AIMS/HYPOTHESIS: The pathophysiological role of gut incretin hormone argumentation on acute insulin release in the genesis of type 2 diabetes (TDM2) is uncertain. We examined retrospectively at 0 year and 10 years the endogenous incretin hormone action (IHA) on acute insulin release and glucose tolerance in normoglycemic relatives (REL) of TDM2 and control (CON) subjects. METHODS: At 0 year and 10 years, glucose tolerance, paired oral glucose tolerance test (OGTT)- and i.v. glucose tolerance test (IVGTT)-induced acute (0-30 min) insulin release (insulinogenic index IGIOGTT and IGIIVGTT), and IHA were calculated in 19 REL and 18 CON subjects by cross-correlation linear regression slope analyses of the OGTT (0-30 min) matched insulin/glucose profiles vs the early (0-5 min) and delayed (10-30 min) IVGTT profiles. RESULTS: At 0 year, REL and CON IGIOGTT and IGIIVGTT were similar, but the REL 2- to 5-min IVGTT-induced insulin responses were reduced (P < .03). By 10 years, glucose tolerance deteriorated in nine dysglycemic REL (RELDGT), with raised fasting glucose and 2-hour OGTT glucose. Retrospective analyses of RELDGT at 0 year demonstrated raised proinsulin/insulin molar ratios and fasting glucose and a reduced IVGTT insulin/glucose slope, but the RELDGT IHA was similar to normoglycemic REL (RELNGT) and CON. By 10 years, RELDGT OGTT insulin/glucose slopes were reduced (P = .03-.01), but more so for the early (P < .01-.003) and delayed (P < .005-.002) IVGTT slopes, compared to the normoglycaemic REL and CON subjects. CONCLUSIONS: IHA on acute insulin release is maintained in normoglycemic REL and CON subjects over 10 years. The apparent deterioration in IHA in RELDGT is consistent with a progressive failure of acute β-cell function over 10 years.
Journal of Clinical Endocrinology and Metabolism, 2014, Vol 99, Issue 10