New Study Hints Cancer Risk Increased in Type 1 Diabetes

Liam Davenport

March 01, 2016

Type 1 diabetes is associated with an increased risk of a range of non–sex-specific cancers, in particular soon after the diabetes diagnosis, the results of a new multicountry registry study indicate.

Looking at over 9000 incident cancers across almost four million person-years in individuals with type 1 diabetes, the researchers found that rates of stomach, liver, pancreatic, and kidney cancer were increased in both men and women compared with the general population.

The cancer risk was more than doubled in men and women during the first year after diabetes diagnosis. However, the risk fell back to population levels during subsequent years, an effect that may be due to increased scrutiny of newly diagnosed diabetes patients.

Lead author Bendix Carstensen, MSc, Steno Diabetes Center, Gentofte, Denmark, told Medscape Medical News: "From a population perspective, I think the major conclusion is that the excess risk of cancer among persons with type 1 diabetes is not a major worry.

"It turns out that the types of cancer that are elevated among type 1 diabetes patients are pretty much the same as those that are elevated among type 2 diabetes patients, and the elevation among type 1 diabetes patients is somewhat smaller than the elevation found among type 2 diabetes patients."

A previous study reported by Medscape Medical News, involving approaching one million Australian diabetes patients, indicated that both type 1 and type 2 diabetes patients had increased risks of developing cancer, although the risk was higher with type 2 diabetes.

Linking Diabetes and Cancer Registries

Mr Carstensen emphasized that it was possible to conduct the current study, which was published online in Diabetologia on February 29, only because the countries involved maintain registers of people with diabetes and those with cancer and that it is possible to link them.

He explained that diabetes registration is "fairly recent," beginning in the 1980s and 1990s. "That means that it's only people who have a diagnosis of diabetes after that date...and that means it's only fairly young people that we can classify as type 1 diabetes," he said.

There are consequently few type 1 diabetes patients with cancers within each diabetes national registry, "and that's why it has been done in multiple countries in order to get enough information."

For the current study, the team was able to draw on nationwide diabetes registers in Australia (for the years 2000–2008), Denmark (1995–2014), Finland (1971–2012), Scotland (1995–2012), and Sweden (1987–2012). These were then linked to their respective national cancer registries to provide the incidence of cancers in type 1 diabetes patients and in the general population.

Overall, there were 9149 first-incident cancers over 3.9 million person-years of follow-up across the five registries. The majority of cancer cases occurred between the ages of 40 and 60 years, with a median age at diagnosis of 51.1 years.

The overall hazard ratio (HR) for type 1 diabetes patients to develop cancer compared with the general population was 1.01 for men and 1.07 for women. When sex-specific cancers, including prostate, testicular, breast, cervical, endometrial, and ovarian cancer, were excluded, the HRs became 1.19 and 1.17, respectively.

The results indicate that the risk of developing cancer in type 1 diabetes was increased for tumors of the stomach (HRs, 1.23 in men and 1.78 in women), the liver (HRs, 2.00 and 1.55, respectively), the pancreas (HRs, 1.53 and 1.25, respectively), and the kidney (HRs, 1.30 and 1.47, respectively).

The risk of cancer of the endometrium was also increased in women (HR, 1.42), but the risk of prostate cancer was reduced in men with type 1 diabetes (HR, 0.56) and the risk of breast cancer was lower in women with the condition vs the general population (HR, 0.90).

Just a Consequence of Increased Surveillance, Rather Than Biology?

Mr Carstensen acknowledged that the definition of type 1 diabetes used in the study — defined as a recorded diabetes diagnosis below 40 years of age — means that some patients with type 2 diabetes will be included in the study population. However, he emphasized that it would be only a "small fraction."

To account for this, the team repeated the analyses with a definition of type 1 diabetes as a diabetes diagnosis at 35 years of age or younger, and again with a cutoff of 30 years of duration.

There were no differences in the overall pattern of results using these different definitions. However, Mr Carstensen said: "If you make a tighter definition of what type 1 diabetes is, you have fewer persons, basically, and shakier results. But the type of results is the same."

Given the heterogeneity of the impact of type 1 diabetes between different types of cancers, Dr Carstensen believes that there are multiple potential mechanisms linking the two conditions: "I don't think that anyone thinks it's the same mechanism that is behind the associations between diabetes and different types of cancer."

However, one factor that is unlikely to be driving the link between cancer and diabetes is that of glucose-lowering medications. As the authors note in the paper, the increased incidence of cancer in type 1 diabetes patients is lower than that previously reported in patients with type 2 disease.

Another notable finding is that the increased incidence of cancer decreased with diabetes duration.

The HR for overall cancer occurrence in the first year following diabetes diagnosis was 2.28 in men and 2.34 in women, which fell to 1.23 and 1.03, respectively, following the first year after diagnosis.

Mr Carstensen believes that this reflects people newly diagnosed with diabetes being "much more intensely looked after in the healthcare system."

He explained: "Suppose you didn't have a diagnosis of type 1 diabetes, the cancers that you are carrying might not have been diagnosed until sometime in the next 2 or 3 years.

"But because you get this diagnosis of type 1 diabetes, you are under increased scrutiny, and then you have your cancer diagnosis earlier than you would do otherwise.

"You could say there's no biology in it; that it's a surveillance thing," he concluded.

This study was funded by the European Foundation for the Study of Diabetes. Mr Carstensen is a stockholder of Novo Nordisk and an employee of the Steno Diabetes Center, a diabetes clinic and research institution owned by Novo Nordisk. Disclosures for the coauthors are listed in the article.

Diabetologia. Published online February 29, 2016. Article


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