Decline in the acute insulin response in relationship to plasma glucose concentrations.

ABSTRACT

BACKGROUND: To investigate (1) whether the decline in acute insulin response (AIR) precedes or coincides with defined glucose regulation categories and whether acute insulin response decline varies by race and adiposity, (2) linearity of the relationship between acute insulin response and increasing plasma glucose concentrations, (3) longitudinal changes in acute insulin response accounting for changes in insulin action across categories of glucose tolerance. METHODS: Clinical cross-sectional and longitudinal study of nondiabetic subjects. Inpatient assessment of oral glucose tolerance (2-h PG, fasting PG), and acute insulin response (intravenous glucose tolerance test) in 326 and 84 Native Americans of full and ≤6/8th Southwestern heritage, respectively, and 115 Whites. Linearity of acute insulin response vs plasma glucose concentrations investigated using spline analyses. Follow-up (average = 2.07 years) glucose tolerance, acute insulin response, and insulin action (hyperinsulinemic-euglycemic clamp) assessed in 230 full Native Americans. RESULTS: In certain groups, the relationship between acute insulin response and increasing plasma glucose levels was non-linear. In all groups, acute insulin response decline preceded the cut-offs for traditional glucose regulation categories, although the timing with respect to increasing plasma glucose varied by race and adiposity. Longitudinal data indicated that improvement in insulin action is the key factor to preserve insulin secretion, underlying the reversion of glucose tolerance in prediabetic individuals. CONCLUSIONS: With worsening insulin action, the decline in insulin secretion occurred prior to current diagnostic guidelines for impaired glucose regulation. However, the relationship between acute insulin response and increasing plasma glucose varies and was not always non-linear. Understanding the dynamics of this relationship may determine when to initiate preventive pharmacotherapy directed at the preservation of ß-cell failure.