Cancer and Type 1 Diabetes: Insulin an Unlikely Carcinogen

Becky McCall

September 22, 2014

VIENNA — A new population-based study from 5 countries has found that, overall, new cancer incidence appears to be about the same for type 1 diabetes as it is for type 2 diabetes patients.

The findings also likely rule out any major carcinogenic effect of insulin in type 1 diabetes patients, said Bendix Carstensen, MSc, statistician at the Steno Diabetes Center, a research hospital owned by Novo Nordisk, in Gentofte, Denmark, who presented his findings at this year's European Association for the Study of Diabetes 2014 Meeting.

Type 2 diabetes patients are known to be at increased risk for certain cancers, but there is little information on the risk in type 1 patients, as most studies on cancer in diabetes look at all patients, so effectively, mainly type 2 diabetes, he explained.

To examine cancer incidence specifically in type 1 diabetes, he and his colleagues used data on type 1 diabetes patients drawn from diabetes registers and linked to national cancer registers in Denmark, Sweden, Finland, Scotland, and Australia.

"This way, we know who, among the type 1 diabetes patients, has acquired a cancer and when," he explained. They also compared these cancer rates among the type 1 diabetes patients with the background rate of cancer in the entire population in each country.

The findings show that "the general cancer pattern in type 1 diabetes is the same as in all diabetes patients, and there's no overall excess in type 1 patients vs the general population," Mr. Carstensen said.

And he added: "I think we can exclude a major carcinogenic effect of insulin in type 1 diabetes patients — if there were such an effect we would have seen an increase in some cancer rates as duration [of diabetes] rises."

Slight Excess Risk of Cancer Seen in Women With Type 1 Diabetes

There were a total of almost 9369 cancers among type 1 diabetes patients during 4.6 million person-years of follow-up in the 5 countries, with median age at cancer diagnosis of 51 years.

Patients had their type 1 diabetes diagnosed before the age of 40. Follow-up was carried out between date of diagnosis and death or end of study.

The overall rate ratio (RR) for all cancer for all type 1 patients and the effect of time since type 1 diabetes diagnosis were calculated with adjustment for age, date of follow-up, and date of birth.

When cancer rates in type 1 patients were compared with those in the entire populations of each of the 5 countries and stratified by gender, "a remarkable heterogeneity of rate ratio was seen among men," reported Mr. Carstensen.

"If we pool all the results then we get a rate ratio among men of 1, and a rate ratio of 1.04 among women."

One notable exception was Swedish men, who showed a surprisingly low rate ratio [around 0.88], he noted.

"Overall, there is no excess risk among men, and a small excess risk among women," he said.

"Also, if exogenous insulin has any effect on cancer occurrence, this should be reflected," he said, but they saw no evidence for this.

Mr Carstensen noted one limitation, that the patients included in the study were still relatively young in terms of risk for cancer, so the findings may change as they grow older, he pointed out.

Cancer Pattern in Type 1 Similar to Type 2 Diabetes

Regarding cancer sites, the findings showed a similar pattern to that found in patients with type 2 diabetes: ie, an increased risk of certain types of cancer and a reduction in risk for others compared with the general population.

Rate Ratios From Different Cancer Sites for Type 1 Diabetes Patients

Type of Cancer Men, RR Women, RR
Stomach 1.19 1.75
Colorectal 1.13 1.09
Liver 2.18 1.63
Pancreatic 1.70 1.36
Kidney 1.29 1.42
Thyroid 1.27 1.48
Endometrial 1.53

With respect to reduced risk, there was a 10% lower risk of breast cancer in women with type 1 diabetes (RR = 0.89); and among men, a 40% lower rate of prostate cancer (RR = 0.59) and a 10% lower rate of testicular carcinoma (RR = 0.89).

Mr. Carstensen said that it is a recognized phenomenon that there is a high cancer incidence rate ratio between diabetes and nondiabetes patients 6 to 12 months after diagnosis of diabetes, "but this is usually attributed to increased surveillance of newly diagnosed people," he explained.

Indeed, they found a strong effect of diabetes duration, with an RR of 2.5 for cancers during the first year, decreasing to less than 1.2 after 2 to 5 years.

Mr. Carstensen also noted that they did not have data on body mass index, and some of the increase in risk of certain cancers could be due to obesity; however, this likely plays a smaller role in type 1 diabetes than in type 2, he said.

Moderating the session, Edwin Gale, MD, emeritus professor at the University of Bristol, United Kingdom, remarked, "This is a beautiful study, and I just wonder about one thing. One conclusion you didn't make was that hyperglycemia itself is not a risk factor for cancer. Is this secure?"

Mr. Carstensen answered that he had no data on glucose levels and that more specific cohort studies with this information would be required to answer this question.

The study was supported by the European Foundation for the Study of Diabetes. Mr. Carstensen has declared he has shares in Novo Nordisk worth approximately half his annual salary. Dr. Gale has reported no relevant financial relationships.

European Association for the Study of Diabetes; September 19, 2014; Vienna, Austria. Abstract 245


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