O acúmulo de tecido adiposo visceral (TAV) está relacionado com a piora da sensibilidade à insulina (SI) e, por isso, tem sido hipotetizado que a retirada de parte deste depósito, lipectomia (L), poderia melhorar este quadro. No entanto, a L pode ocasionar um aumento compensatório ou uma regeneração do tecido retirado. Para investigar se a L e o exercício afetam ou não a SI e a adiposidade, 36 ratos machos Wistar foram submetidos à dieta hiperlipídica e divididos em 4 grupos: LT (treinado), LS (sedentário), FT (falso operado) e FS, sendo submetidos à L e/ou treinamento aeróbio. O peso corporal e consumo de ração foram medidos semanalmente. A glicemia de jejum e tolerância à glicose foram avaliados pré e pós-intervenções. Índice HOMA, adiposidade e expressão gênica (mRNA) PPAR, PPAR e TNF- e expressão protéica do PGC1- foram analisados pós-intervenções. O grupo L apresentou maior consumo de ração após L (p<0,05). Foi verificada pior tolerância à glicose no grupo LS (p<0,03) e diminuída insulina de jejum nos grupos LT e FT (p<0,00). O grupo LT apresentou melhor SI (p<0,04). Não houve diferença na adiposidade dos animais (p>0,1). Os grupos LT e FS apresentaram maior expressão gênica do PPAR no TAV comparados aos LS e FT, já no músculo o LT apresentou menor expressão gênica comparado ao FS (p<0,05). O grupo LS apresentou maior mRNA do TNF- comparado aos demais grupos (p<0,05) e maior expressão protéica de PGC1- que o grupos LT e FS (p<0,05). Nossos resultados demonstram que o treinamento melhorou a ação da insulina e em associação à L melhorou a SI. Além disso, a L ocasionou aumento no consumo de ração que pode ter colaborado com a recuperação da adiposidade neste grupo / Increased visceral adipose tissue (VAT) may account for the impairment in peripheral and hepatic insulin sensitivity (IS). It has been hypothesized that the partial removal of VAT known as lipectomy (L) could result in the improvement, while a re-growth of the excised tissue and/or a compensatory growth of non-excised depots seem to occur. To investigate whether or not VAT removal and exercise affect IS and adiposity 36 male Wistar rats were fed a high-fat diet and assigned to 4 experimental groups: EL (exercised), ES (sham-lipectomized), CL (control-sedentary), and CS; animals were submitted to L and/or exercise training. Body weight and food intake were recorded weekly. Fasting glucose and glucose tolerance were assessed pre and post-interventions. HOMA Index, body fat content, PPAR, PPAR e TNF- mRNA and PGC1- protein expression were assessed post-interventions. L group showed increased food intake post-L (p<0,05). CL group presented worsening on glucose tolerance (p<0,03). ET and ES showed lower fast insulin (p<0,00) and EL group showed better IS (p<0,04). There were no significant difference on body fat (p>0,1). EL and CL groups showed higher PPAR mRNA on VAT compared to CL and ES, EL showed decreased PPAR mRNA on skeletal muscle compared to CS (p<0,05). CL group showed greater TNF- mRNA (p<0,05) and greater PGC1- protein expression compared to EL and CS (p<0,05). Our results showed that short-term swimming training improved insulin action and, in association with L improve IS. Moreover, lipectomy has induced increased food intake which may be related with an increase in adiposity at this group

A hipótese do presente estudo sugere que a baixa fertilidade de vacas Holandesas (Bos taurus) repetidoras de serviço (RS) está relacionada à baixa qualidade oocitária que, por sua vez, é associada ao quadro de resistência periférica a insulina (RPI). Ainda, a indução de lactação (IL) em vacas Holandesas (Bos taurus) RS pode reverter o quadro de RPI e, consequentemente, melhorar a qualidade oocitária e a produção in vitro de embriões (PIVE). Para testar a hipótese proposta, este estudo objetivou avaliar o efeito da fase da lactação e da gestação [Exp. 1], o efeito da secagem de RS [Exp. 2] e o efeito da IL [Exp. 3] sobre a RPI, a qualidade oocitária e a PIVE em vacas da raça Holandesa (Bos taurus). Nos três estudos foram realizados testes de tolerância à glicose (TTG) para avaliar a RPI através do perfil hormonal sérico de insulina e glicose. Além disso, avaliou-se o perfil bioquímico sérico e folicular e a qualidade oocitária através da PIVE. Verificou-se que, em resposta à infusão de 0,3mg glicose/kg PV, as vacas RS no final da lactação secretaram 53% mais insulina e captaram 40% menos de glicose quando comparadas as vacas no terço inicial de lactação (Exp 1). Esses achados são indicativos do estabelecimento do quadro de RPI nas vacas RS em lactação. Durante o período seco, as vacas RS secretaram 96% mais insulina e captaram 56% menos glicose que as vacas no terço inicial da lactação e as vacas RS em lactação, respectivamente (Exp. 2). Ainda, as vacas com lactação induzida secretaram 11% menos insulina e captaram a mesma quantidade de glicose que vacas paridas em fases semelhantes de lactação (Exp 3), demonstrando que o protocolo de IL foi eficiente em alterar o perfil metabólico, revertendo o quadro de RPI presente nas vacas RS. Nos Exp. 1, 2 e 3 foram verificadas maiores concentrações plasmática de triglicérides (TG; P &lt; 0,05), colesterol total (COL; P < 0,05) e LDL (P < 0,05) no soro sanguíneo em vacas RS quando comparadas com vacas no terço inicial de lactação. Durante o período seco (Exp. 2 e 3), observou-se incremento desses metabólitos, destacando aumento na concentração de TG (P < 0,05), COL (P < 0,05) e LDL (P < 0,05) plasmático em vacas secas quando comparadas as vacas em lactação [início e final (RS) da lactação]. No liquido folicular foram observadas variações no perfil bioquímico para COL e TG. Nos Exp. 1, 2 e 3, verificou-se que vacas RS possuem maior concentração de TG (P < 0,05) e COL (P < 0,05) no fluido folicular do que vacas no terço inicial de lactação. Contrariando a hipótese inicialmente proposta, as vacas RS em lactação e as vacas secas apresentaram maior taxa de blastocisto (P < 0,05) e número de blastocistos por OPU (P < 0,05) que as vacas no terço inicial de lactação (Exp. 1, 2 e 3). Através do perfil de insulina circulante em resposta ao TTG foi possível demonstrar o estabelecimento do quadro de RPI em vacas RS (P < 0,05). Além disso, constatou-se agravamento da RPI em vacas secas (P < 0,05). Esse quadro foi associado ao aumento do escore de condição corporal (P < 0,05) e do peso vivo (kg; P < 0,05) nas vacas RS. Em conclusão, não foi verificada associação negativa entre RPI, qualidade oocitária e PIVE em vacas Holandesas (Bos taurus) RS. Apesar da indução de lactação em vacas Holandesas (Bos taurus) RS alterar o metabolismo e diminuir o quadro de RPI, não foi verificado efetivo positivo na qualidade oocitária e na PIVE. / The hypothesis of the present study suggests that low fertility of repeat breeders (RB) Holstein (Bos taurus) cows is related to low oocyte quality, which is associated with peripheral insulin resistance (PIR). Also, induction of lactation (IL) in RB Holstein (Bos taurus) cows can revert PIR and, consequently, improve oocyte quality and in vitro embryo production (IVEP). In order to test the proposed hypothesis, the objective of this study was to evaluate the effect of phase of lactation and gestation [Exp. 1], effect of drying RB [Exp. 2] and effect of IL [Exp. 3] on PIR, oocyte quality and IVEP of Holstein (Bos taurus) cows. In all three studies, glucose tolerance tests (GTT) were performed to evaluate PIR through the serum hormonal insulin and glucose profile. In addition, we evaluated the serum and follicular biochemical profile and oocyte quality through IVEP. It was verified that, in response to a 0.3mg glucose/kg of body weight (BW), RB cows at the end of lactation secreted 53% more insulin and captured 40% less glucose when compared to cows in the initial third of their lactation (Exp. 1). These findings are indicative of the establishment of PIR in RB lactating cows. During the dry period, RB cows secreted 96% more insulin and captured 56% less glucose than cows in the initial third of their lactation and RB lactating cows, respectively (Exp. 2). Also, cows with induced lactation secreted 11% less insulin and captured the same amount of glucose than calved cows in similar lactation phase (Exp. 3), demonstrating that the IL protocol was efficient to alter the metabolic profile, reverting PIR present in RB cows. In Exp. 1, 2 and 3 higher plasmatic concentrations of triglycerides (TG; P<0.05), total cholesterol (COL; P<0.05) and LDL (P<0.05) were verified in the blood serum in RB cows when compared to cows in the initial third of their lactation. During the dry period (Exp. 2 and 3), we observed the increment of these metabolites, and a notable elevation of the plasmatic TG (P < 0.05), COL (P < 0.05) and LDL (P < 0.05) in dry cows when compared to lactating cows [beginning and end (RB) of lactation]. In the follicular fluid, it was possible to observe variations in the biochemical profile for COL and TG. In Exp. 1, 2 and 3, it was verified that RB cows have higher concentration of TG (P < 0.05) and COL (P < 0.05) in the follicular fluid than cows in the initial third of their lactation. Contrary to the initially proposed hypothesis, RB lactating cows and dry cows presented higher blastocyst rate (P<0.05) than cows in the initial third of lactation (Exp. 1, 2 and 3). Through the circulating insulin profile in response to the GTT it was possible to demonstrate the establishment of PIR in RB cows (P<0.05). Also, it was observed worsening of the PIR in dry cows (P<0.05). This condition was associated with an increase in body condition score (P<0.05) and BW (kg; P<0.05) in RB cows. In conclusion, no negative association between PIR, oocyte quality and IVEP was observed in RB Holstein (Bos taurus) cows. Although induction of lactation in RB Holstein (Bos taurus) cows altered the metabolism and reduced PIR, no positive effect was observed in oocyte quality and IVEP.

Introdução: Altas prevalências de diabetes mellitus tipo 2 e outros fatores de risco cardiovascular previamente detectadas na população nipo-brasileira motivaram a implementação de um programa de intervenção em mudança de estilo de vida. Objetivos: Avaliar os efeitos de 2 anos de intervenção comportamental sobre o perfil cardiometabólico desses indivíduos, independente da condição de tolerância à glicose no início do estudo. Métodos: A existência de dados relativos a 2000-2005 permitiu conhecer o comportamento de variáveis no período pré-intervenção. Em 2005, 728 indivíduos iniciaram o seguimento, sendo, 650 reavaliados em 2006 e 500 em 2007. Nestas ocasiões, os indivíduos foram submetidos a exames médico e laboratorial e consulta com nutricionista e educador físico. O programa constou de atendimentos individualizados e em grupo, enfocando as metas do programa: redução 5% de peso corporal; prática de 150minutos/semana de exercício; ingestão de <10% de ácidos graxos saturados do valor calórico total; ingestão de 400g/dia de frutas, verduras ou legumes. Resultados: Comparado ao período pré-intervenção, o comportamento de variáveis antropométricas e metabólicas durante o programa foi significantemente mais favorável. O impacto do programa dependeu do alcance de metas em indivíduos sem diabetes. As frequências de intolerância à glicose e diabetes reduziram após um ano de intervenção (de 58,4% para 35,4%; p<0,001 e de 30,1% para 21,7%; p<0,001, respectivamente). Após excluir os indivíduos com diabetes no início do estudo, 71,7% dos participantes mantiveram ou regrediram seu estado de tolerância à glicose (\"non-progressors\") no final de 2 anos de seguimento. A presença de intolerância à glicose e níveis mais baixos de PCR no início do estudo associaram-se independentemente com a não deterioração da tolerância à glicose, ajustado para idade e variáveis antropométricas. As mudanças em peso e estilo de vida não se associaram com a nãodeterioração da tolerância à glicose após intervenção. Conclusões: A intervenção trouxe benefícios no perfil cardiometabólico de nipo-brasileiros de alto risco cardiovascular após o primeiro e o segundo anos do programa, independente do grau de tolerância à glicose no início do estudo. As mudanças em fatores de risco cardiovascular foram proporcionais ao sucesso no alcance das metas do porgrama. A maioria dos indivíduos sem diabetes manteve ou melhorou a tolerância à glicose após 2 anos de intervenção. Os achados sugerem que níveis mais baixos de PCR e a presença inicial de intolerância à glicose podem ser características preditivas dos indivíduos que se beneficiam desta estratégia de intervenção em termos de não-deterioração do metabolismo da glicose, independente da adiposidade corporal. Esse estudo deve encorajar profissionais da saúde a instituir estratégias simples de intervenção comportamental em grupos populacionais com alto risco cardiometabólico, independente do estado de tolerância à glicose. / Introduction: High prevalence rates of diabetes mellitus type 2 and other cardiovascular risk factors, previously reported in the Japanese-Brazilian population, motivated an intervention program for change in lifestyle. Aims: To evaluate the effect of 2-year behavioral intervention on cardiometabolic profile of these individuals, independent of the glucose tolerance status at the beginning of the study. Methods: The availability of data regarding the period 2000-2005 provided information about the behavior of variables during the pre-intervention period. In 2005, 728 individuals started in the program; 650 were re-examined in 2006 and 500 in 2007. In each occasion, participants were scheduled for laboratory procedures, medical exams and visits with nutritionist and physical educator. Participants were scheduled for individualized dietary counseling and group sessions, focusing the achievement of the goals: 5% weight loss from baseline for individuals with excessive adiposity; 150 minutes/week of physical activities; intake £ 10% of saturated fat of total energy consumed per day; intake of 400g/day of fruits and vegetables. Results: Compared to the pre-intervention period, the changes in metabolic variables induced by the program were significantly more favorable. The impact of the program was dependent on the number of goals achieved in individuals without diabetes at baseline. Prevalence rates of glucose tolerance disturbances decreased after the first year of intervention (from 58.4% to 35.4%, p<0.001; and from 30.1% to 21.7%, p<0.001, respectively). After excluding individuals with diabetes at baseline, 71.7% of participants improved or maintained their glucose tolerance status (non-progressors) after 2-year intervention. Lower levels of CRP and the diagnosis of glucose intolerance at baseline were associated with improvement or maintenance of glucose tolerance status, adjusted age and anthropometric variables. Changes in lifestyle and anthropometric variables after intervention were not associated with non-deterioration of glucose tolerance status. Conclusion: The intervention induced benefits on cardiometabolic profile of the japanese-Brazilians with high cardiovascular risk after the first and second years of the program, independent of the glucose tolerance status at baseline. Most of the participants maintained or improved the glucose tolerance status following the intervention. Our findings suggest that lower levels of CRP and the presence of glucose intolerance at baseline may be predictive characteristics of those who benefit from this intervention strategy regarding non-deterioration of glucose metabolism, independent of body adiposity. This study should encourage health care providers to make efforts to achieve and maintain a healthy diet and physically active lifestyle in subsets of the population at high cardiometabolic risk.

Daily rhythms in physiology and behaviour are orchestrated by theautonomously rhythmic cells of the suprachiasmatic nucleus (SCN).Restricting food intake to the rest phase of nocturnal rodents, leads to thedevelopment of meal anticipatory behaviour, corticosterone and bodytemperature. Given that lesions to the SCN fail to abolish meal anticipation, asecond oscillator of unknown location, referred to as the food-entrainableoscillator (FEO) is thought to exist. Although the site of the FEO is unknown,several hypothalamus nuclei, including the dorsomedial hypothalamus(DMH) are thought to play a role in meal anticipation. Given thatadrenalectomy is reported to abolish meal anticipation, an intact HPA axis isalso thought to contribute to the functioning of the FEO. Some forms ofobesity are characterised by high basal levels of circulating corticosterone. Inaddition, limited access to high fat diet, fails to induce the development ofrobust meal anticipation in rats. During our initial studies, the effect of a standard and 45% high fat diet onthe development of meal anticipatory behaviour and hypothalamic c-Fosexpression were investigated. Restricted access to high fat diet led toattenuation of meal anticipation compared to those fed standard diet. Thiswas concurrent with a failure to develop an anticipatory rise in DMH c-Fosexpression. A meal anticipatory rise in corticosterone is thought to benecessary for the presence of meal anticipation as well as adaptation ofmetabolism to daily restricted feeding. In the next set of studies, weconfirmed that restricted access to standard diet leads to the development ofa meal anticipatory rise in plasma corticosterone. In contrast we observed adramatic post-anticipatory rise in plasma corticosterone in rats givenrestricted access to the 45% high fat diet. We hypothesised that the highcorticosterone levels resulting from high fat diet were a contributing factor tothe lack of meal anticipation in high fat fed rats. With the aid of apharmacokinetic study, a suitable experiment was designed for daily dosingof a potent glucocorticoid receptor antagonist, RU486, with the aim ofrescuing meal anticipation in high fat fed rats. Interestingly, treatment withRU486 successfully rescued meal anticipation in high fat fed rats, butattenuated meal anticipation in standard diet restricted fed rats. In the finalseries of studies the effect of diet and feeding regime on glucose toleranceand metabolism were investigated. High fat feeding was found to reduceglucose tolerance in both ad lib and restricted fed rats, with RU486 treatmentimproving glucose tolerance in a time dependant manner. Restricted accessto food was found to induce post satiation lipogenesis in both standard dietfed and to a lesser extent in high fat fed rats, an effect which may bebeneficial in reducing obesity. Overall the results provide further insight intothe complex role of corticosterone in promoting or preventing mealanticipatory behaviour. An anticipatory rise in plasma corticosterone isrequired for meal anticipation, as repeated daily dosing of RU486 inhibit mealanticipation. The high basal levels of corticosterone in high fat fed rats mayprevent meal anticipation, insulin secretion and post-satiation lipogenesiswhich may in fact be a homeostatic mechanism to prevent obesity. Nonetheless, treatment with RU486 rescues behavioural meal anticipationand glucose tolerance.

Trinta ovelhas, mestiças (Santa Inês X Dorper), adultas e hígidas foram selecionadas para avaliar o efeito da suplementação intramuscular com as vitaminas D e E no perfil bioquímico, metabolismo energético, metabolismo oxidativo, sensibilidade insulínica e imunidade no periparto. Após confirmação da gestação essas fêmeas foram distribuídas em três grupos de dez animais e no 108&deg; dia de gestação receberam veículo oleoso (grupo controle-GC); ou 70.000 UI/kg de P.V. de vitamina D3 (colecalciferol) (grupo tratado-GD); ou 60UI/kg de P.V. de vitamina E (-tocoferol) (grupo tratado-GE). As amostras de sangue foram coletadas previamente à aplicação da vitamina (-45), quatro (-30); e duas semanas (-15) antes do parto; até duas horas do parto (0), uma (7); duas (15); e quatro semanas após o parto (30). Foram analisadas as concentrações plasmáticas de glicose, beta hidroxibutirato (BHB), ácidos graxos não esterificados (AGNEs) e as concentrações séricas de colesterol, triglicérides, ureia, creatinina, cálcio total, cálcio iônico, proteína total, ácido úrico, aspartato amino transferase (AST), gamaglutamil transferase (GGT), e ainda a creatina quinase (CK). Foram também analisadas as concentrações de insulina e cortisol. Do metabolismo oxidativo foram determinadas as atividades da superóxido dismutase (SOD) e glutationa peroxidase (GSH-Px), a habilidade de redução férrica plasmática (HRFP), substâncias reativas ao ácido tiobarbitúrico (TBARS), bem como o status antioxidante total (TAS). Para avaliar aspectos relacionados à imunidade de monócitos e neutrófilos, por método in vitro, em 24 ovelhas (seis de cada tratamento). As amostras de sangue foram coletadas nos momentos 30; 0; e 30 e avaliadas sem estímulo (burst basal) e com estímulo por DCFH-DA, SaPI e PMA. A imunofenotipagem com anticorpos monoclonais CD8, CD4, CD14, CD16, CD45R, WC1, CD206, foi realizada aos dias -30, -15,0,7 e 30. Foram determinadas as concentrações das vitaminas D e E, nos momentos pré-determinados das coletas e no dia do teste de tolerância à glicose (TTG), realizado para avaliar a sensibilidade insulínica, e foi calculado RQUICKI e RQUICKI BHB. Todas as variáveis estudadas apresentaram efeito de tempo. Houve interação tempo*tratamento em TBARS (P=0,0217) e tendência para vitamina E (0,0811), SOD (0,0886) e GSH-Px (P=0,0643). Houve efeito de tratamento no colesterol (P=0,0088) e vitamina D (P<0,0001) e tendência para TAS (P=0,0830). No TTG, com resultados de AUC de BHB e AGNE apresentaram efeito de número de fetos gestados (P=0,0006 e 0,0005 respectivamente) e o RQUICKIBHB mostrou-se melhor indicador de sensibilidade insulínica do que o RQUICKI em ovelhas. A suplementação com vitamina D influenciou os teores plasmáticos de alfa tocoferol e a resposta imune das ovelhas. A suplementação com vitamina E reduziu a peroxidação lipídica no parto e relacionou-se positivamente com a melhora oxidativa dos monócitos sem estímulo e estimulados por PMA. / Thirty healthy adult ewes were selected to evaluate the effect of supplementation with intramuscular vitamins D and E in peripartum period on the biochemical profile, energetic metabolism, oxidative metabolism, insulin sensitivity and immunity. After pregnancy confirmation these females were distributed into three groups of ten animals treated with intramuscular injection containing oily vehicle (control-to-control group) on the 108th day of pregnancy, (CG); or 70,000 IU / kg of body weight of vitamin D3 (cholecalciferol) (treated group-GD); or 60 IU / kg of body weight of vitamin E (-tocopherol) (treated group-GE). Blood samples were collected before the application of the vitamins and vehicle (-45), four (-30); and two weeks (-15) before lambing; until 2 hours of lambing (0); one (7), two (15) and four weeks postpartum (30). Plasma concentrations of glucose, beta hydroxybutyrate (BHB), non-esterified fatty acids (NEFA) and serum concentrations of cholesterol, triglycerides, urea, creatinine, total calcium, ionic calcium, total protein, uric acid, aspartate amino transferase (AST), gammaglutamyl transferase (GGT), and creatine kinase (CK) were measured. The concentrations of insulin and cortisol, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), plasma ferric reduction ability (FRAP), thiobarbituric acid reactive substances (TBARS), as well as total antioxidant status (TAS) were determinate. Monocytes and neutrophils were assessed by in vitro method to identify aspects related to immunity in 24 ewes (six from each treatment) at -30, 0 and 30. Blood samples were evaluated without stimulus (basal burst), with DCFH-DA, SaPI and PMA stimulus. Immunophenotyping with monoclonal antibodies CD8, CD4, CD14, CD16, CD45R, WC1, CD206 were performed at -30, -15, 0, 7 and 30. The concentrations of vitamins D and E were determinate at the predetermined collection times and on the day of the Intravenous Glucose Tolerance Test (IVGTT), realized to evaluate the insulin sensitivity, as well as RQUICKI and RQUICKI BHB. All variables studied showed time effects. There were interaction time * treatment in TBARS (P = 0.0217) and tendency for vitamin E (0.0811), SOD (0.0886) and GSH-Px 16 (P = 0.0643). Treatment effect on cholesterol (P = 0.0088) and vitamin D (P &lt;0.0001) and tendency for TAS (P = 0.0830) were observed. About of IVGTT, AUC results of BHB and AGNE showed number of fetuses effect (P = 0.0006 and 0.0005 respectively). RQUICKIBHB was a better indicator of insulin sensitivity than RQUICKI in ewes. Vitamin D supplementation influenced the plasma levels of alpha tocopherol and the immune response of ewes. Vitamin E supplementation reduced lipid peroxidation at parturition and was positively related to the oxidative improvement of the monocytes without stimulation and stimulated by PMA. High doses of vitamins D or E administered 45 days before parturition on healthy ewes can be beneficial; however more studies are needed about this topic.

The development of type 2 diabetes over time involves defects in insulin action and insulin secretion. Defects in insulin action alone can be compensated with appropriate hyperinsulinemia. However, the progressive loss of pancreatic beta-cell function leads eventually to the development of persistent hyperglycemia that characterizes type 2 diabetes. Insulin secretion patterns reflect two phases when beta-cells are exposed to acute and sustained glucose stimulation. Through the study and understanding of the roles of these two phases in the regulation of glucose homeostasis, it is clear that insulin must not only be secreted in sufficient amounts, but also at the right time. In type 2 diabetes, the timing and magnitude of insulin secretion are altered, and an abnormal first-phase release initiates before the onset of the disease. Only a few pharmacokinetic/pharmacodynamic (PK/PD) models have considered the biphasic nature of insulin secretion. This study is aimed at describing the biphasic dynamics of insulin secretion through developing a PK/PD model based on current knowledge of the cellular mechanism of biphasic insulin secretion. The objectives of this work are to 1) evaluate the insulin-glucose kinetics using nonparametric analysis, 2) develop a physiologically based mechanistic PK/PD model to dynamically describe the biphasic insulin secretion, 3) evaluate the impact of ethnicity on insulin secretion kinetics following an intravenous glucose administration using population analysis and 4) extend the proposed model to oral glucose administration and utilize the co-secretion kinetics of insulin and C-peptide in a population PK/PD analysis of the prehepatic insulin secretion. Population analysis was done using a nonlinear mixed-effects model combined with the proposed PK/PD model to estimate population parameters and their variations between- and within-subjects and the covariates' effects on model parameters. The proposed model describes biphasic insulin behavior, accounts for first-phase insulin secretion, and also applies to oral glucose administration for estimating prehepatic insulin secretion in vivo and in liver extraction. This is done by an analysis that simultaneously uses plasma insulin and C-peptide concentrations. A significant higher first-phase insulin secretion was identified in healthy youths of African-American compared to Caucasians. The analysis showed no significant differences in the clearance of insulin from the plasma and the liver extraction of insulin between subjects with various levels of glucose tolerance. Obesity leads to a higher insulin production rate and lower elimination rate from the plasma than normal weight subjects. Also, type 2 diabetes and impaired glucose tolerance were found to reduce insulin production rate and resulted in a delayed insulin secretion from the beta-cells.

<p>The appropriateness of universal screening for gestational diabetes mellitus (GDM) has been strongly questioned, since it does not satisfy ethical principles for screening. </p><p> The aims of these studies were to determine the prevalence of GDM, expressed in terms of impaired glucose tolerance (IGT) and diabetes mellitus (DM), to evaluate different screening models using traditional anamnestic risk factors and repeated random B-glucose, to determine whether GDM increases risks for maternal complications such as preeclampsia, and to determine whether IGT during pregnancy, if left untreated, is associated with increased maternal or neonatal morbidity. </p><p> Of 4,918 pregnant non-diabetic women attending maternal health care, 73.5% agreed to have a 75 g oral glucose tolerance test (OGTT). GDM was diagnosed in 1.7%, IGT in 1.3% and DM in 0.4%. Traditional risk factor criteria were fulfilled by 15.8%. Prior GDM and a prior macrosomic infant showed the highest association with GDM. No selective or two-step universal screening model would have detected all cases of GDM. A constructed model comprising prior GDM, a prior LGA/macrosomic infant, or a cut-off random B-glucose level of 8 mmol/l as an indication for OGTT reduced the need for OGTT to 7.3% compared to the selective screening model with traditional risk factors. Such a universal two-step screening model had 100% sensitivity for DM, and 44.7% sensitivity for IGT.</p><p> The Swedish Medical Birth Register was used to evaluate GDM as risk factor for preeclampsia. GDM occurred in 0.8% and preeclampsia in 2.9% of 430,852 singleton pregnancies. There is an independent and significant association between GDM and preeclampsia. Obesity is a major confounding factor, but cannot explain the total excess risk. </p><p> In a prospective population-based case-control study 213 women with untreated IGT during pregnancy were identified. For each case, four controls were recruited from the same delivery department. The analyses confirmed that maternal and fetal morbidity were increased in the cases in terms of cesarean section rate, pre-term delivery, Erb’s palsy and admission to NICU. There was a marked, independent increase in the proportion of LGA infants (OR 7.3; 95% CI 4.1-12.7). To determine whether treatment has an effect when IGT is diagnosed during pregnancy, a randomized study is required.</p>

The appropriateness of universal screening for gestational diabetes mellitus (GDM) has been strongly questioned, since it does not satisfy ethical principles for screening. The aims of these studies were to determine the prevalence of GDM, expressed in terms of impaired glucose tolerance (IGT) and diabetes mellitus (DM), to evaluate different screening models using traditional anamnestic risk factors and repeated random B-glucose, to determine whether GDM increases risks for maternal complications such as preeclampsia, and to determine whether IGT during pregnancy, if left untreated, is associated with increased maternal or neonatal morbidity. Of 4,918 pregnant non-diabetic women attending maternal health care, 73.5% agreed to have a 75 g oral glucose tolerance test (OGTT). GDM was diagnosed in 1.7%, IGT in 1.3% and DM in 0.4%. Traditional risk factor criteria were fulfilled by 15.8%. Prior GDM and a prior macrosomic infant showed the highest association with GDM. No selective or two-step universal screening model would have detected all cases of GDM. A constructed model comprising prior GDM, a prior LGA/macrosomic infant, or a cut-off random B-glucose level of 8 mmol/l as an indication for OGTT reduced the need for OGTT to 7.3% compared to the selective screening model with traditional risk factors. Such a universal two-step screening model had 100% sensitivity for DM, and 44.7% sensitivity for IGT. The Swedish Medical Birth Register was used to evaluate GDM as risk factor for preeclampsia. GDM occurred in 0.8% and preeclampsia in 2.9% of 430,852 singleton pregnancies. There is an independent and significant association between GDM and preeclampsia. Obesity is a major confounding factor, but cannot explain the total excess risk. In a prospective population-based case-control study 213 women with untreated IGT during pregnancy were identified. For each case, four controls were recruited from the same delivery department. The analyses confirmed that maternal and fetal morbidity were increased in the cases in terms of cesarean section rate, pre-term delivery, Erb’s palsy and admission to NICU. There was a marked, independent increase in the proportion of LGA infants (OR 7.3; 95% CI 4.1-12.7). To determine whether treatment has an effect when IGT is diagnosed during pregnancy, a randomized study is required.

Diabetes typ 2 ökar i hela världen, beräkningar har visat att prevalensen troligen kommer att öka till det dubbla år 2030. Att identifiera och behandla patienter som riskerar att utveckla sjukdomen är angeläget då personer med diabetes typ 2 löper ökad risk för att få komplikationer och andra sjukdomstillstånd som leder till stort lidande och förtida död. Syftet med denna litteraturstudie var att utifrån distriktssköterskans ansvarsområde beskriva primärpreventiva åtgärder och dess effekter för att förebygga diabetes typ 2 hos personer med nedsatt glukostolerans. En litteraturstudie med analys av 14 vetenskapliga artiklar genomfördes och resultatet visade att studier som innehöll både kost och motionsintervention inklusive individuell eller gruppbaserad rådgivning hade goda långtidseffekter på riskfaktorerna för insjuknande av diabetes typ 2. Patienter med nedsatt glukostolerans har behov av stöd för att förändra sina levnadsvanor i strävan mot att förebygga eller skjuta upp insjuknande i diabetes typ 2.

INTRODUCTION/OBJECTIVES: Current screening guidelines for pre-diabetes and type 2 diabetes mellitus note that there are discrepancies in diagnosing the disease using the fasting plasma glucose test, oral glucose tolerance test, and HbA1c in high-risk populations. The objective of this study is to compare the effectiveness of screening methods for type 2 diabetes mellitus (T2DM) and pre-diabetes by race/ethnicity and gender. METHODS: Secondary analyses of the National Health and Nutrition Examination Survey (NHANES, 2005-2008) were performed using SPSS 19.0. Screening outcomes were assessed and compared for a sample of n=10,566, NHW, NHB, MA, and Multiracial/other men and women. Analyses included cross tabulations, ANOVA and partial correlations to establish disease prevalence, effectiveness of screenings, and statistical significance. RESULTS: It was found that the HbA1c test is comparable in precision, and is correlated with the FPG for racial and ethnic minorities. The specificities for detecting pre-diabetes using the HbA1c were higher (64-66%) for these groups than by using the standard, FPG screening method (42-49%). There were no strong, significant differences for screening effectiveness for men versus women. DISCUSSION: This study revealed that the HbA1c test might be an effective method for screening for pre-diabetes in racial and ethnic minorities instead of the FPG test alone. Screening in high-risk populations will help delay the onset of T2DM, with increased prevention during the pre-clinical phase.