Interaction of sulfonylureas and exercise on glucose homeostasis in type 1diabetic patients

OBJECTIVE - To determine whether the plasma glucose-lowering effects of sul fonylureas and acute submaximal exercise are additive and, accordingly to d etermine whether they may increase the risk of hypoglycemia when combined i n fasting patients. RESEARCH DESIGN AND METHODS - Eight postabsorptive type 2 diabetic patients were examined at three occasions: after oral sulfonylurea (7 mg glibenclam ide), during 60 min of ergometer cycle exercise at 57 +/- 3% of (V) over do t O-2max and during exercise after glibenclamide. RESULTS - Heart rate, (V) over dot O-2, and lactate responses to exercise w ere comparable (P > 0.05) on days with and without glibenclamide. Plasma in sulin concentrations were always increased by glibenclamide, and they were lowered identically by exercise with and without glibenclamide. However, th roughout exercise, absolute concentrations of insulin were lower on days wi thout glibenclamide compared with days with glibenclamide (34.5 +/- 4.7 vs. 47.4 +/- 5.5 pmol/l; P < 0.05). Ar the start of exercise, glucose concentr ations were similar between experiments (P > 0.05). The rate of decrease in glucose during exercise was higher (P < 0.05) on days with both glibenclam ide and exercise, compared with days with glibenclamide alone and days with exercise alone (-0.035 +/- 0.009 vs. -0.016 +/- 0.002 and -0.022 +/- 0.005 mmol.l(-1). min(-1), respectively). Consequently, the glucose nadir was lo wer on days with glibenclamide and exercise than on days with glibenclamide or exercise alone (6.7 +/- 1.1 vs. 8.1 +/- 0.9 and 7.6 +/- 1.0 mmol/l, res pectively; P < 0.05). During exercise, the rate of appearance of plasma glu cose determined by 3-[H-3]glucose infusion was lower on days with glibencla mide than on days without glibenclamide (2.3 +/- 0.1. vs. 2.9 +/- 0.1 mg.mi n(-1).kg(-1); P < 0.05). In contrast, glucose clearance was identical (P > 0.05). CONCLUSIONS - In postabsorptive type 2 diabetic patients, the hypoglycemic action of glibenclamide and exercise is enhanced when the treatments are co mbined. The interaction reflects an increased inhibition by glibenclamide-e nhanced insulin levels of hepatic glucose production when hepatic glucose p roduction is accelerated by exercise.