Thesis (MScMedSc)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Introduction: A westernized diet rich in saturated fats and sugars, together with a sedentary lifestyle, has contributed to the dramatic increase in obesity during the last decade (Zimmett et al, 2001; Wild et al, 2004). Obesity is associated with dyslipidemia and insulin resistance which are major risk factors for the development of type 2 diabetes (T2D) (Zimmet et al, 2001, Kahn et al, 2006; Schröder et al, 2007). High-fat feeding in rodents induces symptoms similar to the human metabolic syndrome without progression to T2D (Woods et al, 2002; Weir and Bonner-Weir, 2007). The addition of fructose to a high-fat diet exacerbates the insulin resistance and leads to impaired pancreatic function of insulin secretion and glucose intolerance (Basciano et al, 2005; Stanhope et al, 2009). Aims: The aim of this study was to establish the effect of a high-fat and sucrose/fructose diet on glucose metabolism, the development of insulin resistance and β-cell dynamics. Methods: Weanling Wistar rats were randomized into two study groups; study one over an experimental period for three months and study two for twelve months. Each study consisted of a control group that received standard rat chow and water; and two experimental groups receiving either a high-fat diet and water (HFD) or a café diet consisting of HFD with the addition of 15% sucrose/fructose (CFD). Fasting glucose and insulin concentrations, intravenous glucose tolerance test (IVGTT), glucose stimulated insulin secretion rates and 2-deoxy-[3H]-D-glucose uptake in muscle, liver and fat were measured. The pancreata were harvested for immunohistochemical labeling of β-cells (insulin), α-cells (glucagon), GLUT2 (glucose transport) and MIB5 (proliferation). Samples of the pancreata were also collected for electron microscopy. Results and discussion: Feeding Wistar rats a CFD induced obesity, insulin resistance and glucose intolerance. By twelve months the rats had an impaired glucose response with increased IVGTT peak values, area under the curve (AUC) values and glucose clearance rates. Concomitantly, the glucose stimulated insulin secretion rate (GS-ISR) was attenuated. Stimulated glucose disposal as measured by 2-deoxy-[3H]-D-glucose uptake was reduced in muscle and adipose tissue at three months. By twelve months, due to the age of the rats, stimulated glucose uptake declined compared to three months with no difference between groups. After three months the diets had no observable effect on the islets using light microscopy. However, by twelve months morphological changes were observed in both the HFD and CFD groups. In the HFD group large hypertrophied irregular islets with fibrous changes were observed. In the CFD group these morphological changes were more prominent with fibrous segregation and disruption of the normal endocrine arrangement. In addition, the presence of inflammatory cells within the affected islets is consistent with T2D. Conclusion: High-fat diet fed to Wistar rats induced obesity, abdominal adiposity and insulin resistance. The addition of sucrose/fructose to a high-fat diet exacerbated the insulin resistance and resulted in glucose intolerance and mild hyperglycemia. Morphological changes in the large islets were observed which are consistent with the development of T2D. / AFRIKAANSE OPSOMMING: Inleiding: ‘n Verwesterde dieët, ryk aan versadigde vette en suikers tesame met 'n passiewe lewenstyl, het bygedra tot die dramatiese verhoging in vetsug gedurende die laaste dekade (Zimmett et al, 2001; Wild et al, 2004). Vetsug word met dislipidemie en insulienweerstandigheid geassosieer wat hoof risikofaktore is vir die ontwikkeling van tipe 2 diabetes (T2D) (Zimmet et al, 2001; Kahn et al, 2006; Schröder et al, 2007). Hoë-vet voeding in knaagdiere induseer simptome soortgelyk aan menslike metaboliese sindroom sonder die ontwikkeling van T2D (Woods et al, 2002; Weir and Bonner-Weir, 2007). Die byvoeging van fruktose tot 'n hoë-vet dieët vererger insulienweerstandigheid en lei tot verswakte pankreas funksie, insuliensekresie en glukoseintoleransie (Basciano et al, 2005; Stanhope et al, 2009). Doelwitte: Die doelwitte van die studie was om die effek van hoë-vet en sukrose/fruktose voeding op glukosemetabolisme, die ontwikkeling van insulienweerstandigheid en β-sel dinamika te bepaal. Metodes: Gespeende Wistar rotte was in twee groepe gerandomiseer; studie een oor ʼn tydperk van drie maande en studie twee oor ʼn tydperk van twaalf maande onderskeidelik. Elke studie het 'n kontrole groep met standaard rot kos en water (control); en twee experimentele diëte wat of ʼn hoë-vet dieët en water (HFD) of 'n kafeedieët groep wat die HFD met die byvoeging van 15% sukrose/fruktose in hul drink water (CFD) ontvang. Fastende glukose en insulien, binneaarse glukose toleransie toets (IVGTT), glukose gestimuleerde insulien sekresie tempo en 2-deoxi-[3H]-D-glukose opname in spier, lewer en vet is gebruik om die effek van die dieët op glukosemetabolisme te bepaal. Die pankreata is uitgehaal vir immunohistochemiese identifisering van β-selle (insulien), α-selle (glukagoon), GLUT2 (glukose transport) en MIB5 (proliferasie). Monsters van die pankreata was ook vir elektronmikroskopie versamel. Resultate en bespreking: Voeding van ʼn CFD aan Wistar rotte induseer vetsug, insulienweerstandigheid en glukose-intoleransie Teen twaalf maande toon die rotte 'n verswakte respons tot glukose met verhoogde IVGTT piekwaardes, AUC waardes en glukose opruimingswaardes. Terselfdetyd is die glukose gestimuleerde insuliensekresie tempo (GS-ISR) ook verswak. Gestimuleerde glukose opruiming, soos deur 2-deoxi-[3H]-D-glukose opname bepaal, was verlaag in spier en vetweefsel teen drie maande. Teen twaalf maande, weens die ouderdom van die rotte, is die gestimuleerde glukose opname verlaag in vergelyking met drie maande sonder 'n verskil tussen groepe. Na drie maande kon geen sigbare morfologiese verskille met ligmikroskopie tussen die diëte waargeneem word nie. Teen twaalf maande is morfologiese verskille waargeneem in beide die HFD en die CFD groepe. In die HFD groep is groot hipertrofiese onreëlmatige eilande met fibrotiese verandering waargeneem. In die CFD groep was die morfologiese verandering meer gevorder met fibrotiese onderverdeling en ontwrigting van die normale endokriene rangskikking. Die teenwoordigheid van inflammatoriese selle in die geaffekteerde eilande is verenigbaar met T2D. Afleiding: Die voer van 'n hoë-vet dieët aan Wistar rotte veroorsaak vetsug, abdominale adipositeit en insulienweerstandigheid. Die byvoeging van sukrose/ fruktose tot die hoë-vet dieët vererger die insulienweerstandigheid en veroorsaak glukoseintoleransie en matige hiperglukemie. Morfologiese veranderings in die groter eilande was verenigbaar met T2D.

Intermittent fasting (IF) is a recently popularized meal timing strategy whereby individuals abstain continuously from any energy intake for 16 to 20 hours each day, subsequently condensing energy intake into a short period spanning 4 to 8 hours. We aimed to test the effects of intermittent fasting in 10 individuals with Type 2 Diabetes Mellitus in conjunction with recommendations to consume a high protein diet in a 6 to 8 week withdrawal study. This study consisted of three phases: baseline, intervention, and follow-up. During the 2-week baseline and intervention phases participants consumed meals at regular times. Biochemical, anthropometric, and physical activity measurements were taken at the end of each phase. Participants reported morning, afternoon and evening self-monitored blood glucose and fasting duration on a daily basis, in addition to completing a remote food photography diary three times within each study phase. Despite the short duration of the intervention phase, intermittent fasting led to significant decreases in weight, BMI, morning SMBG, and overall reductions in waist circumference, C-reactive protein, energy intake, carbohydrate intake, and fat intake. There were significant variations between participants in response to intermittent fasting in respect to changes in lipids and insulin sensitivity, which could not be explained by baseline biochemical or anthropometric measures, fasting duration, energy intake, or physical activity. Upon cessation of intermittent fasting, biochemical changes regressed towards baseline values during the follow-up period. Intermittent fasting was well tolerated by most participants, and no severe adverse events were noted. Morning nausea was the most common complaint, which abruptly ceased when medication timing was changed.

Introduction: Type 2 diabetes continues to be one of the most common non-communicable diseases worldwide and complications due to type 2 diabetes, such as cardiovascular disease (CVD) can cause severe disability and even death. Despite advances in the development and validation of cardiovascular risk scores, those used in clinical practice perform inadequately for people with type 2 diabetes. Research has suggested that particular non-traditional biomarkers and novel omics data may provide additional value to risk scores over-and-above traditional predictors. Aims: To determine whether a small panel of non-traditional biomarkers improve prediction models based on a current cardiovascular risk score (QRISK2), either individually or in combination, in people with type 2 diabetes. Furthermore, to investigate a set of 228 metabolites and their associations with CVD, independent of well-established cardiovascular risk factors, in order to identify potential new predictors of CVD for future research. Methods: Analyses used the Edinburgh Type 2 Diabetes Study (ET2DS), a prospective cohort of 1066 men and women with type 2 diabetes aged 60-75 years at baseline. Participants were followed for eight years, during which time 205 had a cardiovascular event. Additionally, for omics analyses, four cohorts from the UCL-LSHTM-Edinburgh-Bristol (UCLEB) consortium were combined with the ET2DS. Across all studies, 1005 (44.73%) participants had CVD at baseline or experienced a cardiovascular event during follow-up. Results: In the ET2DS, higher levels of high sensitivity cardiac troponin (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) and lower levels of ankle brachial pressure index (ABI) were associated with incident cardiovascular events, independent of QRISK2 and pre-existing cardiovascular disease (odds ratios per one SD increase in biomarker 1.35 (95% CI: 1.13, 1.61), 1.23 (1.02, 1.49) and 0.86 (0.73, 1.00) respectively). The addition of each biomarker to a model including just QRISK2 variables improved the c-statistic, with the biggest increase for hs-cTnT (from 0.722 (0.681, 0.763) to 0.732 (0.690, 0.774)). When multiple biomarkers were considered in combination, the greatest c-statistic was found for a model which included ABI, hs-cTnT and gamma-glutamyl transpeptidase (0.740 (0.699, 0.781)). In the combined cohorts from the UCLEB consortium, a small number of high-density lipoprotein (HDL) particles were found to be significantly associated with CVD: concentration of medium HDL particles, total lipids in medium HDL, phospholipids in medium HDL and phospholipids in small HDL. These associations persisted after adjustment for a range of traditional cardiovascular risk factors including age, sex, blood pressure, smoking and HDL to total cholesterol ratio. Conclusions: In older people with type 2 diabetes, a range of non-traditional biomarkers increased predictive ability for cardiovascular events over-and-above the commonly used QRISK2 score, and a combination of biomarkers may provide the best improvement. Furthermore, a small number of novel omics biomarkers were identified which may further improve risk scores or provide better prediction than traditional lipid measurements such as HDL cholesterol.

Syfte: Att undersöka patienters upplevelser av livskvalitet vid nydiagnostiserad typ 2 Diabetes Mellitus. Metod: En empirisk studie med en kvalitativ ansats som innefattade tio deltagare med nydiagnostiserad typ 2 Diabetes Mellitus. Semistrukturerade intervjuer genomfördes utifrån en intervjuguide där insamlad data analyserades med kvalitativ manifest innehållsanalys. Resultat: Studien resulterade i fyra huvudkategorier och tio subkategorier. Upplevelsen av att få ett diagnosbesked varierade mellan deltagarna, för vissa deltagarna var beskedet inte förvånande medan andra upplevde känslor av chock och förnekelse. Deltagarna upplevde positiva förändringar, exempelvis viktnedgång och förbättrad hälsa men även negativa förändringar, exempelvis att vara beroende av läkemedel. Vissa upplevde ingen förändring alls. Typ 2 Diabetes Mellitus påverkade inte deltagarnas fysiska eller psykiska hälsa i de flesta fall. Deltagarna ansåg det som viktig att få stöd från både omgivningen och hälso- och sjukvården. Konklusion: Känslorna över ett diagnosbesked kunde variera men upplevelsen av livskvalitet påverkades inte av Typ 2 Diabetes Mellitus i de flesta fall i studien. Patientens inställning till att leva med Typ 2 Diabetes Mellitus inverkade på förmågan till att utföra egenvård, och distriktsköterskans stöd och engagemang ansågs vara betydelsefullt i sjukdomsprocessen. / Aim: To examine patients’ experiences of the quality of life in newly-diagnosed type 2 Diabetes Mellitus. Method: An empirical study with a qualitative approach that included ten participants with newly diagnosed type 2 Diabetes Mellitus. Semi-structured interviews were conducted on the basis of an interview-guide and the collected data was analyzed using qualitative manifest content analysis. Results: The study resulted in four main categories and ten subcategories. The experience of receiving a diagnosis varied between the participants, some participants did not experience the news as surprising, while others experienced feelings of shock and denial. The participants experienced positive changes, for example weight loss and improved health but also negative changes, such as being dependent of medicine. Some participants experienced no change at all. Type 2 Diabetes Mellitus did not affect the participants’ physical and mental health. The participants considered it important to get support from both surrounding people and health care. Conclusion: The feelings of a diagnosis could vary but the experience of quality of life is not affected by Type 2 Diabetes Mellitus in most cases in the study. The patient's attitude to living with Type 2 Diabetes Mellitus affects the ability to perform self-care, and the district nurse support and involvement is considered to be important in the process of the disease.

Background Obesity and associated metabolic dysregulation are linked to impaired cognitive function and alterations in brain structure, which increases the risk of age-related dementia. Increased glucocorticoid (GC) exposure may be a potential mediator of these negative effects on the brain. Methods and results In paper 1, we tested the relationship between cortisol levels, brain morphology and cognitive function in 200 women and men. Salivary cortisol levels were negatively related to cortical surface areas in prefrontal brain regions in both sexes. In participants with type 2 diabetes, high salivary cortisol levels were associated with lower memory performance. In paper 2, we tested in 70 overweight women the effects on tissue-specific GC metabolism of a Paleolithic diet or a diet following the Nordic nutrition recommendations. The 24-month interventions led to decreased expression of the GC-activating enzyme 11βHSD1 in adipose tissue, interpreted as a normalization of an obesity-related disturbance in GC metabolism. Furthermore, GC metabolism by 5α-reductase increased substantially after 2 years, an unexpected and novel result. The outcomes did not differ by diet. In paper 3, 20 women included in paper 2 were examined with functional magnetic resonance imaging (fMRI) while performing a memory task at baseline and after 6 months. Memory performance improved and functional brain responses increased in the hippocampus. Once again, the results were similar in both diet groups. In paper 4, 24 overweight participants with type 2 diabetes were examined with fMRI, using the same memory test as in paper 3, at baseline and after 12 weeks of intervention with a Paleolithic diet with or without exercise training. Functional brain response increased in the hippocampus, but memory was not improved. The addition of physical exercise did not alter the results. Conclusion Cortisol levels are linked to prefrontal brain structure and, at least in type 2 diabetes, lower memory performance. Furthermore, the dysregulated GC metabolism in obesity can be reversed by long-term diet- induced weight loss. Finally, dietary interventions with associated metabolic improvements alter functional brain responses during memory testing, including increased activation of the hippocampus. Whether these changes are linked to alterations in GC exposure and mediate improved cognition requires further study.

Bakgrund: Typ 2-diabetes är en kronisk sjukdom som står för 90 procent av alla diabetesfall i världen och beräknas öka de kommande åren, på grund av bland annat ohälsosamma levnadsvanor såsom kost och fysisk aktivitet. Egenvård innebär att patienten tar ansvar och för att hantera det behövs kunskap och stöd från vårdpersonalen. Syfte: att beskriva upplevelser av egenvården vid typ 2-diabetes, med fokus på livsstilsförändringar. Metod: En allmän litteraturöversikt baserad på tolv kvalitativa vetenskapliga artiklar genomfördes. Resultat: Det har framkommit olika upplevelser av egenvården och dessa har kategoriserats i teman med subteman: 1) Känsla av kontroll: Olika uppfattningar av betydelsen av typ 2-diabetes, 2) Upplevelser av livsstilsförändringar: Kostomläggning och Fysisk aktivitet och 3) Upplevelser av omvårdnadsåtgärder: Rådgivning, Motiverande samtal, MI och Gruppbaserad patientutbildning. Slutsats: Att ändra på sin livsstil kan upplevas som krävande och omställningen behöver stödjas och anpassas utefter patientens behov. Klinisk betydelse: Patientens upplevelser av egenvård med behov, krav och brister kan fungera som ett kunskapsverktyg för vårdpersonalen vid omvårdnaden av typ 2-diabetes. / Background: Type 2-Diabetes is a chronic disease that accounts for 90 percent of all diabetes cases in the world and is expected to increase in the upcoming years, due to unhealthy habits such as diet and physical activity. Self-management means that the patient takes responsibility and in order to manage it knowledge is needed and support from caregivers. Objective: To describe the experiences of self-management in Type 2-Diabetes, focusing on lifestyle changes. Method: A literature review based on twelve qualitative scientific articles were conducted. Results: It has turned out that there have been different experiences of self-management and these have been categorized into themes with subthemes: 1) Sense of control: Different views of the importance of Type 2-Diabetes, 2) Experiences of lifestyle changes: Change of diet and Physical activity and 3) Experiences of nursing interventions: Counseling, Motivational interviewing, MI and Group-based patient education. Conclusion: To change the lifestyle may be perceived as demanding and conversion needs to be adjusted to the patient's needs. Clinical significance: Patient’s experiences of self-management with needs, demands and deficiencies can serve as a knowledge tool for the care staff in the care of Type 2-Diabetes.

<p>A central aim in drug development is to ensure that the new drug is efficacious and safe in the intended patient population.</p><p>Mathematical models describing the pharmacokinetic-pharmacodynamic (PK-PD) properties of a drug are valuable to increase the knowledge about drug effects and disease and can be used to inform decisions. The aim of this thesis was to develop mechanism-based PK-PD-disease models for important safety and efficacy biomarkers used in anti-diabetic drug development. </p><p>Population PK, PK-PD and disease models were developed, based on data from clinical studies in subjects with varying degrees of renal function, non-diabetic subjects with insulin resistance and patients with type 2 diabetes mellitus (T2DM), receiving a peroxisome proliferator-activated receptor (PPAR) α/γ agonist, tesaglitazar.</p><p>The PK model showed that a decreased renal elimination of the metabolite in renally impaired subjects leads to increased levels of metabolite undergoing interconversion and subsequent accumulation of tesaglitazar. Tesaglitazar negatively affects the glomerular filtration rate (GFR), and since renal function affects tesaglitazar exposure, a PK-PD model was developed to simultaneously describe this interrelationship. The model and data showed that all patients had decreases in GFR, which were reversible when discontinuing treatment. </p><p>The PK-PD model described the interplay between fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c) and haemoglobin in T2DM patients. It provided a mechanistically plausible description of the release and aging of red blood cells (RBC), and the glucose dependent glycosylation of RBC to HbA1c. The PK-PD model for FPG and fasting insulin, incorporating components for β-cell mass, insulin sensitivity and impact of disease and drug treatment, realistically described the complex glucose homeostasis in the heterogeneous patient population. </p><p>The mechanism-based PK, PK-PD and disease models increase the understanding about T2DM and important biomarkers, and can be used to improve decision making in the development of future anti-diabetic drugs. </p>

Pancreatic beta-cells are responsible for secreting insulin into the circulation to maintain whole body glucose homeostasis. While pancreatic beta-cells have a large capacity to secrete insulin, their function progressively deteriorates during the pathogenesis of type 2 diabetes as a result of both genetic predisposition and environmental factors. Obesity is the largest risk factor for developing type 2 diabetes and is associated with various conditions that can impair normal beta-cell function, including excess free fatty acids, inflammation and insulin resistance. Accumulating evidence in the literature suggests that endoplasmic reticulum (ER) stress contributes to the molecular mechanism of pancreatic beta-cell failure during the progression of type 2 diabetes. In this thesis, I have examined the role of the ER stress sensor ATF6-alpha and also the ER-resident chaperone GRP78 in pancreatic beta-cell homeostasis and function. Work presented in Chapter 2 examined the function of naturally occurring ATF6-alpha protein variants associated with type 2 diabetes. I also examined the role of endogenous ATF6-alpha in pancreatic beta-cells, which is described in Chapter 3. Results from these analyses suggest that the ATF6-alpha gene is not a type 2 diabetes susceptibility gene; however, ATF6-alpha protein expression is important to beta-cell function and survival. Finally, ER stress markers have been detected in pancreatic beta-cells and insulin sensitive tissues (such as adipose and liver), which promote beta-cell dysfunction and insulin resistance, respectively. In Chapter 4, I examined the contribution of ER stress in beta-cell dysfunction specifically by generating transgenic mice over-expressing GRP78. The mice were subsequently challenged by high fat diet to determine their susceptibility to developing symptoms of type 2 diabetes. Indeed increased chaperone capacity in pancreatic beta-cells protected against obesity-induced glucose intolerance and insulin resistance. Overall, these data support the hypothesis that ER stress contributes to beta-cell dysfunction in type 2 diabetes progression.

Bakgrund: Diabetes typ 2 är en kronisk sjukdom som kan drabba människor i alla åldrar. Sjukdomen orsakar lidande och kan även påverka patienters livskvalitet. Förmåga till egenvård har en avgörande betydelse för att undvika komplikationer i samband med diabetes typ 2. Syfte: Studiens syfte är att beskriva patienters upplevelse av att leva med diabetes typ 2. Metod: Metoden som valdes var en litteraturöversikt bestående av 15 kvalitativa artiklar. Resultat: I resultatet framkom sex teman; begränsningar i vardagar, väcker många känslor, vikten av egenvårdsförmåga, vikten av kunskap och information, att bli stärkt i mötet med vårdpersonalen och behov av stöd från sin omgivning. Livet med diabetes innebär en kamp med krav i samband med sjukdomshantering. Patienter upplever avsaknad av motivation för att utföra egenvård kring förändringar av levnadsvanor och hantering av sjukdomen. Kunskap resulterar i en förbättrad sjukdomshantering. Patienter uttrycker sina behov av information. Stöd från vårdpersonal och omgivning underlättar patienters vardag med diabetes. Slutsats: Genom att förstå patienters upplevelser av att leva med diabetes kan vårdpersonal identifiera varje persons behov och förväntningar och därigenom erbjuda en personcentrerad vård. Vårdpersonal har en avgörande roll för att främja patienters förmåga att hantera sin sjukdom och uppleva välbefinnande. / Background: Type 2 diabetes is a chronic disease that can affect people of all ages. The disease causes suffering and even can affects patient’s quality of life. Ability for self-care is crucial to avoid the complications associated with diabetes. Aim: The study aims to describe patients' experience of living with type 2 diabetes. Method: The method chosen was a literature review consisting of 15 qualitative articles. Result: The result showed six themes; limitations in everyday life, evokes many emotions, the importance of self-care ability, the importance of knowledge and information, to be strengthened in the meeting with healthcare professionals and the need of support from their surroundings. Life with diabetes means a struggle with the requirements associated with disease management. Patients experience lack of motivation to perform self-care around the changes of living habits and management of disease. Knowledge results in an improved disease management. Patients express their need of information. Support from health professionals and environment facilitates patient’s daily life with diabetes. Conclusion: By understanding the experiences of patients living with diabetes, healthcare professionals can identify each individual's needs and expectations, and thereby offer a person-centered care. Health care professionals have a crucial role in promoting patients' ability to manage their illness and experiencing wellness.

Résumé : Problématique : Une augmentation importante de la prévalence du diabète a été observée au Nouveau-Brunswick au cours de la dernière décennie. Sachant que le diabète est associé à des complications de santé nombreuses et à des coûts élevés infligés au système de soins de santé, il devient important d’identifier les facteurs pouvant expliquer l’augmentation de la prévalence du diabète. L’étude a pour objectif de décrire l’évolution de ces facteurs afin de prioriser les interventions en lien avec cette maladie. Méthodes : Une revue critique de la littérature a permis l’identification de l’ensemble des facteurs pouvant expliquer l’augmentation de la prévalence du diabète. Des données administratives disponibles au Nouveau-Brunswick et des données tirées d’enquêtes de Statistique Canada ont été utilisées afin de décrire l’évolution de plusieurs des facteurs tirés de la revue critique de la littérature. Résultats : Une augmentation de 120% de la prévalence du diabète de type 2 au Nouveau-Brunswick a été observée entre 2001 et 2014. Cette augmentation pourrait être explicable par l’ensemble des cinq catégories de facteurs pouvant expliquer une augmentation de la prévalence dont plusieurs facteurs de risque individuels (dont l’obésité, le prédiabète et l’hypertension), de facteurs de risque environnementaux (dont l’urbanisation), de l’évolution de la maladie (exprimée par une diminution du taux de mortalité et une augmentation de l’incidence), de l’effet de détection (augmentation du nombre de personnes testées, diminution de la valeur d’HbA1c et de l’âge à la détection) et d’un effet du changement dans l’environnement (exprimé par un effet de période et de cohorte). Conclusion: L’augmentation de la prévalence du diabète notée au Nouveau-Brunswick pourrait s’expliquer par plusieurs facteurs de risque individuels, environnementaux, de l’évolution de la maladie, de l’effet de détection et d’un effet du changement dans l’environnement. Cette étude permettra de guider les actions sur le diabète au Nouveau-Brunswick et d’inspirer les autres provinces et pays à identifier les facteurs pouvant contribuer à l’augmentation de la prévalence du diabète grâce à la liste de l’ensemble des facteurs potentiellement explicatifs. / Abstract : Background: A major increase in the prevalence of diabetes in New Brunswick was observed over the last decade. Because diabetes is associated with many health complications and increases healthcare system costs, it is important to identify factors that could explain the increase in prevalence of diabetes in New Brunswick to help government prioritize interventions to reduce the burden of diabetes. The objective of this study is to describe factors potentially involved in the increase in prevalence of diabetes. Methods: A critical review of the literature was used to identify a list of factors that could explain an increase in prevalence of diabetes. Administrative data available in New Brunswick from 2001 to 2014 and data from Statistics Canada were used to conduct a repeated cross sectional descriptive study. Results: A 120% increase in the prevalence of type 2 diabetes was observed in New Brunswick between 2001 and 2014. The increase in prevalence of diabetes could be explained by an increase in the prevalence of many individual risk factors (such as obesity, hypertension and rediabetes), environmental risk factors (like urbanization), the evolution of the disease (expressed by an increase in incidence rate and a decrease in mortality rate), a detection effect (observed by an increase in number of people tested and a decrease in HbA1c values and age at detection) and environmental changes (with a period and cohort effect). Conclusion: The major increase in prevalence of diabetes in New Brunswick could be explained by many individual risk factors, environmental risk factor, the evolution of the disease, the detection effect and an environmental change. The comprehensive overview of factors presented will help guide actions about diabetes in New Brunswick and will inspire others jurisdictions to identify factors that could explain the increase in their country or province.