Long-term Outcomes Among Young Adults With Type 2 Diabetes Based on Durability of Glycemic Control: Results From the TODAY Cohort Study

Abstract

Objective: To examine the effect of different patterns of durable glycemic control on the development of comorbidities among youth with type 2 diabetes (T2D) and to assess the impact of fasting glucose (FG) variability on the clinical course of T2D.

Research design and methods: From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, 457 participants (mean age, 14 years) with mean diabetes duration <2 years at entry and a minimum study follow-up of 10 years were included in these analyses. HbA1c, FG concentrations, and β-cell function estimates from oral glucose tolerance tests were measured longitudinally. Prevalence of comorbidities by glycemic control status after 10 years in the TODAY study was assessed.

Results: Higher baseline HbA1c concentration, lower β-cell function, and maternal history of diabetes were strongly associated with loss of glycemic control in youth with T2D. Higher cumulative HbA1c concentration over 4 years and greater FG variability over a year within 3 years of diagnosis were related to higher prevalence of dyslipidemia, nephropathy, and retinopathy progression over the subsequent 10 years. A coefficient of variability in FG ≥8.3% predicted future loss of glycemic control and development of comorbidities.

Conclusions: Higher baseline HbA1c concentration and FG variability during year 1 accurately predicted youth with T2D who will experience metabolic decompensation and comorbidities. These values may be useful tools for clinicians when considering early intensification of therapy.

Figure 1

FG-CV during year 1 ((A) and FG concentration levels at study baseline, month 6, and month 12 (B) by groups of glycemic control based on HbA_1c values. The UNC group was further divided into Late-UNC) and Early-UNC. A: FG-CV (%) during year 1 (based on three FG values assessed at study baseline, month 6, and month 12) across the four groups of glycemic control based on HbA_1c; P values for differences across the groups (STABLE [white bar], RISING [black bar], Late-UNC [solid grey bar], and Early-UNC [dashed grey bar]) are shown within panel A. ns, P > 0.05. B: A boxplot of FG levels at each visit during year 1 (study baseline, month 6, and month 12) when FG levels were assessed, across the four groups of glycemic control based on HbA_1c.

Figure 2

ROC curve for predicting glycemic failure as a function of baseline HbA_1c and FG-CV during year 1. Durable control (RISING and STABLE) groups were combined, and the early UNC group that reached glycemic failure during year 1 was excluded. The AUC (95% CIs and Youden optimal cutoffs for baseline HbA_1c and FG-CV for year 1 are shown in the figure. Baseline HbA_1c, previously reported to be a strong predictor of glycemic failure (P < 0.0001), is shown for comparison (4).