Aims: To investigate the sex-specific associations of prediabetes with major clinical outcomes including incident type 2 diabetes, chronic kidney disease, hypertension, coronary heart disease, stroke and all-cause mortality.
Methods: Among 8498 Iranian adults from the Tehran Lipid and Glucose Study, aged ≥30 years and without diagnosed type 2 diabetes, gender-interactions were assessed for each outcome, followed by sex-separated multivariate-adjusted Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals (CIs) of different prediabetes categories, including impaired fasting glucose (IFG), defined by the American Diabetes Association (ADA) and World Health Organization (WHO), as fasting plasma glucose of 5.6-6.9 mmol/L and 6.1-6.9 mmol/L, respectively, and impaired glucose tolerance, defined as 2-h post challenge plasma glucose of 7.8-11 mmol/L.
Results: Sex-specific associations existed for men between IFG-ADA and chronic kidney disease (hazard ratio: 1.28, 95% CI 0.99-1.65; pinteraction = 0.008) and between IFG-WHO and stroke (hazard ratio: 2.15, 95% CI 1.08-4.27; pinteraction = 0.21); and for women between IFG-ADA and hypertension (hazard ratio: 1.24, 95% CI 1.04-1.48; pinteraction = 0.06) and between impaired glucose tolerance and coronary heart disease (hazard ratio: 1.57, 95% CI 1.14-2.16; pinteraction = 0.05). Among both genders, all prediabetes definitions were associated with type 2 diabetes but none with mortality.
Conclusions: The hazards of prediabetes definitions may differ between genders depending on the outcome of interest. IFG-WHO among men and impaired glucose tolerance among women are particularly important because of their association with incident stroke and coronary heart disease, respectively. Considering these sex differences could improve personalized management of prediabetes.
Keywords: Prediabetic state; cardiovascular disease; hypertension; impaired fasting glucose; impaired glucose tolerance; renal insufficiency.