Diabetes and Cancer: ADA Consensus Statement

doi:10.1177/155989771006016

Summary

The association between diabetes and elevated cancer risk is of increasing concern. Some investigators suggest that in addition to the pathology of type 2 diabetes mellitus, the diabetes treatments themselves may play a malignant role. These issues, as highlighted in recent journal and mass media articles as well as in conjunction with the release of a related consensus statement from the American Diabetes Association are discussed.

Hyperglycemia/Hypoglycemia
Gastrointestinal Cancers
Insulin
Breast Cancer
Diabetes Mellitus

The association between diabetes and elevated cancer risk is of increasing concern. Some investigators suggest that in addition to the pathology of type 2 diabetes mellitus (T2DM), the diabetes treatments themselves may play a malignant role. These issues, as highlighted in recent journal and mass media articles as well as in conjunction with the release of a related consensus statement from the American Diabetes Association (ADA), were addressed at a symposium at the 70th Scientific Session of the ADA.

Jeffrey Johnson, PhD, University of Alberta, Edmonton, Canada, presented an epidemiological overview that reviewed the mortality statistics. Cancer is the second leading cause of death in patients with T2DM (27%), with cardiovascular disease being the first (43%; Lin et al. Ann Fam Med 2009). For specific cancer types, meta-analyses suggest that increased risk of incidence ranges from 1.2 times for breast cancer to as high as 2.5 times the normative risk for liver cancer in patients with T2DM.

That individuals with diabetes are at elevated risk for certain cancers seems clear. Explaining the specific mechanism(s) by which this association occurs is not as straightforward (Figure 1). As pointed out by Dr. Johnson, the two disease states share certain risk factors, the most prominent being obesity, which studies have consistently demonstrated increases cancer incidence and worsens treatment outcomes [Renehan et al. Lancet 2008].

Figure 1.

Conceptual Framework for Obesity, Diabetes, Cancer, and Mortality.

Reproduced with permission from F. Brancati, MD.

Hyperglycemia has also been considered. An analysis from a 10-year prospective study of over 1.23 million individuals in Korea demonstrated that fasting blood glucose values in excess of 90 mg/dL for men or 125 mg/dL for women were associated with increased cancer risk (p<0.003 and p<0.03, respectively; Jee et al. JAMA 2005). Conversely, a recent meta-analysis of over half a million individuals in the United States and the United Kingdom failed to show any relationship between elevated cancer risk and hyperglycemia or, for that matter, glycemic control [Johnson et al. submitted].

The accumulating evidence suggests, however, that hyperinsulinemia is likely a more important biological link. In a large cohort of women from New York City, the biological activity of elevated insulin-like growth factor-I levels was demonstrated to have only a modest negative impact on the incidence of colorectal cancer (Ma J et al. JNCI 2004).

Could Treatment Play a Role?

Turning to the recent controversy surrounding the use of insulin glargine as a driver of increased cancer incidence, Jay S. Skyler, MD, MACP, University of Miami, Miller School of Medicine, Miami, FL, explained the origin of and media reaction to the proposed theory that insulin glargine may be a carcinogen.

The controversy began in 2009 with an analysis of a German database that suggested that patients who were using higher doses of insulin glargine had an increased risk for cancers of all types but only when adjusted for dose (Figure 2).

Figure 2.

Hazard Ratios for Risk of All Forms of Cancer.

This conclusion resulted in several high-profile news articles [Hemkens et al. Diabetologia 2009]. This finding prompted the Diabetologia editors to request a confirmatory analysis based on unrelated datasets from the United Kingdom, Scotland, and Sweden. The resultant submissions from these public health databases were in general agreement that the association between insulin glargine and cancer was unfounded.