Diagnosis and genetic analysis of a case with Bardet-Biedl syndrome caused by compound heterozygous mutations in the BBS12 gene.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy, which is caused by mutations mainly in genes encoding BBSome complex and IFT complex. Here, we reported a 21-year-old female with BBS characterized by three primary features including obesity, retinitis pigmentosa sine pigmento and bilateral renal cysts. She also had some secondary features such as diabetes mellitus, nonalcoholic fatty liver disease, subclinical hypothyroidism and mild conductive hearing damage. Whole exome sequencing revealed two compound heterozygous mutations in exon 2 of the BBS12 gene (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) in this patient. Sanger sequencing showed that her father and mother carried c.188delC (p.T63fs) and c.1993_1995del (p.665_665del) variants, respectively, while her parents were free of BBS-related symptoms. In conclusion, this case reported two novel mutations (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) of the BBS12 gene in a girl presented with BBS, which provides novel genetic resources for studies of the disease. Meanwhile, the BBS case shows the entire development progress from her birth to adulthood, which helps facilitate clinicians' understanding of BBS.

Identification of circulating sphingosine kinase-related metabolites for prediction of type 2 diabetes.

BACKGROUND: Sphingosine Kinase (SphK) that catalyzes sphingosine (Sph) to sphingosine 1-phosphate (S1P), plays a key role in both sphingolipid metabolism and cellular signaling. While SphK has been implicated in type 2 diabetes mellitus (T2DM), it is unexplored in humans. Herein, we investigated whether circulating SphK-related metabolites are associated with T2DM incidence in an established prospective cohort. METHODS: Levels of SphK-related sphingolipid metabolites, including Sph, S1P, dihydrosphingosine (dhSph) and dihydro-S1P (dhS1P) in serum were measured by targeted-lipidomic analyses. By accessing to an established prospective cohort that involves a total of 2486 non-diabetic adults at baseline, 100 subjects who developed T2DM after a mean follow-up of 4.2-years, along with 100 control subjects matched strictly with age, sex, BMI and fasting glucose, were randomly enrolled for the present study. RESULTS: Comparison with the control group, medians of serum dhS1P and dhS1P/dhSph ratio at baseline were elevated significantly prior to the onset of T2DM. Each SD increment of dhS1P and dhS1P/dhSph ratio was associated with 53.5% and 54.1% increased risk of incident diabetes, respectively. The predictive effect of circulating dhS1P and dhS1P/dhSph ratio on T2DM incidence was independent of conventional risk factors in multivariate regression models. Furthermore, combination of serum dhS1P and dhS1P/dhSph ratio with conventional clinical indices significantly improved the accuracy of T2DM prediction (AUROC, 0.726), especially for normoglycemic subjects (AUROC, 0.859). CONCLUSION: Circulating levels of dhS1P and dhS1P/dhSph ratio are strongly associated with increased risk of T2DM, and could serve as a useful biomarker for prediction of incident T2DM in normoglycemic populations.

The PNPLA3 rs738409 C>G variant interacts with changes in body weight over time to aggravate liver steatosis, but reduces the risk of incident type 2 diabetes.

AIMS/HYPOTHESIS: The rs738409 C>G variant of the patatin-like phospholipase domain containing 3 gene (PNPLA3) increases the risk of non-alcoholic fatty liver disease (NAFLD) with no predisposition for insulin resistance. In this study, we aimed to investigate the influence of PNPLA3 polymorphisms on liver fat content (LFC) and glucose metabolic variables, and the associations between these, during the natural course of body weight changes in a Chinese adult cohort. METHODS: The LFC, measured using a quantitative ultrasound method, was prospectively monitored in 2189 middle-aged and elderly adults from the Shanghai Changfeng Study, together with changes in body weight and metabolic variables. General linear models were used to detect interactive effects between the PNPLA3 rs738409 genotype and 4 year changes in body weight on liver steatosis and glucose metabolism. RESULTS: The PNPLA3 homozygous GG genotype dissociated the changes in the LFC and OGTT 2 h post-load blood glucose (PBG) in relation to 4 year changes in body weight. PNPLA3 GG genotype carriers showed greater increases in the LFC and serum alanine aminotransferase (ALT) but lower PBG elevation and incident diabetes than PNPLA3 wild-type (CC) genotype carriers exhibiting the same degree of body weight increase. The interactions between the PNPLA3 genotype and changes in body weight on the LFC (false discovery rate [FDR]-adjusted pinteraction = 0.044) and ALT (FDR-adjusted pinteraction = 0.044) were significant. Subgroup analyses showed that the effect of the PNPLA3 GG genotype on changes in the LFC and PBG was only observed in metabolically unhealthy participants with insulin resistance or abdominal obesity. CONCLUSIONS/INTERPRETATION: The PNPLA3 GG genotype interacted with changes in body weight to aggravate liver steatosis but reduced the risk of incident type 2 diabetes in metabolically unhealthy participants.

Association of visceral adiposity and its longitudinal increase with the risk of diabetes in Chinese adults: A prospective cohort study.

OBJECTIVE: A Chinese visceral adiposity index (CVAI) was recently established to estimate the visceral fat area in Chinese adults. This study aimed to investigate the risk of incident prediabetes and diabetes in relation to visceral adiposity calculated by CVAI. METHODS: A total of 2558 subjects with normal plasma glucose levels from the Shanghai Changfeng Study were enrolled in a prospective cohort study. The independent associations of basal visceral fat area by CVAI and its longitudinal change with incident prediabetes and diabetes were identified using Cox regression analyses. RESULTS: During an average of 4.4 years of follow-up, 546 (21.3%) and 99 (3.9%) of 2558 nondiabetic subjects developed prediabetes and diabetes, respectively. Visceral fat area by CVAI and its longitudinal increase were independently associated with incident prediabetes and diabetes in Chinese adults. In a multivariable-adjusted regression model, CVAI, as well as its annual change, was the strongest independent predictor of incident prediabetes (HR, 1.383 [1.162-1.647]) and diabetes (HR, 1.607 [1.092-2.364]) compared with other estimates of obesity (BMI and waist circumference). Receiver operating characteristic curve analyses showed that CVAI had better performance than BMI and waist circumference for the prediction of prediabetes and diabetes in Chinese adults. CONCLUSIONS: Visceral adiposity plays a pivotal role in the pathogenesis of diabetes, and the visceral adiposity estimated by CVAI is superior to the traditional estimates of obesity for the prediction of incident prediabetes and diabetes in Chinese adults.

The association of liver fat content and serum alanine aminotransferase with bone mineral density in middle-aged and elderly Chinese men and postmenopausal women.

BACKGROUND: Recent studies have linked non-alcoholic fatty liver disease (NAFLD) to a reduced bone mineral density (BMD). We aimed to detect the quantitative association of liver fat content (LFC) and serum alanine aminotransferase (ALT) with BMD in a middle-aged and elderly Chinese population. METHODS: The lumbar spine, hip and whole body BMDs were measured using dual-energy x-ray absorptiometry (Lunar iDXA, GE Healthcare) in 1659 Chinese (755 men and 1028 postmenopausal women) from Shanghai Changfeng community. Liver fat content was quantified via an ultrasound quantitative method. Multivariate linear regression analyses were carried out to determine the independent association of LFC and serum ALT with BMD and bone metabolic biomarkers. We also attempted to investigate the synergistic association between LFC and ALT as risk factors for bone mineral loss in Chinese. RESULTS: Subjects with higher LFC had significantly lower BMD at all skeletal sites. Univariate correlation analysis showed that both LFC and ALT were inversely associated with BMD at the spine (r = -0.116, P < 0.001 and r = -0.102, P = 0.005), hip (r = -0.095, P = 0.014 and r = -0.075, P = 0.041) and whole body sites (r = -0.134, P < 0.001 and r = -0.164, P < 0.001) in men. After confounders were controlled for, LFC and ALT remained associated with BMD and bone formation biomarkers in men, but not postmenopausal women. When both NAFLD and elevation of ALT were present, there was a significant synergistic worsening of the BMDs at all bone sites. CONCLUSIONS: Liver fat content and serum ALT were inversely correlated with BMD in middle-aged and elderly men. The underlying mechanism might relate to a reduction in osteoblast activity. Elevation of the hepatotoxic biomarker ALT may indicate high risk for osteoporosis in patients with NAFLD.

A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

[Liver disease spectrum in hospitalized type 2 diabetes and related risk factors analysis of non-alcoholic fatty liver disease].

OBJECTIVE: To explore the liver disease spectrum in patients with type 2 diabetes (T2DM) and the risk factors of non-alcoholic fatty liver disease (NAFLD). METHODS: From September 2009 to October 2011, 1069 hospitalized patients with T2DM in Department of Endocrinology and Metabolism were involved in the study. The history informations, results of laboratory examination, hepatic ultrasound and hepatic proton magnetic resonance spectrum ((1)H MRS) of all patients were collected to analysis. RESULTS: (1) The detectable rate of raised liver enzymes in T2DM patients was 28.7% (307/1069), composed mainly of NAFLD (39.4%, 121/307). After excluding the factors such as alcoholic abuse, viral hepatitis, the detect rate of raised liver enzymes in T2DM patients was 26.9% (185/688). (2) The detectable rate of fatty liver by ultrasound in T2DM patients was 56.7% (500/882), composed mainly of NAFLD (72.6%, 363/500), and the detectable rate of NAFLD was 58.0% (363/626). (3) The detectable rate of fatty liver by hepatic (1)H MRS was 72.8% (227/312), composed mainly of NAFLD (69.6%, 158/227). The detectable rate of NAFLD was 69.6% (158/227). (4) Of the three methods for diagnosing NAFLD, (1)H MRS had the highest detectable rate, followed by ultrasound, and the hepatic enzymes was the lowest. Set the hepatic (1)H MRS as gold diagnosing standard of NAFLD, the combination of hepatic enzymes and ultrasound increase the sensitivity. The optional cut-off points of ALT were 19.7 U/L (male, ROCAUC = 0.689, P < 0.01) and 17.0 U/L (female, ROCAUC = 0.727, P < 0.01). (5) Logistic stepwise regression analysis showed sex, BMI, hemoglobin, fasting C-peptide and uric acid (OR = 3.803, 1.195, 1.037, 2.896, 1.011, all P < 0.05) were positively correlated with NAFLD, and diabetes duration (OR = 0.948, P < 0.05) was positively correlated with NAFLD independently. CONCLUSIONS: The detectable rate of fatty liver was high in T2DM which was composed mainly of NAFLD. High abnormal liver enzymes detectable rate indicated that NAFLD with T2DM are prone to NASH.

Quantitative Diagnosis of Nonalcoholic Fatty Liver Disease with Ultrasound Attenuation Imaging in a Biopsy-Proven Cohort.

RATIONALE AND OBJECTIVES: To evaluate the performance of attenuation imaging (ATI) based on ultrasound for detection of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This prospective study was approved by our institutional review board (B2021-092R). Written informed consent was obtained from all patients. This study included 60 patients who had clinical suspicion of NAFLD and were referred for liver biopsy after ATI and controlled attenuation parameter (CAP) examinations between September 2020 and December 2021. The histologic hepatic steatosis was graded. The area under curve (AUC) analysis was performed. RESULTS: The success rate of the ATI examination was 100%. The intraobserver reproducibility of ATI was 0.981. The AUCs of ATI for detecting ≥S1, ≥S2, and S3 were 0.968 (cut-off value of 0.671 dB/cm/MHz), 0.911 (cut-off value of 0.726 dB/cm/MHz), and 0.766 (cut-off value of 0.757 dB/cm/MHz), respectively. The AUCs of CAP for detecting ≥S1, ≥S2, and S3 were 0.916 (cut-off value of 258.5 dB/m), 0.872 (cut-off value of 300.0 dB/m), and 0.807 (cut-off value of 315.0 dB/m), respectively. The diagnostic values showed no significant difference between ATI and CAP in detecting ≥S1, ≥S2, and S3 (P = .281, P = .254, and P = .330, respectively). The ATI had significant correlations with high-density lipoprotein cholesterol (P < .001), and with triglycerides (P = .015). CONCLUSION: ATI showed good feasibility and diagnostic performance in the detection of varying degrees of hepatic steatosis in NAFLD patients.

Renal function-dependent association of serum uric acid with metabolic syndrome and hepatic fat content in a middle-aged and elderly Chinese population.

The effect of uric acid (UA) on the pathogenesis of metabolic disorders is highly dependent on its physicochemical properties, and hyperuricaemia associated with different conditions may have different clinical meanings. The aim of the present study was to investigate the association of serum UA levels with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in a middle-aged and elderly population with normal and impaired renal function. The cross-sectional study was performed on 1141 participants (426 men, 715 women; mean age 62 years) enrolled from the Shanghai Changfeng community. Each participant underwent a standard interview, with anthropometric and laboratory measurements. Hepatic fat content (HFC) was determined by a newly established quantitative ultrasound method. Univariate correlation analysis showed that serum UA was associated with all components of metabolic syndrome and HFC (r = 0.193, P < 0.001), especially in participants with a normal estimated glomerular filtration rate (eGFR; r = 0.255, P < 0.001). Logistic regression analysis demonstrated an independent association of serum UA with metabolic syndrome and NAFLD in participants with normal renal function, but not in those with eGFR < 90 mL/min per 1.73 m(2) . Furthermore, multivariate linear analysis showed that UA levels were independently associated with HFC (P = 0.003), but only in participants with normal eGFR. Elevated serum UA is independently associated with metabolic syndrome and NAFLD in patients with normal renal excretory function. However, in those with renal insufficiency, hyperuricaemia has no association with metabolic disorders.

The effects of berberine on hyperhomocysteinemia and hyperlipidemia in rats fed with a long-term high-fat diet.

BACKGROUND: The study was undertaken to examine the effects of berberine (BBR) on serum homocysteine, lipids and the aortic lesion in Sprague-Dawley (SD) rats fed with a long-term high-fat diet (HFD). METHODS: Healthy male SD rats weighing 190-210 g received randomly standard diet or a high-fat diet for 24 weeks. After 8 weeks of feeding, rats fed with HFD were randomized to receive berberine (200 mg · kg-1· day-1) or vehicle by gavage for 16 weeks. After overnight fasting, all rats were sacrificed and total blood samples were also collected for determinant of fasting serum homocysteine (Hcy), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-c) levels. The aorta was stained with hematoxylin and eosin (HE) and Sudan Ш to evaluate aortic lesion. The livers were dissected out and snap-frozen in liquid nitrogen for hepatic TC content and molecular analysis. 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), Lipoprotein receptors and apolipoproteins gene expression in the liver were determined by real-time PCR. RESULTS: Intragastrical administration with berberine for 16 weeks lowered serum Hcy in rats fed with a high-fat diet. In parallel, it also decreased body weight and improved serum TC and LDL-c. Berberine also tended to decrease hepatic cholesterol. Consistently, berberine also upregulated LDL receptor (LDLR) mRNA level and suppressed HMGR gene expression. Meanwhile, upon berberine-treated rats, there was a significant increase in apolipoprotein E (apoE) mRNA, but no change in apoAI and scavenger receptor (SR) mRNA in the liver. Further, no atherosclerotic lesions were developed in berberine-treated rats for 16 weeks. CONCLUSION: Berberine can counteract HFD-elicited hyperhomocysteinemia and hyperlipidemia partially via upregulating LDLR and apoE mRNA levels and suppressing HMGR gene expression.

Metabolically healthy obesity: Is it really healthy for type 2 diabetes mellitus?

Metabolically healthy obese (MHO) individuals are reported to have a lower risk of developing cardiovascular diseases in comparison with individuals with metabolic syndrome. However, the association between MHO and type 2 diabetes (T2DM) is still controversial. Some studies indicated that MHO is a favorable phenotype for T2DM, but more studies showed that MHO individuals have an increased risk of developing T2DM compared with metabolically healthy normal-weight individuals, especially among those who would acquire metabolically unhealthy obesity. This has been supported by finding insulin resistance and low-grade inflammatory responses in MHO individuals with a tendency for impaired beta-cell dysfunction. Studies also showed that liver fat accumulation increased the risk of incidence of T2DM in MHO. Here, we reviewed current literature on the relationship between MHO and T2DM, discussed the determinants for the development of diabetes in MHO, and summarized the measures for the prevention of T2DM in MHO.

Elevation of liver enzymes within the normal limits and metabolic syndrome.

1. Metabolic syndrome is frequently associated with elevated liver enzymes. However, the current 'normal' limits for liver enzymes often fail to identify patients with metabolic syndrome and the associated non-alcoholic fatty liver disease (NAFLD). 2. In the present study, 1503 participants, aged between 18 and 95 years, were recruited from the physical examination centre of Shanghai Zhongshan Hospital and Shanghai Changfeng Community Health Centre. The association between liver enzymes within the 'normal' range and metabolic syndrome was investigated and optimal cut-off values for liver enzymes in metabolic syndrome were determined. We further compared the diagnostic performance of the new cut-off values for liver enzymes in metabolic syndrome and NAFLD with the traditional 'normal' range for liver enzymes. 3. Serum liver enzymes within the traditional 'normal' limits, especially alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT), were correlated with most of components of the metabolic syndrome, as determined by Spearman's partial correlation analysis. Logistic regression analysis revealed that within the 'normal' range of liver enzymes, the frequency of metabolic syndrome was significantly increased in the higher quintile for ALT and GGT compared with the lowest quintile. Receiver operating characteristic curve analysis revealed that the optimal cut-off values for ALT, aspartate aminotransferase and GGT to identify metabolic syndrome were 26, 25 and 29 U/L, respectively, in men and 20, 23 and 21 U/L, respectively, in women. These values were much more effective in detecting patients with potential metabolic syndrome and NAFLD than the traditional cut-off values. 4. A slight elevation of liver enzymes within the 'normal' limits, especially ALT and GGT, indicates the presence of metabolic syndrome and NAFLD. Revision of the current normal limits for liver enzymes is advisable so that patients with potential metabolic disorders can be identified.

Effect of Electro-acupuncture on Expression of IRS-1/PI3K/GLUT4 Pathway in Ovarian Granulosa Cells of Infertile Patients with Polycystic Ovary Syndrome-Insulin Resistance of Phlegm-Dampness Syndrome.

OBJECTIVE: To evaluate the effect of electro-acupuncture (EA) in infertile patients with phlegm-dampness polycystic ovary syndrome-insulin resistance (PCOS-IR). METHODS: Seventy-six PCOS-IR patients who underwnet in vitro fertilization and embryo transfer (IVF-ET) were equally assigned to two groups according to a random digital table: the EA group and the control group, with 38 cases in each group. Before undergoing IVF, the two groups were treated with EA or pseudo-acupuncture, respectively, for 3 menstrual cycles. The intervention was 25 min twice a week until the day of oocyte collection. The selected acupoints were Zhongwan (RN 12), Tianshu (ST 25), Daheng (SP 15), Daimai (GB 26), Qihai (CV 6), Guanyuan (CV 4), and bilateral points including Xuehai (SP 10), Fenglong (ST 40), Zusanli (ST 36), and Yinlingquan (SP 9). Evaluation of phlegm-dampness syndrome score and IR score were carried out before and after treatment. Additionally, the number of oocytes retrieved, transplantable embryo rate, high-quality embryo rate, clinical pregnancy rate and live birth rate were compared between the two groups. Real-time polymerase chain reaction analysis was used to monitor the mRNA expression of the insulin receptor substrate (IRS-1), phosphatidylinositiol 3-kinase (PI3K) and glucose transport factor 4 (GLUT4) in ovarian granulosa cells. RESULTS: EA treatment reduced the phlegm-dampness syndrome score as well as the IR scores compared with the control group (P<0.05). No significant differences in the number of oocytes retrieved and clinical pregnancy rate between the two groups (P>0.05). Moreover, the transplantable embryo rate [49.0% (284/580) vs. 41.9% (273/652)], high-quality embryo rate [36.6% (104/284) vs. 27.8% (76/273)], and live birth rate [50% (19/38) vs. 26.3% (10/38)] in the EA group were significantly higher than in the control group (P<0.05). Gene expression analyses revealed significantly elevated IRS-1, PI3K and GLUT4 mRNA in ovarian granulosa cells of the EA group compared with the control group (P<0.05). CONCLUSIONS: EA may ameliorate the effects of phlegm-dampness syndrome and ovarian IR in PCOS-IR patients. Mechanistically, this effect might be through an upregulation of the IRS-1/PI3K/GLUT4 signaling pathway, which may result in improved oocyte quality and embryonic development potential. (Registration No. ChiCTR1800015453).

Prediction of Metabolic Disorders Using NMR-Based Metabolomics: The Shanghai Changfeng Study.

A metabolically healthy status, whether obese or not, is a transient stage with the potential to develop into metabolic disorders during the course of life. We investigated the incidence of metabolic disorders in 1078 metabolically healthy Chinese adults from the Shanghai Changfeng Study and looked for metabolites that discriminated the participants who would develop metabolic disorders in the future. Participants were divided into metabolically healthy overweight/obesity (MHO) and metabolically healthy normal weight (MHNW) groups according to their body mass index (BMI) and metabolic status. Their serum metabolomic profile was measured using a 1H nuclear magnetic resonance spectrometer (1H-NMR). The prevalence of diabetes, hypertriglyceridemia, hypercholesterolemia and metabolic syndrome was similar between the MHNW and MHO participants at baseline. After a median of 4.2 years of follow-up, more MHO participants became metabolically unhealthy than MHNW participants. However, a subgroup of MHO participants who remained metabolically healthy (MHO → MHO) had a similar prevalence of metabolic disorders as the MHNW participants at the follow-up examination, despite a significant reduction in their serum concentrations of high-density lipoprotein (HDL) and an elevation in valine, leucine, alanine and tyrosine. Further correlation analysis indicated that serum intermediate-density lipoprotein (IDL) and very low-density lipoprotein cholesterol (VLDL-CH) might be involved in the transition from metabolically healthy to unhealthy status and could be valuable to identify the MHNW and MHO with increased metabolic risks.

Skeletal muscle loss is associated with diabetes in middle-aged and older Chinese men without non-alcoholic fatty liver disease.

BACKGROUND: Skeletal muscle, a key insulin target organ, has been reported to be associated with diabetes mellitus (DM). Compared to non-diabetic patients, diabetic patients have decreased muscle mass and a higher prevalence of sarcopenia, and patients with sarcopenia may be at increased risk of developing diabetes. In individuals with nonalcoholic fatty liver disease (NAFLD), sarcopenia is associated with the severity of fibrosis and steatosis. Previous studies have demonstrated that NAFLD is strongly associated with DM and sarcopenia. AIM: To determine the relationship between skeletal muscle mass and DM in Chinese middle-aged and elderly men, and whether the association is affected by NAFLD. METHODS: Skeletal muscle mass was calculated as appendicular skeletal muscle mass (ASM) in kg/body weight × 100%. Liver fat content (LFC) was measured using a quantitative ultrasound method. RESULTS: As the ASM decreased, fasting blood glucose (FBG), 2-h postprandial blood glucose (2hBG), and LFC increased in both genders, as did the prevalence of DM and NAFLD. Spearman analysis showed that the ASM was negatively correlated with the FBG, 2hBG, and LFC. Stepwise logistic regression analysis showed that after adjustments, the ASM quartile was negatively associated with the presence of DM in males, but not in females. Subgroup analysis showed that the ASM quartiles remained negatively correlated with the presence of DM in the non-NAFLD population (including males and females), but no correlation was found between ASM quartiles and the presence of DM in the NAFLD population. When stratified by LFC quartiles, ASM was negatively correlated with the presence of DM in the first and second LFC quartiles in males. CONCLUSION: Skeletal muscle mass loss was shown to be associated with the presence of DM in males, but not in females; NAFLD weakens this association. The results suggested that the stratified management of diabetes mellitus should be considered according to skeletal muscle mass and NAFLD.

Sarcopenia, sarcopenic overweight/obesity and risk of cardiovascular disease and cardiac arrhythmia: A cross-sectional study.

BACKGROUND: Sarcopenia is an age-dependent skeletal muscle disorder that is common in patients with heart failure. The current study aimed to investigate the associations of sarcopenia with carotid atherosclerosis, cardiovascular disease and cardiac arrhythmia in a middle-aged and elderly population without clinical heart failure. METHODS: A total of 2432 participants (992 men and 1440 women) from Shanghai Changfeng Study were included for analysis. The degree of sarcopenia was measured using height-adjusted appendicular skeletal muscle mass (ASM/height2). Carotid plaques were detected by carotid artery ultrasonography, and myocardial ischemia, infarction and cardiac arrhythmia were diagnosed based on electrocardiogram, past history and clinical manifestations. RESULTS: Sarcopenia was associated with higher prevalence of carotid atherosclerosis (26.4% vs 20.4%, P = 0.027), myocardial infarction (4.0% vs 1.1%, P = 0.001), and premature ventricular contraction (4.0% vs 2.0%, P = 0.034) in the participants with normal body weight, and higher prevalence of carotid atherosclerosis (45.0% vs 31.2%, P = 0.016), myocardial infarction (10.0% vs 4.3%, P = 0.020) and atrial fibrillation (7.5% vs 1.3%, P < 0.001) in those with overweight/obese status. After adjustment for age, gender, cigarette smoking, alcohol drinking, menopausal status in women and other metabolic and inflammatory confounding factors, sarcopenia was independently associated with the risk of myocardial infarction in the whole population, and the risk of atrial fibrillation in the overweight/obese participants (all P < 0.05). Compared with nonsarcopenic lean participants, the risk of myocardial infarction was gradually increased in sarcopenic lean (OR 3.08 [1.28-7.45], P = 0.012) and sarcopenic overweight/obese participants (OR 4.07 [1.31-12.62], P = 0.015). For the atrial fibrillation, the participants with either sarcopenia or overweight/obesity alone showed no higher risk. However, concomitant sarcopenia and overweight/obesity was associated with approximately 5-fold risk of atrial fibrillation (OR 5.68 [1.34-24.12], P = 0.019) after multiple adjustment. CONCLUSION: Sarcopenia is associated with myocardial infarction and atrial fibrillation in middle-aged and elderly adults without clinical heart failure.

[Relationship between liver fat content and liver enzymes in individuals with various statuses of glucose metabolism].

OBJECTIVE: To study the relationship between liver fat content (LFC) and liver enzymes in individuals with various statuses of glucose metabolism. METHODS: A total of 109 subjects including with impaired glucose regulation (IGR) (n = 31), newly diagnosed type 2 diabetes (NT2DM) (n = 31) and normal glucose tolerance (NGT) (n = 47) were recruited. The level of LFC was measured by (1)H magnetic resonance spectroscopy ((1)H-MRS) to study the relationship between liver fat content (LFC) and alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) and γ-glutamyltransferase (GGT). The receiver operating characteristic curve (ROC) was employed to obtain the optimal cut-off point of ALT to predict the occurrence of nonalcoholic fatty liver disease (NAFLD). RESULTS: (1) The levels of LFC were progressively raised in NGT, IGR and NT2DM groups respectively [3.83 (2.35 - 7.59)%, 12.82 (8.10 - 21.37)% and 21.99 (11.89 - 34.43)%, P < 0.01]; (2) the subjects were divided into four subgroups by the method of LFC quartile. And quartile subgroups Q1-4 were associated with the increase of LFC. Waist, BMI, systolic blood pressure, triglyceride, total cholesterol, fasting plasma glucose, OGTT 2 h postprandial glucose and HOMA-IR had a rising trend from Q2. But HDL-C showed a declining trend from Q2; (3) ALT and GGT significantly increased from Q3 (P < 0.01) while AST and AKP significantly increased in Q4 (P < 0.01); (4) adjusted by gender, age and body mass index (BMI), LFC was positively correlated with AST (r = 0.329, P < 0.05), ALT (r = 0.454) and GGT (r = 0.378) (All P < 0.01). But it was negatively correlated with AST/ALT (r = -0.364, P < 0.01); (5) the analysis of stepwise regression demonstrated that LFC was a predictor of ALT, AST, GGT and AST/ALT; (6) ALT had a ROC(AUC) of 0.813 (male) and 0.769 (female) (All P < 0.01). The optimal cut-off point of 23.5 U/L (male) and 17.5 U/L (female) might predict the occurrence of NAFLD. CONCLUSIONS: Liver enzymes are correlated with LFC even in normal range. The optimal cut-off point of 23.5 U/L (male) and 17.5 U/L (female) might predict the occurrence of NAFLD. The current used ALT upper limit could underestimate the NAFLD.

Three new secoiridoid glycosides from the flower buds of Lonicera japonica.

Three new secoiridoid glycosides, named lonijapoglycol A (1), aldosecolohanin C (2) and aldosecolohanin B (3), together with three known ones (4-6), have been isolated from the flower the buds of Lonicera japonica. All the structures were identified by spectroscopic analyses. Lonijapoglycol A (1) expressed significant anti-inflammatory activity to inhibit the release of ß-glu-curonidase induced by platelet-activating factor in rat polymorphonuclear leukocytes with an IC50 value of 3.76 µmol·L-1.

NAFLD and Diabetes: Two Sides of the Same Coin? Rationale for Gene-Based Personalized NAFLD Treatment.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly and at the forefront of worldwide concern. Characterized by excessive fat accumulation in the liver, NAFLD regularly coexists with metabolic disorders, including type 2 diabetes, obesity, and cardiovascular disease. It has been well established that the presence of NAFLD increases the incidence of type 2 diabetes, while diabetes aggravates NAFLD to more severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, recent progress on the genotype/phenotype relationships in NAFLD patients indicates the development of NAFLD with a relative conservation of glucose metabolism in individuals with specific gene variants, such as the patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 protein (TM6SF2) variants. This review will focus on the clinical and pathophysiological connections between NAFLD and type 2 diabetes and will also discuss a disproportionate progression of NAFLD and diabetes, and the different responses to lifestyle and drug intervention in NAFLD patients with specific gene variants that may give insight into personalized treatment for NAFLD.

The PNPLA3 rs738409 C>G variant influences the association between low skeletal muscle mass and NAFLD: the Shanghai Changfeng Study.

BACKGROUND: Age-related skeletal muscle loss and patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphisms are both associated with increased liver steatosis and fibrosis in the absence of obesity. AIM: To investigate the influence of PNPLA3 polymorphism on the relationship between skeletal muscle loss and non-alcoholic fatty liver disease (NAFLD). METHODS: Liver fat content was measured using a quantitative ultrasound method, and liver fibrosis was assessed by NAFLD fibrosis, BARD and FIB-4 scores in 3969 Chinese adults. The degree of sarcopenia was measured by weight-adjusted appendicular skeletal muscle mass (ASM% = appendicular skeletal muscle mass(kg)/body weight(kg)  100%). RESULTS: The NAFLD proportion increased from 19.9% to 41.2% in men and 26.3% to 42.3% in women with decreasing ASM% quartiles (P < 0.001). Low ASM% was inversely associated with NAFLD in PNPLA3 CC (odds ratio [OR]: men, 0.735 [0.610-0.885] and women, 0.812 [0.718-0.918], both P = 0.001) and CG (OR: men, 0.673 [0.573-0.790] and women, 0.798 [0.713-0.893], both P < 0.001) but not GG genotype carriers. The association remained significant after adjustment for age, cigarette smoking, fat mass, interaction between fat mass and ASM%, obesity, diabetes and all components of metabolic syndrome. Subgroup analyses found that PNPLA3 GG gene variant did not increase the risk for NAFLD in individuals with low ASM% regardless of obesity status. Low ASM% also increased risk for liver fibrosis (all P < 0.05), which became insignificant after multiple adjustments. CONCLUSIONS: Low ASM% is associated with NAFLD and liver fibrosis. Dissociation of sarcopenia and NAFLD was found in PNPLA3 GG genotype carriers. A stratification based on PNPLA3 genotypes might facilitate personalised treatment for NAFLD.