Much to be Learned in Relationship between Diabetes and Cancer

The headlines read, “Glargine causes cancer,” and “Possible link between insulin glargine and cancer prompts urgent call for more research.” This led many diabetes patients last year to wonder if they were putting themselves at risk by treating their chronic disease. After the blaring headlines, controversy ensued, and researchers put their nose to the grindstone to see if the link could be substantiated.

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But despite the hoopla, those claims are not only unsubstantiated, they are unwarranted and unproven, according to Jay S. Skylar, MD, professor of medicine, pediatrics and psychology, at the University of Miami’s Miller School of Medicine, who spoke today at the American Diabetes Association’s 70 Scientific Sessions, in the session “Lessons from the Diabetologia Story.”

After German, Scottish, Swedish, and British studies all investigated the relationship between glargine and cancer, the press rushed to conclusions they shouldn’t have. The German study had a large imbalance in proportion of patients in the highest disease category and insulin glargine was only administered to about 13% of participants, while human insulin was given to over 40%. There was also no information on how long each person had diabetes, the degree to which it was controlled, or their BMI.

The other three studies had similar issues. The Swedish study showed neutral risk for all cancers with insulin glargine. The Scottish study had a lopsided cohort, with 18,455 patients in the non-glargine cohort compared to 411 in the glargine group.

The British study also showed no statistical difference for all cancers. So, according to Dr. Skylar, the press was way out of line when they made those claims. In fact, the authors of the Scottish study even said that no significant difference in cancer risk was found between the groups, which they said was reassuring.

Further analysis of these studies caused several major organizations like the ADA and FDA to issue press releases of their own, imploring patients to listen to their doctors and ignore the reports that were being issued by the press. The issue seemed to be over with and Dr. Skylar would have concluded his talk there, simply stating that the press had made unwarranted claims. But then came a study from Florence, Italy about 10 days ago that was published online in Diabetes Care.

The study claims to confirm what the German study by Hemkens concluded, that there is indeed a link between glargine and cancer risk. But Dr. Skylar believes something’s amiss in the study and doesn’t believe that it confirms the German study’s claims. In the University of Florence study no significant difference was observed between cases and controls in the proportion of patients who were exposed to each insulin; cases had higher a higher defined daily dose of glargine, 0.24 versus 0.16. There was also no association of mean daily dose of glargine and cancer risk if entered as a continuous variable and incident cancer risk was associated with a dose of glargine of 0.3 U/kg/day or less—an adjusted OR of 5.43. There was no association of glargine dose with any specific cancer. Dr. Skylar also noted issues with the sample size and distribution of participants.

But Dr. Skylar’s main concerns were that there was no discussion of how insulin switchers were dealt with or how multiple types of insulin were considered in the analysis. The cases also had higher CCS comorbidity scores and less retinopathy, while the incidence of cancer was very high compared to the rest of the Tuscan population, the Tuscan average is 399 per 100,000 in men and 303 per 100,000 in women, yet the study showed 1,900 per 100,000.

To deal with the controversy, the ADA and American Cancer Society (ACS) have released a joint consensus statement stating that the link between diabetes and cancer is unclear. There may be many factors at risk, and since they have a lot of the same risk factors and biologic links, it is easy to jump to conclusions. But according to Dr. Skylar, much remains to be learned about the relationship between diabetes and cancer. It is a fertile area for research but researchers must make sure their studies are carefully designed and appropriately controlled in order to ensure the most reliable outcomes.

Dr. Skylar emphasized that physicians and patients review the ADA/ACS guidelines and recommendations for care. He then concluded with a quote that perfectly summarized his presentation:

“…claims of harm not backed by adequate evidence can provoke unnecessary alarms ad anxieties and seriously interfere with good medical practice.”

—Pocock and Smeeth