Glucagon-like peptide-1 (7-37) augments insulin-mediated glucose uptake inelderly patients with diabetes

Background. Glucagon-Like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments glucose-induced insulin secretion in patients with t ype 2 diabetes. It has also been proposed that a substantial component of t he glucose-lowering effects of GLP-1 occurs because this hormone enhances i nsulin-mediated glucose disposal. However, interpretations of the studies h ave been controversial. This study determines the effect of GLP-1 on insuli n-mediated glucose disposal in elderly patients with type 2 diabetes. Methods. Studies were conducted on 8 elderly patients with type 2 diabetes (age range, 76 +/- 1 years; body mass index, 28 +/- 1 kg/m(2)). Each subjec t underwent two 180-minute euglycemic (insulin infusion rate, 40 mU/m(2)/mi n) insulin clamps in random order. Glucose production (Ra) and disposal (Rd ) rates were measured using tritiated. glucose methodology. In one study, g lucose and insulin alone were infused. In the other study, a primed-continu ous infusion of GLP-1 was administered at a final rate of 1.5 pmol . ka(-1) . min(-1) from 30 to 180 minutes. Results. Glucose values were similar between the control and GLP-1 infusion studies. 120- to 180-minute insulin values appeared to be higher during th e GLP-1 infusion study (control, 795 +/- 63 pmol/l; GLP-1, 1140 +/- 275 pmo l/l; p = not significant [NS]). The higher insulin values were largely due to 2 subjects who had substantial insulin responses to GLP-1 despite euglyc emia and hyperinsulinemia. The 120- to 180-minute insulin values were simil ar in the other 6 subjects (Control, 746 +/- 35 pmol/l; GLP-1, 781 +/- 41 p mol/l; p = NS). Basal (control, 2.08 +/- 0.05 mg/kg/min; GLP-1, 2.13 +/- 0. 04 mg/kg/min; p = NS) and 120- to 180-minute (control, 0.50 +/- 0.18 mg/kg/ min; GLP-1, 0.45 +/- 0.14 mg/kg/min; p = NS) Ra was similar between studies . The 120- to 180-minute Rd values were higher during the GLP-1 infusion st udies (control. 4.73 +/- 0.39 mg/kg/min; GLP-1, 5.52 +/- 0.43 mg/kg/min; p < 0.1). When the 2 subjects who had significant insulin responses to GLP-1 during the euglycemic clamp were excluded, the 120- to 180-minute Rd values were still higher in the GLP-1 infusion study (control, 5.22 +/- 0.32 mg/k g/min; GLP-1, 6.05 +/- 037 mg/kg/min; p < .05). Conclusions. We conclude that GLP-1 may enhance insulin sensitivity in elde rly patients with diabetes.