Fernando Gerchman

Endothelin-1 levels and albuminuria in patients with type 2 diabetes mellitus☆

AIMnTo evaluate the relationship of plasma endothelin-1 (ET-1) levels, a marker of endothelial dysfunction, and urinary albumin excretion in patients with type 2 diabetes mellitus (DM).nnnMETHODSnCross-sectional study was conducted in 279 patients (132 males, mean age: 58.7+/-11.0 years, mean DM duration: 11.3+/-8.1 years). Urinary albumin excretion, ET-1, and insulin were measured. Insulin sensitivity was estimated by homeostasis model assessment (HOMA-ir) index.nnnRESULTSnET-1 was associated with urinary albumin excretion after controlling for age, gender, body mass index, blood pressure, HbA1c test, and total cholesterol (R=0.436; adjusted R(2)=0.190, P<0.01). Furthermore, there was a progressive increase in plasma ET-1 levels from patients with normoalbuminuria (n=187, 0.92+/-0.50pg/ml), microalbuminuria (n=68, 1.13+/-0.52pg/ml) to macroalbuminuria (n=24, 1.93+/-1.10pg/ml, P<0.01).nnnCONCLUSIONnThere is an independent association of plasma ET-1 levels with urinary albumin excretion. In addition, plasma ET-1 levels started to increase in the normal values of urinary albumin excretion suggesting that in patients with type 2 DM endothelial dysfunction is already present, in urinary albumin excretion values considered normal.

Medida da cintura e razão cintura/quadril e identificação de situações de risco cardiovascular: estudo multicêntrico em pacientes com diabetes melito tipo 2

Abdominal obesity is associated with cardiovascular disease. This study aims to compare two measures of abdominal obesity [waist and wais-to-hip ratio (WHR)] in patients with DM2 to identify cardiovascular risk factors: ischemic cardiopathy, hypertension, dislipidemia, obesity and diabetic nephropathy. A multicentric study was performed in 820 patients with type 2 DM. Waist circumference strongly correlated with body mass index (BMI), for men (r= 0.814; P< 0.05) and women (r= 0.770; P< 0.05). On the other hand, WRH was weakly correlated (r= 0.263, P< 0.05 for men; r= 0.092, P< 0.05 for women). Only waist circumference correlated with systolic pressure (r= 0.211, P< 0.05 for men; r= 0,224, P< 0.05 for women). ROC curve analysis demonstrated the superiority of waist circumference measurement compared to WHR regarding obesity and hypertension for men and women, and dyslipidemia for men. In conclusion, waist circumference is better correlated with cardiovascular risk factor than WRH.

Effect of dietary lipids on circulating adiponectin: a systematic review with meta-analysis of randomised controlled trials

Different dietary interventions have been identified as potential modifiers of adiponectin concentrations, and they may be influenced by lipid intake. We identified studies investigating the effect of dietary lipids (type/amount) on adiponectin concentrations in a systematic review with meta-analysis. A literature search was conducted until July 2013 using databases such as Medline, Embase and Scopus (MeSH terms: adiponectin, dietary lipid, randomized controlled trials (RCT)). Inclusion criteria were RCT in adults analysing adiponectin concentrations with modification of dietary lipids. Among the 4930 studies retrieved, fifty-three fulfilled the inclusion criteria and were grouped as follows: (1) total dietary lipid intake; (2) dietary/supplementary n-3 PUFA; (3) conjugated linoleic acid (CLA) supplementation; (4) other dietary lipid interventions. Diets with a low fat content in comparison to diets with a high-fat content were not associated with positive changes in adiponectin concentrations (twelve studies; pooled estimate of the difference in means: -0·04 (95% CI -0·82, 0·74) μg/ml). A modest increase in adiponectin concentrations with n-3 PUFA supplementation was observed (thirteen studies; 0·27 (95% CI 0·07, 0·47) μg/ml). Publication bias was found by using Eggers test (P= 0·01) and funnel plot asymmetry. In contrast, CLA supplementation reduced the circulating concentrations of adiponectin compared with unsaturated fat supplementation (seven studies; -0·74 (95% CI -1·38, -0·10) μg/ml). However, important sources of heterogeneity were found as revealed by the meta-regression analyses of both n-3 PUFA and CLA supplementation. Results of new RCT would be necessary to confirm these findings.

Association of ADIPOQ variants, total and high molecular weight adiponectin levels with coronary artery disease in diabetic and non-diabetic Brazilian subjects

OBJECTIVEnTo investigate the association of ADIPOQ variants, total and high molecular weight adiponectin (HMW) adiponectin levels with the prevalence of diabetes mellitus and coronary artery disease (CAD) diagnosed by coronary angiography in Brazilian subjects with high cardiovascular risk.nnnMETHODSn603 subjects undergoing coronary angiography were studied in regard to their glycemic status and presence of CAD (lesions >0%). We evaluated baseline concentrations of total and HMW adiponectin and three ADIPOQ variants: -11391G>A (rs17300539), +45T>G (rs2241766) and+276G>T (rs1501299).nnnRESULTSnThe G-allele of rs2241766 was associated with higher levels of total and HMW adiponectin, and the A-allele of rs17300539 was associated with higher levels of HMW adiponectin. Lower levels of total and HMW adiponectin were independently associated with CAD. The G-allele of rs2241766 (OR 2.45, 95% C.I. 1.05-6.04, p=0.04) and the G-allele of rs1501299 (OR 1.89, 95% C.I. 1.04-3.45, p=0.03) were associated with CAD, and these associations were independent of circulating levels of adiponectin.nnnCONCLUSIONSnIn Brazilian subjects with high cardiovascular risk, CAD was associated with lower total and HMW adiponectin levels. The rs2241766 and rs1501299 polymorphisms were associated with CAD. The rs2241766 variant was associated with total and HMW adiponectin levels, while rs17300539 was associated with HMW adiponectin levels.

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 (nu2009=u2009172). A replication analysis was performed in subjects (nu2009=u2009422) 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 (Pu2009<u20090.05). 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 (Pu2009=u20090.001).ConclusionsAdiponectin levels decreased with increasing number of MS criteria, and it is in part determined by its relationship with HDL, triglycerides and abdominal adiposity.

Pré-diabetes : diagnóstico, avaliação de complicações crônicas e tratamento

Type 2 diabetes mellitus accounts for 90% of diabetes cases and is associated with macro- and microvascular complications of high morbidity and mortality. Individuals with increased risk for type 2 diabetes include those with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and especially those with combined IFG and IGT. These individuals are part of a group known as prediabetes patients. Approximately 25% of individuals with prediabetes will develop type 2 diabetes in three to five years. Hyperglycemia, in the absence of diabetes, is also associated with increased risk of cardiovascular disease. Studies have shown that changes in lifestyle and drug interventions are effective in delaying or preventing type 2 diabetes in patients with prediabetes. Metformin is the drug of choice when medical treatment is warranted. IGT and IFG are associated with type 2 diabetes and, despite controversy, most studies reinforce the importance of these conditions in the development of micro- and macrovascular disease. Thus, therapeutic interventions in patients with prediabetes are important in primary prevention of type 2 diabetes and its chronic complications.

Avaliação e tratamento da hiperglicemia em pacientes graves

Hyperglycemia is a commonly encountered issue in critically ill patients in the intensive care setting. The presence of hyperglycemia is associated with increased morbidity and mortality, regardless of the reason for admission (e.g., acute myocardial infarction, status post-cardiovascular surgery, stroke, sepsis). However, the pathophysiology and, in particular, the treatment of hyperglycemia in the critically ill patient remain controversial. In clinical practice, several aspects must be taken into account in the management of these patients, including blood glucose targets, history of diabetes mellitus, the route of nutrition (enteral or parenteral), and available monitoring equipment, which substantially increases the workload of providers involved in the patients care. This review describes the epidemiology, pathophysiology, management, and monitoring of hyperglycemia in the critically ill adult patient.

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.

Evaluation of the DDAVP test in the diagnosis of Cushing's Disease

To analyse the performance of the desmopressin (DDAVP) test in the diagnosis of Cushings disease (CD).

The role of K121Q ENPP1 polymorphism in diabetes mellitus and its complications

The aim of the present study was to analyze the frequency of K121Q polymorphism in the ENPP1 gene of Brazilian subjects according to ethnic origin and to determine its possible association with diabetes mellitus (DM) and/or diabetic complications. A cross-sectional study was conducted on 1027 type 2 DM patients and 240 anonymous blood donors (BD). Ethnicity was classified based on self-report of European and African descent. The Q allele frequency was increased in African descendant type 2 DM patients (KK = 25.9%, KQ = 48.2%, and QQ = 25.9%) and BD (KK = 22.0%, KQ = 53.8%, and QQ = 24.2%) compared to European descendant type 2 DM patients (KK = 62.7%, KQ = 33.3%, and QQ = 4.1%) and BD (KK = 61.0%, KQ = 35.6%, and QQ = 3.4%). However, there was no difference in genotype distribution or Q allele frequency between diabetic and non-diabetic subjects (European descendants: DM = 0.21 vs BD = 0.21, P = 0.966, and African descendants: DM = 0.50 vs BD = 0.51, P = 0.899). In addition, there were no differences in clinical, laboratory or insulin resistance indices among the three genotypes. The prevalence of DM complications was also similar. In conclusion, K121Q polymorphism is more common among Afro-Brazilian descendants regardless of glycemic status or insulin sensitivity indices. Likewise, insulin sensitivity and DM chronic complications appear not to be related to the polymorphism in this sample.