Renal insufficiency in non-diabetic subjects: relationship of MTHFR C677t gene polymorphism and left ventricular hypertrophy.

BACKGROUND: Association of methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism with hyperhomocysteinemia, renal failure, and cardiovascular events is controversial. We investigated the relationship of MTHFR 677C>T polymorphisms with left ventricular hypertrophy (LVH) and renal insufficiency. METHODS: Glomerular filtration rate (GFR) and left myocardial ventricular mass/m2 were assessed in 138 non-diabetic subjects (age, 50.93 ± 14.85 years; body mass index, 27.95 ± 5.98 kg/m(2)), 38 no-mutation wild MTHFR C677CC, 52 heterozygous MTHFR C677CT, and 48 homozygous MTHFR C677TT, all with adequate adherence to current international healthy dietary guidelines. Serum homocysteine, insulin resistance, high-sensitivity C-reactive-protein (hsCRP), parathyroid hormone, and renal artery resistive index (RRI) were challenged by odds ratio analysis and multiple linear regression models. RESULTS: MTHFR 677C>T polymorphism showed higher GFR (73.8 ± 27.99 vs. 58.64 ± 29.95; p= 0.001) and lower renal failure odds (OR, 0.443; 95% confidence interval, 0.141-1.387) in comparison with wild MTHFR genotype. A favorable effect on GFR of MTHFR polymorphism is presented independently by the negative effects of LVH, increased intra-renal arterial resistance, and hyperparathyroidism; GFR is the significant predictive factor to LVH. CONCLUSIONS: Renal insufficiency in non-diabetic subjects is explained by interactions of MTHFR C677T polymorphism mutation with LVH, hsCRP, intact parathyroid hormone (iPTH), and RRI. Sign of these predictive effects is opposite: subjects with MTHFR 677C>T polymorphism have lower likelihood of renal insufficiency; differently, wild-type MTHFR genotype subjects have lower GFR and greater hsCRP, iPTH, RRI, and LVH.

Ad36 adipogenic adenovirus in human non-alcoholic fatty liver disease.

AIMS: Infection with specific pathogens may lead to increased adiposity. The human adenovirus 36 (Ad36) is a relatively new factor in promoting adipogenesis. It seems to improve the metabolic profile, expanding adipose tissue and enhancing insulin sensitivity in animal models. The aim of this study was to investigate whether any association or predictor effect of Ad36 seropositivity is present in non-alcoholic fatty liver disease (NAFLD), a condition associated with obesity and insulin resistance (IR). METHODS: Sixty-five NAFLD patients and 114 controls were investigated. Ultrasound bright liver score (BLS), body composition, IR evaluated by homeostasis model assessment of insulin resistance index (HOMA or HOMA-IR) and serum neutralization assay for antibodies to Ad36 were assessed. RESULTS: Ad36-seropositive patients have a lower risk of bright liver [OR 0.505 (95% confidence interval (CI) 0.265-0.962)]; greater IR leads to a higher risk of bright liver [OR 9.673 (95% CI 4.443-21.058)]. Among NAFLD, Ad36-seropositive vs. Ad36-seronegative patients did not show a significant IR difference. Ad36-seropositive NAFLD patients, with the same levels of HOMA and BLS, had greater body mass index and body fat mass, in comparison with seronegative NAFLD patients. By a multiple linear regression model, BLS was explained by HOMA (beta 0.513; P<0.0001), high density lipoprotein cholesterol (beta-0.219, P<0.006) and Ad36 seropositivity (beta-0.202, P<0.005); Ad36 seropositivity did not explain HOMA in the other multiple logistic regression model. CONCLUSIONS: Ad36 seropositivity is not associated with a significant difference of IR in NAFLD patients, but is associated with a greater adiposity. Ad36 seropositivity is associated with a lower occurrence of NAFLD and bright liver, which, conceivably, is not directly mediated by IR.

Protective role of coffee in non-alcoholic fatty liver disease (NAFLD).

AIM: The benefits of coffee on abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma have been reported, but there is a lack of satisfactory explanation. Thus, this study aims to investigate if coffee use has any relationship with bright liver, measured by ultrasound bright liver score (BLS), in patients with non-alcoholic fatty liver disease (NAFLD), and which relationship, if any, is present with BMI and insulin resistance. METHODS: This study was performed on 245 patients, 137 with NAFLD and 108 controls. Coffee drinking was defined according to the absolute number of cups of coffee (only espresso coffee), and also graded as 1 (0 cups of coffee/day), 2 (1-2 cups of coffee/day) 3 (≥3 cups of coffee/day). Insulin resistance was assessed by homoeostasis model-insulin resistance index (HOMA). RESULTS: Less fatty liver involvement is present in coffee vs. non-coffee drinkers. Odds ratios show that obesity, higher insulin resistance, lower HDL cholesterol, older age and arterial hypertension are associated with a greater risk of more severe BLS; to the contrary, coffee drinking is associated with less severe BLS. In the multiple logistic regression (MLR) model, number of cups of coffee, HOMA and BMI account for 35.8% of the variance to BLS. Coffee use is inversely associated with the degree of bright liver, along with insulin resistance and obesity, which, to the contrary, are directly associated with greater likelihood and severity of bright liver appearance. CONCLUSIONS: A possible opposite, if not antagonistic, role of coffee with regard to overweightness and insulin resistance, similar to that reported in hepatocarcinoma and cirrhosis, is envisaged in the natural history of NAFLD.

Lifestyle interventions, insulin resistance, and renal artery stiffness in essential hypertension.

The study investigates lifestyle and effective anti-hypertensive intervention in overweight-obese patients can influence insulin-resistance (HOMA-IR) and US Renal-Resistive-Index (RRI). After a 1-year interventional program (including a personalized Mediterranean diet, physical activity increase, smoking withdrawal counseling), 156 Essential Hypertension (EH) patients still have abnormal HOMA-IR, significantly higher in comparison to 159 control group patients. Body mass index (BMI) and cholesterol-high-density-lipoprotein improvement are the best predictors of a HOMA-IR decrease; RRI improves in EH according to lifestyle interventions, but no predictor to RRI is identified. Persistence of IR can be tentatively assumed as a steady sign, persistent also after extended lifestyle intervention in EH, further warranting more intensive dietary interventions.

Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) because of its association with obesity, diabetes and insulin resistance (IR), is the hepatic expression of metabolic syndrome. Exercise and nutritional intervention can improve and prevent these inter-related conditions; the relationships between the degree of IR and ultrasound (US) morphological post-interventional changes are not defined. AIMS: The aim of our study was to assess the relationship, if any, in NAFLD patients, among IR, BMI and degree of bright liver, before and after 6 months of a moderately hypocaloric/balanced dietary/lifestyle treatment. Fifty outpatients with a clinical and US diagnosis of NAFLD were studied. METHODS: Liver echogenicity [Bright Liver Score (BLS)] was scored on a four-graded scale. IR was assessed by homoeostasis model-insulin resistance (HOMA-IR). Body composition was assessed by bioimpedance assessment and skinfold measurements. RESULTS: A significant decrease of BLS was observed, with a concurrent decrease of body weight, body mass index (BMI) and HOMA-IR. Bright liver decrease has a trend parallel to IR, much less steep than the trend of bright liver reduction against US liver dimensions, body weight and BMI decrease. HOMA-IR is the only baseline variable that enters significantly in the multiple regression and, alone, explains 21.4% of variance in predicting bright liver degree. After dietary interventions, both HOMA-IR and BMI are significantly involved in the multiple regression and explain, together, 42.3% of variance in predicting bright liver degree; variation in BLS can be predicted by variation of body weight and of US longitudinal measurement of the liver. CONCLUSIONS: Liver US BLS appears to be a useful tool, both alone and along with other US measurements and body weight changes, for the assessment of clinical-metabolic amelioration in patients treated with dietetic interventions. The clinical-diagnostic role, if any, of other assessed laboratory analyses, in the subset of NAFLD, does not appear to be definite.