En lien avec l’augmentation constante de l’obésité, de plus en plus de personnes sont atteintes de résistance à l’insuline ou de diabète de type 2. Ce projet doctoral s’est surtout intéressé à l’une des conséquences majeures des pathologies cardiométaboliques, soit la dyslipidémie diabétique. À cet égard, les gens présentant une résistance à l’insuline ou un diabète de type 2 sont plus à risque de développer des perturbations lipidiques caractérisées essentiellement par des taux élevés de triglycérides et de LDL-cholestérol ainsi que de concentrations restreintes en HDL-cholestérol dans la circulation. Les risques de maladies cardiovasculaires sont ainsi plus élevés chez ces patients. Classiquement, trois organes sont connus pour développer l’insulino-résistance : le muscle, le tissu adipeux et le foie. Néanmoins, certaines évidences scientifiques commencent également à pointer du doigt l’intestin, un organe critique dans la régulation du métabolisme des lipides postprandiaux, et qui pourrait, conséquemment, avoir un impact important dans l’apparition de la dyslipidémie diabétique. De façon très intéressante, des peptides produits par l’intestin, notamment le GLP-1 (glucagon-like peptide-1), ont déjà démontré leur potentiel thérapeutique quant à l’amélioration du statut diabétique et leur rôle dans le métabolisme intestinal lipoprotéinique. Une autre évidence est apportée par la chirurgie bariatrique qui a un effet positif, durable et radical sur la perte pondérale, le contrôle métabolique et la réduction des comorbidités du diabète de type 2, suite à la dérivation bilio-intestinale. Les objectifs centraux du présent programme scientifique consistent donc à déterminer le rôle de l’intestin dans (i) l’homéostasie lipidique/lipoprotéinique en réponse à des concentrations élevées de glucose (à l’instar du diabète) et à des peptides gastro-intestinaux tels que le PYY (peptide YY); (ii) la coordination du métabolisme en disposant de l’AMPK (AMP-activated protein kinase) comme senseur incontournable permettant l’ajustement précis des besoins et disponibilités énergétiques cellulaires; et (iii) l’ajustement de sa capacité d’absorption des graisses alimentaires en fonction du gain ou de la perte de sa sensibilité à l’insuline démontrée dans les spécimens intestinaux humains prélevés durant la chirurgie bariatrique. Dans le but de confirmer le rôle de l’intestin dans la dyslipidémie diabétique, nous avons tout d’abord utilisé le modèle cellulaire intestinal Caco-2/15. Ces cellules ont permis de démontrer qu’en présence de hautes concentrations de glucose en basolatéral, telle qu’en condition diabétique, l’intestin absorbe davantage de cholestérol provenant de la lumière intestinale par l’intermédiaire du transporteur NPC1L1 (Niemann Pick C1-like 1). L’utilisation de l’ezetimibe, un inhibiteur du NPC1L1, a permis de contrecarrer cette augmentation de l’expression de NPC1L1 tout comme l’élévation de l’absorption du cholestérol, prouvant ainsi que le NPC1L1 est bel et bien responsable de cet effet. D’autre part, des travaux antérieurs avaient identifié certains indices quant à un rôle potentiel du peptide intestinal PYY au niveau du métabolisme des lipides intestinaux. Toutefois, aucune étude n’avait encore traité cet aspect systématiquement. Pour établir définitivement l’aptitude du PYY à moduler le transport et le métabolisme lipidique dans l’intestin, nous avons utilisé les cellules Caco-2/15. Notre étude a permis de constater que le PYY incubé du côté apical est capable de réduire significativement l’absorption du cholestérol et le transporteur NPC1L1. Puisque le rôle de l'AMPK dans l'intestin demeure inexploré, il est important non seulement de définir sa structure moléculaire, sa régulation et sa fonction dans le métabolisme des lipides, mais aussi d'examiner l'impact de l’insulino-résistance et du diabète de type 2 (DT2) sur son statut et son mode d’action gastro-intestinal. En employant les cellules Caco-2/15, nous avons été capables de montrer (i) la présence de toutes les sous-unités AMPK (α1/α2/β1/β2/γ1/γ2/γ3) avec une différence marquée dans leur abondance et une prédominance de l’AMPKα1 et la prévalence de l’hétérotrimère α1/β2/γ1; (ii) l’activation de l’AMPK par la metformine et l’AICAR, résultant ainsi en une phosphorylation accrue de l’enzyme acétylCoA carboxylase (ACC) et sans influence sur l'HMG-CoA réductase; (iii) la modulation négative de l’AMPK par le composé C et des concentrations de glucose élevées avec des répercussions sur la phosphorylation de l’ACC. D’autre part, l’administration de metformine au Psammomys obesus, un modèle animal de diabète et de syndrome métabolique, a conduit à (i) une régulation positive de l’AMPK intestinale (phosphorylation de l’AMPKα-Thr172); (ii) la réduction de l'activité ACC; (iii) l’augmentation de l’expression génique et protéique de CPT1, supportant une stimulation de la β-oxydation; (iv) une tendance à la hausse de la sensibilité à l'insuline représentée par l’induction de la phosphorylation d'Akt et l’inactivation de la phosphorylation de p38; et (v) l’abaissement de la formation des chylomicrons ce qui conduit à la diminution de la dyslipidémie diabétique. Ces données suggèrent que l'AMPK remplit des fonctions clés dans les processus métaboliques de l'intestin grêle. La preuve flagrante de l’implication de l’intestin dans les événements cardiométaboliques a été obtenue par l’examen des spécimens intestinaux obtenus de sujets obèses, suite à une chirurgie bariatrique. L’exploration intestinale nous a permis de constater chez ceux avec un indice HOMA élevé (marqueur d’insulinorésistance) (i) des défauts de signalisation de l'insuline comme en témoigne la phosphorylation réduite d'Akt et la phosphorylation élevée de p38 MAPK; (ii) la présence du stress oxydatif et de marqueurs de l'inflammation; (iii) la stimulation de la lipogenèse et de la production des lipoprotéines riches en triglycérides avec l’implication des protéines clés FABP, MTP et apo B-48. En conclusion, l'intestin grêle peut être classé comme un tissu insulino-sensible et répondant à plusieurs stimuli nutritionnels et hormonaux. Son dérèglement peut être déclenché par le stress oxydatif et l'inflammation, ce qui conduit à l'amplification de la lipogenèse et la synthèse des lipoprotéines, contribuant ainsi à la dyslipidémie athérogène chez les patients atteints du syndrome métabolique et de diabète de type 2. / In relation with the constant increase in obesity, more and more people suffer from insulin resistance and type 2 diabetes (DT2). This doctoral research program especially emphasizes lipid disorders, one of the major consequences of cardiometabolic diseases. In this respect, people with insulin resistance or DT2 are at higher risk of developing lipid disturbances characterized mainly by high levels of triglycerides and LDL-cholesterol concentrations and HDL cholesterol in the blood circulation. The risks of cardiovascular disease are higher in these patients. Classically, three organs are known to develop insulin resistance: muscle, adipose tissue and liver. Nevertheless, important studies begin to point out the small intestine as a major organ in the regulation of postprandial lipids, which may have a significant impact on the development of diabetic dyslipidemia. In addition, the intestine produces peptides, including GLP-1 (glucagon-like peptide-1), that have already demonstrated their therapeutic potential with regard to diabetic status and intestinal lipoprotein metabolism. Further evidence is also is provided by the advent of bariatric surgery that has a positive effect on radical and sustainable weight loss, metabolic control and reduction of comorbidities of DT2, following biliopancreatic diversion. The central objectives of this scientific program are therefore to determine the role of the intestine in (i) lipid/ lipoprotein homeostasis in response to high concentrations of glucose (mimicking diabetes) and to gastrointestinal peptides such as PYY; (ii) the coordination of metabolism by involving AMPK (AMP-activated protein kinase) as an essential sensor for fine tuning of cellular energy needs; and (iii) adjusting absorption capacity of dietary fat in the gain or loss of insulin sensitivity demonstrated in intestinal specimens collected during bariatric surgery. In order to confirm the role of the intestine in diabetic dyslipidemia, we first used the intestinal Caco-2/15 cell model. The use of this epithelial cell line has shown a marked stimulation of cholesterol uptake via the transporter NPC1L1 (Niemann-Pick C1-like 1) in the presence of high glucose concentrations (as is the case in diabetic conditions) in basolateral compartment (compared to apical). The use of ezetimibe, an inhibitor of NPC1L1, helped to counteract this elevation of cholesterol absorption, thus proving that NPC1L1 is indeed behind this effect. If previous reports have identified some clues as to the potential role of intestinal PYY (peptide YY) in lipid metabolism disorders, no study has yet addressed this issue systematically. To definitively establish the ability of PYY to modulate lipid transport and metabolism in the intestine, we have used Caco-2/15 cells. Our recent investigation has shown that PYY (administered in the apical compartment) is able to significantly reduce cholesterol absorption via NPC1L1 transporter. Since the role of AMPK in the intestine remains unexplored, it is important to define not only its molecular structure, regulation and function in lipid metabolism, but also its impact on insulin resistance and T2D on its status and mode of action in the gastrointestinal tract. Using Caco-2/15 cells, we have been able to show (i) the presence of all AMPK subunits (α1/α2/β1/β2/γ1/γ2/γ3) with a marked difference in their abundance, but with a predominance of AMPKα1 and the prevalence of α1/β2/γ1 heterotrimer; (ii) the activation of AMPK by metformin and AICAR, resulting in increased phosphorylation of the downstream target acetylCoA carboxylases (ACC) without no influence on HMG-CoA reductase; (iii) the negative modulation of AMPK by compound C and glucose concentrations with high impact on ACC phosphorylation. On the other hand, administration of metformin to Psammomys obesus with insulin resistance and T2D led to (a) an upregulation of intestinal AMPK signaling pathway essentially typified by ascending AMPKα-Thr172 phosphorylation; (b) a reduction in ACC activity; (c) an elevation in the gene and protein expression of CPT1, supporting a stimulation of β-oxidation; (d) a trend of increase in insulin sensitivity portrayed by augmentation of Akt and GSK3β phosphorylation; (e) an inactivation of the stress-responsive p38-MAPK and /ERK1/2 exemplified by their phosphorylation lessening; and (f) a decrease in diabetic dyslipidemia following lowering of intracellular events that govern lipoprotein assembly. Therefore these data suggest that AMPK fulfills key functions in metabolic processes in the small intestine. The clear evidence for the involvement of the gut in cardiometabolic events has been obtained through the scrutiny of intestinal specimens obtained from obese subjects after bariatric surgery. Intestine of insulin-resistant subjects shows defects in insulin signaling as demonstrated by reduced Akt phosphorylation but increased p38 MAPK phosphorylation. These defects were accompanied with increased oxidative stress and inflammation markers in intestine of insulin-resistant subjects. Enhanced de novo lipogenesis rate and apo B-48 biogenesis along with increased triglyceride-rich lipoprotein production was also observed in the intestine of insulin-resistant subjects. Concomitantly, fatty acid binding proteins (FABP) and microsomal transfer protein (MTP) expression was increased in the intestine of insulin-resistant subjects. In conclusion, the small intestine may be classified as an insulin-sensitive tissue. Its deregulation, possibly triggered by oxidative stress and inflammation, may lead to amplification of lipogenesis and lipoprotein synthesis and may therefore represent a key mechanism for atherogenic dyslipidemia in patients with metabolic syndrome and T2D.

Le diabète de type 2 (DT2) apparaît lorsque la sécrétion d’insuline par les cellules β des îlots du pancréas ne parvient plus à compenser la résistance à l’insuline des organes cibles. Parmi les médicaments disponibles pour traiter le DT2, deux classes agissent en améliorant la sensibilité à l’insuline : les biguanides (metformine) et les thiazolidinediones (pioglitazone et rosiglitazone). Des études suggèrent que ces médicaments protègent également la fonction des cellules β. Dans le but d’identifier des mécanismes par lesquels les médicaments insulinosensibilisateurs protègent les cellules β, nous avons étudié les effets aigus de la metformine et de la pioglitazone sur le métabolisme et la fonction des cellules INS 832/13, sécrétrices d’insuline et des îlots pancréatiques isolés de rats. Nous avons aussi validé in vivo avec des rats Wistar les principales observations obtenues en présence de pioglitazone grâce à des clamps glucidiques et par calorimétrie indirecte. Le traitement aigu des cellules β avec de la pioglitazone ou de la metformine inhibe la sécrétion d’insuline induite par le glucose en diminuant la sensibilité des cellules au glucose (inhibition en présence de concentrations intermédiaires de glucose seulement). Dans les mêmes conditions, les traitements inhibent aussi plusieurs paramètres du métabolisme mitochondrial des nutriments et, pour la pioglitazone, du métabolisme des lipides. Les composés affectent le métabolisme en suivant un patron d’inhibition similaire à celui observé pour la sécrétion d’insuline, que nous avons nommé « décélération métabolique ». La capacité de la pioglitazone à inhiber la sécrétion d’insuline et à ralentir le métabolisme mitochondrial de façon aigüe se confirme in vivo. En conclusion, nous avons identifié la décélération métabolique de la cellule β comme nouveau mode d’action pour les médicaments insulinosensibilisateurs. La décélération métabolique causée par les agents insulinosensibilisateurs les plus utilisés semble provenir d’une inhibition du métabolisme mitochondrial et pourrait être impliquée dans les bienfaits de ceux-ci dans un contexte de stress métabolique. Le fait que les deux agents insulinosensibilisateurs étudiés agissent à la fois sur la sensibilité à l’insuline et sur la sécrétion d’insuline, les deux composantes majeures du DT2, pourrait expliquer pourquoi ils sont parmi les agents antidiabétiques les plus efficaces. La décélération métabolique est une approche thérapeutique à considérer pour le traitement du DT2 et d’autres maladies métaboliques. / Type 2 diabetes (T2D) appears when insulin secretion by pancreatic β-cells fails to compensate for insulin resistance. Two classes of anti-diabetic drugs have been used to target insulin resistance: biguanides (metformin) and thiazolidinediones (pioglitazone and rosiglitazone). Some studies suggest that these compounds also protect β-cell function. In order to identify the mechanisms whereby insulin-sensitizing agents protect β-cell function, we used INS 832/13 insulin secreting cells and isolated pancreatic rat islets to study the acute effects of pioglitazone and metformin on β-cell metabolism and function. Key observations obtained with pioglitazone were also validated in vivo in Wistar rats with the use of glucose clamps and indirect calorimetry. In vitro, acute pioglitazone or metformin treatment inhibits glucose-induced insulin secretion by lowering β-cell sensitivity to glucose (inhibition only at sub-maximal glucose concentrations). The same treatments also inhibit parameters of nutrient mitochondrial metabolism and, in the case of pioglitazone, parameters of lipid metabolism. Both compounds alter metabolism following a pattern similar to that observed with insulin secretion, a pattern that we label “metabolic deceleration”. Pioglitazone also acutely inhibits insulin secretion and slows down mitochondrial metabolism in vivo. In conclusion, we identified metabolic deceleration of the pancreatic β-cell as a new mode of action for insulin-sensitizing agents. Pioglitazone and metformin both seem to cause metabolic deceleration of the β-cell via inhibition of mitochondrial metabolism. This mode of action could participate in the beneficial effects of these compounds in the context of metabolic stress. The fact that these drugs affect both insulin sensitivity and insulin secretion, the two major components of T2D, may explain why they are among the most powerful anti-diabetic agents. Metabolic deceleration is a new therapeutic approach worth considering for the treatment of T2D and other metabolic diseases.

Aquesta tesi pretén respondre a la pregunta: Què pot fer la infermeria d'atenció primària i què és el què fa, en els problemes del peu en persones amb diabetis tipus 2 a Catalunya?. L'estat del tema exposa la importància de les complicacions en el peu i la possibilitat de reduir-les amb un paper rellevant de la infermeria d'atenció primària. La investigació s'ha centrat en conèixer de què disposa, les activitats que desenvolupa, i què li manca a la infermeria per desenvolupar el seu potencial. Els resultats observats són representatius i mostren clares desigualtats assistencials entre centres, regions sanitàries i tipus de gestió. Suggerint que en l'atenció primària convé organitzar i coordinar l'atenció als problemes del peu en la diabetis, millorar la formació i la capacitació infermera en el tema, fomentar i optimitzar la presència de professionals especialitzats, i potenciar l'educació en diabetis i la promoció de la salut. / This doctoral thesis intends to reply to the question: what can make primary care nursing and what it makes in the problems of the foot in type two diabetic patients in Catalonia? The state the subjects sets forth the importance of the foot complications and the possibility to reduce them with a relevant role of the primary care nursing.The research has focused on knowing of what the orders, the activities that it develops and what needs the nursing to develop its potential. The observed results are representative and they show clear welfare inequalities among centers, sanitary regions and type of management. Suggesting that in primary care, it agrees on organizing and coordinating the attention in diabetic foot problems, improving the nursing training in this topic, fostering and optimizing the presence of specialized professionals and promoting the diabetes education and the health promotion.

By the year 2025, it is anticipated that over 300 million individuals world wide will have type 2 diabetes, with a projected increase from 84 to 288 million (170%) in developing countries and from 51 to 72 million (42%) in developed countries. Diabetes leads to a markedly increased risk of heart disease and renal failure and to expensive and debilitating retinopathy and neuropathy. Cognitive decline is also increased. As there is accumulating evidence of the beneficial effects of moderate carbohydrate, low fat dietary patterns compared to high carbohydrate diets, this thesis will focus on the effects of moderate carbohydrate high protein dietary patterns (total carbohydrate: protein: fat ratio of 40%:34%:26%) on glycemic control, risk factors for macrovascular disease and cognitive function. Information on two key areas in type 2 diabetes will be presented, 1. Acute effects of dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels assessed using continuous glucose monitoring systems (CGMS) with verification of these results through a small repeat study. 2. Chronic effects of energy restricted dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels, HbA1c, cognitive function, cardiovascular disease (CVD) risk markers and renal function. In the acute study, we recruited 23 subjects with type 2 diabetes. The participants were randomized to each of 4, 3-day interventions in a cross over design with a 4 day wash out period in which the carbohydrates were distributed differently at each meal; carbohydrates evenly distributed across the day, or carbohydrates loaded at breakfast, lunch or dinner. Glucose levels were continuously measured using CGMS. Outcomes were assessed by postprandial peak glucose (Gmax), time spent above 12 mmol/L (T>12) and total area under the glucose curve (AUC20). The intervention showed that an even distribution of carbohydrates did not optimise blood glucose control, whereas carbohydrates loaded at the lunch time meal provided the most favourable postprandial profile. To verify these results we conducted a repeat study. Six of the previous participants accepted the invitation to return and complete the even distribution arm of the study after a 20 week time lag. The intervention showed that although HbA1c, fasting blood glucose (FBG), AUC, exercise and ambient temperature remained constant there was a significant effect of change in sunlight hours on Gmax, suggesting an effect of sunlight. To assess the chronic effects of energy restricted dietary patterns on the determinants of HbA1c, cognitive function, CVD risk markers and renal function under conditions of weight loss, we recruited 82 participants with type 2 diabetes. These participants were randomised to one of two high protein energy restricted dietary patterns that differed in cholesterol content, for a 12 week period, in a parallel design. A sub group of these participants completed cognitive function testing with (n=34) or without (n=17) CGMS at baseline and at 8 weeks. After 8 weeks of the intervention the determinants of HbA1c under conditions of energy restriction were evaluated. The intervention showed the change in FBG accounted for most of the variance in change in HbA1c, but % energy reduction also contributed independently of FBG. Both energy restricted high protein diets equally improved glycemic control, particularly T>12, AUC, HbA1c and FBG. Fifty one participants completed cognitive testing to evaluate the effect of weight loss and blood glucose control on cognition. Cognitive function was not altered by time, diet, baseline lipid levels. Working memory was predicted by FBG. Short term memory was predicted by FBG, Gmax and AUC24. Sixty five participants completed 12 weeks of the intervention to assess CVD risk markers and renal function. Renal function was maintained and CV markers improved on both dietary patterns, with greatest improvement in HDL-C observed in the group consuming a high protein, energy restricted dietary pattern, high in dietary cholesterol. In conclusion, in the context of a high protein, carbohydrate restricted dietary pattern, cognitive function and renal function did not change, while glycemia and CV risk profiles improved with weight loss over the short term. Under conditions of energy balance diurnal glucose profiles were optimal when the carbohydrates were loaded in the lunch meal. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342253 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

Objective The aim of this study firstly, was to translate and test the validity and reliability of two diabetes-specific self-efficacy instruments (the Diabetes Management Self-Efficacy Scale; DMSES and the Perceived Therapeutic Efficacy Scale; PTES) in a Taiwanese population. The main aim of this study was then to develop an intervention based on self-efficacy theory that was appropriate for the Taiwanese population and to examine the effects of a self-efficacy enhancing intervention program (SEEIP). Background In Taiwan, the prevalence, mortality rate and healthcare cost of diabetes has dramatically increased. People with diabetes have low participation rates in performing self-care activities, with some two-thirds of diabetic patients not controlling their disease appropriately. Moreover, few studies in Taiwan have conducted randomised controlled trials or had improvement in patient self-care or self-management as their primary goal and no instruments that measure self-efficacy related to the management of diabetes (especially for outcome expectations) have yet been found and appropriately used to measure the effectiveness of self-management. Therefore, there is a particular need for research on self-efficacy enhancing intervention programs for people with type 2 diabetes. Design A convenience sample survey (n=230) was used in order to test the validity and reliability of C-DMSES and C-PTES in a Taiwanese population. Moreover, a randomised controlled trial (RCT) (n=145; the intervention group (72); the control group (73)) design was conducted in the main study with pre (baseline) and post-testing (undertaken at 3 months and 6 months following baseline collection). Intervention Both the control group and intervention group received the standard diabetic educational program in the outpatient clinic. The intervention group participants received the standard diabetic educational program and the following additional interventions: (1) viewed a 10-minute DVD (2) received a &quotDiabetes Self-Care" booklet (3) participated in four efficacy- enhancing counselling intervention sessions, and (4) participated in telephone follow-up. The self-efficacy model was adapted from Shortridge-Baggett & van der Bijl (1996). Diabetes self-management principles were used in program development and evaluation. Main outcome measures Instruments used in data collection included 1) Self-efficacy towards management of type 2 diabetes (as measured by the Chinese version of the Diabetes Management Self-Efficacy Scale; C-DMSES and the Chinese version of the Perceived Therapeutic Efficacy Scale; C-PTES); 2) self management behavior (as measured by the Summary of Diabetes Self-Care Activities; SDSCA); 3) health-related quality of life for diabetes (as measured by the Short Form-12; SF-12); 4) psychosocial well-being (as measured by the Medical Outcomes Study (MOS), Social Support Survey (SSS) tool and the Center for Epidemiology Studies Short Depression Scale; CES-D) and 5) health care utilisation (as measured by health care utilisation self report instrument). Data analysis Data were double-entered for verification using SPSS® statistical software. Study I: Descriptive statistics, regression analysis, Pearson's correlation, Cronbach's alpha-coefficients, factor analysis and Bland-Altman plots with 95% limits of agreement (LOA) were performed to evaluate validity and reliability of C-DMSES and C-PTES. Study II: Descriptive analysis was used to examine demographic variables and outcome variables. T-tests were used to analyse differences on continuous data between mean scores for the intervention and control groups. Categorical data were analysed using Chi-square statistics to test the significance of different proportions. To assess the group differences of dependent variable changes, repeated measures ANOVA/ ANCOVA were used. Results Study I: Convergent validity showed that C-DMSES correlated well with the validated measure of the General Self-Efficacy Scale (GSE) in measuring self-efficacy. Criterion-related validity showed that the C-DMSES was a significant predictor of the Summary of Diabetes Self-Care Activities (SDSCA) scores. Factor analysis supported the C-DMSES being composed of four subscales with good internal consistency (Cronbach's alpha=.77 to .93) and stability (ICC=.82). Similarly, significant criterion-related validity was demonstrated between the C-PTES and SDSCA scores. Convergent validity was confirmed as the C-PTES converged well with the GSE Scale in measuring self-efficacy. Construct validity of the C-PTES was confirmed through factor analysis and a single subscale formed. Internal consistency with a Cronbach's alpha was .95 and the test-retest reliability (ICC) was .77 and a Bland-Altman plot showed 97% of the subjects were within 2 standard deviations of the mean. Study II: The 3- and 6-month benefits of the intervention over usual care were increases in self-efficacy, outcome expectation, self-care activities, and social support. However, the results of the health-related quality of life and depression scores indicated that the change over time was not different in the two groups. A smaller proportion of the participants significantly in the intervention group, had been hospitalised and visited the emergency room than participants who were in the control group at the 6-month period. However, health-related quality of life and depression were not significantly increased in the intervention group at the 3- and 6-month compared to the control group. Conclusion Results of Study I support the psychometric properties of C-DMSES and C-PTES in providing a measure for self-efficacy specific to persons with type 2 diabetes in Taiwan. The main study revealed that the SEEIP for type 2 diabetes based on self-efficacy theory was culturally acceptable to Taiwanese people with diabetes and that the SEEIP was effective in the self-management of people with type 2 diabetes.

By the year 2025, it is anticipated that over 300 million individuals world wide will have type 2 diabetes, with a projected increase from 84 to 288 million (170%) in developing countries and from 51 to 72 million (42%) in developed countries. Diabetes leads to a markedly increased risk of heart disease and renal failure and to expensive and debilitating retinopathy and neuropathy. Cognitive decline is also increased. As there is accumulating evidence of the beneficial effects of moderate carbohydrate, low fat dietary patterns compared to high carbohydrate diets, this thesis will focus on the effects of moderate carbohydrate high protein dietary patterns (total carbohydrate: protein: fat ratio of 40%:34%:26%) on glycemic control, risk factors for macrovascular disease and cognitive function. Information on two key areas in type 2 diabetes will be presented, 1. Acute effects of dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels assessed using continuous glucose monitoring systems (CGMS) with verification of these results through a small repeat study. 2. Chronic effects of energy restricted dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels, HbA1c, cognitive function, cardiovascular disease (CVD) risk markers and renal function. In the acute study, we recruited 23 subjects with type 2 diabetes. The participants were randomized to each of 4, 3-day interventions in a cross over design with a 4 day wash out period in which the carbohydrates were distributed differently at each meal; carbohydrates evenly distributed across the day, or carbohydrates loaded at breakfast, lunch or dinner. Glucose levels were continuously measured using CGMS. Outcomes were assessed by postprandial peak glucose (Gmax), time spent above 12 mmol/L (T>12) and total area under the glucose curve (AUC20). The intervention showed that an even distribution of carbohydrates did not optimise blood glucose control, whereas carbohydrates loaded at the lunch time meal provided the most favourable postprandial profile. To verify these results we conducted a repeat study. Six of the previous participants accepted the invitation to return and complete the even distribution arm of the study after a 20 week time lag. The intervention showed that although HbA1c, fasting blood glucose (FBG), AUC, exercise and ambient temperature remained constant there was a significant effect of change in sunlight hours on Gmax, suggesting an effect of sunlight. To assess the chronic effects of energy restricted dietary patterns on the determinants of HbA1c, cognitive function, CVD risk markers and renal function under conditions of weight loss, we recruited 82 participants with type 2 diabetes. These participants were randomised to one of two high protein energy restricted dietary patterns that differed in cholesterol content, for a 12 week period, in a parallel design. A sub group of these participants completed cognitive function testing with (n=34) or without (n=17) CGMS at baseline and at 8 weeks. After 8 weeks of the intervention the determinants of HbA1c under conditions of energy restriction were evaluated. The intervention showed the change in FBG accounted for most of the variance in change in HbA1c, but % energy reduction also contributed independently of FBG. Both energy restricted high protein diets equally improved glycemic control, particularly T>12, AUC, HbA1c and FBG. Fifty one participants completed cognitive testing to evaluate the effect of weight loss and blood glucose control on cognition. Cognitive function was not altered by time, diet, baseline lipid levels. Working memory was predicted by FBG. Short term memory was predicted by FBG, Gmax and AUC24. Sixty five participants completed 12 weeks of the intervention to assess CVD risk markers and renal function. Renal function was maintained and CV markers improved on both dietary patterns, with greatest improvement in HDL-C observed in the group consuming a high protein, energy restricted dietary pattern, high in dietary cholesterol. In conclusion, in the context of a high protein, carbohydrate restricted dietary pattern, cognitive function and renal function did not change, while glycemia and CV risk profiles improved with weight loss over the short term. Under conditions of energy balance diurnal glucose profiles were optimal when the carbohydrates were loaded in the lunch meal. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342253 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Contexte Les programmes de promotion de la santé dans le milieu du travail sont des interventions complexes qui requièrent une compréhension des facteurs de risque pour l’identification des populations à cibler. Leur développement s’appuie souvent sur des méthodes de montage de projet qui ne tiennent pas compte de principes de promotion de la santé de la Charte d’Ottawa. Des approches méthodologiques adaptées sont nécessaires pour comprendre le fonctionnement de ces programmes. Objectifs Mener une réflexion autour de la promotion de la santé dans le milieu du travail à travers : (i) le développement de la « théorie de programme » d’une intervention de promotion de la santé intitulée « Plus Saine la Vie » réalisée à la Société Nationale des Chemins de Fer Français (SNCF) et (ii) l’identification des déterminants du diabète de type 2 et de l’hypertension artérielle que l’on peut mesurer en routine auprès d’une population de salariés en surpoids en milieu du travail. Méthodes L’outil de catégorisation des résultats de Promotion Santé Suisse a été utilisé pour développer la « théorie de programme » à l’aide d’une approche inductive fondée sur la documentation disponible sur l’intervention et l’observation de celle-ci sur le terrain. Vingt réunions itératives du comité de pilotage de l’intervention ont assuré la validation du processus qui a abouti au modèle final. Ensuite, nous avons utilisé la méthode de conception de programme proposée par Fry et Zask (2016) pour comprendre quels leviers d’action de la Charte d’Ottawa ont été mobilisés par l’intervention. L’identification des déterminants du diabète de type 2 et de l’hypertension artérielle a été réalisée par deux études transversales auprès des salariés en surpoids de la SNCF volontaires pour participer à un dépistage lors de la visite périodique de médecine du travail (janvier 2011- mars 2015). Résultats Une première « théorie de programme » a été développée avec des informations détaillées sur les activités, les résultats intermédiaires et les objectifs de l’intervention. Quatre axes stratégiques de la Charte d’Ottawa ont été mobilisés par l’intervention : création d’environnements favorables à la santé, renforcement de l’action communautaire, acquisition d’aptitudes individuelles et réorientation des services de santé. Dans la deuxième partie de notre travail, les quatre déterminants suivants ont été identifiés pour expliquer une hyperglycémie chez les salariés en surpoids : le sexe masculin, un âge ≥50 ans, une pression artérielle élevée (≥140/90 mm Hg), et une consommation quotidienne de produits sucrés. De plus, six déterminants ont été identifiés pour expliquer une pression artérielle élevée : le sexe masculin, un âge ≥40 ans, un indice de masse corporelle compris entre 27,5 et 29,9 kg/m², une hyperglycémie (mesurée par la glycémie capillaire ≥ 7 mmol/L), un risque élevé d'apnée du sommeil, et le travail de nuit. À l'inverse, être cadre au sein de la SNCF a été identifié comme un facteur protecteur de pression artérielle élevée. Discussion Notre travail propose un cadre conceptuel pour modéliser les programmes de promotion de la santé dans le milieu du travail et relève ainsi, par l’exemple concret de l’action « Plus Saine la Vie », comment certains des axes stratégiques de la Charte d’Ottawa ont pu être mobilisés dans le milieu du travail. Enfin, l’identification de déterminants du diabète de type 2 et de l’hypertension artérielle au cours d’une visite systématique de médecine du travail des salariés en surpoids montre la faisabilité d’interventions ciblées de promotion de la santé dans le milieu du travail. / Background Workplace health promotion programmes are complex interventions that need a wide understanding of risk factors to target high risk populations. The implementation of these programmes often requires the mobilization of classical methods of programme design and planning. However, these methods usually are not based on the Ottawa Charter five priority areas which provides a framework ensuring programme effectiveness. Understanding how a specific program is supposed to work is a crucial point in health promotion and could contribute to the appropriate programme planning and implementation. Thus, programme theory is a practical tool which captures the complexity of a programme by clarifying its objectives, activities and expected outcomes. Objective The aim of this work was to provide a deep insight about workplace health promotion by (i) developping the underlying programme theory of a health promotion programme entitled “Plus Saine la Vie” (“Healthier Life”) carried out in the French National Railways Company (SNCF) and (ii) identifying the factors that are associated with type 2 diabetes and hypertension and can be routinely measured in French overweight employees to develop targeted preventive strategies in the workplace. Methods The “Swiss Model for Outcome Classification in Health Promotion and Prevention” was used to develop the programme theory. Then, we used the design process proposed by Fry and Zask (2016) to understand which levers of action from the Ottawa Charter for Health Promotion had been mobilised in the programme. Secondly, two cross-sectional studies were conducted to identify the determinants of type 2 diabetes and hypertension among SNCF overweight employees who participated in a health screening conducted during their regular occupational health check-up (January 2011-March 2015). Results Our work provides a programme theory with detailed information regarding how this health promotion programme was supposed to work and what it was expected to be implemented in the workplace setting. Moreover, the programme design analysis showed that the programme had mobilised the following Ottawa Charter’s action areas in the workplace setting: “creating supportive environments”, “strengthening community action”, “developing personal skills” and “reorienting health services”. Significant predictors of hyperglycaemia were male sex, age ≥50 years, high blood pressure, and daily intake of sugary food. In addition, male sex, older age (age ≥40), body mass index between 27.5 and 29.9 kg/m², hyperglycaemia, high risk of sleep apnoea, and night work schedule were significantly associated with high blood pressure. Conversely, high job position was identified as a protective factor for high blood pressure. Discussion Our work provides an example of a programme theory which can be used as a framework to develop health promotion programmes in the workplace setting. Moreover, our work presents an analysis of the programme concerning the mobilisation of the Ottawa Charter’s action areas for health promotion in the workplace. Our findings could be used by occupational health professionals to design specific health promotion interventions in the workplace setting to target individuals at high risk for developing hypertension and type 2 diabetes.

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