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"At-risk" severely obese subjects are characterized by insulin resistance, and higher visceral fat and plasma lipid levels compared with metabolically healthy obese (MHO) subjects, although both groups have a high BMI and fat mass. The aim of this study was to measure several serum adipokines and gastrointestinal hormones in a young severely obese population from Southern Italy to identify biochemical markers of the "at-risk" insulin-resistant obese profile. We studied 160 unrelated white young adults (mean age = 25.2 years, mean BMI = 44.9 kg/m(2), 65% women) affected by obesity for at least 5 years. Serum concentrations of glucagon, ghrelin, gastric inhibitory peptide, glucagon like peptide-1, interleukin-6, tumor necrosis factor α, leptin, adiponectin, adipsin, and visfatin were measured. The leptin/adiponectin (L/A) ratio and fatty liver index (FLI) were calculated. We found a prevalence of 21.3% of MHO patients in our young severely obese patients. At univariate analysis, the "at-risk" group had higher mean levels of BMI (P < 0.0001), leptin (P = 0.039, men) and the L/A ratio (P = 0.003), and lower mean levels of visfatin (P = 0.026) than the MHO group. The L/A ratio, serum triglycerides, and male sex were significantly associated with "at-risk" obesity and accounted for 19.5% of insulin resistance at multivariate analysis. In conclusion, we demonstrate that a high serum L/A ratio and high levels of serum triglycerides may be markers of "at-risk" obesity, independent of waist circumference (WC) and BMI, in young severely obese population.

Antithrombin is a major plasma protein inhibitor of proteinases generated during blood coagulation; it plays an important role in the regulation of thrombin in blood. The anticoagulant heparin greatly accelerates the rate of inactivation of proteinases by antithrombin, predominantly through its well defined, highly specific binding reaction with the inhibitor, but also through a less strictly defined interaction with some of the proteinases (such as thrombin). There is evidence for an analogous acceleratory mechanism in vivo, that functions by the binding of antithrombin to a subpopulation of heparan sulphate proteoglycans intercalated in the surface of endothelial cells. The location and structure of the gene for antithrombin are known. Both its overall organization and the structure of the subdomains of the expressed protein can be considered in terms of their relationships to a serine proteinase inhibitor superfamily, which is believed to have evolved from a common ancestor. The region of the antithrombin gene 5' to the coding region has been characterized. Unlike other members of the serpin family, there is no TATA-like promoter sequence. Two enhancer sequences have been identified that are homologous to enhancer regions of other genes. There are two polymorphisms: an intragenic polymorphism arising from a translationally silent A to G transition in codon 305, and a length polymorphism arising from the presence of 32 bp or 108 bp non-homologous sequences 345 bp upstream from the translation initiation codon. Inherited deficiency of antithrombin is associated with familial thromboembolism. The molecular genetic basis of some subtypes of deficiency is increasingly yielding to investigation. It is interesting to note that a number of mutations have been identified in CpG dinucleotides, supporting the suggestion that this dinucleotide sequence may represent a mutation hotspot in the human genome.