Subclinical abnormalities of glucose metabolism in Brazilian women with a history of gestational diabetes mellitus

Background. To evaluate insulin release and insulin sensitivity in women with prior gestational diabetes mellitus (GDM) to gain a better understanding of type 2 diabetes pathogenesis.Methods. GDM women were individually matched for age, body mass index, and waist/hip ratio with those who were normal glucose tolerant in a previous pregnancy (NGT). All women presented with normal glucose tolerance. Twenty pairs were submitted to the oral glucose tolerance test (OGTT) with plasma glucose, insulin, and C-peptide determinations. of the 20 pairs, 18 participated in hyperglycemic (10.0 mmol/l) clamp experiments with frequent plasma glucose and insulin determinations, allowing us to calculate first- and second-phase insulin release and the insulin sensitivity index. GDM and NGT women were compared using Student's t-test, the Mann-Whitney U-test, Friedman's non-parametric test, and the two proportion test for independent groups.Results. GDM women showed higher glycosylated hemoglobin values; at OGTT, they showed late insulin peak with increased plasma insulin levels only during the second hour, and a similar plasma C-peptide response despite a higher plasma glucose curve; during hyperglycemic clamp procedures, they showed similar biphasic insulin release and insulin sensitivity index. Considering that a woman with previous GDM had a defect in insulin release and/or insulin sensitivity, if its magnitude was at least 25% lower than that of the matched NGT woman, 43.8% showed impairment of first-phase insulin release and 55.6% insulin resistance.Conclusions. GDM women showed some degree of glucose intolerance. It is therefore necessary to follow them for a longer time.

High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

HIPERTENSAO ARTERIAL EM PACIENTES OBESOS COM HIPERTROFIA CARDIACA. EFEITOS DO CAPTOPRIL SOBRE A SENSIBILIDADE A INSULINA E HORMONIO DE CRESCIMENTO

Purpose. To evaluate the effects of captopril (Cpt) on carbohydrate metabolism and growth hormone (GH) in adults hypertensive obese patients with normal (NGT) or impaired (IGT) glucose tolerance and left ventricular hypertrophy. Methods. Ten patients (53 ± 8 years), 8 women and 2 men, white, body mass index (BMI) ≥ 26 kg/m2, left ventricular mass index (LVMI) > 135 g/m2 in man and > 110 g/m2 in woman, with diastolic blood pressure (DBP) 95-115 mmHg after 3 weeks of placebo, were identified by oral glucose tolerance test (OGTT-75 g) as either with NGT or IGT, and treated with Cpt 25 mg t.i.d. for 8 weeks. At the 8 weeks, dosage was increased to 50 mg b.i.d. if DBP > 90 mmHg or the decrease of the DBP < 10%, during the next 8 weeks. OGTT and clonidine tests (0,04 mg/kg) with determinations, every 30 minutes of glucose, insulin, and GH during 2 hours, were performed. Results. Cpt lowered SBP and DBP in the NGT group and IGT group. The LVMI and the left ventricular mass (LVM) decreased in the IGT group with no significant change in the NGT group. Cpt promoted in the IGT group decrease in the area under the curve (AUC) of glucose, and AUC of insulin, with increase of the AUC of the percent of the β cell function, AUC of HC, and insulin sensitivity index with no significantly change in the NGT group. Conclusion. Adults hypertensive obese patients with IGT had decreased significantly in mean fasting level of GH concentrations compared to age, race, and BMI matched hypertensive patients with NGT. Treatment with Cpt induced a significant increased of the GH, with improvement of the metabolism in patients with IGT.

Free diet selection by broilers as influenced by dietary macronutrient ratio and corticosterone supplementation. 1. Diet selection, organ weights, and plasma metabolites

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Pancreatic β-cell defects in women at risk of type 2 diabetes

We evaluated insulin release and insulin sensitivity in women with basal and/or postprandial hyperglycemia but normal oral glucose tolerance test (OGTT) in previous pregnancy (GHG). These women were individually matched with females without previous hyperglycemia (NGT). Both groups consisted of normal glucose-tolerant women at the time of this study. They underwent OGTT (75g; n= 32 pairs) and hyperglycemic clamp experiments (10mmoll-1; n=27 pairs) with plasma glucose, insulin, and C-peptide measurements and calculation of insulinogenic index, first- and second-phase insulin release, and insulin sensitivity index (ISI). The GHG group showed higher glycosylated hemoglobin levels (6.2±0.6% versus 5.8±0.8%; P<0.05); lower insulinogenic index at 30min (134.03±62.69pmolmmol-1 versus 181.59±70.26pmolmmoll-1; P<0.05) and diminished C-peptide response in relation to glucose (4.05±0.36nmolmmol-1 versus 4.23±0.36nmolmmol-1; P<0.05) at OGTT. Both groups did not show difference in insulin secretion and ISI by hyperglycemic clamp technique. We concluded that in up to 12 years from index pregnancy, women with previous GHG, presenting normal glucose tolerance and well-matched with their controls, showed β-cell dysfunction without change in ISI. As women with previous GHG are at risk of type 2 diabetes, β-cell dysfunction may be its primary defect. © 2003 Elsevier B.V. All rights reserved.

Monosodium glutamate in standard and high-fiber diets: Metabolic syndrome and oxidative stress in rats

Objective: This study determined the effects of adding monosodium glutamate (MSG) to a standard diet and a fiber-enriched diet on glucose metabolism, lipid profile, and oxidative stress in rats. Methods: Male Wistar rats (65 ± 5 g, n = 8) were fed a standard diet (control), a standard diet supplemented with 100 g of MSG per kilogram of rat body weight, a diet rich in fiber, or a diet rich in fiber supplemented with 100 g of MSG per kilogram of body weight. After 45 d of treatment, sera were analyzed for concentrations of insulin, leptin, glucose, triacylglycerol, lipid hydroperoxide, and total antioxidant substances. A homeostasis model assessment index was estimated to characterize insulin resistance. Results: Voluntary food intake was higher and feed efficiency was lower in animals fed the standard diet supplemented with MSG than in those fed the control, fiber-enriched, or fiber- and MSG-enriched diet. The MSG group had metabolic dysfunction characterized by increased levels of glucose, triacylglycerol, insulin, leptin, and homeostasis model assessment index. The adverse effects of MSG were related to an imbalance between the oxidant and antioxidant systems. The MSG group had increased levels of lipid hydroperoxide and decreased levels of total antioxidant substances. Levels of triacylglycerol and lipid hydroperoxide were decreased in rats fed the fiber-enriched and fiber- and MSG-enriched diets, whereas levels of total antioxidant substances were increased in these animals. Conclusions: MSG added to a standard diet increased food intake. Overfeeding induced metabolic disorders associated with oxidative stress in the absence of obesity. The fiber-enriched diet prevented changes in glucose, insulin, leptin, and triacylglycerol levels that were seen in the MSG group. Because the deleterious effects of MSG, i.e., induced overfeeding, were not seen in the animals fed the fiber-enriched diets, it can be concluded that fiber supplementation is beneficial by discouraging overfeeding and improving oxidative stress that is induced by an MSG diet. © 2005 Elsevier Inc. All rights reserved.

Bezafibrate for the treatment of hypertriglyceridemia in HIV1-infected patients on highly active antiretroviral therapy

The use of highly active antiretroviral therapy (HAART) in HIV-infected patients has been associated with the development of risk factors for cardiovascular diseases (CD) including dyslipidemia and insulin resistance, hypertriglyceridemia being the most frequent metabolic disturbance in these patients. Fibrates are indicated when hypertriglyceridemia is accentuated and persists for over six months. We evaluated the efficacy and safety of bezafibrate for the treatment of hypertriglyceridemia in HIV-infected individuals on HAART. All patients received 400mg/day of bezafibrate and were evaluated three times: Mo (pre-treatment), M1 (one month after treatment), and M2 (six months after treatment). Fifteen adult individuals, eight males and seven females with mean age = 41.2 ± 7.97 years and triglyceride serum levels ≥400mg/dL were included in the study. Smoking, alcohol ingestion and sedentarism rates were 50%, 6.66% and 60%, respectively. Family history of CD, hypertension and diabetes mellitus was reported in 33.3%, 40% and 46.7% of the cases, respectively, while dyslipidemia was reported by only 13.3%. More than half of the patients were using a protease inhibitor plus a nucleotide analog transcriptase inhibitor. Eutrophy and tendency toward overweight were observed at all three study time points. There were significant reductions in triglyceride serum levels from Mo to M1 and from Mo to M2. No significant changes were observed in the serum levels of creatine phosphokinase, hepatic enzymes, CD4 +, CD8 + and viral load. Therefore, bezafibrate seems to be safe and effective for the reduction of hypertriglyceridemia in HIV-infected patients on HAART. © 2006 by The Brazilian Journal of Infectious Diseases and Contexto Publishing. All rights reserved.

Daytime variations in glucose tolerance in people with impaired glucose tolerance

To determine whether glucose tolerance varies throughout the day in people with impaired glucose tolerance (IGT). We studied 15 healthy IGT, and 18 matched normal glucose tolerant (NGT) individuals. Blood samples were taken every 30-120 min during a 24 h period in which all individuals had three mixed meals and nocturnal sleep. We measured glucose, free fatty acids, specific insulin, intact proinsulin, cortisol and growth hormone. Variable responses were considered as concentrations and areas under the curves. Comparison between the groups was by Student's t-test, Mann-Whitney, and analysis of variance. Higher total glucose response, inappropriate normal total insulin response, and unproportionally increased proinsulin total response were observed in the IGT group. Lower glucose tolerance occurred in IGT after dinner, as in the NGT, and after breakfast associated with increased insulin response after breakfast, and similar proinsulin response after all three meals. IGT had higher glucose response than NGT after breakfast and lunch, similar insulin responses, and increased proinsulin-insulin ratio after all three meals. Data from this study demonstrate that IGT individuals present lower glucose tolerance in the evening, as those with NGT, and in the morning, as reported in patients with type 2 diabetes. © 2006 Elsevier B.V. All rights reserved.

Age related obesity-induced shortening of GLUT4 mRNA poly(A) tail length in rat gastrocnemius skeletal muscle

Obese insulin resistant animals and humans have shown reduced GLUT4 gene expression. Yet, in skeletal muscle, discrepancy between mRNA and protein regulation has been frequently observed, suggesting a post-transcriptional modulation. We investigated the GLUT4 expression in adipose tissue and muscle of obese 12-month-old (12-mo) rats, comparing with lean 2-month-old (2-mo) animals. Obesity was accompanied by insulin resistance, and 65% reduction (P < 0.01) in GLUT4 mRNA and protein in adipose tissue. However, in muscle, despite increased (P < 0.05) mRNA content, GLUT4 protein was unchanged. RNase H and poly(A) test assays showed a reduction (P < 0.01) of ∼80 adenines in the GLUT4 mRNA poly(A) tail of muscle from 12-mo rats, recognizing that the poly(A) tail length correlates with translation efficiency. Concluding, age related obesity of 12-mo rats involves suppression of GLUT4 expression in adipose tissue; however, in muscle, GLUT4 mRNA content increases, but with a shorter poly(A) tail, thus unchanging the protein content. © 2007 Elsevier B.V. All rights reserved.

Metabolic syndrome signs in Wistar rats submitted to different high-fructose ingestion protocols

In search of an adequate model for the human metabolic syndrome, the metabolic characteristics of Wistar rats were analysed after being submitted to different protocols of high fructose ingestion. First, two adult rat groups (aged 90 d) were studied: a control group (C1; n 6) received regular rodent chow (Labina, Purina) and a fructose group (F1; n 6) was fed on regular rodent chow. Fructose was administered as a 10 % solution in drinking water. Second, two adult rat groups (aged 90 d) were evaluated: a control group (C2; n 6) was fed on a balanced diet (AIN-93G) and a fructose group (F2; n 6) was fed on a purified 60 % fructose diet. Finally, two young rat groups (aged 28 d) were analysed: a control group (C3; n 6) was fed on the AIN-93G diet and a fructose group (F3; n 6) was fed on a 60 % fructose diet. After 4-8 weeks, the animals were evaluated. Glucose tolerance, peripheral insulin sensitivity, blood lipid profile and body fat were analysed. In the fructose groups F2 and F3 glucose tolerance and insulin sensitivity were lower, while triacylglycerolaemia was higher than the respective controls C2 and C3 (P < 0.05). Blood total cholesterol, HDL and LDL as well as body fat showed change only in the second protocol. In conclusion, high fructose intake is more effective at producing the signs of the metabolic syndrome in adult than in young Wistar rats. Additionally, diet seems to be a more effective way of fructose administration than drinking water.

Prevention of hypertension in patients with pre-hypertension: Protocol for the PREVER-prevention trial

Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.Methods: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.Discussion: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.Trial Registration: Clinical Trials NCT00970931. © 2011 Fuchs et al; licensee BioMed Central Ltd.

Efeitos terapêuticos da suplementação de L-arginina nas doenças cardiovasculares e endócrino-metabólicas

Nitric oxide is synthesized from L-arginine and plays an important role in blood pressure regulation, platelets aggregation and atherosclerosis development. Most of the studies have shown that the beneficial effects of the L-arginine supplementation are related to an increasing of nitric oxide bioavailability to the cells, improving the endothelial dysfunction, decreasing oxidative stress, ameliorating lipid profile and insulin resistance. However some studies show conflicting results. Considering the role of the endothelium on the pathogenesis of the cardiovascular diseases as well as on the endocrine-metabolic diseases, this review will update studies involving the role of nitric oxide and its signaling pathways in the regulation of vascular function. Furthermore, this review will focus on the main results of the clinical trials using oral L-arginine supplementation, with or without physical exercise, in an attempt to obtain beneficial effects on the cardiovascular and endocrine-metabolic systems in patients and healthy subjects.

Associação do padrão de ingestão lípidica com a qualidade da dieta, resistência insulínica e homocisteinemia em adultos

Objectives: To evaluate the association between the consumption of different dietary fats with the quality of the diet, insulin resistance, and hyperhomocysteinemia in adults. Methods: Cross-sectional study conducted with 624 overweight subjects (73.7% females). Assessments of food intake (24h food recall and health eating index-HEI), anthropometry, and biochemical assays of fasting glucose, insulin (HOMA-IR and β calculus) and homocysteinemia were performed. Results: The low quality of diet was associated with the vegetable oil at 3rd quintile (≥1.5-2.0 servings) showed risk 2.9 times and cholesterol at quintiles 2nd, 3rd, and 4th was 2.0 times. HOMA-IR was higher at 5th quintile of saturated fat (≥10,7% - total caloric value) with risk of 60% and hyperhomocysteinemia the vegetable oil at 3rd quintile (>1.5-2.0 servings) with risk of 12.0 times and 5th (≥3.5 servings) 7.1 times. However, significance disappeared when adjusted for anthropometric variables. Conclusion: Dietary fats were associated with the harm diet quality, insulin resistance, and hyperhomocysteinemia. However, associations are dependant of demographic variables, dietetic, and nutritional state. © 2011 CELOM.

Diet-induced obesity impairs AKT signalling in the retina and causes retinal degeneration

Retinopathy, a common complication of diabetes, is characterized by an unbalanced production of nitric oxide (NO), a process regulated by nitric oxide synthase (NOS). We hypothesized that retinopathy might stem from changes in the insulin receptor substrate (IRS)/PI3K/AKT pathway and/or expression of NOS isoforms. Thus, we analysed the morphology and apoptosis index in retinas of obese rats in whom insulin resistance had been induced by a high-fat diet (HFD). Immunoblotting analysis revealed that the retinal tissue of HFD rats had lower levels of AKT1, eNOS and nNOS protein than those of samples taken from control animals. Furthermore, immunohistochemical analyses indicated higher levels of iNOS and 4-hydroxynonenal and a larger number of apoptotic nuclei in HFD rats. Finally, both the inner and outer retinal layers of HFD rats were thinner than those in their control counterparts. When considered alongside previous results, these patterns suggest two major ways in which HFD might impact animals: direct activity of ingested fatty acids and/or via insulin-resistance-induced changes in intracellular pathways. We discuss these possibilities in further detail and advocate the use of this animal model for further understanding relationships between retinopathy, metabolic syndrome and type 2 diabetes. © 2012 John Wiley & Sons, Ltd.