Mellor DD, Georgousopoulou EN, D’Cunha NM, et al. - Given that a causal association between low HDL cholesterol and T2D has been suggested in Mendelian randomization studies, researchers focused on the impacts of gender, polymorphisms and lifestyle, all known to impact HDL cholesterol, in a prospective cohort. In the ATTICA study, recruitment of a random sample of 1,514 males (18-87 years old) and 1,528 females (18-89 years old) was done in 2001-2002. A 10-year follow-up (2011-2012) was performed on 1,485 individuals. Measurements were obtained for lipids and lipoproteins levels, glucose and insulin levels, combined with apolipoprotein A1 (apoA1) 75 G/A genotype, which is recognized to impact HDL-cholesterol. Reduced T2D risk in relation to ApoA1 and increased risk of T2D in relation to triglycerides/ApoA1 and apolipoprotein B/LDL was evident only in males. Findings revealed an impact of ApoA1 polymorphism, which is related to lower HDL cholesterol, on the predictive influences of HOMA-IR on T2D incidence, which seemed to be moderated by physical activity, implying possible scope for more targeted prophylactic strategies.