Objective To investigate whether adverse differences in levels of cardiovascular risk factors in women than men, already established when comparing individuals with and without diabetes, are also present before type 2 diabetes onset.
Research design and methods In a population-based cohort study of individuals aged 40-75 years (n=3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated associations with cardiometabolic and lifestyle risk factors of (1) pre-diabetes and type 2 diabetes (reference category: normal glucose metabolism) and (2) among non-diabetic individuals, of continuous levels of hemoglobin A1c (HbA1c). Age-adjusted sex differences were analyzed using linear and logistic regression models with sex interaction terms.
Results In pre-diabetes, adverse differences in cardiometabolic risk factors were greater in women than men for systolic blood pressure (difference, 3.02 mm Hg; 95% CI:−0.26 to 6.30), high-density lipoprotein (HDL) cholesterol (difference, −0.10 mmol/L; 95% CI: −0.18 to −0.02), total-to-HDL cholesterol ratio (difference, 0.22; 95% CI: −0.01 to 0.44), triglycerides (ratio: 1.11; 95% CI: 1.01 to 1.22), and inflammation markers Z-score (ratio: 1.18; 95% CI: 0.98 to 1.41). In type 2 diabetes, these sex differences were similar in direction, and of greater magnitude. Additionally, HbA1c among non-diabetic individuals was more strongly associated with several cardiometabolic risk factors in women than men: per one per cent point increase, systolic blood pressure (difference, 3.58 mm Hg; 95% CI: −0.03 to 7.19), diastolic blood pressure (difference, 2.10 mm Hg; 95% CI: −0.02 to 4.23), HDL cholesterol (difference, −0.09 mmol/L; 95% CI: −0.19 to 0.00), and low-density lipoprotein cholesterol (difference, 0.26 mmol/L; 95% CI: 0.05 to 0.47). With regard to lifestyle risk factors, no consistent pattern was observed.
Conclusion Our results are consistent with the concept that the more adverse changes in cardiometabolic risk factors in women (than men) arise as a continuous process before the onset of type 2 diabetes.
- sex difference
- cardiovascular risk factors
- women's health
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Contributors RdR wrote this paper, under supervision of SJSS, CJHvdK, SAEP, and CDAS. All authors reviewed the draft paper and provided critical intellectual content. All authors approved the final version of the manuscript and its submission to BMJ Open Diabetes Research & Care. CDAS is taking responsibility for the contents of the article.
Funding This study was supported by ZonMw (project no 849200001), the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs (grant 31O.041), Stichting De Weijerhorst (Maastricht, the Netherlands), the Pearl String Initiative Diabetes (Amsterdam, the Netherlands), CARIM, School for Cardiovascular Diseases (Maastricht, the Netherlands), School CAPHRI, Care and Public Health Research Institute (Maastricht, the Netherlands), NUTRIM, School of Nutrition and Translational Research in Metabolism (Maastricht, the Netherlands), Stichting Annadal (Maastricht, the Netherlands), Health Foundation Limburg (Maastricht, the Netherlands) and by unrestricted grants from Janssen-Cilag B.V. (Tilburg, the Netherlands), Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands) and Sanofi-Aventis Netherlands B.V. (Gouda, the Netherlands).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study has been approved by the institutional medical ethical committee (NL31329.068.10) and the Minister of Health, Welfare and Sports of the Netherlands (Permit 1 31 088–1 05 234 PG).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.