Impact of a mild decrease in fasting plasma glucose on beta-cell function in healthy subjects and patients with type 2 diabetes

Restoring euglycaemia for weeks or months improves insulin secretion in patients with type 2 diabetes (T2D). We tested whether mild decrements in fasting glucose (FPG) acutely affect ?-cell function and insulin sensitivity. Thirteen normotolerant (NGT) and 10 T2D patients volunteered in pairs. In an isoglycemic test (Iso), after 100 min of stabilization, an incremental glucose infusion over 3 h was applied to raise plasma glucose to >22 mmol/l, followed by an arginine challenge; in a subisoglycemic test (Sub), a glucose infusion matching the plasma glucose time course of Iso was preceded by an insulin infusion period (100 min) aimed at maintaining a mild FPG reduction while avoiding hypoglycaemia. ?-cell function was assessed by mathematical modeling, whereas the acute insulin response (AIR) to arginine was determined from C-peptide levels. In the Sub, FPG was lowered by 17% in NGT and 31% in T2D patients. On the glucose ramp, total insulin release was lower in Sub than in Iso in both groups [from 106 (43) to 75 (39) nmol/m-2 in NGT and from 71 (63) to 64 (41) nmol/m-2 in T2D, P = 0.001]. In the Sub, ?-cell glucose sensitivity was significantly (P = 0.008) reduced in NGT [from 50 (31) to 43 (21) pmol·min-1·m-2·mM-1] but not in T2D [19 (20) to 20 (20) pmol·min-1·m-2·mM-1]. Likewise, AIR was lowered in NGT [8.9 (4.6) to 7.1 (4.4) nmol/l, P = 0.048] but not in T2D [4.7 (3.3) to 5.3 (3.2) nmol/l]. Insulin sensitivity improved in NGT but only marginally in T2D. Prestimulatory glucose levels acutely influence both ?-cell function and insulin sensitivity differentially in nondiabetic and type 2 diabetic individuals.