COMMENTARY

Gender Differences in the Pathophysiology of Diabetes: What Do We Know?

Franck Mauvais-Jarvis, MD, PhD

Disclosures

July 01, 2015

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Hi. I am Franck Mauvais-Jarvis, professor of medicine at Tulane University Health Sciences Center in New Orleans, Louisiana. This year at the American Diabetes Association 75th Scientific Sessions, I gave a talk[1] about the role of gender and sex hormones in diabetes. This is a very important topic because men and women have evolved different ways to store and use glucose; therefore, many aspects of the regulation of glucose homeostasis are different in men vs women. These differences have implications for the development of diabetes.

For example, type 1 diabetes has a known gender dimorphism. More boys than girls develop type 1 diabetes, suggesting that the female hormones protect against type 1 diabetes. Type 2 diabetes also has a sex dimorphism in the human population, and after menopause and the loss of estrogen production, more women than men have diabetes.

Even the prediabetes syndromes differ by sex. For example, impaired fasting glucose is mostly observed in men, whereas impaired glucose tolerance is observed more in women. Thus, most of these differences are believed to be the consequence of the effect of male and female hormones after puberty.

A Deeper Look Into the Differences

As mentioned, estrogen protects and maintains insulin sensitivity and insulin secretion, and helps the insulin-producing beta cell of the pancreas adapt to metabolic stresses. These effects are mediated via estrogen receptors. When women stop producing estrogen at menopause, they become predisposed to type 2 diabetes.

In men, testosterone is converted into estrogen, which has an antidiabetic action on the estrogen receptors in men. Most effects of androgen in men result from the effect of testosterone on the androgen receptor, which enhances insulin sensitivity and prevents the development of visceral fat. We know now that there also are androgen receptors in beta cells that help these insulin-secreting beta cells to produce more insulin. As a result, men who lose androgen production during aging or in cases of androgen-deprivation therapy for prostate cancer, and men with hypogonadism and low testosterone, are predisposed to type 2 diabetes.

What are the clinical implications? Our population is aging, and therefore men and women will be spending an increasingly large part of their lives in a state of estrogenic or androgenic deficiency. We must continue to study the effects of androgen and estrogen on metabolism, because in the future we will be able to harness the beneficial effects of these hormones to develop adjuvant antidiabetes therapy in a sex-specific manner.

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