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diabetes

Endocrinology

The Future of Type 1 Diabetes Management

The future of type 1 diabetes management may involve more than just insulin. (Stock photo)

Think type 1 diabetes (T1D), and you think of insulin. You think incurable. You think forever. But the introduction of the first disease-modifying drug, the immunomodulator teplizumab, along with investigational approaches such as beta-cell preservation, gene editing and stem cell therapy, show that what we thought was the final word was really just the opening argument.

“For so long, we treated type 1 diabetes symptomatically with insulin alone, which is absolutely essential and life-saving,” Children’s of Alabama pediatric endocrinologist Ambika P. Ashraf, M.D., said. “But if we recognize it as an autoimmune disease, then we need to treat the immune process driving it, not just the high blood sugars. You don’t treat rheumatoid arthritis by just controlling inflammation alone,” she said.

To highlight where the field is at this important point in time, Ashraf co-edited a journal supplement, a special collection of research articles on T1D, in Frontiers in Endocrinology.

The supplement, published as a collection of 14 peer-reviewed articles, brings together researchers from around the world to address immune modulation, beta-cell preservation, remission, screening, gene editing, stem cell therapies and metabolic memory. The goal was not to champion one therapy, Ashraf said, but to show how the future of type 1 diabetes care will be built from complementary approaches to slow, stop or even prevent disease progression.

Two articles are authored by researchers at Children’s and the University of Alabama at Birmingham (UAB).

“When you look at all this work together as a collection, you start thinking about different ways to approach the management of type 1 diabetes,” she said.

The idea emerged while Ashraf and her colleagues were outlining a chapter on disease-modifying therapy for a pediatric diabetes textbook. “There was simply too much important work happening,” she said. “It became clear that disease-modifying approaches in type 1 diabetes deserved a deeper, more focused conversation.”

When Frontiers invited proposals for a themed issue, the timing was perfect.

“We knew this was it—bringing together the growing body of research that is shifting type 1 diabetes from a condition we only manage to one we may be able to change, delay or even prevent,” she said.

The supplement focuses on three questions: Can we slow or stop the immune destruction of beta cells? Can we preserve insulin production?  Can we delay or prevent the onset of symptomatic type 1 diabetes?”

“Remission is so important because if you stop autoimmunity, then you can get back to having normal function,” she said. At the same time, beta cell preservation is also key. “They go hand in hand.”

Another theme in the supplement is screening for antibodies that predict type 1 diabetes risk before symptoms appear, which opens the door to interventions when they are most beneficial. But universal screening is only practical if therapies are effective and accessible, Ashraf said. “If we had a medication that we could confidently say, ‘Take this, and it would reliably reduce your risk of developing T1D,’ then universal screening would be transformative,” she added.

Several articles in the collection explore therapies that support beta‑cell health without suppressing the immune system but by strengthening the cells themselves. These include medications like verapamil, experimental TXNIP‑targeting drugs and high‑dose GABA, all of which aim to help insulin‑producing cells survive longer.

Perhaps the most important message of the supplement is that there likely will not be a one-size-fits-all approach for people with T1D, but a mix of options based on the individual patient. As Ashraf and her co-editors wrote in an editorial in the issue: “The innovative concepts highlighted here will undoubtedly shape the future of diabetology and inspire further research into state-of-the-art, disease-modifying therapies for T1D.”

February 12, 2026 by
Endocrinology

Increasing Foot Exams in Kids With Type 2 Diabetes

A QI project at Children’s helped improve the rate of foot exams for patients with type 2 diabetes. (Stock illustration)

When you think about type 2 diabetes in kids, you likely think about blood sugar, insulin and diet. But what about feet?

For kids—and adults—with diabetes, feet can be the canary in the coal mine when it comes to microvascular damage from high glucose levels. In the feet, neuropathy increases the risk of foot ulcers and even amputation. In the eyes, it can lead to vision loss, and in the kidneys to chronic kidney disease.

“Young people with type 2 diabetes are very different from adults,” said Mary Margaret Barr, M.D., a pediatric endocrinology fellow at Children’s of Alabama. “Their disease is usually much more aggressive. It causes issues earlier, and it can be harder to control.”

Current American Diabetes Association guidelines call for comprehensive foot exams upon diagnosis of type 2 diabetes and annually thereafter.

Yet when Barr set out to see how well clinicians documented complete foot exams in medical charts at Children’s, a large gap emerged.

Her review came after the hospital transitioned to a new electronic health record (EHR) system. She found that after the transition, documented foot exams in pediatric patients with type 2 diabetes fell from about one in four visits to almost none. “Basically, one or two kids out of 30 or 40 had a documented foot exam,” she said.

It wasn’t that clinicians didn’t know the guidelines; it was just different in the new system.

Recognizing that reality, the team launched a formal quality improvement project—later named UndeFEETed—to understand what was getting in the way and how to fix it.

A Small Exam That Takes Time—and Intention

A proper diabetic foot exam is not a glance at a pair of sockless feet. It requires time, tools and attention.

It starts with a neurological exam to test nerve sensation in the foot. A monofilament (soft strand of nylon) is tapped gently on the foot and toes to assess if the patient can feel where it is tapping without looking, followed by tuning fork vibration tests, a pinprick test, or a tendon hammer test to assess ankle reflexes. The vascular assessment includes checking blood flow in the foot and ankle.

For children—especially those who are younger or developmentally delayed—this exam can be challenging. And in a busy clinic, where providers juggle multiple screening requirements, preventive exams that aren’t automated can quietly fall away.

“There’s a really big list of screenings that come along with diabetes visits,” Barr noted. “It does get overwhelming.” But most of these other screenings are incorporated into the daily clinic flow, with documentation rates averaging more than 80%.

Plus, there’s no reimbursement for foot exams despite the time required to properly do one. “That’s frustrating,” Barr said.

She’s not surprised that when she presents the UndeFEETed data at conferences with other endocrinologists around the country. “Everyone’s like: Yeah—no one does foot exams.”

But a documented foot exam is more than just paperwork: it’s a safeguard that problems won’t be missed.

“If a foot problem was found, it could be addressed early rather than later,” Barr said.

That matters because children diagnosed with type 2 diabetes today will live with the disease for decades. Large studies show that by their mid-20s many already show signs of permanent nerve damage, Barr said.

Her team identified four main barriers to documented foot exams: lack of standardized documentation, limited access to exam tools, time pressures, and uncertainty about how to record the exam in the new EHR.

Physicians, nurse practitioners and clinic nurses worked together to redesign workflows. A new diabetes note template embedded foot exam documentation directly into routine visits. Supplies were in all exam rooms. Nurses helped flag when exams were due.

The team resisted adding pop-up alerts in the new EHR, which also helped. Instead, they built seamless, non-intrusive reminders into the charting process.

The results were striking. Within months, documented foot exams rose from less than 5% to more than 20%. Once more providers adopted the new template, documentation climbed to 50%—double the original goal.

However, after the initial changes were implemented and the system was running for a while, that figure dropped to about 30%. So Barr and her team are continuing to investigate other options in the EHR to help. They are also working with the nurses to identify the best way to communicate with the clinicians they work with most often, whether it’s a sticker or a certain word to help them remember to conduct a foot exam.

Barr hopes the work eventually leads to tracking long-term outcomes, including whether earlier and more consistent screening reduces complications. For now, the focus remains on getting the fundamentals right. “Our biggest goal is to make sure that kids who are about to graduate from pediatric care and go into the adult world have foot exams on record,” she said.

February 12, 2026 by
Endocrinology

QI Project decreasing no-shows in endocrinology clinic

Thanks to a QI project, fewer patients are missing appointments in an endocrinology clinic at Children’s of Alabama.

Missed appointments are nothing unusual in the world of clinical care. In Children’s of Alabama’s subspecialty clinics, a no-show rate of around 30% is not out of the ordinary. In some cases, these absences can derail a patient’s progress or allow their condition to worsen.

That’s why a team of clinicians at Children’s of Alabama started a quality improvement (QI) project to increase retention in the hospital’s Prediabetes and Metabolic Syndrome Clinic. Led by Grant Adams, CRNP; Christy Foster M.D.; and Jessica Schmitt M.D., MSHQS, the project has reduced no-show rates for return patients in the clinic from 37% to 18% in less than a year with support from the KPRI Quality and Safety Award.

The clinic, which opened in late 2022, was established to provide a centralized and dedicated clinic within the Division of Endocrinology and Diabetes for youth with metabolic syndrome and/or prediabetes. “Obesity and prediabetes are all too common in our youth,” Schmitt said. “When patients are referred to us, we want to be able to provide solutions beyond what pediatricians can provide. Further, some health care providers feel less experienced or comfortable managing obesity-related complications in children and counseling on lifestyle interventions. We felt it would be beneficial to assign these patients to a specialized team equipped to provide comprehensive, compassionate care focused on addressing these specific health concerns. As this patient population is a special area of interest for Grant, he was an ideal provider to lead this clinic.”

But when patients don’t return for follow-up appointments, it’s difficult for providers to achieve those solutions. That’s why the QI project was necessary. And it’s been effective; the team achieved the no-show decrease in the clinic by encouraging more patient-oriented options when educating and refining healthy habits. They operated under the motto: EMPOWER Healthy Habits. Providers adopted a modified version of the American College of Lifestyle Medicine (ACLM) pillars of health: sleep, social connections, stress management, activity, nutrition and mental health. They encouraged each patient to set SMART goals addressing one or two of these health domains.

Once a patient chose their goals, the team offered tools to help them succeed—for  example, a sound machine for sleep; activity dice for activity; portion containers for nutrition; craft kits for stress management; card games for social connections; journals for mental health.

All subjects were offered a body composition analysis and had access to a digital exercise platform, if interested. Same-day consultations with social work and nutrition were offered and encouraged. “Providing a human-to-human connection with a focus beyond the scale engaged patients and their families, particularly those who previously felt that healthy habits were out of reach,” Adams said.

Providers also worked with the families to determine the best methods for contacting them. When medically appropriate, they allowed shared decision making to guide follow-up frequency and modality (phone, MyChart, telemedicine, or in-person visits). “We’re working with families to make changes that meet their goals where they currently are, not a provider’s ideal change behaviors. This promoted the patients’ and families’ autonomy and agency,” Foster said. “This changed the dialogue from provider-dictated change to patient-centered.”

Provider training also played a crucial role. They received training in motivational interviewing (MI). “MI is frequently quoted as the ideal way to promote patient-led behavior change, but most providers have not received any training,” Schmitt said. “After working with Dr. Matthew McKenzie, the MI trainer working with the team, when I lean into MI techniques, I find visits more collaborative, rewarding and effective than when I try to tell a patient or family what to do.” The training is ongoing.

The team’s initial goal when they began the project in the December 2023 was to reduce no-show rates for return visits by 19% for a reduction from a baseline of 37% to 30% by July 2025. They nearly met that goal in the first stage alone, reducing missed appointments to 31% between December 2023 and July 2024. By the end of stage two in November 2024, the rate had fallen to 18%.

The work is evolving and continues as the EMPOWER Healthy Habits team continues to find better ways to serve their patients and families. “We are reassured by this success and look forward to working on sustaining these results,” Adams said. “In future endeavors, we look forward to evaluating if increased retention has health benefits for our patients, which is the ultimate goal.”

January 9, 2025 by
Endocrinology

Connection between weight and type 2 diabetes

Children’s of Alabama is one of 15 institutions across the U.S. involved in the DISCOVERY study. (Stock photo)

It’s a troubling trend: Type 2 diabetes diagnoses have rapidly increased in children and teens, especially during the COVID pandemic. Now, University of Alabama at Birmingham (UAB) and Children’s of Alabama investigators are joining others from 15 prominent institutions across the United States to reveal the factors leading to this phenomenon, which poses massive public health implications worldwide.

The DISCOVERY study aims to determine why some children who are overweight or obese develop type 2 diabetes while others do not. Children with diabetes tend to have a more rapid progression than adults to other serious health conditions and complications such as high blood pressure, kidney disease and retinopathy, experts say. So it’s crucial to fully understand the contributing factors in order to more precisely predict which children are at the highest risk—and potentially prevent them from developing the condition.

“Very few longitudinal studies have been done to determine which of these kids converts to type 2 diabetes,” said DISCOVERY co-investigator Barbara Gower, Ph.D., who’s also a professor and chair of the Department of Nutrition Sciences at UAB. “This study is designed to recruit at-risk children and see who actually converts to type 2 diabetes, looking at a broad suite of factors—everything from social risk factors to biological factors.”

Ambika Ashraf, M.D., study co-investigator and director of the Division of Pediatric Endocrinology at Children’s, agrees. “Even though we understand that high BMI predisposes someone to type 2 diabetes, what is really unclear is what prompts a child who has all these risk factors to convert,” she said.

The issue is particularly relevant to Alabama, which is one of 15 states considered to be in the “Diabetes Belt” because the incidence of type 2 diabetes is about one-third higher than the national average. Children’s cares for more than 80% of the state’s pediatric type 2 diabetes patients, with nearly 650 such children referred for evaluation for new-onset cases between March 2017 and March 2021. Additionally, hospital admissions for new-onset pediatric type 2 diabetes cases in Alabama more than doubled over a two-year span that led up to the early stages of the pandemic.

Over the next two years, DISCOVERY will enroll approximately 3,600 children and teens ages 9-14, all with a BMI at or above the 85th percentile and HbA1c levels of 5.5% or higher. Children will be tracked for between two-and-a-half and four years, completing comprehensive annual visits, including a three-hour oral glucose tolerance test and detailed physiological assessments. They will also undergo a brief visit every six months, along with telephone checks every three months to monitor for type 2 diabetes.

The study’s size is a huge strength, says Gower, also a senior scientist at UAB’s Diabetes Research Center. “Because the actual conversion rate to type 2 diabetes is still quite low, we need a lot of sites and participants in order to have enough children to analyze,” she explained.  

Ideally, Ashraf and Gower say, the DISCOVERY trial will produce new insights that help clinicians pinpoint exactly which children with high BMIs are most vulnerable to developing diabetes and stop the process.

“If we can determine the risk factors that predispose certain individuals to develop type 2 diabetes, that could have a huge impact,” said Ashraf, also a professor of pediatric endocrinology and associate director of the Comprehensive Diabetes Center at UAB. “It may have a global impact, too, because type 2 diabetes is going to cause a huge economic impact throughout the world.”

January 7, 2025 by
Endocrinology

Ashraf’s study shows characteristics of hybrid diabetes

A study led by Ambika Ashraf, M.D., shows the unique challenges that patients with hybrid diabetes face.

A study led by Children’s of Alabama endocrinologist Ambika Ashraf, M.D., highlights the unique characteristics of hybrid diabetes (HD) or double diabetes, distinguishing it from both type 1 and type 2 diabetes. It is pivotal in understanding the different trajectories of diabetes in children and may pave the way for more targeted treatment strategies.

The study, titled “Children and Adolescents With Hybrid Diabetes: A Management Conundrum” is a retrospective analysis from 2016 to 2020, examining 102 subjects with type 1 diabetes (T1DM), hybrid diabetes (HD), and type 2 diabetes (T2DM). It was published in the journal Endocrine Practice.

Key findings of the study indicate that children with HD show a blend of autoimmune diabetes autoantibody positivity (a hallmark in T1DM) and insulin resistance (a hallmark of T2DM), creating a complex treatment and management scenario.

Researchers found that patients with HD were still insulin dependent at a two-year follow-up, like patients with T1DM. Patients with HD also had a strong positive family history of T2DM and preserved endogenous c-peptide production, like patients with T2DM.

“Our study findings underscore the need for healthcare providers to be vigilant in diagnosing and managing this distinct form of diabetes, which poses unique challenges due to its hybrid nature,” said Ashraf, who’s the director of the Division of Pediatric Endocrinology and  Diabetes at the University of Alabama at Birmingham (UAB). “The study calls for further research to develop precision treatment strategies for pediatric patients with hybrid diabetes. Our team of researchers wants to encourage more research specifically on using insulin sensitizers and incretin based therapies.”

Other study authors included first author Charles A. Gagnon BS, UAB Heersink School of Medicine medical student, and Jessica Schmitt M.D., assistant professor in the Division of Pediatric Endocrinology and Diabetes.

August 12, 2024 by
Endocrinology

On the Front Lines of the Pediatric Obesity Crisis

In the Children’s of Alabama SHINE clinic, a multidisciplinary team take a holistic approach to helping patients with obesity.

About one in five children and adolescents in the U.S., representing nearly 15 million individuals, have obesity.[i] That puts the multidisciplinary Strategies for Health, Interventions, Nutrition, and Exercise (SHINE), clinic at Children’s of Alabama on the front lines of this complex issue. “It’s not just about weight loss,” pediatric endocrinologist Christy Foster, M.D., said. “We address the root causes of obesity and the various comorbidities associated with it. This holistic approach is vital for the long-term success of our patients.”

The clinic is run by adolescent medicine specialist Stephenie B. Wallace, M.D. In addition to Foster, the team includes a registered dietician, a physical therapist, an exercise physiologist and a social worker. Together, they create individualized plans for each patient focused on achievable goals.

Soon after starting in the clinic, Foster cared for a teenaged girl with obesity. The patient’s mother had type 2 diabetes, and the teenager had pre-diabetes. “Mom was just very worried and concerned for her,” Foster said. “But the girl was just very defeated. She felt it was her fault.” That’s not unusual, she said. “That’s one of the things that is tough around this condition. There’s a lot of shame and guilt.”

Christy Foster, M.D.

Foster assured the girl that her weight did not define who she was. She asked her to pick a goal to work toward. “She wanted to be a nurse,” she said. “So that became her motivation. I told her that if you want to take care of your patients, you have to take care of yourself first.”

When the teen returned for her next appointment, “she had such a light,” Foster said, and she’d started going to the gym. “There wasn’t a huge change all at once,” she said. “But she found the motivation. And that was one of the things she needed.”

The clinic’s philosophy is that obesity is a chronic disease, not a personal failing. “There are genetic, environmental, and psychological factors at play,” Foster said. “What I appreciate most about this clinic is our collective willingness to find creative solutions. We meet families where they are and tailor our recommendations to their unique circumstances. This adaptability is crucial for making a real difference in our patients’ lives.”

The clinic also emphasizes early intervention, encouraging primary care clinicians to refer patients before they develop the metabolic diseases of obesity, such as type 2 diabetes. “We now see that type 2 diabetes constitutes most of our new onset diabetes cases in children. This is a stark increase from a few decades ago,” Foster said.

New guidelines on childhood obesity from the American Academy of Pediatrics call for an aggressive approach to treatment, including pharmacotherapy and, in some situations, bariatric surgery. “We’re navigating these new recommendations carefully,” Foster said, “always weighing the benefits and potential risks. Cost is also a consideration, as insurance coverage varies.” In addition, the two newest weight-loss drugs, semaglutide and terzepatide, are only approved for use in adults, although they may be used off-label for children.

[i] Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/php/data-research/childhood-obesity-facts.html.

August 5, 2024 by
Endocrinology

Going ‘beyond the scale’ in prediabetes treatment

A Children’s of Alabama clinic offers a family-centered approach to prevent prediabetes from progressing to diabetes. (Stock photo)

A lag in care for children with obesity and its complications can spell the difference between prediabetes and a full-blown case of diabetes. Recognizing this, Children’s of Alabama pediatric nurse practitioner Grant Adams, CRNP—who has always had a “big heart for children struggling with obesity”—spearheaded a new clinic at Children’s to fill the gap.

The result is the Prediabetes and Metabolic Syndrome Clinic, which was established in late 2022 and runs half-days every Tuesday at the Children’s Diabetes and Endocrine Clinic. The clinic is meant to prevent delays in care for children referred by their pediatricians for prediabetes, weight management and related issues.

These young people face the high risk that their prediabetes will progress into diabetes, a disease which affects more than 350,000 children and adolescents under age 20 in the United States, according to the Centers for Disease Control and Prevention (CDC). Nearly 20% of children and adolescents nationwide cope with obesity, predisposing them to diabetes as well as other health conditions.

Children’s pediatric endocrinologist Christy Foster, M.D.,  assisted Adams in establishing the clinic, which also includes physicians, a registered dietitian and a social worker. The team aims to move “beyond the scale” with a family-centered approach that emphasizes healthy eating habits and movement as well as medication management.

“My vision was to instill habits that would be lifelong,” Adams said. “We want to reinforce that just because there’s a family history of diabetes, it’s certainly not inevitable.”

To that end, clinic visits—which take place every three to six months—deeply involve parents and other caregivers. While staff members closely monitor patients’ well-being and lab work, the resulting positive changes often have ripple effects on the entire family.

“Rather than doing more prescriptive-style medicine where everyone is assigned the same interventions, we work with families to see what can be reasonably done for and with them,” said endocrinologist Jessica Schmitt, M.D.,  an assistant professor in the Division of Pediatric Endocrinology and Diabetes at Children’s and the University of Alabama at Birmingham (UAB).

“At every visit, we talk about how food is fuel,” Adams added. “Regardless of a child’s age, it’s not their responsibility to buy and cook the food, especially if they’re not teenagers. They rely on a family approach—and families buy in.”

Even so, results are mixed. Some children and teens who visit the clinic improve their diets and lifestyles dramatically, with associated improvements in their weight, blood sugar levels, and problems such as high cholesterol.

“This is a lifelong commitment, not a diet,” Adams said. “It isn’t a sprint, it’s a marathon.

“If we can affect this generation, my vision is that their kids will be affected positively,” he added. “Obesity is a pandemic, and we’ve got to stop it somewhere. I’ve decided it needs to start with kids. This is a generational problem, and we can make a positive impact.”

January 29, 2024 by
Endocrinology

Exploring GABA and GAD for Type 1 Diabetes

A study led by Gail J. Mick, M.D., shows promising results for treating new-onset cases of type 1 diabetes with GABA and GAD.

Could an over-the-counter supplement help save insulin production in new-onset type 1 diabetes? That’s the question pediatric endocrinologists Gail J. Mick, M.D., Kenneth McCormick, M.D. (now retired) and colleagues at Children’s of Alabama set out to explore. The answer, according to their recently published article in the journal Nature Communications, is, quite possibly.

The study explored the potential of the amino acid gamma-aminobutyric acid (GABA), found in health food stores, and glutamic acid decarboxylase (GAD), an enzyme that acts on glutamate to form GABA, to preserve pancreatic islet function.

GABA is an important neurotransmitter in the brain. However, it is also critical to insulin production, with GABA receptors found within the islet beta cells responsible for insulin production. Meanwhile, GAD converts abundant circulating glutamate from dietary protein and intestinal microbiota into GABA. 

Animal studies showed their potential to stimulate insulin secretion, inhibit glucagon overproduction, dampen inflammation and promote beta cell regeneration. Still, getting a clinical trial approved in a pediatric population took years.

“Nobody does first-line studies in children,” Mick said. “For safety reasons, studies are typically conducted in adults, but in type 1 diabetes, adults differ from children. In children, the autoimmune destruction of insulin secretion is faster.

“It took a lot of luck, hope and a dream we were going to cure diabetes with something safe and oral” to get FDA approval for the trial, she said.

The study randomized 97 children (average age of 11) within five weeks of their diagnosis to oral GABA with or without a GAD-alum injection. However, the researchers were constrained to low doses of the compounds, given the FDA’s concern about potential side effects.

Although the study didn’t meet its primary goal of preserving beta cell insulin production, the GABA/GAD combination significantly reduced glucagon levels, improving blood sugar levels. The study also found lower levels of the inflammatory cytokine expression implicated in the pathogenesis of type 1 diabetes. There were no adverse effects.

“Not only did we see reduced glucagon, but there were also beneficial immunologic effects,” Mick said. “We’re delighted by that.” The immunology results were recently published in the journal Biomedicines.

The positive outcomes show enough promise that further studies with higher GABA doses are warranted, Mick said, perhaps in combination with other agents, such as GLP-1 receptor agonists, which also have beta-cell regeneration effects.

“It’s fascinating,” Mick said. “Just fascinating.”

January 29, 2024 by
Endocrinology

Children’s, UAB to study diabetes in minority youth

Cases of Type 2 diabetes are on the rise among minorities in the U.S.

By Emma Shepard (UAB)

The prevalence of Type 2 diabetes in youth is increasing in the U.S., primarily among minorities, with Black and Hispanic youth showing the greatest increase. Neither the reason for the increase nor the mechanism underlying the disproportionate risk in minority youth is known.

Researchers at Children’s of Alabama and the University of Alabama at Birmingham (UAB) have received more than $3.7 million from the National Institutes of Health to study the increasing prevalence of diabetes in youth as part of a nationwide consortium. Ambika Ashraf, M.D., director of the Division of Pediatric Endocrinology and Diabetes at Children’s of Alabama and UAB, and Barbara Gower, Ph.D., interim chair and professor in the UAB Department of Nutrition Sciences, will lead the UAB site.

The study is part of a project designed to identify the predictors of Type 2 diabetes in youth. UAB and Children’s, located in the U.S. diabetes belt and home to the UAB Comprehensive Diabetes Center and Diabetes Research Center, were collectively one of 15 institutions selected to participate.

“Our research aims to further understand health disparities in diabetes prevalence, as well as study the impact of particular risk factors on the conversion of prediabetes to Type 2 diabetes,” Ashraf said. “This knowledge would allow us to better treat children, especially minority children, who have prediabetes.”

Prediabetes is a serious health condition in which blood sugar levels are higher than normal, but not high enough yet to be diagnosed as Type 2 diabetes. 

Over the course of the project, which will end in November 2027, researchers hope to enroll 1,500-3,000 youth who are at risk for diabetes. The main objective of the study is to identify factors that predict conversion to Type 2.

All participants will be non-diabetic, but at risk, at the time of recruitment and baseline testing. The team of researchers will record body composition, beta-cell function, insulin sensitivity, diet, physical activity, psycho-social factors, the intra-uterine environment, genetic polymorphisms related to diabetes risk and other factors that may affect risk for Type 2 diabetes.

August 23, 2023 by
Endocrinology

Can Diabetes Prematurely Age DNA in Teens and Adolescents?

Dr. Christy Ann Foster is a pediatric endocrinologist at Children’s of Alabama.

How does diabetes change a teenager’s gene expression? That’s the question researchers in the Endocrinology and Diabetes Division at Children’s of Alabama are exploring. The topic is vital given the stratospheric rise in Type 2 diabetes in adolescents.[1] In addition, the disease appears to be more aggressive than adult-onset diabetes, with adolescents losing up to 15 years of life expectancy due to comorbidities.

Research in adults shows that many complications of diabetes, including increased risk of cardiovascular and kidney disease, diabetic retinopathy, nerve damage and early mortality, appear to be related to epigenetic aging, in which gene expression changes while the underlying DNA remains the same. Epigenetic age is an indicator of biological aging, capturing the impact of environmental and behavioral influences across time on cellular function and the potential for disease. The higher a person’s epigenetic age acceleration, the higher their all-cause mortality and morbidity is. Ideally, a person’s epigenetic age corresponds to their chronological age; the epigenetic age of a patient with diabetes may be years older than their chronological age.

“I think the study of epigenetics is fascinating because it shows the way our genes can be changed by other influences,” Children’s pediatric endocrinologist and study leader Christy Anne Foster, M.D., said. “If we can understand these influences and how they can modify the impact of our genetics, there is potential for intervention.”

However, little research has been done on such epigenetic changes in children, and none in those with diabetes and/or obesity. Which is exactly what the study focuses on.

“With the impact of seeing such an increase in Type 2 diabetes in adolescents, and even pre-adolescents, we want to understand what developing this condition so early means for their long-term health,” Foster said.

The first step is a pilot study using the DNA of children and adolescents ages 12-18. Researchers are comparing the DNA of patients with diabetes and obesity to the DNA of those without either. They’re also comparing the DNA of patients with obesity to that of normal-weight children and adolescents. Researchers hope the study will establish that epigenetic aging occurs in adolescents with diabetes and/or obesity and will help them identify risk factors that can be addressed.. If the study is promising, researchers plan to do longitudinal studies to follow the impact of dietary and therapeutic interventions on epigenetic age acceleration.

One challenge will be determining whether the changes are the result of diabetes or something else, which is why the control group is so important, Foster said.

If the investigators do find a direct link between diabetes and DNA methylation, they may not be able to directly modify it, Foster said, but they could potentially support patients based on their social determinants of health and manage their risks that way.

Foster is partnering with Bertha Hidalgo, Ph.D., an associate professor at the University of Alabama at Birmingham’s School of Public Health. She’s also collaborating with researchers at the University of Minnesota, who are analyzing the DNA for epigenetic changes. “Given the prevalence of Type 2 diabetes in pediatric patients, understanding these changes in that population is critical,” Foster said. “These young people are at such high risk for complications with such a long-term diagnosis. The more we understand, the more we can hopefully improve their quality of life.”

[1] Lawrence JM, Divers J, Isom S, et al. Trends in Prevalence of Type 1 and Type 2 Diabetes in Children and Adolescents in the US, 2001-2017. JAMA. 2021;326(8):717-727. doi:10.1001/jama.2021.11165

January 16, 2023 by