Effect of hyperinsulinemia on renal function in a general Japanese population: The Hisayama study

Background. Insulin resistance and hyperinsulinemia induce glomerular hypertension and hyperfiltration, which may result in glomerulosclerosis. However, the relationship between hyperinsulinemia and renal function is uncertain. Methods. To elucidate whether hyperinsulinemia plays a significant part in the initiation and development of renal dysfunction, we examined in 1988 the relationship between serum insulin and renal function on data from a cross-sectional community survey conducted among residents from Hisayama Town, Japan, who were aged 40 to 79 years old. A total of 1065 men (72.0% of the total population in the same age range) and 1381 women (79.0%) without renal failure (creatinine clearance of more than 30 ml/min) underwent a comprehensive examination, including a 75 g oral glucose tolerance test. Results. The correlation analysis showed that serum insulin, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index were all negatively correlated with the reciprocal of serum creatinine level (P < 0.01), and alcohol intake was positively correlated (P < 0.05) in both sexes. High-density lipoprotein cholesterol and smoking habits were positively correlated (P < 0.05) in men. When the subjects were divided into quartiles based on the sum of fasting and two-hour postloading insulin levels, the averages of the reciprocal of serum creatinine were significantly lower in the fourth quartile (0.90 ± 0.10 for men and 1.10 ± 0.14 for women) compared with the lowest quartile (0.95 ± 0.12 and 1.13 ± 0.13, respectively) in both sexes (P < 0.05). In multiple regression analysis, the correlation between the sum of insulin levels and the reciprocal of serum creatinine remained significant even after controlling for age, sex, body mass index, blood pressure, total cholesterol, high- density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, alcohol intake, and smoking habits. We could not find appropriate correlations of creatinine clearance calculated by the Cockcroft- Gault formula with the covariates including serum insulin. Conclusions. The findings of this study suggest that hyperinsulinemia is a significant relevant factor of renal function in the general population.