Association of Age at Type 2 Diabetes Onset With Diabetes Progression

To examine whether age at type 2 diabetes onset affects disease progression, assessed by changes in glycemic control and clinical biomarkers during follow-up.

Participants in the Kerala Diabetes Prevention Program (K-DPP) and U.S. Diabetes Prevention Program (US-DPP) who developed type 2 diabetes during the trial were analyzed. Data on fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), triglycerides (TGs), HDL, LDL, BMI, blood pressure, and estimated glomerular filtration rate (eGFR) were collected at diabetes onset and end of follow-up. Linear and mixed-effects regressions assessed the association and rate of biomarker change by age at onset.

We included 802 US-DPP (mean age 52.6 years) and 146 K-DPP participants (mean age 47.7 years). Younger-onset participants had a higher BMI at onset and end of follow-up (mean follow-up 7.9 and 7.6 years for US-DPP and K-DPP, respectively), with a relatively small BMI change over time in US-DPP participants. In fully adjusted models, FPG and HbA1c at onset were not associated with age at onset. Both measures increased faster in younger-onset participants, although the association was not significant in K-DPP participants. In US-DPP participants, younger age at onset was associated with higher eGFR and lower HDL and systolic blood pressure (SBP); similar directions were seen in K-DPP participants, but the association with HDL was nonsignificant. SBP fell slightly in older-onset US-DPP participants during follow-up but not in younger-onset participants.

Younger-onset diabetes was associated with greater adiposity, lower HDL, and better SBP and eGFR at onset, with differences largely persisting during follow-up. During follow-up, glycemia increased slightly faster in individuals with younger-onset diabetes.