Analysis shows greater diversification in mortality

Cancer is now the leading cause of excess death associated with diabetes.

An epidemiological analysis of primary care records in England over the past two decades, published in The Lancet Diabetes and Endocrinology, showed large declines in vascular mortality rates and a greater diversification of causes of death among diabetes patients, with cancer as the leading contributor.

In their study, Jonathan Pearson-Stuttard, FRSPH, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, and colleagues suggested that prevention efforts among diabetes patients should reflect this finding.

They pointed out that diabetes has a long-established association with an increased risk of vascular complications, such as heart disease, stroke, and renal and neuropathic conditions. However, they noted that mortality rates from these causes have declined by as much as 50% in the United Kingdom, as well as other high-income countries, over the past several decades.

Moreover, little in the way of research has looked at trends in specific causes of death, “leaving the contemporary burden of diabetes-related mortality poorly characterized,” the authors wrote.

In a commentary accompanying the study, Mingyang Song, MBBS, ScD, Departments of Epidemiology and Nutrition, Harvard TH Chan School of Public Health, Boston, wrote that the study “provides important data that have substantial clinical and research implications.” This, she pointed out, is particularly important as the prevalence of diabetes continues to rise.

Song noted that cardiovascular disease in individuals with diabetes has an estimated prevalence of 27%. “Thus, the two diseases are frequently grouped together and termed as cardiometabolic diseases,” she wrote. Further, she added that while cancer has been a notably major cause of death, and “has been traditionally considered as a distinct spectrum of disease, increasing evidence supports the importance of metabolic disturbances in the cause of cancer.”

In their study, Pearson-Stuttard and colleagues used the Clinical Practice Research Datalink (CPRD) GOLD, a primary care database of over 45 million patients, to estimate the death rates and the cause composition of deaths in adults in England with and without diabetes from 2001 to 2018.

The study authors identified 313,907 individuals with diabetes in the database and linked their data to the U.K. Office for National Statistics mortality data. They found that all-cause mortality rates declined by 32% (from 40.7 deaths per 1,000 person-years to 27.8 per 1,000 person years) in men and 31% (42.7 deaths per 1,000 person-years to 29.5 per 1,000 person-years) in women with diabetes.

Similar declines were seen in those persons without diabetes. “Thus, the absolute gap in death rates between individuals with and without diabetes was maintained throughout this period,” the authors noted.

The authors also estimated annual death rates from specific causes, including ischemic heart disease, stroke, other circulatory disease, renal, liver, respiratory, diabetes, injuries, dementia, diabetes-associated cancers, all-other cancers, and other causes. They found that death rates declined in all of these categories, with the exception of dementia and liver disease.

In individuals with diabetes the largest absolute declines in causes of death were seen in ischemic heart disease (7.2 deaths per 1,000 person-years), stroke (3.6 deaths per 1,000 person-years), and diabetes (2.8 deaths per 1,000 person-years). And while there were substantial gaps in cause-specific death rates for ischemic heart disease, diabetes, stroke, and diabetes-related cancers between individuals with and without diabetes in 2001, these gaps have declined substantially since then for ischemic heart disease and stroke, but increased for other causes including dementia, other cancers, diabetes-associated cancers, and respiratory diseases.

“As a result, by 2018, cancers had replaced vascular diseases as the greatest cause of excess death associated with diabetes,” wrote Pearson-Stuttard and his colleagues, adding that there has also been a general diversification of causes of death away from vascular causes towards dementia, cancer, and liver disease.

The authors suggested that further efforts to improve longevity gains in persons with diabetes, as well as to reduce longevity gaps between individuals without and without the disease, “will require a shift in clinical and preventative approaches to encompass the wider set of disease risks.”

But there are some limitations to the study, Song pointed out. These include:

  • Within the large sample, there was a low number of deaths from specific cancer types — “precluding precise assessment of the cause -of-death composition according to cancer types.”
  • Age was matched by decade, rather than birth year, which could lead to confounding when comparing those with or without diabetes.
  • Key risk factors such as BMI, smoking and blood pressure were missing from the study.

But Song pointed out that the study is important despite these limitations. “As the burden of diabetes continues to rise, especially in low-income and middle-income countries, prevention of complications is a high priority,” she wrote. “Now with cancer replacing vascular complications as the leading cause of excess death in people with diabetes, enhanced cancer prevention measures should be considered for patients with diabetes, including early cancer screening, behavioral interventions, and chemoprevention.”

Thus, she concluded, there is “an urgent need for more research to better understand the underlying causes of the increased risk of cancer associated with diabetes and develop effective preventive strategies to minimize the cancer incidence and death in individuals with diabetes.”

  1. Cancer has overtaken vascular disease as the leading cause of excess death in diabetes patients.

  2. The study authors suggest that research and prevention efforts should reflect this trend in order to reduce mortality related to diabetes.

Michael Bassett, Contributing Writer, BreakingMED™

The study was funded by the Wellcome Trust.

Pearson-Stuttard reports personal fees from Novo Nordisk A/S and Lane Clark & Peacock LLP.

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