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


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.
Mannucci
Edoardo
E
Diabetes Agency, Careggi Teaching Hospital, Florence, Italy. edoardo.mannucci@unifi.it
Monami
Matteo
M
Balzi
Daniela
D
Cresci
Barbara
B
Pala
Laura
L
Melani
Cecilia
C
Lamanna
Caterina
C
Bracali
Ilaria
I
Bigiarini
Michela
M
Barchielli
Alessandro
A
Marchionni
Niccolo
N
Rotella
Carlo Maria
CM
D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology
D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine