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

Abstract

BackgroundFamily 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.MethodsCross-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] ≥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-α (TNF-α), MPO, glutathione reductase (GRd), glutathione peroxidase, and superoxide dismutase.ResultsMPO, TNF-α, 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-α: 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 (β, 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).ConclusionMPO 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.

Levels of Nitric Oxide Metabolites and Myeloperoxidase in Subjects with Type 2 Diabetes Mellitus on Metformin Therapy *

“…Resultsofourstudyshowedasignificantlyhigherconcentration of MPO in plasma of T2DM group of patients compared to the control group, which is in an agreement with other studies [13]. However, the results of Gorudko et al [14].…”

“…Therefore, the MPO-H 2 O 2 -Cl system can contribute to the initiation and propagation of atherosclerotic plaque formation in T2DM [12]. However, some studies showed contradictory results regarding the relationship between MPO and T2DM in patients without developed CVD [13,14]. So far, the association between MPO levels and concentration of metabolites of NO in vivo and development of T2DM and diabetic complications were not investigated simultaneously.…”

A CONSORT-Compliant, Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Purified Anthocyanin in Patients With Nonalcoholic Fatty Liver Disease

“… 37 A recent study demonstrated that plasma MPO was positively associated with insulin resistance and inflammation parameters in overweight subjects. 38 In NASH patients, both hepatic MPO expression and plasma MPO levels were elevated compared with patients with similar BMI but without NASH. 39 Our results suggest that anthocyanin supplementation reduced plasma MPO and showed a trend toward improvement in NAFLD fibrosis score.…”

Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation

“…This has been suggested to be one of the earlier defects in atherogenic processes, and may thus increase risk of cardiovascular disease in these individuals 37 38. It is known that circulating immune cells (neutrophils and monocytes) in overnight fasted, overweight insulin-resistant individuals with a heredity of T2DM are in a pro-oxidative, proinflammatory state 20. This was evident by significant upregulation of plasma levels of TNFα, IL-6 as well as myeloperoxidase, an ROS-generating enzyme that is known to strongly correlate with increased risk for cardiovascular and inflammatory diseases 39 40…”

“…Major T2DM risk factors such as anthropometric measures, lifestyle risk factors and genetic risk score all together have been shown to explain only 13% of the risk of T2DM associated with family history 17. Accumulating evidence suggests an association of heredity of T2DM and enhanced levels of systemic inflammatory and oxidative stress in the fasted state,18–20 which is aggravated after an acute high-fat meal challenge 21 22. Cumulative perturbations in the regulation of oxidative stress and inflammatory responses to meal ingestion may contribute to the greater risk for T2DM and its cardiovascular complications among FDRT individuals 23 24…”