<p>Excessive weight gain has frequently been reported in adolescents with type 1 diabetes, especially in girls. In general, puberty is associated with reduced insulin sensitivity that is further diminished by overweight. The causes and consequences of excessive weight gain in adolescents with type 1 diabetes are not fully understood. The studies described in this thesis addressed body composition in adolescents with type 1 diabetes and the relationships between physical activity, energy intake and changes in body composition. Furthermore, the effect of metformin as additional therapy on glycaemic control and insulin sensitivity was examined in a randomised placebo-controlled study. Body mass index (BMI) and percentage body fat (%BF) were significantly higher in girls with type 1 diabetes compared to healthy control girls. Mean HbA1c during puberty, but not mean insulin dose, was positively related to BMI at the age of 18 in girls with diabetes. A centralised fat distribution was associated with poor glycaemic control, increased daily dosage of insulin and elevated cholesterol and triglyceride levels. Neither total physical activity nor total energy intake differed between adolescent girls with type 1 diabetes and healthy age-matched control girls. A high dietary fat intake was positively related to gain in %BF in girls with type 1 diabetes. Additional therapy with metformin for three months improved glycaemic control and peripheral insulin sensitivity in adolescents with poorly controlled type 1 diabetes. The improvement in glycaemic control was related to insulin sensitivity at baseline, implying that the most insulin resistant subjects benefited most from the metformin therapy. It is concluded that the excessive weight gain observed in girls with type 1 diabetes is mainly attributable to an increased fat mass and that dietary fat intake is of importance for this gain in body fat. Additional treatment with metformin improves glycaemic control in adolescents with poorly controlled type 1 diabetes.</p>

Excessive weight gain has frequently been reported in adolescents with type 1 diabetes, especially in girls. In general, puberty is associated with reduced insulin sensitivity that is further diminished by overweight. The causes and consequences of excessive weight gain in adolescents with type 1 diabetes are not fully understood. The studies described in this thesis addressed body composition in adolescents with type 1 diabetes and the relationships between physical activity, energy intake and changes in body composition. Furthermore, the effect of metformin as additional therapy on glycaemic control and insulin sensitivity was examined in a randomised placebo-controlled study. Body mass index (BMI) and percentage body fat (%BF) were significantly higher in girls with type 1 diabetes compared to healthy control girls. Mean HbA1c during puberty, but not mean insulin dose, was positively related to BMI at the age of 18 in girls with diabetes. A centralised fat distribution was associated with poor glycaemic control, increased daily dosage of insulin and elevated cholesterol and triglyceride levels. Neither total physical activity nor total energy intake differed between adolescent girls with type 1 diabetes and healthy age-matched control girls. A high dietary fat intake was positively related to gain in %BF in girls with type 1 diabetes. Additional therapy with metformin for three months improved glycaemic control and peripheral insulin sensitivity in adolescents with poorly controlled type 1 diabetes. The improvement in glycaemic control was related to insulin sensitivity at baseline, implying that the most insulin resistant subjects benefited most from the metformin therapy. It is concluded that the excessive weight gain observed in girls with type 1 diabetes is mainly attributable to an increased fat mass and that dietary fat intake is of importance for this gain in body fat. Additional treatment with metformin improves glycaemic control in adolescents with poorly controlled type 1 diabetes.

Energy intake (EI) and energy expenditure (EE) across the menstrual cycle (MC), while considering body adiposity, have not been previously evaluated in the same individuals. This study mainly examined the variations in energy balance (EB) across MC. Seventeen women (Body fat-DXA:28.5%) participated in three identical sessions during distinct phases of the MC: Early-follicular, Late-follicular/ovulation and Mid-luteal (confirmed by basal temperature and sex-steroid hormones). EI, resting metabolic rate (RMR), physical-activity EE (PAEE), severity of PMS, leptin and relative-reinforcing value (RRV) of preferred foods were measured during each phase. No differences in body fat, EI, RMR, PAEE, leptin and RRV of food were noted across MC. Trends were noted in preferred snack (p=0.06) and combined snack/fruit (p=0.06) intakes, while differences were noted in severity of PMS (p<0.05) across phases. Changes in EB across the MC were not noted. PMS was more severe, and preferred snack and combined snack/fruit intakes were slightly higher during mid-luteal phase.

Energy intake (EI) and energy expenditure (EE) across the menstrual cycle (MC), while considering body adiposity, have not been previously evaluated in the same individuals. This study mainly examined the variations in energy balance (EB) across MC. Seventeen women (Body fat-DXA:28.5%) participated in three identical sessions during distinct phases of the MC: Early-follicular, Late-follicular/ovulation and Mid-luteal (confirmed by basal temperature and sex-steroid hormones). EI, resting metabolic rate (RMR), physical-activity EE (PAEE), severity of PMS, leptin and relative-reinforcing value (RRV) of preferred foods were measured during each phase. No differences in body fat, EI, RMR, PAEE, leptin and RRV of food were noted across MC. Trends were noted in preferred snack (p=0.06) and combined snack/fruit (p=0.06) intakes, while differences were noted in severity of PMS (p<0.05) across phases. Changes in EB across the MC were not noted. PMS was more severe, and preferred snack and combined snack/fruit intakes were slightly higher during mid-luteal phase.

Energy intake (EI) and energy expenditure (EE) across the menstrual cycle (MC), while considering body adiposity, have not been previously evaluated in the same individuals. This study mainly examined the variations in energy balance (EB) across MC. Seventeen women (Body fat-DXA:28.5%) participated in three identical sessions during distinct phases of the MC: Early-follicular, Late-follicular/ovulation and Mid-luteal (confirmed by basal temperature and sex-steroid hormones). EI, resting metabolic rate (RMR), physical-activity EE (PAEE), severity of PMS, leptin and relative-reinforcing value (RRV) of preferred foods were measured during each phase. No differences in body fat, EI, RMR, PAEE, leptin and RRV of food were noted across MC. Trends were noted in preferred snack (p=0.06) and combined snack/fruit (p=0.06) intakes, while differences were noted in severity of PMS (p<0.05) across phases. Changes in EB across the MC were not noted. PMS was more severe, and preferred snack and combined snack/fruit intakes were slightly higher during mid-luteal phase.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

The acute effects of exercise on appetite, ad libitum energy intake and gut hormone responses have received much attention over the past two decades. The experiments in this thesis have contributed to this research by examining appetite, acylated ghrelin, peptide-YY (PYY), leptin and ad libitum energy intake responses to two consecutive days of moderate-high intensity running. To achieve this 15 individuals aged 21 (2) y, with a BMI of 23.0 (1.9) kg·m-2 were recruited. Additionally, appetite, acylated ghrelin, PYY, glucagon-like peptide-1 (GLP-1), and ad libitum energy intake responses to an acute bout of moderate intensity treadmill exercise were compared in lean and overweight/obese (ow/ob) males and females. Two separate cohorts of individuals were recruited; 22 lean individuals and 25 ow/ob individuals (aged 38 (15) and 45 (12) y, with a BMI of 22 (2) and 29 (3) kg·m 2, for lean and ow/ob individuals, respectively). In Chapter 4, two consecutive days of 60 min treadmill running at 70% VO₂ peak did not produce compensatory changes in appetite or energy intake over two days. There were no main effects of trial for acylated ghrelin or leptin. However a main effect of trial for PYY indicated higher concentrations on the exercise than control trial. A meta-analysis was completed in Chapter 5, suggesting further research in the effects of acute exercise on appetite regulatory hormones in individuals who are ow/ob was necessary. In Chapter 6, 60 min of treadmill exercise at 60% VO₂ peak did not alter appetite sensations or energy intake in the 7 h after exercise in lean and ow/ob males and females. There were no main effects of sex, BMI or trial for acylated ghrelin; however, PYY and GLP-1 concentrations were higher in exercise than control trials. This thesis has demonstrated that over two days, high volume exercise does not stimulate compensatory appetite regulatory changes, in lean healthy males. In the short term, lean and ow/ob males and females respond similarly to acute exercise, showing no alterations in appetite or food intake responses, whilst PYY and GLP-1 concentrations are higher in exercise than control trials.

Introdução: No período de hipermetabolismo em que se encontra o paciente politraumatizado, é necessário que a administração calórica seja adequada e suficiente para suprir o intenso gasto energético do organismo. Com suporte nutricional inadequado, as reservas de aminoácidos dos músculos esqueléticos e respiratórios são exigidas, expondo o paciente crítico ao risco nutricional e suas consequências. Objetivos: Quantificar o aporte calórico administrado a pacientes em ventilação mecânica (VM), analisar a adequação da prescrição e correlacionar as calorias ofertadas com o tempo em VM. Métodos: Estudo de coorte prospectivo observacional conduzido na Unidade de Terapia Intensiva de um hospital público de Porto Alegre (RS) no período de abril de 2008 a julho de 2009. Foram estudados 60 pacientes politraumatizados em Nutrição Enteral e VM e internados por mais de 5 dias na UTI. Foram verificados o tempo de permanência em VM e a oferta calórica durante o período que permaneceram em terapia nutricional enteral. Resultados: A média do percentual de calorias administradas foi de 68,6% (±12,3) do prescrito. Nove pacientes (15,0%) receberam menos da metade do que deveriam, apenas 16 (26,7%) receberam no mínimo 80,0%. Apenas 25,0% dos pacientes receberam prescrição calórica adequadamente (entre 90% e 110%). Não houve associação significativa entre o Valor Energético Total administrado e o tempo de VM (rs=0,130; p=0,321), tempo de UTI (rs=-0,117; p=0,372) e tempo de internação hospitalar (rs=-0,152; p=0,246). Conclusão: Neste estudo foi verificado que maioria dos pacientes politraumatizados em ventilação mecânica não recebeu um aporte energético adequado, ficando assim expostos aos riscos da desnutrição e seus desfavoráveis desfechos clínicos. / Introduction: During the period of hypermetabolism faced by multiple trauma patients, their calorie intake has to be appropriate and sufficient to meet their high energy expenditure. When there is not appropriate nutritional care, the amino acids from the skeletal and respiratory muscles are used; thus critical patients are exposed to nutritional risk and its consequences. Objectives: To quantify the calories provided to patients on mechanical ventilation (MV); to analyze the appropriateness of the prescription; and to correlate the calories offered with the period of time on MV. Methods: Prospective observational cohort study conducted at the intensive care unit (ICU) of a public hospital in Porto Alegre (RS), Brazil, from April 2008 to July 2009. We studied 60 multiple trauma patients on MV receiving enteral nutrition who remained longer than 5 days at the ICU. We investigated the length of time patients were on MV and their calorie intake while receiving enteral nutrition. Results: The mean percentage of calories was 68.6% (±12.3) of the amount prescribed. Nine patients (15.0%) received less than half of the prescription. Only 16 (26.7%) patients received at least 80.0%. Only 25.0% of patients received the amount of calories according to the prescription (between 90% and 110%). There was no significant association between total energy value and the period of time on MV (rs = 0.130, p = 0.321), length of ICU stay (rs = -0.117, p = 0.372), and length of hospital stay (rs = -0.152, p = 0.246). Conclusion: We found that most multiple trauma patients on MV did not receive an adequate energy intake; therefore, they were exposed to the risks of malnutrition and its adverse clinical outcomes.

Current methods of energy restriction are not successful for achieving long-term weight loss and maintenance for the majority of individuals. As a result, the prevalence of obesity and obesity related diseases continue to increase. This calls for the development of novel lifestyle interventions to combat the obesity epidemic. Hunger has been highlighted as a major factor influencing the long-term success of weight management methods and therefore how a given dietary intervention affects the appetite regulatory system may dictate the success of the diet by augmenting long-term adherence. In addition, the effect of a given dietary intervention on exercise may determine its suitability for exercising individuals and may influence the energy deficit that can be achieved by the diet. This thesis investigated the acute effects of two novel methods of dietary restriction; breakfast omission and severe energy restriction. The main aims for this thesis were to determine the effect of these methods of energy restriction on ad-libitum energy intake, subjective appetite sensations, and peripheral concentrations of hormones involved in appetite regulation. In addition, this thesis also investigated the effects of these methods of energy restriction on metabolism and glycaemic control at rest, and performance and perceived exertion during exercise. This work found that moderate and severe energy deficits induced by breakfast omission and 24 h of severe energy restriction, respectively, resulted in either no (Chapter VIII) or partial (Chapters IV and VII) energy intake compensation over the subsequent 24-48 h. Subjective appetite was increased during (Chapters IV, V, VII and VIII) and shortly after (Chapter VII) energy restriction, but this effect was transient and was offset after an ad-libitum (Chapters IV and VII) or standardised (Chapters V and VIII) meal. In addition, none of the work presented in this thesis demonstrated an appetite hormone response to energy restriction that was indicative of compensatory eating behaviour. Compared to breakfast omission, breakfast consumption resulted in an increased in resting energy expenditure and carbohydrate oxidation, with a concurrent reduction in fat oxidation during the morning. However, there were no differences after lunch (Chapter V). In response to a standardised breakfast, resting energy expenditure was suppressed (Chapter VII) or not different (Chapter VIII) the following morning, after 24 h severe energy restriction compared to energy balance. Plasma NEFA and fat oxidation was greater, carbohydrate oxidation was reduced, and postprandial insulin sensitivity was impaired in the after 24 h severe energy restriction (Chapter VI, VII and VIII). In Chapter IV, omission of breakfast in the morning was shown to reduce exercise performance in evening, even after provision of an ad-libitum lunch 4 h before. However, there was no difference in perception of effort during steady state exercise, independent of breakfast consumption or omission in the morning (Chapters IV and V). Collectively, breakfast omission and 24 h severe energy restriction reduce energy intake and promote an appetite regulatory response conducive to maintenance of a negative energy balance. Chronic intervention studies are now required to confirm whether these effects persist after long-term practice of these dietary interventions.