Determinants of longitudinal change in insulin clearance: the Prospective Metabolism and Islet Cell Evaluation cohort

OBJECTIVE: To evaluate multiple determinants of the longitudinal change in insulin clearance (IC) in subjects at high risk for type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Adults (n=492) at risk for T2D in the Prospective Metabolism and Islet Cell Evaluation cohort, a longitudinal observational cohort, had four visits over 9 years. Values from oral glucose tolerance tests collected at each assessment were used to calculate the ratios of both fasting C peptide-to-insulin (IC(FASTING)) and areas under the curve of C peptide-to-insulin (IC(AUC)). Generalized estimating equations (GEE) evaluated multiple determinants of longitudinal changes in IC. RESULTS: IC declined by 20% over the 9-year follow-up period (p<0.05). Primary GEE results indicated that non-European ethnicity, as well as increases in baseline measures of waist circumference, white cell count, and alanine aminotransferase, was associated with declines in IC(FASTING) and IC(AUC) over time (all p<0.05). There were no significant associations of IC with sex, age, physical activity, smoking, or family history of T2D. Both baseline and longitudinal IC were associated with incident dysglycemia. CONCLUSIONS: Our findings suggest that non-European ethnicity and components of the metabolic syndrome, including central obesity, non-alcoholic fatty liver disease, and subclinical inflammation, may be related to longitudinal declines in IC.