Among patients with type 2 diabetes (T2D) onset in youth, the risk of complications increases steadily over time and affects most of this population by young adulthood, according to a study in the New England Journal of Medicine.

Researchers initially enrolled 572 patients from the Treatment Options for Type 2 Diabetes in Children in Adolescents and Youth (TODAY) trial in the TODAY2 follow-up study. In the first phase, from March 2011 to February 2014, participants were treated with metformin with or without insulin to maintain glycemic control. From March 2014 through January 2020, 500 participants were included in the phase 2 analysis. They had a median age of 26.4 ± 2.8 years (65.4% female) and a mean time of 13.3 ± 1.8 years since their diagnosis of diabetes.

The cohort had a 19.2% prevalence of hypertension at baseline, and the cumulative incidence was 67.5% at 15 years. Dyslipidemia was present in 20.8% of participants at baseline, and the cumulative incidence at 15 years was 51.6%. The prevalence of kidney disease was 8.0% at baseline, and the cumulative incidence was 54.8% at 15 years. About 1.0% of the cohort had nerve disease at baseline, and the cumulative incidence was 32.4% at 15 years.


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Retinal disease was assessed twice during the study. In the first retinal disease assessment in 2010 or 2011, 13.7% of patients had very mild nonproliferative diabetic retinopathy. After 7 years (in 2017 or 2018) 51% had eye disease, including 8.8% with moderate-to severe-retinal changes and 3.5% with macular edema.

The cumulative incidence of any microvascular complication was 50% by 9 years after a T2D diagnosis, and 80.1% by 15 years. Minority race or ethnic group, a high glycated hemoglobin level, low insulin sensitivity, hypertension, and dyslipidemia were associated with an increased risk of developing microvascular complication.

Overall, the data indicated that diabetes-related complications appear early in youth-onset type 2 diabetes, with at least one microvascular complication developing in over 60% of the participants in the study. Another 28.4% had 2 or more diabetes complications after a mean age of 26.4 years, approximately 13.3 years after being diagnosed with T2D.   

The study authors noted that incomplete follow-up in about one-fourth of the original cohort may have led to under-representation of the number and accumulation of clustering of events. Also, owing to a lack of longitudinal data on microvascular complications in adolescents without diabetes but with a comparable degree of obesity, the researchers were unable to compare the same complications in youth without type 2 diabetes. Still, the researchers noted, the most diabetic-specific complications, such as eye disease, are widely recognized not to occur in populations without diabetes.

“These data show a high burden of diabetes-specific complications in youth-onset type 2 diabetes, with an early and severe effect on persons with this disease, as well as substantial public health implications,” stated the investigators.

Disclosure: One of the study authors declared affiliations with pharmaceutical companies. Some pharmaceutical companies donated medications and supplies. Please see the original reference for a full list of disclosures.

Reference

TODAY Study Group; Bjornstad P, Drews KL, Caprio S, et al, and the TODAY Study group.  Long-term complications in youth-onset type 2 diabetes. N Engl J Med. 2021;385(5):416-426. doi: 10.1056/NEJMoa2100165