METHODS: Six hundred and thirty-six adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration-controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis.

METHODS: We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries.

FINDINGS: During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; pinteraction=0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; pinteraction=0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; pinteraction=0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; pinteraction=0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; pinteraction <0·0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2·95; 2·25-3·87; pinteraction <0·0001), but not of cardiovascular diseases or mortality.

INTERPRETATION: The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance.

STUDY DESIGN: A wide range of socio-demographic characteristics of Chinese, Malay and Indian women attending routine gynecologic care in Singapore were prospectively collected. Physical performance was objectively measured by hand grip strength and the Short Physical Performance Battery. Percent VAT was determined by dual-energy X-ray absorptiometry. Fasting serum concentrations of glucose, insulin, IL-6, TNF- α, and hs-CRP were measured.

MAIN OUTCOME MEASURE: was insulin resistance, expressed as the homeostatic model assessment of insulin resistance (HOMA-IR).

RESULTS: 1159 women were analyzed, mean age 56.3 (range 45-69) years, comprising women of Chinese (84.0%), Indian (10.2%), and Malay (5.7%) ethnic origins. The adjusted mean differences for obesity (0.66, 95% CI 0.32-1.00), VAT area in the highest vs lowest tertile (1.03, 95% CI 0.73-1.34), low physical performance (0.63, 95% CI 0.05-1.24), and highest vs lowest tertile of TNF- α (0.35, 95% CI 0.13-0.57) were independently associated with HOMA-IR. Women of Malay and Indian ethnicity had higher crude HOMA-IR than Chinese women. However, after adjustment for obesity, VAT, physical performance, and TNF- α, no differences in mean HOMA-IR remained, when comparing Chinese women with those of Malay ethnicity (0.27, 95% CI -0.12 to 0.66) and with those of Indian ethnicity (0.30, 95% CI -0.01 to 0.66).

Materials and Methods: A cross-sectional study was conducted at Hospital Universiti Sains Malaysia (Hospital USM), Health Campus, Kubang Kerian, Kelantan, Malaysia. Thirty newly diagnosed patients with PCOS attending gynecology clinic between July 2016 and April 2017 were recruited. Fasting venous blood samples were collected from the subjects. Serum AMH, insulin, adiponectin, triglycerides, high-density lipoprotein cholesterol (HDL-C), and plasma glucose levels were measured, and insulin resistance was calculated based on homeostasis model of assessment-insulin resistance (HOMA-IR). The serum AMH level was estimated, and the correlation of serum AMH level with the metabolic parameters was analyzed.

Results: The median of serum AMH levels in women with PCOS was 6.8 ng/mL (interquartile range: 7.38 ng/mL). There was a significant negative correlation between serum AMH and HOMA-IR or triglyceride levels (r = -0.49, P = 0.006 and r = -0.55, P = 0.002, respectively). A significant positive correlation was observed between serum AMH and serum HDL-C or serum adiponectin levels (r = 0.56, P = 0.001 and r = 0.44, P = 0.014, respectively) in all study subjects.