Effect of Early Glycemic Control in Youth-Onset Type 2 Diabetes on Longer-Term Glycemic Control and β-Cell Function: Results from the TODAY Study

Objective: Little is known about the impact of early attainment of tight glycemic control on long-term β-cell function and glycemic control in youth-onset type 2 diabetes. We examined the effect of the initial 6 months of glycemic control on β-cell function and glycemic control longitudinally over 9 years, and the impact of sex, race/ethnicity, and BMI on these relationships in adolescents with youth-onset type 2 diabetes in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

Research Design and Methods: Oral glucose tolerance tests were performed longitudinally through year 9 to derive estimates of insulin sensitivity and secretion. Early glycemia was defined as mean HbA1c during the first 6 months post-randomization, categorized into 5 HbA1c groups (<5.7%, 5.7-<6.4%, 6.4-<7.0%, 7.0-<8.0%, and ≥8.0%). The long-term period was defined as the period between years 2-9. 

Results: 656 participants (64.8% female, baseline mean age 14 years, diabetes duration <2 years) had longitudinal data available over an average of 6.4±3.2 years of follow-up. HbA1c significantly increased in all early glycemic groups during years 2-9, with a steeper increase (+0.40%/year) among participants with the tightest initial control (mean early HbA1c<5.7%), in parallel to a decline in the C-peptide derived disposition index. Nevertheless, the lower HbA1c categories continued to have relatively lower HbA1c over time. 

Conclusions: Early tight glycemic control in TODAY was related to β-cell reserve, and translated to better long-term glycemic control. However, tight early glycemic control on the randomized treatment in TODAY did not prevent deterioration of β-cell function.