Spotlight on youth-onset type 2 diabetes

Two recent studies looked at patients diagnosed with type 2 diabetes before age 18 years.

A follow-up analysis of a randomized trial, published by the New England Journal of Medicine (NEJM) on July 29, found a high risk of complications, including microvascular complications, in patients who developed type 2 diabetes in youth. The initial TODAY trial included patients 10 to 17 years of age who had type 2 diabetes for less than two years. At the end of the current follow-up, in January 2020, participants' mean age was 26.4 years, and their mean time since diagnosis of diabetes was 13.3 years. More than half of the 500 participants were found to have hypertension (67.5%), dyslipidemia (51.6%), or diabetic kidney disease (54.8%) at follow-up. The incidence of nerve disease was 32.4%, and the prevalence of retinal disease was 13.7% in 2010 to 2011 and 51.0% in 2017 to 2018. The majority (60.1%) had developed at least one complication of diabetes, and risk factors for complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. “Taken together, these data illustrate the serious personal and public health consequences of youth-onset type 2 diabetes in the transition to adulthood. The gravity of these data are underscored by comparison with the risk of microvascular complications reported in type 1 diabetes and adult-onset type 2 diabetes,” which are significantly lower, the study authors noted. The finding that complications were associated with hyperglycemia, hypertension, and dyslipidemia suggests that “primary and secondary prevention strategies based on extrapolation of data from studies in adults, including the use of medications not yet approved for youths, need to be considered,” they added.

Another study, published by Diabetes Care on Aug. 6, looked at underdiagnosis of maturity-onset diabetes of the young (MODY). (The NEJM report of the TODAY study follow-up had excluded 22 participants found to have MODY based on genetic testing—this study included patients from TODAY and other databases.) Researchers used whole-exome sequence data to assess the prevalence of MODY among 3,333 patients who were under age 20 years and had been diagnosed with type 2 diabetes. They found that 93 patients (2.8%) had a genetic variant considered pathogenic or likely pathogenic for MODY. Compared with patients without these variants, patients with MODY had lower fasting C-peptide levels (4.7 ng/mL vs. 3.0 ng/mL; P<0.0001) and were less likely to have hypertension (19.5% vs. 6.9%; P=0.007). MODY was found in White, Black, and Hispanic participants and was not identified by family history—nearly half of participants with a MODY variant did not have a parent diagnosed with diabetes. The study also showed the diagnosis to be clinically important, the authors noted. “Of 93 youth whom we identified as having MODY, 83 (89%) had a specific genetic diagnosis that would change clinical management: 23 had a GCK variant for which treatment is usually not needed and 60 had variants in HNF1A or HNF4A, which are likely to respond better to sulfonylureas than insulin or other antihyperglycemic medications,” they wrote. They called for clinicians to consider MODY in patients with youth-onset diabetes, no autoantibodies, and preserved beta-cell function, regardless of body mass index, family history, race/ethnicity, lipid levels, or presence of hypertension.