Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects

BackgroundA soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy.MethodsWe assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome).ResultsFasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels.ConclusionSerum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c.     

血清chemerin 水平与代谢综合征患者合并冠心病的相关性研究

目的:旨在探讨血清脂肪因子chemerin水平与代谢综合征患者合并冠心病的相关性。方法:共纳入116名代谢综合征患者,将所有患者分为两组,合并冠心病组(CAD+,n=47)及未合并冠心病组(CAD-,n=69),使用酶联免疫吸附(ELISA)法测量每组血清的血清chemerin水平。结果:CAD+组患者的血清chemerin水平较CAD-组患者显著升高(129.83±29.18 vs 94.01±23.54 ng/mL;P<0.01),多元Logistic回归分析结果显示血清chemerin水平与代谢综合征患者合并冠心病存在独立相关性(优势比1.565,95%可信区间1.104-2.876;P<0.05)。结论:血清chemerin水平是代谢综合征患者合并冠心病的独立危险因子,血清chemerin可能是预测代谢综合征患者发生冠心病风险的重要的生物学标记物。     

达格列净对2型糖尿病合并非酒精性脂肪性肝病患者血清FGF-21水平的影响

摘要 目的：分析血清成纤维细胞生长因子-21（FGF-21）与2型糖尿病（T2DM）合并非酒精性脂肪性肝病（NAFLD）患者常见指标及NAFLD纤维化评分（NFS）的相关性,进一步探讨达格列净对T2DM合并NAFLD患者血清FGF-21水平的影响。方法：选取2022年1月至2022年6月徐州医科大学附属徐州市立医院收治的80例T2DM合并NAFLD患者为研究对象（T2DM合并NAFLD组）,选择同期80例T2DM不合并NAFLD患者为T2DM组。收集腰围（WC）、身高、体重数据,计算体重指数（BMI）。测定空腹血糖（FPG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-c）,低密度脂蛋白胆固醇（LDL-c）、肌酐（Cr）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST ）、白蛋白（Alb）、血小板计数（PLT）等指标,计算胰岛素抵抗指数（HOMA-IR）、NFS。采用酶联免疫吸附（ELISA）法测定FGF-21水平。比较T2DM组和T2DM合并NAFLD组各项指标的差异,探讨血清FGF-21水平与T2DM合并NAFLD患者其他指标的相关性,Logistic回归分析T2DM合并NAFLD的影响因素,受试者工作特征曲线（ROC）分析各影响因素对T2DM合并NAFLD的诊断价值。将80例T2DM合并NAFLD患者按随机数字表法随机分为二甲双胍组和达格列净组各40例,治疗前后观测各项指标变化,并密切监测不良反应。结果：T2DM合并NAFLD组患者WC、BMI、FINS、HbA1c、TG、AST、ALT、HOMA-IR、NFS及FGF-21均高于 T2DM组（P＜0.05）。相关性分析显示,FGF-21水平与T2DM合并NAFLD组患者WC、BMI、HbA1c、TG、HOMA-IR、NFS均存在正相关（P<0.05）。Logistic回归分析显示,BMI、HbA1c、FGF-21、HOMA-IR为影响T2DM患者合并NAFLD的危险因素。ROC曲线分析显示,BMI、HbA1c、FGF-21、HOMA-IR对T2DM合并NAFLD均具有一定预测价值,其中以FGF-21的预测效能最佳。治疗后,达格列净组TG、AST、ALT、NFS、FGF-21水平较二甲双胍组降低更为明显（P＜0.05）。结论：血清FGF-21水平为T2DM合并NAFLD的危险因素,参与了T2DM合并NAFLD发病及进展,且对T2DM合并NAFLD有较好的预测效能。相较于二甲双胍,达格列净可明显降低T2DM合并NAFLD患者血清FGF-21水平并改善NFS,具有一定程度的肝脏保护作用。     

Association of Alanine Aminotransferase Levels (ALT) with the Hepatic Insulin Resistance Index (HIRI): a cross-sectional study

ABSTRACT: BACKGROUND: The association between serum alanine aminotransferase (ALT) levels and hepatic insulin resistance (IR) has been evaluated with the hyperinsulinemic-euglycemic clamp. However, there is no information about the association of ALT with the Hepatic Insulin Resistance Index (HIRI). The aim of this study was to evaluate the association between serum ALT levels and HIRI in subjects with differing degrees of impaired glucose metabolism. METHODS: This cross-sectional study included subjects that had an indication for testing for type 2 diabetes mellitus (T2DM) with an oral glucose tolerance test (OGTT). Clinical and biochemical evaluations were carried out including serum ALT level quantification. HIRI was calculated for each participant. Correlation analyses and lineal regression models were used to evaluate the association between ALT levels and HIRI. RESULTS: A total of 324 subjects (37.6 % male) were included. The mean age was 40.4 [PLUS-MINUS SIGN] 14.3 years and the mean body mass index (BMI) was 32.0 [PLUS-MINUS SIGN] 7.3 kg/m2. Individuals were divided into 1 of 5 groups: without metabolic abnormalities (n = 113, 34.8 %); with the metabolic syndrome (MetS, n = 179, 55.2 %), impaired fasting glucose (IFG, n = 85, 26.2 %); impaired glucose tolerance (IGT, n = 91, 28.0 %), and T2DM (n = 23, 7.0 %). The ALT (p < 0.001) and HOMA2-IR (p < 0.001) values progressively increased with HIRI quartiles, while ISI-Matsuda (p < 0.001) progressively decreased. After adjustment for sex, age, and BMI, we identified a significant correlation between HIRI and ALT in persons with the MetS (r = 0.22, p = 0.003), IFG (r = 0.33, p < 0.001), IGT (r = 0.37, p < 0.001), and T2DM (r = 0.72, p < 0.001). Lineal regression analysis adjusting for age, HDL-C, TG and waist circumference (WC) showed an independent association between ALT and HIRI in subjects with the MetS (beta = 0.07, p = 0.01), IFG (beta = 0.10, p = 0.02), IGT (beta = 0.09, p = 0.007), and T2DM (beta = 0.31, p = 0.003). This association was not identified in subjects without metabolic abnormalities. CONCLUSIONS: ALT levels are independently associated with HIRI in subjects with the MetS, IFG, IGT, and T2DM. The ALT value in these subjects may be an indirect parameter to evaluate hepatic IR.     

Serum Adiponectin Confers Little Protection Against Diabetes and Hypertension in Turkish Men

We determined serum adiponectin's role as a biomarker of metabolic syndrome (MetS), type 2 diabetes (DM) and hypertension among Turkish adults who have a high prevalence of MetS. Individuals with measured serum adiponectin concentrations, constituting a random sample of Turkish adults, were studied cross‐sectionally. MetS was identified by criteria of the Adult Treatment Panel‐III modified for male abdominal obesity. Median age of 547 men and 652 women was 54 years. MetS was identified in 46%. Linear regression analysis among nine variables revealed homeostatic model assessment (HOMA) index in both sexes and C‐reactive protein (CRP) only in men as inversely associated covariates of adiponectin, and sex hormone‐binding globulin (SHBG) as positive covariate in women. Age‐adjusted sex‐specifically dichotomized high vs. low adiponectin levels were significantly associated with DM (odds ratio (OR) 0.55, P = 0.01) and hypertension (OR 0.64, P = 0.012) in women, but not in men. Further adjustment for smoking status and presence of high/low BMI did not alter this sex‐based relationship. As regards association with MetS, low adiponectin and high BMI interacted significantly in each sex. Yet adiponectin was associated only in men additively to the simultaneously adjusted five MetS components. We conclude that adiponectin concentrations, clearly linked to metabolic disorders, may diverge among sexes regarding protection against cardiometabolic risk through anti‐inflammatory or antioxidative function, Turkish men alone revealing significant dysfunction independent of obesity. This dysfunction may underlie also the association of adiponectin levels with MetS in men to be independent of the MetS components.     

The MMP-9 -1562 C/T Polymorphism in the Presence of Metabolic Syndrome Increases the Risk of Clinical Events in Patients with Coronary Artery Disease

Background and Objectives

Elevated levels of matrix metalloproteinase (MMP)-9 have been associated with the metabolic syndrome (MetS) and cardiovascular events. The MMP-9 −1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD). The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 −1562 C/T polymorphism in subjects with CAD and MetS.

Methods

Patients (n = 1000) with verified CAD stratified in Mets +/− (n = 244/756), were analyzed for the MMP-9 −1562 C/T polymorphism and related to clinical events after 2 years follow-up. Serum levels of total MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1were analyzed in all, whereas MMP-9 activity, extracellular matrix metalloproteinase inducer (EMMPRIN), and expression of the two genes were analyzed in a subset of 240 randomly selected patients.

Results

Totally, 106 clinical endpoints were recorded. In MetS; the T-allele associated with 5.5 fold increase in event rate (p<0.0001), increased with number of MetS components, a 117% increase in total MMP-9 levels (TT homozygous, p = 0.05), significantly higher total- and endogenous active MMP-9 and TIMP-1 levels (p<0.01 all), and EMMPRIN was inversely correlated with pro- and endogenous active MMP-9 (p<0.05, both). In non-MetS; the T-allele was not associated with new events, nor higher MMP-9 levels. EMMPRIN was significantly correlated with total MMP-9 and TIMP-1 (p<0.01, both) and the two genes were inter-correlated (p<0.001).

Conclusion

In CAD patients with MetS, the MMP-9 T-allele increased the risk of clinical events, probably mediated through elevated MMP-9 levels and altered MMP-9 regulation.     

老年2型糖尿病患者血清ANGPTL4、Betatrophin、Vaspin水平与血糖、血脂及下肢血管病变的关系研究

摘要 目的：探讨老年2型糖尿病（T2DM）患者血清脂肪因子血管生成素样蛋白4（ANGPTL4）、促代谢因子（Betatrophin）、腹腔脂肪型丝氨酸蛋白酶抑制剂（Vaspin）水平与血糖、血脂、下肢血管病变（LVD）的关系。方法：选取我院2018年8月～2019年8月收治的老年T2DM患者108例,根据患者是否合并LVD,分成LVD组（n=38）和无LVD组（n=70）,比较两组临床资料、血清ANGPTL4、Betatrophin、Vaspin水平、血糖指标[空腹血糖（FPG）、餐后2 h血糖（2hPG）、糖化血红蛋白（HbA1c）]、血脂指标[总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）]。经Pearson线性相关分析患者血清ANGPTL4、Betatrophin、Vaspin水平与血糖、血脂指标相关性。经Logistic多因素回归模型分析患者LVD发生的影响因素。结果：LVD组舒张压、收缩压均高于无LVD组（P＜0.05）。LVD组血清Betatrophin水平及TC、TG、LDL-C、FPG、2hPG、HbA1c高于无LVD组,血清ANGPTL4、Vaspin水平及HDL-C低于无LVD组（P＜0.05）。Pearson线性相关分析显示,血清ANGPTL4、Vaspin与TC、TG、LDL-C、FPG、2hPG、HbA1c呈负相关,与HDL-C呈正相关（P＜0.05）。血清Betatrophin与TC、TG、LDL-C、FPG、2hPG、HbA1c呈正相关,与HDL-C呈负相关（P＜0.05）。Logistic多因素回归模型分析结果显示,血清ANGPTL4、Betatrophin、Vaspin以及舒张压、TC、TG、HDL-C、LDL-C、FPG、2hPG、HbA1c是患者LVD发生的影响因素（P＜0.05）。结论：老年T2DM合并LVD患者的血清ANGPTL4、Vaspin水平明显下降,而血清Betatrophin水平升高,且三者与血糖、血脂指标均存在相关性,并且是患者发生LVD的影响因素,临床可考虑通过检测血清ANGPTL4、Betatrophin、Vaspin水平,辅助评估LVD的发生风险。     

血清CTRP5、CTRP12、CTRP13与老年2型糖尿病患者糖脂代谢和颈动脉粥样硬化的关系

摘要 目的：探讨血清补体1q/肿瘤坏死因子相关蛋白（CTRP）5、CTRP12、CTRP13与老年2型糖尿病（T2DM）患者糖脂代谢和颈动脉粥样硬化（CAS）的关系。方法：选取2021年1月～2023年1月徐州医科大学附属医院收治的198例老年T2DM患者纳入T2DM组,另选取同期100名体检健康老年人纳入对照组,根据是否CAS将老年T2DM患者分为CAS组131例和非CAS组67例。检测血清CTRP5、CTRP12、CTRP13和糖脂代谢指标[空腹血糖（FPG）、餐后2h血糖（2hBG）、糖化血红蛋白（HbA1c）、稳态模型评估-胰岛素抵抗指数（HOMA-IR）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）]。采用Pearson相关性分析老年T2DM患者血清CTRP5、CTRP12、CTRP13与糖脂代谢指标水平的相关性,采用多因素Logistic回归模型和受试者工作特征（ROC）曲线分析老年T2DM患者CAS的影响因素及血清CTRP5、CTRP12、CTRP13水平对其的诊断价值。结果：与对照组比较,T2DM组血清CTRP5、FPG、2hBG、HbA1c、HOMA-IR、TC、TG、LDL-C水平升高,CTRP12、CTRP13、HDL-C水平降低（P＜0.05）。Pearson相关性分析显示,老年T2DM患者血清CTRP5与FPG、2hBG、HbA1c、HOMA-IR、TC、TG、LDL-C水平呈正相关,与HDL-C水平呈负相关（P＜0.05）;血清CTRP12、CTRP13与FPG、2hBG、HbA1c、HOMA-IR、TC、TG、LDL-C水平呈负相关,与HDL-C水平呈正相关（P＜0.05）。多因素Logistic回归模型分析显示,HbA1c、HOMA-IR、LDL-C、CTRP5升高为老年T2DM患者CAS的独立危险因素,CTRP12、CTRP13升高为独立保护因素（P＜0.05）。ROC曲线分析显示,血清CTRP5、CTRP12、CTRP13水平联合诊断老年T2DM患者CAS的曲线下面积（AUC）为0.915,大于血清CTRP5、CTRP12、CTRP13水平单独诊断的0.790、0.785、0.789。结论：老年T2DM患者血清CTRP5水平升高,CTRP12、CTRP13水平降低,与糖脂代谢紊乱和CAS密切相关,血清CTRP5、CTRP12、CTRP13水平联合对老年T2DM患者CAS具有较高的诊断价值。     

Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk

Background

Macrovascular diseases (MVD) in type 2 diabetes mellitus (T2DM) are often considered all together, without discriminating the areas involved. The aim of our study was to analyse MVD prevalence in a large population of T2DM patients by dividing the cases into subgroups according to MVD sites (NMVD, no MVD; NSCS, non-significant carotid stenosis; CBVD, cerebrovascular disease; CAD, coronary artery disease; PAD, peripheral artery disease; PVD, polyvascular disease) and studying the anthropometric, clinical and laboratory parameters in each group.

Methods

A diabetic outpatient cohort (n = 1199) was retrospectively studied. Demographic, clinical and laboratory parameters were included in analyses. A thorough cardiovascular history as documented by previous medical records (including medical and hospital records) and vascular laboratory studies (including standardised electrocardiogram, echocardiogram, provocative tests for cardiac ischaemia, ankle/brachial index, duplex ultrasonography of the carotid and lower limbs and, in selected cases, computed tomography angiography, carotid and peripheral arteriography and evaluation of transcutaneous oxygen pressure), was collected for all of the patients. Standardised procedures were used to assess microvascular complications as well as metabolic syndrome (Mets).

Results

The unadjusted MVD prevalence was 46.4% among the participants. The majority of patients with MVD were in the PVD group. In the multivariate analysis, age, male sex and diabetes duration were independent risk factors for PAD and PVD (P < 0.01). A low HDL-C value was an independent risk factor in the CAD and PVD groups (P = 0.03). Very high frequencies of MetS were observed in the PAD and PVD groups (94.9 and 95.7% respectively). The most MetS diagnostic criteria were recorded among members of the CAD group (all or all-1 criteria were present in 73% of patients). The average age in the CAD group (64.5 y) was comparable to that of the NMVD group. Microvascular complications were more frequent in the PAD and PVD patients.

Conclusion

Phenotypic heterogeneity is associated with different macrovascular complications in T2DM patients. These findings might have clinical implications for developing diagnostic and therapeutic strategies targeting type 2 diabetes.     

Plasma HMGB-1 Levels in Subjects with Obesity and Type 2 Diabetes: A Cross-Sectional Study in China

Object

To detect the levels of plasma High-Mobility Group Box-1(HMGB1) in Chinese subject with obesity and type 2 diabetes mellitus (T2DM), and to investigate the correlations between plasma HMGB1 concentration and parameters of body fat, insulin resistance (IR) metabolism and inflammation.

Methods

This study recruited 79 normal glucose tolerance (NGT) subjects and 76 newly diagnosed T2DM patients. NGT and T2DM groups were divided into normal weight (NW) and obese (OB)subgroups respectively. Anthropometric parameters such as height, weight, waist circumference, hip circumference and blood pressure were measured. Plasma concentrations of HMGB1, IL-6, fasting plasma glucose (FPG), 2 hours post challenge plasma glucose (2hPG), serum lipid, glycated hemoglobin (HbA_1C) and fasting insulin (FINS) were examined. The homeostasis model assessment (HOMA) was performed to assess IR status.

Results

Plasma HMGB1 levels were higher in T2DM group than that in NGT group. The concentrations of serum HMGB1 were also higher in subjects with OB than those in subjects with NW both in NGT and T2DM groups. Plasma levels of HMGB1 were positively correlated with waist hip ratio (WHR), blood pressure, FPG, FINS, HOMA-IR, TG, IL-6 and negatively correlated with HOMA-βand high-density lipoprotein-cholesterol (HDL-c) independent of age, gender and BMI. Plasma levels of HMGB1 were significantly correlated with diabetes in fully adjusted models.

Conclusion

Plasma HMGB1 levels were increased in Chinese subjects with pure T2DM, which might be caused by IR. Serum HMGB1 participated in the pathological process of obesity and T2DM via its proinflammatory effect.     

Heritability and genetic correlations explained by common SNPs for metabolic syndrome traits

We used a bivariate (multivariate) linear mixed-effects model to estimate the narrow-sense heritability (h(2)) and heritability explained by the common SNPs (h(g)(2)) for several metabolic syndrome (MetS) traits and the genetic correlation between pairs of traits for the Atherosclerosis Risk in Communities (ARIC) genome-wide association study (GWAS) population. MetS traits included body-mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), fasting glucose (GLU), fasting insulin (INS), fasting trigylcerides (TG), and fasting high-density lipoprotein (HDL). We found the percentage of h(2) accounted for by common SNPs to be 58% of h(2) for height, 41% for BMI, 46% for WHR, 30% for GLU, 39% for INS, 34% for TG, 25% for HDL, and 80% for SBP. We confirmed prior reports for height and BMI using the ARIC population and independently in the Framingham Heart Study (FHS) population. We demonstrated that the multivariate model supported large genetic correlations between BMI and WHR and between TG and HDL. We also showed that the genetic correlations between the MetS traits are directly proportional to the phenotypic correlations.     

Relationships of Obesity and Fat Distribution With Atherothrombotic Risk Factors: Baseline Results From the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

The impact of obesity on cardiovascular disease (CVD) outcomes in patients with type 2 diabetes mellitus (T2DM) and established coronary artery disease (CAD) is controversial; whether BMI and/or waist circumference correlate with atherothrombotic risk factors in such patients is uncertain. We sought to evaluate whether higher BMI or waist circumference are associated with specific risk factors among 2,273 Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study participants with T2DM and documented CAD (baseline data, mean age 62 years, 66% non‐Hispanic white, 71% men). Multiple linear regression models were constructed after adjusting for sex, age, race/ethnicity, US vs. non‐US site, diabetes duration, exercise, smoking, alcohol, and relevant medication use. First‐order partial correlations of BMI with risk factors after controlling for waist circumference and of waist circumference with risk factors after controlling for BMI were also evaluated. Ninety percent of the patients were overweight (BMI ≥25 kg/m²); 68% of men and 89% of women had high‐risk waist circumference measures (≥102 and ≥88 cm, respectively). BMI and waist circumference, in separate models, explained significant variation in metabolic (insulin, lipids, blood pressure (BP)) and inflammatory/procoagulation (C‐reactive protein, PAI‐1 activity and antigen, and fibrinogen) risk factors. In partial correlation analyses BMI was independently associated with BP and inflammatory/procoagulation factors, waist circumference with lipids, and both BMI and waist circumference with insulin. We conclude that, in cross‐sectional analyses, both BMI and waist circumference, independently, are associated with increased atherothrombotic risk in centrally obese cohorts such as the BARI 2D patients with T2DM and CAD.     

Potential risk modifications of GSTT1, GSTM1 and GSTP1 (glutathione-S-transferases) variants and their association to CAD in patients with type-2 diabetes

Background

Type-2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease (CAD) resulting in high morbidity and mortality. Glutathione S-transferases (GSTM1, GSTT1 and GSTP1) are known for their broad range of detoxification and in the metabolism of xenobiotics. Recent studies revealed the relationship of GSTs variants with T2DM and CAD. In this case-control study we ascertained the association of GSTs variants in association with the development of CAD in patients with T2DM.

Methods

From the Southern part of India, we enrolled 222 T2DM patients, 290 T2DM patients with CAD and 270 healthy controls matched for age, sex and origin. Serum lipid profiles were measured and DNA was extracted from the blood samples. Multiplex PCR for GSTM1/T1 (null polymorphism) and PCR-RFLP for GSTP1 (105 A > G), were performed for genotyping of study participants. Gene frequency and lipid profiles were statistically analyzed for disease association.

Results

Regression analysis showed that, GSTM1-null genotype is associated with a 2-fold increase (OR = 2.925; 95% CI = 2.078–4.119; P < 0.0001) and GSTT1-null genotype is associated with a 3-fold increase (OR = 3.114; 95% CI = 2.176–4.456; P < 0.0001) to T2DM development. Ile/Val and Val/Val genotypes of GSTP1 also showed a significant risk for T2DM (OR = 1.423, CI = 1.041–1.946; P = 0.027 and OR = 1.829, CI = 1.064–3.142; P = 0.029). Increased odds ratio showed that GSTT1-null genotype had a moderately higher occurrence in T2DM–CAD patients (OR = 1.918, 95% CI = 1.144–3.214; P = 0.014) than T2DM patients without CAD. The level of HDL has significantly decreased in GSTT1-present than in GSTT1-null genotype (43.50 ± 4.10 vs. 45.20 ± 3.90; P = 0.004) when compared with control and T2DM patients. However, LDL level showed a significant increase in GSTT1-null than GSTT1-present genotype (108.70 ± 16.90 vs. 102.20 ± 12.60; P = 0.005). Although the GSTM1-null polymorphism showed no correlation with lipid profiles among T2DM and T2DM with CAD patients, GSTT1-null polymorphism attained a statistical significance for the level of LDL (127 ± 28.20 vs. 134 ± 29.10; P = 0.039) and triglycerides in T2DM with CAD patients (182.10 ± 21.10 vs. 191.20 ± 24.10; P = 0.018).

Conclusion

Our work concludes that GSTM1, GSTT1 and GSTP1 variants might contribute to the development of T2DM and GSTT1 variant alone is involved in the development of T2DM associated CAD complications in the South Indian population.     

Amelioration of hyperglycaemia and hyperlipidaemia by adjusting the interplay between gut microbiota and bile acid metabolism: Radix Scutellariae as a case

BackgroundOur previous clinical research showed that the interaction between gut microbiota and bile acids (BAs) in patients with type 2 diabetes mellitus (T2DM) changed significantly. We hypothesized that T2DM could be improved by adjusting this interaction mediated by farnesoid X receptor (FXR). T2DM belongs to the category of “xiaoke” in traditional Chinese medicine. Radix scutellariae has the effects of clearing away heat and eliminating dampness, curing jaundice and quenching thirst and is widely used alone or in combination with other medicines for the treatment of T2DM in China and throughout Asia. Additionally, the interaction between Radix scutellariae and gut microbiota may influence its efficacy in the treatment of T2DM.PurposeThis study chose Radix scutellariae to validate that T2DM could improve by adjusting the interaction between gut microbiota and bile acid metabolism.Study design and methodsRadix scutellariae water extract (WESB) was administered to a T2DM rat model established by a high-fat diet combined with streptozotocin. The body weight and blood glucose and insulin levels were measured. The levels of serum lipids, creatinine, uric acid, albumin and total bile acid were also detected. Changes in the pathology and histology of the pancreas, liver and kidney were observed by haematoxylin-eosin staining. The 16S rRNAs of gut microbiota were sequenced, and the faecal and serum BAs were determined by liquid chromatography tandem mass spectrometry. The expression levels of BA metabolism-associated proteins in the liver and intestine were evaluated by immunoblot analysis.ResultsThe results showed that WESB improved hyperglycaemia, hyperlipaemia, and liver and kidney damage in T2DM rats. In addition, the abundances of key gut microbiota and the concentrations of certain secondary BAs in faeces and serum were restored. Moreover, there was a significant correlation between the restored gut microbiota and BAs, which might be related to the activation of liver cholesterol 7α-hydroxylase (CYP7A1) and the inhibition of FXR expression in the intestine rather than the liver.ConclusionsThis study provided new ideas for the prevention or treatment of clinical diabetes and its complications by adjusting the interaction between gut microbiota and bile acid metabolism.     

Serum adipocyte fatty acid binding protein levels in patients with type 2 diabetes mellitus and obesity: the influence of fenofibrate treatment

Recent studies have demonstrated that adipocyte fatty acid binding proteins (FABP) may play a role in the etiopathogenesis of insulin resistance. The aim of our study was to assess serum FABP levels in obese patients with type 2 diabetes mellitus (T2DM) before and after 3 months of treatment with PPAR-alpha agonist fenofibrate (F) and to explore the relationship of FABP to biochemical parameters and measures of insulin sensitivity assessed by hyperinsulinemic-isoglycemic clamp. We measured biochemical parameters by standard laboratory methods, insulin sensitivity by hyperinsulinemic-isoglycemic clamp and serum concentrations of FABP by commercial ELISA kit in 11 obese females with T2DM before and after three months of treatment with PPAR-alpha agonist fenofibrate and in 10 lean healthy control women (C). Serum FABP levels were 2.5-fold higher in T2DM group relative to C and were not affected by fenofibrate treatment (C: 20.6+/-2.1 microg/l, T2DM before F: 55.6+/-5.7 microg/l, T2DM after F: 54.2+/-5.4 microg/l, p 0.0001 for C vs. T2DM before F). Hyperinsulinemia during the clamp significantly suppressed FABP levels in both C and T2DM group. FABP levels positively correlated with BMI, triglyceride levels, blood glucose, glycated hemoglobin, atherogenic index and insulin levels. An inverse relationship was found between FABP and HDL levels, metabolic clearance rate of glucose, M/I and MCR(glc)/I sensitivity indexes. We conclude that FABP levels are closely related to BMI, parameters of insulin sensitivity, HDL levels and measures of diabetes compensation. This combination makes FABP a valuable marker of metabolic disturbances in patients with type 2 diabetes mellitus.     

The mitochondrial T16189C polymorphism is associated with coronary artery disease in Middle European populations

Background

The pivotal role of mitochondria in energy production and free radical generation suggests that the mitochondrial genome could have an important influence on the expression of multifactorial age related diseases. Substitution of T to C at nucleotide position 16189 in the hypervariable D-loop of the control region (CR) of mitochondrial DNA (mtDNA) has attracted research interest because of its suspected association with various multifactorial diseases. The aim of the present study was to compare the frequency of this polymorphism in the CR of mtDNA in patients with coronary artery disease (CAD, n = 482) and type 2 diabetes mellitus (T2DM, n = 505) from two study centers, with healthy individuals (n = 1481) of Middle European descent in Austria.

Methodology and Principal Findings

CR polymorphisms and the nine major European haplogroups were identified by DNA sequencing and primer extension analysis, respectively. Frequencies and Odds Ratios for the association between cases and controls were calculated. Compared to healthy controls, the prevalence of T16189C was significantly higher in patients with CAD (11.8% vs 21.6%), as well as in patients with T2DM (11.8% vs 19.4%). The association of CAD, but not the one of T2DM, with T16189C remained highly significant after correction for age, sex and body mass index (BMI) and was independent of the two study centers.

Conclusions and Significance

Our results show for the first time a significant association of T16189C with CAD in a Middle European population. As reported in other studies, in patients with T2DM an association with T16189C in individuals of European decent remains questionable.     

Thyroid function and metabolic syndrome in the population-based LifeLines cohort study

Background

The metabolic syndrome (MetS) is a combination of unfavourable health factors which includes abdominal obesity, dyslipidaemia, elevated blood pressure and impaired fasting glucose. Earlier studies have reported a relationship between thyroid function and some MetS components or suggested that serum free thyroxine (FT4) or free triiodothyronine (FT3) levels within the normal range were independently associated with insulin resistance. We assessed how thyroid function relates to MetS prevalence in a large population-based study.

Methods

Data of 26,719 people of western European descent, aged 18–80 years from the Dutch LifeLines Cohort study, all with normal thyroid stimulating hormone (TSH), FT4 and FT3 levels (electrochemiluminescent immunoassay, Roche Modular E170 Analyzer), were available. MetS was defined with the revised National Cholesterol Education Programs Adults Treatment Panel III (NCEP ATP III) criteria. We calculated prevalence of all MetS components according to TSH, FT4 and FT3 quartiles.

Results

At similar TSH levels and age (mean 45 yrs), men had significantly higher levels of FT4, FT3, blood pressure (BP), heart rate, total and LDL-cholesterol, triglycerides (TG), and creatinine, but lower HDL-cholesterol compared to women (all p < 0.001). In total, 11.8% of women and 20.7% of men had MetS. In men, lower FT4 levels were associated with higher prevalence of MetS and all MetS components. In women, lower FT4 quartile was only associated with a higher prevalence of elevated TG, waist circumference, and MetS. However, when corrected for confounding factors like age, BMI, current smoking and alcohol consumption, a significant relationship was found between FT3 and three MetS components in men, and all five components in women. Moreover, the highest quartiles of FT3 and the FT3FT4 ratio predicted a 49% and 67% higher prevalence of MetS in men, and a 62 and 80% higher prevalence in women.

Conclusions

When corrected for possible confounding factors, higher plasma levels of FT3 are associated with several components of the MetS. Only in men, lower FT4 is related to MetS. In the highest FT3 and FT3FT4 quartiles, there is a 50–80% increased risk of having MetS compared to the lowest quartile. Further studies are needed to assess the possible causality of this relationship.

     

老年2型糖尿病患者血清促甲状腺激素水平及其与冠脉病变程度的相关性分析

目的:探讨老年2型糖尿病(T2DM)患者血清促甲状腺激素(TSH)水平及其与患者冠脉病变程度的相关性。方法:回顾性分析2015年6月～2017年6月我院收治的88例老年T2DM患者(T2DM组)、50例健康体检者(对照组)的临床资料,根据血清TSH水平将T2DM组分为四个亚组,A组(0.45～1.49 m IU/L,n=18)、B组(1.50～2.49 m IU/L,n=23)、C组(2.50～3.49 m IU/L,n=22)、D组(≥4.5 m IU/L,n=25)。比较T2DM组与对照组TSH水平的差异,并根据计算机断层血管造影(CTA)结果计算Gensini评分,分析Gensini评分与血清TSH水平的相关性。结果:T2DM组血清TSH水平显著高于对照组,且随着血清TSH水平的升高,T2DM患者的年龄、TC、TG、LDL-C明显增加,而HDL-C、T3明显降低(P0.05)。C组病变支数显著多于A组,重度病变的比例明显升高,而D组病变支数、病变程度与A组、B组、C组比较差异均有统计学意义(P0.05)。血清TSH水平与Gensini评分呈显著正相关(r=0.577,P0.05)。结论:老年T2DM患者血清TSH水平显著升高,且与患者冠脉病变严重程度呈显著正相关,血清TSH水平有助于评估老年T2DM患者冠脉病变的严重程度。