Insulin Use Associated With Increased Mortality in Older Women

Excess mortality, common among Medicare-age diabetics, is greatest for women who use insulin to control their diabetes, according to an analysis of data from the Cardiovascular Health Study. Women who used insulin had an almost fourfold higher mortality risk (hazard ratio 3.61 (95% confidence intervals 2.83-4.60) P<0.001), than non-diabetic controls.

Both older men and women who used either oral hypoglycemic agents or insulin to treat diabetes had a higher mortality risk than non-diabetics, including more than a doubling of risk for cardiovascular or coronary artery disease mortality, found Joshua Barzilay, M.D., of Emory University and Kaiser Permanente of Georgia, and co-investigators, in the study.

But the magnitude of diabetes-associated increased mortality was greater between diabetic women and non-diabetic women, than between diabetic and non-diabetic men, they pointed out. Moreover, when mortality was analyzed by treatment type, the overall increased mortality of women than men with diabetes appears to be accounted for by insulin therapy, a finding that was not previously reported, Dr. Barzilay said.

Thee investigators recruited 5,201 patients ages 65 or older in 1989 and 1990. In 1992 and 1993, the study enrolled an additional 687 African-Americans.

At baseline 322 participants had diabetes treated with oral hypoglycemic agents and 194 used insulin for diabetes.

Participants were followed for a mean of 11.1 years to track total mortality as well as cardiovascular deaths, coronary heart disease deaths, and non-cardiovascular/non-cancer mortality. There were 2,391 deaths during follow-up.

Among the findings: Deaths due to dementia and renal disease were more common among patients using oral hypoglycemic agents. Median survival for patients using insulin was about 7.5 years, with 75% dead by the 12-year follow-up. Median survival for patients using oral hypoglycemic agents was slightly less than 10 years.

Earlier studies have confirmed that diabetes significantly increased cardiovascular and coronary artery disease mortality among young and middle-age individuals, but this study provided evidence that the increased risk extends into old age, the authors wrote.

In this study participants with pharmacologically treated diabetes were roughly twice as likely to die of cardiovascular disease as non-diabetic controls (oral hypoglycemic agents, HR:1.99, 95% CI, 1.54 to 2.57 and insulin treated: HR2.16 95% CI, 1.54 to 3.03); and 2.5 times more likely to die of coronary artery disease (oral agents: HR 2.47, 95% CI, 1.89 to 3.24, and insulin: HR 2.75, 95% CI, 1.95 to 3.87).

Only patients who reported using oral hypoglycemic agents or insulin were considered diabetic in the study, a definition that was so strict that it may have excluded people who were considered diabetic in prior studies, a methodological difference that might explain some of the findings.

This study reinforces the need for aggressive glucose control as well as control of comorbidities including obesity, hypertension, and dyslipidemia in older patients with diabetes as well as younger patients.

Kronmal RA, et al "Mortality in pharmacologically treated older adults with diabetes: The cardiovascular health study 1989-2001." PLoS Med 2006; 3(10): e400.

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