Sopio Tatulashvili1, Gaelle Gusto2, Emmanuel Cosson1,3, Beverley Balkau4, Pierre Gourdy5, Fabrice Bonnet2,6, Hélène Bihan1,3, Guy Fagherazzi2,7. 1. AP-HP, Endocrinology, Diabetes and Metabolic Diseases Unit, Avicenne Hospital, Bobigny, France. 2. Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP) "Health Across Generations" Team, Université Paris-Saclay, Gustave Roussy, Espace Maurice Tubiana, Villejuif, France. 3. Université Paris 13, Equipe de Recherche en Epidémiologie Nutritionnelle (EREN), Centre d'Epidémiologie et Statistiques Paris Nord, Inserm U1153, Inra U1125, Cnam, COMUE Sorbonne Paris Cité, Bobigny, France. 4. Clinical Epidemiology, Université Paris-Saclay, UVSQ, Inserm u1018, CESP, Villejuif, France. 5. Diabetology Department, CHU Toulouse, Institute of Metabolic and Cardiovascular Diseases (I2MC, UMR1048 Inserm/UPS), University of Toulouse, Toulouse, France. 6. Department of Endocrinology, Diabetology and Nutrition, CHU Rennes, Université de Rennes 1, Rennes, France. 7. Department of Population Health, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.
Abstract
BACKGROUND: In many populations the incidence of type 2 diabetes is higher in men than in women. This may be explained by exposure to female gonadal hormones, but so far, there is no consensus on their role over the life course in type 2 diabetes etiology. METHODS: Data are from 83 799 French women from the E3N (Etude Épidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale) cohort study, followed for 22 years. Multivariable Cox models including classical risk factors were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) between gonadal hormonal factors and incident type 2 diabetes. RESULTS: Older age at menarche, more menstrual cycles, older age at menopause, longer duration of exposure to gonadal hormones and breastfeeding were inversely associated with incident type 2 diabetes cases (n = 4806). While a longer duration of menstrual cycles (HR = 1.23 [95% CI: 1.07-1.41] comparing ≥32 vs ≤24 days) and use of contraceptive pills (HR = 1.33 [1.25-1.42]) were associated with a greater risk of type 2 diabetes. CONCLUSIONS: In women, a longer exposure to endogenous gonadal hormones with a later menopause as well as breastfeeding were associated with a lower risk of developing type 2 diabetes, independently of classical diabetes risk factors. In contrast, the use of contraceptive agents was associated with incident diabetes, but the influence of each type of contraception and of exposure duration remain to be investigated.
BACKGROUND: In many populations the incidence of type 2 diabetes is higher in men than in women. This may be explained by exposure to female gonadal hormones, but so far, there is no consensus on their role over the life course in type 2 diabetes etiology. METHODS: Data are from 83 799 French women from the E3N (Etude Épidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale) cohort study, followed for 22 years. Multivariable Cox models including classical risk factors were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) between gonadal hormonal factors and incident type 2 diabetes. RESULTS: Older age at menarche, more menstrual cycles, older age at menopause, longer duration of exposure to gonadal hormones and breastfeeding were inversely associated with incident type 2 diabetes cases (n = 4806). While a longer duration of menstrual cycles (HR = 1.23 [95% CI: 1.07-1.41] comparing ≥32 vs ≤24 days) and use of contraceptive pills (HR = 1.33 [1.25-1.42]) were associated with a greater risk of type 2 diabetes. CONCLUSIONS: In women, a longer exposure to endogenous gonadal hormones with a later menopause as well as breastfeeding were associated with a lower risk of developing type 2 diabetes, independently of classical diabetes risk factors. In contrast, the use of contraceptive agents was associated with incident diabetes, but the influence of each type of contraception and of exposure duration remain to be investigated.