Effect of glucagon-like peptide 1 on non-insulin-mediated glucose uptake in the elderly patient with diabetes

An important cause of elevated glucose levels in elderly patients with diab etes is an alteration in non-insulin-mediated glucose uptake (NIMGU). Gluca gon-like peptide 1 (GLP-1) is an intestinal insulinotropic hormone. It has been proposed that this hormone also lowers glucose levels by enhancing NIM GU. This study was conducted to determine whether GLP-1 augments ;NIMGU in elderly patients with diabetes, a group in which NIMGU is known to be impai red. Studies were conducted on 10 elderly patients with type 2 diabetes (ag ed 75 +/- 2 years, BMI 27 +/- 1 kg/m(2)) who under-went paired 240-min gluc ose clamp studies. In each study, octreotide was infused to suppress endoge nous insulin release, and tritiated glucose methodology was used to measure glucose production and disposal rates. For the first 180 min, no glucose w as infused. From 180 to 240 min, glucose was increased to 11 mmol/l using t he glucose clamp protocol. In the GLP-1 study, GLP-1 was infused from 30 to 240 min. In a subsequent control Study, insulin was infused using the gluc ose clamp protocol from 30 to 240 min to match the insulin levels that occu rred during the GLP-1 infusion study, During hyperglycemia, GLP-1 enhanced glucose disposal (control study: 2.52 +/- 0.19 mg . kg(-1). min(-1) GLP-1 s tudy: 2.90 +/- 0.17 mg . kg(-1). min(-1); P < 0.0001). Hepatic glucose outp ut,vas not different between studies. We conclude that GLP-1 may partially reverse the defect in NIMGU that occurs in elderly patients with diabetes.