<p>The glycaemic responses to various carbohydrate-rich foods are partly dependent on the rate at which the carbohydrate is digested and absorbed. The glycaemic index (GI) is a way of ranking foods according to their glycaemic response and is recommended as a useful tool in identifying starch-rich foods that give the most favourable glycaemic response. This investigation was undertaken to determine whether carbohydrate-rich foods with a low GI and a high content of dietary fibre (DF) could have beneficial metabolic effects in the insulin resistance syndrome. This question was addressed both in single-meal studies and in randomised controlled clinical trials. Starch-rich foods with low GI values incorporated into composite meals resulted in lower postprandial responses of both glucose and insulin than foods with a high GI in meals with an identical macronutrient and DF composition, in subjects with type 2 diabetes. After three weeks on a diet including low GI starchy foods metabolic profile was improved in subjects with type 2 diabetes, compared with a corresponding high GI diet. The glucose and insulin responses throughout the day were lower, the total and low density lipoprotein cholesterol was decreased, and the fibrinolytic activity was normalised. In subjects with impaired insulin sensitivity and diabetes low GI foods rich in soluble DF for breakfast gave a more favourable metabolic profile, with smaller glucose fluctuations from baseline during the day, than a breakfast with high GI foods low in DF. A low GI breakfast high in DF also resulted in lower responses of insulin and C-peptide after breakfast and a lower triacylglycerol response after a standardised lunch. However, none of the tested breakfasts improved the glucose and insulin responses after lunch. Similar results were obtained in obese subjects after including a breakfast with a low GI high in soluble DF for a period of four weeks in comparison with a breakfast with a high GI and low content of DF.</p><p>These results support the therapeutic potential of a diet with a low GI in the treatment of diabetes and also in the treatment of several of the metabolic disturbances related to the insulin resistance syndrome.</p>

This work has tried to provide better insight in some pathophysiological factors involved in functional dyspepsia. We have identified several experimental evidences supporting the hypothesis that activation of transducers of wall tension at the level the proximal stomach might be the key to the genesis of at least some of the symptoms. One of the mechanisms by which this activation may be enhanced in patients is the presence of defective accommodation of the proximal stomach in response to a meal. This abnormality was present in a large subgroup of patients and was associated to the presence of early satiety. Pharmacological modulation of the gastric wall tension resulted in concomitant changes in symptom severity, both in health and in functional dyspepsia patients. Special attention has been given to provide the clinician with better tools to investigate his patient, in the perspective of the prescription of a treatment aimed at restoring a defective mechanism. / Ce travail a tenté d'améliorer la compréhension de certains mécanismes physiopathologiques de la dyspepsie fonctionnelle. Nous avons identifié plusieurs arguments expérimentaux soutenant l'hypothèse disant que c'est l'activation de mécanorécepteurs sensibles à la tension pariétale qui est reponsable d'au moins un des symptômes de l'affection. Un des mécanismes par lesquels cette activation peut accrue chez les patients est la présence d'un défaut de l'accommodation gastrique post-prandiale. Cette anomalie a été retrouvée dans une large proportion des patients et est associée à la présence de satiété précoce. Les modifications du tonus gastrique ont résulté dans de modifications concomitantes des symptômes aussi bien chez les volontaires que chez les patients atteints de dyspepsie fonctionnelle.Une attention particulière a été portée sur le développement de nouveaux outils permettant de caractériser les patients dans la perspective de la prescription d'un traitement visant à corriger un mécanisme défectueux.

This work has tried to provide better insight in some pathophysiological factors involved in functional dyspepsia. We have identified several experimental evidences supporting the hypothesis that activation of transducers of wall tension at the level the proximal stomach might be the key to the genesis of at least some of the symptoms. One of the mechanisms by which this activation may be enhanced in patients is the presence of defective accommodation of the proximal stomach in response to a meal. This abnormality was present in a large subgroup of patients and was associated to the presence of early satiety. Pharmacological modulation of the gastric wall tension resulted in concomitant changes in symptom severity, both in health and in functional dyspepsia patients. Special attention has been given to provide the clinician with better tools to investigate his patient, in the perspective of the prescription of a treatment aimed at restoring a defective mechanism. / Ce travail a tenté d'améliorer la compréhension de certains mécanismes physiopathologiques de la dyspepsie fonctionnelle. Nous avons identifié plusieurs arguments expérimentaux soutenant l'hypothèse disant que c'est l'activation de mécanorécepteurs sensibles à la tension pariétale qui est reponsable d'au moins un des symptômes de l'affection. Un des mécanismes par lesquels cette activation peut accrue chez les patients est la présence d'un défaut de l'accommodation gastrique post-prandiale. Cette anomalie a été retrouvée dans une large proportion des patients et est associée à la présence de satiété précoce. Les modifications du tonus gastrique ont résulté dans de modifications concomitantes des symptômes aussi bien chez les volontaires que chez les patients atteints de dyspepsie fonctionnelle.Une attention particulière a été portée sur le développement de nouveaux outils permettant de caractériser les patients dans la perspective de la prescription d'un traitement visant à corriger un mécanisme défectueux.

The glycaemic responses to various carbohydrate-rich foods are partly dependent on the rate at which the carbohydrate is digested and absorbed. The glycaemic index (GI) is a way of ranking foods according to their glycaemic response and is recommended as a useful tool in identifying starch-rich foods that give the most favourable glycaemic response. This investigation was undertaken to determine whether carbohydrate-rich foods with a low GI and a high content of dietary fibre (DF) could have beneficial metabolic effects in the insulin resistance syndrome. This question was addressed both in single-meal studies and in randomised controlled clinical trials. Starch-rich foods with low GI values incorporated into composite meals resulted in lower postprandial responses of both glucose and insulin than foods with a high GI in meals with an identical macronutrient and DF composition, in subjects with type 2 diabetes. After three weeks on a diet including low GI starchy foods metabolic profile was improved in subjects with type 2 diabetes, compared with a corresponding high GI diet. The glucose and insulin responses throughout the day were lower, the total and low density lipoprotein cholesterol was decreased, and the fibrinolytic activity was normalised. In subjects with impaired insulin sensitivity and diabetes low GI foods rich in soluble DF for breakfast gave a more favourable metabolic profile, with smaller glucose fluctuations from baseline during the day, than a breakfast with high GI foods low in DF. A low GI breakfast high in DF also resulted in lower responses of insulin and C-peptide after breakfast and a lower triacylglycerol response after a standardised lunch. However, none of the tested breakfasts improved the glucose and insulin responses after lunch. Similar results were obtained in obese subjects after including a breakfast with a low GI high in soluble DF for a period of four weeks in comparison with a breakfast with a high GI and low content of DF. These results support the therapeutic potential of a diet with a low GI in the treatment of diabetes and also in the treatment of several of the metabolic disturbances related to the insulin resistance syndrome.

Thesis (Ph. D.)--University of Oklahoma. / Includes bibliographical references (leaves 148-162).

Adiponectin is an adipose-derived protein (adipocytokine) that is secreted by adipose tissue. It has insulin-sensitizing, anti-inflammatory and cardio-protective properties, and is thought to be protective against obesity-related diseases such as type 2 diabetes. Humans and cats are two species that commonly develop type 2 diabetes associated with insulin resistance, impaired beta cell function and spontaneous islet amyloid deposition. The domestic cat (Felis catus) has recently been proposed as an animal model for human type 2 diabetes. However, little is known about the physiology of adiponectin in cats. Therefore, we set out to investigate the association of adiponectin profiles with dietary carbohydrate intake, feeding, body weight, fat mass, and insulin sensitivity in healthy young adult cats (n=32; 2-4 years old; gender ratio 1:1; body condition 4-5/9). Cats were fed a moderate carbohydrate diet (37% ME) at maintenance energy requirements for four weeks. Cats were then assigned to either receive a low (19% ME) or high (52% ME) carbohydrate diet and fed at maintenance energy requirements for another four weeks, followed by ad-libitum feeding for eight weeks to facilitate weight gain. Adiponectin profiles including total circulating adiponectin and its distribution [low molecular weight (LMW) and high molecular weight (HMW) adiponectin], and proportion of adiponectin that is HMW (SA) were measured by ELISA and velocity sedimentation using sucrose gradients, followed by Western blotting, respectively. We demonstrated inter-animal variation in total adiponectin concentration at baseline (0.6 to 15.0 g/mL), with the adiponectin present in both LMW and HMW forms. Feeding with a high carbohydrate diet for four weeks at maintenance energy requirements resulted in increased total adiponectin concentration, which was associated with an increased concentration of LMW adiponectin. In contrast, feeding with a low carbohydrate diet for four weeks at maintenance energy requirements resulted in increased concentration of HMW adiponectin, decreased LMW adiponectin concentration, and increased SA, without a change in total adiponectin concentration. In cats fed the high carbohydrate diet, total adiponectin and HMW adiponectin concentrations become lower at six hours after feeding, as compared to the fasting concentrations. This phenomenon was not observed in cats fed a low carbohydrate diet, indicating a diet-dependent postprandial effect. There was no effect of gender on any of the adiponectin profiles in cats. Unlike other studies in humans and mice in which adiponectin concentrations decreased as fat mass increased, our data indicate that a moderate weight gain achieved by ad libitum feeding of a low carbohydrate diet for eight weeks correlated with increased adiponectin concentrations. Total adiponectin concentration (mirrored by HMW adiponectin) was positively correlated with body weight gain and fat mass gain (but not absolute fat mass) in our overweight cats. Furthermore, the fat mass-related increases in plasma adiponectin over eight weeks correlated with insulin sensitivity (higher adiponectin concentration corresponded to greater insulin sensitivity in overweight cats). These data hint at the possibility that in overweight animals, adiponectin is similar to other adipokines that rise concomitantly with increased of moderate fat mass gain and thus increases insulin sensitivity. Overall, the knowledge in this study therefore provides useful information to veterinarians and cat food manufacturers, and forms a foundation for future studies to extend our knowledge of adiponectin in cats. Data gathered in cats may also be applicable to humans and could therefore inform research using cats as an animal model of human obesity and type 2 diabetes.

[Formulae and special characters can only be approximated here. Please see the pdf version of the abstract for an accurate reproduction.] Atherosclerosis is a common degenerative disease in which the clinical manifestations are often through stroke or myocardial infarction. Some of the established risk factors for atherosclerosis include elevated plasma low-density lipoprotein (LDL)-cholesterol levels, obesity, diabetes mellitus (DM) and cigarette smoking. Of the risk factors, an elevation in plasma LDL is one of the most established and the most researched. This is partly a consequence of the deposition of cholesterol within arterial intima being a crucial step in the progression of atherosclerosis, combined with the finding that LDL particles are a major transporter of cholesterol in circulation. Recently there is increasing evidence showing a role of the other major transporter of cholesterol in circulation, chylomicron remnants, in the progression of atherosclerosis. The notion of atherosclerosis as a postprandial phenomenon has been further substantiated by the emergence of evidence showing a direct role of chylomicron remnants in arterial cholesterol deposition. Based on evidence that chylomicron remnants are proatherogenic, the suggestion arises that accumulation of postprandial lipoproteins in plasma may add another dimension of risk to the development of coronary artery disease (CAD). This thesis tests the general hypothesis that individuals with or at high risk of CAD have postprandial dyslipidaemia and that this metabolic abnormality is correctable with a class of lipid-lowering drugs called statins. To test the hypothesis, clinical studies were conducted in normolipidaemic CAD patients, heterozygous familial hypercholesterolaemia (FH) and postmenopausal women with type 2 DM. Determination of postprandial dyslipidaemia by comparison with control populations were conducted initially in each patient group (Studies 1, 3 and 5), followed by intervention studies investigating possible modulation of the dyslipidaemia with a statin (Studies 2, 4 and 6). Six observation statements based on case-control comparisons of postprandial lipaemia in patients with or at risk of CAD and the effects of statins on postprandial dyslipidaemia in the patient groups were derived from the general hypothesis. The observation statements were examined in the individual studies described below. Postprandial lipoprotein metabolism was assessed using a number of methods. For comparison of postprandial lipaemia in Studies 1 and 2, a classic oral fat challenge was utilised. As markers of chylomicrons and chylomicron remnants, retinyl palmitate and triglyceride were measured postprandially as well as apolipoprotein (apo) B48 concentrations, a specific marker of intestinal lipoproteins. ApoB48 was also measured in the fasting state and found to predict the postprandial responses of retinyl palmitate, triglyceride and apoB48. This suggested that fasting measurement of apoB48 could be used as a simple indicator of postprandial dyslipidaemia. Consequently for Studies 3 - 6, fasting apoB48 measurements were used as primary markers of postprandial dyslipidaemia. Other markers for chylomicrons and their remnants utilised were fasting plasma concentrations of remnant-like particle-cholesterol (RLP-C) and apoC-III. As well as these static markers, chylomicron remnant catabolism was measured using a stable isotope breath test. The breath test involves the intravenous injection of a chylomicron remnant-like emulsion labelled with ¹³C-oleate and measurement of enriched ¹³CO2 in expired breath by isotope ratio mass spectrometry. The fractional catabolic rate (FCR) of the injected emulsion was subsequently calculated using multi-compartmental modeling (SAAM II). The studies are presented in this thesis as published and unpublished works. In Study 1, postprandial lipoprotein metabolism was compared between 18 normolipidaemic CAD patients (cholesterol 4.54 ± 0.12 mmol/L, triglyceride 1.09 ± 0.16) with 13 asymptomatic healthy controls using an oral fat challenge. Normolipidaemic CAD patients had higher postprandial area-under-curve (AUC) for triglyceride (+34%, p=0.019), retinyl palmitate (+74%, p=0.032) and apoB48 (+36%, p<0.001). Fasting apoB48 was also higher (+41%, p=0.001) and found to correlate significantly with AUC of triglyceride (p=0.017), retinyl palmitate (p=0.001) and apoB48 (p<0.001). The data suggest that normolipidaemic CAD patients have increased concentrations of intestinal lipoproteins in the fasting and postprandial state. In addition to these findings, significant correlations of fasting apoB48 with postprandial markers (p<0.02) suggests the fasting marker to be a simpler surrogate marker for the degree of total postprandial lipaemia. Study 2 investigated the effect of atorvastatin treatment on postprandial dyslipidaemia found in the 18 near-normolipidaemic CAD patients from Study 1. The trial was conducted in a randomised, placebo-controlled design, using oral fat challenges before and after 12-weeks atorvastatin/placebo treatment. Compared with the placebo group, atorvastatin decreased the total postprandial AUC for iii triglyceride (-22%, p=0.05) and apoB48 (-34%, p=0.013). Fasting markers of apoB48 (-35%, p=0.019) and RLP-C (-36%, p=0.032) also decreased significantly. Atorvastatin was also found to increase LDL-receptor activity by +218% (p<0.001) as reflected in binding studies. The data suggest atorvastatin reduces the fasting levels of intestinal lipoproteins as well as total postprandial lipaemia, but without acute dynamic changes in postprandial lipaemia. The reduction in fasting and total postprandial lipoprotein levels could be partly attributed to an increase in LDL-receptor mediated removal from circulation. In Study 3, postprandial lipaemia was compared in 15 heterozygous FH patients with 15 healthy controls. FH patients had higher fasting concentrations of apoB48 (+56%, p<0.001) and RLP-C (+48%, p=0.003). The elevation in these fasting markers of chylomicrons and their remnants suggests FH patients have postprandial dyslipidaemia due to an accumulation of these particles in plasma. Study 4 examined the effects of long- (> 6 months) and short-term (4 weeks) simvastatin treatment on modulating postprandial dyslipidaemia found in the 15 FH patients from Study 3. Short- and long-term simvastatin treatment decreased the fasting concentrations of apoB48 (-29% and 15% respectively, p<0.05) and RLP-C (both -38%, p<0.001), but did not significantly alter the FCR of the injected chylomicron remnant-like emulsion. The data suggest that in heterozygous FH both long- and short-term simvastatin treatments decrease the fasting markers of postprandial lipoproteins by mechanisms that may not be mediated via processes differentiated by the 13CO2 breath test. This implies that the effect on postprandial lipaemia may be from a decrease in production and/or a possible increase in catabolism of triglyceride-rich lipoproteins (TRLs). In Study 5, postprandial lipaemia was compared in 24 postmenopausal women age and body mass index matched with 14 postmenopausal women with type 2 DM. Postmenopausal diabetic women were found to have higher fasting concentrations of apoB48 (+21%, p=0.021) and apoC-III (+16%, p=0.042) as well as lower FCR of the chylomicron remnant-like emulsion (-50%, p<0.001). The data suggest that postmenopausal diabetic women have postprandial dyslipidaemia, and that this is due to delayed catabolism of chylomicron remnants. Study 6 was an hypothesis-generating exercise examining the effects of 4-weeks pravastatin treatment on postprandial dyslipidaemia found in 7 postmenopausal women with type 2 DM from Study 5. Although plasma LDL-cholesterol was reduced (-19%, p=0.028), there were no significant effects found on fasting apoB48 concentrations (-12%, p=0.116) or the FCR of the chylomicron remnant-like emulsion (+38%, p=0.345). A larger sample size of patients and/or treatment with a more potent statin at a dosage known to affect chylomicron remnant metabolism would be required to demonstrate a significant reduction in postprandial dyslipidaemia in postmenopausal women with type 2 DM. The results of the above mentioned studies combined support the general hypothesis that postprandial dyslipidaemia is a feature of patients with or at risk of CAD. This defect may be demonstrated using fasting apoB48 as an indicator of the degree of postprandial lipaemia. Postprandial dyslipidaemia may reflect a reduction in catabolism, as suggested with the breath test in type 2 DM, and/or an over overproduction of chylomicrons. Both these mechanisms would also increase competition for lipolysis and clearance pathways between hepatically and intestinally-derived lipoproteins. The exact mechanisms by which postprandial dyslipidaemia occurs are yet to be determined. Statins appear to improve defective postprandial lipaemia in patients with or at risk of CAD, which is in agreement with the general hypothesis. The effectiveness of a statin is dependant on their potency in inhibiting cholesterol biosynthesis and increasing receptor mediated clearance of LDL and chylomicron remnants. The studies conducted in this thesis show that postprandial dyslipidaemia can be reduced by statins but not to the extent demonstrated in controls. However, the demonstrated reduction in fasting and total postprandial lipaemia translates to a lowering in overall arterial exposure to circulating proatherogenic particles. The elevation in fasting and postprandial levels of proatherogenic chylomicron remnants found in the patient groups described in this thesis indicates another dimension to their risk of coronary disease. The reductions in the overall levels of proatherogenic particles in patients with or at high CAD risk, infers a possible reduction in the risk of coronary disease in these patients.

[Truncated abstract] The low density lipoprotein receptor-related protein (LRP), a member of the low-density lipoprotein (LDL) receptor gene family is involved in numerous biological processes including lipoprotein metabolism. This thesis concerns investigations into some aspects of LRP metabolism/regulation and possible roles in coronary artery disease (CAD). Specific aims were: to investigate the association between polymorphisms in the LRP gene and in its associated protein, the lipoprotein receptor-associated protein (RAP), with the risk of CAD; to extensively examine the influence of the LRP exon 22 C200T polymorphism on lipid metabolism; to develop and characterise assays for the mRNA expression of LRP and 2 other genes relevant to lipid metabolism, the LDL receptor (LDLR), and HMG CoA reductase (HMGCR); and finally, to apply the latter techniques to studies on the influence of genetic variation in LRP, and dietary and drug interventions, on LRP, LDLR and HMGCR mRNA expression in nucleated blood cells from healthy human subjects. Six hundred CAD subjects and 700 similarly aged controls were genotyped for 8 LRP gene polymorphisms as well as for the RAP V311M polymorphism. ... In the final phase of my studies, I examined the influence of 4 weeks therapy with a cholesterol lowering drug, an HMGCR inhibitor, atorvastatin (20mg daily), on the mRNA expression of LDLR, LRP and HMGCR in human nucleated blood cells. Twelve normal Caucasian male subjects aged 49 ? 5 (SD) years were studied. Plasma total cholesterol and LDL-C decreased by averages of 29 % and 41 % after the 4 week period. This was accompanied by an elevation in LDLR mRNA expression by approximately 30 35 %. In contrast, there was no significant effect on LRP and HMGCR mRNA expression. In conclusion, the original findings in this thesis included: demonstration of a strong influence of the LRP exon 22 C200T polymorphism on coronary artery disease and LDLR expression, but without a clear effect on fasting or postprandial lipid levels; data on the biological variation in LDLR and LRP gene expression in nucleated blood cells from normal subjects; the influence of an oral fat load on the expression viii of these genes, finding that LDLR was significantly depressed; and finally, the observation that statin therapy upregulated LDLR in nucleated blood cells.

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Agradecemos a compreensão. on 2017-01-24T13:40:19Z (GMT) / Submitted by Luá Taibo Timpone null (101010913@rc.unesp.br) on 2018-03-02T20:05:16Z No. of bitstreams: 1 Dissertação_VersãoFinal_Completa_Luá.pdf: 1544050 bytes, checksum: 3ff859d190848f5e447a8680e9b509cb (MD5) / Approved for entry into archive by Vivian Rosa Storti null (vstorti@reitoria.unesp.br) on 2018-04-04T12:42:54Z (GMT) No. of bitstreams: 1 timpone_lt_me_rcla.pdf: 1544050 bytes, checksum: 3ff859d190848f5e447a8680e9b509cb (MD5) / Made available in DSpace on 2018-04-04T12:42:54Z (GMT). No. of bitstreams: 1 timpone_lt_me_rcla.pdf: 1544050 bytes, checksum: 3ff859d190848f5e447a8680e9b509cb (MD5) Previous issue date: 2016-10-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O tamanho do alimento e a temperatura corpórea são dois fatores que reconhecidamente influenciam a resposta metabólica pós-prandial dos vertebrados ectotérmicos. Leptodactylus latrans é uma espécie generalista que consome desde invertebrados até pequenos vertebrados, de forma que sua dieta é composta por itens de tamanho variável, os quais sempre são ingeridos inteiros. A temperatura corpórea de L. latrans está sujeita a disponibilidade de nichos térmicos adequados nos ambientes onde ocorre, os quais são possivelmente explorados através da termorregulação comportamental. No presente estudo, nós avaliamos os efeitos do tamanho da presa e da temperatura corpórea sobre a resposta metabólica pós-prandial, em indivíduos adultos da rã-manteiga, Leptodactylus latrans (Anura, Leptodactylidae) através da quantificação das taxas de consumo de oxigênio antes e após a alimentação. A resposta metabólica pós-prandial de L. latrans pode ser caracterizada por um rápido aumento nas taxas de consumo de oxigênio logo após a ingestão do alimento, até atingir valores máximos entre 85,93 ± 9,92 e 224,54 ± 26,08 mLO2.kg-1. h-1, dentro de 1-2 dias. Após este pico, houve um retorno paulatino da taxa metabólica aos níveis de jejum entre 3 a 7 dias após a alimentação. De maneira geral, encontramos que a ingestão de presas maiores causa um maior incremento metabólico e aumenta a duração da digestão. Já o incremento da temperatura é acompanhado pela diminuição da duração da digestão às expensas de taxas metabólicas pós-prandiais mais elevadas. Tanto em um caso como no outro, não encontramos indicações de que fatores cardiorrespiratórios pudessem atuar na limitação do tamanho da presa ou na temperatura na qual a digestão pode ocorrer. No entanto, é plausível que outros fatores de cunho ecológico sejam relevantes na consideração dos efeitos do tamanho do alimento e da temperatura na digestão de L. latrans. Em especial, um maior retorno energético absoluto ao se alimentar de presas maiores e a diminuição do tempo de digestão em temperaturas mais elevadas, ambos aspectos documentados em L. latrans, podem representar benefícios ecológicos importantes. / Meal size and body temperature affect markedly the post-prandial metabolic response of ectothermics vertebrates. Leptodactylus latrans is a generalist anuran species feeding on diverse prey itens, from invertebrates to small vertebrates, with considerable size variation and that are always ingested whole. The body temperature of L. latrans is largely dependent of the availability of thermal niches in the environment, which are possibly explored by means of behavioral thermoregulation. In the present study, we investigated the effects of meal size and body temperature on the post-prandial metabolic response of adults of the Neotropical leptodatylid frog, Leptodactylus latrans (Anura, Leptodactylidae) by quantifying the rates of oxygen consumption before and after meal ingestion. The post-prandial metabolic response of L. latrans can be characterized by the rapid increase in the rates of oxygen consumption shortly after meal ingestion, until reach peak between 85,93 ± 9,92 e 224,54 ± 26,08 mLO2.kg-1. h-1, within 1-2 days post-feeding. Thereafter, metabolism gradually return to the pre-feeding values within 3 to 7 days post-feeding. In general, we found that the ingestion of larger meals were followed by greater metabolic increment and by longer digestion duration. Temperature increment caused digestion duration to decrease at the expenses of greater post-prandial metabolic rates. In both cases, we did not found evidences that cardiorespiratory compromises could limit meal size or the temperature in which meal digestion could occur. On the other hand, some ecological considerations seems to be relevant in considering the effects of meal size and body temperature on the digestion of L. latrans. More specifically, the greater gross energetic gain when feeding on larger prey and the shortening of digestion duration at higher temperatures, both observed in L. latrans, are likely to yield substantial ecological advantages. / Capes Demanda Social

Diabetes mellitus is a frequent endocrinopathy in dogs. Exogenous insulin and nutritional management are the mainstays of therapy. High carbohydrate and fibre diets have been traditionally recommended for canine diabetes mellitus. However, recent studies in healthy and diabetic dogs have challenged the use of these traditional diabetic diets. In addition, dietary carbohydrate content was found to be the main determinant of postprandial blood glucose concentrations over 1.5 hours in healthy dogs. Increasing carbohydrate content increased blood glucose concentration. In a search of the literature, no studies in dogs were found comparing the effects on postprandial plasma glucose, insulin, triglyceride and free fatty acid concentrations of a traditionally recommended high carbohydrate and fibre diabetes diet with a moderate carbohydrate and fibre diet, or a commercially-available maintenance diet. Although fasting plasma triglyceride concentrations are commonly used for diagnosis and management of canine hyperlipidemia, a review of the literature found that in human beings, it may not to be predictive of the highest postprandial concentration. Importantly, in overweight and obese dogs with postprandial plasma triglyceride concentrations >5 mmol/L (>445 mg/dL), it was found there was a 6 fold increase in risk of laboratory evidence of exocrine pancreatic disease. However, there are limited studies on the effect of maintenance diets on postprandial plasma triglyceride concentrations in dogs, and no reference intervals determined for a triglyceride meal challenge test in healthy dogs. For the dietary studies in this thesis, animal welfare was of paramount importance, and minimally invasive peripheral venous catheterization and blood collection techniques were needed to collect 4 mL blood samples over 13 hours in conscious dogs. A search of the literature found no studies evaluating the reliability of using peripheral catheterization via the cephalic vein for the collection of larger blood volumes (for example, 4 mL). The aims of this thesis were firstly, to investigate the influence of three diets with varying carbohydrate and fibre content on postprandial plasma glucose, insulin, triglyceride and free fatty acid concentrations in healthy dogs over 12 hours; secondly, to develop a triglyceride meal challenge test and associated reference intervals; and finally, to evaluate a minimally invasive catheterization and blood collection technique for reliability in collecting the blood volumes required for these studies. For the studies in this thesis, twelve healthy dogs were fed each of three diets for three weeks in a three period cross-over design. For the meal response test at the end of each three-week period, 10 blood samples were collected over 13 hours. Reference intervals for fasting and postprandial triglyceride concentrations at single and multiple time points after eating a standard meal were determined in healthy dogs. Associations between fasting and postprandial triglyceride concentrations, and time to measure highest postprandial triglyceride concentration were also evaluated. Blood volume obtained, resistance on aspirating the blood sample, and methods used to improve blood flow during collection were recorded for the 358 samples collected. The results of the studies in this thesis demonstrated that a moderate carbohydrate diet resulted in lower peak and postprandial glucose concentrations compared with a traditional diabetic diet (CHO 55 %ME) and a maintenance diet (CHO 45 %ME). Fasting triglyceride concentrations were found not to be predictive of peak postprandial triglyceride concentrations. The highest triglyceride concentration measured at 2, 5, and 6 hours after eating had the closest agreement with peak postprandial triglyceride concentration. Glucose, insulin and triglyceride concentrations in some dogs were significantly above baseline concentrations at 12 hours after eating each of the diets. Of 358 blood samples collected, 93 % achieved the required 4 mL volume, while the remaining samples were greater than 1.5 mL, and 87 % were obtained with minimal resistance. It was concluded that the moderate carbohydrate and fibre test diet warrants evaluation in diabetic dogs. It was found that when following the same protocol, blood samples should be collected 2, 5, and 6 hours after eating to determine the highest postprandial plasma triglyceride concentration. For future nutritional studies, dogs may need to be fasted for at least 12 hours, and analytes measured over at least 12 hours after feeding to evaluate fasting and postprandial plasma analyte concentrations. Finally it was demonstrated that percutaneous catheterization of the cephalic vein using a 20-gauge catheter allows for successful collection of multiple 4 mL blood samples over 13 hours in conscious dogs. This thesis presents new information for future nutritional studies in healthy and diabetic dogs by suggesting that there may be no glycemic benefit feeding the high carbohydrate and fibre diet compared with a moderate carbohydrate and fibre diet. A triglyceride meal challenge test was developed to assist the diagnosis of canine hyperlipidemia. Finally, a minimally invasive method for obtaining serial blood samples was evaluated and described. These findings are expected to help in designing future studies in the nutritional management in healthy dogs, and dogs with diabetes mellitus and hyperlipidemia.