It is increasingly recognized that alterations in non-insulin-mediated glucose uptake (NIMGU) play an important pathogenic role in disorders of carbohydrate metabolism. This study was conducted to determine whether NIMGU is impaired in elderly patients with type 2 diabetes. Healthy elderly control subjects (n = 19, age 76 +/- 1 years, BMI 26.8 +/- 1.1 kg/m2) and elderly patients with type 2 diabetes (n = 19, age 76 +/- 2 years, BMI 27.5 +/- 0.9 kg/m2) underwent a 240-min glucose clamp study. Octreotide was infused to suppress endogenous insulin release, and tritiated glucose methodology was used to measure glucose uptake and disposal rates. For the first 180 min, glucose was kept at fasting levels. From 180 to 240 min, glucose was increased to 11 mmol/l. At fasting glucose levels, glucose uptake was similar in both groups. However, glucose clearance was reduced in patients with diabetes (control 1.68 +/- 0.05 ml x kg(-1) x min(-1); diabetes 1.34 +/- 0.07 ml x kg(-1) x min(-1), P < 0.0001). During hyperglycemia, glucose uptake was reduced in patients with diabetes (control 3.16 +/- 0.09 mg x kg(-1) x min(-1); diabetes 2.57 +/- 0.11 mg x kg(-1) x min(-1), P < 0.0001). Peripheral glucose effectiveness (SG) was less in patients with diabetes (control 1.28 +/- 0.04 ml x kg(-1) x min(-1); diabetes 0.94 +/- 0.08 ml x kg(-1) x min(-1), P < 0.0001). Hepatic glucose output and hepatic SG were not different between groups. We conclude that the effect of glucose on glucose uptake is impaired in elderly patients with type 2 diabetes, a finding that may have therapeutic implications for this patient population.

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