Ren and colleagues have undertaken a cross-sectional study of 8191 women (median age 56 years, interquartile range 47–65 years) recruited in rural China to determine the association between menopause and the likelihood of developing type 2 diabetes (T2D) [1]. The diagnosis of T2D in women was established by a fasting plasma glucose of 7.0 mmol/l or greater, and/or the use of insulin or an oral hypoglycemic agent and/or a self-reported history of diabetes (excluding type 1 diabetes, gestational diabetes mellitus, or diabetes due to other causes).

Of note, 38% of the women in the study were overweight, 22% were obese and 30% had hypertension. Only 7.8% reported a family history of T2D.

The study reported an overall prevalence of T2D of 13% amongst the included women. After adjusting for age, smoking, alcohol drinking, body mass index (BMI), age at menarche, systolic and diastolic blood pressures, and family history of diabetes, the risk of T2D was greater for women who were postmenopausal versus premenopausal women (adjusted odds ratio (AOR) 1.90, 95% CI 1.51–2.37). The strongest association between T2D and menopause in the adjusted model was for normal weight women (a BMI < 24 kg/m2), such that postmenopausal normal-weight women had a more than three-fold risk of having T2D versus premenopausal women (AOR 3.35, 95% CI 1.98–5.32). Age was a mediating factor in the apparent effect of menopause, but an effect of menopause persisted despite adjustment for age.

Comment

This is an interesting study that highlights several issues, in addition to indicating an association between menopause and T2D. The issues of note are that the majority of the women recruited to this study from rural China were overweight or obese and that there were alarming numbers of women with either hypertension and/or T2D. Together, the high prevalence of these risk factors in themselves predicts an imminent tsunami of cardiovascular disease in this aging population. The study also suggests that woman of normal weight, who are apparently metabolically ‘healthy’, are also at significantly increased risk of developing T2D in association with the menopause transition and midlife aging.

Why does menopause influence the risk of diabetes? Animal models of estrogen deficiency demonstrate that estrogen deficiency results in increased body fat, insulin resistance and increased blood lipids [2]. As predicted by animal models, menopause is associated with greater abdominal fat accumulation independent of any change in body weight and a more adverse lipid profile [3]. Furthermore, before menopause, women are more insulin-sensitive and handle glucose loads more effectively than men [4]. Elegant studies demonstrate a direct role of estrogen receptors in muscle as mediators of insulin sensitivity. Thus, the fall in estrogen at menopause results in impaired muscle glucose metabolism [5]. Consistent with this, after menopause muscle insulin sensitivity declines [6]. Together, the available animal and human studies provide biological evidence that the increased risk of T2D seen in postmenopausal women is partly explained by loss of ovarian estrogen production, not just aging.

Susan R. Davis

Professor of Women's Health and NHMRC Senior Principal Research Fellow, Director, Women's Health Research Program, President, International Menopause Society; Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University Australia

References

1. Ren Y, Zhang M, Liu Y, et al. Association of menopause and type 2 diabetes mellitus. Menopause 2018 Aug 20. Epub ahead of print
   http://www.ncbi.nlm.nih.gov/pubmed/30130291
2. Jones ME, Thorburn AW, Britt KL, et al. Aromatase-deficient (ArKO) mice accumulate excess adipose tissue. J Steroid Biochem Mol Biol 2001;79:3-9
   http://www.ncbi.nlm.nih.gov/pubmed/11850201
3. Davis SR, Castelo-Branco C, Chedraui P, et al. Understanding weight gain at menopause. Climacteric 2012;15:419-29
   http://www.ncbi.nlm.nih.gov/pubmed/22978257
4. Yki-Jarvinen H. Sex and insulin sensitivity. Metabolism 1984;33:1011-15
   http://www.ncbi.nlm.nih.gov/pubmed/6387364
5. Hevener AL, Zhou Z, Moore TM, Drew BG, Ribas V. The impact of ERalpha action on muscle metabolism and insulin sensitivity - Strong enough for a man, made for a woman. Mol Metab 2018;15:20-34
   http://www.ncbi.nlm.nih.gov/pubmed/30005878
6. Mandrup CM, Egelund J, Nyberg M, et al. Effects of menopause and high-intensity training on insulin sensitivity and muscle metabolism. Menopause 2018;25:165-75
   http://www.ncbi.nlm.nih.gov/pubmed/28953212

Content updated 23 September 2018