Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial

Background: Diabetic kidney disease is a major cause of premature mortality in type 2 diabetes mellitus (T2DM). Worsening insulin sensitivity independent of glycemic control may contribute to the development of diabetic kidney disease. We investigated the longitudinal association of insulin sensitivity with hyper-filtration and increased albumin excretion in adolescents with T2DM. Study Design: Observational prospective cohort study. Setting & Participants: 532 TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) participants aged 12 to 17 years with T2DM duration less than 2 years at baseline. The TODAY Study was a multicenter randomized clinical trial that examined the efficacy of 3 treatment regimens (metformin monotherapy, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention program) to achieve durable glycemic control. Predictors: Natural log-transformed estimated insulin sensitivity (reciprocal of fasting insulin), hemoglobin A(1c) concentration, age, race-ethnicity, treatment group, body mass index, loss of glycemic control, and hypertension. Outcomes: Hyperfiltration was defined as 99th percentile or higher of estimated glomerular filtration rate (>= 140 mL/min/1.73 m(2)) when referenced to healthy adolescents (NHANES 1999-2002) and albumin-creatinine ratio >= 30 mu g/mg at 3 consecutive annual visits. Results: Hyperfiltration was observed in 7.0% of participants at baseline and in 13.3% by 5 years, with a cumulative incidence of 5.0% over 5 years. The prevalence of increased albumin excretion was 6% at baseline and 18% by 5 years, with a cumulative incidence of 13.4%. There was an 8% increase in risk for hyperfiltration per 10% lower estimated insulin sensitivity in unadjusted and adjusted models (P = 0.01). Increased albumin excretion was associated with hemoglobin A(1c) concentration, but not estimated insulin sensitivity. Limitations: Longer follow-up is needed to capture the transition from hyperfiltration to rapid glomerular filtration rate decline in youth-onset T2DM. Conclusions: Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM.