Doses of insulin and its analogues and cancer occurrence in insulin-treated type 2 diabetic patients

Abstract

Objective: Recent epidemiological studies suggested that some insulin analogues could be associated with increased risk of cancer. The present study is aimed at assessing the long-term association of different insulin analogues with cancer incidence.

Research design and methods: A nested case-control study dataset was generated from the cohort study dataset (n = 1,340 insulin-treated diabetic outpatients) by sampling control subjects from the risk sets. For each case subject, the control subjects (up to five) were chosen randomly from those members of the cohort who are at risk for the same follow-up time of the case subject. Five-year age classes, sex, and BMI classes (<18.5, 18.5-24.9, 25-29.9, and >or=30 kg/m(2)) were considered as additional categorical matching variables.

Results: During a median follow-up of 75.9 months (interquartile range 27.4-133.7), 112 case subjects of incident cancer were compared with 370 matched control subjects. A significantly higher mean daily dose of glargine was observed in case subjects than in control subjects (0.24 IU/kg/day [0.10-0.39] versus 0.16 IU/kg/day [0.12-0.24], P = 0.036). Incident cancer was associated with a dose of glargine >or=0.3 IU/kg/day even after adjusting for Charlson comorbidity score, other types of insulin administration, and metformin exposure (odds ratio 5.43 [95% CI 2.18-13.53], P < 0.001). No association between incident cancer and insulin doses was found for human insulin or other analogues.

Conclusions: The possibility of association between cancer and higher glargine doses suggests that dosages should always be considered when assessing the possible association of insulin and its analogues with cancer.

Figure 1

Risk of cancer associated with doses of each insulin type ≥0.3 IU/kg/day, adjusted for comorbidity, exposure to metformin, and doses of other types of insulin. ○, all case subjects; ●, after exclusion of case subjects with cancer occurring within the first 12 months of observation and of their matched control subjects.