Abstract P455: Insulin Resistance, Secretion and Risk of Incident Coronary Heart Disease in Non-diabetic Japanese Population: The Circulatory Risk in Communities Study
Authors: Imano Hironori , Kitamura Akihiko , Yamagishi Kazumasa , Kiyama Masahiko , Ohira Tetsuya , Cui Renzhe , Umesawa Mitsumasa , Okada Takeo , Iso Hiroyasu ,   CIRCS Investigators
Published: July 2021

Background:
Both high insulin resistance and low insulin secretion are the causes of diabetes mellitus. Japanese level of insulin secretion said to be lower than Western people. However, the association between insulin resistance, secretion and risk of coronary heart disease (CHD) or stroke in non-diabetic population remains unknown.

Hypothesis:
We assessed the hypothesis that each higher insulin resistance and lower insulin secretion is associated with increased risk of CHD even in non-diabetic population.

Methods:
A prospective study of Japanese subjects aged 40-79 years was undertaken using data collected from 5,639 participants (1,971 men and 3,668 women) who had no past history of cardiovascular disease or diabetes mellitus in cardiovascular risk surveys conducted in three communities of the Circulatory Risk in Communities Study (CIRCS) in 2000 and 2001. Insulin resistance was calculated on the basis of fasting glucose (mg/dL) and insulin levels (μU/mL) according to the homeostasis model assessment (HOMA-r) method: glucose x insulin / 405. The HOMA-beta cell function (HOMA-b) was calculated by using the following formula: 360 x fasting insulin (μU/mL) / (fasting glucose (mg/dL) - 63). Each incidence of CHD and stroke was ascertained by systematic surveillance. The hazard ratios (HRs) of incidence of CHD and 95% confidence intervals (CI) associated with a 1 standard deviation (SD) increase in log(HOMA-r) and in log(HOMA-b) were calculated with adjustment for age and other potential confounding factors using the Cox proportional hazards model.

Results:
During an average follow up of 9.8-years, 39 incident CHD (including 23 myocardial infarction) and 123 incident stroke occurred. Higher insulin resistance tended to increase risk of CHD or myocardial infarction, but all HRs did not reach statistical significance. The multivariable HRs in log(HOMA-r) for risk of CHD were 1.30(95% CI: 0.23 to 7.42) for men, 2.84(0.60 to 13.56) for women, and 1.56(0.40 to 6.04) for total subjects. The corresponding HRs of myocardial infarction were 3.73(0.31 to 44.87) for men, 2.45(0.46 to 12.98) for women, and 2.71(0.48 to 15.36) for total subjects. Lower insulin secretion associated with risk of CHD or myocardial infarction, and some of HRs reached statistical significance. The multivariable HRs in log(HOMA-b) for risk of CHD were 1.17(0.56 to 2.45) for men, 0.31(0.10 to0.96, p=0.042) for women, and 0.75(0.40 to1.42) for total subjects. The corresponding HRs of myocardial infarction were 0.53(0.18 to1.53) for men, 0.31(0.07 to 1.35) for women, and 0.42(0.18 to1.00, p=0.049) for total subjects. There was no interaction between HOMA-r and HOMA-b. HOMA-r and HOMA-b did not associated with incidence of stroke.

Conclusions:
Lower insulin secretion may be associated with increased risk of coronary heart disease among non-diabetic Japanese population.