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Diabetes Ups Risk of Death from All Causes

Posted: Monday, March 14, 2011

Diabetes not only doubles vascular death risk but also substantially raises risk of death from nonvascular causes, including cancer and infectious disease, researchers found.

John Danesh, MSc, DPhil, of the University of Cambridge, England, and colleagues in the Emerging Risk Factors Collaboration reported that a 50-year-old with diabetes can expect to die six years earlier than a nondiabetic peer, with nonvascular deaths accounting for about 40% of the survival difference.

By comparison, smoking takes about seven years off life expectancy, the group noted.

Their patient-level pooled analysis of 820,900 individuals across 97 prospective studies appeared in the March 3 issue of the New England Journal of Medicine.

Richard Bergenstal, MD, of the International Diabetes Center at Park Nicollet in Minneapolis, Minn., commented, "The magnitude of both the study and the risks highlights how serious and complicated diabetes is… We should be taking a broader view of diabetes." "We sometimes get completely wrapped up in the metabolism of the A1c and glucose and we forget about the associated effects on quality of life and depression, and other consequences."

The researchers examined 12.3 million person-years of mortality follow-up for individuals without a history of vascular disease at enrollment in the 97 studies. The baseline diabetes prevalence was 6%. Those with diabetes were 80% more likely to die from any cause during the study periods, after adjustment for age, sex, smoking status, and body mass index (95% confidence interval 1.71 to 1.90). Vascular disease took top place as a cause of death, followed by cancer.

Not surprisingly, diabetes patients carried a 2.32-fold higher adjusted risk of death from vascular causes than their non-diabetic counterparts (95% CI 2.11 to 2.56). But they were also at significantly elevated risk of death from cancer (adjusted HR 1.25, 95% CI 1.19 to 1.31) and from other nonvascular, non-cancer causes (adjusted HR 1.73, 95% CI 1.62 to 1.85).

Diabetes moderately increased risk of death from the following as well:

    * Cancers of the liver, pancreas, ovary, colorectum, lung, bladder, and breast
    * Renal disease
    * Liver disease
    * Pneumonia and other infectious diseases
    * Mental disorders
    * Nonhepatic digestive diseases
    * External causes
    * Intentional self-harm
    * Nervous-system disorders
    * Chronic obstructive pulmonary disease

Links with kidney, digestive, and infectious disease could reflect nephropathy, fatty liver disease, and suppression of cellular immunity from diabetes, the researchers suggested. The greater risk of injury-related deaths could be related to end-organ complications, such as neuropathy and eye disease, or episodes of hypoglycemia, they added.

The elevated mortality risk with diabetes appeared independent of blood pressure, lipids, the inflammatory marker C-reactive protein, fibrinogen, alcohol use, kidney function, and socioeconomic status.

Fasting glucose or HbA1c, though, appeared to account for some of the mortality risk of diabetes, as adjustment for these factors "considerably" attenuated the excess risk associated with diabetes.

Each 18 mg/dL higher fasting glucose level above 100 mg/dL was associated with a 5% higher risk of death from cancer, 13% higher risk of vascular death, and 10% higher risk of death from other causes -- for a 10% overall higher risk of death from any cause, all statistically significant. Fasting glucose levels in the 70 to 100 mg/dL range were not significantly associated with death.

These findings support a direct impact of hyperglycemia on mortality risk, Danesh's group argued.

A consensus statement from the ADA and American Cancer Society last year cautioned that it wasn't clear whether the elevated cancer risk seen with diabetes is direct or due to shared risk factors or other indirect factors. Bergenstal warned that this is still the case.   "We still can't say if it's the glucose or something associated with the hypoglycemia," he commented, noting that the study did not control for diet, activity, and many other potentially confounding factors. However, he agreed with the researchers that the findings reinforce the need for people with diabetes to get appropriate cancer screening tests on a regular basis.

Practice Pearls:

    * Explain that an analysis of 97 prospective studies found that diabetes and fasting blood sugars >100 mg/dL were associated with increased all-cause mortality.
    * Note that an association with increased mortality was found for vascular disease but also nonvascular conditions such as cancer, infectious diseases, injury, liver and renal disease, self-harm, and nervous system disorders.

Source:, Emerging Risk Factors Collaboration "Diabetes mellitus, fasting glucose, and risk of cause-specific death" N Engl J Med 2011; 364: 829-841.

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