The estimates of cancer free survival for

The estimates of cancer-free survival for the groups with 10-min Phenformin levels below and above the median showed an increasing divergence over the 40-year follow-up (Fig. 2). Thus, it is unlikely that causal factors related to glucose disposal at baseline were temporary in nature. It is more likely that causality was related to some individual characteristics that were substantially constant throughout life. An example of an individual characteristic might be a polymorphism in a gene that is critical for insulin-independent uptake of plasma glucose into cells. This study had several strengths. We analyzed multiple measurements of plasma glucose, which made it possible to examine both the first and the second phase responses to an IVGTT, in a healthy cohort. In addition, we implemented a long-term prospective study design, where individuals were followed over a 40-year period to determine cancer incidence. Moreover, the data retrieved from the Cancer Registry of Norway provided complete, valid information on cancer diagnoses and vital status (i.e., death) during the time-span covered. Lastly, the cohort was representative of the age-group of men within the given time-period, with regard to cancer incidence in their counties of residence (Oslo and Akershus) (Heir et al., 2016).
Funding Sources
Conflicts of Interests
Data Availability Data are from the Oslo Ischemia Study. Public availability would compromise privacy of the respondents. According to the approval from the Norwegian Regional committees for medical and health research ethics, the data is to be stored properly and in line with the Norwegian Law of privacy protection. However, provision can be made for inspection of the data, pending ethical approval from our Ethics committee. Interested researchers can contact first author Ragnhild S Falk (r.s.falk@medisin.uio.no) or Prof. Trond Heir (trond.heir@medisin.uio.no) with requests for the data underlying our findings.
Author Contributions
Introduction The knowledge of the crucial role played by the tumor necrosis factor α (TNFα) on the pathophysiology of auto-immune inflammatory disorders, such as inflammatory bowel diseases (IBD), led to the development of a class of biological drugs that target this cytokine. Infliximab (IFX) was the first anti-TNFα approved for the treatment of IBD (Danese et al., 2015). Since its introduction, IBD patients experienced an improvement in their quality of life, a decrease on the number of bowel-related surgeries and hospitalizations, and an increase in steroid-free remission and mucosal healing rates (Gecse et al., 2016; Strik et al., 2016). Notwithstanding, and despite the therapeutic success of these biological drugs, some patients fail to respond to anti-TNFα in the induction period (primary non-responders), whereas others initially benefit from the treatment but eventually loose response (secondary non-responders) (Mould et al., 2016). Immunogenicity, i.e., the development of anti-drug antibodies, is an unavoidable drawback of biological treatments and a possible explanation for the lack or loss of response. Antibodies to infliximab (ATIs) can directly neutralize the IFX effects by interfering with the TNFα-binding domain, or can affect the drug\'s clearance rate by forming immune complexes with IFX, thereby promoting its removal from the circulating system (Gecse et al., 2016). Therapeutic drug monitoring (TDM)-based dosing is an interesting and efficient strategy to overcome IFX lack or loss of response. In order to establish an accurate algorithm to support the decision-making process on a TDM approach, many studies have attempted to elucidate IFX pharmacokinetics and to define therapeutic thresholds for IFX exposure (often using serum trough levels [TLs] as a proxy) and for ATI levels that can guide dose adjustments (Strik et al., 2016; Moore et al., 2016; Williet et al., 2016; Vande Casteele et al., 2015; Warman et al., 2015; Paul et al., 2013; Cornillie et al., 2014).