Branched-chain amino acids promote occurrence and development of cardiovascular disease dependent on triglyceride metabolism via activation of the mTOR/SREBP-1/betatrophin pathway.

Branched-chain amino acid (BCAA) metabolism is associated with triglyceride (TG) metabolism and the development of cardiovascular disease (CVD). However, the underlying mechanism remains uncertain. This study included 1302 subjects and followed for 4-5 years. A hyperbranched-chain aminoacidemia rat model was induced by high fructose diet (HFTD). The relationship between BCAAs and TG level and its regulatory mechanism was investigated in vitro. As results, as baseline BCAA percentile increased, subjects had higher prevalence and incidence of T2DM, NAFLD, and CVD risk (P < 0.05). In animal model, the accumulation of BCAAs and TG and betatrophin expression were significantly elevated in the HFTD group when comparing with those in the SD group(P < 0.05). Immunofluorescence and Masson's trichrome staining revealed that the area of interstitial fibrosis was significantly increased in the HFTD group compared with control group. Met treatment significantly decreased TG levels and betatrophin expression and reversed myocardial fibrosis (P < 0.05). In vitro, LO2 cells, stimulated with 0.1-5 mM BCAAs, displayed a significant dose-dependent increase in betatrophin expression (P < 0.05). And 5 mM BCAAs stimulation significantly increased the p-mTOR and SREBP-1 expression (P < 0.05). However, this effect could be reversed by using the corresponding inhibitor or siRNAs. In conclusions, BCAAs promote occurrence and development of cardiovascular disease dependent on TG metabolism via activation of the mTOR/SREBP-1/betatrophin pathway. The study provides a new theory for the pathogenesis of CVD caused by amino acid metabolism disorders.

Effects of a calorie-restricted dietary intervention on weight loss and gut microbiota diversity in obese patients with sleep deprivation.

OBJECTIVES: This study aimed to investigate the effects of a calorie-restricted dietary (CRD) intervention on weight and gut microbiota diversity in obese patients with sleep deprivation (SD). METHODS: Twenty obese patients were divided into a sleep deprivation group (SD group, n = 10) and a nonsleep deprivation group (NSD group, n = 10), both of which underwent a CRD intervention for 12 weeks. Measurement of anthropometric parameters, biochemical examinations and gut microbiota detection were performed at baseline and at the end of week 12. Mi Smart Bands 1 (Standard Option) were used to monitor sleep and exercise. RESULTS: (1) The CRD intervention improved body weight (BW), waist circumference (WC), blood pressure (BP), basal metabolic rate (BMR), body fat content (BFC), and insulin resistance index (HOMA-IR) in all obese patients. (2) In the NSD group, BW, BFC, VFA (visceral fat area), BMR and total cholesterol (TC) were significantly reduced after the CRD intervention (P < 0.05). (3) The alpha diversity of the gut microbiota remained unchanged after the intervention in the two groups. (4) There was a negative correlation between Mollicutes and BMR in the NSD group. CONCLUSIONS: The effects of a CRD intervention weaken on weight loss and the metabolism of blood lipids may be weakened by SD. The abundance of Mollicutes bacteria may be related to weight loss after a CRD intervention in obese patients. LEVEL OF EVIDENCE: III, prospective cohort study.

High L-Valine Concentrations Associate with Increased Oxidative Stress and Newly-Diagnosed Type 2 Diabetes Mellitus: A Cross-Sectional Study.

OBJECTIVE: Branched-chain amino acids (BCAAs) are essential AAs which are widely used as antioxidants in patients with liver and kidney dysfunction. However, BCAAs are strongly correlated with insulin resistance (IR) and diabetes. This study aimed to evaluate the relationship among BCAAs, oxidative stress, and type 2 diabetes mellitus (T2DM) in a Chinese population. METHODS: Anthropometric and biochemical examinations were performed in 816 individuals who participated in the Huai'an Diabetes Prevention Program. Serum BCAAs concentrations were measured by hydrophilic interaction chromatography-tandem mass spectrometric method. Oxidative stress was evaluated by malondialdehyde (MDA) as an index of lipid peroxidation and the superoxide dismutase (SOD) activity. RESULTS: A total of 816 participants were divided into three groups: normal glucose metabolism (NGM), prediabetes, and newly-diagnosed diabetes mellitus (NDM). Subjects in NDM group show higher MDA and lower SOD levels than subjects in other groups. L-Val levels positively correlated with MDA levels and negatively with SOD in NDM groups. After adjusting for T2DM risk factors, high L-Val levels were significantly associated with higher BMI, WC, FPG, increased LnTG and decreased HDL-C. L-Val was also independently associated with NDM (OR 1.06, 95% CI 1.02-1.10; P = 0.005). Furthermore, the odds ratios for NDM among participants with high L-Val (≥35.25µg/mL) levels showed a 2.25-fold (95% CI 1.11-4.57; P = 0.024) increase compared to participants with low L-Val (<27.26 µg/mL) levels after adjusting for MDA and confounding factors. CONCLUSION: High serum L-Val levels are independently associated with oxidative stress, thus promoting IR and NDM. Further study should be done to clarify the mechanism.

Effects of PPM1K rs1440581 and rs7678928 on serum branched-chain amino acid levels and risk of cardiovascular disease.

OBJECTIVE: This study aimed to investigate the effects of PPM1K rs1440581 and rs7678928 single nucleotide polymorphisms (SNPs) on the serum branched-chain amino acids (BCAAs) levels and cardiovascular disease (CVD) risk. METHODS: Anthropometric and biochemical examinations were performed at baseline and the end of 4 years in 234 individuals who were randomly recruited from the Diabetes Prevention Programme in Huai'an and received lifestyle intervention and follow up for 4 years. Serum BCAAs (leucine, isoleucine and valine (Val)) levels were measured by hydrophilic interaction chromatography-tandem mass spectrometric method and the PPM1K rs1440581 and rs7678928 were detected by high-throughput SNP genotyping at baseline. The associations of rs1440581 and rs7678928 with serum BCAA levels and risk for CVD after 4 years were further evaluated. RESULTS: The distribution frequencies of PPM1K rs1440581 and rs7678928 met the Hardy-Weinberg equilibrium (p> .05). The baseline serum levels of Val (p = .022) and total BCAAs (p = .026) in subjects with rs1440581 CC genotype were higher than in those with TT genotype. There were no significant differences in the serum levels of BCAAs among subjects with different genotypes of rs7678928. After 4-year follow-up, the subjects with rs1440581 CC genotype had higher systolic blood pressure (SBP) (p = .027), diastolic blood pressure (DBP) (p = .019), triglycerides (TGs) (p = .019) and lower high-density lipoprotein cholesterol (HDL-c) (p = .008) than those with TT genotype, and had higher AST level than those with TT (p = .030) or TC (p = .003) genotype; the subjects with rs7678928 TT genotype had higher SBP (p = .039) and DBP (p = .019) and lower HDL-c than those with CC (p = .017) genotype. Lifestyle intervention had little influence on the serum levels of fasting plasma glucose (FPG), TG, HDL-c, alanine aminotransferase (ALT), AST and creatinine (CREA) in subjects with rs1440581 CC genotype or rs7678928 TT genotype (p> .05). The incidences of CVD and non-alcoholic fatty liver disease (NAFLD) in subjects with rs1440581 CC genotype were higher than in those with TT genotype; the incidence of CVD in subjects with rs7678928 TT genotype was higher than in those with CC (p < .05) genotype. CONCLUSIONS: Allele C of PPM1K rs1440581 was associated with elevated serum Val, total BCAAs and CVD risks. rs1440581 CC genotype may be a better marker than baseline serum BCAAs in predicting the risk for CVD. TRIAL REGISTRATION: Diabetes Prevention Programme in Huai'an of Huai'an Second People's Hospital, ChiCTR-TRC-14005029.KEY MESSAGEAllele C of PPM1K rs1440581 was relevant to elevated serum Val and total BCAAs.PPM1K rs1440581 CC and rs7678928 TT genotypes were associated with CVD risk.PPM1K rs1440581 CC genotype carriers were more likely to have liver injury and develop NAFLD.

Anti-aging effects of a functional food via the action of gut microbiota and metabolites in aging mice.

Wushen (WS) is a mixed food containing 55 natural products that is beneficial to human health. This study aimed to reveal the preventive effect of WS on aging via a combined analysis of gut microbiome and metabolome. Senescence-accelerated mouse prone 8 (SAMP8) mice were used as aging model and senescence-accelerated mouse resistant 1 (SAMR1) mice as control. The mice were fed four diet types; control diet (for SAMR1 mice), standard diet (for SAMP8 mice, as SD group), WS diet, and fecal microbiota transplantation (FMT; transplanted from aging-WS mice). Our results showed that the weight, food intake, neurological function, and general physical conditions significantly improved in WS-fed mice compared to those fed with SD. The CA1 hippocampal region in WS-fed aged mice showed fewer shriveled neurons and increased neuronal layers compared to that of the SD group. WS-fed mice showed a decrease in malondialdehyde and an increase in superoxide dismutase levels in the brain; additionally, IL-6 and TNF-α levels significantly decreased, whereas IL-2 levels and the proportion of lymphocytes, CD3+CD8+ T, and CD4+IFNγ+T cells increased in WS-fed mice. After fed with WS, the abundance of Ruminococcus and Butyrivibrio markedly increased, whereas Lachnoclostridium and Ruminiclostridium significantly decreased in the aging mice. In addition, 887 differentially expressed metabolites were identified in fecal samples, among these, Butyrivibrio was positively correlated with D-glucuronic acid and Ruminococcus was positively associated with 5-acetamidovalerate. These findings provide mechanistic insight into the impact of WS on aging, and WS may be a valuable diet for preventing aging.

A Functional Food Inhibits Azoxymethane/Dextran Sulfate Sodium-Induced Inflammatory Colorectal Cancer in Mice.

PURPOSE: This study aimed to investigate the potential antitumor effects and mechanisms underlying the action of a functional food containing 55 different natural food ingredients. MATERIALS AND METHODS: Azoxymethane/dextran sulfate sodium was used to establish a mouse model of colorectal cancer. Serum levels of cytokines, diamine oxidase, D-lactate, and endotoxin were measured using enzyme-linked immunosorbent assays. Immune cells from the mouse spleen and tumor tissue were analyzed by flow cytometry. Finally, 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were used to study the fecal microbiota and microbial metabolites, respectively. RESULTS: The tumor growth was significantly lower in the FFD group than in the model group. The intestinal barrier function, fat mass, and lean body mass were significantly improved in the FFD group compared with the model group. The levels of interleukin-6 and tumor necrosis factor-α were significantly lower in the FFD group, while the proportions of total T cells, CD3+CD4+, CD3+CD8+, and interferon-γ-producing CD4+ T cells were significantly higher. Analysis of the diversity of the gut microbiota identified 60 differential bacterial genera between the FFD and model groups, with lower abundances of Desulfovibrio and unclassified Ruminococcaceae and higher abundances of the beneficial bacterial genera Bacteroides and Parasutterella in the FFD group. The fecal metabolite analysis revealed 635 differential metabolites between the FFD and model groups, with lower levels of deuteroporphyrin IX and citrulline and higher levels of acetic acid and ascorbic acid in the FFD group. CONCLUSION: Our results demonstrate that the functional food tested can inhibit the growth of colorectal cancer. This effect may be due to the ability of this food to improve nutritional status, enhance intestinal barrier function, and regulate the tumor microenvironment via changes in the intestinal microbiota and metabolites.

Inhibitory Effect of a Microecological Preparation on Azoxymethane/Dextran Sodium Sulfate-Induced Inflammatory Colorectal Cancer in Mice.

This study aims to investigate the antitumor effect and the possible mechanism of a microecological preparation (JK5G) in mice. The mice treated with AOM/DSS were then randomly divided into the two model groups and the JK5G group, and the blank control group was included. Fecal samples were used for liquid chromatography-mass spectrometry and 16S rRNA gene sequencing analyses to reveal metabolic perturbations and gut flora disorders to demonstrate the effects of JK5G. Compared with the mice in the control group, the weight and food intake of mice after JK5G treatment were both upregulated. Moreover, JK5G could inhibit the growth of colon tumors and prolong the survival rate of mice, as well as inhibit the levels of cytokines in serum. The proportions of lymphocytes, T cells, CD3+CD4+ T cells, and CD3+CD8+ T cells in the spleen of the JK5G mice were all significantly increased compared to those in the control group (p < 0.05). Similarly, compared with the model group, the proportions of lymphocytes, B cells, T cells, natural killer T cells, CD3+CD4+ T cells, and CD3+CD8+ T cells in the intestinal tumors of the JK5G mice were significantly increased (p < 0.05). Furthermore, 16S rRNA high-throughput sequencing data revealed that Alloprevotella in the JK5G group was significantly upregulated, and Ruminiclostridium, Prevotellaceae_UCG_001, and Acetitomaculum were significantly downregulated. Fecal and serum metabolite analysis detected 939 metabolites, such as sildenafil and pyridoxamine, as well as 20 metabolites, including N-Palmitoyl tyrosine and dihydroergotamine, which were differentially expressed between the JK5G and model groups. Integrated analysis of 16s rRNA and metabolomics data showed that there were 19 functional relationship pairs, including 8 altered microbiota, such as Ruminiclostridium and Prevotellaceae_UCG_001, and 16 disturbed metabolites between the JK5G and model groups. This study revealed that JK5G treatment was involved in the growth of colorectal cancer, which may be associated with the role of JK5G in improving the nutritional status of mice and regulating the tumor microenvironment by regulating the changes of intestinal microbiota and metabolite bands on different pathways.

Correlation between income and non-alcoholic fatty liver disease in a Chinese population.

OBJECTIVE: The aim of the study was to analyze the correlation between income and non-alcoholic fatty liver disease (NAFLD) in a Chinese population. METHOD: subjects were divided into three groups according to liver fat content (LFC). (1) normal: LFC < 9.15%, 197 cases; (2) low LFC: LFC 9.15-20%, 532 cases; and (3) high LFC: LFC > 20%, 201 cases. Participants' clinical and social background were collected, including a routine fasting test to assess the relevant indices. Intergroup differences were compared on 1-way ANOVA, to analyze the relation between income and each index on Pearson correlation, and independent factors for LFC were identified on binary logistic regression. RESULTS: (1) In retired persons, prevalence of NAFLD was greater in females (81.2%) than males (75%), but fell with age: the highest prevalence was between 40 and 49 years of age (87.5%), and the lowest above 70 years (68%). (2) Income correlated positively with triglyceride and serum uric acid levels and LFC (P < 0.05) and negatively with alanine aminotransferase (P = 0.01). (3) As income increased from level I to V, prevalence of NAFLD increased progressively (P < 0.05). In the study, LFC was taken as the dependent variable, and the traditional NAFLD risk factors and income level (I-V) were taken as independent variables. Income emerged as an independent risk factor for NAFLD. Risk in group V was 1.964-fold higher than in group I. CONCLUSION: Prevalence of NAFLD was closely related to socio-economic level. Demographic risk factors include female gender, age 40-49 years, and monthly income > 5,000 RMB. Thus, if income is increased without improving educational level and health awareness, NAFLD prevalence will rise.

Epidemiological characteristics and risk factors of T2DM in Chinese premenopausal and postmenopausal women.

OBJECTIVE: This study was to analyse the prevalence of type 2 diabetes mellitus (T2DM) in premenopausal and postmenopausal women. METHODS: A total of 3227 women met the requirements from June to December in 2014, including 207 cases of premenopausal women and 3020 cases of postmenopausal women. The prevalence of T2DM and the associated risk factors in the two groups were analysed. RESULTS: The prevalence of premenopausal women with T2DM was 12.1%, while the prevalence in postmenopausal women was 19.4% (P < 0.05). Total serum protein (TP) (OR = 1.164 95% CI = 1.023-1.324) (P = 0.021) is a major risk factor for premenopausal women with T2DM. The prevalence of T2DM increased with the increase in TP. In postmenopausal groups, the prevalence of T2DM was associated with age (OR = 1.037 95% CI = 1.024-1.051) (P < 0.001), BMI (OR = 1.076 95% CI = 1.044-1.109) (P < 0.001), blood pressure (OR = 1.521 95% CI = 1.234-1.875) (P < 0.001), triglycerides (TG) (OR = 1.106 95% CI = 1.027-1.190) (P = 0.008), blood urea nitrogen (BUN) (OR = 1.065 95% CI = 1.004-1.129) (P = 0.036), alanine aminotransferase (ALT) (OR = 1.009 95% CI = 1.003-1.016) (P = 0.004) and TP (OR = 1.031 95% CI = 1.005-1.057) (P = 0.018). CONCLUSIONS: Postmenopausal women have a higher rate of type 2 diabetes than premenopausal women. TP is a major risk factor for premenopausal women with T2DM. TP, ALT, and BUN are postmenopausal risk factors in addition to traditional risk factors such as obesity, lipidaemia and blood pressure. We should monitor risk factors and take early prevention and intervention measures to reduce the prevalence of diabetes and improve the quality of life of postmenopausal women. TRIAL REGISTRATION: ChiCTR, ChiCTR-TRC-14005029. Registered 29 July 2014, http://www.chictr.org.cn/showproj.aspx?proj=4545.

Association of OSAHS Hypoxia Indicators with Early Renal Injury and Serum Fibroblast Growth Factor 21 in Obese Type 2 Diabetic Patients.

OBJECTIVE: This study aimed to explore the association of obstructive sleep apnea-hypopnea syndrome (OSAHS) hypoxia indicators with early renal injury and serum fibroblast growth factor 21 (FGF21) in obese type 2 diabetic patients. METHODS: A total of 109 obese patients with type 2 diabetes mellitus (T2DM) were recruited, including 70 males and 39 females, with an average age of 52.77 ± 13.57 years and average BMI of 29.08 ± 4.36 kg/m2. Overnight sleep monitoring was performed with a portable monitor to record respiratory parameters [apnea-hypopnea index (AHI), oxygen desaturation index (ODI), lowest oxygen saturation (LSaO2), mean oxygen saturation (MSaO2/MPO2) and cumulative time of oxygen saturation < 90% (CT < 90%)]. Ultrasonography was done to detect the quantitative liver fat content (LFC). The urine microalbumin and creatinine ratio (ACR) were determined by immunoturbidimetry. FGF21 was measured at baseline by enzyme-linked immunosorbent assay. Patients were divided into the proteinuria group (n = 42) and non-proteinuria group (n = 67). Correlation analysis and multivariate linear regression analysis were used to analyze the related data. In addition, patients were divided into the T2DM without OSAHS group (n = 16) and T2DM with OSAHS group (n = 93) according to the AHI value. The correlation analysis was used to assess the relationship between FGF21 and clinical variables. RESULTS: (1) ACR positively correlated with waist circumference (WC), AHI, ODI, CT < 90% and LFC, but negatively with MSaO2 and LSaO2. (2) AHI, ODI, CT < 90% and LFC were independent risk factors for ACR, LSaO2 and MSaO2 was a protective factor. (3) Serum FGF21 decreased in the OSAHS group compared with the non-OSAHS group. After adjustment for age, WC and TG, FGF21 correlated negatively with AHI, but positively with MSaO2. CONCLUSIONS: AHI, ODI, CT < 90% and LFC are independent risk factors for ACR. FGF21 is associated with hypoxia indicators, and improving OSAHS status and reducing liver fat content may be helpful for the prevention and treatment of early diabetic nephropathy (DN). CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IOR-15006225.

Cross-sectional survey of biosimilar insulin utilization in Asia: The Joint Asia Diabetes Evaluation Program.

AIMS/INTRODUCTION: Biosimilar insulin can reduce treatment costs, although the extent of its use is largely unknown. We examined biosimilar insulin use and its associations with the quality of glycemic control using the Joint Asia Diabetes Evaluation register. MATERIALS AND METHODS: We carried out a cross-sectional analysis in 81,531 patients with type 1 and type 2 diabetes enrolled into the Joint Asia Diabetes Evaluation Program from 2007 to 2014. All insulin related terms are extracted from the Joint Asia Diabetes Evaluation portal, and compared clinical profiles between biosimilar and originator insulin users. Multivariate analysis was performed to assess the association of biosimilar insulin compared with originator insulin with dosage, glycated hemoglobin and hypoglycemia events. RESULTS: Amongst 81,531 patients, 20.5% (n = 16,738) were insulin-treated. In four countries with high use of biosimilar insulin, 4.7% (n = 719) of insulin users (n = 10,197) were treated with biosimilar insulin (India n = 507, 70.3%; the Philippines n = 90, 12.5%; China n = 62, 8.6%; Vietnam n = 60, 8.3%). Biosimilar insulin users were younger and had higher body mass index, glycated hemoglobin, insulin dosage and more frequent hypoglycemia than originator insulin users. These associations were non-significant after adjustment for confounders. Only age, college education, diabetes education, lipid control, physical activity and history of cardiovascular complications were independently associated with these quality measures. CONCLUSIONS: Biosimilar insulin use is not uncommon in Asia. Data exclusion due to incomplete capturing of brand names suggests possibly higher use. The multiple determinants of the quality of glycemic control call for establishment of prospective cohorts and diabetes registers to monitor the safety and efficacy of different brands of biosimilar insulin and their impacts on clinical outcomes.

Low ketolytic enzyme levels in tumors predict ketogenic diet responses in cancer cell lines in vitro and in vivo.

The ketogenic diet (KD) is a high-fat, very-low-carbohydrate diet that triggers a fasting state by decreasing glucose and increasing ketone bodies, such as ß-hydroxybutyrate (ßHB). In experimental models and clinical trials, the KD has shown anti-tumor effects, possibly by reducing energy supplies to cells, which damage the tumor microenvironment and inhibit tumor growth. Here, we determined expression levels of genes encoding the ketolytic enzymes 3-hydroxybutyrate dehydrogenase 1 (BDH1) and succinyl-CoA: 3-oxoacid CoA transferase 1 (OXCT1) in 33 human cancer cell lines. We then selected two representative lines, HeLa and PANC-1, for in vivo examination of KD sensitivity in tumors with high or low expression, respectively, of these two enzymes. In mice with HeLa xenografts, the KD increased tumor growth and mouse survival decreased, possibly because these tumors actively consumed ketone bodies as an energy source. Conversely, the KD significantly inhibited growth of PANC-1 xenograft tumors. ßHB added to each cell culture significantly increased proliferation of HeLa cells, but not PANCI-1 cells. Downregulation of both BDH1 and OXCT1 rendered HeLa cells sensitive to the KD in vitro and in vivo. Tumors with low ketolytic enzyme expression may be unable to metabolize ketone bodies, thus predicting a better response to KD therapy.

Metabolic syndrome is independently associated with a mildly reduced estimated glomerular filtration rate: a cross-sectional study.

BACKGROUND: Association between metabolic syndrome (MS) and mildly reduced estimated glomerular filtration rates (eGFRs) remains unclear. Therefore, we aimed to evaluate the association between MS and a mildly reduced eGFR in Chinese adults. METHODS: Anthropometric and biochemical examinations were performed in 2992 individuals. The eGFR was calculated from the creatinine level. MS was defined according to the Adult Treatment Panel III criteria as the presence of three or more risk factors. Mildly reduced eGFR was defined as a value between 60 and 90 mL/min/1.73 m2. Multiple linear regression and multiple logistic regression analysis were used to evaluate association between metabolic syndrome and estimate glomerular filtration rate. RESULTS: After adjusting for several potential confounders, the participants with MS showed a 1.29-fold increased odds ratio for a mildly reduced eGFR compared with those without MS. Additionally, the odds ratios (and 95% confidence intervals (CIs)) for mildly reduced eGFR in participants with elevated triglycerides (TG), decreased high-density lipoprotein (HDL), obesity and elevated fasting blood glucose (FPG) after multivariable adjustment were 1.25 (1.05-1.49), 1.23 (1.03-1.48), 1.22 (1.03-1.45) and 0.64 (0.52-0.78), respectively. The odds ratios (95% CIs) for hyperfiltration in participants with elevated FPG and HbA1c levels after multivariable adjustment were 1.53 (1.30-1.81) and 2.86 (2.00-4.09), respectively. CONCLUSIONS: MS is associated with an increased risk of a mildly reduced eGFR in the Chinese population, and several individual components of MS have different impacts on eGFR levels. MS had dual roles on renal damage. TRIAL REGISTRATION: ChiCTR-TRC- 14005029 . Registered 28 July 2014.

Continuous Glucose Monitoring in Newly Diagnosed Type 2 Diabetes Patients Reveals a Potential Risk of Hypoglycemia in Older Men.

Objectives. We performed continuous glucose monitoring (CGM) to define the features of patients with newly diagnosed type 2 diabetes (T2D) before and after Continuous Subcutaneous Insulin Infusion (CSII) therapy. Methods. This was a retrospective analysis. Newly diagnosed T2D patients (106) were admitted from eight centers in China. They were divided into a younger patient group (<60 years) and an older patient group (≥60 years). Each group was further divided into male and female patients. CSII therapy was maintained for 3 weeks after the glycemic target was reached. CGM was performed 2 times before and after completion of insulin treatment. Results. CGM data showed the expected significant improvement of mean amplitude glycemic excursion (MAGE) with CSII therapy. The older patients had lower hourly glucose concentrations from 0200 to 0700 o'clock compared to the younger patients at baseline. Surprisingly, in the older patient group, the male patients had a potential risk of hypoglycemia after CSII therapy, especially during periods from 2300 to 2400 and 0400 to 0600. Conclusions. Our data suggested that older male patients with newly diagnosed T2D may have lower nocturnal glucose concentrations. This may potentially increase the risk of nocturnal hypoglycemia during CSII therapy. This study was registered with Chinese Clinical Trial Registry, number CliCTR-TRC-11001218.

Relationship of Serum Betatrophin with Nonalcoholic Fatty Liver in a Chinese Population.

OBJECTIVE: This study aimed to investigate the association of serum betatrophin with the status and progression of nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 249 subjects who received ultrasonic examination of liver fat content (LFC) were recruited. Anthropometric and biochemical examinations were performed. Serum betatrophin was measured by ELISA. RESULTS: Compared with control group, serum betatrophin significantly increased in NAFLD group (P < 0.05). There was significant difference in serum betatrophin among control, low liver fat content (LLFC), and high liver fat content (HLFC) groups (P < 0.01). After adjustment for gender, age, BMI, FPG and HbA1c, the betatrophin positively correlated with LFC (r = 0.185, P < 0.01) and TG (r = 0.195, P < 0.01). Stepwise multiple regression analysis indicated serum betatrophin was independently related to LFC (P < 0.05). Multivariate logistic regression analysis revealed subjects in the highest tertile of serum betatrophin had higher odds of having NAFLD after adjustment for traditional NAFLD risk factors (OR = 2.88, 95%CI: 1.15-7.19) (P<0.05). CONCLUSION: Serum betatrophin is an independent risk factor for NAFLD and potential non-invasive marker for its progression. Serum betatrophin may be helpful for the early diagnosis of NAFLD and improvement of its prognosis.

Relationship between Branched-Chain Amino Acids, Metabolic Syndrome, and Cardiovascular Risk Profile in a Chinese Population: A Cross-Sectional Study.

Objective. This study aimed to evaluate the relationship between branched-chain amino acids (BCAAs), metabolic syndrome (MS), and other cardiovascular (CV) risk factors in middle-aged and elderly Chinese population at high risk for the development of cardiovascular disease (CVD). Methods. 1302 subjects were enrolled from the Huai'an Diabetes Prevention Program. Results. BCAAs levels were positively correlated with MS, its components, and CV risk profile. The odds ratio (OR) for MS among subjects in the fourth quartile of BCAAs levels showed a 2.17-fold increase compared with those in the first quartile. BCAAs were independently associated with high Framingham risk score even after adjusting for MS and its components (P < 0.0001). Additionally, the OR for high CV risk was 3.20-fold (P < 0.0001) in participants in the fourth BCAAs quartile with MS compared with participants in the first BCAAs quartile without MS. Conclusions. Increased BCAAs levels are independent risk factors of MS and CVD in addition to the traditional factors in middle-aged and elderly Chinese population. The development of CVD in MS patients with high level BCAAs is accelerated. Intervention studies are needed to investigate whether the strategy of BCAAs reduction has impacts on endpoints in patients with higher CV risk. This study is registered with ChiCTR-TRC-14005029.

The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients.

Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobinA1c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1DM patients (duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.

Association of elevated glycosylated hemoglobin A1c with hyperfiltration in a middle-aged and elderly Chinese population with prediabetes or newly diagnosed diabetes: a cross-sectional study.

BACKGROUND: To examine whether elevated glycosylated hemoglobin A1c (HbA1c) is associated with hyperfiltration in a middle-aged and elderly Chinese population. METHODS: Anthropometric and biochemical examinations were performed in 2491 individuals from the general population, aged 40-79 years, who participated in the Huaian Diabetes Prevention Program. The estimated glomerular filtration rate (eGFR) was calculated from creatinine levels using the CKD-EPI formula. Hyperfiltration was defined as eGFR >90(th) percentile. RESULTS: After adjustment [for age, gender, waistline, body mass index, blood pressure, smoking, alcohol consumption, cholesterol, log(triglycerides), high-density lipoprotein, low-density lipoprotein, serum uric acid, sodium intake, hypertension, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers], HbA1c and fasting plasma glucose (FPG) were found to be independently positively associated with eGFR. Additionally, after multivariate adjustment, the odds ratios (95 % CI) for hyperfiltration calculated for a 1-unit increase in HbA1c and FPG were 1.396 (1.089-1.790) and 1.306 (1.117-1.526), respectively. Compared with participants with HbA1c levels <5.7%, the odds ratios (95 % CI) for hyperfiltration were 2.344 (1.025-5.364) in participants with HbA1c levels of 6.21-6.49%, and 2.965 (1.537-5.720) in those with HbA1c levels ≥ 6.5%. CONCLUSION: Elevated HbA1c (≥ 6.21%) is associated with an increased odds of hyperfiltration in middle-aged and elderly Chinese. Longitudinal studies are needed to explore whether hyperfiltration increases the odds of diabetic nephropathy in individuals with prediabetes.

Serum copeptin as a new biomarker in the early diagnosis of decline in renal function of type 2 diabetes mellitus patients.

OBJECTIVE: This study aimed to investigate the correlation between serum copeptin and glomerular filtration rate (GFR) in type 2 diabetes mellitus (T2DM) patients and to investigate the role of serum copeptin in the diagnosis of early DN in T2DM patients. METHODS: 120 T2DM inpatients were recruited and divided into 2 groups according to 24-h urine albumin excretion (UAE): normal UAE group (UAE<30 mg/24 h) and microalbuminuria group (30 mg/24 h≤UAE≤300 mg/24 h). RESULTS: Decline in GFR was found in 6.1% of patients in normal UAE group and 26.4% in microalbuminuria group. However, serum copeptin was comparable between two groups. Serum copeptin was negatively related to GFR (r=-0.586, P<0.001). Multivariate logistic regression analysis showed, after adjustment for age and gender, the OR of copeptin, 24-h UAE was 1.234 (95% CI: 1.003-1.456) (P<0.05) and 1.068 (95% CI: 1.005-1.187) (P<0.05), respectively. Univariate analysis of ROC showed the sensitivity of copeptin and 24-h UAE was 78.9% and 63.2%, respectively and the specificity was 88.9% and 89.7%, respectively in the diagnosis of DN, but the area under ROC of copeptin in combination with 24-h UAE was 0.90 (95% CI: 0.82-0.99) with the sensitivity of 80.9% and specificity of 91.1%. CONCLUSION: Serum copeptin is an independent risk factor of decline in renal function of T2DM patients. Copeptin in combination with 24-h UAE are helpful for the early diagnosis of DN. The causative relationship between serum copeptin and GFR is required to be further studied in long-term follow up.

Evaluation of serum ischemia-modified albumin levels in pregnant women with and without gestational diabetes mellitus.

OBJECTIVE: To investigate serum ischemia-modified albumin (IMA) levels in gestational diabetes mellitus and the effect of treatment with continuous subcutaneous insulin infusion on the biomarker. METHODS: The gestational diabetes mellitus women in the second trimester were evaluated before and after the two kinds of treatments with continuous subcutaneous insulin infusion and medical nutrition therapy for 6 weeks. Maternal serum ischemia-modified albumin and metabolic parameters were measured at baseline and at the 6th week. RESULTS: Serum ischemia-modified albumin levels and metabolic parameters were higher in patients with gestational diabetes mellitus at baseline than in controls. Ischemia-modified albumin levels were correlated with plasma glucose (p < 0.05). Variables of glycemic control and ischemia-modified albumin levels were significantly reduced at the 6th week. The effect of insulin treatment was generally better than diet therapy. Linear regression analysis showed that fasting plasma glucose was an independent determinant for IMA levels (ß = 0.611, p = 0.035).Fetal outcome was similar except for macrosomia and Apgar score at 5 min. CONCLUSION: Serum ischemia-modified albumin levels were higher in gestational diabetes mellitus compared to normal pregnancy. Continuous subcutaneous insulin infusion consistently improved metabolic disorder control. Gestational diabetes mellitus women were associated to a higher risk of oxidative stress and pregnancy complications.