May 03, 2018
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Reproductive factors influence diabetes risk in women

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Girls who enter menarche at age 10 years or younger are 18% more likely to develop type 2 diabetes vs. girls who enter menarche at age 13 years or older, whereas women who have never given birth are at greater risk for the disease vs. women who have had at least two children, according to an analysis of pooled data published in Diabetes, Obesity and Metabolism.

“Although the ongoing epidemic of overweight and obesity has fueled much of the observed increase in diabetes rates globally, there has been growing attention paid to a possibly etiological role for female-specific markers of reproductive health, such as age at menarche, parity and age at menopause, in the development of diabetes,” Nirmala Pandeya, MMedSc, PhD, of the School of Public Health at the University of Queensland in Brisbane, Australia, and colleagues wrote in the study background. “Notable trends in the prevalence of female-specific risk factors, such as an increase in the rate of gestational diabetes ... observed in populations, and a decline in the mean age of menarche ... have added to the speculation that they may play a role in the diabetes pandemic.”

Pandeya and colleagues analyzed pooled data from 126,721 middle-aged women without diabetes at baseline participating in eight cohort studies contributing to InterLACE, a large study of reproductive health and chronic disease events in 10 countries. Across studies, most women (72%) were born between 1940 and 1959 (mean age at baseline survey, 49 years; mean age at follow-up, 56 years). Researchers used generalized linear mixed models to assess the association between several reproductive factors and incident diabetes, including age at menarche, age at first birth, parity, menopausal status and hormone therapy use at baseline.

Across studies, mean age at menarche was 13 years, with 15% of women reporting menarche at age 11 years or younger. Three-quarters of women reported having at least two children, and 50.2% of women were premenopausal or perimenopausal at baseline, 2.5% experienced early menopause and 14% reported having had a hysterectomy or oophorectomy.

During a median follow-up of 9 years, researchers observed 4,073 cases of diabetes. The crude incidence of diabetes was 4.3 per 1,000 person-years.

Researchers observed a nonlinear association between age at menarche and incident diabetes. Compared with menarche at age 13 years, menarche at age 10 years or younger was associated with an 18% increased risk for diabetes after adjusting for BMI (95% CI, 1.02-1.37). In tests for BMI interaction, researchers found the association persisted only for women with BMI at least 25 kg/m² who reported menarche at age 10 years or younger, with the risk for incident diabetes rising to 33% (RR = 1.33; 95% CI, 1.13-1.55) compared with women reporting menarche at age 13 years.

Researchers also observed a nonlinear association between age at first birth and incident diabetes; however, any association was attenuated once adjusted for other reproductive factors, according to researchers. An association between parity and incident diabetes was U-shaped and persisted after adjustment for other reproductive factors and BMI — nulliparous women had an 18% increased risk for incident diabetes vs. women with two children (95% CI, 1.06-1.31), whereas women who had at least four children had a 13% greater risk for the disease vs. women with two children (95% CI, 1.03-1.24).

No association was observed between early menopause and diabetes risk, according to researchers, but women who reported having had a hysterectomy or oophorectomy at baseline had a 17% increased risk for diabetes (95% CI, 1.07-1.29).

“Whether the relationships that we, and others, have observed between markers of reproductive health and incident diabetes are truly causal and predictive of diabetes in later life, remain to be determined and subject to investigation by future studies,” the researchers wrote. – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.