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diabetes

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
Endocrinology, Inside Pediatrics

High-Risk Diabetes Clinic Keeps Kids Out of the Hospital

Children’s of Alabama offers clinic to help high-risk diabetes patients.

The 2018 death of a teenage patient was a wake-up call for Children’s of Alabama pediatric endocrinologist Mary Lauren Scott, MD. The patient had type 1 diabetes and had been admitted numerous times over the previous few years with sky-high blood sugar. He died at home from diabetic ketoacidosis (DKA), a diabetic emergency in which the body breaks down fat for fuel because it doesn’t have enough insulin.

In response, Scott, who also has type 1 diabetes, took action. She and her team searched their data and found 10 patients in the previous year who had been admitted three or more times with DKA. Such admissions are a red flag that the patient isn’t taking their insulin doses at home and that they have a risk of dying or having a medical emergency they can’t recover from. 

“When you’re dealing with a chronic disease such as diabetes and patients have recurrent hospitalizations, we get burnt out too,” she said. “That makes it difficult to have the kind of positivity, motivation and drive to help them surmount the insurmountable and deal with what, for them, feels impossible. It’s hard, it’s complicated, and it’s not uplifting when you feel like you’re not able to help the patient.”

Scott, who was already directing a clinic for children and adolescents with type 2 diabetes, started another clinic in 2018 specifically for these high-risk patients. The primary goals of the clinic are to prevent hospitalizations and saving lives. The patients are all adolescents, at an age when they—instead of their parents—typically start handling their insulin injections and blood glucose tracking. 

The clinic meets half a day each month. The focus is on communication. Parents, social workers, nurses, nurse practitioners, diabetes educators and counselors work as a team to build trust with the teenagers. “We speak to them differently to get them to open up to us more than they perhaps ever have with other providers,” Scott said.

That means ensuring them there is no shame attached to missing insulin doses; what’s important is that they talk about it. “We tell them, ‘We need to know how to help you, so we can help you find success,’” Scott said. “We try to make the focus more about what’s working for [them] with [their] diabetes, what’s not working, and what [they] think would make things easier.” 

Patients must go six months without hospitalization before they graduate from the program.

The clinic is not just for patients, but for their families, as well. The patients are often drawn from minority and low-income backgrounds and have single parent households, Scott said. “The parent works and is also trying to manage a teenager who’s depressed or burnt out,” she said. “They can’t do everything.”

Because many of the parents have a history of interaction with child protective services, they rarely opened up to the staff about their child’s difficulties. With the new approach, parents are now more likely to talk about what’s happening at home and what they need help with. “That’s where we typically find success for these patients,” she said. 

The results have been impressive. 

  • 14 of the original 15 patients graduated. The one remaining is the youngest patient with significant home life issues. 
  • 8 of the 14 had a lower A1C when discharged. 
  • 6 of the 14 had no DKA admissions while in the clinic; all had three or more before joining the clinic. 
  • 12 of the 14 had fewer missed visits even though they came to clinic monthly instead of every three to four months.
  • Half had lower rates of DKA.
  • 12 of the 14 started continuous glucose monitoring while in clinic, and four also received insulin pumps, leading to a dramatic improvement in their health.
  • No patients died.

There are currently eight more patients enrolled, and more will be invited in the coming months, Scott said.

September 5, 2022 by