by Kristina Fiore

More than one in 10 heart disease deaths may be attributable to diabetes, researchers say.

In a meta-analysis of more than 100 studies, diabetes was associated with a twofold increased risk of the disease and was estimated to be accountable for 11% of vascular deaths, according to Nadeem Sarwar, MD, of the University of Cambridge in England, and colleagues.

They reported their findings online in The Lancet and will present them during an oral session at the American Diabetes Association meeting.

“In this decade, about 10% of vascular deaths in populations in developed countries have been attributable to diabetes in adults, corresponding to an estimated 325,000 deaths per year in high-income countries alone,” Sarwar and colleagues wrote.

“This burden will increase if the incidence of diabetes continues to rise, even if rates of vascular disease continue to fall because of decreases in smoking, improvements in treatment, or other reasons,” they added.

There have been uncertainties about the magnitude of associations between heart disease risk and stroke, and diabetes and fasting glucose concentration.

So to quantify those associations for a wide range of circumstances, the researchers conducted a meta-analysis of individual risk factors in patients without vascular disease from studies in the Emerging Risk Factors Collaboration.

They included 698,782 patients in 102 prospective studies. The mean age was 52 and 43% were women, with the majority in Europe, North America, and Australia, and the remainder in Japan or the Caribbean.

A total of 7% of patients reported a history of diabetes at baseline.

Over the study periods, there were 52,765 nonfatal or fatal vascular outcomes.

The researchers found that patients with diabetes had around a twofold increased risk of heart disease, ischemic stroke, and other vascular deaths:

* Coronary heart disease: HR 2.0, 95% CI 1.83 to 2.19
* Ischemic stroke: HR 2.27, 95% CI 1.95 to 2.65
* Hemorrhagic stroke: HR 1.56, 95% CI 1.19 to 2.05
* Unclassified stroke: HR 1.84, 95% CI 1.59 to 2.13
* Other vascular deaths: HR 1.73, 95% CI 1.51 to 1.98

The researchers said that risk was about a third higher for fatal than nonfatal myocardial infarction, “perhaps suggestive of more severe forms of coronary lesions in people with diabetes than those without, differential response of the myocardium to ischemia, or possibly in part, differential coding of deaths from coronary heart disease.”

Risk of heart disease among diabetics was higher in women than in men, in patients ages 40 to 59 than those 70 and up, in nonsmokers than in smokers, and in those with below-average systolic blood pressure.

Risk of stroke was higher in women, the same younger age group, and in those with above average body mass index (BMI).

These findings, the researchers said, warrant further study.

Also, at an adult population-wide prevalence of 10%, diabetes was estimated to account for 11% of vascular deaths, they added.

Yet only moderate associations were found between impaired fasting glucose and risk of heart disease and stroke.

Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3.90 mmol/L and 5.59 mmol/L.

But risk of heart disease increased with increasing plasma glucose concentrations:

* 5.60 to 6.09 mmol/L: HR 1.11, 95% CI 1.04 to 1.18
* 6.10 to 6.99 mmol/L: HR 1.17, 95% CI 1.08 to 1.26

The researchers added that risk was “substantially higher” among those with concentrations of 7 mmol/L or higher.

The study was limited in that it may not be generalizable to patients in low- or middle-income countries.

In an accompanying commentary, Hertzel C. Gerstein, MD, of McMaster University in Hamilton, Ontario, said it remains unknown whether the spectrum of dysglycemia is causally related to cardiovascular outcomes.

Trials of glucose-lowering therapies have shown a modest reduction in myocardial infarction, but “the size of the effect strongly suggests that glucose is not the only player,” he wrote. Others could include fatty acid and lipoprotein metabolism, visceral fat deposition, hepatic function, and renin-angiotensin, among others.

“Any or all of these factors (and others) might promote cardiovascular disease through various known and unknown mechanisms,” Gerstein wrote. “Large, long-term clinical trials of insulin-replacement therapy, incretins, and other approaches targeting one or more of these abnormalities … are certain to shed more light on the link between dysglycemia and serious outcomes.”

Kristina Fiore is a MedPage Today staff writer.

Originally published in MedPage Today. Visit MedPageToday.com for more diabetes news.