Glycemic Control in Youth with Type 2 Diabetes Declines as Early as Two Years after Diagnosis

Abstract

To determine the course of glycemic decline in a pediatric cohort with type 2 diabetes mellitus (T2DM) by defining longitudinal changes in hemoglobin A1c (HbA1c) and insulin requirement. We also followed markers of insulin reserve (fasting C-peptide and IGFBP-1) over time. Participants included two groups: (1) T2DM Nonacidotic (NA) (n = 46); and (2) T2DM diabetic ketoacidosis (n = 13). HbA1c, insulin dose, and fasting C-peptide and IGFBP-1 were obtained at baseline and every 6 months for 4 years. At baseline, Mann Whitney tests demonstrated that the diabetic ketoacidosis group had higher HbA1c (P = .002), required more insulin (P = .036), and had lower C-peptide (P = .003) than the NA group. Baseline insulin dose (Spearman r = -0.424, P = .009) and baseline IGFBP-1 (Spearman r = -0.349, P = .046) correlated negatively with C-peptide. Over time, HbA1c, insulin dose, and C-peptide changed significantly in a complex manner, with group differences. HbA1c reached a nadir at 6 to 12 months and began to rise after 1.5 years. Insulin requirements reached a nadir at 1 year and began to rise after 2 years. Unlike adults, children with T2DM require increasing insulin doses over a 4-year period, and diabetic ketoacidosis at diagnosis predicts greater β-cell decline over time.