Long-Term Complications in Youth-Onset Type 2 Diabetes

Abstract

Background: The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.

Methods: We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated.

Results: At the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up.

Conclusions: Among participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).

Figure 1.. Glycated Hemoglobin Level over Time.

Shown are the mean and median glycated hemoglobin levels (Panel A) and the distribution of glycated hemoglobin levels (Panel B) according to year. Percentages may not total 100 because of rounding.

Figure 2.. Diabetes-Related Complications That Occurred during the Study.

Panel A shows the baseline prevalences and cumulative incidences of hypertension, dyslipidemia (low-density-lipoprotein or triglyceride dyslipidemia), kidney disease, and nerve disease. Panel B shows the baseline prevalence and cumulative incidence of any microvascular complication. The dashed lines in Panels A and B indicate the time when the cumulative incidence reached 50%, and the shaded bands represent 95% confidence intervals. Baseline refers to the time of enrollment in the clinical trial. Panel C shows the numbers of patients with kidney, nerve, and retinal complications. Panel D shows the years to onset of the first and subsequent (if applicable) microvascular complications among participants with one, two, or three complications. The bottoms and tops of the boxes represent the first and the third quartiles, respectively, and the horizontal lines inside the boxes indicate medians. The symbols inside the boxes indicate means, and the symbols outside the boxes outliers. I bars indicate the minimum and maximum range, excluding outliers.