Health & Medical Menopause health

Menopause and the Risk of Diabetes

´╗┐Menopause and the Risk of Diabetes

Abstract


Objective: The study objectives were to examine the association between menopause status and diabetes risk among women with glucose intolerance and to determine if menopause status modifies response to diabetes prevention interventions.
Methods: The study population included women in premenopause (n = 708), women in natural postmenopause (n = 328), and women with bilateral oophorectomy (n = 201) in the Diabetes Prevention Program, a randomized placebo-controlled trial of lifestyle intervention and metformin among glucose-intolerant adults. Associations between menopause and diabetes risk were evaluated using Cox proportional hazard models that adjusted for demographic variables (age, race/ethnicity, family history of diabetes, history of gestational diabetes mellitus), waist circumference, insulin resistance, and corrected insulin response. Similar models were constructed after stratification by menopause type and hormone therapy use.
Results: After adjustment for age, there was no association between natural menopause or bilateral oophorectomy and diabetes risk. Differences by study arm were observed in women who reported bilateral oophorectomy. In the lifestyle arm, women with bilateral oophorectomy had a lower adjusted hazard for diabetes (hazard ratio [HR], 0.19; 95% CI, 0.04-0.94), although observations were too few to determine if this was independent of hormone therapy use. No significant differences were seen in the metformin (HR, 1.29; 95% CI, 0.63-2.64) or placebo arms (HR, 1.37; 95% CI, 0.74-2.55).
Conclusions: Among women at high risk for diabetes, natural menopause was not associated with diabetes risk and did not affect response to diabetes prevention interventions. In the lifestyle intervention, bilateral oophorectomy was associated with a decreased diabetes risk.

Introduction


Several types of evidence suggest that menopause could be associated with more rapid progression of glucose intolerance. First, postmenopause may be a relatively androgenic state compared with premenopause due to cessation of ovarian estrogen production and continuation of androgen production. Second, greater levels of endogenous androgens are associated with glucose intolerance in both premenopausal and postmenopausal women. Third, postmenopausal estrogen therapy reduces fasting plasma glucose (FPG) levels.

It is unknown if menopause per se is associated with higher glucose levels, particularly among women who are already glucose intolerant. Because diabetes is typically defined by glucose levels, the presence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) is a strong risk factor for diabetes, and the menopausal state may not have any additional effect. Although several longitudinal studies have found no association between menopause and glucose, these studies did not measure the associations between menopause and the key mediators of glucose tolerance, specifically insulin secretion and insulin resistance, or other biomarkers. Furthermore, these studies did not compare diabetes risk among the population of women with bilateral oophorectomy with those with natural menopause. Bilateral oophorectomy reduces testosterone levels, and high testosterone is a risk factor for diabetes in women. Finally, it is also unknown if diabetes prevention interventions are more effective in premenopausal compared with postmenopausal women.

If menopause status is a risk factor for diabetes among women who are already at high risk or modifies response to diabetes prevention interventions, this has implications for targeted diabetes prevention interventions. The Diabetes Prevention Program (DPP) was a randomized trial of diabetes prevention interventions among adults with IFG and IGT. Using the data from the DPP, we examined diabetes risk associated with menopause status, comparing women who were premenopausal with women who were postmenopausal at baseline. We also examined if menopause status modified the effect of DPP interventions on a number of metabolic variables, including adiposity, insulin metabolism, glucose, adiponectin, C-reactive protein (CRP), fibrinogen, and tissue plasminogen activator antigen (tPA). Finally, we examined whether the associations between natural menopause and diabetes risk differed from those of bilateral oophorectomy and diabetes risk before and after consideration of hormone therapy (HT).

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