No abstract

End-stage renal disease (ESRD) patients treated with maintenance haemodialysis (MHD) have alarmingly high atherosclerotic cardiovascular disease morbidity and mortality. Nitric oxide (NO) is the principal endogenous antiatherosclerotic molecule. Increased asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, was strongly implicated in endothelial dysfunction, premature atherosclerosis, vascular events, and mortality. Regular physical exercise effectively decreased serum ADMA in several patient cohorts, but this potential benefit has not been specifically explored among MHD patients. Forty-four middle-aged ESRD patients treated with thrice-weekly MHD for ≥6 months completed a 6-months regimen of peridialytic lower limb exercise comprising predialytic 10–12 stretching cycles and 20–30 minutes of intradialytic pedaling cycles. Before and after the study, predialytic haemoglobin, serum ADMA, urea, creatinine, calcium, phosphorus, and C-reactive protein (CRP) were measured. Dialysis adequacy was assessed by single-pool Kt/V. The average total physical activity (PA) level was assessed by the International Physical Activity Questionnaire (IPAQ). P values <0.05 denoted a statistical significance. The overall level of PA, on both categorical and continuous scales, has significantly increased after application of the exercise program. However, S. ADMA increased from a median of 2375 to 3000 ng/mL ( P = 0.016 ). Thirty-one patients sustained an increase in S. ADMA (ADMA_Inc), whereas 13 patients had a declining or stable S. ADMA (ADMA_Dec). Compared with ADMA_Inc, ADMA_Dec patients had significantly higher Kt/V ( P = 0.02 ), higher grade of the basal general PA level ( P = 0.017 ), and significantly fewer intradialytic hypotension episodes (IDHs) ( P = 0.019 ). The increase in the S. ADMA and the poststudy S. ADMA level had statistically significant positive correlations with the number of IDHs (r = 0.401, P = 0.007 and r = 0.305, P = 0.044 , respectively). A 6-month program of combined aerobic and resistance peridialytic exercise failed to reduce S. ADMA in most MHD patients studied. A modest S. ADMA decline, however, occurred in patients with higher basal PA levels, higher Kt/V, and less IDHs. A potential exercise benefit may be promoted by a multidisciplinary approach targeting increased PA, improved dialysis efficiency, and prevention of IDHs.

Background Insulin receptor substrate-1 (IRS1) plays a critical role in insulin signaling. IRS-1 gene polymorphism with glycine to arginine substitution (GGG ↔ AGG substitutions) in codon 972 (G972R) (rs1801278) is a common polymorphism of the IRS-1 gene, which may have a pathogenic role in the development of type 2 diabetes mellitus (type 2 DM) due to insulin resistance and impaired insulin secretion. In hepatitis C virus infection (HCV), the IRS proteins might be counter-regulated by degradation, differential expression, or modification by phosphorylation in cells expressing HCV core protein, which inhibits the interactions of IRS-1 with both the insulin receptor and the downstream effectors of IRS-1. The present retrospective case–control study aimed to evaluate IRS-1 G972R (rs 1801278) SNP in Egyptian patients with HCV and type 2 DM, two hundred and two subjects including 100 males and 102 females The present work is a retrospective case–control study aimed to detect IRS-1 G972R (rs 1801278) SNP in Egyptian patients with chronic HCV infection and DM. The subjects were divided into the control group (group I) which included 50 apparently healthy volunteers of comparable age, gender, and socioeconomic status to patients; group II included 50 type 2 diabetic patients without chronic hepatitis C infection; group III included 52 chronic HCV-infected patients without type 2 diabetes mellitus; and group IV included 50 chronic hepatitis C-infected patients with type 2 diabetes mellitus. IRS-1 G972R (rs 1801278) genotyping was done by using polymerase chain reaction (PCR-RFLP) technique with restriction enzymes BstNI. Results HOMA-IR and QUICKI index was significantly higher in the patient groups (groups II, III, and IV) than controls (P < 0.001, P = 0.019, and P < 0.001 respectively). There was a significant increase in minor allele (A) in groups II, III, and IV than controls (P = 0.007, P = 0.017, and P = 0.007 respectively). There was increased frequency of mutant allele (A) than wild allele (G) of IRS-1 G972R polymorphism in type 2 diabetic patients with BMI < 25 kg/m2. The DM patients without HCV infection (group II), HCV patients without DM (group III), and HCV patients with DM (group IV) showed a significant decrease in GG genotypes and a significant increase in AA genotypes than the controls (P = 0.017, P = 0.019, and P = 0.009 respectively). Body mass index and waist to hip ratio were significantly higher in DM patients without chronic hepatitis C infection (group II) and in HCV patients with type 2 diabetes (group IV) than controls, in hepatitis C patients with type 2 diabetes (group IV) than controls, and in group IV than group III (P < 0.001). Conclusion IRS-1 G972R (rs 1801278) polymorphism might be a contributing risk factor for the development of type 2 DM. The mutant allele (A) of IRS-1 suggests the role of this SNP as risk factors for type 2 diabetes mellitus even in subjects with normal body weight. The increase of body mass index may be an independent risk factor for the development of type 2 diabetes mellitus.