Medscape...Patients with type 1 or type 2 diabetes have a higher incidence of cancer and death from cancer, with risks highest for certain specific tumors, compared with the general population, a new Australian study shows. The findings highlight the importance of screening for carcinomas in patients with diabetes to aid early detection and reduce premature mortality, say the researchers.
The highest excess risks were observed for cancers of the pancreas, liver, endometrium, kidney, thyroid, and gallbladder and for chronic myeloid leukemia, say the scientists, led by PhD candidate Jessica Harding (Baker IDI Heart and Diabetes Institute, Melbourne, Australia), in their paper published online in Diabetes Care.
The researchers note that the heightened medical attention given directly after a diabetes diagnosis, as well as reverse causality, might partly explain the increased cancer risk seen initially, but these factors "do not explain increased risks 2 years following diabetes diagnosis, particularly for cancers of the pancreas, liver, kidney, and endometrium."
In an interview, Ms Harding told Medscape Medical News that these results suggest that "clinicians should be vigilant in screening for cancers in people with diabetes, as early detection will be key to preventing early morbidity and mortality from cancer."
Data From One of World's Largest Diabetes Registries
The study included 953,382 registrants from the National Diabetes Service Scheme (NDSS) in Australia: 80,676 (8.5%) with type 1 diabetes and 872,706 (91.5%) with type 2 diabetes, diagnosed between the years 1997 and 2008.
The NDSS is one of the world's largest diabetes registries, and the data were linked to the National Death Index (NDI).
This information was then linked to data from the Australian Cancer Database (ACD) to calculate standardized incidence and mortality rates of cancer overall and site-specific cancers in patients with diabetes. Cancer rates in Australia's general population served as a comparison.
Individuals were followed from January 1, 1997 (or registration date if later) to December 31, 2008, date of death, or date of event (death or cancer occurrence).
Ms Harding pointed out that with the aging population and increasing obesity, both the incidence of cancer and diabetes are on the rise, and given these increases are occurring over the same time periods, she and her colleagues had postulated there must be a link between the two.
Also, she said, "Given that insulin…may promote the growth of cancer cells, we wanted to explore whether type 1 patients — treated with insulin — had a higher risk for cancer compared with type 2 patients.
"In particular, are rising glucose levels and/or obesity in diabetes leading to the development of cancer? Such theories are supported by animal data, but large studies on human populations are lacking," she explained.
Excess Risk of Cancer in Both Type 1 and Type 2 Diabetes
This study is one of the first to explore site-specific cancer mortality in type 1 diabetes, the researchers note.
Standardized incidence ratios in patients with type 1 diabetes for all cancers combined were 1.02 for males and 1.10 for females.
Among females with type 1 diabetes, there were significant excess risks for cancers of the pancreas, liver, esophagus, colon and rectum, stomach, thyroid, brain, and lung, as well as ovarian and endometrium cancer, and a decreased risk for melanoma, compared with the general population.
For men, a similar pattern was seen, but fewer associations were significant. A decreased incidence of prostate cancer was found.
Significant increased mortality ratios were seen for cancers of the pancreas and liver and non-Hodgkin's lymphoma among those with type 1 diabetes and for cancers of the kidney (in males only) and, in women, for brain and endometrial cancers.
For type 2 diabetes, the standardized incidence ratios for cancers overall were 1.08 for males and 1.22 for females.
Significant elevated incidence ratios were seen for all cancers in type 2 diabetes, excluding brain, anal (in females), testicular cancers (in men), and esophageal cancer (in females).
Melanoma and prostate cancers showed significant decreased risk, while the highest excess risks were observed for cancers of the liver and pancreas.
For type 2 diabetes, significantly increased death rates were found for cancers of the pancreas, liver, and kidney and Hodgkin's lymphoma. In females only, significant increased mortality was also found for stomach and gallbladder cancer and non-Hodgkin's lymphoma.
With regard to the impact of factors such as obesity, the researchers note that in a populationwide study, "it is not possible to explore the extent to which obesity, smoking, socioeconomic position, family history of cancer, and/or pharmaceutical treatments contributed to the observed association between diabetes and cancer."
However, studies based on cohorts with detailed information on type 2 diabetes that were able to account for obesity, lifestyle-related factors, and diabetes treatment have still observed elevated risks for a number of cancers, they point out.
"Therefore, it is unlikely that these factors explain the entire association between diabetes and cancer."
Is Hyperglycemia the Driving Cause?
As a similar level of excess risk for cancer was found for both types of diabetes (although fewer outcomes were significant for type 1 diabetes, most likely due to limited power) it is unlikely that insulin is the driving force, the researchers say.
Instead, they suggest that hyperglycemia may be a contributing factor.
"We provide evidence to suggest that high blood glucose may be the driver between diabetes and cancer," explained Ms Harding.
The study also explored the relationship between diabetes and cancer at different time periods following diabetes diagnosis, which helped to eliminate those cancers diagnosed due to detection bias or reverse causality.
"This 'detection bias' did not explain all of the association between diabetes and cancer. Cancers diagnosed many years after diabetes diagnosis are more likely to have occurred as a consequence of diabetes," concluded Ms Harding.
Ms Harding and coauthors report no relevant financial relationships.
Diabetes Care. Published online December 8, 2014. Abstract
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