Diabetes, cancer and treatment - a mini-review.
OBJECTIVE
To conduct a systematic review of the published pre-clinical in vitro and in vivo evidence for plausible mechanisms underlying the risk of cancer associated with insulin and insulin analogues.


METHODS
The review was developed according to the PRISMA guidelines. A systematic search of Pubmed was performed using the key words: "insulin analogue", "insulin derative", "insulin homologue", "glargine", "Lantus", "degludec", "tresiba", "NPH", "lispro", "humalog", "detemir", "levemir", "glulisine", "apidra", "aspart", "novolog", "insulin treatment", "diabetes treatment", "insulin therapy" or "diabetes therapy" combined with "neoplasia", "tumor", "cancer", "carcinoma", "malignan*", "carcinog*" or " mitoge*". Eligible studies were those reporting on potential biological mechanisms, studies reporting on statistical or epidemiological associations were excluded.


RESULTS
Per October 8, 2013, the search produced 28,276 hits in Pubmed. All studies were either mechanistic speculations based on epidemiological association studies, a few randomized controlled trials (several unpublished), or non-human studies (cell cultures or animal studies). The evidence level in human terms was low.


CONCLUSIONS
In general many studies on pre-clinical in vitro and in vivo evidence for plausible mechanisms underlying the risk of cancer associated with insulin and insulin analogues exist. However, the level of evidence of a causal association between diabetes and the treatment of diabetes and cancer is low.
Peter
P
Vestergaard
Clinical Institute, Aalborg University, Room C2-201, Fredrik Bajers Vej 7C, DK-9220 Aalborg, Denmark. p-vest@post4.tele.dk.
Jakob
J
Starup-Linde
D048909:Diabetes Complications / Q000453:epidemiology* / Q000209:etiology*; D003920:Diabetes Mellitus / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D019317:Evidence-Based Medicine; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology*
D007004:Hypoglycemic Agents; D007328:Insulin