ALTERATIONS IN GLUCOSE-METABOLISM IN THE ELDERLY PATIENT WITH DIABETES

OBJECTIVE - To determine the alterations in glucose metabolism in elde rly patients with NIDDM. RESEARCH DESIGN AND METHODS - We studied 9 he althy 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 glu cose 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 gl ucose production and disposal rates during the euglycemic clamp. RESUL TS - 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 O GTT (16.0 +/- 0.6 vs. 6.7 +/- 0.3 mM in control subjects vs. NIDDM pat ients, respectively, P < 0.01) than the healthy control subjects. Duri ng the hyperglycemic clamp, patients with NIDDM had an absent first-ph ase insulin response (112 +/- 6 vs. 250 +/- 31 pM in control subjects vs. NIDDM patients, respectively, P < 0.01), and a blunted second-phas e insulin response (159 +/- 11 vs. 337 +/- 46 pM in control subjects v s. NIDDM patients, respectively, P < 0.0 1). Before the euglycemic cla mp, 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 mumol . kg-1 . min-1 in control subjects vs. N IDDM 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 mumol . kg-1 . min-1 in control subjects vs. NIDDM p atients, respectively, NS). CONCLUSIONS - We conclude that NIDDM in no nobese elderly subjects is characterized by a marked impairment in ins ulin release. This may be attributable to the toxic effects of chronic hyperglycemia on the beta-cell. When compared with age-matched contro l subjects, the NIDDM patients showed no increase in fasting insulin o r hepatic glucose production, and insulin resistance was mild.