Carolina S.V. Oliveira

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.

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.

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

OBJECTIVE To 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. METHODS 603 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). RESULTS The 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. CONCLUSIONS In 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.

ADIPOQ and adiponectin: the common ground of hyperglycemia and coronary artery disease?

Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.

Estimation of Diabetes Risk in Brazilian Population by Typing for Polymorphisms in HLA-DR-DQ, INS and CTLA-4 Genes

The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Brazilian population and test the capability of a low resolution full-house DR-DQ typing method to find subjects at diabetes risk. Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients. Genotypes with two risk haplotypes or a combination of a susceptibility associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control subjects (P < 0.0001). Insulin gene −2221 C/T polymorphism was also associated with diabetes risk: CC genotype was found among 83.1% of patients compared to 69.3% of healthy controls (P = 0.0369, OR 1.98) but CTLA-4 gene +49 A/G polymorphism did not significantly differ between patients and controls. Despite the diversity of the Brazilian population the screening sensitivity and specificity of the used method for T1D risk was similar to that obtained in Europe.

Two novel mutations in the EIF2AK3 gene in children with Wolcott–Rallison syndrome

Reis AF, Kannengiesser C, Jennane F, Manna TD, Cheurfa N, Oudin C, Savoldelli RD, Oliveira C, Grandchamp B, Kok F, Velho G. Two novel mutations in the EIF2AK3 gene in children with Wolcott–Rallison syndrome.

The Ala45Thr polymorphism of NEUROD1 is associated with type 1 diabetes in Brazilian women

BACKGROUND NEUROD1 encodes a transcription factor expressed in the endocrine pancreas, and involved in beta-cell development, function and mechanisms of apoptosis. In this study, we investigated the association of a frequent polymorphism in exon 2 of NEUROD1 (G > A; Ala45Thr) with Type 1 diabetes in Brazilian subjects. METHODS A population/association study comprising 246 unrelated Type 1 diabetic and 275 nondiabetic white Brazilian subjects. The Ala45Thr variant was genotyped by a PCR-RFLP method. RESULTS The frequency of the Thr allele was significantly higher in patients with Type 1 diabetes than in controls (42.3% vs 35.3%, P=0.02). Stratification by gender showed that homozygosity for the Thr allele was associated with Type 1 diabetes in women with odds ratio of 3.66 (95% C.I. 1.43-10.11, P=0.009) as compared to homozygosity for the Ala allele. This effect was not observed in men. CONCLUSIONS We found a gender-specific association of the Ala45Thr variant of NEUROD1 with Type 1 diabetes in Brazilian women. Our results suggest that gender as well as ethnicity might modulate the association of NEUROD1 with Type 1 diabetes.

Individuals with prediabetes identified by HbA1c undergoing coronary angiography have worse cardiometabolic profile than those identified by fasting glucose

BackgroundType 2 diabetes mellitus has well known deleterious effects on coronary artery disease (CAD). The role of milder hyperglycemic states such as prediabetes (PD) on CAD is debatable. Glycated hemoglobin (HbA1c) has recently been advocated as a diagnostic tool for diabetes mellitus (DM) and PD. This study aims to assess the cardiometabolic risk profile and coronary lesions of patients with PD undergoing coronary angiography identified either by fasting plasma glucose (FPG) or HbA1c levels.MethodsWe studied 514 individuals without previously known glucose disturbances. Their glycemic status was assessed by FPG and HbA1c (HPLC) and classified according to ADA guidelines, using each parameter independently, as having normal glucose tolerance (N), PD, or DM. CAD was defined as stenosis greater than 50% in one major coronary vessel or branch. Framingham score was calculated.ResultsSubjects with PD had a similar frequency of CAD compared do N individuals by both FPG (61 vs. 59.3%) and HbA1c (55.4 vs 61.2%) (p non-significant for linear-by-linear association). PD individuals identified by FPG had worse HOMA2B (mean [95% CI] 65.4 [60.9-69.9] vs. 76.6 [71.4-81.9]) and HOMA2-IR (1.10 [0.98-1.22] vs. 0.80 [0.72-0.89]) when compared to N controls. PD individuals identified by HbA1c had higher frequency of Framingham risk above 20% (25.4 vs 11.8%), arterial hypertension (87.8 vs 72.6%), and dyslipidemia (83.8 vs 72%) compared to N individuals. PD associated with an increased number of coronary lesions only when diagnosed by HbA1c (median [interquartile interval] 2 [0–4] PD versus 1 [0-3.75] N, p = 0.03 for trend).ConclusionsHbA1c was more effective than FPG in identifying individuals with PD associated with high cardiovascular risk profile in a sample of individuals undergoing coronary angiography.

High rate of abnormal glucose tolerance in Brazilian individuals undergoing coronary angiography

INTRODUCTION Undiagnosed hyperglycemia is common in high cardiovascular risk individuals, especially in those with coronary artery disease (CAD). There is no consensus about the optimal method for the screening of hyperglycemia in this population. SUBJECTS AND METHODS Five hundred and fourteen Brazilian individuals undergoing coronary angiography, without previously known diabetes mellitus (DM), had their glycemic status evaluated by both fasting plasma glucose (FPG) and HbA1c, being classified in normal (N), prediabetes (PD), and DM according to American Diabetes Association criteria. Concordance between both methods was assessed by Cohens κ. Accuracy of FPG and HbA1c to diagnose CAD was evaluated as proof-of-concept. RESULTS Among individuals screened by FPG, 41.2% had PD and 6% had DM. Among those screened by HbA1c, 52.7% had PD and 12.7% had DM. Concordance for a positive screening of PD occurred in 125 individuals (κ = 0.084). Eighteen individuals had a concordant positive screening of DM (κ = 0.310). As a predictor of CAD, accuracy of FPG was 0.554 (p = 0.009) and of HbA1c 0.557 (p = 0.006). CONCLUSION a high frequency of hyperglycemia, between 47 and 65%, was found in individuals submitted to coronary angiography without previously known glucose disturbances, using FPG and HbA1c as screening methods respectively.HbA1c detected significantly more individuals with both PD and DM than FPG. Concordance between both methods is low. The question of which is the gold-standard method to diagnose hyperglycemia in this population is still open.

Biological activity screening of seven Plectranthus species: Pesquisa de actividade biológica de sete espécies de Plectranthus

Natural products from Plectranthus spp. plants have an ethnopharmacological use, inspiring several scientific investigations. As such, this work aims to perform a biological activity screening in order to scientifically validate the use of these plants. Assays on in vitro acetylcholinesterase (AChE) inhibition, antioxidant effects, antimicrobial activity and Artemia salina lethality were performed on seven Plectranthus spp. extracts (P. swynnertonii, P. welwischii, P. woodii, P. cylindraceus, P. spicatus, P. ramosior and P. petiolaris). Acetonic extracts were obtained by sonication (10% w/v), where P. ramosior had the highest yield of dry extract (13.49% w/w). In the AChE inhibition assay, only P. cylindraceus extract decreased enzymatic activity (30.2 ± 3.78%). The antimicrobial activity was screened using the well diffusion method, against Gram positive and negative bacteria and yeast. P. ramosior extract showed not only an inhibition zone against S. aureus and C. albicans (15 and 11 mm, respectively), but also the highest scavenging activity (DPPH method, 36.4 ± 0.04%). On the lethality test in A. salina, P. swynnertonnii extract was the most toxic (LC50 = 0.036 mg/L). These preliminary results showed that P. cylindraceus, P. ramosior and P. swynnertonnii are potential bioactive extracts for further isolation and antimicrobial and cytotoxic studies.