The effect of insulin resistance and hepatic insulin clearance on the risk of non-insulin-dependent diabetes mellitus.

目的：探讨胰岛素抵抗和肝脏胰岛素清除对日本男性工人非胰岛素依赖型糖尿病发病的影响。研究对象与方法：研究对象为某铁路公司职工。有1805名符合纳入标准的受试者进行以下分析（1：空腹静脉穿刺；2：存在葡萄糖、胰岛素和c肽数据；3：充分的人体测量数据，如身高、体重、腰围和臀围）。受试者被分为糖尿病患者和非糖尿病患者。体重指数（BMI），定义为体重（kg）除以身高(m)的平方，腰臀比和肝功能障碍（GOT≧40 IU和/或GPT≧35 IU）被视为潜在的混杂因素。采用学生t检验来检验糖尿病患者和非糖尿病患者之间变量均值的差异。采用多元logistic回归分析，探讨反映肝脏胰岛素清除率的胰岛素抵抗（HOMA）和c肽-胰岛素比值对糖尿病发生风险的影响。p值小于0.05为显著性。结果：糖尿病患者腰臀比、胰岛素、胰岛素抵抗明显高于非糖尿病患者。糖尿病患者的c肽与胰岛素比值明显较低。胰岛素抵抗每增加一个单位，糖尿病风险增加1.19倍，与一般肥胖、腹部肥胖和肝功能障碍无关。另一方面，c肽与胰岛素比值每增加1个单位，糖尿病的风险就会提高。结论：胰岛素抵抗和肝脏胰岛素清除率分别与糖尿病发生风险呈正相关或负相关，与肥胖和肝功能障碍无关。这一发现可能为糖尿病的发展提供了另一种途径。

Purpose : To investigate the effect of insulin resistance and hepatic insulin clearance on the risk of non-insulin-dependent diabetes mellitus among the Japanese male workers.Subjects and Methods : The study subjects were recruited from the employees of a railway company. There were 1805 eligible subjects for the following analysis who fitted in the inclusion criteria (1 : Fasting venipuncture, 2 : Existence of glucose, insulin, and C-peptide data, 3 : Sufficient anthromopetric data, such as height, weight, and waist and hip circumferences). The subjects were classified into diabetics or non-diabetics. Body mass index (BMI), which was defined as weight (kg) divided by the square of height (m), Waist-to-hip ratio, and liver dysfunction (GOT≧40 IU and/or GPT≧35 IU) were treated as potential confounding factors. Student's t-test was employed in order to examine the difference of the mean value of variables between diabetics and non-diabetics. The effect of insulin resistance (HOMA) and C-peptide-to-insulin ratio, which reflected hepatic insulin clearance, on the risk of diabetes was examined by means of multiple logistic regression analysis. P-values less than 0.05 were used as significant.Results : Waist-to-hip ratio, insulin, insulin resistance were significantly high among the diabetics compared with the non-diabetics. C-peptide-to-insulin ratio was significantly low among the diabetics. One unit increase of insulin resistance showed 1.19times risk of diabetes, independent of general and abdominal obesity and liver dysfunction. On the other hand, 1 unit increase of C-peptide-to-insulin ratio improved the risk of diabetes.Conclusion : Insulin resistance and hepatic insulin clearance may affect the risk of diabetes, respectively positively or inversely, independent of obesity and liver dysfunction. This finding may suggest another pathway into the development of diabetes.