The relationship between the exposure time of insulin glargine and risk of breast and prostate cancer: An observational study of the time-dependent effects of antidiabetic treatments in patients with diabetes

摘要

Aims: To elucidate methodological questions in assessing the relationship between insulin treatment and cancer, since the risk of tumour growth generally increases with longer exposure time and higher dose of a growth promoting substance. Methods: Continuous hazard functions for risk of breast and prostate cancer were estimated in relation to exposure of insulin glargine among diabetic patients included in the record system, Diab-Base, as well as in the general population in Sweden. Results: In 7942 female diabetic patients, mean follow-up 7.0 years, 2014 patients initiated insulin glargine with a mean follow-up of 3.5 years. Among 11,613 men, mean follow-up 6.9 years, 2760 had a mean follow-up with glargine of 3.4 years. Risk of prostate cancer decreased significantly with longer exposure to insulin glargine (p = 0.032), although average risk versus non-glargine was non-significantly higher (HR 1.37, 95% CI 0.78-2.39). The breast cancer risk did not change with longer exposure to insulin glargine (p = 0.35) and the mean risk was similar for glargine and non-glargine (p = 0.12). With higher dose of insulin glargine, there was an increase in risk of prostate (p = 0.037) and breast cancer (p = 0.019). In diabetics, the mean risk of prostate cancer was decreased (HR 0.68, 95% CI 0.59-0.79) but similar for breast cancer (HR 0.95, 95% CI 0.78-1.14) compared to the general population and did not change with longer diabetes duration (p = 0.68 and p = 0.53 respectively). Conclusions: Analysing continuous hazard functions for cancer risk in relation to exposure time to an antidiabetic agent is an important complementary tool in diabetes and cancer research.