Boden G, Chen X, Urbain J L
Division of Endocrinology Diabetes and Metabolism, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Diabetes. 1996 Aug;45(8):1044-50. doi: 10.2337/diab.45.8.1044.
Diurnal variation in insulin sensitivity in patients with NIDDM has long been suspected but has been difficult to document mainly because of the interdependence of changes in glucose and insulin. Stable serum insulin levels during hyperglycemic clamping in patients with NIDDM in the present study provided the opportunity to examine changes in insulin sensitivity unaffected by changes in blood glucose and insulin concentrations. Six patients with NIDDM (four men and two women, BMI 33.9 +/- 2.5) underwent hyperglycemic (11.1 mmol/l, approximately 200 mg/dl) clamping for 72 h. Measured were serum insulin, free fatty acid (FFA), cortisol, and growth hormone concentrations and rates of insulin secretion, insulin clearance, and glucose infusion rate (GIR) needed to maintain hyperglycemia. In addition, five patients (three men and two women, BMI 32.6 +/- 0.6) underwent hyperglycemic clamping for 24 h with hourly determinations of hepatic glucose production (HGP) and glucose disappearance rates (GRd). GIR, reflecting insulin sensitivity, changed rhythmically with a cycle duration of 22.9 +/- 1.4 h and an amplitude of 47.8 +/- 11.2%. GIR was lowest at 8:31 a.m. (+/- 52 min) and highest at 7:04 p.m. (+/- 58 min). Circadian changes in GIR were completely accounted for by changes in HGP, while GRd remained unchanged. Plasma levels of FFAs and cortisol also exhibited circadian fluctuations, and their blood levels correlated negatively with GIR (r = -0.72 and -0.64, respectively). We concluded that insulin sensitivity in patients with NIDDM changed with circadian (approximately 24 h) rhythmicity (decreasing during the night and increasing during the day). These changes were unrelated to blood levels of glucose and insulin, insulin clearance, exercise, food intake, and sleep. They were caused by circadian changes in HGP, which in turn were closely correlated with circadian changes in blood FFA and cortisol levels. We believe that recognition of these circadian changes has implications for the diagnosis and the treatment of patients with NIDDM.
非胰岛素依赖型糖尿病（NIDDM）患者胰岛素敏感性的昼夜变化早就受到怀疑，但一直难以证实，主要是因为血糖和胰岛素变化之间存在相互依存关系。本研究中，NIDDM患者在高血糖钳夹期间血清胰岛素水平稳定，这为研究不受血糖和胰岛素浓度变化影响的胰岛素敏感性变化提供了机会。6例NIDDM患者（4例男性和2例女性，体重指数33.9±2.5）接受了72小时的高血糖（11.1 mmol/L，约200 mg/dl）钳夹。测定了血清胰岛素、游离脂肪酸（FFA）、皮质醇和生长激素浓度，以及维持高血糖所需的胰岛素分泌率、胰岛素清除率和葡萄糖输注率（GIR）。此外，5例患者（3例男性和2例女性，体重指数32.6±0.6）接受了24小时的高血糖钳夹，每小时测定肝葡萄糖生成（HGP）和葡萄糖消失率（GRd）。反映胰岛素敏感性的GIR有节律地变化，周期为22.9±1.4小时，幅度为47.8±11.2%。GIR在上午8:31（±52分钟）时最低，在下午7:04（±58分钟）时最高。GIR的昼夜变化完全由HGP的变化引起，而GRd保持不变。血浆FFA和皮质醇水平也表现出昼夜波动，它们的血药浓度与GIR呈负相关（r分别为-0.72和-0.64）。我们得出结论：NIDDM患者的胰岛素敏感性随昼夜（约24小时）节律而变化（夜间降低，白天升高）。这些变化与血糖和胰岛素的血药浓度、胰岛素清除率、运动、食物摄入及睡眠无关。它们是由HGP的昼夜变化引起的，而HGP的昼夜变化又与血FFA和皮质醇水平的昼夜变化密切相关。我们认为，认识到这些昼夜变化对NIDDM患者的诊断和治疗具有重要意义。
