Kidney function, β-cell function and glucose tolerance in older men.

CONTEXT: Kidney dysfunction induces insulin resistance, but it is unknown if β cell function is affected. OBJECTIVE: To investigate insulin release (β cell function) and glucose tolerance following a standardized oral glucose tolerance test (OGTT) across kidney function strata. SETTING AND DESIGN: Community-based cohort study from the Uppsala Longitudinal Study of Adult Men (ULSAM). PARTICIPANTS AND MAIN OUTCOME MEASURE: Included were 1015 nondiabetic Swedish men aged 70-71 years. All participants underwent OGTT and euglycaemic hyperinsulinaemic clamp (HEGC) tests, allowing determination of insulin sensitivity, β cell function, and glucose tolerance. Kidney function was estimated by cystatin C-algorithms. Mixed models were used to identify determinants of insulin secretion after the hyperglycemic load. RESULTS: As many as 466 (46%) of participants presented moderate-advanced kidney disease. Insulin sensitivity (by HEGC) decreased across decreasing kidney function quartiles. After the OGTT challenge, however, β cell function indices (area under the curve for insulin release, the estimated first phase insulin release, and the insulinogenic index) were incrementally higher. Neither the oral disposition index nor the 2-h postload glucose tolerance differed across the kidney function strata. Mixed models showed that dynamic insulin release during the OGTT was inversely associated with kidney function, despite the correction for each individual's insulin sensitivity or its risk factors. CONCLUSIONS: In older men, β cell function after a hyperglycemic load appropriately compensated the loss in insulin sensitivity that accompanies kidney dysfunction. As a result, the net balance between insulin sensitivity and β cell function was preserved.