Interactions between myoblasts and macrophages under high glucose milieus result in inflammatory response and impaired insulin sensitivity

BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal muscle.However,despite of the decades of research,whether macrophages infiltration and polarization in skeletal muscle under high glucose(HG)milieus results in the development of IR is yet to be elucidated.C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to stimulation.Further exploration of macrophages'role in myoblasts IR and the dynamics of their infiltration and polarization is warranted.AIM To evaluate interactions between myoblasts and macrophages under HG,and its effects on inflammation and IR in skeletal muscle.METHODS We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical staining.Then,we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG milieus.The effects of myoblasts on macrophages were explored through morphological observation,CCK-8 assay,Flow Cytometry,and enzyme-linked immunosorbent assay.The mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation,CCK-8 assay,Immunofluorescence,and 2-NBDG assay.RESULTS The F4/80 and co-localization of F4/80 and CD86 increased,and the myofiber size decreased in IR group(P<0.01,g=6.26).Compared to Mc group,F4/80+CD86+CD206-cells,tumor necrosis factor-α(TNFα),inerleukin-1β(IL-1β)and IL-6 decreased,and IL-10 increased in McM group(P<0.01,g>0.8).In McM+HG group,F4/80+CD86+CD206-cells,monocyte chemoattractant protein 1,TNFα,IL-1βand IL-6 were increased,and F4/80+CD206+CD86-cells and IL-10 were decreased compared with Mc+HG group and McM group(P<0.01,g>0.8).Compered to M group,myotube area,myotube number and E-MHC were increased in MMc group(P<0.01,g>0.8).In MMc+HG group,myotube area,myotube number,E-MHC,GLUT4 and glucose uptake were decreased compared with M+HG group and MMc group(P<0.01,g>0.8).CONCLUSION Interactions between myoblasts and macrophages under HG milieus results in inflammation and IR,which support that the macrophage may serve as a promising therapeutic target for skeletal muscle atrophy and IR.

Short-Term Effects of Liraglutide versus Vildagliptin on Insulin Secretion and Sensitivity in Type 2 Diabetes: A Single Blinded Randomized Controlled Trial (LIRAVIS Study)

Background: We aimed to evaluate the short-term metabolic effects of a GLP-1a, (liraglutide) versus a DPP-4i, (vildagliptin) in a group of sub-Saharan type 2 diabetes patients. Methods: We conducted a randomized controlled single blinded clinical trial in 14 uncontrolled type 2 diabetes patients (HbA1c ≥ 53 mmol/mol) with mean duration of diabetes of 8 [1 - 12] years and median age of 57 [49 - 61] years. Baseline treatment consisted of metformin in monotherapy or metformin plus sulfonylureas. Participants were randomly allocated to 2 groups of add-on 1.2 mg/day subcutaneous liraglutide in group 1 or 100 mg/day of oral vildagliptin in group 2 for 2 weeks. In all participants, insulin secretion in response to mixed meal tolerance test, insulin sensitivity by 80 mU/m2/min hyperinsulinemic-euglycemic clamp, body composition, and lipid profile were measured before and after intervention. Results: At the end of intervention, insulin sensitivity remained unchanged both with liraglutide from 6.6 [4.2 - 7.9] to 6.9 [4.3 - 10.8] mg/kg/min;p = 0.61 and vildagliptin from 7.1 [5.3 - 9.0] to 6.5 [5.6 - 9.4] mg/kg/min (p = 0.86). The area under the C-peptide curve varied from 5.5 [1.0 - 10.9] to 14.9 [10.8 - 17.2] nmol/L/120min, p = 0.09 in group 1 and from 1.1 [0.5 - 14.1] to 13.0 [9.6 - 16.9] nmol/L/120min (p = 0.17) in group 2. LDL Cholesterol levels decreased significantly with liraglutide from 0.85 g/L [0.51 - 1.02] to 0.54 g/L [0.50 - 0.73] (p = 0.04) but not with Vildagliptin. Body weight tended to decrease in group 1 (−0.6 kg) versus modest increase in group 2 (+1.1 kg). Conclusion: Short-term metabolic effects of Liraglutide and Vildagliptin add-on therapy are comparable in sub-Saharan type 2 diabetes patients with a more favorable trend for Liraglutide on body weight, lipid profile, and insulin secretion.

Association of vitamin D and magnesium with insulin sensitivity and their influence on glycemic control

Insulin resistance increases the risk of developing diabetes,and the degree of resistance influences the glycemic control of patients with diabetes.Numerous researchers have focused on improving insulin sensitivity in order to prevent diabetes-related complications and other chronic diseases.Several studies have also linked vitamin D levels to insulin secretion and resistance,given that both vitamin D and its receptor complex play important roles in regulating pancreaticβ-cells.It has been suggested that vitamin D supplementation improves vitamin D levels,but further research is needed to confirm this as neither insulin function nor glycemic control improves when vitamin D levels increase.Magnesium is a cofactor for many enzymes.Although the role of magnesium in the management of diabetes has long been evaluated,it has not yet been determined whether magnesium supplements improve insulin function.However,several researchers have found that patients with good glycemic control have high magnesium levels.Magnesium is closely related to vitamin D and is necessary for the transport and activation of vitamin D in humans.Combined supplementation with vitamin D and magnesium improves glycemic control in patients with diabetes.

Association of point in range withβ-cell function and insulin sensitivity of type 2 diabetes mellitus in cold areas

Background and Objective:Self-monitoring of blood glucose(SMBG)is crucial for achieving a glycemic target and upholding blood glucose stability,both of which are the primary purpose of anti-diabetic treatments.However,the association between time in range(TIR),as assessed by SMBG,andβ-cell insulin secretion as well as insulin sensitivity remains unexplored.Therefore,this study aims to investigate the connections between TIR,derived from SMBG,and indices representingβ-cell functionality and insulin sensitivity.The primary objective of this study was to elucidate the relationship between short-term glycemic control(measured as points in range[PIR])and bothβ-cell function and insulin sensitivity.Methods:This cross-sectional study enrolled 472 hospitalized patients with type 2 diabetes mellitus(T2DM).To assessβ-cell secretion capacity,we employed the insulin secretion-sensitivity index-2(ISSI-2)and(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,while insulin sensitivity was evaluated using the Matsuda index and HOMA-IR.Since SMBG offers glucose data at specific point-in-time,we substituted TIR with PIR.According to clinical guidelines,values falling within the range of 3.9-10 mmol were considered"in range,"and the corresponding percentage was calculated as PIR.Results:We observed significant associations between higher PIR quartiles and increased ISSI-2,(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,Matsuda index(increased)and HOMA-IR(decreased)(all P<0.001).PIR exhibited positive correlations with log ISSI-2(r=0.361,P<0.001),log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index(r=0.482,P<0.001),and log Matsuda index(r=0.178,P<0.001)and negative correlations with log HOMA-IR(r=-0.288,P<0.001).Furthermore,PIR emerged as an independent risk factor for log ISSI-2,log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,log Matsuda index,and log HOMA-IR.Conclusion:PIR can serve as a valuable tool for assessingβ-cell function and insulin sensitivity.

Insulin Sensitivity of Term Newborns Exposed in Utero to HIV and Antiretrovirals in Yaoundé

Introduction: Antiretrovirals (ARVs) and the human immunodeficiency virus (HIV) are implicated in the onset of insulin resistance. They cross the placental barrier thereby inducing early modifications of the fetal environment. The aim of our study was to assess insulin sensitivity in full-term newborns exposed in utero to HIV and ARVs in Yaoundé. Materials and Methods: We conducted an analytical cross-sectional study in 2 maternities in the city of Yaoundé from November 2021 to June 2022. We generated two groups of newborns (NBs): one group born to HIV positive mothers on ARVs and the other control group born to HIV negative mothers. Clinical data from mothers and NBs were collected. A homeostatic model assessment of insulin resistance (HOMA-IR) like index with C peptide served to assess insulin sensitivity. We used the Spearman correlation to measure the strength of association between insulin sensitivity and the different variables. A p-value Results: Of 70 neonates included, 35 were born to HIV positive mothers on ARVs and 35 to HIV negative mothers. The median age of HIV positive and negative mothers was 30 (27 - 32) and 34 (24 - 47) years, respectively (p = 0.791). The body mass index before pregnancy as well as the average newborn weights were comparable in both groups. The ARV protocol associating Tenofovir, Lamivudine, Efavirenz was used by 97.1% of HIV positive mothers. In the exposed NBs group, C peptide was significantly lower (p < 0.001) and blood glucose significantly higher (p < 0.001). The median values of HOMA-IR were 1.4 (0.8 - 1.9) and 2 (1.4 - 2.6) (p = 0.001) for exposed and unexposed NBs, respectively. Conclusion: Newborns exposed to HIV and ARVs had lower C peptide levels and were more sensitive to insulin. Close metabolic monitoring of these newborns would allow early diagnosis and management of any glucose regulation disorder.

Perspectives on diacylglycerol-induced improvement of insulin sensitivity in type 2 diabetes

Diacylglycerol(DAG)-based edible oils have attracted increasing research interest owing to their healthpromoting properties.Recent animal and human studies showed that an increased 1,2-DAG content in the liver and skeletal muscle may cause insulin resistance.However,earlier studies using animal models or humans reported that dietary DAGs with a 1,2-DAGs to 1,3-D AGs ratio of approximately 3:7 could improve insulin sensitivity in type 2 diabetic patients.This conflict raises the question of whether there is a link between the ingested DAGs and endogenous DAGs during their metabolism.To make a contribution to this field,this review provides an overview of the metabolic pathways of ingested DAGs and biological roles of DAGs(ingested and endogenous)in the change of insulin sensitivity.Accordingly,strategies for further investigations on the metabolism of DAGs are proposed.

Effect of resistance exercise on insulin sensitivity of skeletal muscle

Insulin resistance(IR)is the common pathophysiological basis of many metabolic diseases.IR is characterized by decreased glucose uptake in skeletal muscle and adipose tissue,especially in skeletal muscle.Skeletal muscle is the main target tissue of glucose uptake under insulin stimulation.Glucose uptake by skeletal muscle is complex,and it is controlled by many pathways.The PI3K/AKt/GSK-1 signaling pathway is not only the main pathway for insulin signal transduction but also an important mechanism for regulating blood glucose.From the binding of insulin to its receptors on the surface of target cells to the transportation of glucose from extracellular fluid to skeletal muscle,a series of signal transduction processes is completed,any of which potentially affects the physiological effects of insulin and leads to IR.Resistance exercise(RT)can reduce skeletal muscle IR and effectively improve blood glucose control and glycosylated hemoglobin level in patients with type 2 diabetes mellitus(T2DM).However,the exact mechanism by which RT improves skeletal muscle IR remains unclear.Therefore,this paper discusses the above problems by tracking the progress of the literature to deepen the correlation between RT and skeletal muscle insulin sensitivity and provide further evidence for the application of exercise therapy in IR.In conclusion,RT mainly improves insulin sensitivity of skeletal muscle by increasing muscle mass,microvascular blood flow,and glucose transporter-4 expression in skeletal muscle,as well as by reducing lipid accumulation and inflammation in skeletal muscle.Thus,it is potentially useful in the prevention and treatment of T2DM.

Insulin Resistance in Pregnancy Is Correlated with Decreased Insulin Receptor Gene Expression in Omental Adipose: Insulin Sensitivity and Adipose Tissue Gene Expression in Normal Pregnancy

Aims: To determine correlations of insulin sensitivity to gene expression in omental and subcutaneous adipose tissue of non-obese, non-diabetic pregnant women. Methods: Microarray gene profiling was performed on subcutaneous and omental adipose tissue from 14 patients and obtained while fasting during non-laboring Cesarean section, using Illumina HumanHT-12 V4 Expression BeadChips. Findings were validated by real-time PCR. Matusda-Insulin sensitivity index (IS) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated from glucose and insulin levels obtained from a frequently sampled oral glucose tolerance test, and correlated with gene expression. Results: Of genes differentially expressed in omental vs. subcutaneous adipose, in omentum 12 genes were expressed toward insulin resistance, whereas only 5 genes were expressed toward insulin sensitivity. In particular, expression of the insulin receptor gene (INSR), which initiates the insulin signaling cascade, is strongly positively correlated with IS and negatively with HOMA-IR in omental tissue (r = 0.84). Conclusion: Differential gene expression in omentum relative to subcutaneous adipose showed a pro-insulin resistance profile in omentum. A clinical importance of omental adipose is observed here, as downregulation of insulin receptor in omentum is correlated with increased systemic insulin resistance.

Human skeletal muscle perilipin 2 and 3 expression varies with insulin sensitivity

Background: Impaired insulin sensitivity may partly arise from a dysregulated lipid metabolism in human skeletal muscle. This study investigates the expression levels of perilipin 2, 3, and 5, and four key lipases in human skeletal muscle from the subjects that exhibit a range from normal to very low insulin sensitivity. Methods: 25 middle aged male participants were matched for lean body mass and recruited into three groups;type 2 diabetes patients (T2D), impaired glucose tolerance (IGT), and healthy sedentary controls (CON) according to their glucose tolerance and VO2peak. A muscle biopsy was obtained from vastus lateralis, and a two-step sequential euglycaemic-hyperinsulinaemic clamp was performed. Muscle samples were analyzed by Western blot for expression of perilipin 2, 3, 5, adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), endothelial lipase (EL) and lipoprotein lipase (LPL). Results: Perilipin 3 expression was higher in T2D compared to CON. Perilipin 2 expression was higher in CON than T2D. We observed no difference in expression of perili pin 5, ATGL, HSL, EL or LPL between the groups. Conclusions: In the present study the muscle perilipin 3 expression and perilipin 2 expression varied markedly with insulin sensitivity. This difference in perilipin expression may indicate that the lipid droplet function and thus storage and release of fatty acid-vary with insulin sensitivity.

ASSOCIATION OF INSULIN RESISTANCE AND C-REACTIVE PROTEIN WITH CORONARY ARTERY DISEASE IN PATIENTS WITH NORMAL GLUCOSE TOLERANCE

Objective To examine insulin resistance and high sensitivity C-reactive protein （hsCRP） association with clinical and angiographic severity of coronary artery disease （CAD） in patients with normal glucose tolerance. Methods In 638 consecutive patients with normal glucose tolerance, 221 had atypical chest pain and normal coronary artery （control group）, 279 had stable angina and CAD （SAP group ）, and 138 suffered acute myocardial infarction （ MI group）. The degree of CAD was further divided into borderline lesion （ lumen diameter narrowing 50% - 69% ）, significant 1-, 2- or 3-vessel disease （ luminal diameter narrowing 〉I 70% ）. Fasting serum glucose, insulin and hsCRP levels and lipid profiles were measured, and homeostasis model assessment for insulin resistance （ HOMA-IR ） was calculated. Multivariate analysis was performed to assess risk factors for 3-vessel disease or acute MI. Results Serum hsCRP, lipoprotein （a） levels, and insulin resistance index （IRI） were higher in AMI group than those in SAP and control groups. Serum hsCRP level and IRI were also higher in 3-vessel disease than those in other groups. Multivariate regression analysis revealed that insulin resistance, cigarette smoking, serum hsCRP, and lipoprotein （a） levels were independent risk factors for acute MI. Lipoprotein （ a ） elevation was an independent risk factor for 3-vessel disease. Conclusion Insulin resistance and high serum hsCRP level were associated with occurrence of acute MI and angiographic severity of coronary disease in patients with normal glucose tolerance.

Nano-chromium picolinate and heat stress enhance insulin sensitivity in cross-bred sheep

This study evaluated the effects of heat stress(HS)and dietary nano chromium picolinate(nCrPic)on metabolic responses of sheep to an intravenous glucose tolerance test(IVGTT),an intravenous insulin tolerance test(ITT)and an intramuscular adrenocorticotropin hormone(ACTH)challenge in sheep.Thirty-six sheep housed in metabolic cages were randomly allocated within 3 dietary groups(0,400 and 800 mg/kg supplemental nCrPic)to either thermoneutral(22℃)or cyclic HS(22 to 40℃)conditions for 3 wk.Basal plasma glucose tended to be increased during HS(P=0.052)and decreased by dietary nCrPic(P=0.013)while plasma non-esterified fatty acid concentrations were decreased(P=0.010)by HS.Di-etary nCrPic reduced the plasma glucose area under the curve(P=0.012)while there were no significant effects of HS on plasma glucose area under the curve in response to the IVGTT.The plasma insulin response over the first 60 min after the IVGTT was decreased by HS(P=0.013)and dietary nCrPic(P=0.022)with the effects being additive.In response to the ITT plasma glucose reached a nadir sooner(P=0.005)in sheep exposed to HS,although there was no effect on the depth of the nadir.Dietary nCrPic decreased(P=0.007)the plasma glucose nadir after ITT.Over the duration of the ITT plasma insulin concentrations were lower in sheep exposed to HS(P=0.013)whereas there was no significant effect of supplemental nCrPic.There was no effect of either HS or nCrPic on cortisol response to ACTH.Dietary nCrPic supple-mentation decreased(P=0.013)mitogen-activated protein kinase-8(JNK)and increased(P=0.050)carnitine palmitoyltransferase 1B(CPT1B)mRNA expression in skeletal muscle.Results of this experiment demonstrated that animals under HS and supplemented with nCrPic had greater insulin sensitivity.

Modulating Effects of Chlorogenic Acid on Lipids and Glucose Metabolism and Expression of Hepatic Peroxisome Proliferator-activated Receptor-α in Golden Hamsters Fed on High Fat Diet

Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α） in these effects. Methods Twenty male golden hamsters were randomly divided into CGA treatment group （n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily）, and control group （n=10, given PBS i.p. at the average volume of the treatment group）. Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-α were determined. Results Eight weeks after treatment with CGA, the levels of fasting serum triglyceride （TG）, free fatty acid （FFA）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glucose （FSG）, and insulin （FSI） were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase （HL） lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase （LPL） in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-α. Conclusion CGA can modify lipids and glucose metabolism, which may be attributed to PPAR-α facilitated lipid clearance in liver and improved insulin sensitivity.

Beneficial effects of a diabetes specific formula on insulin sensitivity and free fatty acid in patients with type 2 diabetes mellitus

Background This prospective, randomized, controlled study was designed to investigate the effects of a diabetes specific formula （Diason low energy： 313.8 k J/100 ml）, compared with a standard formula, on insulin sensitivity, serum C peptide, serum lipids and free fatty acid （FFA） in type 2 diabetics. Methods In total of 71 type 2 diabetics completed the study. Enteral formulas were given orally as the sole source of nutrition to the subjects for 6 days. Venous blood samples （0.5, 1, 2, 3 hours） were collected at day -7 after a 75 g oral glucose tolerance test （OGTT）, day 1 after a standard test meal （1673.6 k J） and after 6 days of either the test diabetes specific formula or a standard formula. Plasma glucose, serum insulin, C peptide and lipids were.measured. Results After the intervention period, the diabetes specific formula resulted in a significantly lower postprandial rise in blood glucose concentrations at 0.5 hour （P 〈0.05） and 1 hour （P 〈0.01）; significantly lower peak height of plasma glucose （P=0.05）; significantly lower plasma insulin concentrations at 0.5 hour （P〈0.01）, 1 hour （P〈0.01） and 2 hours （P 〈0.01）; and a significantly lower plasma insulin peak compared to controls; both OGTT and a standard test meal （P 〈0.05）. The glucose and insulin area under the curve after the diabetes specific formula compared to the standard formula were significantly lower. The C peptide level was lower after 6 days of both nutrition formulas compare to 75 g OGTT, but not different from the standard mixed meal. Both formulas were well tolerated. Conclusions In summary the diabetes specific formula with a relatively high monounsaturated fatty acid and high multi fiber proportion significantly improved glycemic control. On top of this, the insulin sensitivity （HOMA-IS） was significantly improved and may therefore directly improve the impact on long term complications. The disease specific formula should therefore be the preferred option to be used by diabetic and hyperglycemic patients in need of nutritional support.

Fast track surgery accelerates the recovery of postoperative insulin sensitivity

Background Few clinical studies or randomized clinical trial results have reported the impact of fast track surgery on postoperative insulin sensitivity. This study aimed to investigate the effects of fast track surgery on postoperative insulin sensitivity in patients undergoing elective open colorectal resection. Methods Controlled, randomized clinical trial was conducted from November 2008 to January 2009 with one-month post-discharge follow-up. Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into two groups： a fast track group （35 cases） and a conventional care group （35 cases）. All included patients received elective open colorectal resection with combined tracheal intubation and general anesthesia. Clinical parameters （complication rates, return of gastrointestinal function and postoperative length of stay）, stress index and insulin sensitivity were evaluated in both groups perioperatively. Results Sixty-two patients finally completed the study, 32 cases in the fast-track group and 30 cases in the conventional care group. Our findings revealed a significantly faster recovery of postoperative insulin sensitivity on postoperative day 7 in the fast-track group than that in the conventional care group. We also found a significantly shorter length of postoperative stay and a significantly faster return of gastrointestinal function in patients undergoing fast-track rehabilitation. Conclusion Fast track surgery accelerates the recovery of postoperative insulin sensitivity in elective surgery for colorectal carcinoma with a shorter length of postoperative hospital stay.

Association between four adipokines and insulin sensitivity in patients with obesity, type 1 or type 2 diabetes mellitus,and in the general Chinese population

Background Hyperinsulinemic euglycemic clamp is the gold standard to evaluate the insulin sensitity, but it is too complicated and expensive to use in clinic.We tried to find an alternative indicator to reflect insulin sensitivity.To evaluate the association between the four adipokines, adiponectin, leptin, resistin and tumor necrosis factor-α （TNF-α） with insulin sensitivity, we used a hyperinsulinemic euglycemic clamp to test insulin sensitivity in Chinese patients with obesity and type 1 or type 2 diabetes mellitus versus controls.Methods In this parallel control study, we tested insulin sensitivity using a hyperinsulinemic euglycemic clamp in different groups, then examined levels of adiponectin, leptin, resistin and TNF-α in serum, and the relationship between the different adipokines and glucose disposal rate （M value）, as well as insulin sensitivity index （M value/insulin, M/I）,which are the ＂gold standard＂ indices of insulin sensitivity.Results There were significant differences in mean leptin values in the four adipokines from the four different groups （P〈0.001; comparison of the variation between different groups was analyzed by variance analysis）.Compared to controls （using multiple comparison two-way Dunnett t test）, only the leptin level showed significant differences in the four adipokines from the four different groups at the same time （P 〈0.001）.The association analysis between the different adipokines and M or M/I values also showed that only leptin negatively correlated with M （r=-0.64, P 〈0.001） or M/I values （r=-0.56, P〈0.001）; there was no relationship between the other three adipokines and M or M/I values.Conclusion Only leptin was associated with M or M/I values.Therefore, leptin might be one of the predictive factors of the degree of insulin resistance and risk of the accompanying disease.

Association of traditional Chinese exercises with glycemic responses in people with type 2 diabetes:A systematic review and meta-analysis of randomized controlled trials

Background： There is increasing evidence showing the health benefits of various forms of traditional Chinese exercises （TCEs） on the glycemic profile in people with type 2 diabetes. However, relatively little is known about the combined clinical effectiveness of these traditional exercises. This study was designed to perform a systematic review and meta-analysis of the overall effect of 3 common TCEs （Tai Ji Quan, Qigong, Ba Duan Jin） on glycemie control in adults with type 2 diabetes. Methods： We conducted an extensive database search in Cochrane Library, EMBASE, PubMed, Web of Science, EBSCO, and China National Knowledge Infrastructure on randomized controlled trials published between April 1967 and September 2017 that compared any of the 3 TCEs with a control or comparison group on glycemic control. Data extraction was performed by 2 independent reviewers. Study quality was evaluated using the Coehrane Handbook for Systematic Reviews of Interventions, which assessed the risk of bias, including sequence generation, allocation concealment, blinding, completeness of outcome data, and selective outcome reporting. The resulting quality of the reviewed studies was characterized in 3 grades representing the level of bias： low, unclear, and high. All analyses were performed using random effects models and heterogeneity was quantified. We a priori specified changes in biomarkers of hemoglobin A1 c （in percentage） and fasting blood glucose （mmol/L） as the main outcomes and triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein-cholesterol, 2-h plasma glucose, and fasting plasma glucose as secondary outcomes.Results： A total of 39 randomized, controlled trials （Tai Ji Quan = 11; Qigong= 6; Ba Duan Jin= 22） with 2917 type 2 diabetic patients （aged 41-80 years） were identified. Compared with a control or comparison group, pooled meta-analyses of TCEs showed a significant decrease in hemoglobin Alc （mean difference （MD）= -0.67%; 95% confidence interval （CI）：-0.86% to-0.48%; p 〈 0.00001） and fasting blood glucose （MD = -0.66 mmol/L; 95%CI： -0.95 to -0.37 mmol/L; p 〈 0.0001）. The observed effect was more pronounced for interventions that were medium range in duration （i.e., 〉3-〈 12 months）. TCE interventions also showed improvements in the secondary outcome measures. A high risk of bias was observed in the areas of blinding （i.e., study participants and personnel, and outcome assessment）. Conclusion： Among patients with type 2 diabetes, TCEs were associated with significantly lower hemoglobin Alc and fasting blood glucose. Further studies to better understand the dose and duration of exposure to TCEs are warranted.2018 Published by Elsevier B.V. on behalf of Shanghai University of Sport. This is an open access article under the CC BY-NC-ND license. （http：//creativecommons.org/licenses/by-nc-nd/4.0/）.

Non-alcoholic fatty liver disease:Epidemiology,pathophysiology and an update on the therapeutic approaches

Non-alcoholic fatty liver disease(NAFLD)denotes a spectrum of fatty liver disease in individuals without significant alcohol consumption.NAFLD is set to be the most common etiology of serious liver diseases in numerous nations when accompanied by obesity and type 2 diabetes.It is further histologically categorized into the non-alcoholic fatty liver(NAFL;steatosis without hepatocellular injury)and non-alcoholic steatohepatitis(NASH)which is characterized by the coexistence of hepatic steatosis and inflammation and is accompanied by hepatocyte injury(ballooning),either with or without fibrosis.NAFL is considered the benign and reversible stage arising from the excessive accumulation of triglycerides in hepatocytes.However,NASH is a more progressive stage of NAFLD,due to the increased risks of evolving more serious diseases such as cirrhosis,hepatocellular carcinoma.This concept,however,has been lately challenged by a hypothesis of multiple parallel hits of NAFLD,in which steatosis and NASH are separate entities rather than two points of the NAFLD spectrum,not only from a set of histological patterns but also from a pathophysiological perspective.The current review highlights the epidemiology and pathophysiology of NAFLD,and its progression towards steatohepatitis,with special focus on the novel imminent therapeutic approaches targeting the molecular aspects and the pathogenic pathways involved in the development,and progression of NAFLD.

Sterols and Terpenoids from Viburnum odoratissimum

A new stigmasterol type natural product,viburodorol A(1),along with eleven known sterols and terpenoids(2–12),were isolated from the aerial parts of Viburnum odoratissimum.The structure of 1 was elucidated on the basis of comprehensive spectroscopic analysis.It’s noteworthy that compound 2,the major constituent of this plant,can signifi-cantly stimulate glucose absorption in insulin resistant HepG2 cells without affecting cell viability.Furthermore,this compound can also restore the glucose absorption in DXMS-induced insulin resistant 3T3-L1 cells.

Testosterone replacement therapy improves insulin sensitivity and decreases high sensitivity C-reactive protein levels in hypogonadotropic hypogonadal young male patients

Background Many clinical studies suggest the inverse relationship between testosterone levels and insulin sensitivity in men, however the causative relationship of these two events is still not determined. The purpose of this study was to investigate the effects of testosterone replacement therapy （TRT） on insulin sensitivity, body composition, serum lipid profiles and high sensitivity C-reactive protein （hsCRP） in hypogonadotropic hypogonadal （HH） puberty undeveloped male patients. Methods In this prospectively designed study, we compared homeostasis model assessment of insulin resistance （HOMA-IR）, insulin areas under the curves （AUC） of 3-hour oral glucose tolerance test （OGTT） and other metabolic parameters between 26 HH patients and 26 healthy men. The patients＇ HOMA-IR, insulin AUC, body composition, lipid profiles, hsCRP and other parameters were compared before and after nine-month TRT. Results The average levels of total testosterone （TT） in HH and healthy group were （0.9±0.6） nmol/L and （18.8±3.4） nmol/L, respectively. HOMA-IR in HH group was significantly higher than the healthy group （5.14±5.16 vs 2.00±1.38, P 〈0.005）. Insulin AUC in 3-hour OGTT in HH group was significantly higher than the healthy group （698.6±414.7 vs 414.2±267.5, P 〈0.01）. Fasting glucose level in H H group was significantly higher than control group （（5.1±0.6） mmol/L vs （4.7±0.3） mmol/l, P 〈0.005）. Height, weight and grasp strength of the patients were significantly increased after 9-month TRT. Significant reductions in HOMA-IR （from 5.14±5.16 to 2.97±2.16, P 〈0.01）, insulin AUC （from 698.6±414.7 to 511.7±253.9, P 〈0.01） and hsCRP （from （1.49±1.18） mg/L to （0.70±0.56） mg/L, P 〈0.05） were found after TRT. Serum total cholesterol, LDL-C, HDL-C and triglyceride were all decreased, albeit with no significant difference compared to the level prior to TRT. Conclusions HOMA-IR, insulin AUC and fasting glucose level in HH young male patients were significantly higher than those of the control group, which suggests that low level of testosterone in male adolescents might be a risk factor for insulin resistance. TRT can significantly improve patients＇ insulin sensitivity and suppress serum hsCRP, which in return suggests that TRT may prevent the HH patients from developing diabetes mellitus and cardiovascular diseases （CVD） in future.

LDL,LDL receptors,and PCSK9 as modulators of the risk for type 2 diabetes:a focus on white adipose tissue

Type 2 diabetes(T2D) and cardiovascular disease(CVD) share many risk factors such as obesity,unhealthy lifestyle,and metabolic syndrome,whose accumulation over years leads to disease onset.However,while lowering plasma low-density lipoprotein cholesterol(LDLC) is cardio-protective,novel evidence have recognised a role for common LDLC-lowering variants(e.g.in HMGCR,PCSK9,and LDLR) and widely used hypocholesterolemic drugs that mimic the effects of some of these variants(statins) in higher risk for T2D.As these conditions decrease plasma LDLC by increasing tissue-uptake of LDL,a role for LDL receptor(LDLR)pathway was proposed.While underlying mechanisms remain to be fully elucidated,work from our lab reported that native LDL directly provoke the dysfunction of human white adipose tissue(WAT) and the activation of WAT NLRP3(Nucleotide-binding domain and Leucine-rich repeat Receptor,containing a Pyrin domain 3)inflammasome,which play a major role in the etiology of T2D.However,while elevated plasma numbers of apolipoprotein B(apoB)-containing lipoproteins(measured as apoB,mostly as LDL) is associated with WAT dysfunction and related risk factors for T2D in our cohort,this relation was strengthened in regression analysis by lower plasma proprotein convertase subtilisin/kexin type 9(PCSK9).This supports a central role for upregulated pathway of LDLR and/or other receptors regulated by PCSK9 such as cluster of differentiation 36(CD36) in LDL-induced anomalies.Targeting receptor-mediated uptake of LDL into WAT may reduce WAT inflammation,WAT dysfunction,and related risk for T2D without increasing the risk for CVD.