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People with type 1 diabetes on higher daily doses of insulin faced a higher cancer risk, researchers found.

Daily insulin dose was significantly linked with a higher risk for cancer (HR 4.13, 95% CI 1.13-15.17) after adjustment for factors including HDL cholesterol and exercise habits in a cohort of 1,303 patients with type 1 diabetes followed for 28 years.

Incidence of newly-diagnosed cancers was 2.8 (95% CI 2.2-3.3) per 1,000 person-years overall, with 7% of participants receiving a diagnosis, reported Wenjun Zhong, PhD, of Merck Research Labs in West Point, Pennsylvania, and Yuanjie Mao, MD, PhD, of Ohio University in Athens in a research letter appearing in .

That incidence climbed with average daily insulin dose these individuals were on, Zhong and Mao found:

• Low-dose insulin (<0.5 units/kg): 2.11 per 1,000 person-years
• Medium-dose insulin (≥0.5 and <0.8 units/kg): 2.87 per 1,000 person-years
• High-dose insulin (≥0.8 units/kg): 2.91 per 1,000 person-years

Though not as strongly tied to cancer risk as daily insulin dose was, other factors that were also significantly linked included age (HR 1.09, 95% CI 1.06-1.13) and female sex (HR 2.02, 95% CI 1.28-3.19).

In the adjusted model, engaging in moderate or strenuous exercise versus a sedentary lifestyle appeared to be protective against cancer (HR 0.31, 95% CI 0.16-0.59). The same model didn't find any link between HDL cholesterol, however.

Data for the analysis was taken from participants in the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Among these individuals with type 1 diabetes that received a new cancer diagnosis, most were female (61%).

Skin cancer was the most common new cancer diagnosis among this patient population, with 27 new cases recorded. The "other" category of cancers accounted for 21 cases, breast for 15, reproductive for eight, digestive for six, head and neck for five, bone or blood for four, prostate for four, urinary for two, and thoracic for two. Two cancers were of unknown type.

A total of 58% of cancers were diagnosed towards the end of the nearly 3 decade-long follow-up -- diagnosed between years 21 and 28 of follow-up. A third developed between years 11 and 20 of follow-up, and only 9% developed within 10 years.

At the time of first cancer diagnosis, the average patient age was 50, with a diabetes duration of 25 years.

Zhong and Mao pointed out that there has been conflicting prior evidence on the link between insulin and cancer, referencing one that found no significant association between exogenous insulin treatment and cancer risk in 13 of 16 studies. They explained that this might have been due to the fact that the daily insulin dose in those cohorts was on the low side -- averaging usually less than 0.3 units/kg per day. On top of that, they said many of those patients discontinued insulin use during follow-up.

Because of this, the research duo suggested future studies aim to find out more about the link between daily insulin dose and specific cancer types.

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