Insulin 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. We 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. For 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). TyG-BMI is a simple, powerful, and clinically useful surrogate marker for early identification of IR.

Previous genome-wide association studies have indicated an association between CDH13 genotypes and adiponectin levels. In this study, we used mediation analysis to assess the statistical association between CDH13 locus variants and adiponectin levels, metabolic syndrome, and related metabolic phenotypes. A sample population of 530 Taiwanese participants was enrolled. Four CDH13 gene variants in the promoter and intron 1 regions were genotyped. After adjustment for clinical covariates, the CDH13 genotypes/haplotypes exhibited an association with the adiponectin levels (lowest P = 1.95 × 10⁻¹¹ for rs4783244 and lowest P = 3.78 × 10⁻¹³ for haplotype ATTT). Significant correlations were observed between the adiponectin levels and the various metabolic syndrome-related phenotypes (all P ≤ 0.005). After further adjustment for the adiponectin levels, participants with a minor allele of rs12051272 revealed a considerable association with a more favorable metabolic profile, including higher insulin sensitivity, high-density lipoprotein cholesterol levels, lower diastolic blood pressure, circulating levels of fasting plasma glucose, and triglycerides, and as a lower risk of metabolic syndrome (all P < 0.05). The mediation analysis further revealed a suppression effect of the adiponectin levels on the association between CDH13 genotypes and metabolic syndrome and its related phenotypes (Sobel test; all P < 0.001). The genetic polymorphisms at the CDH13 locus independently affect the adiponectin levels, whereas the adiponectin levels exhibit a suppressive effect on the association between CDH13 locus variants and various metabolic phenotypes and metabolic syndrome. In addition, these results provide further evidence of the association between the CDH13 gene variants and the risks of metabolic syndrome and atherosclerotic cardiovascular disease.

Plasma GDF15 concentrations were measured in 612 Taiwanese individuals without overt systemic disease. Clinical parameters, GDF15 genetic variants, and 22 biomarker levels were analyzed. We further enrolled 86 patients with PAD and 481 patients with CAD, who received endovascular intervention and coronary angiography, respectively, to examine the role of GDF15 level in predicting all-cause mortality. Significant associations were found between GDF15 genotypes/haplotypes and GDF15 levels. The circulating GDF15 level was positively associated with age, smoking, hypertension, and diabetes mellitus as well as circulating levels of lipocalin 2 and various biomarkers of inflammation and oxidative stress. Kaplan-Meier survival analysis showed that baseline GDF15 levels of above 3096 pg/mL and 1123 pg/mL were strong predictors of death for patients with PAD and CAD, respectively (P=0.011 and P<0.001). GDF15 more accurately reclassified 17.3% and 29.2% of patients with PAD and CAD, respectively (P=0.0046 and P=0.0197), compared to C-reactive protein. Both genetic and nongenetic factors, including cardiometabolic and inflammatory markers and adipokines, were significantly associated with GDF15 level. A high level of GDF15 was significantly associated with an increase of all-cause mortality in patients with high-risk PAD and in patients with angiographically documented CAD.

Recent studies suggest that hyperuricemia is a potential risk factor for cardiovascular disease (CVD). Hyperuricemia is highly heritable and is associated with sex and body weight. Previous genome-wide association studies have found that the ABCG2 single nucleotide polymorphism (SNP) rs2231142 is an important genetic factor for increased uric acid (UA) levels, and the degree of association between rs2231142 and hyperuricemia is affected by both sex and ethnicity. This investigation aimed to analyze the association between ABCG2 polymorphisms and UA levels, as well as their interactions with sex and obesity in Taiwanese. Two genetic polymorphisms around the ABCG2 gene were genotyped in 459 patients. After adjusting for clinical covariates, the rs2231142 SNP was found significantly associated with UA levels using a dominant inheritance model. Patients carrying the rs2231142-A allele had a higher frequency of hyperuricemia than those with the rs2231142-CC allele. Subgroup analysis revealed an association of rs2231142 with UA levels in male or obese patients, and there was no association in nonobese female patients. The rs2231142 SNP is associated with serum UA levels and hyperuricemia in Taiwanese patients and it occurs predominantly in male or obese patients. Hyperuricemia might be controlled differently by sex and obesity.