Excess Mortality of Type 1 Diabetes Far Greater in Women

Miriam E Tucker

February 06, 2015

Women with type 1 diabetes have about a 40% greater risk of dying compared with men with the condition, when mortality is contrasted with that of the general population, and twice the risk for both fatal and nonfatal vascular events, a new meta-analysis reveals.

The findings were published online February 6 in Lancet Diabetes & Endocrinology by Rachel R Huxley, DPhil, chair of epidemiology, University of Queensland, Australia, and colleagues.

"Greater awareness of the increased hazards of death associated with type 1 diabetes — especially in women — should be promoted to both clinicians and their patients," Dr Huxley told Medscape Medical News.

"Closer scrutiny of how well women in particular manage their insulin dosing and blood glucose levels may help to reduce the disparity between women and men with the disease," she added.

In an accompanying editorial, Dr David Simmons, of the Wolfson Diabetes and Endocrinology Clinic, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom, writes, "[Dr] Huxley and colleagues rightly suggest that the sex difference in excess mortality in those with type 1 diabetes should stimulate some kind of action."

However, Dr Simmons says, "This action should not be sex based: health and funding systems should systematically support improvements in glycemic control from diagnosis, for all patients with type 1 diabetes, through tailored therapy…including mental-health support and personalized strategies that help avoid hypoglycemia. Sex differences in management of cardiovascular disease and its risk factors also need to be rectified."

The gender imbalance may be due to worse glycemic control among females compared with males, but studies on this have mostly been conducted in youth with type 1 diabetes, and the data have been conflicting.

"This is still a very controversial area, and there are very few data on these issues — hopefully, this paper will prompt future studies to look really closely at how women and men with the condition differ," Dr Huxley said.

Significant Female-Male Differences

Dr Huxley and colleagues explain in their paper that it is known that individuals with type 1 diabetes have shorter life expectancies than the general population, as result of both acute and long-term diabetic complications. But until now, it has not been clear whether this excess risk of mortality is the same in women and men with the disease.

Their results show that from 26 studies involving a total of 14,682 deaths among 197,396 individuals, the pooled standardized mortality ratio for all-cause mortality in women with type 1 diabetes was 5.80 compared with women without type 1 diabetes, vs 3.80 for men with the condition vs without.

Compared with men with type 1 diabetes, women with the condition had a 37% significantly greater excess risk for all-cause mortality (P < .0001).

From a subsequent analysis of 1427 deaths among 59,383 individuals, the pooled standardized mortality ratio for fatal and nonfatal coronary heart disease in women with type 1 diabetes vs women without the condition was 13.32, whereas among men that ratio was just 5.62. Here, the excess event rate for women was 154% greater than for men (P < .0001).

For fatal and nonfatal stroke, the standardized mortality ratio was 5.7 for women with type 1 diabetes vs without and 4.89 for men with vs without the condition, with a 37% excess among the women vs the men (P = .0308).

And for deaths from cardiovascular disease, these figures were 11.30 in women and 5.68 for men, with an 86% greater risk for women compared with men ( P < .0001). Women with type 1 diabetes also had a 44% greater risk for renal disease mortality than men.

No gender differences were found for deaths due to cancer, accidents, or suicide.

"Our findings would suggest that individuals — irrespective of gender — require additional support and assistance in managing not only their blood glucose levels but also the levels of their other cardiovascular risk factors, such as blood pressure," Dr Huxley said.

Is the Gender Difference Due to Glycemic Control?

Previous studies have suggested that there is a greater adverse effect of hyperglycemia and diabetes on vascular risk in women with type 1 diabetes compared with men with the condition and that women have increased rates of coronary artery calcification and other markers of endothelial dysfunction than do men.

"It could be that poor glycemic control worsens the endothelial functioning and increases calcification, but these processes may also be exacerbated by sex hormones — we just don't know yet," Dr Huxley told Medscape Medical News.

Studies of adolescents with type 1 diabetes have suggested that poorer glycemic control in females compared with males may be due to impairment of insulin sensitivity during puberty, as well as an increased propensity toward eating disorders and underdosing insulin as a form of weight control, a phenomenon that has been dubbed "diabulimia."

Dr Simmons notes that the current study raises key clinical questions that can't yet be answered. "For example, should women with mildly raised HbA1c concentrations (eg, higher than 7%) be commenced on statins or ACE inhibitors as young adults (with appropriate contraception, taking into account their teratogenic effects)? Should blood pressure be treated at a lower threshold in younger women (eg, less than 130/80 mm Hg if younger than 40 years)?"

He concludes, "Achievement of a reduction in the high type 1 diabetes mortality rates will need additional expenditure on the care of patients with the disorder, many of the benefits from which might not be seen for up to 20 years. The additional investment in the services and equipment to improve glycemic control must start now."

The study authors and Dr Simmons report no relevant financial relationships.

Lancet Diabetes Endocrinol. Published online February 6, 2015. Abstract, Editorial

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