Exposure of benzo[a]pyrene induces HCC exosome-circular RNA to activate lung fibroblasts and trigger organotropic metastasis

Background:Benzo[a]pyrene(B[a]P),a carcinogen pollutant produced by combustion processes,is present in the western diet with grilled meats.Chronic exposure of B[a]P in hepatocellular carcinoma(HCC)cells promotes metastasis rather than primary proliferation,implying an unknown mechanism of B[a]P-induced malignancy.Given that exosomes carry bioactive molecules to distant sites,we investigated whether and how exosomes mediate cancer-stroma communications for a toxicologically associated microenvironment.Method:Exosomes were isolated from B[a]P stimulated BEL7404 HCC cells(7404-100Bap Exo)at an environmental relevant dose(100 nmol/L).Lung preeducation animal model was prepared via injection of exosomes and cytokines.The inflammatory genes of educated lungs were evaluated using quantitative reverse transcription PCR array.HCC LM3 cells transfected with firefly luciferase were next injected to monitor tumor burdens and organotropic metastasis.Profile of B[a]P-exposed exosomes were determined by ceRNA microarray.Interactions between circular RNA(circRNA)and microRNAs(miRNAs)were detected using RNA pull-down in target lung fibroblasts.Fluorescence in situ hybridization and RNA immunoprecipitation assay was used to evaluate the“on-off”interaction of circRNA-miRNA pairs.We further developed an adenoassociated virus inhalation model to examine mRNA expression specific in lung,thereby exploring the mRNA targets of B[a]P induced circRNA-miRNA cascade.Results:Lung fibroblasts exert activation phenotypes,including focal adhesion and motility were altered by 7404-100Bap Exo.In the exosome-educated in vivo model,fibrosis factors and pro-inflammatory molecules of are up-regulated when injected with exosomes.Compared to non-exposed 7404 cells,circ_0011496 was up-regulated following B[a]P treatment and wasmainly packaged into 7404-100Bap Exo.Exosomal circ_0011496 were delivered and competitively bound to miR-486-5p in recipient fibroblasts.The down-regulation of miR-486-5p converted fibroblast to cancer-associated fibroblast via regulating the downstream of Twinfilin-1(TWF1)and matrix metalloproteinase-9(MMP9)cascade.Additionally,increased TWF1,specifically in exosomal circ_0011496 educated lungs,could promote cancer-stroma crosstalk via activating vascular endothelial growth factor(VEGF).These modulated fibroblasts promoted endothelial cells angiogenesis and recruited primary HCC cells invasion,as a consequence of a pre-metastatic niche formation.Conclusion:We demonstrated that B[a]P-induced tumor exosomes can deliver circ_0011496 to activate miR-486-5p/TWF1/MMP9 cascade in the lung fibroblasts,generating a feedback loop that promoted HCC metastasis.

Regulation of microbiota–GLP1 axis by sennoside A in diet-induced obese mice

Sennoside A(SA) is a bioactive component of Chinese herbal medicines with an activity of irritant laxative, which is often used in the treatment of constipation and obesity. However, its activity remains unknown in the regulation of insulin sensitivity. In this study, the impact of SA on insulin sensitivity was tested in high fat diet(HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR(homeostatic model assessment for insulin resistance) and glucose tolerance test(GTT). SA restored plasma level of glucagon-like peptide 1(GLP1) by 90% and mRNA expression of Glp1 by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids(SCFAs), and mucosal structure in the colon. A mitochondrial stress was observed in the enterocytes of HFD mice with ATP elevation, structural damage, and complex dysfunction. The mitochondrial response was induced in enterocytes by the dietary fat as the same responses were induced by palmitic acid in the cell culture. The mitochondrial response was inhibited in HFD mice by SA treatment. These data suggest that SA may restore the function of microbiota–GLP1 axis to improve glucose metabolism in the obese mice.

Chiglitazar monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes:a randomized,double-blind,phase 3 trial(CMAS)

Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this randomized phase 3 trial,we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen.Eligible patients were randomized(1:1:1)to receive chiglitazar 32 mg(n=245),chiglitazar 48 mg(n=246),or sitagliptin 100 mg(n=248)once daily for 24 weeks.The primary endpoint was the change in glycosylated hemoglobin A_(1C)(HbA_(1c))from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin.Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of-1.40%,-1.47%,and-1.39%for chiglitazar 32 mg,chiglitazar 48 mg,and sitagliptin 100 mg,respectively.Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg,with mean differences of-0.04%(95%confidential interval(Cl)-0.22 to 0.15)and-0.08%(95%Cl-0.27 to 0.10),respectively.Compared with sitagliptin,greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar.Overall adverse event rates were similar between the groups.A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported.The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.

Efficacy and safety of chiglitazar,a novel peroxisome proliferatoractivated receptor pan-agonist,in patients with type 2 diabetes:a randomized,double-blind,placebo-controlled,phase 3 trial(CMAP)

Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies.This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone.Eligible patients were randomly assigned to receive chiglitazar 32 mg(n=167),chiglitazar 48 mg(n=166),or placebo(n=202)once daily.The primary endpoint was the change in glycosylated hemoglobin A_(1c)(HbA_(1c))at week 24 with superiority of chiglitazar over placebo.The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA_(1c),and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were-0.87%(95%confidential interval(CI):-1.10 to-0.65;P<0.0001)and-1.05%(95%CI:-1.29 to-0.81;P<0.0001),respectively.Secondary efficacy parameters including glycemic control,insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups.The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups.Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups.The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.

Altered intestinal microbiota associated with colorectal cancer

The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal-luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in Eubacterium, which is a butyrate-producing genera of bacteria, and a significant increase in Devosia in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to Eubacterium and Devosia may serve as a promising biomarker for the early detection of CRC.

Hyocholic acid and glycemic regulation:comments on‘Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism’

Hyocholic acid species(HCA,hyodeoxycholic acid,and their glycine and taurine conjugated forms)comprise 80%of the composition of pig bile(Haslewood,1956).An interesting fact about pigs is that they do not get diabetes even though they eat almost everything and in abundant amounts,a diabetes-promoting diet.The first use of pig bile for treatment of‘xiao-ke’.

miRNAs in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease （NAFLD） is a major cause of liver cirrhosis and hepatocellular carcinoma and is a considerable threat to public health, miRNAs are important post-transcriptional regulators of gene expression, and the dysregulation of miRNAs is involved in various biological processes in the liver, including lipid homeostasis, inflammation, apoptosis, and cell proliferation. Recently, a number of studies have described the association between miRNAs and NAFLD progression and have shown that circulating miRNAs reflect histological changes in the liver. Therefore, circulating miRNAs have potential use for the evaluation of NAFLD severity. In this review, we discuss the involvement of miRNAs in NAFLD pathogenesis and the key role of miRNAs in the screening, diagnosis, and staging of NAFLD.

Whole-exome sequencing identifies a novel INS mutation causative of maturity-onset diabetes of the young 10

Monognnic diabetes is often misdiagnosed with type 2 diabetes due to overlapping characteristics. This study aimed to discover novel causative mutations of monogenic diabetes in patients with clinically diagnosed type 2 diabetes and to explore potential molecular mechanisms. Whole-exome sequencing was performed on 31 individuals clinically diagnosed with type 2 diabetes. One novel heterozygnus mutation （p^la2Thr） in INS was identified. It was further gnnotyped in an additional case-control population （6523 cases and 4635 controls）, and this variant was observed in 0.09% of cases. IntraceUular trafficking of insulin proteins was assessed in INSl-E and HEK293T cells, p.Ala2Thr preproinsuUn-GFP was markedly retained in the endoplasmic reticulum （ER） in INS1-E cells. Activation of the PERK-elF2a-ATF4, IREla-XBP1, and ATF6 pathways as well as upregulated ER chaperones were detected in INS1-E cells transfected with the p.Ala2Thr mutant. In conclusion, we identified a causative mutation in IN5 respon- sible for maturity-onset diabetes of the young 10 （MODYIO） in a Chinese population and demonstrated that this mutation affected 13 cell function by inducing ER stress.

Effects and mechanisms of berberine in diabetes treatment

Berberine from Rhizoma Coptidis is an oral hypoglycemic agent with anti-dyslipidemia and anti-obesity activities.Its metabolic activity of regulating blood glucose and lipids has been widely studied and evidenced in patients and various animal models.Berberine is known as an AMP-activated protein kinase(A MPK)activator.Its insulin-independent hypoglycemic effect is.related to inhibition of mitochondrial function,stimulation of glycolysis and activation of AMPK pathway.Additionally,berberine may also act as an x-glucosidase inhibitor.In the newly-diagnosed type 2 diabetic patients,berberine is able to lower blood insulin level via enhancing insulin sensitivity.However,in patients with poorβ-cell function,berberine may improve insulin secretion via resuscitating exhausted islets.Furthermore,berberine may have extra beneficial effects on diabetic cardiovascular complications due to its cholesterol-lowering,anti arrhythmias and nitric oxide(NO)inducing properties.The antioxidant and aldose reductase inhibitory activities of berberine may be useful in alleviating dia betic nephropathy.Although evidence from animal and human studies consistently supports the therapeutic activities of berberine,large-scale multicenter trials are still necessary to evaluate the efficacy of berberine on diabetes and its related complications.

Insulin resistance and the metabolism of branched-chain amino acids

Insulin resistance(IR)is a key pathological feature of metabolic syndrome and subsequently causes serious health problems with an increased risk of several common metabolic disorders.IR related metabolic disturbance is not restricted to carbohydrates but impacts global metabolic network.Branched-chain amino acids(BCAAs),namely valine,leucine and isoleucine,are among the nine essential amino acids,accounting for 35%of the essential amino acids in muscle proteins and 40%of the preformed amino acids required by mammals.The BCAAs are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in insulin resistant conditions and/or insulin deficiency.Although increased circulating BCAA concentration in insulin resistant conditions has been noted for many years and BCAAs have been reported to be involved in the regulation of glucose homeostasis and body weight,it is only recently that BCAAs are found to be closely associated with IR.This review will focus on the recent findings on BCAAs from both epidemic and mechanistic studies.

Multi-omics profiling:the way toward precision medicine in metabolic diseases

Metabolic diseases including type 2 diabetes mellitus(T2DM),non-alcoholic fatty liver disease(NAFLD),and metabolic syndrome(MetS)are alarming health burdens around the world,while therapies for these diseases are far from satisfying as their etiologies are not completely dear yet.T2DM,NAFLD,and MetS are all complex and multifactorial metabolic disorders based on the interactions between genetics and environment.Omics studies such as genetics,transcriptomics,epigenetics,proteomics,and metabolomics are all promising approaches in accurately characterizing these diseases.And the most effective treatments for individuals can be achieved via omics pathways,which is the theme of precision medicine.In this review,we summarized the multi-omics studies of T2DM,NAFLD,and MetS in recent years,provided a theoretical basis for their pathogenesis and the effective prevention and treatment,and highlighted the biomarkers and future strategies for precision medicine.

Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy(STRATEGY):a multicenter,randomized,controlled,non-inferiority clinical trial

Despite the current guideline's recommendation of a timely stepwise intensification therapy,the "clinical inertia",termed as the delayed treatment intensification,commonly exists in the real world,which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy.In this clinical trial performed in 237 centers in China,5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks.The patients who did not reach the glycated hemoglobin A1c(HbA1c) goal were then further randomized into glimepiride,gliclazide,repaglinide,or acarbose group for an additional 24-week triple therapy.A mean HbAlc reduction of 0.85%was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks.Further HbAlc reductions in the 24-week triple therapy stage were 0.65%in glimepiride group,0.70%in gliclazide group,0.61%in repaglinide group,and 0.45%in acarbose group.The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide,but not for acarbose,compared with glimepiride,when added to metformin/sitagliptin dual therapy.The incidences of adverse events(AEs) were 29.2%in the dual therapy stage and30.3%in the triple therapy stage.Metformin/sitagliptin as baseline therapy,with the addition of a third oral antihyperglycemic agent,including glimepiride,gliclazide,repaglinide,or acarbose,was effective,safe and well-tolerated for achieving an HbAlc<7.0%goal in type 2 diabetic patients inadequately controlled with previous therapies.The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia.

Association between serum somatostatin levels and glucose-lipid metabolism in the Jino ethnic minority and Han Chinese population

We aim to investigate the relationship between serum somatostatin(SST) levels and glucose-lipid metabolism at various stages of glucose tolerance in the Jino ethnic minority(n=111) and Han population(n=113) of Yunnan Province, southwest China.Anthropometric parameters and biochemical traits were measured. Serum SST and plasma glucagon levels were tested. Participants were divided into three subgroups: isolated fasting hyperglycemia(IFH), isolated post challenge hyperglycemia(IPH)and normal glucose tolerance(NGT). SST levels were found lower while glucagon levels were significantly higher in the Jino ethnic with IPH(P=0.0026 and P=0.0069, respectively). Fasting glucose and high density lipoprotein-cholesterol(HDL-C)levels were higher(P=0.0055 and P=0.0021, respectively) and fasting insulin levels and homeostasis model assessments β-cell function were lower(P=0.0479 and P=0.0007, respectively) in the Jino population. After adjusting for confounding factors, the serum SST level was associated with glucagon(P<0.0001) in both populations. The SST level was correlated with fasting Cpeptide(P=0.0267) in Jino and HDL-C levels in Han(P=0.0079). Our findings suggest that serum SST levels and plasma glucagon levels may vary in subjects with IPH between two ethnics.

Effectiveness of quality of care for patients with type 2 diabetes in China:findings from the Shanghai Integration Model(SIM)

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai,China.A total of 173235 patients with type 2 diabetes in 2017 were included in the analysis.Profiles of risk factors and intermediate outcomes were determined.The patients had a mean age of 66.43±8.12(standard deviation(SD))years and a mean diabetes duration of 7.95±5.53(SD)years.The percentage of patients who achieved the target level for HbA_(1c)(<7.0%)was 48.6%.Patients who achieved the target levels for blood pressure(BP)<130/80 mmHg and low-density lipoprotein-cholesterol(LDL-c)<2.6 mmol/L reached 17.5%and 34.0%,respectively.A total of 3.8%achieved all three target levels,and the value increased to 6.8%with an adaptation of the BP target level(<140/90 mmHg)for those over 65 years.Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels:male,young age,short diabetes duration,low body mass index,macrovascular complications,no microvascular complications,prescribed with lipid-lowering medication,and no prescription of antihypertensive medication.In conclusion,nearly 50%and one-third of the patients with diabetes met the target levels for HbA_(1c)and LDL-c,respectively,with a low percentage achieving the BP target level.The percentage of patients who achieved all three target levels needs significant improvement.

NF-κB regulates brown adipocyte function through suppression of ANT2

The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells(NF-κB)is expressed in brown adipocytes,but its role remains largely unknown in the cells.This issue was addressed in current study by examining NF-κB in brown adipocytes in vitro and in vivo.NF-κB activity was increased by differentiation of brown adipocytes through elevation of p65(RelA)expression.The transcriptional activity of NF-κB was induced by the cold stimulation with an elevation in S276 phosphorylation of p65 protein.Inactivation of NF-κB in brown adipocytes made the knockout mice[uncoupling protein 1(Ucp1)-CreER-p65^(f/f),U-p65-KO]intolerant to the cold environment.The brown adipocytes exhibited an increase in apoptosis,a decrease in cristae density and uncoupling activity in the interscapular brown adipose tissue(iBAT)of p65-KO mice.The alterations became severer after cold exposure of the KO mice.The brown adipocytes of mice with NF-κB activation(p65 overexpression,p65-OE)exhibited a set of opposite alterations with a reduction in apoptosis,an increase in cristae density and uncoupling activity.In mechanism,NF-κB inhibited expression of the adenine nucleotide translocase 2(ANT2)in the control of apoptosis.Data suggest that NF-κB activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression.

Fibroblast growth factor 21:a novel metabolic regulator from pharmacology to physiology

Fibroblast growth factor 21(FGF21)is a member of the fibroblast growth factor family.It actually functions as endocrine hormones but does not regulate cell growth and differentiation.It is demonstrated that FGF21 acts on multiple tissue to coordinate carbohydrate and lipid metabolism,including enhancing insulin sensitivity,decreasing triglyceride concentrations,causing weight loss,ameliorating obesity-associated hyperglycemia and hyperlipidemia.Moreover,FGF21 also plays important roles in some physiological processes,such as fasting and feeding,growth hormone axis and thermogenic function of brown adipose tissue.Clinical relevance of FGF21 in humans is still unclear,and the basis and consequences of increased FGF21 in metabolic disease remain to be determined.Both the pharmacological actions and physiological roles make FGF21 attractive drug candidates for treating metabolic disease,but some questions remain to be answered.This article concentrates on recent advances in our understanding of FGF21.

Ultra rapid lispro improves postprandial glucose control versus lispro in combination with insulin glargine/degludec in adults with type 2 diabetes:a prospective,randomized,double-blind,phase 3 trial

Ultra rapid lispro(URLi)is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal,with the aim of improving postprandial glucose(PPG)control.We conducted a multinational,multicenter,randomized,double-blind,treat-to-target,26-week,phase 3 trial to evaluate the efficacy and safety of URLi in adults with type 2 diabetes(T2D).After an 8-week lead-in period during which basal insulin glargine or degludec was optimized,adults with T2D were randomized(2:1)to prandial URLi(n=395)or lispro(n=200).The primary endpoint was non-inferiority of URLi versus lispro in glycated hemoglobin A1c(HbA_(1c))change from baseline to week 26.Multiplicity-adjusted analyses were performed to assess the superiority of URLi in 1-and 2-h PPG excursions during a mixed-meal tolerance test(MMTT)and HbA_(1c) change at week 26.URLi showed non-inferiority for Hb Achange at week 26 versus lispro(least-squares mean[LSM]difference,0.07%;95%confidence interval:-0.07,0.21).HbA_(1c) was reduced by 0.56%and 0.63%with URLi and lispro,respectively,with no significant treatment difference(P=0.321).URLi provided superior PPG excursion control versus lispro at1 h(LSM difference:-14.6 mg/d L,P<0.001)and 2 h(LSM difference:-21.8 mg/d L,P<0.001)as well as other time points(30–240 min)during the MMTT.Incremental area under the glucose curve during the MMTT was also significantly lower with URLi versus lispro.The safety profiles were generally similar between treatment groups.In conclusion,URLi was superior to lispro for PPG control,with noninferiority in HbA_(1c) improvement,in adults with T2D.

Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation

Most information used to evaluate diabetic statuses is collected at a special time-point,such as taking fasting plasma glucose test and providing a limited view of individual’s health and disease risk.As a new parameter for continuously evaluating personal clinical statuses,the newly developed technique“continuous glucose monitoring”(CGM)can characterize glucose dynamics.By calculating the complexity of glucose time series index(CGI)with refined composite multi-scale entropy analysis of the CGM data,the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes(P for trend<0.01).Furthermore,CGI was significantly associated with various parameters such as insulin sensitivity/secretion(all P<0.01),and multiple linear stepwise regression showed that the disposition index,which reflectsβ-cell function after adjusting for insulin sensitivity,was the only independent factor correlated with CGI(P<0.01).Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized clinical trial

Lifestyle interventions,including dietary adjustments and exercise,are important for obesity management.This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet(LCD)or exercise is more effective in metabolism improvement.Forty-five eligible subjects were randomly divided into an LCD group(n=22)and an exercise group(EX,n=23).The subjects either adopted LCD(carbohydrate intake<50 g/day)or performed moderate-to-vigorous exercise(≥30 min/day)for 3 weeks.After the interventions,LCD led to a larger weight loss than EX(−3.56±0.37 kg vs.−1.24±0.39 kg,P<0.001),as well as a larger reduction in fat mass(−2.10±0.18 kg vs.−1.25±0.24 kg,P=0.007)and waist circumference(−5.25±0.52 cm vs.−3.45±0.38 cm,P=0.008).Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance.Triglycerides decreased in both two groups,whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group.Various glycemic parameters,including serum glycated albumin,mean sensor glucose,coefficient of variability(CV),and largest amplitude of glycemic excursions,substantially declined in the LCD group.Only CV slightly decreased after exercise.This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance.Compared with exercise,LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.

Metabolomics in human type 2 diabetes research

The high prevalence of diabetes and diabetic complications has caused a huge burden on the modern society.Although scientific advances have led to effective strategies for preventing and treating diabetes over the past several decades,little progress has been made toward curing the disease or even getting it under control,from a public health and overall societal standpoint.There is still a lack of reliable biomarkers indicative of metabolic alterations associated with diabetes and different drug responses,highlighting the need for the development of early diagnostic and prognostic markers for diabetes and diabetic complications.The emergence of metabolomics has allowed researchers to systemically measure the small molecule metabolites,which are sensitive to the changes of both environmental and genetic factors and therefore,could be regarded as the link between genotypes and phenotypes.During the last decade,the progression made in metabolomics has provided insightful information on disease development and disease onset prediction.Recent studies using metabolomics approach coupled with statistical tools to predict incident diabetes revealed a number of metabolites that are significantly altered,including branched-chain and aromatic amino acids,such as isoleucine,leucine,valine,tyrosine and phenylalanine,as diagnostic or highly-significant predictors of future diabetes.This review summarizes the current findings of metabolomic studies in human investigations with the most common form of diabetes,type 2 diabetes.