Metabolic alterations in middle-aged and elderly obese patients with type 2 diabetes.

OBJECTIVE: We conducted this study to assess the metabolic alterations in middle-aged and elderly obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Healthy control subjects (9 middle-aged, aged 42 +/- 2 years, BMI 33 +/- 1 kg/m2; 10 elderly, aged 71 +/- 1 years, BMI 29 +/- 1 kg/m2) and patients with type 2 diabetes (11 middle-aged, aged 43 +/- 2 years, BMI 34 +/- 2 kg/m2; 23 elderly, aged 73 +/- 1 years; BMI 30 +/- 1 kg/m2) underwent a 3-h oral glucose tolerance test (OGTT), a 2-h hyperglycemic glucose clamp, and a 3-h euglycemic glucose clamp study with tritiated glucose methodology to measure hepatic glucose production and peripheral disposal rates. RESULTS: Middle-aged and elderly control subjects and patients with diabetes were similar in percentage of body fat. Waist-to-hip ratio was greater in elderly patients with diabetes than in elderly control subjects (P < 0.01), but was similar in both middle-aged groups. VO2max was less in control subjects than in both middle-aged and elderly patients with diabetes (P < 0.05). Insulin responses during the OGTT were similar in elderly control subjects and patients with diabetes, but were less in middle-aged patients with diabetes than in control subjects (305 +/- 49 vs. 690 +/- 136 pmol/l, P < 0.01). Patients with type 2 diabetes had absent first-phase insulin responses during the hyperglycemic clamp. Second-phase (80-120 min) insulin values were similar in elderly patients and control subjects, but were reduced in middle-aged patients with diabetes compared with control subjects (285 +/- 35 vs. 894 +/- 143 pmol/l, P < 0.0001). During the euglycemic clamp, basal and steady-state (150-180 min) hepatic glucose output values were less in middle-aged control subjects than in patients with diabetes (basal, 3.03 +/- 0.10 vs. 3.69 +/- 0.09 mg.kg-1 lean body mass.min-1, P < 0.0001; steady-state, 0.72 +/- 0.10 vs. 1.84 +/- 0.20 mg.kg-1 lean body mass.min-1, P < 0.0001). Basal and steady-state hepatic glucose output values were similar in elderly patients and control subjects. Finally, steady-state (150-180 min) glucose disposal rates were higher in control subjects than in patients with diabetes in both the middle-aged (7.51 +/- 0.85 vs. 4.62 +/- 0.24 mg.kg-1 lean body mass.min-1, P < 0.01) and elderly (9.91 +/- 0.61 vs. 6.78 +/- 0.60 mg.kg-1 lean body mass.min-1, P < 0.01) groups. CONCLUSIONS: We conclude that type 2 diabetes in obese middle-aged subjects is characterized by impaired glucose-induced insulin release, altered regulation of hepatic glucose output, and resistance to insulin-mediated glucose disposal. In contrast, the primary defect in elderly obese patients with type 2 diabetes is resistance to insulin-mediated glucose disposal. Our findings may have important therapeutic implications for these patient populations.