ERT may reduce diabetes risk and severity

New benefits of post-menopausal hormone therapy

New studies released at the American Diabetes Association's 58th Annual Scientific Sessions in Chicago show that post-menopausal women who take estrogenreplacement therapy (ERT) are less likely to develop diabetes and, if they do have the disease, are better able to maintain good blood sugar control, decreasing their risk of complications.

"Our survey of more than 14,000 women with diabetes age 50 and over found that those who take estrogen replacement therapy had significantly better blood sugar control, reaching lower levels that have been associated with a sizable reduction in the risk of complications," says Joe V. Selby, MD, MPH, assistant director for Health Services Research in the Division of Research at Kaiser Permanente in Oakland, CA.

Similar findings emerged from a randomized blind placebo-controlled trial of estrogen replacement in 18 post-menopausal women with diabetes at Tulane University in New Orleans.

A Milwaukee survey found that women who do not take ERT are nearly five times as likely to develop diabetes as those who do. When women with diabetes assess the pros and cons of estrogen replacement therapy based on their own personal risk profile, these findings may be a factor to take into consideration and discuss with their physicians," says Leslie O. Schulz, PhD, professor and chair of Health Sciences at the University of Wisconsin in Milwaukee.

A link with questions

It is well known that the incidence of Type II diabetes is higher among women after, rather than prior to, menopause. However, no linkage to declining estrogen levels has been shown.

Further, women with diabetes have been excluded from studies of the benefits of ERT because of problems in early studies of high dose, estrogen-containing oral contraceptives in younger women, says Karen Friday, MD, associate professor of medicine at Tulane University School of Medicine. Such contraceptives were shown to increase the risk of blood clots, which could present serious problems to women with diabetes, who have a higher risk of cardiovascular disease.

The Kaiser Permanente project surveyed 14,601 women with diabetes. Age adjusted mean levels of HbA1C were significantly lower in women using ERT. (See chart, below.)

These benefits persisted even when the statistics were controlled for age, body mass index, education, and type of diabetes therapy.

The researchers had different theories of why ERT may influence diabetes risk and severity.

"It's been suggested that body fat distribution - development of an apple rather than a pear shape - raises diabetes risk, and such central body obesity is often seen in women after menopause," says Schulz. "The degree to which ERT reduces that shift may underlie the reduced diabetes risk."

Friday says she leans toward a theory of hormonal interaction - estrogen may reduce insulin resistance and thus improve the body's ability to handle blood sugar.

Another study, conducted at the University of Washington in Seattle, offers another possibility. This study focused on indicators of the function of the beta cell in the pancreas, where insulin is produced from a precursor called proinsulin. Normally, most of the precursor is converted into insulin.

Effect on beta cell

When proinsulinemia occurs, a higher than expected level of proinsulin is present in the blood compared to insulin, suggesting that the beta cell is not functioning properly.

"As a group, the women using ERT had a lower level of proinsulinemia than the non-users, suggesting the possibility that the estrogen deficiency of menopause can interfere with beta cell," says Steven Kahn, MD, associate professor of medicine at the University of Washington School of Medicine. "ERT might be beneficial for the beta cell and reduce the risk of diabetes."

Proinsulinemia has been found to not only be a feature of Type II diabetes, but it has also been observed in people who develop diabetes later in life.