国产吡格列酮治疗2型糖尿病患者的临床研究

目的观察国产吡格列酮对2型糖尿病(T2DM)病人血糖、血脂代谢和胰岛素抵抗(IR)的作用,并检测治疗前后血清脂联素水平的变化。方法用随机双盲法、与安慰剂平行对照,比较48例T2DM病人用吡格列酮30mg和安慰剂(1:1)干预治疗12w后的血糖、血脂、IR、血清脂联素水平改变。结果吡格列酮治疗12w后,空腹血糖和餐后2h(2hPG)血糖、糖化血红蛋白(HbA1c)与治疗前比较明显下降(P<0·05或P<0·01);空腹胰岛素(FINS)及HOMA模型IR指数(HOMA-IR)较治疗前也减低(P<0·05或P<0·01);血清脂联素水平、高密度脂蛋白(HDL-C)在12w治疗后显著升高,低密度脂蛋白(LDL-C)与治疗前比较明显降低(P<0·05或P<0·01),上述指标与安慰剂组比较差异均有显著意义(P<0·05或P<0·01)。但是总胆固醇(TC)、甘油三酯(TG)治疗前后无明显差异。结论国产吡格列酮可改善T2DM病人血糖及血脂代谢,降低IR并升高血清脂联素水平,有助于防治T2DM血管并发症。     

吡格列酮对2型糖尿病大鼠骨骼肌脂联素受体1表达的影响

目的观察吡格列酮对2型糖尿病大鼠血清脂联素以及骨骼肌脂联素受体1(AdipoR1)表达的影响,探讨吡格列酮对2型糖尿病胰岛素抵抗的改善作用及机制。方法 40只8周龄健康雌性SD大鼠,随机分为正常对照组(n=10)、糖尿病组(n=15)及吡格列酮组(n=15)。用高糖高脂饲料加小剂量链脲佐菌素建立2型糖尿病大鼠模型,成模后吡格列酮组给予10 mg/(kg.d)吡格列酮灌胃,正常对照组和糖尿病组给予同体积生理盐水灌胃,共12周。3个月后股静脉取血,酶联免疫吸附法(ELISA)测定血清脂联素水平,留取大鼠骨骼肌,光、电镜观察骨骼肌结构,免疫组织化学染色法测定骨骼肌AdipoR1蛋白的表达。结果与正常对照组(1.73±0.32 mg/L)比较,糖尿病组血清脂联素(1.01±0.27 mg/L)水平显著降低,而吡格列酮组(1.34±0.43 mg/L)较糖尿病组显著升高,差异有统计学意义(P<0.05)。骨骼肌AdipoR1免疫组织化学染色正常对照组着色深且广泛,糖尿病组较正常对照组染色浅,吡格列酮组较糖尿病组染色深,但较正常对照组浅。光镜及电镜结果显示大鼠骨骼肌结构未见明显异常。结论 2型糖尿病大鼠血清脂联素水平及骨骼肌AdipoR1表达降低并导致糖脂代谢紊乱及胰岛素抵抗。吡格列酮可上调血清脂联素及骨骼肌AdipoR1的表达,从而调节糖脂代谢,改善胰岛素抵抗。     

Pioglitazone increases circulating adiponectin levels and subsequently reduces TNF-alpha levels in Type 2 diabetic patients: a randomized study.

BACKGROUND: Adipocytokines are involved in the development of insulin resistance and endothelial dysfunction in diabetic patients. However, the relationship between these factors remains unclear. We observed a chronological change in circulating adipocytokines and blood pressure levels with administration of oral hypoglycaemic agents in Type 2 diabetic (T2DM) subjects. METHODS: Thirty poorly controlled T2DM subjects (aged 60.1 +/- 1.5 years, 11 males and 19 females) were randomized into two groups: voglibose (initial dose 0.6 mg/day, increased to 0.9 mg/day) and pioglitazone (initial dose 15 mg/day, increased to 30 mg/day). RESULTS: Both treatment groups showed a similar improvement in glycaemic control. In pioglitazone-treated patients, circulating adiponectin levels were significantly increased from 4 weeks after the start of treatment, and until the end of the study at 12 weeks. Plasma tumour necrosis factor-alpha (TNF-alpha) levels were significantly decreased only at 12 weeks. In contrast, no significant changes in plasma adiponectin or TNF-alpha levels were observed in voglibose-treated patients. Plasma PAI-1 and leptin levels were not significantly changed at 12 weeks in either treatment group. Pioglitazone significantly decreased systolic and diastolic blood pressure levels at 12 weeks, but voglibose had no effect. CONCLUSION: In summary, pioglitazone caused an immediate increase in circulating adiponectin levels, followed by a reduction of TNF-alpha. The observed increase in circulating adiponectin could be related to decreases in both systolic and diastolic blood pressure.     

Comparison of the effects of pioglitazone and voglibose on circulating total and high-molecular-weight adiponectin, and on two fibrinolysis inhibitors, in patients with Type 2 diabetes.

BACKGROUND: To investigate short-term effects of pioglitazone and voglibose on serum concentrations of both total and high-molecular-weight (HMW) adiponectin measured with a novel sandwich enzyme-linked immunosorbent assay (ELISA) ,and on plasma fibrinolysis indicators, in Type 2 diabetic patients with inadequate glycaemic control on sulphonylureas. METHODS: Thirty-four diabetic patients were randomized to receive pioglitazone or voglibose treatment for 12 weeks, after which serum HMW adiponectin was measured. Plasma plasminogen activator inhibitor (PAI) 1 and thrombin-activatable fibrinolysis inhibitor (TAFI), a recently identified inhibitor of fibrinolysis, were measured as fibrinolysis inhibitors. RESULTS: At baseline, serum HMW adiponectin correlated negatively with plasma TAFI in all patients with Type 2 diabetes (r = -0.367, P = 0.0423). Both groups showed similar improvements in glycaemic control. Serum total and HMW adiponectin increased in patients treated with pioglitazone, but did not change in patients treated with voglibose. The HMW : total adiponectin ratio increased significantly after treatment with pioglitazone (P = 0.0004). The change in HbA(1c) correlated negatively with changes in serum HMW adiponectin in patients treated with pioglitazone (r = -0.694, P = 0.0034). Plasma PAI-1 and TAFI did not change with pioglitazone treatment. CONCLUSION: Increased serum HMW adiponectin may contribute to the improvement in glycaemic control after pioglitazone treatment. Plasma PAI-1 and TAFI were unchanged by either drug.     

新诊断2型糖尿病患者脂肪细胞因子水平与代谢综合征的关系

目的 探讨新诊断2型糖尿病患者血清脂联素及视黄醇结合蛋白4(RBP4)水平与代谢综合征(MS)的关系. 方法分别将糖尿病组及对照组分为年龄≥60岁组及<60岁组,根据2004年中华医学会糖尿病学会提出的关于MS的定义将对照组及糖尿病组分为不同代谢异常组.采用ELISA法测定95例新诊断2型糖尿病患者(糖尿病组)与55例非精尿病者(对照组)空腹血清脂联素、RBP4浓度,同时检测血糖、血脂、血压、血清胰岛素水平,采用胰岛素抵抗指数(HOMA-IR)评价各组胰岛素敏感性,分析各项指标与脂联素、RBP4的相关性. 结果 (1)糖尿病组与对照组比较,血清脂联素水平显著降低,分别为(7.26±4.69)mg/L和(11.93±4.89)mg/L;RBP4水平显著升高,分别为(16.48±7.82)mg/L和(10.91±5.26)mg/L;(2)糖尿病组与对照组比较,MS患病率显著增高,分别为46.3%和7.3%;(3)随着MS组分的增多,脂联素含量均呈下降趋势,而RBP4水平呈升高趋势;(4)糖尿组血清脂联素与MS、腰围、体质指数呈负相关,RBP4与腰围、HOMA-IR、体质指数、MS、三酰甘油呈正相关. 结论血清脂联素、RBP4与MS密切相关,低脂联素血症、高RBP4在MS发病中可能具有重要的作用.     

Association of circulating levels of leptin and adiponectin with metabolic syndrome and coronary heart disease in patients with various coronary risk factors

The aim of this study was to investigate the associations of adiponectin and leptin with metabolic syndrome (MetS) and coronary heart disease (CHD) in patients with various coronary risk factors. We determined serum adiponectin, leptin, and metabolic syndrome components in 104 patients (59 men and 45 women; aged 40-86 years) with various coronary risk factors at a cardiovascular out-patient clinic. Natural logarithmic transformed (ln) leptin was lower in men and smokers, and positively correlated with body mass index (BMI) (r = 0.59, P < 0.0001), waist circumference (r = 0.60, P < 0.0001), and homeostasis model assessment of insulin resistance (HOMA-IR) levels (r = 0.24, P < 0.02). Ln adiponectin was higher in women and nonsmokers, and was correlated with age and high-density lipoprotein cholesterol (HDL-C). Patients with MetS (n = 69) had significantly higher BMI, HOMA-IR, and ln leptin and lower ln adiponectin than those without Mets (Ln leptin, 2.14 ± 0.08 versus 1.30 ± 0.11; Ln adiponectin, 2.29 ± 0.06 versus 2.54 ± 0.09). In contrast, patients with coronary heart disease (CHD: n = 40) had significantly lower serum ln adiponectin concentrations than non-CHD patients (n = 64) (1.79 ± 0.12 versus 1.91 ± 0.10) as well as lower HDL-C and a higher smoking percentage. Consistent results were obtained by multivariate analyses. In conclusion, this study disclosed factors associated with the increase in serum leptin and adiponectin. Serum levels of leptin may be associated positively with MetS, whereas adiponectin levels are associated negatively with MetS and CHD, even in patients with various coronary risk factors.     

Prevalence of metabolic syndrome in Japanese type 2 diabetic patients and its significance for chronic vascular complications

Prevalence of metabolic syndrome (MetS) in type 2 diabetes and its association with vascular complications were studied in 637 Japanese type 2 diabetic patients. MetS was diagnosed using criteria proposed by the Japanese study group for the definition of MetS in 2005. The prevalence of MetS in patients studied was higher in males (45.9%) than females (28.0%). The prevalence of MetS was 53.0% in males and 35.4% in females in patients with duration of less than 10 years, and decreased with an increase in duration. Upon comparing patients groups complicated with and without MetS, we determined the MetS group had significantly higher levels of fasting serum C-peptide and high-sensitivity C-reactive protein, and a significantly lower level of serum adiponectin. However, the prevalence of coronary heart disease, brain infarction, or peripheral arterial disease was not significantly different between these groups. On the other hand, the prevalence of microangiopathy in the group with MetS was significantly higher than in that without MetS, and became significantly higher along with an increase in duration. This study clarifies the prevalence of MetS in Japanese type 2 diabetic patients, and suggests that MetS is associated with microangiopathy rather than macroangiopathy in Japanese type 2 diabetic patients.     

Endothelial dysfunction in metabolic syndrome: Prevalence,pathogenesis and management

The metabolic syndrome (MetS) is characterized by the presence of central obesity, impaired glucose metabolism, dyslipidemia and hypertension. Several studies showed that MetS is associated with increased risk for type 2 diabetes mellitus (T2DM) and vascular events. All components of MetS have adverse effects on the endothelium. Endothelial dysfunction plays a role in the pathogenesis of atherosclerosis and might also increase the risk for insulin resistance and T2DM. We review the prevalence and pathogenesis of endothelial dysfunction in MetS. We also discuss the potential effects of lifestyle measures and pharmacological interventions on endothelial function in these patients. It remains to be established whether improving endothelial function in MetS will reduce the risk for T2DM and vascular events.     

Relationship between metabolic syndrome and follicle-stimulating hormone in postmenopausal women

Depletion of ovarian reserve during menopausal transition raises follicle-stimulating hormone (FSH) markedly and menopause is related to an increased risk for metabolic syndrome (MetS). This study examined the relationship between FSH and MetS in postmenopausal women.We evaluated the anthropometric values, lipid profiles, high-sensitivity C-reactive protein (hs-CRP) level, Homeostasis model assessment for insulin resistance (HOMA-IR), and serum adipokines levels in 219 postmenopausal women. Serum FSH and estradiol levels were significantly lower in the MetS group than in the non-MetS group. An inverse correlation was observed between FSH with body fat mass (BFM), and HOMA-IR, and a positive correlation was found between FSH and adiponectin level after adjustment for age, years since menopause, BMI, and serum estradiol.The odds ratio for MetS was higher significantly in the lowest quartile of FSH level than the highest quartile of FSH level (odd ratio = 1.32, 95% CI = 1.09–1.75). Our study showed an increased FSH level favored insulin sensitivity with a higher adiponectin and lower HOMA-IR as well as a lower incidence of MetS in postmenopausal women.These findings suggest a new approach to the role of FSH for regulating energy metabolism and for use as a biomarker of MetS risk in postmenopausal women.This systematic review is based on published researches, so there is no ethical approval required.     

Genetic variants in the leukemia-associated Rho guanine nucleotide exchange factor (ARHGEF12) gene are not associated with T2DM and related parameters in Caucasians (KORA study)

OBJECTIVE: The aim of our study was to determine the variant pattern of the leukemia-associated Rho guanine nucleotide exchange factor (LARG, or ARHGEF12) gene and investigate whether LARG variants are associated with diabetes mellitus type 2 (T2DM), the metabolic syndrome (MetS), or related parameters such as insulin sensitivity in German Caucasians. DESIGN: We analyzed single nucleotide polymorphisms (SNPs) in the LARG gene in the 55-74-year-old individuals of the population-based German Caucasian Cooperative Health Research in the region of Augsberg (KORA) survey 4 (S4). METHODS: Sequencing of Tyr1306Cys, which was of functional relevance in Pima Indians, in 48 randomly selected individuals and genotyping of 11 additional LARG SNPs in 1653 subjects were performed. Four linkage disequilibrium (LD) blocks (r(2)> or =0.8) were established and each block was statistically analyzed for association with metabolic traits. The association with T2DM and the MetS was analyzed by logistic regression in 1462 subjects, and HOMA-IR (homeostasis model assessment of insulin resistance) as a measure of insulin sensitivity was analyzed by the Kruskal-Wallis test in 1346 fasting subjects. RESULTS: The polymorphism Tyr1306Cys, which was significantly associated with insulin sensitivity in Pima Indians, was not found in the KORA S4 population. Statistical analysis yielded no significant associations (P>0.05) between the analyzed LARG variants and T2DM, the MetS, or related parameters such as insulin sensitivity. CONCLUSIONS: Caucasian individuals and Pima Indians differ in their genetic variance pattern in the LARG gene region. There is no evidence in the Caucasian KORA study that variants of the LARG gene confer susceptibility for T2DM, insulin sensitivity, or the MetS.     

Menopause impacts the relation of plasma adiponectin levels with the metabolic syndrome

Abstract. Henneman P, Janssens ACJW, Carola Zillikens M, Frolich M, Frants RR, Oostra BA, van Duijn CM, van Dijk KW (Leiden University Medical Center, Leiden; Erasmus Medical Center, Rotterdam, The Netherlands). Menopause impacts the relation of plasma adiponectin levels with the metabolic syndrome. J Intern Med 2010; 267 : 402–409. Objective. Plasma adiponectin is negatively correlated with metabolic syndrome (MetS) components obesity and insulin sensitivity. Here, we set out to evaluate the effect of menopause on the association of plasma adiponectin with MetS. Design. Data on plasma adiponectin and MetS were available from 2256 individuals participating in the Erasmus Rucphen Family study. Odds ratios for MetS were calculated by logistic regression analysis using plasma adiponectin quartiles. The discriminative accuracy of plasma adiponectin for MetS was determined by calculating the area under the curve (AUC) of receiver operator. Analyses were performed in women and men, pre‐ and postmenopausal women and younger and older men. Results. Virtually all determinants of MetS differed significantly between groups. Low plasma adiponectin showed the highest risk for MetS in postmenopausal women (odds ratio = 18.6, 95% CI = 7.9–44.0). We observed a high discriminative accuracy of age and plasma adiponectin for MetS not only in postmenopausal women (AUC = 0.76) but also in other subgroups (AUC from 0.67 to 0.87). However, in all groups, the discriminative accuracy of age and body mass index (BMI) for MetS was similar to the discriminative accuracy of age and plasma adiponectin. Conclusions. Low plasma levels of adiponectin are associated with increased prevalence of MetS, especially in postmenopausal women. Age and BMI have similar discriminatory accuracies for presence of MetS when compared with age and plasma adiponectin. Thus, we conclude that the association of plasma adiponectin with MetS is significantly affected by menopause but challenge the additional value of adiponectin for the discriminatory accuracy for presence of MetS.     

Impact of metabolic syndrome risk factors in first-degree relatives of type 2 diabetic patients

OBJECTIVE: Family members of patients with an established diagnosis of type 2 diabetes mellitus (T2DM) are theoretically at risk of having the metabolic syndrome (MetS). A sample of these family members was studied from a population in a small township in Argentina, which has a high prevalence of T2DM. METHODS: We examined the clinical and metabolic characteristics of 132 first-degree relatives of T2DM patients (FDR) and 112 age-matched controls. The subjects were categorized according to the International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria for MetS. RESULTS: The prevalence of MetS in the FDR group was 34.8 (IDF) and 26.5% (NCEP-ATPIII) respectively, which was significantly different to the prevalence in controls (p < 0.025). According to IDF criteria, the most prevalent factors among FDR subjects with MetS were low HDL-cholesterol (87%) followed by hypertriglyceridemia (69.5%). In the MetS group, which ranged between 20-29 years old (36%), the major risk factor in women was a low HDL-cholesterol serum level. In the MetS group, which ranged between 30-39 years old (44.4%), the most important risk factor in men was hypertriglyceridemia. CONCLUSION: This study revealed that the prevalence of MetS is high in young FDR adults, who need urgent preventive treatment, including lifestyle changes. The risk of developing T2DM is five times higher in non-diabetic people with MetS than in those without the syndrome.     

Phospholipid transfer protein activity is determined by type 2 diabetes mellitus and metabolic syndrome, and is positively associated with serum transaminases

Background The extent to which plasma phospholipid transfer protein (PLTP) activity is affected by type 2 diabetes mellitus (DM) and metabolic syndrome (MetS) is still unknown. PLTP is synthesized in the liver, and elevated serum transaminases are considered to predict nonalcoholic fatty liver disease (NAFLD). In this study, we examined the relationship between plasma PLTP activity and liver enzymes in subjects with and without DM and MetS. Design Plasma PLTP activity, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in 71 subjects without DM or MetS, 21 without DM but with MetS, 26 with DM but without MetS and 55 with DM and MetS (WHO and NCEP‐ATP III criteria). Results After controlling for age, sex and alcohol intake, PLTP activity was positively related to both MetS (P < 0·001) and DM (P = 0·001). Serum ALT (P = 0·006) and AST (P = 0·04) were both associated with MetS, but only ALT was associated with DM (P < 0·001). In multiple linear regression models, serum ALT and AST were positively and independently associated with PLTP activity (P < 0·01 for all), even when the presence of MetS and DM was taken into account, as well as after controlling for glycated haemoglobin (HbA_1c), insulin resistance, triglycerides, free fatty acids (FFA), C‐reactive protein (CRP), leptin and adiponectin. Conclusions Plasma PLTP activity is determined by MetS and by diabetes per se. Serum transaminases are independently associated with PLTP activity. We suggest that this lipid transfer protein may be a marker for NAFLD.     

The triglyceride-waist circumference index is a valid biomarker of metabolic syndrome in African Americans

BackgroundThe hypertriglyceridemia waist (HTGW) phenotype is associated with visceral adiposity, metabolic syndrome, type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Since the cut points for abdominal obesity and hypertriglyceridemia, differ for different race groups, investigators have developed the product of triglycerides (TG) and waist circumference (WC) as the TG.WC index. We compared this TG.WC index to the TG:HDL-C ratio in the National Health and Nutrition Examination Survey (NHANES) study to predict metabolic syndrome (MetS) in African Americans (AAs).MethodsParticipants included 950 AAs and 2651 non-Hispanic Whites (NHWs) for comparison from the NHANES data set. Persons with diabetes, ASCVD and macro-inflammation were excluded. Fasting blood was obtained for lipids, insulin and CRP.ResultsIn AAs and NHWs, both the TG.WC index and TG:HDL-C ratio were significantly increased in MetS patients. Also, both increased with increasing severity of MetS and correlated with all features of MetS, insulin resistance and inflammation. Receiver operating characteristic (ROC) curve analysis showed that discrimination with TG.WC for MetS was superior to the TG:HDL-C ratio especially in AAs.ConclusionsTG.WC index is a superior biomarker to TG:HDL-C for predicting MetS in AAs despite their lower TG levels.     

Positive correlations of liver enzymes with metabolic syndrome including insulin resistance in newly diagnosed type 2 diabetes mellitus

It has long been proposed that elevation of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT) may be associated with insulin resistance (IR). In the present study, we aimed to investigate the association of the above mentioned liver enzymes with IR by using hyperinsulinemic euglycemic clamp, as well as their relationship with individual component of metabolic syndrome (MetS) in 95 newly diagnosed type 2 diabetes (T2DM) Chinese patients. All the diagnosed patients did not use drugs for treatment of diabetes or dyslipidemia previously and were divided into IR and non-IR groups. The results showed that IR group had significantly higher ALT, AST, and GGT (P<0.01, P<0.01, and P<0.05, respectively) compared with non-IR group. According to the individual MetS component, ALT and AST were significantly increased in patients with high blood pressure compared with those without (both P<0.001); ALT and GGT were increased in patients with high triglyceride (P<0.05 and P<0.01); AST was increased in patients with central obesity (P<0.05). In correlation analysis, a significant association was found between the three liver enzymes and clamp insulin sensitivity index (all P<0.001). In the linear regression analysis, ALT was the determinant of clamp ISI, independent of age, sex, BMI, and fasting and OGTT 2 h plasma glucose (P<0.0001). In conclusion, liver enzymes, especially ALT, were significantly associated with IR according to direct clamp assessment, which were independent of the traditional risk factors in diabetic patients; and individual liver enzymes may have different relationship with individual component of MetS.     

Ezetimibe added to atorvastatin compared with doubling the atorvastatin dose in patients at high risk for coronary heart disease with diabetes mellitus,metabolic syndrome or neither

Aim: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are both associated with increased risk for atherosclerotic coronary heart disease (CHD). Thus, it is useful to know the relative efficacy of lipid‐altering drugs in these patient populations. Methods: A double‐blind, parallel group trial of adult patients with hypercholesterolaemia at high‐CHD risk receiving atorvastatin 40 mg/day compared atorvastatin 40 mg plus ezetimibe 10 mg (ezetimibe) vs. doubling atorvastatin to 80 mg. This post hoc analysis reports lipid efficacy results in patients grouped by diagnosis of T2DM, MetS without T2DM or neither. Per cent change from baseline at week 6 was assessed for LDL‐C, total cholesterol, HDL‐C , non‐HDL‐C , Apo A‐I, Apo B and triglycerides. Safety was monitored through clinical and laboratory adverse events (AEs). Results: Compared with doubling atorvastatin, atorvastatin plus ezetimibe resulted in greater reductions in LDL‐C, triglycerides, Apo B, non‐HDL‐C, total cholesterol and lipid ratios in the T2DM, MetS and neither groups. Treatment effects were of similar magnitude across patient groups with both treatments, except triglycerides, which were slightly greater in the T2DM and MetS groups vs. neither group. Changes in HDL‐C , Apo A‐I and high sensitivity C‐reactive protein (hs‐CRP) were comparable for both treatments in all three groups. Safety and tolerability profiles were generally similar between treatments and across patient groups, as were the incidence of liver and muscle AEs. Conclusions: Compared with doubling atorvastatin to 80 mg, addition of ezetimibe to atorvastatin 40 mg produced greater improvements in multiple lipid parameters in high‐CHD risk patients with T2DM, MetS or neither, consistent with the significantly greater changes observed in the full study cohort (clinical trial # NCT00276484).     

Impact of non-alcoholic fatty liver disease on accelerated metabolic complications

Insulin resistance is the basis of both non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), the two conditions are often found in the same individual. The mortality of patients with NAFLD is significantly higher than that among the general population and cardiovascular risk may compete with liver-related risk in dictating the final outcome. Recent prospective studies have reported that NAFLD is associated with an increased incidence of MetS and type 2 diabetes mellitus, independent of obesity and other components of MetS. Thus, NAFLD may not only be a liver disease but also an early mediator of type 2 diabetes mellitus and MetS. The biological mechanisms by which NAFLD contributes to a higher risk of developing metabolic disorders are not fully understood. However, the fatty liver could contribute in the same way as visceral adipose tissue to insulin resistance, systemic inflammation and oxidative stress, while the decreased serum adiponectin concentrations might also be part of the mechanism. In contemporary clinical practice, it has become mandatory to evaluate the metabolic risk factors in NAFLD patients and to consider careful surveillance and aggressive treatment, not only of the resultant liver disease, but also of the possible underlying metabolic and vascular complications. Future studies might address the question whether earlier adjustment to a more efficient lifestyle or a pharmacological treatment that mobilizes fat out of the liver could reduce these risks.     

Association of serum ferritin concentrations with prevalence of prediabetes,type 2 diabetes mellitus,and metabolic syndrome in a Chinese population from Sichuan

Body iron stores reflected by serum ferritin levels have been implicated in many chronic diseases. We investigated associations between serum ferritin concentrations and the risk of prediabetes, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) in a Chinese population. For a cross-sectional study, 3040 subjects were recruited from three communities in Sichuan. Subjects were grouped by prediabetes or T2DM status, or components of MetS. Subjects with prediabetes were classified as having impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG + IGT). The odds ratios, assessed by gender, for the associations between serum ferritin concentration and prediabetes, T2DM, and MetS were calculated using multivariate logistic regression. The prevalence of IGT, IFG + IGT, T2DM, and MetS in the highest quartile of ferritin concentrations was higher than those in the lowest quartile, in both genders. In women, the adjusted odds ratios of IGT, IFG + IGT, T2DM, and MetS were higher in the highest ferritin quartile than the lowest; in men, only that of IFG + IGT was higher. In both genders, high ferritin levels were associated with higher odds ratios of hypertriglyceridemia and hyperglycemia, components of MetS. IGT, IFG + IGT, T2DM, and MetS were more common in the highest ferritin quartile for both genders. Elevated ferritin concentrations were associated with an increased risk for IGT and IFG + IGT in prediabetes, T2DM, and MetS, especially in women.

     

Body fat,metabolic syndrome and hyperglycemia in South Asians

The prevalence of overweight and obesity is escalating in South Asian countries. South Asians display higher total and abdominal obesity at a lower BMI when compared to Whites. Consequently, metabolic dysfunction leading to metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) will account for a majority of the health burden of these countries. In this review, we discuss those factors that contribute to MetS and T2DM in South Asians when compared to whites, focusing on adiposity. Abdominal obesity is the single-most important risk factor for MetS and its predisposition to T2DM. Excessive ectopic fat deposition in the liver (non-alcoholic fatty liver disease) has been linked to insulin resistance in Asian Indians, while the effects of ectopic fat accumulation in pancreas and skeletal muscle need more investigation. South Asians also have lower skeletal muscle mass than Whites, and this may contribute to their higher risk T2DM. Lifestyle factors contributing to MetS and T2DM in South Asians include inadequate physical activity and high intakes of refined carbohydrates and saturated fats. These are reflective of the recent but rapid economic transition and urbanization of the South Asian region. There is need to further the research into genetic determinants of dysmetabolism as well as gene x environment interactions. Collectively, MetS and T2DM have multi-factorial antecedents in South Asians and efforts to combat it through low-cost and socio-culturally appropriate lifestyle interventions need to be supported.     

Interleukin-10 associates with adiponectin predominantly in subjects with metabolic syndrome.

BACKGROUND: Inflammation and the metabolic syndrome (MetS) are important risk factors in cardiovascular disease. There is accumulating evidence that decreased adiponectin levels are associated with MetS. Recently, it was shown that adiponectin induces the expression of a potent anti-inflammatory cytokine, interleukin (IL)-10, in vitro. The aim of this study is to investigate the association of IL-10 levels with other pro-inflammatory and anti-inflammatory factors including adiponectin levels in vivo. METHODS AND RESULTS: MetS components were assessed in 117 drug-na?ve middle-aged men. Serum levels of high-sensitive C-reactive protein (hs-CRP), IL-6, adiponectin, IL-10 and tumor necrosis factor-alpha (TNF-alpha) were measured in these subjects. A significant decrease in adiponectin (5.15+/-1.79 microg/ml vs 6.87+/-3.55 microg/ml, p<0.02) and an increase in IL-6 (1.50+/-1.50 pg/ml vs 1.06+/-0.78 pg/ml, p<0.05) levels were associated with MetS. The serum IL-10 level exhibited a significant positive correlation with IL-6, hs-CRP, and TNF-alpha levels, but not with adiponectin in healthy individuals. However, IL-10 exhibited a significant correlation with adiponectin, especially in the subjects with MetS. CONCLUSIONS: Serum IL-10 levels correlated with inflammatory proteins, but not with adiponectin. However, IL-10 positively associated with adiponectin especially in the subjects with MetS. IL-10 might be involved in the inflammatory network of MetS in relation to adiponectin.