André Fernandes Reis

Visfatin, glucose metabolism and vascular disease: a review of evidence

The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further evidence about this adipocytokine. Its findings may contribute in the identification of higher risk individuals for diabetes and cardiovascular disease with a better comprehension about the complex intercorrelation between adiposity, glucose metabolism and vascular disease.

Alterações metabólicas da síndrome lipodistrófica do HIV

A introducao da highly active antiretroviral therapy (HAART) - terapia anti-retroviral fortemente ativa - vem reduzindo a morbidade e a mortalidade em pacientes infectados com o virus da imunodeficiencia humana (HIV). Entretanto, tratamentos prolongados, com combinacoes de drogas, sao de dificil manutencao devido a ma aderencia e aos efeitos toxicos. O tratamento com agentes anti-retrovirais, especialmente os inibidores da protease, fez surgir uma sindrome caracterizada por redistribuicao anormal da gordura corporal, alteracoes no metabolismo glicemico, resistencia insulinica e dislipidemia, chamada de sindrome lipodistrofica do HIV (SLHIV). Atualmente nao existe nenhum consenso para prevencao ou tratamento da sindrome, cuja causa permanece desconhecida. Esta revisao enfatiza os achados clinicos e dados da literatura a respeito da SLHIV, pois um melhor entendimento desta sindrome por infectologistas, cardiologistas e endocrinologistas e essencial para o manejo da doenca.The introduction of highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with the human immunodeficiency virus (HIV). However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. Treatment with antiretroviral agents--protease inhibitors in particular--has uncovered a syndrome of abnormal fat redistribution, impaired glucose metabolism, insulin resistance and dyslipidemia, collectively termed lipodystrophy syndrome (SLHIV). Nowadays, no clinical guidelines are available for the prevention or treatment of SLHIV, and its cause have yet to be totally elucidated. This review emphasizes the clinical features and the data from previous studies about the SLHIV taking into account that a better understanding of this syndrome for HIV specialists, cardiologists and endocrinologists is fundamental for the disease control.The introduction of highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with the human immunodeficiency virus (HIV). However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. Treatment with antiretroviral agents - protease inhibitors in particular - has uncovered a syndrome of abnormal fat redistribution, impaired glucose metabolism, insulin resistance and dyslipidemia, collectively termed lipodystrophy syndrome (SLHIV). Nowadays, no clinical guidelines are available for the prevention or treatment of SLHIV, and its cause have yet to be totally elucidated. This review emphasizes the clinical features and the data from previous studies about the SLHIV taking into account that a better understanding of this syndrome for HIV specialists, cardiologists and endocrinologists is fundamental for the disease control.

Genetic and clinical characteristics of maturity-onset diabetes of the young.

Genetic factors play an important role in various forms of diabetes mellitus (DM), but inheritance is complex and interacts with environmental factors. Although in most cases type 2 DM (T2DM) and T1DM are polygenic disorders, several monogenic forms have been identified. Among them, maturity‐onset diabetes of the young (MODY) has been the most intensively investigated. MODY is a group of six different forms of monogenic diabetes, characterized by insulin secretion defects in pancreatic β‐cells, supposed to be responsible for 2–5% of all cases of diabetes. The most common are MODY2 and MODY3, caused by mutations in the genes encoding glucokinase and hepatocyte nuclear factor 1‐alpha respectively. MODY2 is characterized by glucose sensing defects, leading to an increase in insulin secretion threshold. This causes lifelong sustained and mild hyperglycaemia from birth, most often in non‐diabetic levels. Diagnosis is incidental in most cases. These patients are asymptomatic, seldom need treatment and rarely present chronic complications. MODY3 is characterized by a severe insulin secretion defect in response to glucose. Diagnosis is made usually in adolescence and early adulthood, often by osmotic symptoms. Hyperglycaemia is progressive, and patients frequently need treatment with oral drugs or insulin some time in their follow up. This group seems to have a marked sensitivity to sulphonylureas compared to other types of diabetes. The recognition of MODY as a monogenic disorder and a thorough understanding of its pathophysiology are important for correct diagnosis and treatment, with great impact on prognosis. Besides, the study of these forms of diabetes brings important contributions to the understanding of glucose homeostasis as a whole.

The Common 866G>A Variant in the Promoter of UCP2 Is Associated With Decreased Risk of Coronary Artery Disease in Type 2 Diabetic Men

OBJECTIVE—Uncoupling protein 2 (UCP2) is a physiological downregulator of reactive oxygen species generation and plays an antiatherogenic role in the vascular wall. A common variant in the UCP2 promoter (−866G>A) modulates mRNA expression, with increased expression associated with the A allele. We investigated association of this variant with coronary artery disease (CAD) in two cohorts of type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—We studied 3,122 subjects from the 6-year prospective Non–Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events, and Ramipril (DIABHYCAR) Study (14.9% of CAD incidence at follow-up). An independent, hospital-based cohort of 335 men, 52% of whom had CAD, was also studied. RESULTS—We observed an inverse association of the A allele with incident cases of CAD in a dominant model (hazard risk 0.88 [95% CI 0.80–0.96]; P = 0.006). Similar results were observed for baseline cases of CAD. Stratification by sex confirmed an allelic association with CAD in men, whereas no association was observed in women. All CAD phenotypes considered—myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), and sudden death—contributed significantly to the association. Results were replicated in a cross-sectional study of an independent cohort (odds ratio 0.47 [95% CI 0.25–0.89]; P = 0.02 for a recessive model). CONCLUSIONS—The A allele of the −866G>A variant of UCP2 was associated with reduced risk of CAD in men with type 2 diabetes in a 6-year prospective study. Decreased risk of myocardial infarction, angina pectoris, CABG, and sudden death contributed individually and significantly to the reduction of CAD risk. This association was independent of other common CAD risk factors.

A 6-month randomized controlled trial to test the efficacy of a lifestyle intervention for weight gain management in schizophrenia

BackgroundPatients with schizophrenia have lower longevity than the general population as a consequence of a combination of risk factors connected to the disease, lifestyle and the use of medications, which are related to weight gain.MethodsA multicentric, randomized, controlled-trial was conducted to test the efficacy of a 12-week group Lifestyle Wellness Program (LWP). The program consists of a one-hour weekly session to discuss topics like dietary choices, lifestyle, physical activity and self-esteem with patients and their relatives. Patients were randomized into two groups: standard care (SC) and standard care plus intervention (LWP). Primary outcome was defined as the weight and body mass index (BMI).Results160 patients participated in the study (81 in the intervention group and 79 in the SC group). On an intent to treat analysis, after three months the patients in the intervention group presented a decrease of 0.48 kg (CI 95% -0.65 to 1.13) while the standard care group showed an increase of 0.48 kg (CI 95% 0.13 to 0.83; p=0.055). At six-month follow-up, there was a significant weight decrease of −1.15 kg, (CI 95% -2.11 to 0.19) in the intervention group compared to a weight increase in the standard care group (+0.5 kg, CI 95% -0.42–1.42, p=0.017).ConclusionIn conclusion, this was a multicentric randomized clinical trial with a lifestyle intervention for individuals with schizophrenia, where the intervention group maintained weight and presented a tendency to decrease weight after 6 months. It is reasonable to suppose that lifestyle interventions may be important long-term strategies to avoid the tendency of these individuals to increase weight.Clinicaltrials.gov identifierNCT01368406

Low prevalence of MODY2 and MODY3 mutations in Brazilian individuals with clinical MODY phenotype

Prevalence of MODY2 and MODY3 mutations has been assessed in 23 Brazilian families with MODY phenotype. Mutations in HNF-1alpha have been found in 3 families (13%) and 2 families (8.7%) had new glucokinase mutations. These genes do not explain the majority of MODY cases in Brazilian population.

Distribution of HOMA-IR in Brazilian subjects with different body mass indexes.

N THE CLINICAL SETTING, assessment of insulin resistance (IR) can be made without any laboratory test, but by evaluating data such as weight or BMI, among others. However, in the last few years laboratories have been asked to provide direct or indirect measures of IR. Homeostatic model assessment (HOMA-IR) is a simple and inexpensive technique to evaluate IR from basal (fasting) glucose and insulin or C-peptide concentrations, validated against a variety of physiological methods (1-4). To validate the potential use of HOMA-IR values in clinical practice, it is important to establish its distribution in a sample of normoglycemic individuals from a population with the same genetic background (2). In this regard, we aim to describe the distribution of HOMA-IR values in a large sample of Brazilian population. We analyzed retrospectively fasting insulin and glucose levels in 1,898 Brazilian adults (25% males, age range 18-90 years). All had fasting glucose 30 (n= 391) (table 1). A recent publication in a group of 312 non-obese, normoglicemic Brazilian subjects found a mean HOMA-IR of 1.7, and a threshold value for insulin resistance of 2.71 (3). The use of HOMA ‐IR to quantify insulin sensitivity can be helpful in clinical practice for comparisons of insulin sensitivity, gathering of longitudinal data in subjects at risk for development of abnormal glucose tolerance. Also, HOMA ‐IR can be used to assess longitudinal changes of IR in patients with diabetes in order to examine the natural history of the disease and to assess the effects of treatment, as demonstrated for example in the U.K. Prospective Diabetes Study (UKPDS) (5). Our results can be useful as a reference for further Brazilian studies using HOMA-IR values as a measure of IR in this particular population.

Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study

Aims/hypothesisWe investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study.MethodsWe studied 5,110 unrelated French men and women who participated in the prospective Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Additional cross-sectional analyses were performed on 4,472 French individuals with type 2 diabetes and 3,065 controls. Three single nucleotide polymorphisms (SNPs) were genotyped: rs10010131, rs1801213/rs7672995 and rs734312.ResultsWe observed statistically significant associations between the major alleles of the three variants and prevalent type 2 diabetes in the DESIR cohort at baseline. Cox analyses showed an association between the G-allele of rs10010131 and incident type 2 diabetes (HR 1.34, 95% CI 1.08–1.70, p = 0.007). Similar results were observed for the G-allele of rs1801213 and the A-allele of rs734312. The GGA haplotype was associated with an increased risk of diabetes as compared with the ACG haplotype (HR 1.26, 95% CI 1.04–1.42, p = 0.02). We also observed statistically significant associations of the three SNPs with plasma glucose, HbA1c levels and insulin secretion at baseline and throughout the study in individuals with type 2 diabetes or at risk of developing diabetes. However, no association was observed in those who remained normoglycaemic at the end of the follow-up. Associations between the three variants and type 2 diabetes were replicated in cross-sectional studies of type 2 diabetic patients in comparison with a non-diabetic control group.Conclusions/interpretationThe most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.

The Gly482Ser polymorphism in the peroxisome proliferator-activated receptor-γ coactivator-1 gene is associated with hypertension in type 2 diabetic men

Aims/hypothesisPeroxisome proliferator-activated receptor-γ coactivator-1 (PPARGC1) acts as a cofactor for several nuclear hormone receptors in many tissues and organs implicated in blood pressure regulation. Here, we assessed the association between the Gly482Ser variant of PPARGC1 and the arterial hypertension frequently found in subjects with type 2 diabetes.MethodsWe studied a group of 479 men and 253 women with type 2 diabetes. Arterial hypertension was present in 70% of the men and in 73% of the women. Genotypes were examined by PCR restriction fragment length polymorphism. A logistic regression analysis was performed to assess the covariables associated with arterial hypertension.ResultsThere was an association between Ser allele homozygosis and arterial hypertension in type 2 diabetic men (odds ratio of 2.52 vs Gly allele homozygosis; 95% CI: 1.32–5.00; p=0.0064), but not in women. The prevalence of arterial hypertension in type 2 diabetic men was 77% vs 73% vs 67% for Ser-Ser, Gly-Ser and Gly-Gly carriers respectively (p=0.021). Age, BMI, the use of insulin, and triglyceride and creatinine levels were also independently associated with arterial hypertension in this cohort.Conclusions/interpretationWe have observed a sex-specific association between the PPARGC-1 gene Gly482Ser polymorphism and arterial hypertension in type 2 diabetic men. Further studies are needed to investigate the genetic, biochemical and pathophysiological basis of this allelic association.

Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: The DIABHYCAR prospective study

AIM Vitamin D deficiency is associated with coronary artery disease (CAD), and the actions of vitamin D are mediated by binding to a specific nuclear vitamin D receptor (VDR). This study investigated the associations of VDR gene variants with CAD in two cohorts of type 2 diabetes patients. METHODS A cohort of 3137 subjects from the prospective DIABHYCAR study (CAD incidence: 14.8%; follow-up: 4.4 ± 1.3 years) and an independent, hospital-based population of 713 subjects, 32.3% of whom had CAD, were assessed. Three SNPs in the VDR gene were genotyped: rs1544410 (BsmI); rs7975232 (ApaI); and rs731236 (TaqI). RESULTS In the DIABHYCAR cohort, an association was observed between the A allele of BsmI and incident cases of CAD (HR: 1.16, 95% CI: 1.05-1.29; P = 0.002). Associations were also observed between BsmI (P = 0.01) and TaqI (P = 0.04) alleles and baseline cases of CAD. The AAC haplotype (BsmI/ApaI/TaqI) was significantly associated with an increased CAD prevalence at the end of the study compared with the GCT haplotype (OR: 1.12, 95% CI: 1.02-1.28; P = 0.04). In a cross-sectional study of the independent hospital-based cohort, associations of ApaI (P = 0.009) and TaqI (P = 0.03) alleles with CAD were observed, with similar haplotype results (OR: 1.33, 95% CI: 1.03-1.73; P = 0.03). CONCLUSION The haplotype comprising the minor allele of BsmI, major allele of ApaI and minor allele of TaqI of VDR (AAC) was associated with an increased risk of CAD in type 2 diabetes patients. This effect was independent of the effects of other known cardiovascular risk factors.