• 1.

    Mayer-Davis EJ, et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N Engl J Med 2017; 376:14191429. doi: 10.1056/NEJMoa1610187

  • 2.

    Lawrence JM, et al. Trends in prevalence of type 1 and type 2 diabetes in children and adolescents in the US, 2001–2017. JAMA 2021; 326:717727. doi: 10.1001/jama.2021.11165

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    • Search Google Scholar
    • Export Citation
  • 3.

    TODAY Study Group; Bjornstad P, et al. Long-term complications in youth-onset type 2 diabetes. N Engl J Med 2021; 385:416426. doi: 10.1056/NEJMoa2100165

  • 4.

    TODAY Study Group; Zeitler P, et al. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med 2012; 366:22472256. doi: 10.1056/NEJMoa1109333

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Kahn SE, et al.; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355:24272443. doi: 10.1056/NEJMoa066224

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Nadeau KJ, et al. Youth-onset type 2 diabetes consensus report: Current status, challenges, and priorities. Diabetes Care 2016; 39:16351642. doi: 10.2337/dc16-1066

  • 7.

    Tamborlane WV, et al.; Ellipse Trial Investigators. Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med 2019; 381:637646. doi: 10.1056/NEJMoa1903822

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Laffel LM, et al.; DINAMO Study Group. Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): A multicentre, randomized, double-blind, parallel group, phase 3 trial. Lancet Diabetes Endocrinol 2023; 11:169181. doi: 10.1016/S2213-8587(22)00387-4

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Growing Concern for Youths with Type 2 Diabetes

Karen Blum
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The prevalence of type 2 diabetes has been increasing dramatically among youths over the past decade, yet young people do not seem to be responding as favorably as adults to many existing diabetes medications, according to a Kidney Week 2023 presentation in cooperation with the American Diabetes Association.

Incidence data reported between 2003 and 2012 by investigators in the multicenter SEARCH for Diabetes in Youth study found “a constant and rather scary increase” in type 2 diabetes rates of approximately 7% per year and were higher among Native Americans and non-Hispanic Black youths in that time period (1), said Steven Kahn, MBChB, professor of medicine and director of the Diabetes Research Center at the University of Washington (UW) and staff physician at the U.S. Department of Veterans Affairs Puget Sound Health Care System in Seattle.

Updated data from 2 years ago (2) indicated that type 2 diabetes rates continued to increase but were observed more prominently in older adolescents (aged 15–19 years) and females than they were in younger children and males, Kahn said. Information from the International Diabetes Federation suggests that type 2 diabetes in youths is being recognized worldwide, including in countries such as Kuwait, Qatar, Japan, and Canada. “This is a disease that is becoming very prevalent,” said Kahn. “If you haven't seen much of it up until now—especially as a nephrologist because it tends to present later with kidney problems—let me assure you, you will be getting your practice soon.”

The complications of the disease are significant, he said. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study (3) that followed youths with type 2 diabetes over time, starting at approximately aged 14 years, found that after 9 years of follow-up, 50% had some microvascular disease. Half of these adolescents also developed other health concerns such as hypertension, kidney diseases, and nerve disease within 9 to 15 years of follow-up. “Youth with diabetes are experiencing exactly what we see in adults but experience it at a really young age, and, therefore, it's going to have a major impact on their lives going forward,” Kahn said.

Looking at interventions, the effects of glucose-lowering medications in youths compared with adults are not yet well known, he said, but comparing results from a trial by the TODAY Study Group (4) in youths with those from the A Diabetes Outcome Progression Trial (ADOPT) study (5) in adults may provide some clues, he said. In the TODAY trial, youths were randomized to receive either metformin alone or in combination with rosiglitazone or with lifestyle changes. By 36 months, approximately one-third of those taking metformin plus rosiglitazone failed to maintain glycemic control on those agents and had to try something else. The same was true for approximately 40% of those taking metformin along with lifestyle changes and half of those taking metformin alone. By contrast, among adults in the ADOPT trial randomized to rosiglitazone versus either metformin or glyburide, only approximately 10% had glycemic failure after 3 years.

A report that reviewed these and other studies indicated that the loss of beta cell function—the ability to adequately secrete insulin—is far greater and more rapid in youths than in adults (6), Kahn said, “suggesting that once [youths] get the disease to the time they will need insulin…is much too rapid in this cohort of our population.”

Since 2000, a plethora of glucose-lowering medications have been available for adults with type 2 diabetes, Kahn said. Three of these classes—sodium-glucose cotransporter-2 (SGLT2) inhibitors, dipeptidyl peptidase 4 (DPP-4) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists—have made a big impact, but their performance among youths is still being uncovered. In one study of the GLP-1 receptor agonist liraglutide, youths taking the drug initially had a reduction in hemoglobin A1c (HbA1c) levels within 3 months, but then that effect seemed to subside (7). Interestingly, Kahn noted, is that 12 months after starting therapy, a much smaller percentage of those taking an active drug versus placebo needed rescue medications. “Clearly, we’re getting a benefit of the GLP-1 receptor agonist that slows progression of hyperglycemia, but it doesn't seem to slow progression of the disease.”

In other classes, a recent study among youths comparing the DDP-4 agent linagliptin with placebo and the SGLT2 inhibitor empagliflozin with placebo, linagliptin had no impact on glycemia, whereas empagliflozin did produce a difference in HbA1c. However, the disease did continue to progress despite intervention (8).

Medications approved for treating glycemia in type 2 diabetes in children continue to lag several years behind those for adults, Kahn said, but young people with diabetes are at increased risk for “devastating” complications. “We desperately need approaches that could stop or slow the development of these complications,” such as through new medications, he said.

However, the future appears bright, he added, with a number of new agents being built around GLP-1s that are approved or being studied for type 2 diabetes in adults. These include orforglipron, tirzepatide (current clinical trial among youths), CagriSema, and retatrutide. Given how aggressive this disease can be in young people, Kahn said, “it's time that we should be using these agents wherever possible in youth.”

The basis for the more aggressive loss of beta cell function in youths and its unresponsiveness to interventions remain an enigma, he added. But given the rapid increase in type 2 diabetes cases in young people, “it is incumbent on us that we urgently have to get a better understanding on the pathophysiology of diabetes in youth compared to adults, because that will ultimately allow us to develop interventions that in youth will have an ability to slow progression of disease that we desperately need,” he said.

References

  • 1.

    Mayer-Davis EJ, et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N Engl J Med 2017; 376:14191429. doi: 10.1056/NEJMoa1610187

  • 2.

    Lawrence JM, et al. Trends in prevalence of type 1 and type 2 diabetes in children and adolescents in the US, 2001–2017. JAMA 2021; 326:717727. doi: 10.1001/jama.2021.11165

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    TODAY Study Group; Bjornstad P, et al. Long-term complications in youth-onset type 2 diabetes. N Engl J Med 2021; 385:416426. doi: 10.1056/NEJMoa2100165

  • 4.

    TODAY Study Group; Zeitler P, et al. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med 2012; 366:22472256. doi: 10.1056/NEJMoa1109333

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Kahn SE, et al.; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355:24272443. doi: 10.1056/NEJMoa066224

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Nadeau KJ, et al. Youth-onset type 2 diabetes consensus report: Current status, challenges, and priorities. Diabetes Care 2016; 39:16351642. doi: 10.2337/dc16-1066

  • 7.

    Tamborlane WV, et al.; Ellipse Trial Investigators. Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med 2019; 381:637646. doi: 10.1056/NEJMoa1903822

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Laffel LM, et al.; DINAMO Study Group. Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): A multicentre, randomized, double-blind, parallel group, phase 3 trial. Lancet Diabetes Endocrinol 2023; 11:169181. doi: 10.1016/S2213-8587(22)00387-4

    • PubMed
    • Search Google Scholar
    • Export Citation
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