Anize Delfino von Frankenberg

Effects of Dietary Fat and Saturated Fat Content on Liver Fat and Markers of Oxidative Stress in Overweight/Obese Men and Women under Weight-Stable Conditions

Dietary fat and oxidative stress are hypothesized to contribute to non-alcoholic fatty liver disease and progression to steatohepatitis. To determine the effects of dietary fat content on hepatic triglyceride, body fat distribution and markers of inflammation and oxidative stress, overweight/obese subjects with normal glucose tolerance consumed a control diet (CONT: 35% fat/12% saturated fat/47% carbohydrate) for ten days, followed by four weeks on a low fat (LFD (n = 10): 20% fat/8% saturated fat/62% carbohydrate) or high fat diet (HFD (n = 10): 55% fat/25% saturated fat/27% carbohydrate). Hepatic triglyceride content was quantified by MRS and abdominal fat distribution by MRI. Fasting biomarkers of inflammation (plasma hsCRP, IL-6, IL-12, TNFα, IFN-γ) and oxidative stress (urinary F2-α isoprostanes) were measured. Body weight remained stable. Compared to the CONT, hepatic triglyceride decreased on the LFD (mean (95% CI): change −2.13% (−3.74%, −0.52%)), but did not change on the HFD and there was no significant difference between the LFD and HFD. Intra-abdominal fat did not change significantly on either diet, but subcutaneous abdominal fat increased on the HFD. There were no significant changes in fasting metabolic markers, inflammatory markers and urinary F2-α isoprostanes. We conclude that in otherwise healthy overweight/obese adults under weight-neutral conditions, a diet low in fat and saturated fat has modest effects to decrease liver fat and may be beneficial. On the other hand, a diet very high in fat and saturated fat had no effect on hepatic triglyceride or markers of metabolism, inflammation and oxidative stress.

Major components of metabolic syndrome and adiponectin levels: a cross-sectional study

BackgroundAdiponectin is a major regulator of glucose and lipid homeostasis by its insulin sensitizer properties. Since decreased insulin sensitivity is linked to metabolic syndrome (MS), decreased adiponectin levels may be related to its development. The purpose of the study was to investigate the relationship between adiponectin levels and MS.MethodsFirstly, we cross-sectionally examined subjects with or without MS submitted to an oral glucose tolerance test at Hospital de Clínicas de Porto Alegre (n = 172). A replication analysis was performed in subjects (n = 422) undergoing cardiac angiography at Hospital São Paulo. Subchronic inflammation (US-CRP), coagulation marker (fibrinogen), insulin sensitivity and resistance (Matsuda ISI and HOMA-IR) were estimated. Plasma total and high molecular weight (HMW) adiponectin were measured.ResultsTotal and HMW adiponectin levels were lower in MS subjects (P < 0.05). Total adiponectin levels were lower in the presence of high waist circumference, low HDL-cholesterol and elevated triglyceride criteria in both samples and by elevated blood pressure and glucose criteria in Porto Alegre. HMW adiponectin levels were lower in the presence of low HDL-cholesterol, elevated triglycerides, and glucose criteria. Total adiponectin levels were positively related with HDL-cholesterol and ISI Matsuda, negatively related with waist circumference, glucose, triglycerides, HOMA-IR, and US-CRP and not related with blood pressure. While adjusting for sex and age, increased adiponectin levels remained associated with a reduced prevalence ratio for MS in both cohorts (P = 0.001).ConclusionsAdiponectin levels decreased with increasing number of MS criteria, and it is in part determined by its relationship with HDL, triglycerides and abdominal adiposity.

The Antioxidant N-Acetylcysteine Does Not Improve Glucose Tolerance or β-Cell Function in Type 2 Diabetes

UNLABELLED Hyperglycemia induces oxidative stress and thereby may exacerbate β-cell dysfunction in type 2 diabetes (T2DM). Notably, glutathione (GSH), synthesized from N-Acetylcysteine (NAC), neutralizes reactive oxygen species within cells and is low in individuals with diabetes. AIM Determine if NAC supplementation improves β-cell function and glucose tolerance by decreasing oxidative stress in T2DM. METHODS Thirteen subjects (6M/7F) with T2DM (duration: 0-13 years, median: 2 years), treated with diet/exercise alone (n=7) or metformin (n=6), underwent a 2-h oral glucose tolerance test (OGTT) at baseline, after 2 weeks supplementation with 600 mg NAC orally twice daily, and again after 2 weeks supplementation with 1200 mg NAC twice daily. The following measurements were made: fasting glucose and fructosamine for glycemic control, incremental AUC glucose (0-120 min) for glucose tolerance, and Δ insulin/Δ glucose (0-30 min) for the early insulin response to glucose. Fasting erythrocyte GSH and GSSG (oxidized glutathione) levels, plasma thiobarbituric acid reactive substances (TBARS), and urine F2α isoprostanes were measured to assess oxidative status. RESULTS Subjects were middle aged (mean ± SEM: 53.9 ± 3.2 years), obese (BMI 37.3 ± 2.8 kg/m(2)), and relatively well-controlled (HbA1c 6.7 ± 0.3%, 50 mmol/mol). Glycemic control, glucose tolerance, insulin release, and oxidative markers did not change with either dose of NAC. CONCLUSIONS Based on the lack of any short-term benefit from NAC supplementation on markers of glucose metabolism, β-cell response, and oxidative status, it is unlikely to be a valuable therapeutic approach for treatment of type 2 diabetes.

Association of HSD11B1 polymorphic variants and adipose tissue gene expression with metabolic syndrome, obesity and type 2 diabetes mellitus: a systematic review

The HSD11B1 gene is highly expressed in abdominal adipose tissue, and the enzyme it encodes catalyzes the interconversion of inactive cortisone to hormonally active cortisol. Genetic abnormalities of HSD11B1 have been associated with the development of abnormal glucose metabolism and body fat distribution. To systematically review studies evaluating the association of HSD11B1 gene expression in abdominal adipose tissue and HSD11B1 polymorphisms with obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2DM), we conducted a search in MEDLINE, SCOPUS, and Cochrane Library databases in April 2015. The inclusion criteria were observational studies (cross-sectional, cohort, or case–control), conducted in adults, which analyzed the relationship of HSD11B1 polymorphisms and/or HSD11B1 expression in abdominal adipose tissue with obesity, MetS, or T2DM. Of 802 studies retrieved, 32 met the inclusion criteria (23 gene expression and 9 polymorphism studies). Twenty one studies analyzed the relationship between abdominal subcutaneous and/or visceral HSD11B1 expression with central and/or generalized obesity. Most studies reported that abdominal adipose HSD11B1 expression increased with increasing body mass index (15 studies) and abnormalities of glucose metabolism (7 studies), and varied with the presence of MetS (3 studies). Nine studies analyzed the association of 26 different HSD11B1 polymorphic variants with obesity, MetS, and T2DM. Only an Indian study found an association between a polymorphic variant at the HSD11B1 gene with MetS whereas in Pima Indians another polymorphic variant was found to be associated with T2DM. While the literature suggests that HSD11B1 is hyperexpressed in abdominal adipose tissue in subjects with obesity and abnormal glucose metabolism, this seems to be not true for HSD11B1 gene expression and MetS. Although an association of polymorphic variants of HSD11B1 with MetS in Indians and in the T2DM population of Pima Indians were found, most studies did not find a relationship between genetic polymorphic variants of HSD11B1 and obesity, MetS, and T2DM. Their reported conflicting and inconclusive results, suggesting that polymorphic variants of HSD11B1 may have only a small role in the development of metabolic abnormalities of susceptible populations in the development of MetS and T2DM.

Underfeeding versus full enteral feeding in critically ill patients with acute respiratory failure: a systematic review with meta-analysis of randomized controlled trials

INTRODUCTION Although guidelines emphasize that the provision of enteral nutrition (EN) should be as close as the patients needs, prospective studies question this strategy. OBJECTIVE To compare the effect of two EN strategies (underfeeding versus full-feeding) on ICU and overall mortality (hospital mortality or 60-day mortality) and length of stay (LOS), duration of mechanical ventilation (MV), infectious complications, and gastrointestional tolerability in ICU patients. METHODS Random effects meta-analysis of randomized controlled trials (RCT). Our search covered MEDLINE, EMBASE, SCOPUS and CENTRAL databases until May 2015. Underfeeding was assigned into to two different groups according to the level of energy intake achieved (moderate feeding 46-72% and trophic feeding 16-25%) for subgroup analysis. RESULTS Five RCTs were included among the 904 studies retrieved (n=2432 patients). No difference was found in overall mortality when all five studies were combined. In the subgroup analysis, moderate feeding (three studies) showed lower mortality compared with full-feeding (RR 0.82;95%CI,0.68-0.98;I2 0% p=0.59 for heterogeneity). No differences were found for ICU mortality, ICU and hospital LOS, duration of MV, and infectious complications. Underfeeding showed lower occurrence of GI signs and symptoms except for aspiration and abdominal distention. CONCLUSIONS This meta-analysis found no differences in ICU and overall mortality, ICU and hospital LOS, duration of MV, and infectious complications between underfeeding and full-feeding. The subgroup analysis showed lower overall mortality among patients receiving moderate underfeeding. This result should be cautiously interpreted due to the limitations of the small number of studies analyzed and their methodology.

Relationships between adiponectin levels, the metabolic syndrome, and type 2 diabetes: a literature review

Elevated hepatic glucose production, impaired insulin secretion, and insulin resistance - abnormalities of glucose metabolism typically found in subjects with obesity - are major factors underlying the pathogenesis of type 2 diabetes (DM2) and the metabolic syndrome (MS). Adiponectin is a major regulator of glucose and lipid homeostasis via its insulin-sensitizing properties, and lower levels seems to be associated with the development of DM2 and MS. The purpose of this review is to clarify the mechanisms whereby adiponectin relates to the development of DM2 and MS and the association between polymorphisms of the adiponectin gene, circulating levels of the hormone, and its relationships with DM2. In addition, the impact of dietary lipids in the circulating levels of adiponectin will be addressed. According to the literature, circulating adiponectin levels seem to decrease as the number of MS components increases. Lower adiponectin concentrations are associated with higher intra-abdominal fat content. Therefore, adiponectin could link intra-abdominal fat with insulin resistance and development of MS. Therapeutic strategies that target the MS and its components, such as lifestyle modification through physical activity and weight loss, have been shown to increase adiponectin concentrations. Possible roles of diets containing either low or high amounts of fat, or different types of fat, have been analyzed in several studies, with heterogeneous results. Supplementation with n-3 PUFA modestly increases adiponectin levels, whereas conjugated linoleic acid supplementation appears to reduce concentrations when compared with unsaturated fatty acid supplementation used as an active placebo.

24-hour blood pressure homeostasis and renal function in subjects with and without metabolic syndrome

Materials and methods We designed a cross-sectional study of consecutive individuals (n=108; females 74%; 52.8±12.7 yrs.; mean±SD) from the Diabetes Clinic of a university hospital. MS was defined by the International Diabetes Federation criteria. BP was measured at office and its circadian variation was determined by 24-h ambulatory BP monitoring, after withdrawal from anti-hypertensive medications. Patients were classified according to their BP behavior: normotension (NT; n=29), white-coat hypertension (WCH; n=19) and ambulatory hypertension (AHT; n=57). Fasting and 2h-plasma glucose levels, lipid profile, creatinine and 24-h urinary albumin excretion (UAER) were measured. Glomerular filtration rate (GFR) was estimated by the CKD-EPI equation. A two-sided P value <0.05 was considered significant. Results Estimated GFR (EGFR) was lower in subjects with MS than in those without MS (Mean±SD; 90±20 vs 98.8±16.5; P=0.047). EGFR was related to age (r=-0.666; P<0.001), fasting glucose (r=0.223; P=0.021), and 24-h systolic BP (r=-0.196; P=0.044), but not to diastolic BP. EGFR was inversely related to sleep-time BP (r=-0.224; P=0.021), morning systolic BP (r=-0.224; P=0.030) and pulse pressure (r=-0.233; P=0.170). Subjects with WCH and AHT compared to those with NT had lower EGFR (Mean±SD; 89.3±18 vs 89.6±26.3 vs 100.2±14.8; P=0.036) and higher UAER (Median [P25-75]; 1 [0-5.3] vs 6.1 [1-19] vs 6.3 [1-16.8]; P=0.031).

Accuracy of insulin resistance indices for metabolic syndrome in a population with different degrees of glucose tolerance

Background Insulin resistance has been associated with the development of metabolic syndrome (MS), which is an interrelated cluster of risk factors for cardiovascular disease and type 2 diabetes (T2D). Several equations derived from the oral glucose tolerance test (OGTT) have been developed as surrogates for the euglycemic hyperinsulinemic clamp technique to estimate insulin resistance and insulin sensitivity.

Waist-to-height ratio as a predictor of metabolic syndrome in a population with different degrees of glucose tolerance

Waist-to-height ratio as a predictor of metabolic syndrome in a population with different degrees of glucose tolerance Tassia Cividanes Pazinato, Barbara Limberger Nedel, Anize Delfino von Frankenberg, Vanessa Piccoli, Luciana Pavan Antoniolli, Mayara Abichequer Beer, Leticia Maria Tedesco Silva, Rodrigo Soares de Souza Marques, Leonardo de Andrade Mesquita, Monique de Moura Machado, Andre Fernandes Reis, Fernando Gerchman