Elevated glucose levels and diabetes associated with a greater risk for cancer

New research involving more than one million people indicates that having high fasting serum glucose levels and diabetes are risk factors for several major cancers, according to a study in the January 12 issue of JAMA.

Diabetes mellitus is a serious and costly disease that is becoming increasingly common in many countries, including Korea, the site of this study, according to background information in the article. Recent data show that approximately 150 million people have diabetes mellitus worldwide, and this number may double by 2025, especially in developing countries, because of population growth, aging, unhealthy diets, obesity, and sedentary lifestyles.

Sun Ha Jee, Ph.D., M.H.S., of the Graduate School of Public Health, Yonsei University, Seoul, Korea, and colleagues examined the relationship between fasting serum glucose and diabetes and risk of all cancers and specific cancers in men and women in Korea. The 10 year Korean Cancer Prevention Study (KCPS) included 1,298,385 Koreans (829,770 men and 468,615 women) aged 30 to 95 years who received health insurance from the National Health Insurance Corp. and had a biennial medical evaluation in 1992-1995.

During the 10 years of follow-up, there were 20,566 cancer deaths in men and 5,907 cancer deaths in women. The researchers found that, while controlling for smoking and alcohol use, the group with the highest fasting serum glucose (140 mg/dL or greater [7.8 mmol/L or greater]) had a higher death rates from all cancers combined (29 percent higher for men; 23 percent higher for women) compared with the group with the lowest level (less than 90 mg/dL [less than 5.0 mmol/L]). By cancer site, the association was strongest for pancreatic cancer, comparing the highest and lowest stratums (91 percent increased risk in men; more than twice the risk for women). Significant associations were also found for cancers of the esophagus, liver, and colon/rectum in men and of the liver and cervix in women, and there were significant trends with glucose level for cancers of the esophagus, colon/rectum, liver, pancreas, and bile duct in men and of the liver and pancreas in women.

Of the 26,473 total cancer deaths in men and women, 848 were estimated as attributable to having a fasting serum glucose level of more than 90/mg/dL. For cancer incidence, the general patterns reflected those found for mortality. For persons with a diagnosis of diabetes or a fasting serum glucose level greater than 125 mg/dL (6.9 mmol/L), risks for cancer incidence and mortality were generally elevated compared with those without diabetes.

“While the generalizability of the findings is uncertain, we have shown that fasting serum glucose level and diabetes are associated with cancer risk in a population far leaner than the Western populations in other studies. These associations do not reflect confounding by obesity, suggesting that the mechanism of increased cancer risk reflects the consequences of hyperinsulinemia. Glucose intolerance may be one pathway by which obesity increases cancer risk, and rising obesity may increase future cancer rates,” the authors write.

In an accompanying editorial, Kathleen A. Cooney, M.D., and Stephen B. Gruber, M.D., Ph.D., M.P.H., of the University of Michigan Medical School, Ann Arbor, discuss the findings by Jee et al.

“How may these results be interpreted in the context of cancer incidence and mortality in the population? Fortunately, the relative risks are modest and, therefore, the fraction of cancers attributable to elevated fasting glucose in the Korean population is small, in part because of the relatively low prevalence of diabetes in Korea (5 percent),” they write. “Some of these cancer deaths may be preventable, and further studies will be required to demonstrate that reductions in hyperglycemia and diabetes will lead to declines in cancer mortality. This is especially true in light of data from the Diabetes Prevention Program Research Group demonstrating a reduction in the incidence of diabetes through lifestyle interventions, including dietary modification and introduction of a regular exercise routine. Since the hazard ratios reported by Jee et al are derived from a Korean population, they cannot be directly implemented to increase understanding of the population-attributable fraction of cancer that may be due to diabetes in the United States. But since the prevalence of diabetes is higher in the United States than in Korea, it is possible that preventing diabetes may have a more important effect in the United States.”

“As diabetes becomes an increasing public health concern in modern societies, the cancer risks looming on the horizon are now being recognized. Strategies to address the emerging epidemics of diabetes and obesity are likely to have a broad impact on public health. Indeed, these approaches may ultimately diminish the burden of cancer for future generations,” they conclude.



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