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 Cohen's 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.

Association of classical risk factors and coronary artery disease in type 2 diabetic patients submitted to coronary angiography.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death among individuals with type 2 diabetes (T2DM). T2DM accelerates atherosclerosis alongside classical risk factors such as dyslipidemia and hypertension. This study aims to investigate the association of hyperglycemia and associated risk factors with CAD in outpatients with T2DM undergoing coronary angiography. METHODS: 818 individuals referred to coronary angiography were evaluated for glucose disturbances. After exclusion of those with prediabetes, 347 individuals with T2DM and 94 normoglycemic controls were studied for BMI, blood pressure, fasting plasma glucose, HbA1c, lipids, HOMA, adiponectin, Framingham risk score, number of clinically significant coronary lesions (stenosis > 50%). RESULTS: Among T2DM subjects, those with CAD (n = 237) had worse glycemic control (fasting glucose 162.3 + 69.8 vs. 143.4 + 48.9 mg/dL, p = 0.004; HbA1c 8.03 + 1.91 vs. 7.59 + 1.55%, p = 0.03), lower HDL (39.2 + 13.2 vs. 44.4 + 15.9 mg/dL, p = 0.003), and higher triglycerides (140 [106-204] vs. 121 [78.5-184.25] mg/dL, p = 0.002), reached more often therapeutic goals for LDL (63.4% vs. 51.4%, p = 0.037) and less often goals for HDL (26.6% vs. 37.3%, p = 0.04), when compared to CAD-free individuals (n = 110). The same differences were not seen in normoglycemic controls. In T2DM subjects HbA1c tertiles were associated with progressively higher number of significant coronary lesions (median number of lesions 2 [A1c < 6.8%]; 2.5 [A1c 6.8-8.2%]; 4 [A1c > 8.2%]; p = 0.01 for trend). CONCLUSIONS: Classic risk factors such as glycemic control and lipid profile were associated with presence of CAD in T2DM subjects undergoing coronary angiography. Glycemic control is progressively associated with number and extent of coronary lesions in patients with T2DM.

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

BACKGROUND: Adiponectin 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. METHODS: Firstly, 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. RESULTS: Total 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). CONCLUSIONS: Adiponectin levels decreased with increasing number of MS criteria, and it is in part determined by its relationship with HDL, triglycerides and abdominal adiposity.

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

BACKGROUND: Type 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. METHODS: We 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. RESULTS: Subjects 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). CONCLUSIONS: HbA1c was more effective than FPG in identifying individuals with PD associated with high cardiovascular risk profile in a sample of individuals undergoing coronary angiography.

Association of circulating levels of nicotinamide phosphoribosyltransferase (NAMPT/Visfatin) and of a frequent polymorphism in the promoter of the NAMPT gene with coronary artery disease in diabetic and non-diabetic subjects.

BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) is the limiting enzyme in one of pathways of synthesis of Nicotinamide Adenine Dinucleotide, a redox coenzyme. NAMPT is considered as an insulin-mimetic factor and a potential regulatory factor in inflammatory and immune processes. Associations of circulating NAMPT levels with cardiovascular disease (CVD) and insulin resistance have been reported. We investigated association of circulating NAMPT levels and the rs9770242 NAMPT gene polymorphism with coronary artery disease (CAD). METHODS: We studied 594 Brazilian subjects undergoing a coronary angiography (49% of whom had type 2 diabetes). CAD, defined as stenosis greater than 50% in one major coronary vessel or branch, was observed in 68% of subjects. Genetic studies were also performed in 858 North-American Non-Hispanic White subjects with type 2 diabetes (49% with CAD). RESULTS: We observed an interaction between glycemic and CAD status on the comparison of NAMPT levels by CAD status. NAMPT levels were higher in type 2 diabetic patients with CAD as compared to those without CAD: 5.27 ± 2.93 ng/ml vs. 4.43 ± 2.94 ng/ml, p = 0.006 (mean ± SD). NAMPT levels were not significantly different in non-diabetic subjects with or without CAD. The T-allele of rs9770242 was associated with CAD in the Brazilian cohort (OR 1.46, 95% CI 1.06 - 2.01, p = 0.02) while no association was observed in the North-American cohort. CONCLUSIONS: Our data suggest that circulating NAMPT levels are associated with CAD in type 2 diabetic patients. NAMPT rs9770242 polymorphism may be associated with CAD in some populations.

A novel glucokinase deletion (p.Lys32del) and five previously described mutations co-segregate with the phenotype of mild familial hyperglycaemia (MODY2) in Brazilian families.

Six Brazilian families with mild familial hyperglycaemia have been screened for glucokinase (GCK) mutations. All had mutations that co-segregated with the phenotype. One of the mutations, the deletion 96_98delAAG (p.Lys32del), had not been previously described, reinforcing the worldwide prevalence of GCK MODY and widespread existence of undetected new mutations.

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.

ADIPOQ and adiponectin: the common ground of hyperglycemia and coronary artery disease? / ADIPOQ e adiponectina: base comum da hiperglicemia e doença arterial coronariana?

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.

Os níveis plasmáticos de adiponectina e o gene codante desta proteína, ADIPOQ, parecem explicar parte da interação de doenças como obesidade, resistência à insulina, diabetes melito tipo 2 (DM2) e doença arterial coronariana (DAC). Apresentamos as evidências do papel tanto dos níveis de adiponectina quanto das variantes no ADIPOQ na modulação da DAC, sobretudo na presença de hiperglicemia. Estudos recentes sugerem que níveis de adiponectina total e de alto peso molecular (HMW) são marcadores de bom prognóstico DAC, sobretudo em pacientes de baixo risco cardiovascular, enquanto nos pacientes de alto risco ou com doença já estabelecida podem se associar com pior prognóstico. Apresentamos também as evidências em relação ao possível controle genético dos níveis circulantes de adiponectina, tanto total quanto da isoforma de alto peso molecular, sobretudo em relação ao ADIPOQ. A análise global dos dados sugere que tanto os níveis circulantes de adiponectina quanto polimorfismos no gene ADIPOQ estão implicados na evolução de DAC em pacientes com hiperglicemia e que essas associações podem existir de forma independente.

May ingestion of leachate from decomposed corpses cause appendicitis? A case report.

The general consensus is that appendicitis is basically provoked by fecaliths or lymphoid hyperplasic obstruction. Several studies based on histological diagnosis have not confirmed this hypothesis. On the contrary, obstruction has been proved in only a minority of cases. Diverse infections by parasites, bacteria, fungus, and noninfective agents have been associated with appendicitis in the medical literature. We describe a firefighter, who ingested a small quantity of leachate from decomposing corpses while working and developed enteritis a few hours later, which lasted several days and evolved to appendicitis. This case raises the possibility that the high quantity of bacteria concentration present in the leachate could have provoked enteritis and the subsequent appendicitis due to a direct effect of the bacteria on the appendix.

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.