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

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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.