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Deaths from Non-Obesity-Related Cancers Higher in T2D

— Even in some obesity-related malignancies, high BMI was inversely tied to cancer death

MedpageToday

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BERLIN -- While confirming obesity as a contributing factor to the higher cancer mortality in type 2 diabetes (T2D), body mass index (BMI) predicts mortality only for some obesity-related cancers, researchers said here.

The large population-based study, presented at the annual meeting, made two unexpected findings in T2D patients: an increased mortality from non-obesity-related cancers and a counterintuitive inverse relationship between BMI and some obesity-related cancer deaths.

The results ran counter to the hypothesis that most cancer deaths in T2D patients stem from obesity-related cancers and that in T2D patients there is a positive association between BMI at diagnosis and cancer mortality.

"Our findings support the idea that obesity-related mechanisms contribute to the increased risk of cancer death in people with type 2 diabetes compared with those without type 2 diabetes," Nasra N. Alam, BM, of the University of Manchester in England, told ľֱ. "However, the higher risk of non-obesity-related cancer death in patients with type 2 diabetes suggests that other pathways are also involved, and other factors associated with obesity and diabetes contribute differentially to specific cancer types."

Drawing on data from the U.K. Clinical Practice Research Datalink, she and her colleagues analyzed 176,886 T2D patients with an average age of 61, who were then age- and gender-matched with 852,946 non-diabetic controls in the period 2008 to 2015. The T2D cohort had 99,767 men and 77,119 women.

The aim was to compare the risk of dying from 13 obesity-related cancers versus non-obesity-related cancers, and to assess the link between BMI and cancer mortality in individuals with T2D. Obesity-related malignancy types included liver, pancreas, gallbladder, colorectal, esophageal, kidney, thyroid, meningioma, multiple myeloma, endometrial, ovarian, and postmenopausal breast cancers.

The BMI analysis sample group consisted of 145,769 individuals whose BMI was recorded before the diagnosis of diabetes. The results were adjusted for potential confounders such as calendar year, age, smoking, ethnicity, and deprivation.

Over an average 7.1 years of follow-up, 9,606 cancer deaths occurred in people with T2D and 37,853 in those without diabetes. The most common cancer deaths in men with T2D were due to lung, prostate, and colorectal cancers; in women the cancer deaths were lung, breast, and pancreatic cancers.

The researchers reported that compared with the diabetes-free control population, T2D was associated with a higher risk of total cancer mortality in both men and women: hazard ratio (HR) for men 1.22 (95% CI 1.18-1.26); HR for women 1.31 (95% CI 1.26-1.37). T2D also correlated to a higher risk of death from obesity-related cancers in both genders: HR 1.84 for men (95% CI 1.72-1.96) and 1.47 for women (95% CI 1.39-1.56).

T2D was also associated with a heightened risk of death from non-obesity cancers in both men (HR 1.06, 95% CI 1.02-1.11) and women (1.18, 95% CI 1.12-1.25).

Surprisingly, in the cohort whose BMI was recorded before T2D diagnosis, BMI was negatively related to all-cause mortality (the so-called obesity paradox in which obesity appears to be in some way protective, with some showing that cancer patients with low-normal BMI or weight loss have worse outcomes than obese patients do).

Although there was no association between BMI and mortality from obesity-related cancers overall, there were strong positive associations with certain obesity-related malignancies. In women with endometrial cancer, for example, a BMI of 35 to 39.9 versus a normal BMI conferred an HR of death of 4.40 (95% CI 1.51-12.84).

T2D affects more than 415 million people worldwide, and cancer is the second leading cause of T2D death after cardiovascular, and in some studies has outstripped cardiovascular deaths. Whether this increased risk is directly related to T2D through exposure to high blood glucose, for example, or indirectly through other common risk factors such as obesity is not known and warrants further investigation, the authors said.

  • author['full_name']

    Diana Swift is a freelance medical journalist based in Toronto.

Disclosures

This study was supported by the Manchester Cancer Research Centre.

The authors reported no competing interests.

Primary Source

European Association for the Study of Diabetes

Alam NN, et al “Cancer mortality in type 2 diabetes: A population-based cohort study quantifying relationships with body mass index” EASD 2018; Abstract 1117.