Effects of short-term hyperglycemia on insulin secretion in normal humans

Abstract

Stepwise glucose clamps were used to study .beta.-cell insulin response to glucose in normal and noninsulin-dependent diabetic subjects and to study changes in response after hyperglycemia. In normal subjects, insulin increment, .DELTA.I, correlated with glucose increment above basal, .DELTA.G, during the first 6 min of hyperglycemia, r = 0.748, P< 0.0001. After 1 h of hyperglycemia, mean .DELTA.I/.DELTA.G was reduced from 50 to 23 (mean difference 23 .+-. 5) pmol/mmol, P = 0.0002; but .DELTA.I/% change in glucose (.DELTA.G'') was unaltered (2.3 vs. 1.7, mean difference 0.4 .+-. 0.3 pmol/%). Second-phase response correlated with mean glucose elevation (r = 0.835, P < 0.0001), and no plateau was reached after 3 h at 3 mmol/l above basal glucose (rate of change of insulin concentration = 0.5; range, 0.3-0.8 pmol .cntdot. l-1 .cntdot. min-1). In diabetic subjects, .DELTA.I/.DELTA.G was 20% of normal, while .DELTA.I/.DELTA.G'' was 63% of normal and second-phase response 30% of normal. We conclude that hyperglycemia per se reduces .DELTA.I/.DELTA.G and must be considered when assessing insulin responses. Noninsulin-dependent diabetic subjects have defective first- and second-phase responses.