Rosângela Roginski Réa

Butyrylcholinesterase activity and metabolic syndrome in obese patients.

Abstract Total butyrylcholinesterase activity (EC 3.1.1.8) was previously suggested as a marker for metabolic syndrome. The present study examined total butyrylcholinesterase activity and the relative and absolute activities of two butyrylcholinesterase electrophoretic bands (C 4/5 and C OF) in 99 obese individuals (body mass index ≥30kg/m 2) presenting the CHE2 C5 − phenotype of the CHE2 gene. Anthropometric, hormonal and biochemical variables already associated with metabolic syndrome were also examined. The data from these obese individuals of the CHE2 C5− phenotype show that total butyrylcholinesterase activity and the absolute activities of the C 4/5 and C OF electrophoretic bands are associated with metabolic syndrome and with variables related to it. These butyrylcholinesterase activities do not behave as independent risk factors for metabolic syndrome, but can be considered as secondary markers for this syndrome in obese individuals with the CHE2 C5− phenotype.

The plasma logarithm of the triglyceride/HDL-cholesterol ratio is a predictor of low risk gestational diabetes in early pregnancy.

BACKGROUND The plasma lipid profile changes atherogenically during normal pregnancy. Gestational diabetes mellitus (GDM) can exacerbate the changes in metabolism. The logarithm of the ratio triglycerides/HDL-cholesterol is an atherogenic index of the plasma (AIP) and can be used as a marker for plasma atherogenicity. METHODS Serum of 576 unrelated Euro-Brazilian pregnant women was collected and the subjects were classified as healthy pregnant women (control, n=288) and gestational diabetic patients (GDM, n=288) according to the ADA 2010 criteria. Both studied groups were sub classified in 4 gestational periods: (i) 12-23, (ii) 24-28, (iii) 29-32 and (iv) >32 weeks of gestation. RESULTS Except for the AIP, the other parameters showed low discrimination between control and GDM groups (ROC curves). When analyzed by ROC curves the AIP of subjects in the early period of gestation showed sensitivity and specificity of 82.6% and 83.4%, respectively, with a cut-off point of 0.099 (AUC 0.886, P<0.0001). CONCLUSIONS The AIP is a valuable index to identify pregnant women with low risk of gestational diabetes before 24 weeks of gestation.

Marcadores para o diagnóstico e tratamento de 924 gestações com diabetes melito gestacional

OBJECTIVES: To evaluate the epidemiological profile and outcomes of women with gestational diabetes mellitus (GDM), determining risk factors for increased vigilance. SUBJECTS AND METHODS: We studied 924 pregnancies in 916 patients between November 6, 2001 and September 21, 2009. RESULTS: Risk factors were found in 95.1% of cases. The prevalence of maternal diabetes, paternal diabetes and diabetes in other family members was 24.3%, 9.4% and 24.7%, respectively. Predictive factors for insulin use were: screening fasting glucose (FG) ≥ 85, Oral Glucose Tolerance Test (OGTT) FG ≥ 95, 2h glucose after 75 g ≥ 200 mg/dL, previous GDM, obesity, HbA1c > 6%, and the association of risk factors including family history of diabetes mellitus and obesity or previous GDM, the last one the most relevant (p < 0,05). CONCLUSIONS: Risk factors were very sensitive for GDM detection, and provision of family history strengthens its relationship with T2DM. Greater vigilance is recommended for patients with predictive factors for insulin requirement.

Prevalência de infecção pelo vírus da hepatite C em pacientes com diabetes melito tipo 2

BACKGROUND: Recently, a possible epidemiological association between hepatitis C virus infection and diabetes mellitus has been suggested and a higher prevalence of HCV antibodies has been found among type 2 diabetic when compared with normal controls. AIM: To evaluate the prevalence of hepatitis C infection in diabetic patients in Curitiba, PR, Brazil. PATIENTS AND METHODS: A total of 145 type 2 and 104 type 1 diabetic patients attending the outpatient diabetic unit of an university hospital were consecutively tested for anti-HCV, using a fourth-generation enzyme-linked immunosorbent assay (ELISA). The control group was constituted by 16,720 volunteer blood donors attending the blood bank of the same hospital during the period of the study. Diabetic patients were also evaluated for clinical, biochemical (aminotransferase levels) and demographic variables and previous exposure to risk factors for hepatitis C infection. RESULTS: A higher prevalence of hepatitis C infection was observed in type 2 diabetic patients in comparison with blood donors. Although anti-HCV prevalence in type 2 diabetic patients was higher than found in type 1, it did not reach statistical significance. Both diabetic groups were predominantly female, and as expected, type 2 diabetic were older than type 1. Race distribution, duration of the disease, and previous exposure to hepatitis C risk factors were similar in both groups, but type 2 diabetic subjects had higher median levels of alanine aminotransferase than type 1. CONCLUSIONS: A higher prevalence of hepatitis C infection was detected in type 2 diabetic patients in comparison with blood donors in our region, in accordance with study data from different populations. If all type 2 diabetic patients should undergo regular screening for hepatitis C infection remains a question.

Polymorphisms in FTO and TCF7L2 genes of Euro-Brazilian women with gestational diabetes

OBJECTIVE To investigate the association between fat mass and obesity-associated (FTO) gene polymorphisms rs8050136C>A and rs9939609T>A, and transcription factor 7-like 2 (TCF7L2) gene polymorphisms rs12255372G>T and rs7903146C>T, in a sample group of pregnant Euro-Brazilian women with or without gestational diabetes mellitus (GDM). METHODS Subjects were classified as either healthy pregnant control (n=200) or GDM (n=200) according to the 2010 criteria of the American Diabetes Association. The polymorphisms were genotyped using fluorescent probes (TaqMan®). RESULTS All groups were in the Hardy-Weinberg equilibrium. The genotype and allele frequencies of the examined polymorphisms did not exhibit significant difference (P>0.05) between the groups. In the healthy and GDM pregnant women groups, the A-allele frequencies (95% CI) of FTO polymorphisms rs8050136 and rs9939609 were 39% (34-44%); 38% (33-43%) and 40% (35-45%); 41% (36-46%), respectively; and the T-allele frequencies of TCF7L2 polymorphisms rs12255372 and rs7903146 were 30% (26-35%), 32% (27-37%) and 29% (25-34%), 36% (31-41%), respectively. CONCLUSION The examined polymorphisms were not associated with GDM in the Euro-Brazilian population studied.

Gestational diabetes mellitus (GDM) decreases butyrylcholinesterase (BChE) activity and changes its relationship with lipids

Many conditions interfere with butyrylcholinesterase (BChE) activity, e.g., pregnancy or presence of the BCHE gene variant −116A can decrease activity whereas obesity and types I and II diabetes mellitus can increase activity. In this study, we examined BChE activity, −116A and 1615A BCHE gene variants, and anthropometric and biochemical variables associated with diabetes in patients with gestational diabetes mellitus (GDM) and in healthy pregnant women. BChE activity was measured spectrophotometrically using propionylthiocholine as substrate and genotyping of the −116 and 1615 sites of the BCHE gene was done with a TaqMan SNP genotyping assay. Three groups were studied: 150 patients with GDM, 295 healthy pregnant women and 156 non-pregnant healthy women. Mean BChE activity was significantly lower in healthy pregnant women than in women from the general population and was further reduced in GDM patients. BChE activity was significantly reduced in carriers of −116A in GDM patients and healthy pregnant women. Although GDM patients had a significantly higher mean body mass index (BMI) and triglycerides than healthy pregnant women, they had lower mean BChE activity, suggesting that the lowering effect of GDM on BChE activity was stronger than the characteristic enhancing effect of increased BMI and triglycerides.

Reproducibility of methods used for the assessment of autonomous nervous system's function.

OBJECTIVE The objective of this study is to investigate the influence of the day-to-day variability of the measures of heart rate variability (HRV) on the sample size calculation for the study of cardiac autonomic neuropathy. MATERIAL AND METHODS We analyzed HRV in the frequency domain [very low (VLF), low (LF), and high frequency (HF) bands] and in the time domain [the root mean squared of successive RR intervals differences (RMSSD); the mean RR intervals (RRNN); the standard deviation of RR intervals (SDNN) and the coefficient of variation (CV)] during a 5-min electrocardiogram record. We also analyzed the heart rate response to deep breathing [expiration:inspiration ratio], to the Valsalva maneuver and to standing [maximum:minimum ratio] and the blood pressure response to standing. The day-to-day variability was assessed by calculating the within-subject standard deviations (WSSD), limits of agreement, typical errors and the ratio of the WSSD to the mean values obtained on days 1 and 2 (WSSD/GM). RESULTS Sixty-seven healthy subjects (45 females), aged 27 (19-39) years, were recruited. The RMSSD, CV, VLF, LF, HF and blood pressure response to standing showed marked variability (WSDD/GM (%)=237.7, 455.1, 69.9, 126.5, 81.3 and 380.5, respectively), while the RRNN, SDNN, Valsalva, expiration:inspiration and maximum:minimum ratio showed less variability (WSSD/GM (%)=6.4, 24.5, 18.6, 11.0 and 14.1, respectively). The minimum differences expected to be statistically significant for the autonomic measurements were calculated. CONCLUSION Some tests that assess HRV showed adequate reproducibility. This study allows the determination of a sample size calculation for longitudinal or drug-testing studies.

The functional polymorphisms -429T > c and -374T > a of the RAGE gene promoter are not associated with gestational diabetes in Euro-Brazilians.

The receptor for advanced glycation end products (RAGE or AGER) is a multiligand member of the immunoglobulin superfamily. RAGE is expressed in several tissues, including human myometrium, chorionic villi and placenta. Advanced glycation end products are the best studied ligands of RAGE; they have pro-inflammatory actions in human gestational tissues, increasing oxidative stress and the release of cytokines and prostaglandins. We investigated the association of RAGE gene promoter polymorphisms -429T>C (rs1800625) and -374T>A (rs1800624) with gestational diabetes. A sample of 750 unrelated European origin pregnant Brazilian women were classified as nondiabetic (control group, N = 600) or having gestational diabetes (N = 150) according to American Diabetes Association 2009 criteria. Genotyping was performed by PCR-RFLP. The frequencies of the rare alleles -429C (6.3 versus 9.1%) and -374A (26 versus 30%) were not significantly different between the gestational diabetes patients and healthy pregnant women. Also, the -429T>C and -374T>A polymorphisms were not associated with body mass index, lipid profile, fasting glycemia, HbA1C, or insulin requirement. We found that functional promoter polymorphisms of the RAGE gene were not associated with gestational diabetes or its complications in these Euro-Brazilian patients.

Butyrylcholinesterase and diabetes mellitus in the CHE2 C5- and CHE2 C5+ phenotypes

OBJECTIVE To investigate the relationship between butyrylcholinesterase (BChE) activities (total and band specific) and diabetes mellitus. SUBJECTS AND METHODS BChE activities (BChEA, AC(4/5), AC(OF) and RC(5)) were analyzed in 101 type 1 (DM1) and in 145 type 2 (DM2) diabetic patients, in relation to phenotype, weight and incidence of metabolic syndrome (MS) in these patients. The C(4/5) and C(5) complex were separated from other molecular forms (C(OF)) using an acid agar gel. RESULTS The BChE activity (BChEA) and the absolute activities of C(4/5) (AC(4/5)) and C(OF) (AC(OF)) showed a high positive correlation coefficient to weight in the CHE2 C5- group, while the relative activity of C5 complex (RC5) showed a negative correlation to weight. CONCLUSIONS The present study suggests that the positive correlation of the BChE activities to diabetes mellitus and to insulin resistance may depend on the CHE2 locus variability. High values of BChE activities were associated with insulin resistance only in CHE2 C5- diabetic patients, while in CHE2 C5+ diabetic patients, the presence of C(5) complex, especially in a relatively high proportion, leads to less fat storage and better protection against metabolic syndrome.

Low prevalence of glucokinase gene mutations in gestational diabetic patients with good glycemic control.

Glucokinase (GCK) plays a key role in glucose homeostasis. Gestational diabetes mellitus increases the risk of gestational complications in pregnant women and fetuses. We screened for mutations in coding and flanking regions of the GCK gene in pregnant women with or without gestational diabetes in a Brazilian population. A sample of 200 pregnant women classified as healthy (control, N = 100) or with gestational diabetes (N = 100) was analyzed for mutations in the GCK gene. All gestational diabetes mellitus patients had good glycemic control maintained by diet alone and no complications during pregnancy. Mutations were detected by single-strand conformation polymorphism and DNA sequencing. Thirteen of the 200 subjects had GCK gene mutations. The mutations detected were in intron 3 (c.43331A>G, new), intron 6 (c.47702T>C, rs2268574), intron 9 (c.48935C>T, rs2908274), and exon 10 (c.49620G>A, rs13306388). None of these GCK mutations were found to be significantly associated with gestational diabetes mellitus. In summary, we report a low frequency of GCK mutations in a pregnant Brazilian population and describe a new intronic variation (c.43331A>G, intron 3). We conclude that mutations in GCK introns and in non-translatable regions of the GCK gene do not affect glycemic control and are not correlated with gestational diabetes mellitus.