The pocket contains proline and glycine residues while Leu99 Ile174 and Trp215 residues are situated

First, we were not able to examine the long-term effect of insulin glargine on cancer although our average length of follow-up is comparable or slightly longer than previous XAV-939 studies. Second, as discussed above, there might be residual RAD001 confounding by duration or severity of diabetes, as well as by obesity, smoking, and physical inactivity. Due to lack of data about the exact extent of glycemic control, we could not examine whether hyperglycemia per se or a higher dose of insulin glargine attributes to the association with a greater risk of certain specific cancer. Third, more frequent clinical visits and hospitalizations among insulin glargine users might have led to more cancer cases being detected in these patients. However, if there was a detection bias, we would expect to see a similarly increased risk for individual sites cancers, including breast, colorectal and liver cancer. And finally, we could not exclude the possibility that some of the associations might be due to chance, as multiple individual sites of cancer were examined simultaneously. In conclusion, we did not find an increased risk of overall cancer incidence associated with insulin glargine use among type 2 diabetes patients. The positive associations between insulin glargine and pancreatic and prostate cancer definitely require further investigations. The National Taiwan University Hospital Research Ethics Committee approved the protocol of this study and waived the need for written informed consent because this is a retrospective study based on data from administrative databases and involved only minimal risk. The Taiwan National Health Insurance database includes complete outpatient visits, hospital admissions, diagnoses, prescriptions, disease and vital status for 99% of the population in Taiwan. We established a longitudinal medical history of each beneficiary by linking the computerized administrative and claims datasets, and the National Cancer and Death Registry through the civil identification number unique to each beneficiary and date of birth. From the source population, we identified beneficiaries with a first prescription of either insulin glargine or intermediate/ long-acting HI between July 1, 2004 and June 30, 2007 .

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