Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance

BACKGROUND Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease featured by insulin resistance(IR)and decreased insulin secretion.Currently,vitamin D deficiency is found in most patients with T2DM,but the relationship between vitamin D and IR in T2DM patients requires further investigation.AIM To explore the risk factors of IR and the effects of vitamin D supplementation on glucose and lipid metabolism in patients with T2DM.METHODS Clinical data of 162 T2DM patients treated in First Affiliated Hospital of Harbin Medical University between January 2019 and February 2022 were retrospectively analyzed.Based on the diagnostic criteria of IR,the patients were divided into a resistance group(n=100)and a non-resistance group(n=62).Subsequently,patients in the resistance group were subdivided to a conventional group(n=44)or a joint group(n=56)according to the treatment regimens.Logistic regression was carried out to analyze the risk factors of IR in T2DM patients.The changes in glucose and lipid metabolism indexes in T2DM patients with vitamin D deficiency were evaluated after the treatment.RESULTS Notable differences were observed in age and body mass index(BMI)between the resistance group and the non-resistance group(both P<0.05).The resistance group exhibited a lower 25-hydroxyvitamin D_(3)(25(OH)D_(3))level,as well as notably higher levels of 2-h postprandial blood glucose(2hPG),fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)than the non-resistance group(all P<0.0001).Additionally,the resistance group demonstrated a higher triglyceride(TG)level but a lower high-density lipoprotein-cholesterol(HDL-C)level than the non-resistance group(all P<0.0001).The BMI,TG,HDL-C,25(OH)D_(3),2hPG,and HbA1c were found to be risk factors of IR.Moreover,the posttreatment changes in levels of 25(OH)D_(3),2hPG,FBG and HbA1c,as well as TG,total cholesterol,and HDL-C in the joint group were more significant than those in the conventional group(all P<0.05).CONCLUSION Patients with IR exhibit significant abnormalities in glucose and lipid metabolism parameters compared to the noninsulin resistant group.Logistic regression analysis revealed that 25(OH)D_(3)is an independent risk factor influencing IR.Supplementation of vitamin D has been shown to improve glucose and lipid metabolism in patients with IR and T2DM.

NLRP3 Inflammasome in Relation to Glucose and Lipid Metabolism, and Insulin Resistance in Diabetes and Pre-Diabetes

Aims: To investigate the relationship among NLRP3 inflammasome, glucose and lipid metabolism, and insulin resistance (IR) in the serum of patients with diabetes and pre-diabetes. Methods: A total of 100 patients with abnormal blood glucose divided into the pre-diabetes mellitus (PDM) group (N = 46) and the type 2 diabetes mellitus (T2DM) group (N = 54). 20 normoglycemic subjects (NG, N = 20) were selected as a control group. The serum levels of glucose and lipid metabolism, IR, and the expression of NLRP3, ASC and Caspase-1 were measured. Besides, the correlations of NLRP3 inflammasome with glucose and lipid metabolism, and IR were analyzed. Results: Compared with the NG group, the levels of NLRP3, ASC, Caspase-1, FBG, HbA1C, TG, LDL-C, FINs, and HOMA-IR were higher (P β were lower (P P β were seen (P P β. Regression analysis further showed that blood glucose related indexes, FINs, and NLRP3 have made a decisive contribution to IR. Conclusions: Collectively, this evidence suggested that NLRP3 is closely related to glucose and lipid metabolism, and IR, and activated in PDM and T2DM.

Functional imaging of skeletal muscle glucose metabolism by ¹⁸FDG PET to characterize insulin resistance in patients at high risk for coronary artery disease

Insulin resistance is associated with several coronary risk factors and is thought to play a critical role for the development of coronary artery disease. Insulin resistance has several causes, including an impaired skeletal muscle glucose utilization rate (SMGU), reduced peripheral blood flow, and altered fatty tissue metabolism, with SMGU being considered the most important. Nonetheless, insulin resistance has only been estimated by the glucose disposal rate (GDR) in previous studies. Methods: Skeletal muscle metabolic imaging with 18FDG and positron emission tomography (PET) was undertaken to measure SMGU during hyperinsulinemiceuglycemic clamping in 22 normotensive type-2 diabetics under no medications (T2- DM), 17 normotensive non-diabetic hypertriglyceridemics, 22 patients with hypertension, and 12 agematched controls. Whole body insulin resistance was assessed by the GDR during hyperinsulinemiceuglycemic insulin clamping. Results: The SMGU and GDR were significantly reduced in T2DM (32.1 ± 16.6 μmol/min/kg and 24.3 ± 13.0 μmol/min/kg, respectively), hypertriglyceridemics (36.5 ± 13.5 μmol/min/ kg and 22.7 ± 8.07 μmol/min/kg respectively) and patients with hypertension (35.4 ± 26.6 μmol/min/kg and 29.0 ± 9.90 μmol/min/kg, respectively) compared with controls (72.2 ± 44.1 μmol/min/kg and 43.0 ± 22.9 μmol/min/kg, p < 0.01, respectively). In all groups studied, SMGU was significantly correlated with GDR (r = 0.76, p < 0.01) and GDR (F = 13.9) was independently related to SMGU (r = 0.81, p < 0.01). Conclusion: Insulin resistance is significantly associated with SMGU to a similar degree among patients with T2DM, essential hypertension and hypertriglyceridemia. 18FDG PET functional imaging allows insulin resistance to be assessed.

Natural products:Regulating glucose metabolism and improving insulin resistance

Compounds with regulating glucose metabolism and improving insulin resistance(IR)activity are abundant in nature and can be obtained from several sources.They have high potential to be used to treat diabetes mellitus.These compounds isolated from natural plants can be classified seven categories:terpenoids,alkaloids,quinones,flavonoids,phenols,phenyl propanoids,steroids,and other types of compounds.They exert biological effects by different ways and mechanisms.This review illustrated the potential natural products as a rich resource in regulation of glucose metabolism and IR,as well as their mechanisms.

Decabromodiphenyl ether causes insulin resistance and glucose and lipid metabolism disorders in mice

BACKGROUND Decabromodiphenyl ether(BDE-209)is the most commonly used brominated flame retardant.Recently,BDE-209 has been suspected of being an environmental risk factor for metabolic diseases such as obesity,insulin resistance(IR),type 2 diabetes mellitus,and hypertension.AIM To investigate the effects of BDE-209 on IR and glucose and lipid metabolism in C57BL/6 mice.METHODS Adult male C57BL/6 mice were randomly divided into high,medium-high,medium,medium-low,and low dose BDE-209 groups,and a control group(n=6 per group),which received 1000,800,600,450,300,and 0 mg/kg BDE-209,respectively.After BDE-209 exposure for 60 d,the mice were fasted overnight,and then sacrificed to obtain tissues.An automatic biochemical analyzer was used to detect serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C);enzymelinked immunosorbent assay kits were used to detect fasting serum insulin(FINS),leptin(LEP),and adiponectin(Adp)levels;a blood glucose meter was used to detect fasting blood glucose(FBG).Morphological changes of the liver were observed by hematoxylin and eosin staining.Real-time quantitative polymerase chain reaction and Western blot were used to determine the messenger ribonucleic acid(mRNA)and protein levels,respectively,of LEP,Adp,and peroxisome proliferators activated receptor-γ(PPARγ)in mouse liver and adipose tissues.RESULTS There was a statistically significant difference in the weight of mice in each group after 45 and 60 d of exposure(P<0.05).After 60 d of exposure,the weight of liver and adipose tissues in the exposure groups were greater than that of the control group(P<0.05).The liver tissue structure was disordered and the liver tissues were accompanied by local inflammatory cell infiltration in the high,mediumhigh,and medium dose BDE-209 groups.The levels of FINS,insulin sensitivity index,Adp,and HDL-C were decreased in the BDE-209 group compared with the control group,as were the mRNA and protein levels of Adp in liver and adipose tissues(P<0.05).Serum level of FBG and LEP were higher in the BDE-209 group than in controls.TC,TG,and LDL-C levels as well as the mRNA and protein expression of LEP and PPARγin liver and adipose tissues were higher than those in the control group(P<0.05).Homeostatic assessment model of IR was higher in the medium and medium-low dose BDE-209 groups(P<0.05).CONCLUSION BDE-209 increases the body weight,fat and liver tissue weight,TC,TG,and LDLC,reduces HDL-C,and causes IR in mice,which may be related to activating the PPARγreceptor.

The relationship between insulin resistance/β-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus： the Desheng Diabetic Eye Study

AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index （BMI）. METHODS： Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment （HOMA） method was employed for IR and β-cell function assessment. RESULTS： After excluding those participants who were treated with insulin （n=352） or had missing data of fasting insulin （n=96）, and further excluding those with poor quality of retinal photographs （n=10）, a total of 1008 subjects were included for the final analysis, 406 （40.3%） were men and 602 （59.7%） were women, age ranging fiom 34 to 86 （64.87±8.28）y. Any DR （levels 14 and above） was present in 278 （27.6%） subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio （OR） 1.51, 95% confidence interval （Cl） 0.87-2.61, P=0.14] or HOMA β-cell （OR 0.71, 95%CI 0.40-1.26, P=0.25）. After stratification by BMI, the presence of any DR was associated positively with HOMA IR （OR 2.46, 95%CI： 1.18-5.12, P=0.016）, and negatively with HOMA β-cell （OR 0.40, 95%CI： 0.19-0.87, P=0.021） in the group of patients with higher BMI （225 kg/m2）. In the group of patients with lower BMI （〈25 kg/m2）, the presence of any DR was not associated with HOMA IR （OR 1.00, 95%C1： 0.43-2.33, P=I.00） or HOMA β-cell （OR 1.41, 95%CI： 0.60-3.32, P=0.43）. CONCLUSION： The data suggest that higher IR and lower 13-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.

A review on mechanisms of action of bioactive peptides against glucose intolerance and insulin resistance

Insulin resistance leads to impaired glucose metabolism by disrupting both insulin secretion and sensitivity.Insulin resistance plays a key role in the pathophysiology of type 2 diabetes and metabolic syndrome.Reviews on the mechanisms of action of bioactive peptides on glucose homeostasis and insulin resistance are scarce.The recent discoveries of pathways and target cells in the management of glucose and energy metabolism have opened up new opportunities for identification of novel bioactive peptides on enhancing adipocyte differentiation and insulin signaling,glucose uptake,cholecystokinin receptor expression and activation,as well as insulin mimetics and incretin stimulants.Examples of food-derived bioactive peptides with glucoregulatory properties include Trp-Glu-Lys-Ala-Phe-Lys-Asp-Glu-Asp(WEKAFKDED),Gln-Ala-MetPro-Phe-Arg-Val-Thr-Glu-Gln-Glu(QAMPFRVTEQE),Glu-Arg-Tyr-Pro-Ile-Leu(ERKPIL),Val-Phe-LysGly-Leu(VFKGL),Phe-Leu-Val(FLV),Val-Pro-Pro(VPP),Ile-Arg-Trp(IRW),Ala-Lys-Ser-Pro-Leu-Phe(AKSPLF),Ala-Thr-Gln-Pro-Leu-Phe(ATNPLF),Phe-Glu-Glu-Leu-Gln(FEELN),Leu-Ser-Val-Ser-Val-Leu(LSVSVL),Val-Arg-Ileu-Arg-Leu-Leu-Gln-Arg-Phe-Asn-Lys-Arg-Ser(VRIRLLQRFNKRS),and Ala-GlyPhe-Ala-Gly-Asp-Asp-Ala-Pro-Arg(AGFAGDDAPR).However,as yet,clinical evidence on the effi cacy of such bioactive peptides is rare but is inevitable to establish their applications against glucose intolerance and insulin resistance.

Measurement of lumbar muscle glucose utilization rate can be as useful in estimating skeletal muscle insulin resistance as that of thigh muscle

Background: Skeletal muscle glucose utilization (SMGU) can be accessed by positron emission tomography (PET) and18F-FDG to characterize insulin resistance. The quantity of skeletal muscle in the lumbar is sufficient to indicate that SMGU in the lumbar (SMGU- lumbar) can be measured with18F-FDG PET of the chest instead of obtaining thigh muscle SMGU (SMGU-thigh). This would reduce PET scan time to avoid thigh muscle PET scan. This study was aimed to compare SMGU-lumbar and thigh muscle SMGU under insulin clamping to identify the validity of measurements of SMGU in the lumbar for studies of insulin resistance. Methods: Thirty-three patients underwent sequential dynamic18F-FDG PET of both the thoracic (37 min) and thigh region (22 min) during hyperinsulinemic euglycemic insulin clamping. Both SMGU-lumbar and SMGU-thigh were calculated by Patlak graphical analysis. Whole body insulin resistance was assessed by a whole body glucose disposal rate during hyperinsulinemic euglycemic insulin clamping. Input function was obtained from the time activity curve of the descending aorta and venous blood sampling as previously validated. Results: SMGU-thigh (0.0506 ± 0.0334 μmol/min/g) was comparable to SMGU-lumbar (0.0497 ± 0.0255 μmol/min/g). The Bland-Altman method of difference plot analysis showed a significant correlationship between SMGU- thigh and SMGU-lumbar (r = 0.506, p = 0.0028). There were seen very good significant correlationship between whole body glucose utilization rate in both thigh (r = 0.737, p = 0.0001) and lumbar (r = 0.772, p = 0.0001). Conclusion: These results support the validity of measuring SMGU-lumbar to estimate insulin resistance during PET imaging of the chest.

The Effect of Tuberculosis Infection on Pancreatic Beta-Cell Function in Patients with Type 2 Diabetes Mellitus

Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.

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.

The Influence of the Pro12Ala Mutation of PPARγ2 Receptor Gene on β-cells Restoration and Insulin Resistance in Type 2 Diabetes with Hypertension

The aim of this investigation was to determine whether a PPAR72 Prol2Ala polymorphism was associated with insulin resistance, β-cellfunction and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes （HbAC1〈6.0） were investigated, including 132 hypertensive diabetic （HTD） subjects, 157 normotensive diabetic （NTD） subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test （OGTT）. Biochemical measurements （high-density lipoprotein （HDL） and low-density lipoprotein-cholesterol （LDL）, triglycerides） and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group （3. 03 %） than in the non-hypertension group （5.7 %） （P〈0.05） after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level （P=0. 0127）, and better glucose tolerance 60 min after oral glucose （P=0. 0361）. Moreover, plasma insulin concentrations at 60 min was lower than those without A variant （P = 0. 0275）, and both hypertensive Ala/Pro in HOMA-β （P ： 0. 0455） and AUC for insulin （P=0. 0473） were higher, and HOMA-IR was lower （P=0. 0375） as compared with hypertensive Pro/Pro subjects. No association was observed between Prol2Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPARγ2 on glucose homeostasis and insulin resistance.

Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease

Metabolic associated fatty liver disease(MAFLD),formerly named“nonalcoholic fatty liver disease”occurs in about one-third of the general population of developed countries worldwide and behaves as a major morbidity and mortality risk factor for major causes of death,such as cardio-vascular,digestive,metabolic,neoplastic and neuro-degenerative diseases.However,progression of MAFLD and its associated systemic complications occur almost invariably in patients who experience the additional burden of intrahepatic and/or systemic inflammation,which acts as disease accelerator.Our review is focused on the new knowledge about the brain-gut-liver axis in the context of metabolic dysregulations associated with fatty liver,where insulin resistance has been assumed to play an important role.Special emphasis has been given to digital imaging studies and in particular to positron emission tomography,as it represents a unique opportunity for the noninvasive in vivo study of tissue metabolism.An exhaustive revision of targeted animal models is also provided in order to clarify what the available preclinical evidence suggests for the causal interactions between fatty liver,dysregulated endogenous glucose production and insulin resistance.

Evaluation of glucose metabolism in women with multiple ovarian follicles

Objective ：To investigate glucose metabolism in women with multiple ovarian follicles （MOF） and explore the relationship between glucose metabolism, insulin resistance and body weight. Methods：We evaluated 46 women with MFO and 30 normal women as controls. All the subjects were given 75g of glucose orally in order to perform the oral glucose tolerance test （OGTT） and insulin releasing test （IRT）, and they were also evaluated for insulin resistance using the insulin resistance index with homeostatic model assessment （HOMA）. Results：The occurrence of impaired glucose tolerance in women with MOF was 10.87%, which was significantly higher than that in the control group （3.33% ,P 〈 0.05）. The rate of insulin resistance was 30.43% in the study group as compared to 10.00% in the control group. The results showed that there was significant difference between the two groups（P 〈 0.05）. The levels of FSH,LH,PRL,E2,T and P between the two groups had no significant difference （P 〉 0.05）. BMI in women with impaired glucose tolerance was correlated positively to insulin resistance （r = 0.567, P 〈 0.05）. Conclusion：Abnormal glucose metabolism was observed in women with unitary multiple ovarian follicles, and this could be attributed to obesity and insulin resistance. Women with MOF and associated obesity should be subjected to OGTT so that their glucose levels can be monitored as a preventive measure.

Effects of Mogroside V on Glucose and Lipid Metabolism in High Fat Diet Mice

[Objectives]To explore the effects and mechanism of mogroside V(MV)on glucose and lipid metabolism in high-fat diet(HFD)mice.[Methods]The experiment fed mice with high-fat diet for 8 weeks,and 40 mice with successful modeling were randomly divided into normal group,model group,and MV dose group(100,200 mg/kg),with 10 mice in each group.From the ninth week,the MV dose group was given intragastric administration,and the normal group and the model group were given an equal volume of distilled water by intragastric administration for 6 weeks,then killed and blood samples and livers were collected.Serum triglycerides(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),Advanced glycation end products(AGE-P)-peptides(AGE-P)and glycosylated hemoglobin(HbA1c)content,and TG and hepatic glycogen content in liver were detected by biochemical method.Fasting blood glucose(FBG)was measured by glucose oxidase method.The fasting serum insulin(FINS)content was detected by enzyme-linked immunosorbent assay(ELISA),and the insulin resistance index(HOMA-IR)was calculated.Oil red O staining was used to observe the fat deposition in liver tissue.[Results]MV(100,200 mg/kg)dose groups could significantly down-regulate the contents of TC,TG,LDL-C,FBG,FINS,AGE-P and HbA1c and HOMA-IR,and up-regulate HDL-C and hepatic glycogen content and reduce the fat deposits.[Conclusions]The mechanism of MV regulating glucose and lipid metabolism in mice may be related to the regulation of insulin resistance.

Hepatitis C virus infection and insulin resistance

Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)and is the primary cause for liver transplantation in the western world.Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of typeⅡdiabetes.Insulin resistance plays an important role in the development of various complications associated with HCV infection.Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis,steatosis,HCC and resistance to anti-viral treatment.Thus,HCV associated insulin resistance is a therapeutic target at any stage of HCV infection.HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway.Various mechanisms have been proposed in regard to HCV mediated insulin resistance,involving up regulation of inflammatory cytokines,like tumor necrosis factor-α,phosphorylation of insulin-receptor substrate-1,Akt,up-regulation of gluconeogenic genes like glucose 6 phosphatase,phosphoenolpyruvate carboxykinase 2,and accumulation of lipid droplets.In this review,we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.

Elevated alanine aminotransferase activity is not associated with dyslipidemias,but related to insulin resistance and higher disease grades in non-diabetic non-alcoholic fatty liver disease

Objective:To explore demographic and metabolic factors associated with increased alanine aminotransferase(ALT)activity in non-diabetic non-alcoholic fatty liver disease(NAFLD)patients.Methods:Overall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences,Tehran,Iran awere diagnosed as NAFLD entered into analysis.Exclusion criteria were having diabetes mellitus and fasting blood glucose over126 mg/dL,active hepatitis B virus infection,having hepatitis C virus positive serology,and to be under corticosteroid therapy.ALT levels were considered pathologically high when it was over30 IU/L for men and over 19 IU/L for women.Results:Bivariate analyses using t test and chisquare test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations(P=0.003).Moreover,these patients represented significantly higher homeostatic model assessment levels(P=0.003),levels of serum insulin(P=0.002),fasting blood glucose(P<0.001),and uric acid(P=0.02).The prevalence of insulin resistance was also higher in patients with increased serum ALT concentrations.Multifactorial logistic regression models showed that ultrasonographic grading of NAFLD(P=0.027)and insulin resistance(P=0.013)were the only variables significantly associated with abnormal ALT levels.Conclusions:This study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed before.By excluding diabetic patients from our population,we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic evaluations.Further studies are needed to confirm our results.

interrelationships between ghrelin, insulin and glucose homeostasis: physiological relevance

Ghrelin is a 28 amino acid peptide mainly derived from the oxyntic gland of the stomach. Both acylated(AG) and unacylated(UAG) forms of ghrelin are found in the circulation. Initially, AG was considered as the only bioactive form of ghrelin. However, recent advances indicate that both AG and UAG exert distinct and common effects in organisms. Soon after its discovery, ghrelin was shown to promote appetite and adiposity in animal and human models. In response to these anabolic effects, an impressive number of elements have suggested the influence of ghrelin on the regulation of metabolic functions and the development of obesityrelated disorders. However, due to the complexity ofits biochemical nature and the physiological processes it governs, some of the effects of ghrelin are still debated in the literature. Evidence suggests that ghrelin influences glucose homeostasis through the modulation of insulin secretion and insulin receptor signaling. On the other hand, insulin was also shown to influence circulating levels of ghrelin. Here, we review the relationship between ghrelin and insulin and we describe the impact of this interaction on the modulation of glucose homeostasis.

Body composition and metabolic syndrome in patients with type 1 diabetes

BACKGROUND In recent years,the prevalence of obesity and metabolic syndrome in type 1 diabetes(T1DM)patients has gradually increased.Insulin resistance in T1DM deserves attention.It is necessary to clarify the relationship between body composition,metabolic syndrome and insulin resistance in T1DM to guide clinical treatment and intervention.AIM To assess body composition(BC)in T1DM patients and evaluate the relationship between BC,metabolic syndrome(MS),and insulin resistance in these indi-viduals.METHODS A total of 101 subjects with T1DM,aged 10 years or older,and with a disease duration of over 1 year were included.Bioelectrical impedance analysis using the Tsinghua-Tongfang BC Analyzer BCA-1B was employed to measure various BC parameters.Clinical and laboratory data were collected,and insulin resistance was calculated using the estimated glucose disposal rate(eGDR).RESULTS MS was diagnosed in 16/101 patients(15.84%),overweight in 16/101 patients(15.84%),obesity in 4/101(3.96%),hypertension in 34/101(33.66%%)and dyslip-idemia in 16/101 patients(15.84%).Visceral fat index(VFI)and trunk fat mass were significantly and negatively correlated with eGDR(both P<0.001).Female patients exhibited higher body fat percentage and visceral fat ratio compared to male patients.Binary logistic regression analysis revealed that significant factors for MS included eGDR[P=0.017,odds ratio(OR)=0.109],VFI(P=0.030,OR=3.529),and a family history of diabetes(P=0.004,OR=0.228).Significant factors for hypertension included eGDR(P<0.001,OR=0.488)and skeletal muscle mass(P=0.003,OR=1.111).Significant factors for dyslipidemia included trunk fat mass(P=0.033,OR=1.202)and eGDR(P=0.037,OR=0.708).CONCLUSION Visceral fat was found to be a superior predictor of MS compared to conventional measures such as body mass index and waist-to-hip ratio in Chinese individuals with T1DM.BC analysis,specifically identifying visceral fat(trunk fat),may play an important role in identifying the increased risk of MS in non-obese patients with T1DM.

Skeletal muscle and whole body insulin resistance but not cardiac muscle insulin resistance could be improved by troglitazone therapy within 12 weeks in type-2 diabetes

Background: Existence of myocardial insulin resistance (IR) has been reported in type II diabetics (T2- DM) and coronary artery disease (CAD). Improvement in heart and skeletal muscle IR after thiazolidinedione’s therapy was reported in T2DM and CAD. However effects of troglitazone therapy (TRO) on myocardial IR remain uncertain. To clarify heart and skeletal muscle and whole body IR in T2DM without CAD by TRO to clarify whether TRO would provide different results. Methods: We analyzed data on 15 T2DM patients who underwent dynamic PET with 18F-FDG under insulin clamping before and during TRO (200 mg/day) and 17 controls. Results: Whole body glucose disposal rate (WBGR mg/min/kg) in T2DM before TRO (3.41 ± 1.72) was significantly lower than in controls (9.76 ± 2.97, p < 0.01) as was the skeletal muscle glucose utilization rate (SMGU mg/min/kg);T2DM (0.367 ± 0.217) vs. controls (1.34 ± 0.613, p < 0.01) and myocardial glucose utilization rate (MGU mg/min/kg;T2DM 5.86 ± 2.03 vs. controls 7.34 ± 1.80, p < 0.05). WBGR in T2DM during TRO (5.17 ± 2.75, p < 0.05) was significantly higher than that before TRO, as was the SMGU (0.782 ± 0.20, p < 0.05). The MGU in T2DM during TRO (6.59 ± 0.72) was comparable with that before TRO. Conclusion: Myocardial IR response to TRO differed from that in skeletal muscle and the whole body in T2DM without CAD.

Loganin regulates glycolipid metabolism by influencing intestinal microbiota and AMPK signaling in obese mice

Objective: We aimed to observe the effects of loganin(Log) on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase(AMPK) signaling in obese mice.Methods: A high-fat diet was given for 12 consecutive weeks to generate the obesity model in institute of cancer research(ICR) mice. Body weight was measured weekly and fasting blood glucose(FBG) was determined every 2 weeks. Both the oral glucose tolerance test and the intraperitoneal insulin tolerance test were performed. The serum levels of total cholesterol(TC), triglyceride, high-density lipoproteincholesterol, low-density lipoprotein-cholesterol(LDL-C), and free fatty acids(FFA) were measured. The expression of key proteins in the AMPK signaling pathway in skeletal muscle tissue was detected by immunoblotting, and gut microbiota were characterized using 16S rDNA sequencing.Results: Log significantly decreased the body weight and the FBG in obese mice(P <.05), and it could restore FBG to normal levels. The total cholesterol, LDL-C, and FFA levels were significantly reduced by Log compared with the obese controls(TC: P =.0020;LDL-C: P =.0233;FFA: P =.0127), and the glucose tolerance of animals was significantly improved(P =.0477). The western blot results showed that Log could upregulate the protein expression of Adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPKa), Sirtuin 1(SIRT1), and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC1a) in skeletal muscle tissue of obese mice. 16S rDNA sequencing indicated that Log reduced the diversity of the gut flora in feces and altered the floral composition of obese mice.Conclusions: Log was effective in reducing body weight and improving glucolipid metabolism in obese mice, probably through activating AMPK signaling and regulating intestinal microbial diversity.