Angiopoietin-Like Protein 2 and Risk ofType2Diabetes inaGeneral Japanese Population The Hisayama Study

OBJECTIVEdTo examine, for the first time, the association between a novel inflammatory cytokine, angiopoietin-like protein (ANGPTL) 2, and the development of type 2 diabetes (T2DM). RESEARCHDESIGNANDMETHODSdA total of 2,164 community-dwelling Japanese individuals aged 40 to 79 years without diabetes were followed up for 7 years. Serum ANGPTL2 levels were divided into quartile categories at baseline:,2.15, 2.16–2.71, 2.72–3.40, and$3.41 ng/mL. During follow-up, 221 participants developed T2DM. RESULTSdIn multivariate analyses, after adjusting for comprehensive risk factors and high-sensitivity C-reactive protein (hs-CRP) levels, the risk of developing T2DM was significantly higher in the highest ANGPTL2 quartile than in the lowest quartile (hazard ratio, 1.80; 95 % CI, 1.14–2.85; P = 0.01). CONCLUSIONSdElevated serum ANGPTL2 levels were positively associated with the de-velopment of T2DM in a general population, independent of other risk factors including hs-CRP levels. Angiopoietin-like proteins (ANGPTLs),which are structurally similar toangiopoietins, are characterized by a coiled-coil domain in the N-terminus and a fibrinogen-like domain in the C-terminus. Seven ANGPTLs have been identified to date (1–3); one of them, ANGPTL2, has been shown to be ex-pressed abundantly in adipose tissues and to be a key mediator linking obesity to adipose tissue inflammation and sys-temic insulin resistance in mice (4,5). In humans, ANGPTL2 is also closely related to adiposity and inflammation (4). How-ever, the association of serum ANGPTL2 levels with the risk of developing type 2 diabetes (T2DM) has not been investi-gated to date. The objective of this study was to examine this issue in a cohort of the general Japanese population, taking into account a comprehensive range of confounders