How Type 2 Diabetes Impacts Children vs. Adults
Coverage of the ADA Scientific Sessions is brought to you by the ADA x BT1 Collab.
Cases of Type 2 diabetes are rising among youth under the age of 20, and if you think Type 2 diabetes progresses in children as it does in adults, think again.
In fact, children with Type 2 diabetes are not little adults, per the name of the session at the ADA’s 81st Scientific Sessions. In this article, we’ll be recapping it below. In this session, we learned:
- How beta-cell secretion differs between youth and adults
- Which groups of children are being impacted by diabetes and which groups are at risk
- About current trials studying Type 2 diabetes in children
- Why it’s difficult to find pediatric participants for clinical research
- Medications available for children with Type 2 diabetes and what’s to come
Type 2 Diabetes Progression in Youth vs. Adults
Tamara Hannon, MD, discussed the pathophysiology of Type 2 diabetes in children and how it compares to adults with diabetes. In the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, it was shown that Type 2 diabetes is not only more aggressive in youth and adolescents than in adults, complications from T2D are accelerated and beta-cell decline happens faster. Beta cells produce and secrete insulin, the hormone that regulates blood glucose levels.
Diabetes is a spectrum of conditions that lead to an official diagnosis – from insulin resistance, beta-cell dysfunction, Two-hour glucose levels of 140-199 mg/dL (7.8 to 11.0 mmol/L) after taking the 75 g oral glucose tolerance test. Also referred to as prediabetes. impaired glucose tolerance, Glucose levels of 100 to 125 mg/dL (5.6 to 6.9 mmol/L) during fasting. Also referred to as prediabetes. impaired fasting glucose, to beta-cell failure, and eventually hyperglycemia and later, diabetes. The risk factors for Type 2 diabetes in children are similar to those in adults:
- Family History/Genetics
- Prenatal exposures
- Life circumstances
Declining beta-cell function is apparent in impaired glucose tolerance. As one’s insulin sensitivity declines, insulin action decreases as well. After a diabetes diagnosis, the effectiveness of oral therapy with metformin fails relatively quickly, as demonstrated in the TODAY study. Failure from medications occurred as insulin’s response to glucose declined.
How was therapeutic failure defined, per Hannon? “Having a sustained elevation of A1C at or above 8 percent for 6 months or the inability to wean from insulin after metabolic decompensation (failure).”
46 percent of the 699 participants over a maximum of 72 months of follow-up experienced failure of medications, in the TODAY study. Even in the three treatment groups, no matter the group, insulin sensitivity didn’t improve. Beta-cell failure was that was associated with failed response to medications in the TODAY study.
In the “A Diabetes Outcome Progression Trial” (ADOPT), which studied the decline of beta-cell function in adults with Type 2 diabetes, who were on average, 56 years old, beta-cell function declined between 0-6 percent over 6 months.
In the TODAY study with children who were on average, 14 years old? Beta-cell function declined by 19 to 25 percent over 6 months.
Another study called the Restoring Insulin Secretion (RISE) pediatric medication study, set out to answer the primary question was: Is it possible to intervene and improve or prevent the loss of beta-cell function in children and adults with prediabetes or early Type 2 diabetes? For 12 months:
- One group was given Insulin glargine (long-acting insulin) for three months and then only metformin for 9 months.
- Another group was given only metformin.
Another goal was to determine if the preservation of beta cells could be maintained for 3 to 9 months after stopping the use of medications.
For both treatments, beta-cell function remained stable for the 12-months they received medication. But after stopping them for the 3 to 9-month period, beta-cell secretion dramatically decreased over time. This didn’t differ between kids with prediabetes or newly diagnosed Type 2 diabetes. Also, the results showed beta-cell secretion loss was greater in youth than adults.
Which Youth Groups Are At Risk for Type 2 Diabetes?
Just like disparities exist among adults with Type 2 diabetes, similarities exist among young adults and children. Angela L. Liese, Ph.D., MPH, FACE, FAHA, and a researcher of the SEARCH for Diabetes in Youth study, led this aspect of the discussion. Liese said children of color had the highest incidences of diabetes, especially Native American ones, and are lowest among non-Hispanic white children. Generally, children in older age groups are showing higher rates of Type 2 diabetes, as well.
Delving deeper into these facts, children of color were more likely to be obese or overweight – one of the primary risk factors Liese pointed out – and were, unfortunately, more likely to start experiencing complications in their early 20s. Complications noted were: diabetic kidney disease, retinopathy, neuropathy, cardiovascular issues, arterial stiffness – which is associated with heart attacks and strokes, and hypertension.
So why are children of color most likely to be impacted by Type 2 diabetes and related complications and risk factors? Socioeconomic conditions are a critical factor. These disparities exist in:
- The likelihood of having a healthcare provider, especially a primary care provider
- Income levels
- Food insecurity
According to the SEARCH study, Liese noted nearly 31% of young people with Type 2 diabetes, ranging from ages 10-34 years old, were food insecure, compared to nearly 18% with Type 1 diabetes.
In general, children with Type 2 diabetes are more likely to have socioeconomic disadvantages and positions which contribute to worse glycemic outcomes. And it’s not getting better – the rate of Type 2 diabetes is increasing in youth in the United States, particularly among children of color.
Ongoing Research in T2D Research in Children/Youth
Even with all of this data, more research is needed to learn how Type 2 diabetes is impacting children, especially when it comes to medications. Elvira Isagnaitius, MD, MPH, from the Joslin Diabetes Center, mentioned that metformin is the first-line drug therapy for children with Type 2 and the only FDA-approved oral medication to treat Type 2 diabetes in this group. But similarly to adults with T2D who take metformin, it doesn’t work for everyone due to its gastrointestinal side effects. Also, as mentioned earlier, metformin, alone, becomes less effective over time in helping youth reach their glycemic goals.
But What if Metformin isn’t Enough?
Dr. Isagnaitius mentioned that the only other medications approved to treat children with Type 2 diabetes are insulin and liraglutide, a GLP-1 commonly known as Victoza. Liraglutide was approved in 2019 for pediatric patients, 19 years after the approval of metformin. Currently, ongoing studies are investigating how well the SGLT-2s, DPP-4s, and other GLP-1s work in pediatric patients. According to the ADA, metabolic surgery can also be considered to treat adolescents with Type 2 diabetes who have a BMI greater than 35 kg/m2, have serious comorbidities despite medication use and lifestyle changes, and are having trouble reaching their glycemic targets. Bariatric surgery earlier after a Type 2 diabetes diagnosis is associated with a higher remission rate.
Barriers and Opportunities in Pediatric T2D Research
Still, according to Isagnatitius researchers are facing barriers to clinical research such as:
- A small pool of patients
- More than 90 percent of Type 2 patients have socioeconomic disadvantages and cannot afford to miss work or school for study visits.
- Patients of color are less likely to trust research due to historical racism.
- Many pediatric patients struggle with taking medications consistently.
- Common co-morbid conditions such as depression and non-alcoholic fatty liver disease may be exclusionary criteria.
Despite the challenges, Sonia Caprio, MD, from the Yale University School of Medicine, says there are opportunities to learn more about the impact of diabetes in youth and children, including:
- Designing studies differently to focus on smaller groups of participants with shorter trial durations.
- Clinical testing of new treatments offers a better opportunity to modify diabetes progression, particularly when it comes to preserving or improving beta-cell function.
For more coverage of the American Diabetes Association’s 81st Scientific sessions, CLICK HERE.