Abstract P337: Association of Glucose Intolerance and Insulin Resistance with Incident Cardiovascular Disease in a Japanese Urban Cohort: The Suita Study
Authors: Kokubo Yoshihiro , Watanabe Makoto , Higashiyama Aya , Nakao Yoko M , Kobayashi Takashi , Watanabe Takuya , Miyamoto Yoshihiro 
Published: July 2021

Introduction:
Glucose intolerance and insulin resistance are known risk factors for cardiovascular disease (CVD). However, few prospective studies were reported the association between combinations of these two factors and incident CVD. We assessed the hypothesis that insulin resistance increased the association between glucose intolerance and CVD in Japanese general population.

Methods:
We studied 4,638 Japanese individuals (mean age 56.1 years, without CVD) who completed a baseline medical examination and a 75g oral glucose tolerance test in the Suita Study. Glucose categories were defined as follows: diabetes mellitus (DM; fasting plasma glucose levels [FPG] ≥126 mg/dL, 2 hours post-loaded glucose levels [2h-PG] ≥ 200 mg/dL, and/or DM medication); impaired glucose tolerance (IGT; FPG <126 mg/dL and 2h-PG =140-199 mg/dL); impaired fasting glucose (IFG; FPG =100-125 mg/dL and 2h-PG <140 mg/dL); and normal glucose tolerance [NGT]. Insulin resistance was the following formula: HOMA-IR = [FPG] x [fasting insulin] / 405. Insulin resistance was defined as HOMA-IR ≥2.5. Multivariable-adjusted Cox proportional hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated after adjusting for age, sex, body mass index, blood pressure category, hyperlipidemia, smoking, and drinking at the baseline.

Results:
During the 11.7-year follow-up, we documented 127 cerebral infarctions, 63 hemorrhagic stroke, 12 unclassified strokes, and 143 coronary heart disease events. The adjusted HRs (95% CIs) of subjects with FPG =100-125 mg/dL and ≥126 mg/dL were 1.38 (1.01-1.89) and 2.00 (1.12-3.58) for stroke and 1.47 (0.99-2.19) and 2.73 (1.43-5.22) for cerebral infarction, respectively, compared with the fasting NGT group. On the basis of the subjects with 2h-PG <140 mg/dL group, the adjusted HRs (95% CIs) of subjects with 2h-PG ≥200 mg/dL were 1.71 (1.07-2.72) for stroke and 2.06 (1.20-3.54) for cerebral infarction. Compared to the NGT group, the adjusted HRs (95% CIs) of the subjects with IFG, IGT, and DM were 1.59 (1.10-2.30), 1.34 (0.89-2.00), and 1.86 (1.16-3.00) for stroke and 1.82 (1.13-2.90), 1.55 (0.93-2.56), and 2.43 (1.39-4.26) for cerebral infarction, respectively. Compared to the subjects with HOMA-IR <1.5, the adjusted HRs (95% CIs) of CVD and stroke with HOMA-IR ≥2.5 were 1.45 (1.07-1.96) and 1.61 (1.07-2.42), respectively. Compared to the NGT group without insulin resistance, the IFG and DM groups with insulin resistance were observed the increased risks of stroke (HRs [95% CIs]; 2.05 [1.17-3.57] and 2.11 [1.17-3.83]) and cerebral infarction (HRs [95% CIs]; 2.45 [1.20-5.00] and 3.56 [1.84-6.88]), respectively.

Conclusions:
Fasting glucose intolerance and insulin resistance are predictive factors for the incidence of stroke and cerebral infarction. Insulin resistance increased the risks of incident stroke and cerebral infarction in general inhabitants with IFG and DM.