BackgroundInsulin resistance (IR) and the consequences of compensatory hyperinsulinemia are pathogenic factors for a set of metabolic abnormalities, which contribute to the development of diabetes mellitus and cardiovascular diseases. We compared traditional lipid levels and ratios and combined them with fasting plasma glucose (FPG) levels or adiposity status for determining their efficiency as independent risk factors for IR.MethodsWe enrolled 511 Taiwanese individuals for the analysis. The clinical usefulness of various parameters—such as traditional lipid levels and ratios; visceral adiposity indicators, visceral adiposity index (VAI), and lipid accumulation product (LAP); the product of triglyceride (TG) and FPG (the TyG index); TyG with adiposity status (TyG-body mass index [BMI]) and TyG-waist circumference index [WC]); and adipokine levels and ratios—was analyzed to identify IR.ResultsFor all lipid ratios, the TG/high-density lipoprotein cholesterol (HDL-C) ratio had the highest additional percentage of variation in the homeostasis model assessment of insulin resistance (HOMA-IR; 7.0% in total); for all variables of interest, TyG-BMI and leptin-adiponectin ratio (LAR) were strongly associated with HOMA-IR, with 16.6% and 23.2% of variability, respectively. A logistic regression analysis revealed similar patterns. A receiver operating characteristic (ROC) curve analysis indicated that TG/HDL-C was a more efficient IR discriminator than other lipid variables or ratios. The area under the ROC curve (AUC) for VAI (0.734) and TyG (0.708) was larger than that for TG/HDL-C (0.707). TyG-BMI and LAR had the largest AUC (0.801 and 0.801, respectively).ConclusionTyG-BMI is a simple, powerful, and clinically useful surrogate marker for early identification of IR.

No abstract

Objective-Scavenger receptor class B type I (SR-BI) is a multiligand cell-surface receptor that mediates the selective uptake of lipid from HDL cholesterol (HDL-C) into cells. This study hypothesized an association between functional variants in the promoter region of SR-BI gene and HDL-C levels. Methods and Results-We identified 2 novel mutations in the SR-BI gene promoter region by using single-strand conformation polymorphism. One mutation was an 11-bp CCCCGCCCCGT deletion mutation from positions Ϫ140 to Ϫ150 relative to the transcription start site, corresponding to an Sp1 binding site; the other was a C3T substitution at position Ϫ142. Twenty-six of 690 unrelated subjects were heterozygous for the Ϫ140 to Ϫ150 deletion mutation, and the allele frequency in this population was 0.02. This study showed that the deletion variant prevented binding of Sp1 to this region of the SR-BI promoter and effectively reduced transcriptional activities in HepG2 cells. Notably, the Ϫ140 to Ϫ150 deletion mutation was significantly associated with increased HDL-C levels and explained Ϸ0.5% of the variation in HDL-C levels in this population. Conclusions-A genetic variant at the SR-BI gene promoter region might explain a significant proportion of individual differences in HDL-C levels among Taiwanese Key Words: deletion Ⅲ mutation Ⅲ scavenger receptor class B type I Ⅲ HDL cholesterol E pidemiologic investigations have demonstrated an inverse relation between the plasma HDL cholesterol (HDL-C) level and the incidence of coronary heart disease (CHD). 1 The main mechanism of CHD protection of HDL-C is believed to be through reverse transport of cholesterol from arterial cells to the liver. 2 In addition, HDL-C uptake by cells involves the selective transfer of cholesterol ester to the cell without HDL protein uptake and degradation, a process termed selective lipid uptake. 3 Acton et al 4 have demonstrated that scavenger receptor class B type I (SR-BI), a multiligand cell-surface receptor isolated from Chinese hamster ovary cells by expression cloning, 5 binds closely with HDL and mediates selective cholesterol uptake in transfected cells. This receptor is mainly expressed in tissues that display selective lipid uptake in vivo, namely, the liver, adrenal gland, and testis. [4][5][6][7] Further in vivo analyses in mice and rats suggested that SR-BI is crucial in HDL metabolism. For example, SR-BI expression is upregulated in the adrenal gland, where HDL-C is used for steroid hormone synthesis, in response to depleted plasma HDL-C levels in apolipoprotein AI-knockout (KO) mice. 6 Adenovirus-mediated overexpression of SR-BI in mouse livers causes a significant reduction in plasma HDL-C levels and a corresponding increase in biliary cholesterol. 8 Targeted disruption of the SR-BI gene in mice reduced selective uptake of cholesterol ester from HDL into the liver 9 and significantly increased plasma HDL-C. 9,10 Furthermore, Acton et al 11 also found an association between several single-nucleotide polymorphisms (SNPs) in the coding r...

No abstract

No abstract