Dietary omega-3 fatty acid and omega-3: omega-6 fatty acid ratio predict improvement in glucose disturbances in Japanese Brazilians

Objective: We investigated whether lifestyle-induced changes in dietary fat quality are related to Improvements on glucose metabolism disturbances in Japanese Brazilians at high risk of type 2 diabetes Methods: One hundred forty-eight first- and second-generation subjects with impaired glucose tolerance or impaired fasting glycemia who attended a lifestyle intervention program for 12 mo were studied in the city of Bauru. State of Sao Paulo, Brazil Dietary fatty acid intakes at baseline and after 12 mo were estimated using three 24-h recalls. The effect of dietary fat intake on glucose metabolism was investigated by multiple logistic regression models Results: At baseline, mean standard deviation age and body mass index were 60 II y and 25 5 4.2 kg/m2, respectively After 12 mo. 92 subjects had normal plasma glucose levels and 56 remained in prediabetic conditions. Using logistic regression models adjusted for age, gender, generation, basal intake of explanatory nutrient, energy intake, physical activity, and waist circumference, the odds ratios (95% confidence intervals) for reversion to normoglycemia were 3 14 (1 22-8 10) in the second wrote of total w-3 fatty acid, 4 26 (1.34-13 57) in the second tunic of eicosapentaenoic acid, and 280 (1 10-7.10) in the second tertile of linolenic acid. Similarly. subjects in the highest wrote of w-3.w-6 fatty acid ratio showed a higher chance of improving glucose disturbances (2 51, 1.01-6.37) Conclusions: Our findings support the evidence of an independent protective effect of omega-3 fatty acid and of a higher omega-3:omega-6 fatty acid ratio on the glucose metabolism of high-risk individuals (C) 2010 Elsevier Inc All rights reserved.

Na+-glucose transporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: Involvement of hepatocyte nuclear factor-1 alpha expression and activity

Mutations in Na+-glucose transporters (SGLT)-2 and hepatocyte nuclear factor (HNF)-1 alpha genes have been related to renal glycosuria and maturity-onset diabetes of the young 3, respectively. However, the expression of these genes have not been investigated in type 1 and type 2 diabetes. Here in kidney of diabetic rats, we tested the hypotheses that SGLT2 mRNA expression is altered; HNF-1 alpha is involved in this regulation; and glycemic homeostasis is a related mechanism. The in vivo binding of HNF-1 alpha into the SGLT2 promoter region in renal cortex was confirmed by chromatin immunoprecipitation assay. SGLT2 and HNF-1 alpha mRNA expression (by Northern and RT-PCR analysis) and HNF-1 binding activity of nuclear proteins (by EMSA) were investigated in diabetic rats and treated or not with insulin or phlorizin (an inhibitor of SGLT2). Results showed that diabetes increases SGLT2 and HNF-1 alpha mRNA expression (similar to 50%) and binding of nuclear proteins to a HNF-1 consensus motif (similar to 100%). Six days of insulin or phlorizin treatment restores these parameters to nondiabetic-rat levels. Moreover, both treatments similarly reduced glycemia, despite the differences in plasma insulin and urinary glucose concentrations, highlighting the plasma glucose levels as involved in the observed modulations. This study shows that SGLT2 mRNA expression and HNF-1 alpha expression and activity correlate positively in kidney of diabetic rats. It also shows that diabetes-induced changes are reversed by lowering glycemia, independently of insulinemia. Our demonstration that HNF-1 alpha binds DNA that encodes SGLT2 supports the hypothesis that HNF-1 alpha, as a modulator of SGLT2 expression, may be involved in diabetic kidney disease.

Lipid and glucose metabolism of broilers (Gallus gallus domesticus) experimentally infected with Eimeria acervulina Tyzzer, 1929 oocysts

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

Decrease in circulating glucose, insulin and leptin levels and improvement in insulin resistance at 1 and 3 months after gastric bypass

Background: Hyperglycemia, insulin resistance and hyperleptinemia are some of the consequences of obesity. Gastric bypass for morbid obesity provides gastric restriction with decreased energy absorption. To confirm and extend previous reports in the literature, We evaluated the plasma glucose, serum insulin and leptin and insulin resistance of patients preoperatively and 1 and 3 months after Roux-en-Y gastric bypass (RYGBP).Methods: We determined body mass index (BMI), plasma glucose (glucose-oxidase method), serum leptin (immunoassay) and insulin (chemiluminescent immunometric assay), and insulin resistance index (IRI) by Homeostasis Model Assessment (HOMA) of 20 patients with morbid obesity both preoperatively and 1 and 3 months after RYGBP.Results: Patients showed a mean decrease in weight of 8 kg/month. Glycemia was above reference levels in 65% of the preoperative patients but dropped significantly 1 month postoperatively, serum insulin and leptin levels and the HOMA index also decreasing significantly in the same period. The percentage of patients with preoperative elevated serum insulin and leptin relative to reference levels decreased significantly following RYGBP. We also observed a weak but significant correlation between BMI and glucose, BMI and insulin, and leptin and insulin.Conclusions: the beneficial effects of bariatric surgery are already noticeable 1 month postoperatively, the reduction in insulin levels being more important for leptin reduction than decreased BMI. Leptin appeared to be subject to multifactorial control and showed a larger reduction than body weight.

Demographic and metabolic characteristics of individuals with progressive glucose tolerance

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

INTERACTION AMONG ZINC, GLUCOSE, AND INSULIN IN NORMAL INDIVIDUALS DURING GLUCOSE AND TOLBUTAMIDE PERFUSION

Reports in the literature have shown that acute or chronic zinc administration may cause hyperglycemia, with a fall in serum or insular insulin occurring in experimental animals. on the other hand, under conditions of both acute and chronic hyperglycemia, an increase, a decrease, or a normal level of blood zinc has been observed in studies conducted on humans. Thus, the objective of the investigation described here was to determine the relationship existing among zinc, glucose, and insulin under acute conditions. Thirty-six subjects of both sexes (mean age, 23 yr) were tested at 7:00 A.M. after a 12-h fast. Two antecubital veins of both forearms were punctured and maintained with physiological saline. Three experiments were performed in which zinc was administered orally, and hypertonic glucose and tolbutamid were administered intravenously. Blood samples were then collected over a period ranging from 93 to 240 min after the basal times of - 30 and 0 min. Hyperzincemia did not cause changes in plasma glucose or insulin either in the absence of or during perfusion of glucose. Hyperglycemia, hypoglycemia, and hyperinsulinemia did not modify serum zinc levels. These results demonstrate that acute zinc administration did not change carbohydrate metabolism and that sudden variations in glucose and insulin levels did not modify the serum profile of zinc.

Dietary macronutrients and performance and plasma hormone and metabolite levels of broiler chickens fat by carbohydrate substitution

The present experiment was aimed to study the effects of an isocaloric substitution of fat by carbohydrate calories while maintaining the same CP content - on some endocrine parameters and key metabolites of the lipid (L), protein (CP) and carbohydrate (CHO) metabolism and muscle cell membrane integrity of broiler chickens. Ninety male broiler chicks (Cobb) were obtained at 1-day old and raised in an environmentally controlled room. Food and water was provided ad libitum. At day 7, the chicks were provided with the experimental diets: Control diet (CON: 20% CP; 9.1% L; 39.6% CHO), Low lipid diet (LowL: 22% CP; 3.36% L; 59.7% CHO), and low carbohydrate diet (LowCHO: 22% CP; 8.09% L; 46.7% CHO). T e chickens fed the CON manifested the best growth rate feed conversion compared to both other groups. The CO chickens showed the highest plasma T-3 Concentrations at 14 days of age as compared to both LowL and LowCHO chickens. At 35 days of age however, LowL chickens were characterized by the highest plasma T-3 levels. Overall, CON birds had the highest plasma T-4 levels (P < 0.0001) compared to LowL and LowCHO chickens. Plasma corticosterone levels were not affected by diet composition. Glucose levels increased towards the end of the experimental period, but there was no overall effect of diet composition on plasma glucose levels. Chickens fed the CON diet were consistently characterized by the highest plasma uric acid levels compared to LowL and LowCHO chickens. Irrespectively of diet, plasma triglyceride levels were high at 14 days of age, then decreased and finally increased again during the last week. This latter increase was most pronounced for the CON chickens and is congruous with their high fat deposition. At 28 days of age, a significant effect of diet was observed, as CON birds had lower plasma free fatty acid (FFA) levels compared to LowL but not to LowCHO chickens. However there was no overall effect of diet composition on plasma FFA levels. Creatine kinase (CK) activities increased significantly with age and were consistently higher in CON chickens. In conclusion, fast growth in broiler chickens is positively correlated with catabolism of protein from dietary or endogenous origin and (muscle) cell membrane disruption as reflected in high plasma uric acid levels and CK activity, respectively. The currently investigated substitution of fat by CHO had no marked effects on endocrine functioning and intermediary metabolism, but this does not exclude that larger substitutions between both nutrients can have an effect.

Brazilian individuals with impaired glucose tolerance are characterized by impaired insulin secretion

Background: To better understand the pathogenesis of type 2 diabetes mellitus, insulin secretion and insulin sensitivity (IS) were evaluated in white Brazilians with impaired glucose tolerance (IGT), using the oral glucose tolerance test (OGTT) and the hyperglycemic clamp technique.Methods: Twenty-five IGT subjects were individually matched with normal glucose-tolerant (NGT) subjects for demographic characteristics, At first, they were submitted to the OGTT and plasma glucose and insulin were measured. of the 25 pairs, 20 could participate in the hyperglycemic clamp procedures, at a second visit. All participants had their plasma glucose levels equally increased to 180 mg/dl; this was maintained for three hours by variable glucose infusion. During the procedure, plasma glucose and insulin were measured at established intervals.Results: In the postabsorptive state, the IGT subjects presented higher levels of plasma glucose, blood HbA(1) and serum triglycerides, but similar plasma insulin levels. After the oral glucose load, early and total insulin release, in relation to glucose levels, were respectively, 43 and 67% lower in the IGT individuals, the index of whole-body IS was increased in the IGT individuals (4.36 +/- 1.71 vs 3.61 +/- 1.28 mg(-1).muU(-1) 100.ml(2); p < 0.05). By the hyperglycemic clamp technique first- (82 &PLUSMN; 26 vs 215 &PLUSMN; 88 μU/ml; p < 0.001) and second- (36 +/- 19 vs 73 +/- 44 muU/ml; p < 0.05) phases of insulin secretion was decreased in the IGT individuals, especially the first one. However, the groups did not differ in relation to the IS: IGT = 13.52 &PLUSMN; 7.27 and NGT = 9.96 &PLUSMN; 6.70 mg.ml/kg.μU.min(-1); p > 0.05. Functional relationship of IS (y) on first-phase insulin release (x) showed a smaller (p < 0,05) regression coefficient for the IGT group.Conclusion: Brazilians with IGT well-matched with NGT ones were characterized by impaired first- and second-phase insulin secretion (mainly the former), while defects in IS were not evident.

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.

Effects of glucose infusion on the endocrine, metabolic and cardiorespiratory responses to halothane anaesthesia of ponies

Glucose was infused intravenously into six ponies during halothane anaesthesia, to evaluate its effect on their endocrine response to anaesthesia. The ponies were premedicated with acepromazine, and anaesthesia was induced with thiopentone and maintained with halothane in oxygen for two hours. Glucose was infused to maintain the plasma glucose concentration above 20 mmol/litre. Anaesthesia was associated with hypothermia, a decrease in haematocrit, hypotension, hyperoxaemia, respiratory acidosis and an increase in the plasma concentrations of lactate and arginine vasopressin. The concentration of β-endorphin in plasma increased transiently after 20 minutes but there were no changes in concentrations of adrenocorticotrophic hormone, dynorphin, cortisol or catecholamines. These data suggest that the glucose infusion attenuated the normal adrenal response of ponies to halothane anaesthesia.

Glycogen storage and muscle glucose transporters (GLUT-4) of mice selectively bred for high voluntary wheel running

To examine the evolution of endurance-exercise behaviour, we have selectively bred four replicate lines of laboratory mice (Mus domesticus) for high voluntary wheel running ('high runner' or HR lines), while also maintaining four non-selected control (C) lines. By generation 16, HR mice ran ∼2.7-fold more than C mice, mainly by running faster (especially in females), a differential maintained through subsequent generations, suggesting an evolutionary limit of unknown origin. We hypothesized that HR mice would have higher glycogen levels before nightly running, show greater depletion of those depots during their more intense wheel running, and have increased glycogen synthase activity and GLUT-4 protein in skeletal muscle. We sampled females from generation 35 at three times (photophase 07:00 h-19:00 h) during days 5-6 of wheel access, as in the routine selection protocol: Group 1, day 5, 16:00 h-17:30 h, wheels blocked from 13:00 h; Group 2, day 6, 02:00 h-03:30 h (immediately after peak running); and Group 3, day 6, 07:00 h-08:30 h. An additional Group 4, sampled 16:00 h-17:30 h, never had wheels. HR individuals with the mini-muscle phenotype (50% reduced hindlimb muscle mass) were distinguished for statistical analyses comparing C, HR normal, and HR mini. HR mini ran more than HR normal, and at higher speeds, which might explain why they have been favored by the selective-breeding protocol. Plasma glucose was higher in Group 1 than in Group 4, indicating a training effect (phenotypic plasticity). Without wheels, no differences in gastrocnemius GLUT-4 were observed. After 5 days with wheels, all mice showed elevated GLUT-4, but HR normal and mini were 2.5-fold higher than C. At all times and irrespective of wheel access, HR mini showed approximately three-fold higher [glycogen] in gastrocnemius and altered glycogen synthase activity. HR mini also showed elevated glycogen in soleus when sampled during peak running. All mice showed some glycogen depletion during nightly wheel running, in muscles and/or liver, but the magnitude of this depletion was not large and hence does not seem to be limiting to the evolution of even-higher wheel running.

Eimeria stiedai: Metabolism of lipids, proteins and glucose in experimentally infected rabbits, Oryctolagus cuniculus

Rabbits were experimentally infected with sporulated Eimeria stiedai oocysts. A total of 50 white adult rabbits, New Zealand race, were distributed into two groups: Group A was infected with 1x10 4 sporulated Eimeria stiedai oocysts, while group B was inoculated with distilled water as a control. The animals generally displayed increased levels of total protein, globulin, total cholesterol, LDL-c and triacylglycerols; however, total levels of liver lipids and HDL-c decreased, and plasma glucose levels varied during the experimental period. In sum, Eimeria stiedai infection of rabbits caused a considerable number of changes in the metabolism of lipids, proteins and glucose, which is likely due to direct effects of liver cirrhosis on normal body function.

Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice

De Angelis K, Senador DD, Mostarda C, Irigoyen MC, Morris M. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice. Am J Physiol Regul Integr Comp Physiol 302: R950-R957, 2012. First published February 8, 2012; doi: 10.1152/ajpregu.00450.2011.-Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 +/- 2 and F60: 118 +/- 2 mmHg) and dark periods (F15: 136 +/- 4 and F60: 136 +/- 5 mmHg) compared with controls (light: 111 +/- 2 and dark: 117 +/- 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.

BNP and Admission Glucose as In-Hospital Mortality Predictors in Non-ST Elevation Myocardial Infarction

Objectives. Admission hyperglycemia and B-type natriuretic peptide (BNP) are associated with mortality in acute coronary syndromes, but no study compares their prediction in-hospital death. Methods. Patients with non-ST-elevation myocardial infarction (NSTEMI), in-hospital mortality and two-year mortality or readmission were compared for area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) of glycemia and BNP. Results. Respectively, AUC, SEN, SPE, PPV, NPV, and ACC for prediction of in-hospital mortality were 0.815, 71.4%, 84.3%, 26.3%, 97.4%, and 83.3% for glycemia = 200 mg/dL and 0.748, 71.4%, 68.5%, 15.2%, 96.8% and 68.7% for BNP = 300 pg/mL. AUC of glycemia was similar to BNP (P = 0.411). In multivariate analysis we found glycemia >= 200mg/dL related to in-hospital death (P = 0.004). No difference was found in two-year mortality or readmission in BNP or hyperglycemic subgroups. Conclusion. Hyperglycemia was an independent risk factor for in-hospital mortality in NSTEMI and had a good ROC curve level. Hyperglycemia and BNP, although poor in-hospital predictors of unfavorable events, were independent risk factors for death or length of stay >10 days. No relation was found between hyperglycemia or BNP and long-term events.

Lipid and glucose profiles of dairy buffaloes during lactation and dry period

The purpose of this study was to analyze the influence of lactation and dry period in the constituents of lipid and glucose metabolism of buffaloes. One hundred forty-seven samples of serum and plasma were collected between November 2009 and July 2010, from properties raising Murrah, Mediterranean and crossbred buffaloes, located in the State of Sao Paulo, Brazil. Biochemical analysis was obtained by determining the contents of serum cholesterol, triglycerides, beta-hydroxybutyrate (β-HBO), non-esterified fatty acids (NEFA) and plasma glucose. Values for arithmetic mean and standard error mean were calculated using the SAS procedure, version 9.2. Tests for normality of residuals and homogeneity of variances were performed using the SAS Guide Data Analysis. Data were analyzed by ANOVA using the SAS procedure Glimmix. The group information (Lactation), Farm and Age were used in the statistical models. Means of groups were compared using Least Square Means (LSMeans) of SAS, where significant difference was observed at P ≤ 0.05. It was possible to conclude that buffaloes during peak lactation need to metabolize body reserves to supplement the lower amounts of bloodstream lipids, when they remain in negative energy balance. In the dry period, there were significant changes in the lipid profile, characterized by decrease of nutritional requirements, with consequent improvement in the general conditions of the animals.