ObjectiveAlterations in plasma adipokines and/or inflammatory parameters in Type 2 DM remain vague as to whether they are due to obesity and/or directly associated with the diabetic state. Our objective was to compare plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and hs-CRP in obese non-diabetic subjects and non-obese Type 2 DM patients, as well as determining the association of these adipokines with MetS and diabetes-related quantitative traits.MethodsIn this study, 92 Yemeni male volunteers aged 25–60 years old were enrolled, 31 of whom were healthy subjects with BMI < 25 kg/m2 served as control; 30 non-diabetic obese subjects BMI ≥ 30 kg/m2 and FBG < 6.1 mmol/l; and 31 non-obese Type 2 DM with FBG > 7 mmol/l and BMI < 25 kg/m2.ResultsAdiponectin was lower in obese subjects, with no differences between non-obese Type 2 DM patients and controls. In contrast, leptin, LAR and hs-CRP were higher in both obese subjects and non-obese Type 2 DM patients. Linear regression analysis showed adiponectin to be associated negatively with BMI, waist circumference, insulin, HOMA-β and HOMA-IR; whereas leptin, LAR and hs-CRP were associated positively with BMI, waist circumference, TG, FBG, insulin, HOMA-β and HOMA-IR. Moreover, adiponectin negatively correlated with leptin, LAR and hs-CRP; whereas leptin and LAR positively correlated with hs-CRP and with each other.ConclusionPlasma adiponectin is not affected by diabetes per se, suggesting that its alterations in Type 2 DM may be due to obesity and may be an important link between adiposity, IR and Type 2 DM.

BackgroundIncreased plasma plasminogen activator inhibitor-1 (PAI-1) activity and decreased tissue plasminogen activator (tPA) activity could be considered a true component of the metabolic syndrome (MetS) associated with an increased risk of developing cardiovascular diseases (CVD) and fibrinolytic abnormalities. The aim of this study was to investigate the association of tPA and its inhibitor PAI-1 with type 2 diabetes (T2D) and MetS and interrelationship between PAI-1and tPA activities and antigens in Malaysian T2D and normal subjects.MethodsThe plasma activities and antigens of PAI-1 and tPA and the levels of the tPA/PAI-1 complex as well as serum insulin, parameter of the coronary risk panel and plasma glucose at fasting state were studied in 303 T2D subjects (227 with MetS and 76 without MetS), 131 normal non-diabetic non-metabolic subjects and 101 non-diabetic MetS subjects.ResultsThe PAI-1 activity was higher in subjects with T2D with MetS (P = 9.8 × 10-19) and non-diabetic subjects with MetS (P = 3.0 × 10-15), whereas the tPA activity was lower in T2D with MetS (P = 0.003) as compare to normal subjects. Plasma tPA antigen levels were higher in subjects with T2D with MetS (P = 8.9 × 10-24), T2D without MetS (P = 1.3 × 10-13) and non-diabetic MetS subjects (P = 0.002). The activity and antigen of PAI-1 in normal subjects were related to insulin resistance (P = 2.2 × 10-4; 0.007). Additionally, the PAI-1 activity was associated with an increased waist circumference (P = 2.2 × 10-4) and decreased HDL-c (P = 0.005), whereas the tPA activity was associated with decreased FBG (P = 0.028). The highest correlation was between PAI-1 activity and its antigen (R2 = 0.695, P = 1.1 × 10-36) in diabetic subjects. The tPA activity negatively correlated with its antigen (R2 = -0.444, P = 7.7 × 10-13) in normal subjects and with the PAI-1 activity and antigen (R2 = -0.319, P = 9.9 × 10-12; R2 = -0.228, P = 3.4 × 10-6) in diabetic subjects.ConclusionsPAI-1 and tPA activities and antigens were associated with diabetes and MetS parameters in Malaysian subjects.

BackgroundGenetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4) gene may play a role in the etiology of type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV).MethodTen DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. The odds ratios (ORs) and their 95% confidence interval (CIs) were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels.ResultsDominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006), dominant model (OR = 1.95, p = 0.008), and additive model (OR = 1.63, p = 0.001). This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019), dominant OR = 3.72, p = 0.003) and additive model (OR = 2.29, p = 0.0009). The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039), and (OR = 1.42, p = 0.020), respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042) in T2DM subjects.ConclusionsDPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian 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.

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