Myeloperoxidase Is Associated with Insulin Resistance and Inflammation in Overweight Subjects with First-Degree Relatives with Type 2 Diabetes Mellitus

BACKGROUND: Family history of type 2 diabetes mellitus (T2DM) is one of risk factors for that in future a subject can develop diabetes. Insulin resistance (IR) is important in the pathogenesis of T2DM. There is evidence that oxidative stress plays an important role in the etiology and/or progression of diabetes. Myeloperoxidase (MPO) participates in developing of inflammation. The objective was to investigate if MPO is associated with IR and inflammation in individuals with first-degree relatives of T2DM. METHODS: Cross-sectional study in 84 overweight individuals with family history of T2DM divided in two groups according to IR, group with IR (homeostasis model assessment [HOMA] > or =2.5; n=43) and control group (CG; HOMA <2.5; n=41). Complete clinical history and a venous blood sample were collected for measuring glucose and lipids profile, insulin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), MPO, glutathione reductase (GRd), glutathione peroxidase, and superoxide dismutase. RESULTS: MPO, TNF-alpha, and IL-6 were higher in patients with IR than in CG (MPO: 308.35 [190.85 to 445.42] vs. 177.35 [104.50 to 279.85], P=0.0001; TNF-alpha: 13.46 [10.58 to 18.88] vs. 9.39 [7.53 to 11.25], P=0.0001; IL-6: 32.93 [24.93 to 38.27] vs. 15.60 [12.93 to 26.27]; P=0.0001, respectively). MPO was associated with IR (rho de Spearman=0.362, P=0.001). In the analysis of lineal regression, MPO predicts IR (beta, 0.263; t, 2.520; P=0.014). In the univariate analysis, MPO had an odds ratio of 9.880 for risk of IR (95% confidence interval, 2.647 to 36.879). CONCLUSION: MPO had relation with IR and inflammation parameters in overweight subjects with first-degree relatives of T2DM. We need studies on a casual relationship and molecular mechanisms among the increased serum MPO levels, inflammation markers, and IR.

A Study of Metabolic Syndrome and its Components in Type 2 Diabetes Mellitus Subjects and their Asymptomatic First-degree Relatives.

Objectives: To study clinical profile of metabolic syndrome and its individual components in type 2 diabetes mellitus subjects and their asymptomatic first-degree relatives. To identify risk factors of glucose intolerance. Material and methods: Randomly selected type 2 diabetes mellitus (T2DM) subjects age >40 years (n = 20, 10 males, 10 females) and their asymptomatic first-degree relatives age >30 years (excluding pregnant women) (n = 80; 46 males; 34 females) subjected to regression analysis with reference to components of metabolic syndrome (waist circumference, serum triglyceride, serum high-density lipoprotein (HDL), fasting plasma glucose, hypertension) and other variables. Student t-test was used for comparison of results. Results: Among T2DM subjects: Ninety percent were hypertensive, 85% had low HDL, 30% males and 80% females had central obesity, 85% had metabolic syndrome. Among asymptomatic first-degree relatives of T2DM subjects: 48.7% had metabolic syndrome; hypertension, low HDL, central obesity, impaired glucose tolerance, T2DM were present in 52.5%, 68.7%, 48.7%, 26.2%, 35%, respectively. In subjects with abnormal glucose level (n = 49) 59.18% subjects and in subjects with normal glucose level (n = 31) 32.25% met the criteria for metabolic syndrome (p = 0.023). Impaired fasting glucose, increased hip circumference and low HDL independently determined two hours glycemia value in OGTT. (R2 = 0.7; p = 0.001). Conclusion: In T2DM and their asymptomatic first-degree relatives, hypertension and low HDL were commonest components of metabolic syndrome, females were more obese. Glucose intolerance was significantly associated with other components of metabolic syndrome. Impaired fasting glucose, increased hip circumference and low HDL levels were risk factors for glucose intolerance.