Prediabetes increases cancer risk in adults by 15%, with significantly increased risk for cancer of the stomach, liver, pancreas, breast, and endometrium, in a meta-analysis published Sept. 8 in Diabetologia.
Moreover, that increase in risk for all cancer types was seen in studies that used the low-threshold cutoff for impaired fasting glucose recommended by the American Diabetes Association, suggesting that international experts should adopt the ADA’s definition.
The meta-analysis included 16 eligible studies comprising 891,426 adults aged 18 and older. The study evaluated cancer risk associated with impaired fasting glucose and impaired glucose tolerance, reported Dr. Yi Huang and associates at the Clinical Medicine Research Center, First People’s Hospital of Shunde, Foshan, China.
Participants met the inclusion criteria of elevated blood glucose at baseline, duration of 3 years’ follow-up or more with a cancer risk assessment, and adjusted relative risk reported for events associated with prediabetes.
Prediabetes was defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both. IFG was defined as a fasting plasma glucose (FPG) range of 5.6-6.9 mmol/L if the study used American Diabetes Association guidelines (Diabetes Care 26[Suppl 1]:S5–S20), or 6.1-6.9 mmol/L if the study used international guidelines. IGT was defined as a 2-hour plasma glucose of 7.8-11.1 mmol/L during an oral glucose tolerance test.
Prediabetes was associated with a 15% increased risk of cancer overall, compared with normoglycemia. The lowered ADA threshold of 5.6 mmol/L resulted in 49% increase in risk, whereas the higher threshold was linked with an 11% increase in risk. Measured by IFG, the cancer risk was 25% higher. However, these differences in risk between prediabetes definitions did not reach statistical significance, the investigators said (Diabetologia 2014 Sept. 8 [doi:10.1007/s00125-014-3361-2]).
Additionally, a secondary analysis of site-specific cancer risk showed that prediabetes was significantly associated with an increased risk of cancer of the stomach, liver, pancreas, breast, and endometrium, but was not associated with cancer of the lung, prostate, ovary, kidney, or bladder.
Subgroup analyses showed no differences in cancer risk by sex, age, or follow-up duration, but did reveal a significantly higher relative risk for Asian (1.50) than non-Asian patients (1.12).
Dr. Huang and colleagues said the results of this study have important implications for the definition and treatment of prediabetes.
"One of the most important arguments against using the lower threshold is that it greatly increases the prevalence of IFG, but without enough data to support the clinical prognostic implications," they wrote.
These results demonstrate similar cancer risk with different definitions of prediabetes, thus providing evidence for the use of the new ADA definition, which has not yet been accepted by the World Health Organization and other international groups, they said.
"These findings support the lower threshold definition IFG proposed by the ADA, and highlight the clinical value of the early management of hyperglycemia to prevent cancer," they said.
They added that several factors – insulin resistance, genetic interferences, and chronic hyperglycemia and its related conditions, such as chronic oxidative stress – may contribute to the increased cancer risk in persons with prediabetes. Typically, lifestyle intervention is the preferred treatment in prediabetes patients, and metformin may be added to delay progression to diabetes in those who present with additional risk factors such as a body mass index of at least 35 kg/m2, dyslipidemia, hypertension, or a family history of diabetes.
Research has shown that metformin may contribute to a 30% decrease in cancer risk in diabetes patients. Future exploration should focus on the possibility of protective anticancer properties of metformin in adults with prediabetes as well, the investigators said.
The study was funded by the Health Ministry of Guangdong province, China, and the Scientific Research Funds of Foshan and Shunde. The authors reported having no conflicts of interest.