Abstract
Aims. We aimed to investigate the sex differences in the renal function decline among patients with type 2 diabetic mellitus (T2DM), focusing on the differences in the risk factors at early stage of renal dysfunction. Methods. A clinic-based retrospective longitudinal study (follow-up duration: 8.1 ± 1.4 years) was conducted to assess the sex differences in the annual estimated glomerular filtration rate (eGFR) change in 344 (247 male and 97 female) Japanese T2DM patients. The sex differences in the risk factors of annual eGFR decline were subjected to linear regression analyses. Results. The mean annual eGFR change was −3.5 ± 2.7%/year in females and −2.0 ± 2.2%/year in males (P < 0.001). Baseline retinopathy and proteinuria were significantly associated with a larger eGFR decline, irrespective of sex, while HbA1c and LDL-cholesterol levels were significantly associated with an eGFR decline in females only. Interactive effects were observed between sex and the HbA1c, LDL-cholesterol, retinopathy, or proteinuria levels on the annual eGFR decline. Conclusions. The increased susceptibility to poor metabolic control seemed to contribute to a higher risk of renal dysfunction in females with T2DM. Our study highlights the importance of aggressive therapeutic intervention to improve metabolic profiles at early stage, especially in females.
Highlights
Elucidating sex differences in diabetes is a necessary step toward personalized medicine and improved public health [1,2,3]
Recent studies suggest that the increased diabetes-related risk of cardiovascular disease (CVD) in females is strongly associated with the chronic increase of their CVD risk profile, both in impaired glucose tolerance (IGT) and in impaired fasting glucose (IFG) states [4, 8, 10, 12, 14]
We previously reported that Japanese females with type 2 diabetes mellitus (T2DM) exhibit a higher incidence of diabetic retinopathy (DR) (HR, 1.85; 95% confidence interval (CI), 1.06–3.24) and are at greater risk for progression to proliferative diabetic retinopathy (PDR) [odds ratio (OR), 2.62; 95% CI, 1.38–4.98] than males [15]
Summary
Elucidating sex differences in diabetes is a necessary step toward personalized medicine and improved public health [1,2,3]. The Japan Public Health Centre-based prospective study revealed that diabetes was associated with an increased risk of death by CVD: hazard ratio (HR) 1.76 [95% confidence interval (CI), 1.53–2.02] for males, and HR 2.49 [95% CI, 2.06–3.01] for females [9]. Donahue et al reported that females who progressed from normoglycemia to a prediabetic state (fasting glucose: 100–125 mg/dL) showed greater endothelial dysfunction and a greater degree of fibrinolysis/thrombosis than males [14]. These findings may emphasize the importance of early aggressive therapeutic interventions to prevent diabetic vascular complications in females [8]
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