Evidence for a circadian rhythm of insulin sensitivity in patients with NIDDM caused by cyclic changes in hepatic glucose production
Evidence for a circadian rhythm of insulin sensitivity in patients with NIDDM caused by cyclic changes in hepatic glucose production
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DOI：
10.2337/diabetes.45.8.1044
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发表时间：
1996-08-01
期刊：
影响因子：
7.7
通讯作者：
Urbain, JL
中科院分区：
文献类型：
--
作者：
Boden, G;Chen, XH;Urbain, JL
长期以来，人们一直怀疑 NIDDM 患者胰岛素敏感性的昼夜变化，但很难记录，主要是因为葡萄糖和胰岛素变化的相互依赖性，本研究中 NIDDM 患者高血糖钳夹期间稳定的血清胰岛素水平提供了检查不受血糖和胰岛素浓度变化影响的胰岛素敏感性变化的机会，六名 NIDDM 患者（四名 NIDDM 患者） 男性和两名女性，BMI 33.9 +/- 2.5）接受高血糖（11.1 mmol/l，类似于 200 mg/dl）钳夹 72 小时，测量血清胰岛素、游离脂肪酸（FFA）、皮质醇和生长激素浓度以及维持维持所需的胰岛素分泌率、胰岛素清除率和葡萄糖输注率（GIR） 高血糖，此外，5 名患者（3 名男性和 2 名女性，BMI 32.6 +/- 0.6）接受了 24 小时的高血糖钳夹，并每小时测定肝葡萄糖产生 (HGP) 和葡萄糖消失率 (G(Rd))。 GIR 反映胰岛素敏感性，有节奏地变化，周期持续时间为 22.9 +/- 1.4 小时，幅度为 47.8 +/- 11.2%，GIR 在上午 8:31（+/-52 分钟）最低，在下午 7:04 最高。 （+/-58 分钟）。 GIR 的昼夜节律变化完全由 HGP 的变化来解释，而 G(Rd) 保持不变。 FFA 和皮质醇的血浆水平也表现出昼夜节律波动，并且它们的血液水平与 GIR 呈负相关（分别为 r = -0.72 和 -0.64）。我们的结论是，NIDDM患者的胰岛素敏感性随昼夜节律（类似于24小时）节律性变化（夜间降低，白天升高），这些变化与血糖和胰岛素水平、胰岛素清除率、运动、食物摄入和睡眠无关，它们是由HGP的昼夜节律变化引起的，而HGP又与血液FFA和FFA的昼夜节律变化密切相关。 皮质醇水平。我们相信，认识到这些昼夜节律变化对于 NIDDM 患者的诊断和治疗具有重要意义。
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, similar to 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 (G(Rd)). 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 G(Rd) 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 (similar to 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.