Meneilly G S, Elliott T
Division of Geriatric Medicine, University of British Columbia, Vancouver, Canada.
Diabetes Care. 1999 Jan;22(1):112-8. doi: 10.2337/diacare.22.1.112.
We conducted this study to assess the metabolic alterations in middle-aged and elderly obese patients with type 2 diabetes.
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.
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.
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.
我们开展这项研究以评估中老年肥胖2型糖尿病患者的代谢改变。
健康对照者（9名中年人，年龄42±2岁，体重指数33±1kg/m²；10名老年人，年龄71±1岁，体重指数29±1kg/m²）以及2型糖尿病患者（11名中年人，年龄43±2岁，体重指数34±2kg/m²；23名老年人，年龄73±1岁，体重指数30±1kg/m²）接受了3小时口服葡萄糖耐量试验（OGTT）、2小时高血糖葡萄糖钳夹试验以及采用氚标记葡萄糖方法进行的3小时正常血糖葡萄糖钳夹试验，以测量肝脏葡萄糖生成及外周处置率。
中老年对照者及糖尿病患者的体脂百分比相似。老年糖尿病患者的腰臀比高于老年对照者（P<0.01），但中年组两者相似。对照者的最大摄氧量低于中年及老年糖尿病患者（P<0.05）。OGTT期间老年对照者及糖尿病患者的胰岛素反应相似，但中年糖尿病患者的胰岛素反应低于对照者（305±49对690±136pmol/L，P<0.01）。2型糖尿病患者在高血糖钳夹试验期间无第一相胰岛素反应。老年患者与对照者的第二相（80 - 120分钟）胰岛素值相似，但中年糖尿病患者的该值低于对照者（285±35对894±143pmol/L，P<0.0001）。在正常血糖钳夹试验期间，中年对照者的基础及稳态（150 - 180分钟）肝脏葡萄糖输出值低于糖尿病患者（基础值，3.03±0.10对3.69±0.09mg·kg⁻¹去脂体重·分钟⁻¹，P<0.0001；稳态值，0.72±0.10对1.84±0.20mg·kg⁻¹去脂体重·分钟⁻¹，P<0.0001）。老年患者与对照者的基础及稳态肝脏葡萄糖输出值相似。最后，中年组（7.51±0.85对4.62±0.24mg·kg⁻¹去脂体重·分钟⁻¹，P<0.01）及老年组（9.91±0.61对6.78±0.60mg·kg⁻¹去脂体重·分钟⁻¹，P<0.01）对照者的稳态（150 - 180分钟）葡萄糖处置率均高于糖尿病患者。
我们得出结论，肥胖中年受试者的2型糖尿病特征为葡萄糖诱导的胰岛素释放受损、肝脏葡萄糖输出调节改变以及对胰岛素介导的葡萄糖处置产生抵抗。相比之下，老年肥胖2型糖尿病患者的主要缺陷是对胰岛素介导的葡萄糖处置产生抵抗。我们的研究结果可能对这些患者群体具有重要的治疗意义。
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