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Glucagon-like Peptide-1 (7-37) Augments Insulin-Mediated Glucose Uptake in Elderly Patients With Diabetes

^a Departments of Medicine, University of British Columbia, Vancouver, Canada
^b Departments of Physiology, University of British Columbia, Vancouver, Canada
^c Laboratory of Molecular Endocrinology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts
^d Linco Research, Saint Charles, Missouri
^e Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
^f Department of Medicine, Massachusetts General Hospital, Boston

Graydon S. Meneilly, Room S169, Vancouver Hospital and Health Sciences Centre, UBC Site, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada E-mail: meneilly{at}interchange.ubc.ca.

Decision Editor: John E. Morley, MB, BCh

Background. Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments glucose-induced insulin secretion in patients with type 2 diabetes. It has also been proposed that a substantial component of the glucose-lowering effects of GLP-1 occurs because this hormone enhances insulin-mediated glucose disposal. However, interpretations of the studies have been controversial. This study determines the effect of GLP-1 on insulin-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/m²). Each subject underwent two 180-minute euglycemic (insulin infusion rate, 40 mU/m²/min) insulin clamps in random order. Glucose production (Ra) and disposal (Rd) rates were measured using tritiated glucose methodology. In one study, glucose and insulin alone were infused. In the other study, a primed-continuous infusion of GLP-1 was administered at a final rate of 1.5 pmol · kg^-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 the GLP-1 infusion study (control, 795 ± 63 pmol/l; GLP-1, 1140 ± 275 pmol/l; p = not significant [NS]). The higher insulin values were largely due to 2 subjects who had substantial insulin responses to GLP-1 despite euglycemia and hyperinsulinemia. The 120- to 180-minute insulin values were similar in the other 6 subjects (control, 746 ± 35 pmol/l; GLP-1, 781 ± 41 pmol/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- to180-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 studies (control, 4.73 ± 0.39 mg/kg/min; GLP-1, 5.52 ± 0.43 mg/kg/min; p < .01). 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/kg/min; GLP-1, 6.05 ± 0.37 mg/kg/min; p < .05).

Conclusions. We conclude that GLP-1 may enhance insulin sensitivity in elderly patients with diabetes.

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