Non-alcoholic fatty liver disease (NAFLD) and MTHFR 1298A > C gene polymorphism.

INTRODUCTION: Non-Alcoholic Fatty Liver Disease (NAFLD) is related to unhealthy habits, mainly to unfavorable dietary profiles. MTHFR gene encodes MethyleneTetraHydroFolate Reductase, a regulatory enzyme whose polymorphisms are associated with hyperhomocysteinemia. Among polymorphisms, C677T, a thermolabile form, but not A1298C, thermostable, was associated with fatty liver and insulin resistance. AIM: to investigate if NAFLD, in subjects referred for nutritional assessment and counselling, has any difference of prevalence and severity when associated with isolated MTHFR A1298C polymorphism and hyperhomocysteinemia. PATIENTS AND METHODS: 94 subjects, age 55.65 ± 15.43 years, BMI 27.88 ± 5.17 kg/m2, 26 with MTHFR Wild type genotype (1298AA) and 68 with MTHFRA1298C single polymorphism were studied: of them, 35 were homozygous (MTHFR1298CC), 33 were heterozygous (MHTFR 1298AC). Insulin resistance was assessed by HOMA-IR, NAFLD by UltraSound Brigh-Liver-Score (BLS). RESULTS: MTHFR subgroups (wild and A1298C single polymorphism) were not different for age, gender, dietary profile and BMI. In NAFLD, MTHFR 1298AC (heterozygous) vs. homozygous wild genotype (MTHFR 1298AA) patients had more severe NAFLD (BLS: 1.12 ± 1.14 vs. 0.54 ± 0.76, p < 0.029), greater insulin resistance (HOMA 3.20±2.35 vs. 2.12 ± 1.12; p < 0.036), higher AST and gammaGT. CONCLUSIONS: MTHFR1298AC gene heterozygous polymorphisms can be weakly predictive for NAFLD severity. This mutation occurs frequently in populations with low prevalence of overall mortality and of atherosclerosis-associated disease: it could have maintained and maintain its persistence by an heterozygosis advantage mechanism, within significant adherence to healthy nutritional profiles. Interactions of nutrition, genetics and health are a part of the aging process throughout the life span and a greater consideration to the genetic characteristics of populations and individuals is warranted.

Human obesity relationship with Ad36 adenovirus and insulin resistance.

OBJECTIVES: Infection with specific pathogens may lead to increased adiposity: a specific adiposity-promoting effect of Ad36 human adenovirus, without the involvement of neurological mechanisms, was reported. The aim of this study is to investigate whether non-diabetic patients with earlier Ad36 infection show greater degrees of overweight obesity, of Insulin Resistance (IR), assessed by homoeostasis-model assessment (HOMA), and/or of other related factors. Moreover, the relationship, if any, among these factors and an earlier Ad36 infection, and the hypothesis of a mechanism involving IR are investigated. SUBJECTS: Ad36 seropositivity is assessed in 68 obese and 135 non-obese subjects, along with body composition, HOMA and laboratory investigations. RESULTS: Age, body mass index (BMI), waist-hip ratio, blood pressure, insulin, HOMA and triglycerides are significantly greater in the Ad36 seropositive group. Ad36 seropositivity, along with HOMA and total cholesterol, explains BMI variance. No Ad36 seropositivity effect to HOMA could be envisaged by the same statistical model. CONCLUSION: A significant association of Ad36 seropositivity with obesity and with essential hypertension in human beings is suggested by our study; this association is mostly significant in women. Our results do not support that any Ad36 adipogenic adenovirus effect is operating in human obesity through an insulin-resistance-related mechanism. Ad36 seropositive status could also be a hallmark of a clinical-metabolic profile possibly preceding obesity and diabetes in non-obese patients.

Insulin resistance in postmenopausal women: concurrent effects of hormone replacement therapy and coffee.

BACKGROUND: In postmenopausal women, an increase in insulin resistance is associated with an increased risk of diabetes, cardiovascular disease and breast cancer. Hormone replacement therapy (HRT) can reduce insulin resistance and coffee use is reported to decrease the incidence of diabetes. The aim of our study was to assess possible concurrent effects of HRT and espresso coffee intake on insulin resistance and on interdependent nutritional and clinical features. METHODS: A total of 478 healthy postmenopausal, non-diabetic women (aged 54.5 +/- 4.2 years) were studied: 360 had been on HRT for at least 2 years and 118 were not treated. Insulin resistance was assessed by a conventional homeostasis model (HOMA-IR). RESULTS: Insulin resistance is directly related to body mass index (p < 0.0001), and not with age and blood pressure; hypertensive menopausal women have a slightly higher body mass index but the same degree of insulin resistance as normotensive women. Women on HRT show lower insulin resistance, but not lower prevalence of arterial hypertension. Coffee use is associated with a decrease in insulin resistance in non-obese women receiving HRT, but not in other subsets. CONCLUSIONS: The combination of coffee consumption and HRT could lower insulin resistance in postmenopausal women. In overweight women, greater insulin sensitivity is associated with intake of espresso coffee and not with HRT; in normal weight women, only HRT is associated with lower insulin resistance.