Endogenous incretin hormone augmentation of acute insulin secretion in normoglycemic relatives of type 2 diabetic subjects: a 10-year retrospective pathophysiological study.

Abstract

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. 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. 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. 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.