Objective— To determine the alterations in glucose metabolism in elderly patients with NIDDM.
Research Design and Methods— We studied 9 healthy elderly control subjects (73 ± 1 yr of age; body mass index 25.7 ± 0.4 kg/m2) and 9 untreated elderly NIDDM patients (72 ± 2 yr of age; BMI 25.9 ± 0.5 kg/m2). Each subject underwent a 3-h oral glucose tolerance test (40 g/m2); a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above basal); and a 4-h euglycemic insulin clamp (40 mM · m2 · min−1). Tritiated glucose methodology was used to measure glucose production and disposal rates during the euglycemic clamp.
Results— Patients with NIDDM had a higher fasting glucose (9.3 ± 0.3 vs. 5.1 ± 0.1 mM in control subjects vs. NIDDM patients, respectively, P < 0.001) and a greater area under the curve for glucose during the OGTT (16.0 ± 0.6 vs. 6.7 ± 0.3 mM in control subjects vs. NIDDM patients, respectively, P < 0.01) than the healthy control subjects. During the hyperglycemic clamp, patients with NIDDM had an absent first-phase insulin response (112 ± 6 vs. 250 ± 31 pM in control subjects vs. NIDDM patients, respectively, P < 0.01), and a blunted second-phase insulin response (159 ± 11 vs. 337 ± 46 pM in control subjects vs. NIDDM patients, respectively, P < 0.01). Before the euglycemic clamp, fasting insulin (99 ± 5 vs. 111 ± 10 pM in control subjects vs. NIDDM patients, respectively) and hepatic glucose production (11.8 ± 0.7 vs. 11.5 ± 0.5 μmol · kg−1 μ min−1 in control subjects vs. NIDDM patients, respectively) were similar. Steady-state (180–240 min) glucose disposal rates during the euglycemic clamp were slightly, but not significantly, higher in the normal control subjects (36.5 ± 1.1 vs. 33.1 ± 1.9 μmol · kg−1 · min−1 in control subjects vs. NIDDM patients, respectively, NS).
Conclusions— We conclude that NIDDM in nonobese elderly subjects is characterized by a marked impairment in insulin release. This may be attributable to the toxic effects of chronic hyperglycemia on the β-cell. When compared with age-matched control subjects, the NIDDM patients showed no increase in fasting insulin or hepatic glucose production, and insulin resistance was mild.
