Mingzhu Lin

Circulating neuregulin 4 levels are inversely associated with subclinical cardiovascular disease in obese adults.

Neuregulin 4 (Nrg4) has been identified as a new secreted adipokine that may protect against development of obesity and metabolic disorders. However, information is not available regarding the association between circulating Nrg4 and subclinical atherosclerosis in humans. We measured serum Nrg4 in 485 obese adult subjects (aged 40 years or older) who had the measurement of carotid intima-media thickness (CIMT) recruited from the community. Individuals with increased CIMT and carotid plaque had lower levels of circulating Nrg4 than controls (p < 0.05). The risks of increased CIMT and atherosclerotic plaque were significantly decreased by 28% and 31% [OR (95% CI): 0.72 (0.53–0.98) and 0.69 (0.50–0.96), respectively], adjusting for age, sex, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, HOMA-IR, and body fat. Importantly, individuals in the lowest quartile of serum Nrg4 were 3.70 times (p < 0.001) more likely to have increased CIMT and 2.06 times (p < 0.05) more likely to have atherosclerotic plaque than those in the highest quartile in multivariable logistic regression analyses. These findings suggest that circulating Nrg4 concentrations are inversely associated with subclinical atherosclerosis in obese adults, and indicating that circulating Nrg4 might play a role in identifying patients at high risk for CVD.

Long-term effect of exercise on improving fatty liver and cardiovascular risk factors in obese adults: A 1-year follow-up study

Exercise training can reduce hepatic fat accumulation and cardiovascular risk among patients with non‐alcoholic fatty liver disease (NAFLD), but how long these benefits extend beyond the period of active intervention is unclear. Intrahepatic triglyceride (IHTG) content, measured by proton magnetic resonance spectroscopy, and metabolic risk factors among 220 obese people with NAFLD, who were randomly assigned to vigorous/moderate exercise, moderate exercise or no exercise (control), were assessed at 1 year after the 12‐month exercise intervention. IHTG content was significantly reduced in the 2 exercise groups compared with the control group over the 12‐month active intervention. It was significantly lower (by −2.39%) in the vigorous/moderate exercise group compared with the control group at the 1‐year follow‐up (95% confidence interval −4.72 to −0.05%; P = .045). Waist circumference and blood pressure remained significantly lower in the vigorous/moderate exercise group and the moderate exercise group compared with the control group at the 1‐year follow‐up. Visceral adipose fat remained significantly reduced, but with no differences among 3 groups. These findings suggest 12‐month exercise intervention induced reductions in hepatic fat accumulation, abdominal obesity and blood pressure for up to 1 year after the active intervention, with some attenuation of the benefits.

Correlations of non-alcoholic fatty liver disease and serum uric acid with subclinical atherosclerosis in obese Chinese adults.

Existing evidence about the associations of non‐alcoholic fatty liver disease (NAFLD) and serum uric acid (SUA) with subclinical atherosclerosis is controversial. The aim of the present study was to examine the associations of NAFLD and SUA with subclinical atherosclerosis.

Hepatic fat content is a determinant of metabolic phenotypes and increased carotid intima-media thickness in obese adults

Individuals with metabolically healthy obesity (MHO) are at relatively low risk for the development of metabolic abnormalities and subclinical atherosclerosis. This study aims to examine whether hepatic fat accumulation determines metabolic phenotype of obesity and associated with subclinical atherosclerosis. A total of 485 obese adults (aged 40–65 years) who received magnetic resonance spectroscopy were divided into metabolically abnormally obesity (MAO) and MHO groups according to metabolic status. MHO individuals had lower levels of intrahepatic triglyceride (IHTG) content and carotid intima-media thickness (CIMT) than MAO individuals. In multivariable linear regression analyses, IHTG content was independently associated with metabolic syndrome components and CIMT. Based on receiver operating characteristic curve analysis, the IHTG content displayed a higher area under the curve (AUC) for detecting the MAO phenotype (AUC = 0.70, 95%CI = 0.65–0.75) and increased CIMT (AUC = 0.60, 95%CI = 0.54–0.66) than BMI, waist circumference, and body fat percent. MHO individuals were 1.9 times (p < 0.001) more likely to have metabolic syndrome per 1 SD change in IHTG content in multivariable-adjusted models. Likewise, the risk for high CIMT increased 29% per 1 SD change in IHTG content [OR (95% CI):1.29(1.01–1.64)]. These findings suggest that hepatic fat is a potential predictor of metabolically unhealthy obesity phenotype and subclinical atherosclerosis.

Elevated Serum Fibroblast Growth Factor 21 Levels in Patients With Hyperthyroidism.

CONTEXT Recent evidence from animal studies indicates that fibroblast growth factor 21 (FGF21), an endocrine hormone that regulates glucose, lipid metabolism, and energy homeostasis, is regulated by T3. However, the role of FGF21 in hyperthyroid patients is unknown. OBJECTIVE The objective was to study serum FGF21 levels in hyperthyroid patients and the association of serum FGF21 levels with hyperthyroidism. DESIGN AND SETTING This was a case-control study. PATIENTS AND INTERVENTIONS A total of 119 hyperthyroid patients and 108 healthy subjects were recruited. Of them, 41 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism was obtained. MAIN OUTCOME MEASURES Serum FGF21 levels were determined using the ELISA method. RESULTS Serum FGF21 levels were significantly elevated in hyperthyroid patients as compared with normal subjects [median 290.67 (interquartile range, 156.60-502.33) vs 228.10 (169.85.25-320.10) pg/mL; P < .001]. After thionamide treatment, serum FGF21 levels in hyperthyroid patients declined markedly from 249.10 (139.10-444.00) to 106.90 (38.70-196.15) pg/mL (P < .001). Logistic regression revealed that FGF21, basal metabolic rate, low-density lipoprotein cholesterol, and alanine transaminase were significantly associated with hyperthyroidism. With adjustment for potential confounders, serum FGF21 remained independently associated with hyperthyroidism, with an adjusted odds ratio of 3.123 (95% confidence interval, 1.306-7.468) (P = .010). CONCLUSION Serum FGF21 levels were elevated in patients with hyperthyroidism and declined after thionamide treatment. And serum FGF21 level was independently associated with hyperthyroidism.

Serum fetuin-B is positively associated with intrahepatic triglyceride content and increases the risk of insulin resistance in obese Chinese adults: A cross-sectional study: 在中国肥胖成年人中血清胎球蛋白B水平与肝内甘油三酯含量呈正相关并增加胰岛素抵抗风险:一项横断面研究

Fetuin‐B impairs insulin action in myotubes and hepatocytes and causes glucose intolerance in mice. This study explored the correlation between serum fetuin‐B and intrahepatic triglyceride (IHTG) content, and the association between fetuin‐B and the risk of insulin resistance in the general adult population.

Fetuin-B links nonalcoholic fatty liver disease to type 2 diabetes via inducing insulin resistance: Association and path analyses

Objective Laboratory models suggested that Fetuin‐B impaired insulin action in myotubes and hepatocytes and caused glucose intolerance in mice. We aimed to explore the independent associations and pathways among serum Fetuin‐B, nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). Methods A cross‐sectional study of 1318 obese adults who underwent serum Fetuin‐B test and hepatic ultrasonography scanning was conducted in Xiamen, China. Multivariable logistic regression was used to calculate adjusted odds ratio (OR) and 95% confidence intervals (CI) of serum Fetuin‐B level and NAFLD for T2D in different models with adjustment for potential confounders. Structural equation modeling (SEM) was used to examine the paths among NAFLD, serum Fetuin‐B, metabolic/insulin resistance syndrome and T2D. Results Subjects with T2D or NAFLD showed significantly increased serum Fetuin‐B levels compared to their controls (4.25 ± 1.35 vs. 4.08 ± 1.38 &mgr;g/ml for diabetes; and 4.26 ± 1.41 vs. 4.07 ± 1.33 &mgr;g/ml for NAFLD; both p‐values < 0.05). NAFLD and higher serum Fetuin‐B were significantly associated with higher risk of T2D with adjustment for sociodemographic and lifestyle habits; and the adjusted ORs (95%CIs) were 2.90 (2.17–3.87, p < 0.001) and 1.16 (1.01–1.32, p = 0.032), respectively. With further adjustment for metabolic/insulin resistance syndrome (BMI, systolic and diastolic BP, triglyceride, total cholesterol, HDL‐ and LDL‐cholesterol, HOMA‐IR and serum uric acid), NAFLD but not serum Fetuin‐B was significantly associated with increased risk of T2D (ORs (95%CIs): 1.58 (1.12–2.21, p = 0.009) and 1.07 (0.92–1.23, p = 0.384), respectively). A one pathway model by using SEM fitted well (χ2 = 497.92, p < 0.001; CFI = 0.965; TLI = 0.926; and RMSEA = 0.097) and showed that NAFLD increased serum Fetuin‐B and elevated Fetuin‐B increased fasting insulin level, which in turn induced insulin resistance and T2D. Besides, NAFLD increased the risk of T2D directly in addition to its indirect effects of inducing metabolic/insulin resistance syndrome which in turn increased the risk of T2D. Conclusions Fetuin‐B links NAFLD to T2D via inducing insulin resistance, and NAFLD contributes to the pathogenesis of T2D via multiple mechanisms.

The rs4686434 variant in the fetuin B (FETUB) locus is associated with intrahepatic triglyceride content in obese Chinese adults: FETUB rs4686434 and IHTG

This study explored associations of genetic variants in the fetuin B (FETUB) locus with intrahepatic triglyceride (IHTG) content.

Effect of exenatide after short-time intensive insulin therapy on glycaemic remission maintenance in type 2 diabetes patients: a randomized controlled trial

Early short-term intensive insulin (STII) therapy can induce drug-free glycemic remission for up to 1 year in half of newly diagnosed type 2 diabetic mellitus (T2DM) patients. Whether exenatide following STII therapy will induce higher long-term glycaemic remission is currently unknown. To assess the effect of STII+ exenatide therapy, compared with STII only, on maintenance of glycaemic remission in newly diagnosed T2DM patients. In this randomized, parallel-group, open-label, controlled trial, 129 patients (66 in STII+ exenatide group and 63 in STII only group) firstly completed 3-week STII therapy, then STII+ exenatide group was treated with exenatide for 12 weeks further. The cumulative probabilities of 1-year and 2-year glycaemic remission in STII+ exenatide group were 68.2 ± 5.7% and 53.0 ± 6.1%, which were significantly higher than STII only group (36.5 ± 6.1% and 31.8 ± 5.9%) (p-values < 0.001). Patients in STII+ exenatide group, compared with STII only group, showed significantly decreased levels of waist (82.2 (81.0, 83.5) cm v.s. 84.2 (82.7, 85.7) cm, p = 0.048) and HbA1c (5.83 (5.60, 6.06)% v.s. 6.49 (6.20, 6.77)%, p < 0.001) after 12-week exenatide treatment, but these differences disappeared after 1-year and 2-year follow-up. As conclusions, Improved effect of sequential exenatide after STII therapy on maintenance of glycaemic remission only occurred during exenatide treatment and lost upon treatment cessation.

Common genetic variants in the FETUB locus, genetically predicted fetuin-B levels, and risk of insulin resistance in obese Chinese adults

Abstract Elevated serum fetuin-B is suggested to be associated with insulin resistance, but it is unknown if this association is causal. The aim of this study was to explore the potential causal relationship between fetuin-B and insulin resistance. We used Mendelian randomization analysis by incorporating information of genetic variants in FETUB and serum fetuin-B concentrations with insulin resistance in 1148 obese Chinese adults. Common genetic variants (FETUB rs4686434, rs6785067, and rs3733159) were significantly associated with serum fetuin-B concentrations but not with insulin resistance. Higher serum fetuin-B levels were significantly associated with increased homeostasis model assessment of insulin resistance (HOMA-IR) (0.17 [95%CI: 0.01 to 0.32, P = .037] 10−6 mol IU L−2 higher per SD). However, Mendelian randomization analysis using 3 single-nucleotide polymorphisms as instrumental variables did not support a significant association between genetically predicted fetuin-B levels and HOMA-IR (−0.09 [95%CI: −0.62 to 0.44, P = .738] 10−6 mol IU L−2 lower per SD). The regression coefficients for measured and genetically predicted fetuin-B concentrations on HOMA-IR were significantly different (P <.001). This study suggests the association between fetuin-B and insulin resistance may not be causal. Future studies on the nongenetic determinants of serum fetuin-B concentration to assess if such unmeasured factors may confound the association between fetuin-B and insulin resistance as well as more pathway analysis for this association are warranted.