When Sheela N. Magge, MD, began her pediatric endocrinology fellowship at Children’s Hospital of Philadelphia in 2001, she began witnessing an extraordinary phenomenon unfolding in the hospital’s pediatric endocrinology ward.
Youngsters coming in with symptoms of diabetic ketoacidosis were leaving with diagnoses of type 2 diabetes mellitus, long considered an adult disease.
“It was remarkable,” said Magge, Lawson Wilkins chair of pediatric endocrinology, and director of the Division of Pediatric Endocrinology, Johns Hopkins School of Medicine, Baltimore.
That once-remarkable diagnosis has become more commonplace in pediatric specialists’ offices. But young people don’t stay young forever. And diabetes just doesn’t disappear. Plus, experts said, there are not enough trained pediatric endocrinologists, or enough obesity-trained professionals either, to handle what’s coming.
Eventually the day will come when these patients will seek care from providers who treat adults. And a large concern among pediatric specialists is that primary care physicians (PCPs), the medical world’s version of baseball’s shortstop, will not be prepared to fully grasp what they are up against, namely a disease that is far more advanced, far more complicated, and far more deadly — from a premature mortality vantage point — than the adult version.
Numerous studies over the years, like the years-long TODAY and SEARCH trials, have proven these statements true; studies to understand why they are true are underway.
At the age of diagnosis, on average around 15 years old, 20% already have one complication, said Stephanie Chung, MBBS, an investigator with the National Institute of Diabetes and Digestive and Kidney Diseases. Ten years later, more than 50% of these patients do, and 15 years later 80% have at least one diabetes-related complication, including hypertension and early diabetic kidney disease. This contrasts with adults with diabetes; 25% develop diabetic kidney disease after 10 years.
An entire generation of these children could be lost to follow-up when they reach adulthood, said Magge.
Even endocrinologists who treat adults might not be well versed in pediatric diabetes. “When the [landmark] TODAY long-term outcomes were published in 2021, an endocrinologist I know called me and said, ‘Oh my God.’”
These adult patients generally have better outcomes if they remain in pediatric care.
An in-tandem consequence of the 1990s surge in obesity, youth-onset diabetes (under 18) is projected to rise in this country to 220,000 cases by 2060. The global incidence of those diagnosed with type 2 before age 25 continues its trend upward: 183.4 in 2019 (per 100,000) up from 117.2 in 1990.
A meta-analysis of 48 studies, published through 2021, showed that childhood prediabetes increased to 10.66% from 0.93%. During prediabetes, mild hyperglycemia could increase unforetold cardiovascular issues. (Studies often distinguish youth-onset as diagnosis under 18 and early or young-onset to be under 40 years old.)
“It is an epidemic,” said Jennifer Sherr, MD, professor of pediatrics and medical director of the pediatric diabetes program at Yale University School of Medicine, New Haven, Connecticut. When asked to explain what makes it an epidemic — uncontrolled glycemic levels, more youngsters being diagnosed — she replied with “All of the above.”
A Different Kind of Disease
This disease, which some say should be treated as a distinct type of diabetes because of its distinct pathophysiology in the young, has complications that require respect. It is affecting tweens and teens, youngsters who are often under stress, especially those who live in less than desirable socioeconomic situations — and many, many do.
And biologically, puberty is a time in which all teens are insulin resistant due to a spike in growth-hormone and insulin-like growth factor; these two increase insulin resistance.
Adherence, to no one’s surprise, does not come easy, and it’s a deep concern. In adults with diabetes, the annual rate of beta cell function decline ranges between 2% and 5%; in youngsters, it’s about 25%.
Youth-onset diabetes assaults young kidneys, the cardiovascular and endocrine systems. A child diagnosed in middle school could be dead by 40; a 2003, real-world study showed that adults with early-onset had twice the hazard — 7.9 vs 3.8 — of any macrovascular complication vs controls. The most common complication was a myocardial infarction; the hazard rate was 14-fold higher.
The phrase “aggressive treatment” was repeated by all interviewed.
Obesity, insulin resistance, prediabetes, and diabetes cause “states of chronic inflammation, leading to a significant increase in risk for premature micro and macrovascular complications,” said Timothy Gilbert, MD, director of the Pennington Biomedical Outpatient Endocrine and Diabetes Clinic in Baton Rouge, Louisiana. These patients have an inflamed endovascular state, leading to more plaque deposition, more arterial thickness, and an increased potential for embolic events, he said.
Genetics Play a Role
Youth-onset also has a significant genetic component. Many of those interviewed described exam-room scenes in which the child was asked if anyone in the family also had diabetes, and the accompanying parent or relative would chime in, “I do.” And sometimes, that person was diagnosed in their 20s or 30s.
“With that genetic predisposition and the really high BMIs that we’re seeing, it’s certainly creeping earlier and earlier,” said psychologist Amanda Staiano, PhD, director of the Pediatric Obesity and Health Behavior Laboratory, Pennington Biomedical Research Center, Baton Rouge, discussing the ages of participants in her trials.
“The window to intervene meaningfully is narrow, and every month of suboptimal glycemic, blood pressure, and lipid control accelerates the path toward complications,” said Petter Bjornstad, MD, Raisbeck endowed chair of diabetes research; executive director of the UW Medicine Diabetes Institute; principal investigator at the Center for Clinical and Translational Research, Seattle Children’s Research Institute.
Treating Youth-Onset Diabetes
As Gilbert put it, “We are not grabbing for metformin first anymore.”
Until the last few years, pediatric clinicians only had metformin and insulin to treat young patients. The FDA has recently approved other medications for youth-onset, namely, the sodium-glucose cotransporter 2 inhibitors — including dapagliflozin, empagliflozin, and empagliflozin/metformin — and GLP-1s, namely dulaglutide, liraglutide, semaglutide, and tirzepatide.
So far, there is no firm guidance for treatment of hypertension and hyperlipidemia in adolescents with type 2 diabetes. Without the data, said Gilbert, “I sort of treat them like an adult from a medical standpoint,” adding that the patients are typically of adult size, so the strategy is to treat the patients as if they have an adult disease.
These additions are welcome, as metformin doesn’t work well in most kids. Metformin was designed to improve blood glucose levels by decreasing glucose production in the liver and increasing insulin sensitivity. But these youngsters have high insulin resistance levels and rapidly declining insulin secretion, said Chung. “Metformin can’t rescue the decline in pancreatic function and b-cell failure, because they continue to be under stress,” she said.
And because they’re kids, they could ignore how they are feeling, letting time pass before seeking treatment. “So long term exposure, that lingering hyperglycemia is always present, causing end-stage organ damage,” Chung added.
Gilbert would like to see his patients use continuous glucose monitors (CGMs) earlier in the treatment course.
“The ADA [American Diabetes Association] is recommending CGM for everyone. We are still in the clinical practice world, bound by insurance coverage. We can want it, but a lot of insurances are still requiring use of a single shot of insulin/day to get CGM.”
Chung was hopeful. “The landscape should change as we get more GLP-1ras approved that can target weight loss and improve beta cell function.”
PCPs Get Advice
The literature is limited regarding the transitioning of youth with type 2 to adult care, Chung et al reported last year. That said, all interviewed gladly gave PCPs advice on helping their adult patients with youth-onset type 2 diabetes.
First, the numbers: What’s considered low in an adult isn’t necessarily low in youth-onset. Magge said a young adult with type 2 whose A1c is low, like 5.8 kind of low, should stay on metformin.
“Parents look at me. ‘You are prescribing 1000 mg twice a day of metformin when I am on less?’” Yes, she said. “We want children to have long and healthy lives.”
Also ask about acanthosis nigricans— a sign of insulin resistance, nocturia, frequent infections, including yeast — because these are signs of hyperglycemia, Chung said.
And screen, screen, screen: kidneys, blood pressure, dyslipidemia. “Make sure they are vigilant about timing of screening. Don’t feel that they are not at high risk,” Magge said. The ADA, she said, recommends A1c testing every 3 months.
Sherr emphasized relationships. Even if a patient has an endocrinologist, that specialist and the PCP have to tell the same story: They can be reinforcing the importance of glucose levels and exercise. Relaying this information should not take long during the exam, she said. And bring in family members; significant others can be very helpful diabetes management enforcers. All interviewed stressed this point.
Staiano discussed a different reality.
“We need PCPs to do this medical management for early prevention and medical management, so the more complicated cases can go to the specialists.”
Of course, there aren’t enough PCPs either.
“I don’t envy the PCPs,” said Magge. “It’s a lot to keep track of.”
Sherr’s institution has received research support from Abbott Diabetes, Dexcom, Breakthrough T1D, Insulet, Medtronic, NIH, Provention Bio, and the T1D Exchange; she consults for Abbott Diabetes, Insulet, Medscape, Medtronic Diabetes, Vertex, and Ypsomed; and served on an advisory board for Cecelia Health, Insulet, MannKind, Medtronic Diabetes, Sequel Med Tech, StartUp Health’s T1D Moonshot, and Vertex. Gilbert is a speaker/consultant for Novo Nordisk, Dexcom, and MiniMed. Magge, Chung, Bjornstad, and Staiano reported no disclosures.
https://www.medscape.com/viewarticle/rise-early-onset-diabetes-looming-crisis-2026a1000c57
