Aims/HypothesisDiabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes.MethodsData source: MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers.ResultsOf 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74–0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36–0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76–0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83–0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma.Conclusions/InterpretationResults suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.

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OBJECTIVEThere is debate over the most appropriate adiposity markers of obesity-associated health risks. We evaluated the relationship between fat distribution and high-sensitivity C-reactive protein (hs-CRP), independent of total adiposity.RESEARCH DESIGN AND METHODSWe studied 350 people with abdominal adiposity (waist-to-hip ratio [WHR] ≥0.9 in male and ≥0.85 in female subjects) and 199 control subjects (WHR <0.9 in male and <0.85 in female subjects) matched for BMI and age. We measured hs-CRP and major cardiovascular risk factors.RESULTSParticipants with abdominal adiposity had BMI similar to that in control subjects (24.8 ± 2.5 vs. 24.7 ± 2.2 kg/m2, respectively), but significantly higher waist circumference (96.4 ± 6.0 vs. 83.3 ± 6.7 cm; P < 0.01) and WHR (1.07 ± 0.08 vs. 0.85 ± 0.05; P < 0.001). Compared with the control subjects, participants with abdominal adiposity had an adverse cardiovascular risk factor profile, significantly higher hs-CRP (1.96 ± 2.60 vs. 1.53 ± 1.74 mg/dl; P < 0.01), and a twofold prevalence of elevated CRP values (>3 mg/dl).CONCLUSIONSIn nonobese people, moderate abdominal adiposity is associated with markers of subclinical inflammation independent of BMI.

Body iron status has been suggested to be related to the development of cardiovascular disease (CVD). Biologically plausible mechanisms for this association have been described, however epidemiological studies on iron status and CVD risk have provided conflicting results. The lack of consistency is likely explained by differences in the study design, the measures used for the assessment of iron status, the definition of outcomes, and adjustment for confounders. To help clarify the available evidence, we report a systematic review of published cross-sectional, longitudinal, and intervention studies evaluating the relationship between different measures of iron status and CVD risk. The most likely scenario that emerges from the available studies is that, in the reference range, iron status has a neutral effect. Extreme conditions of iron deficiency, as well as of iron overload, are associated with modestly increased CVD risk, although with different proposed mechanisms.

Background: It is widely accepted that Type 2 Diabetes Mellitus (T2DM) and other complex diseases are the product of complex interplay between genetic susceptibility and environmental causes. To cope with such a complexity, all the statistical and conceptual strategies available should be used. The working hypothesis of this study was that two wellknown T2DM risk factors could have diverse effect in individuals carrying different genotypes. In particular, our effort was to investigate if a well-defined group of genes, involved in peripheral energy expenditure, could modify the impact of two environmental factors like age and obesity on the risk to develop diabetes. To achieve this aim we exploited a multianalytical approach also using dimensionality reduction strategy and conservative significance correction strategies.