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量对日本男性职工患非胰岛素依赖型糖尿病风险的影响。有1805名符合纳入标准的合格受试者(1：空腹静脉穿刺术，2：是否存在葡萄糖、胰岛素和C-肽数据，3：足够的无血栓数据，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。体重指数定义为体重(Kg)除以身高(M)、腰臀比和肝功能障碍(GOT≧40IU和/或GPT≧35IU)的平方，作为潜在的混杂因素。采用t检验检验糖尿病患者与非糖尿病患者变量均值的差异。用多元Logistic回归分析胰岛素抵抗(HOMA)和反映肝脏胰岛素清除的C-肽/胰岛素比值对糖尿病风险的影响。结果：糖尿病组的腰臀比、胰岛素、胰岛素抵抗均显著高于非糖尿病组。糖尿病患者的C-肽/胰岛素比值明显偏低。胰岛素抵抗每增加一个单位，患糖尿病的风险是1.19倍，与全身肥胖、腹型肥胖和肝功能障碍无关。另一方面，C肽/胰岛素比每增加1个单位，患糖尿病的风险增加。结论：胰岛素抵抗和肝脏胰岛素清除分别对糖尿病的风险有正向或反向影响，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.