although the ClinicalTrials.gov database did not include all clinical trials, the trials registered in the ClinicalTrials.gov database still accounted for most of the clinical studies. Encouragingly, more interventional trials were registered prior to patient recruitment over the years. The majority of T2DM-related clinical trials focused on drug-related treatment, and trials regarding prevention in T2DM should be promoted. More attention should be paid to improve the publication and dissemination of clinical trials results.

Introduction

Diabetes is a chronic disease with an estimated global prevalence of 450 million. 1 The public health toll of diabetes is on an upward trajectory, with its prevalence estimated to increase to 623 million by 2045; approximately 90% of these are type 2 diabetes mellitus (T2DM) patients. 2 The health, social, and economic burdens caused by T2DM and its complications present a major challenge to healthcare systems worldwide. 3

T2DM is a complex endocrine and metabolic disorder. Genetic and environmental factors, including varying degrees of insulin resistance, dysfunction of pancreatic β cells and α cells, and other endocrine disturbances, interact and cause organs damage. 4–7 Over the past two decades, many treatment options have been introduced, and the overall quality of life of T2DM patients has improved. However, due to the heterogeneity of the etiologies and complications of T2DM, glycemic control and complications prevention in T2DM are still challenging. 8–10 A large number of clinical trials have been conducted worldwide to improve the management of T2DM.

Clinical trials, especially well-designed randomized clinical trials (RCTs), are the foundation of evidence-based medicine and the driving force behind the development of clinical medicine. In 2004, the International Committee of Medical Journal Editors (ICMJE) advocated that clinical trials should be registered in a public registry before participants were recruited to ensure transparency of the process. 11 , 12 ClinicalTrials.gov, a web-based registry maintained by the National Library of Medicine (NLM) and National Institutes of Health (NIH), was created to provide the public and healthcare providers with easy access to information about clinical trials. Currently, the ClinicalTrials.gov database provides the most comprehensive information about ongoing and completed clinical studies worldwide. 13 However, despite the availability of information regarding ongoing and completed clinical trials, a thorough evaluation of T2DM-related trials is yet to be conducted, and physicians still lack a comprehensive understanding of clinical trials on T2DM.

A better understanding of the current features of T2DM-related clinical trials is important for improving designs of clinical trials and identifying neglected areas of research, which will in turn improve the translatability of results into benefits for patients. Hence, we conducted this research to present a comprehensive overview of the features of T2DM-related clinical trials registered in the ClinicalTrials.gov database and to evaluate the publication statuses of these trials.

Search and Selection of Relevant Registered Trials

An established research protocol was developed in advance. On July 1, 2020, we searched the ClinicalTrials.gov database for relevant trials using the search term “type 2 diabetes mellitus” or “non-insulin dependent diabetes” or “T2DM”. All available results were downloaded as XML files. Subsequently, all the data were imported into an Excel form to facilitate further data selection, classification, and management. Two investigators (JL and RL) independently screened the “condition”, “brief title”, and “official title” of the trials. For each potentially eligible trial, the full document was retrieved and independently assessed for inclusion (JL and RL). Any discrepancies were resolved by consensus, and those unresolved through consensus were reviewed by a third investigator (FL). Trials started between 2004 and 2019 were included in our study. Trials with withdrawn, unknown, terminated, and expanded access statuses and trials included non-T2DM participants were excluded. Finally, all included clinical trials were classified manually in duplicate by two independent investigators (JL and RL). Inconsistencies were resolved by consensus, and those unresolved through consensus were classified by a third investigator (FL). This study was approved by the Research Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University. Patient consent was not required in this study.

Data Extraction

A data extraction form was developed by a senior investigator (YL). Three investigators (JL, RL, and FL) were pre-trained in a pilot-testing phase to calibrate extraction criteria. The following variables were extracted by two investigators (JL and RL) independently using a standardized data extraction form: age of participants, sample size, study design, primary purpose of the trial, types of interventions, types of therapeutic drugs, region where the study was performed, centers, funding sources, start date, status of trial, duration of trial, and results of primary completed trials. Any disagreements were resolved by consensus, and those unresolved through consensus were reviewed by a third investigator (FL). If an industry was listed as the lead funder, the trial was classified as being funded by the industry. If the NIH was listed as the lead funder, the trial was considered NIH-funded. 14 The time to primary completion was defined as the time from the start of the trial to the time the primary endpoint was reached. The duration of the trial was defined as the time from the start of the trial to the completion of the trial.

Search for the Publication Statuses of Included Trials

Two investigators (JL and RL) independently searched for peer-reviewed publications of trials in a stage of primary completion by using a standardized strategy. The “publications” field in the ClinicalTrials.gov database was identified and used to search for potentially matching publications. We then searched PubMed and Google Scholar by using brief titles and registration numbers in all the fields. The search for the publication statuses of the trials was updated and finalized by July 5, 2020. Publication was confirmed by matching the study characteristics outlined in the ClinicalTrials.gov database with the description in the published manuscript. The earliest article that reported primary outcome results was chosen if multiple publications were obtained from the same registered trial. Study protocols, commentaries, interim analyses, and other non-relevant publication types were excluded. A third investigator (FL) independently reconfirmed the selection and conducted a publication search for the studies that were found to be unpublished by the first two investigators. Differences were resolved by consensus.

Statistical Analysis

The year 2012, which was the mid timepoint of 2004–2019, was chosen as the cutoff to compare the characteristics of interventional trials. The number (percentage) of categorical variables and the median (interquartile range) of continuous variables were calculated. The χ 2 test was used to compare categorical variables. Kaplan–Meier analysis was used to analyze the cumulative publication rates after primary completion of the trials. Trials that did have not a “completed” status were excluded from the analysis. All statistical tests were performed using SAS version 9.4 software (SAS, institute, Cary, NC), and a two-sided P value <0.05 was considered statistically significant.

Distribution of T2DM-Related Clinical Trials

A total of 7823 registered clinical trials were retrieved from the Clinicaltrials.gov database; 2706 of the clinical trials were started before 2004 and after 2019. Trials that had withdrawn (n=120), unknown (n=670), and terminated (n=361) statuses and trials that included non-T2DM participants (n=769) were excluded. A total of 5117 clinical trials were eligible for analysis, including 794 (15.5%) observational trials and 4323 (84.5%) interventional trials ( Figure 1 ). Inter-rater agreement for selecting the trials for full-document review was excellent with a kappa of 0.92 (95% CI =0.91–0.94). The distribution of the eligible trials by year according to the time of registration was summarized in Figure 2 . Overall, the number of registered T2DM-related clinical trials has increased over the years. The number of trials registered between 2004 and 2009 increased rapidly but decreased slightly after 2009. Since 2012, the number of T2DM-related clinical trials registered each year has remained stable.

Flow chart of trial selection.

Distribution of the eligible clinical trials according to the registered year.

Characteristics of the Interventional and Observational Trials

Table 1 presents the characteristics of the interventional and observational trials. Fewer children were enrolled in the interventional trials than in the observational trials (3.3% vs 22.2%). More interventional trials than observational trials were registered before patient recruitment (33.2% vs 23.7%), had fewer than 100 participants (55.3% vs 27.9%), and were mainly focused on drug-related therapy (63.3% vs 52.6%) (all P <0.001). Most T2DM-related clinical trials were conducted in the United States/Canada/Europe (70.6% of the interventional trials and 63.8% of the observational trials). More interventional trials than observational trials were multiple-center studies (33.9% vs 20.8%) and were funded by industries (54.5% vs 46.2%) (both P <0.001). Most of the included trials had a primary completed status (83.3% of the interventional trials and 78.0% of the observational trials). After primary completion of the trials, interventional trials had more results available in the ClinicalTrials.gov database (28.5% vs 8.3%) and more publications (31.8% vs 19.5%) than observational trials (both P <0.001).

Characteristics of Interventional and Observational Trials

Notes: a The participants of trials included both adults and children; b The trials without available data were not included in the analysis; c The sum of number was the number of primary completed trials; d The sum of number was the number of completed trials.

Abbreviations: NA, not available; NIH, National Institutes of Health.

Trend of Changes in the Characteristics of the Interventional Trials

The characteristics of the T2DM-related interventional trials registered between 2004–2011 and 2012–2019 are listed in Table 2 . More of the interventional trials registered between 2012 and 2019 were registered before patient recruitment than those registered between 2004 and 2011 (44.6% vs 19.9%); more of the trials registered between 2012 and 2019 also had fewer than 100 participants (59.2% vs 50.9%), were single-center studies (60.7% vs 50.6%), had non-randomized allocations (11.3% vs 6.3%), and were open-label (49.2% vs 45.6%) (all P <0.001). The proportion of intervention trials conducted in Asia increased from 17.7% to 26.1% during the two periods ( P <0.001). Of all the interventional trials, 71.5% had a primary treatment purpose while only 8.9% were prevention or health service. The proportion of intervention trials that focused on health services or preventive measures increased from 6.7% to 10.7% during the two periods ( P <0.001).

Trend of Changes in the Characteristics of Interventional Trials Registered Between Two Temporal Subsets

Note: a The trials without available data were not included in the analysis.

Distribution of Antidiabetic Drugs

Figure 3 shows the summary of the common antidiabetic drugs studied in T2DM-related clinical trials and the trend of changes that occurred during the two periods between 2004–2011 and 2012–2019. Insulin, metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium glucose cotransporter-2 (SGLT-2) inhibitors were the antidiabetic drugs most commonly studied in the trials. The trials focused less on α-glucosidase inhibitors and sulfonylureas. The proportion of trials that focused on GLP-1RAs and SGLT-2 inhibitors increased rapidly from 2012 to 2019. The proportion of trials that focused on thiazolidinediones (TZDs) shrunk over time.

Distribution of the common antidiabetic drugs studied in all T2DM-related clinical trials ( A ) and in T2DM-related intervention trials ( B ) between two temporal subsets (2004–2011 and 2012–2019). The sum of the percentages may exceed 100% as categories were not mutually exclusive.

Publication Status of Primary Completed Trials

The one-year, three-year, and five-year cumulative publication rates since trial primary completion were 4.3%, 26.0%, and 33.1%, respectively ( Figure 4 ). Table 3 shows the detailed characteristics of the completed intervention trials according to publication status; 82.8% of the published trials reported positive outcomes. More published trials than unpublished trials enrolled more than 100 participants (57.2% vs 38.3%), were multi-center studies (43.5% vs 32.4%), had randomized allocations (95.9% vs 89.6%), and used blinding methods (57.2% vs 51.9%) (all P <0.001). Published trials had more results available in the ClinicalTrials.gov database than unpublished trials (44.7% vs 24.4%, P <0.001).

Characteristics of Completed Interventional Trials According to the Publication Status a

Notes: a Publication statuses of the trials were searched through PubMed and Google Scholar and updated and finalized by July 5, 2020; b The trials without available data were not included in the analysis.

Cumulative publication rate curve since trial primary completion. Kaplan–Meier analysis was used. Trials with a “completed” status were included in the analysis.

The aim of this study was to present a comprehensive overview of the T2DM-related clinical trials registered in the ClinicalTrials.gov database. To the best of our knowledge, this is the first comprehensive assessment of the characteristics of T2DM-related clinical trials. Our results showed that the T2DM-related clinical trials were mostly intervention trials. The interventional trials registered between 2012 and 2019 had smaller sample sizes, included more single-center studies, had more non-randomized allocations, and had more open-label studies than those registered between 2004 and 2011. The T2DM-related clinical trials mainly focused on drug-related therapy rather than preventive strategy. The proportion of trials that involved GLP-1RAs and SGLT-2 inhibitors increased rapidly over the years. The five-year cumulative publication rates after primary completion of the trials were lower than 40%.

The results of the present study showed that more than 80% of T2DM-related clinical trials were interventional trials, a proportion that was similar to that of other chronic disease trials. 15 , 16 Registration of clinical trials has improved significantly since the ICMJE proposed the guideline that clinical trials should be registered in a public registry before participants are recruited. 17 , 18 The results of the present study showed that there were more trials registered prior to patient recruitment between 2012 and 2019 than those registered between 2004 and 2011. However, the design of T2DM-related interventional clinical trials between 2012 and 2019 differed from those between 2004 and 2011. Firstly, the sample sizes of the intervention trials between 2012 and 2019 were generally small. This could probably be due to the rapid development and application of new antidiabetic drugs in the past decade 19 and the increased number of exploratory clinical trials that focused on the safety and efficacy of the new drugs. The new drugs were more expensive than the traditional antidiabetic drugs, and the financial burden on researchers or clinicians limited the recruitment of participants in trials. Another possible reason might be that the small-sample trials were less registered in the early years but forced to be registered in the later years due to the trial publication policy. Secondly, the proportion of multi-center trials was small. A potential reason for this may be that more trials were conducted in Asia between 2012 and 2019. There were huge differences in health policies and inequality in economic development across the Asian region, 20 , 21 which may limit the cooperation of staff and administration in multiple centers. Finally, the proportion of clinical trials that involved blinding and randomized designs shrunk. With the development of evidence-based medicine, well-designed RCTs play an important role in the establishment of health policies and in the decision-making of clinicians. A lack of randomization and blinding greatly increased the risk of bias in the results of trials. 22 Therefore, more attention should be paid to the design of T2DM-related clinical trials.

Drug-related therapy, especially antidiabetic drug therapy, has always been a hot topic in T2DM-related clinical trials. In the past 20 years, many antidiabetic drugs have been introduced, and this influenced the goal/objective of drug-related clinical trials. 23 In the present study, the proportion of clinical trials on insulin and metformin was more than 40%. The number of clinical trials on TZDs decreased significantly after 2012, whereas the number of clinical trials on GLP-1RAs and SGLT-2 inhibitors increased rapidly, a finding which was similar to the results of another study. 24 TZDs were introduced in the late 1990s. Rosiglitazone was discontinued in Europe and its use was restricted in the USA in 2008 after reports of an association with cardiovascular risk. 25 Pioglitazone was discontinued in 2011 in some European countries pending enquires into a possible risk of bladder cancer. 26 Therefore, clinical trials on TZDs decreased significantly between 2012 and 2019. GLP-1RAs were introduced in 2005, and the first SGLT-2 inhibitor, dapagliflozin, was approved in 2013 after the Food and Drug Administration issued its recommendation for the treatment of T2DM. Currently, clinical trials were conducted with special interest in their influence on the cardiovascular system and on nephropathy. 27 , 28

The American Diabetes Association and the International Diabetes Federation emphasized that diabetes prevention should be the focus of future research. 29 , 30 Previous studies demonstrated that lifestyle intervention and health education implementation may delay the onset of diabetes in high-risk persons. 31–33 Therefore, additional research was needed to assess the effectiveness of prevention strategies in clinical practice and standardize their implementation. 34 , 35 We found that most T2DM clinical trials in the ClinicalTrials.gov database focused on drug-related therapy, while only small percentages were primarily concerned with prevention, health services research, supportive care, diagnosis or screening. Although the ideal proportion of trials focused on prevention has not been established, the current T2DM-related clinical trials appeared to be inadequate for expanding and refining preventive strategies into the community setting.

The systematic reporting and publication of clinical research results provide a reliable basis for evidence-based medicine, facilitate the establishment of health policies, aids clinicians in decision-making, and promote the development of public health and clinical medicine. 36 Following the announcement of the ICMJE trial registration policy in 2004, some organizations subsequently enacted laws and policies requiring the systematic reporting of aggregate results. In the USA, the Food and Drug Administration Amendments Act (FDAAA) of 2007 established a legal mandate requiring those responsible for initiating clinical trials to report summary results for certain trials. 37 In 2016, the department of Health and Human Services promulgated regulations to implement, clarify, and expand legal requirements under FDAAA for trial results information submission. 38 The Chinese Trial Registration and Publication Collaboration issued the second statement to implement the publication ethic of clinical trials in 2011. 39 In June 2017, the ICMJE published a statement supporting data-sharing policy for clinical trials. 40 However, in the present study, more than 70% of trials had no results available in the ClinicalTrials.gov database and the five-year cumulative publication rates of T2DM-related clinical trials after primary completion were lower than 40%. Previous studies showed that publication rates among completed trials registered in ClinicalTrials.gov were less than 50%. 41 Selective publication was an important factor that affects the publication of biomedical research. 42 If trial results put either investigators/sponsors at financial risk or trial results contradicted investigators’ beliefs, publications may be delayed or suppressed. 43 In addition, researchers, reviewers, and editors were generally more enthusiastic about positive or equivalence trials and less excited about negative trials. 11 As 82.8% of the published trials in the present study reported positive results, our study results were in accordance with this opinion.

The limitations of our study should be addressed. Firstly, the ClinicalTrials.gov database does not include all clinical trials, and investigators may use other worldwide registries to fulfill the ICMJE-advocated mandatory registration guideline. However, the trials registered in the ClinicalTrials.gov database still account for most of the clinical studies in the World Health Organization International Clinical Trials Registry Platform. Secondly, the data for all clinical trials in the database were reported by researchers and the NLM cannot verify the validity of all trial information in the ClinicalTrials.gov database. Finally, the data of all trials in the ClinicalTrials.gov database were not always complete and up to date.

In summary, this study presented the first comprehensive overview of T2DM-related clinical trials registered in the ClinicalTrials.gov database. Our results indicated that there were more interventional trials registered prior to patient recruitment over the years. The majority of T2DM-related clinical trials focused on drug-related treatment, and trials regarding prevention in T2DM should be promoted. More attention should be paid to improve the publication and dissemination of clinical trials results.

Funding Statement

This work was supported by the Research Fund of Medical Science and Technology of Guangdong Province (A2020132).

Abbreviations

FDAAA, Food and Drug Administration Amendments Act; GLP-1RAs, glucagon-like peptide-1 receptor agonists; ICMJE, International Committee of Medical Journal Editors; NIH, National Institutes of Health; NLM, National Library of Medicine; RCTs, randomized clinical trials; SGLT-2, sodium glucose cotransporter-2; TZDs, thiazolidinediones; T2DM, type 2 diabetes mellitus.

Data-Sharing Statement

The data will be made available at reasonable request from the corresponding author (YL).

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

The authors report no conflicts of interest in this work.

Future Surge in Diabetes Could Dramatically Impact People Under 20 in U.S.

For Immediate Release: Thursday, December 29, 2022 Contact: Media Relations (404) 639-3286

The number of young people under age 20 with diabetes in the United States is likely to increase more rapidly in future decades, according to a new modeling study published today in Diabetes Care . Researchers forecasted a growing number of people under age 20 newly diagnosed with diabetes during 2017–2060.

This expected upward trend may lead to as many as 220,000 young people having type 2 diabetes in 2060 —a nearly 700% increaseand the number of young people with type 1 diabetes could increase by as much as 65% in the next 40 years. Even if the rate of new diabetes diagnoses among young people remains the same over the decades, type 2 diabetes diagnoses could increase nearly 70% and type 1 diabetes diagnoses could increase 3% by 2060.

Type 1 diabetes remains more common in U.S. youth, but type 2 diabetes has substantially increased among young people over the last two decades. Given this upward trend, a total of 526,000 young people may have diabetes (including both type 1 and type 2 diabetes) by 2060. Comparatively, 213,000 young people in the United States had diabetes in 2017.

“This new research should serve as a wake-up call for all of us. It’s vital that we focus our efforts to ensure all Americans, especially our young people, are the healthiest they can be,” said CDC Acting Principal Deputy Director Debra Houry, MD, MPH. “The COVID-19 pandemic underscored how critically important it is to address chronic diseases, like diabetes. This study further highlights the importance of continuing efforts to prevent and manage chronic diseases, not only for our current population but also for generations to come.”

In addition to the overall predictions, analyses of these data by race and ethnicity predicted a higher burden of type 2 diabetes for Black, Hispanic/Latino, Asian, Pacific Islander, and American Indian/Alaska Native youth.

“Increases in diabetes—especially among young people—are always worrisome, but these numbers are alarming,” said Christopher Holliday, PhD, MPH, MA, FACHE, director of CDC’s Division of Diabetes Translation. “This study’s startling projections of type 2 diabetes increases show why it is crucial to advance health equity and reduce the widespread disparities that already take a toll on people’s health.”

There could be several explanations for the rise in type 2 diabetes, including the increasing prevalence of childhood obesity. The presence of diabetes in people of childbearing age might be another important factor, because maternal diabetes increases risk of diabetes in children.

People with diabetes are at higher risk for heart disease or a stroke, diabetes complications, and premature death than those who do not have diabetes. Researchers are actively investigating ways of preventing type 1 diabetes and studies in adults have identified steps that can be taken to reduce the risk factors for type 2 diabetes. To learn more about diabetes and how to prevent type 2 diabetes visit https://www.cdc.gov/diabetes/prevent-type-2 .

These findings come from the SEARCH for Diabetes in Youth study, funded by the Centers for Disease Control and Prevention and the National Institutes of Health.

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Clinical Research in Type 2 Diabetes

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

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

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• Maureen Monaghan Center, Ph.D., CDCES Health Psychology, Behavioral Science, Clinical Management of Diabetes
• Jean M. Lawrence, Sc.D., M.P.H., M.S.S.A. Type 2 diabetes risk and prevention after gestational diabetes; Studies of adults with diabetes/pre-diabetes using secondary data and observational designs, and natural experiments
• Hanyu Liang, M.D., Ph.D. Hepatic Metabolism; Insulin Resistance; Type 2 Diabetes; Obesity; Bariatric Surgery
• Barbara Linder, M.D., Ph.D. Type 2 diabetes in children and youth; human studies of metabolic imprinting
• Saul Malozowski, M.D., Ph.D., M.B.A. Neuroendocrinology of hypothalamic-pituitary axis, neuropeptide signaling and receptors; hormonal regulation of bone and mineral metabolism; HIV/AIDS-associated metabolic and endocrine dysfunction
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• Theresa Teslovich Woo, Ph.D. Human behavior, developmental cognitive neuroscience, and brain-based mechanisms involved in obesity and diabetes

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Too little sleep raises risk of type 2 diabetes, new study finds

Adults who sleep only three to five hours per day are at higher risk of developing type 2 diabetes. This is demonstrated in a new study from Uppsala University, published in JAMA Network Open . It also shows that chronic sleep deprivation cannot be compensated by healthy eating alone.

"I generally recommend prioritising sleep, although I understand it's not always possible, especially as a parent of four teenagers," says Christian Benedict, Associate Professor and sleep researcher at the Department of Pharmaceutical Biosciences at Uppsala University and leading researcher behind the study.

He and a team of researchers have examined the link between type 2 diabetes and sleep deprivation. Type 2 diabetes affects the body's ability to process sugar (glucose), hindering insulin absorption and resulting in high blood sugar levels. A report from 2020 showed that over 462 million people suffer from this disease. Over time, it can cause serious damage, particularly to nerves and blood vessels, and thus represents an escalating public health problem globally.

"Previous research has shown that repeated short daily rest increases the risk of type 2 diabetes, while healthy dietary habits such as regularly eating fruit and vegetables can reduce the risk. However, it has remained unclear whether people who sleep too little can reduce their risk of developing type 2 diabetes by eating healthily," notes Diana Noga, a sleep researcher at the Department of Pharmaceutical Biosciences at Uppsala University.

The researchers therefore used data from one of the largest population databases in the world, the UK Biobank, in which nearly half a million participants from the UK have been genetically mapped and responded to questions on health and lifestyle. They followed the participants for over ten years and found that a sleep duration of between three and five hours was linked to a higher risk of developing type 2 diabetes.

In contrast, healthy eating habits led to a lower risk of developing the disease, but even people who ate healthily but slept less than six hours a day were still at higher risk of type 2 diabetes.

"Our results are the first to question whether a healthy diet can compensate for lack of sleep in terms of the risk of type 2 diabetes. They should not cause concern, but instead be seen as a reminder that sleep plays an important role in health," explains Benedict.

He also argues that the effects of sleep deprivation vary between individuals, depending on aspects such as genetics and a person's actual need for sleep.

• Insomnia Research
• Sleep Disorder Research
• Staying Healthy
• Sleep Disorders
• Obstructive Sleep Apnea
• Disorders and Syndromes
• Sleep deprivation
• Circadian rhythm sleep disorder
• Narcolepsy (sleep disorder)
• Delayed sleep phase syndrome
• Rapid eye movement
• Sleep apnea
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Story Source:

Materials provided by Uppsala University . Note: Content may be edited for style and length.

Journal Reference :

• Diana Aline Nôga, Elisa de Mello e Souza Meth, André Pekkola Pacheco, Xiao Tan, Jonathan Cedernaes, Lieve Thecla van Egmond, Pei Xue, Christian Benedict. Habitual Short Sleep Duration, Diet, and Development of Type 2 Diabetes in Adults . JAMA Network Open , 2024; 7 (3): e241147 DOI: 10.1001/jamanetworkopen.2024.1147

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ORIGINAL RESEARCH article

Clinical features of early-onset type 2 diabetes and its association with triglyceride glucose-body mass index: a cross-sectional study.

• The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China

Objective: The incidence of early-onset type 2 diabetes (T2D) has increased significantly, with insulin resistance (IR) and obesity being the main drivers of its onset. This study aims to investigate the clinical characteristics of early-onset T2D and its association with triglyceride glucose body mass index (TyG-BMI), an emerging surrogate of IR.

Methods: A total of 1000 adults newly diagnosed with T2D were enrolled and divided into early-onset T2D (18~40 years, N=500) and late-onset T2D groups (≥40 years, N=500). Independent t and chi-squared tests were used to compare the characteristics of the two groups, and logistic regression analysis, trend tests, restricted cubic spline curves (RCSs), and receiver operating characteristic (ROC) curves were used to identify the relationship between TyG-BMI and early-onset T2D.

Results: Patients with early-onset T2D were more likely to have a higher body mass index (BMI), hemoglobin A1C (HbA 1c ), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), serum uric acid (SUA), triglyceride glucose index (TyG), and TyG-BMI ( P < 0.05). A higher TyG-BMI was associated with an increased risk of early-onset T2D ( P < 0.001). The RCSs showed a nonlinear relationship between TyG-BMI and early-onset T2D, and the slope of the curve increased with an increase in TyG-BMI ( P for nonlinearity < 0.001). In the subgroup analysis, additive interactions between TyG-BMI and the risk of early-onset T2D were observed for sex, family history of diabetes, BMI, fatty liver, and hypertension ( P < 0.001). ROC curve showed that the area under the curve of TyG-BMI was 0.6781, which was larger than its main components (TyG, BMI, FPG, TG). The best cutoff value was 254.865, the sensitivity was 74.6%, and the specificity was 53.6%.

Conclusion: Patients with early-onset T2D are characterized by severe IR, metabolic disorders, and being overweight/obese and an increase in TyG-BMI is independently associated with an increased risk of early-onset T2D.

1 Introduction

The global prevalence of diabetes and obesity continues to rise, as does the incidence of early-onset type 2 diabetes (T2D), which has dramatically accelerated in the wake of the COVID-19 pandemic ( 1 , 2 ). A systematic review reported that during 1990 to 2019, the early-onset of T2D in the world (here defined as 15 to 39 years) age-standardized prevalence rates increased from of 117.22/100,000 to 183.36/100,000, disability-adjusted life-years rate increased from 106.34/100,000 to 149.61/100,000, and the age-standardized mortality rate in 2019 was 0.77/100, 000(0.76-0.78) ( 3 ). Early-onset T2D is more aggressive, with a more rapid course of disease deterioration and beta-cell failure compared with late-onset T2D or type 1 diabetes (T1D) ( 4 ). Due to the longer duration of exposure to hyperglycemia, patients with early-onset T2D are at a significantly increased risk of microvascular and macrovascular complications, dementia, and tumors, and a decreased quality of life and life expectancy, which seriously increases the burden on patients, families, and society ( 5 – 13 ).

Current evidence shows that the pathogenesis of early-onset T2D is similar to that of late-onset T2D, mainly including β-cell dysfunction, insulin resistance (IR) and obesity ( 14 – 16 ). Several studies suggest that early-onset visceral obesity and associated insulin resistance may be major risk factors for the early progression of T2D ( 10 , 15 , 17 ). A Danish study found that obesity contributes to risk for T2D significantly more than genetic factors or poor lifestyle ( 18 ). The triglyceride-glucose index (TyG), based on triglycerides (TG) and fasting plasma glucose (FPG), has been widely established as an excellent index for evaluating IR ( 19 , 20 ). Recently, a study focused on the triglyceride glucose-body mass index (TyG-BMI), a derivative of body mass index (BMI) and TyG, which can simultaneously capture BMI, blood glucose and lipid profiles, and more closely reflect IR than TyG ( 21 ). Additionally, TyG-BMI has good predictive performance in hypertension, metabolic syndrome, nonalcoholic fatty liver disease, prediabetes, and diabetes ( 22 – 28 ). Since early-onset T2D is closely associated with IR and obesity, we hypothesized that TyG-BMI may be a useful predictor of early-onset T2D.

2.1 Study participants

In this cross-sectional study, we enrolled 1000 patients with newly diagnosed T2D who were admitted to the Department of Endocrinology of the Second Affiliated Hospital of Nanchang University between March 2022 and September 2023. Patients were included in the study cohort if they: (1) met the diagnostic criteria of World Health Organization Diabetes Experts Committee in 1999 for diabetes and HbA 1c ≥ 6.5%; (2) age of onset ≥ 18 years old; (3) none of the patients received hypoglycemic drugs within 3 months before admission. The exclusion criteria were as follows: (1) T1D, special types of diabetes, gestational diabetes, and uncertain types of diabetes; (2) diabetes during pregnancy or lactation; and (3) severe organ dysfunction, tumor, or severe infection. According to previous studies, all participants were divided into an early-onset T2D group (< 40 years old) and a late-onset T2D group (≥ 40 years old). This study was approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University (No. IIT-O-2023-122) and performed in accordance with the principles of the Declaration of Helsinki, revised in 2008. Informed consent was obtained from all participants.

2.2 Data collection and measurement

All participants completed a standardized admission questionnaire containing demographic characteristics, medical history, and lifestyle information under the guidance of a medical worker. Height, weight, and blood pressure were measured and recorded by nurses. Blood pressure was measured using a standard mercury sphygmograph, and all participants were asked to rest for at least 5 minutes in a quiet environment before blood pressure was measured. All participants were required to fast for at least 10 h. Venous blood was drawn from the elbow in the morning and 2 h after breakfast, and midstream urine samples were collected in the morning. Hemoglobin A1c (HbA 1c ), serum glucose, serum C-peptide, total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), serum uric acid (SUA), serum creatinine (Scr), and urinary albumin-to-creatinine ratio (UACR) were measured using an automatic biochemical and immunological analyzer (cobas 8000, Roche, Germany). The estimated glomerular filtration rate (eGFR) was calculated using the CRIC equation. All the samples were tested in the same laboratory. Comorbidities such as hypertension, fatty liver disease, coronary heart disease, and stroke were all diagnosed by medical institutions or had direct laboratory test evidence.

2.3 Definition and calculation

The diagnosis of early-onset T2D in adults was excluded; that is, patients aged 18-40 years could be diagnosed with early-onset T2D in adults after excluding those with T1D, monogenic diabetes, secondary diabetes, gestational diabetes, and no characteristics of undetermined diabetes. Diagnostic age was defined according to the American Diabetes Association (ADA) and World Health Organization (WHO) criteria ( 9 ).

The formulae for calculating BMI, TyG, and TyG-BMI are as follows: BMI = body weight (kg)/height (m 2 ), TyG = ln (fasting triglycerides [mg/dL] × FPG [mg/dL]/2), and TyG-BMI = TyG × BMI ( 19 , 29 ).

2.4 Statistical analysis

All data analyses and graphics were performed using SPSS 26.0 and R language 4.3.1. Participants’ measurement data were tested for normality. The normal distribution was expressed as the mean ± standard deviation, the non-normal distribution was expressed as the median and interquartile range (M[QL, QU]), and the count data was expressed as the number of cases and percentage. The independent sample t-test and Mann-Whitney U test were used to compare the characteristics of continuous variables between the two groups, and one-way analysis of variance and the Kruskal-Wallis rank sum test were used to compare the differences among multiple groups. Differences in characteristics between groups for categorical variables were analyzed using the chi-square and fisher’s exact tests.

BMI, TyG, and TyG-BMI were grouped into quartiles, and logistic regression analysis was used to evaluate the relationship between the risk of early-onset T2D and the three indicators. We reported the odds ratio (OR) and 95% confidence interval (CI) and tested the trend using the first quartile as a reference. We used restricted cubic spline curves (RCSs) to identify the nonlinear associations of BMI, TyG, and TyG-BMI with the risk of early-onset T2D and to explore the nonlinear associations of TyG-BMI with the risk of early-onset T2D from the perspective of sex. The receiver operating characteristic (ROC) curve was used to describe the diagnostic effect of FPG, TG, BMI, TyG, and TyG-BMI on early-onset T2D, and the area under the ROC curve (AUC) was used to evaluate the diagnostic value of each. Subgroup analyses were conducted according to sex, family history of diabetes, body mass index (BMI), smoking, alcohol consumption, fatty liver, and hypertension. BMI was stratified according to the standard recommended by the Working Group on Obesity in China, with 24kg/m 2 as the cut-off point for overweight ( 30 ). P < 0.05 was considered statistically significant.

3.1 Study population

We consecutively recruited 1484 patients from the Department of Endocrinology of the Second Affiliated Hospital of Nanchang University between March 2022 and September 2023. Based on the inclusion criteria, 484 patients were excluded. Details of participant screening are shown in Figure 1 .

Figure 1 The flow chart of participants selection.

3.2 Clinical characteristics of patients with early-onset T2D

Compared with the late-onset T2D group, the proportion of male and family history of diabetes was higher in the early-onset T2D group ( P < 0.05). In the early stage of the disease course, patients with early-onset T2D had a larger average body weight and higher BMI and tended to have lower systolic blood pressure and higher diastolic blood pressure ( P < 0.05). The levels of HbA1c, FPG, 2-hour postprandial plasma glucose (2hPG), 2hC-P, TC, TG, LDL-C, SUA, eGFR, TyG, and TyG-BMI were higher and the levels of HDL-C and Scr were lower in the early-onset T2D group ( P < 0.05). In addition, the prevalence of fatty liver in the early-onset T2D group was higher than that in the late-onset T2D group (57.6% vs. 46.0%), but the prevalence of hypertension (12.4% vs. 55.4%), coronary heart disease (1.8% vs. 20.6%), and stroke (0.4%vs5.0%) was significantly lower than that in the late-onset T2D group ( P < 0.05) ( Table 1 ).

Table 1 The baseline characteristics of participants.

3.3 The multivariate logistic regression for early-onset T2D

With age at onset as the dependent variable and excluding confounding factors, the statistically significant indicators in Table 1 were included in the multivariate logistic regression model as independent variables. The results showed that male, family history of diabetes, BMI, HbA 1c , TG and SUA may have positive effects on the occurrence of early-onset of T2D, among which family history of diabetes had the greatest influence ( P < 0.05) ( Figure 2 ).

Figure 2 Forestplot of risk factors for early-onset T2D.

3.4 Basic characteristics of the early-onset T2D according to TyG index quartiles

When the enrolled patients with early-onset T2D were grouped according to the TyG-BMI quartile, the results showed that the higher quartile of TyG-BMI was more likely to include younger patients, a higher proportion of men, and had higher body weight, BMI, SBP, and DBP. In terms of metabolic indicators, the higher quartile group of TyG-BMI had higher levels of FPG, 2hPG, TC, TG, LDL-C, and SUA; lower levels of HDL-C; and higher proportions of fatty liver and hypertension ( P < 0.05) ( Table 2 ).

Table 2 Basic characteristics of the early-onset T2D according to TyG-BMI quartiles.

3.5 Logistic regression analysis of the relationship between TyG-BMI and early-onset T2D

Table 3 shows the association of BMI, TyG, and TyG-BMI with early-onset T2D using multivariate logistic regression models. In addition to the crude model, two models were constructed and adjusted according to the results of the univariate analysis and potential confounders selected from literature reports. Model 1 was adjusted for sex and family history of diabetes, and Model 2 was adjusted for SBP, DBP, HbA 1c , TC, LDL-C, HDL-C, and SUA levels based on Model 1. The results showed that in Model 3, when TyG-BMI was considered as a continuous variable, the risk of early-onset T2D increased by 9% for every 1-unit increase in TyG-BMI (OR = 1.009, 95%CI 1.006-1.013). When TyG-BMI was evaluated by quartile, using quartile 1 as a reference, a higher TyG-BMI was associated with an increased risk of early-onset T2D ( P < 0.001). The risk in quartile 4 was significantly higher than that in quartiles 2 and 3, and the OR values in the three models were 5.209(3.553-7.637), 4.781(3.242-7.048), 2.771(1.720-4.467), respectively. In multivariate models 1 and 2, the association between TyG-BMI and early-onset T2D was slightly attenuated, but a positive dose-response relationship was maintained. Therefore, TyG-BMI is an independent risk factor of early-onset T2D.

Table 3 Logistic regression analysis of the relationship between TyG-BMI and early-onset T2D.

3.6 Nonlinear relationship between TyG-BMI and early -onset T2D

We used RCSs to fit the curve of the relationship between longitudinal changes in TyG-BMI and early-onset T2D. The results showed a nonlinear dose-response relationship between TyG-BMI and the risk of early-onset T2D. The slope of the curve increased with increasing TyG-BMI ( P for nonlinearity < 0.001) and the inflpoint was 240.82 ( Figure 3A ). This nonlinear dose-response relationship remained stable ( P for nonlinearity < 0.001) when re-fitting the RCSs after adjusting for covariates (sex and family history of diabetes) ( Figure 3B ). The relationships between TyG and BMI and early-onset T2D were similar to that of TyG-BMI ( Figures 3C–F ). We fitted the RCSs of TyG-BMI and early-onset T2D separately according to sex. The results showed that the relationship was more significant in males, with the inflection points of RCSs of 230.3 and 272.6 for males and females, respectively. The risk of early-onset T2D increased with an increase in TyG-BMI when TyG-BMI exceeded the inflection point value ( P for nonlinearity < 0.001). BMI and TyG index also showed a similar curve correlation ( P for nonlinearity < 0.001). The inflection points of RCSs for BMI in men and women were 24.41 and 28.60, respectively, and those for TyG in men and women were 9.64 and 10.46, respectively ( Figure 4 ).

Figure 3 RCSs of the association between TyG-BMI and early-onset T2D. The odd ratios for early-onset T2D (solid line) and 95% confidence intervals (shaded portion) are presented. (A, B) Correlation between TyG-BMI and early-onset T2D in the crude model and multivariate model(adjusts for gender and family history of diabetes). (C, D) Correlation between TyG and early-onset T2D in the crude model and multivariate model. (E, F) Correlation between BMI and early-onset T2D in the crude model and multivariate model.

Figure 4 RCSs of the association between TyG-BMl and early-onset T2D according to gender. As shown on the labels, blue line and area indicates male, pink line and area indicates female.

3.7 Subgroup analysis

To further explore the influence of other risk factors on the correlation between TyG-BMI and the risk of early-onset T2D, subgroup analyses were performed according to the following stratification variables: sex, family history of diabetes, BMI, smoking, alcohol consumption, fatty liver, and hypertension. The results of the subgroup analyses and interactions are summarized in Table 4 . Additive interactions between TyG-BMI and the risk of early-onset T2D were observed for sex, family history of diabetes, BMI, fatty liver disease, and hypertension ( P < 0.001). Stronger associations were found in participants who were male, had a family history of diabetes, were overweight (24 kg/m 2 ≤ BMI < 28 kg/m 2 ), had fatty liver, and had hypertension. However, no significant interaction was observed between smoking and alcohol consumption.

Table 4 Subgroup analysis of the associations between TyG-BMI and the risk of early-onset T2D.

3.8 Diagnostic value of TyG-BMI for early -onset T2D

An ROC curve was used to evaluate the diagnostic value of TyG-BMI in patients with early-onset T2D ( Figure 5 ). The results showed that the AUC of TyG-BMI was 0.6781, which was higher than that of TyG (AUC = 0.6509), BMI (AUC = 0.6368), FPG(AUC = 0.6097), and TG (AUC = 0.6358), all with P < 0.001. The optimal cutoff value of TyG-BMI was 254.865, the sensitivity was 74.6%, and the specificity was 53.6% ( Table 5 ).

Figure 5 The ROC curves of TyG-BMI and its main components for diagnosing early-onset T2D. TyG-BMI, triglyceride glucose-body mass index; TyG, triglyceride glucose index; BMI, Body mass index; FPG, Fasting plasma glucose; TG, Triglycerides.

Table 5 Diagnostic value of TyG-BMI for early-onset T2D.

4 Discussion

In this cross-sectional study based on the Chinese population, we found that patients with early- onset T2D had higher levels of HbA 1c , FPG, TC, TG, and SUA and more severe overweight/obesity, metabolic disorders, and IR at disease onset. In addition, we found a nonlinear dose-response relationship between TyG-BMI and newly diagnosed early-onset T2D, which was more significant in young men, overweight patients, and patients with a family history of diabetes, fatty liver disease, and hypertension.

Since the early 21st century, clinical studies from different countries have reported on the features of early-onset T2D, and the results have been compared with those of late-onset T2D. A cross-sectional retrospective study in South Korea concluded that patients with early-onset T2D were characterized by higher blood glucose levels, more family history of diabetes, early-onset of microalbuminuria, and insulin therapy as initial treatment ( 31 ). The Joint Asia Diabetes Evaluation (JADE) cohort study, conducted at 204 hospitals in Asia, showed that people with early-onset T2D had a more extensive family history of diabetes, as well as higher BMI, HbA 1c , and LDL-C levels ( 7 ). An investigation based on 30-year longitudinal data from the CARDIA study showed that compared with patients with late-onset T2D, patients with early-onset T2D had significantly worse overall and central obesity in early adulthood, with adverse metabolic profiles years before diabetes ( 32 ). In this study, we also found similar features, and severe metabolic disorders in patients with early-onset T2D may be an early manifestation of IR ( 10 , 33 , 34 ).

Studies have shown that traditional risk factors for diabetes are amplified in younger patients, and obesity remains the dominant factor ( 3 , 35 ). In this study, after adjusting for confounders, we found that male sex, family history of diabetes, and high levels of BMI, HbA 1c , TG, LDL-C, and SUA may have positive effects on the onset of early-onset T2D. Among these factors, hyperglycemia, obesity, and atherogenic dyslipidemia (i.e., elevated TG and decreased HDL-C levels) are the main components of metabolic syndrome. A decade of follow-up in the Tehran Lipid and Glucose Study found that among Tehran adults, both men and women with metabolic syndrome had a 2.9 times higher risk of developing T2D than those without metabolic syndrome; high levels of FPG, TG, and stable low levels of HDL-C increased the risk of T2D ( 36 ). We found that people with a family history of diabetes were 1.638 times more likely to develop early-onset T2D than those with late-onset T2D. Genetic predisposition is highly associated with early-onset T2D and has been demonstrated in previous studies. When a first-degree relative has diabetes, the offspring are at high risk of impaired fasting glucose levels, even without obesity. A study in an Iranian population showed that a family history of diabetes and elevated BMI alone increased the lifetime risk of diabetes in both men and women, with obese men with a family history of diabetes having a lifetime risk of about 54% higher at age 20 compared to normal-weight men without a family history of diabetes ( 37 ).

In this study, we observed a J-type nonlinear association between TyG-BMI and the risk of early-onset T2D. Although the underlying mechanism of the association between TyG-BMI and early-onset T2D is unclear, based on the clinical characteristics of patients with early-onset T2D, we speculate that severe IR and overweight/obesity may be important causes of early-onset in patients at high risk for T2D. TyG-BMI can simultaneously capture BMI, blood glucose, and lipid profiles and has emerged as an IR replacement indicator in recent years. Several studies have suggested that TyG-BMI is superior to TyG and some indicators related to lipids and obesity in evaluating IR ( 29 , 38 ). Two Chinese cohort studies respectively found that TyG-BMI was positively associated with prediabetes and diabetes risk, and the risk of developing TyG-BMI related diabetes (prediabetes) was significantly increased in non-obese people and in young and middle-aged people ( 25 , 26 ). We also found that the J-type relationship between TyG-BMI and early- onset T2D was more significant in young male population, and the risk of early-onset T2D increased more significantly with the slope of the TyG-BMI increase curve, which was different from the higher average TyG-BMI level and higher risk of pre-diabetes in the female population in the study by ZOU et al. ( 26 ) Another 5-year cohort study showed a positive, nonlinear relationship between TyG-BMI and diabetes risk in Chinese prediabetic patients, and this positive relationship was stronger in participants < 50 years of age ( 27 ). A number of previous studies have reported that TyG and BMI are independently associated with increased risk of diabetes in young people. For example, Ali et al. investigated the incidence of T1D and T2D in UK children and young adults under 25 years of age in relation to high BMI, showing that obesity leads to a four-fold increased risk of developing T2D in individuals ( 15 ). MA et al. analyzed data from the Chinese Health Screening project and found that elevated TyG index was independently associated with an increased risk of diabetes in individuals and was more sensitive in individuals younger than 40 years and without hypertension and obesity ( 39 ). Whether TyG-BMI, a combined measure of TyG and BMI, improves predictive power is unknown. We explored this issue using ROC curves, and the results showed that TyG-BMI was superior to its main components (TyG, BMI, FPG, and TG) in the diagnosis of early-onset T2D, with moderate AUC value but low specificity. The value of TyG-BMI in the diagnosis of early-onset T2D is limited, and in clinical application, hyperglycemia is still the only criterion for the diagnosis of T2D. Its predictive value needs to be confirmed by large-scale cohort studies. However, the diagnostic or predictive value of TyG-BMI in diabetes may vary among populations. Robinson et al. evaluated the predictive power of 11 obesity- and lipid-related parameters, including TyG, BMI, and TyG-BMI, in a Colombian elderly population at high risk of prediabetes, and showed that the TyG index had the best discernability in predicting prediabetes in older adults ( 40 ). In this study, the superior performance of TyG-BMI also supports that obesity may be an important reason for promoting the early onset of T2D.

In the subgroup analysis, we found that coexisting factors such as male sex, family history of diabetes, overweight, fatty liver, and hypertension with TyG-BMI increased the risk of early-onset T2D. Epidemiological studies in several countries have reported that being overweight/obese in children and adolescents is associated with an increased incidence of T2D in early adulthood ( 7 , 16 , 41 – 44 ). Results from a nationwide population study in Israel showed an interaction between BMI, sex, and adult T2D events. In contrast to this study, several studies have found a stronger association between high BMI in children and adults with T2D in women, all of which were conducted in minors ( 41 , 45 , 46 ). For people with high TyG-BMI, especially young men, combined with the above high-risk factors, strict control of blood pressure, effective weight loss, and treatment of fatty liver to reduce the risk of early-onset T2D.

This cross-sectional study is the first to explore the association between TyG-BMI and early- onset T2D, analyze the risk factors for early-onset T2D from a new perspective, and provide new ideas for the prevention and control of diabetes in high-risk populations. This study had several limitations. First, since the study population was from the same tertiary hospital and the sample size was relatively small, the generalizability was limited; therefore, it is necessary to verify the conclusions in a larger and more diverse population. Second, despite adjusting for common confounding variables, the logistic regression analysis did not completely eliminate the differences between the groups. Third, it would be valuable to further observe the association between TyG-BMI and early-onset T2D during follow-up to evaluate the accuracy of its long-term prediction.

5 Conclusion

Patients with early-onset T2D are characterized by severe IR, metabolic disorders, and being overweight/obese and an increase in TyG-BMI is independently associated with an increased risk of early-onset T2D.

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement

The studies involving humans were approved by The Ethics Committee of the Second Affiliated Hospital of Nanchang University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

Author contributions

YJ: Data curation, Investigation, Methodology, Software, Writing – original draft. XL: Supervision, Validation, Writing – review & editing.

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China (82060160) and Sub-center of National Clinical Medical Research Center for Metabolic Diseases (20221ZDG020067).

Acknowledgments

We thank the Clinical Research Center of the Second Affiliated Hospital of Nanchang University for data support and all patients who participated in this study.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Keywords: early-onset type 2 diabetes, insulin resistance, overweight, obesity, triglyceride glucose-body mass index

Citation: Jiang Y and Lai X (2024) Clinical features of early-onset type 2 diabetes and its association with triglyceride glucose-body mass index: a cross-sectional study. Front. Endocrinol. 15:1356942. doi: 10.3389/fendo.2024.1356942

Received: 16 December 2023; Accepted: 27 February 2024; Published: 11 March 2024.

Reviewed by:

Copyright © 2024 Jiang and Lai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Xiaoyang Lai, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Many type 2 diabetes patients lack potentially lifesaving knowledge about their disease, researchers find

by Frontiers

The body's inability to produce enough insulin or use it effectively often results in type 2 diabetes (T2D), a chronic disease affecting hundreds of millions of people around the globe. Disease management is crucial to avoid negative long-term outcomes, such as limb amputation or heart disease. To counteract adverse consequences, it is crucial that patients have good knowledge about the day-to-day management of the disease.

A team of researchers in Portugal has now assessed how many patients—both insulin-treated and not insulin-treated—have this crucial knowledge about T2D. They published their findings in Frontiers in Public Health .

"Our main motivation was to contribute to the reduction of the existing disparity in the knowledge that diabetic patients have regarding their disease," said first author Prof. Pedro Lopes Ferreira, director of the Center for Health Studies and Research of the University of Coimbra. "With this study we evidenced the need to improve the disease knowledge of type 2 diabetic patients."

Knowledge levels vary widely

To assess diabetes knowledge, the researchers used a knowledge test developed for people with type 1 or type 2 diabetes. Among other questions, the test includes sections about nutrition, signs and symptoms, and medication control. A total of 1,200 people with diabetes participated in the study, of whom almost 40% were insulin-treated. The rest of the sample adhered to specific diets with some of them additionally taking non-insulin oral antidiabetics, while others relied on diet alone.

The results showed that many participants (71.3%) could answer food-related questions correctly, and that more than four out of five respondents demonstrated good knowledge of the positive impact of physical activity. More than 75% of respondents also knew about the best method for testing blood sugar levels.

In other areas, however, the researchers found that knowledge was severely lacking. For example, when asked which food item should not be used to treat low blood sugar levels, only 12.8% of participants answered correctly. The lowest percentage (4.4%) of correct answers was on a question concerning the symptoms of ketoacidosis, a potentially life-threatening, late-stage T2D complication.

"One of the main reasons for this disparity in knowledge is probably the behavior of health professionals and the areas that are prioritized when informing patients," Lopes Ferreira explained.

Equipping patients with knowledge

The researchers found that the use of medication was one factor that impacted T2D knowledge. The percentage of correct answers was 51.8% for non-insulin treated patients, and 58.7% for patients using insulin. Looking at socioeconomic and demographic factors, being younger than 65 years, having a higher education , not living alone, and following a specific diet had a positive impact on disease knowledge.

The researchers said that their results highlight the need to improve T2D knowledge about certain aspects of the disease, for example blood sugar monitoring, which can help to avoid spikes in blood sugar levels that are associated with acute and chronic complications. Knowledge gaps within individual sections of the test are also something that needs to be addressed urgently, the team pointed out.

They also stated that studies with even more participants could help to better understand the role of the socioeconomic and clinical determinants of the disease.

"We focused on patients' own knowledge of their disease, rather than disease management being based solely on biological indicators. We hope that the results obtained will allow professionals to change the way they inform patients," Lopes Ferreira concluded.

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