Menopause and Diabetes Risk

Neither natural menopause nor oophorectomy-induced menopause increased diabetes risk as compared with premenopausal women. In fact, bilateral oophorectomy was associated with a decreased risk of diabetes (HR 0.19) among women who also made lifestyle changes to reduce their risk of the disease, according to a new report.  

Catherine Kim, MD, MPH, of the University of Michigan in Ann Arbor, wrote in conclusion, "The present report has clinical and public health relevance, showing that natural menopause does not modify the impact of diabetes prevention interventions among women at high risk for diabetes."

"Bilateral oophorectomy may have different effects on response to lifestyle interventions than natural menopause, but the role of hormone therapy needs to be assessed," Kim added. In the big picture, however, a decreased risk of diabetes leads to a decreased risk in cardiovascular disease. Heart disease and stroke are the leading causes of death and disability among people with type 2 diabetes. In fact, at least 65% of people with diabetes die of some form of heart disease or stroke. And adults with diabetes are two to four times more likely to die of heart disease than adults without diabetes, according to the American Heart Association.

In the current study, the authors noted that some evidence suggests that menopause might accelerate progression of glucose intolerance. Whether menopause affects diabetes risk in women at high risk for the condition had remained unclear.

Data from the Diabetes Prevention Program (DPP) afforded an opportunity to examine more closely the relationship between menopause and diabetes.

The DPP evaluated the impact of lifestyle interventions and metformin in middle-age men and women who were at high risk for diabetes because of impaired fasting glucose and impaired glucose tolerance.

Kim and colleague used the DPP database to compare diabetes risk in pre- and postmenopausal women and to determine whether menopausal status modified the effect of DPP interventions on various metabolic parameters. The analysis included 1,237 women ages 40 to 65, of whom 708 were premenopausal, 328 had undergone natural menopause, and 201 were surgically postmenopausal (bilateral oophorectomy). Follow-up averaged 3.2 years.

The premenopausal women had an unadjusted diabetes rate of 11.8 per 100 person-years in the placebo group, 6.6 in the metformin group, and 6.8 in the lifestyle group. Postmenopausal women had case rates of 11.5 per 100 person-years in the placebo group, 8.9 in the metformin group, and 3.2 in the lifestyle group.

Naturally postmenopausal women had diabetes case rates of 10.5 per 100 person-years in the placebo arm of the DPP, 5.0 in the metformin arm, and 4.3 in the lifestyle arm. Corresponding rates among surgically postmenopausal women were 12.9, 10.3, and 1.1 per 100 person-years.

None of the differences between pre- and postmenopausal women achieved statistical significance in the unadjusted analysis or after adjustment for age, race/ethnicity, family history of diabetes, history of gestational diabetes, waist circumference, fasting insulin, and corrected insulin response.

The only significant difference between pre- and postmenopausal women occurred in the adjusted analysis of surgically postmenopausal women randomized to the lifestyle intervention arm of the DPP (HR 0.19, 95% CI 0.04-0.94).

Stratification by hormone use also showed no significant difference in diabetes risk, overall or in separate analyses of naturally and surgically postmenopausal women. The significant difference observed in surgically postmenopausal women assigned to lifestyle intervention did not persist in those with hormone therapy.

Acknowledging limitations of the study, Kim and coauthors pointed out that bilateral oophorectomy was self-reported and that study participants were queried only at baseline about menopausal status. The investigators could not account for women who might have transitioned from pre- to postmenopausal status during the three years of follow-up.

Use of oral contraceptives to manage perimenopausal symptoms might have affected progression to diabetes in premenopausal women, but only 6% of women reported OC use.

• Note that this study evaluated risk of development of diabetes and response to prevention interventions as affected by menopause in women at high risk for development of diabetes as determined by glucose intolerance.
• Point out that menopause was not associated with increased diabetes risk and did not affect response to diabetes prevention interventions.

Kim C et al. "Menopause and risk of diabetes in the Diabetes Prevention Program" Menopause 2011; 18(8): 857 - 868