Introduction: Rates of childhood-onset type 1 diabetes (T1D) are steadily increasing among American youth, yet Black Americans are more likely to suffer from serious T1D-related complications caused by poor glycemic control. The aim of this thesis is to determine the external factors that are causing discrepancies in the development, diagnosis, treatment, and long-term management of T1D in Black youth. Methods: Epidemiological studies were compiled from the American Diabetes Association, Center for Disease Control (CDC), International Diabetes Foundation (IDF), Kaiser Family Foundation (KFF), and the Claremont Colleges Library network to identify the sociocultural aspects that negatively affect long-term glycemic control in Black youth. Results: Studies indicate that Black youth with T1D are more likely to face disadvantages in treatment regimen which are attributed to insurance coverage, socioeconomic status, education level, and implicit bias. Most studies demonstrate that these factors result in poor glycemic control, which subsequently leads to severe dysglycemia-related complications later in life. Conclusion and Discussion: Many Black youth who suffer from T1D receive insufficient healthcare, which is often exacerbated by a lack of social and economic resources. As a result, they may not have the means to maintain consistent, healthy glycemic levels. System-level changes are necessary to change the morbidity and mortality of T1D in Black youth. Future research should include the analysis of other racial minority groups in order to uncover additional institutional disparities.

Neuropathic pain affects up to 50% of the 29 million diabetic patients in the United States. Neuropathic pain in diabetes manifests as a disease of the peripheral and central nervous systems. The prevalence of type 2 diabetes is far greater than type 1 (90%), yet the overwhelming focus on type 1 models this has left the mechanisms of pain in type 2 diabetes largely unknown. Therefore I aimed to improve the current mechanistic understanding of pain associated with type 2 diabetes using two preclinical rodent models: Zucker Diabetic Fatty rats and db/db mice. In addition, I highlight the translational importance of simultaneous measurement of evoked/sensory and non-evoked/affective pain-related behaviors in preclinical models. This work is the first to show a measure of motivational-affective pain in a model of type 2 diabetes. I used methodological approaches including: (1) immunohistochemical and calcium imaging to assess stimulus-evoked sensitization; (2) measurement nociceptive behaviors and evoked sensory thresholds as well as pain affect using novel mechanical conflict avoidance and conditioned place preference/aversion assays; (3) pharmacological and genetic manipulation of methylglyoxal, TRPA1, AC1, and PPARγ. I hypothesized that the thiazolidinedione class of peroxisome proliferator-activated receptor gamma (PPARγ) agonists would reduce neuropathic pain-like behavior and spinal neuron sensitization in traumatic nerve injury and type 2 diabetes. As PPARγ is a nuclear receptor, and already targeted clinically to promote cellular insulin sensitization to reduce hyperglycemia, sustained changes in gene expression are widely believed to be the mechanism of pain reduction. In two separate research aims, I challenged this view and tested whether the PPARγ agonist pioglitazone would (1) rapidly alleviate neuropathic pain through a non-genomic mechanism and (2) reduce painful sensitization in nociceptive and neuropathic pain models independent from lowering blood glucose. I aimed to investigate the contribution of the glucose metabolite methylglyoxal to painful type 2 diabetes. I tested the hypothesis that methylglyoxal produces nociceptive, evoked, and affective pain that is dependent on activation of the sensory neuron cation channel TRPA1 and the secondary messenger enzyme AC1. I also tested whether pioglitazone or the novel methylglyoxal scavenging peptide GERP10 could alleviate painful type 2 diabetes.

L'objectif de cette thèse était de faire un bilan des méthodes et outils validés chez les patients DT2 et de développer une méthode d'estimation de la DE précise et adaptée à ces patients. Après avoir défini les activités quotidiennes les plus couramment réalisées dans une population de patients DT2 (Étude 1), nous nous sommes intéressés aux activités statiques et à la marche. Notre seconde étude a montré que le coût énergétique brut et net lors de la marche est respectivement 8,7 et 14,3 % plus élevé chez les patients DT2 en comparaison à un groupe témoin. Ce résultat mettait en avant la nécessité de valider une méthode d'estimation de la DE adaptée aux spécificités de la population diabétique. Les résultats de notre troisième étude ont démontré la validité de la DE estimée à partir d'un capteur intelligent et d'un algorithme existant pour différentes positions statiques et vitesses de marche chez des sujets DT2 et témoins. Enfin, dans une quatrième étude, trois équations d'estimation de la DE totale ont été développées à partir des données d'accélérations issues de trois capteurs intelligents (bas du dos, hanche et cheville) pour une population de sujets DT2 et témoins. Ces trois équations permettent d'estimer une DE totale lors d'activités statiques et de marches avec une différence moyenne respectivement de 0,009, -0,007 et -0,008 kcal/min pour le bas du dos, la hanche et la cheville en comparaison à celle de référence. Ainsi, ce travail de thèse a permis de valider trois équations d’estimation de la DE totale adaptés à une population de patients DT2, normo-pondérés ou en surpoids et âgés de 35 à 80 ans, basés sur les données d'un capteur intelligent. / The aim of this thesis is to review the methods and tools validated in T2D patients and to developed precise and adapted EE estimation method for these patients. After defining the most common daily activity in T2D patients (Study 1), we are interested, in particular, on static activities and walking. The results of our second study showed that the gross and net metabolic rate were 8.7 % and 14.3 % higher in T2D patients than in control subjects, respectively. These results highlight the need to validate an EE estimation method, adapted to diabetic’s specificities. The results of our third study demonstrated the validity of the activity-related EE estimated with a smart sensor and a validated algorithm during static activities and walking in T2D patients and healthy subjects. However, our results showed a lower accuracy of the estimated EE during walking in T2D patients in comparison with healthy subjects. Finally, in a fourth study, three equations estimating the total EE have been developed with acceleration data from three smart sensors (lower back, hip and ankle) and personal data (body mass index, sex, diabetes) from T2D and healthy subjects. These three equations allow to estimate the total EE during static activities and walking with a mean bias of 0.009, -0.007 et -0.008 kcal/min for the lower back, hip and ankle equation, respectively, in comparison with the reference value. Thus, this thesis enables to validate three suitable equations for the estimation of total EE in population including healthy and T2D patients, normal-weighted and overweighed and aged between 35 and 80 years, based on data from a smart sensor.

Albumin provides the vital scaffolding for growth and tissue repair and supports oncotic blood pressure and hemodynamics. In hemodialysis patients, albumin aids with fluid removal by drawing excess fluid from edematous tissues back into the blood where it can then be removed by a dialyzer. The hyperglycemia seen in dialysis patients with Type II diabetes progressively damages kidney glomeruli, which permits albumin seepage into the urine, thus lowering serum albumin. The conceptual framework underpinning this research is the van't Hoff theory of osmotic pressure. Under this framework, the solute-solvent relationship largely contributes to the osmotic movement of fluid. The purpose of this study was to determine if albumin levels differed in Hispanics on dialysis with and without diabetes and if potential differences existed over time. Differences in diabetes incidence in Hispanics suggest albumin levels may be dissimilar. Albumin physiology is abundant in the literature; how and to what magnitude albumin levels are affected in patients with diabetes is unclear. This quantitative, retrospective cohort study employed ANOVA, Repeated Measures t tests, Spearman Correlation, and regression analysis to evaluate potential associations between the research variables. Data were extracted from CMS-2728 forms to amass the final cohort (N = 827). Differences in albumin levels at the first 2 intervals were observed (Baseline 1.29 -± 0.49 mg/dL, F = 2.28, p < .032; 3 months 0.47 -±0.41 mg/dL, F = 1.62, p < .004). Covariables (hypertension, peripheral vascular disease, and infections) were controlled for but showed inconclusive results. Lower serum albumin in Hispanic dialysis patients with diabetes provides the impetus for developing ethnic-specific albumin therapies, thus promoting positive social change.

Although it is known that the prevalence of type 2 diabetes is on the rise in Canada, more information is needed on how well type 2 diabetes patients living in Cambridge, Ontario self-manage their diabetes and what factors influence their adherence to diabetes medication regimens. The objective of this cross-sectional study based on the theory of planned behavior was to determine if there are predictors of adherence to diabetes medications among patients living with type 2 diabetes in Cambridge. The World Health Organization STEPwise Approach to Surveillance was used to collect demographic data. Adherence and diabetes knowledge were assessed with the 8-item Morisky Medication Adherence Scale and the Michigan Diabetes Knowledge Test, respectively. Research subjects were 56 adults recruited through convenience sampling. Predictor variables that were tested included age, gender, level of education, and diabetes education, and the response variable was adherence to diabetes medication. Level of education (p = .001) was the only strong predictor of adherence to diabetes medication in the bivariate logistic regression analysis. In addition, in the multivariate logistic regression analysis, the following combined variables were significantly associated with adherence to type 2 diabetes medication: age and level of education; age and diabetes knowledge; gender and level of education; gender and diabetes knowledge; and level of education and diabetes knowledge. Application of the findings of this study may help to minimize the risk of diabetes-associated complications and improve quality of life for those with type 2 diabetes, thereby reducing type 2 diabetes healthcare costs for patients, insurance payers, and other stakeholders.

En Guadeloupe, la prévalence du diabète est deux fois plus élevée qu'en France hexagonale, avec une prédominance féminine. En dehors des facteurs environnementaux, la vitamine D et certains polymorphismes de gènes impliqués dans son métabolisme seraient associés à un risque de pathologies métaboliques. Les androgènes sont également associés aux anomalies du métabolisme glucidique, soit directement, soit via leur transporteur SHBG (Sex Hormone Binding Protein). Nous avons émis les hypothèses de recherche suivantes: 11 le statut en vitamine D et les polymorphismes des gènes impliqués dans son métabolisme pourraient être associés aux paramètres métaboliques chez des sujets Afro-Caribéens (AC). Ils expliqueraient l'importance des pathologies cardiométaboliques en Guadeloupe. 2/ la SHBG pourrait être associée aux anomalies du métabolisme glucidique, indépendamment des stéroïdes sexuels. Nos travaux sont présentés dans 4 études. Nous avons mis en évidence une prévalence élevée du déficit en vitamine D chez les sujets AC diabétiques de type 2. Nous avons trouvé une association significative entre le statut vitaminique D et le risque cardiométabolique chez ces sujets, mais aussi dans une population de sujets en hémodialyse chronique. Les polymorphismes des gènes impliqués dans le métabolisme de la vitamine D sont aussi associés à ce risque. Chez les sujets dysmétaboliques, une relation entre la SHBG, la graisse intra-hépatique, les hépatokines et les paramètres métaboliques a été mise en évidence, indépendamment des stéroïdes sexuels. En conclusion, la vitamine D et la SHBG pourraient être des marqueurs d'intérêt pour le dépistage des sujets à haut risque cardiométabolique. / In Guadeloupe, the prevalence of diabetes is two times higher than in Metropolitan France, with a female predominance. Apart from environmental factors, vitamin D and polymorphisms of genes involved in vitamin D metabolism would be associated with increased risk of metabolic diseases. Androgens are also associated with abnormal glucose metabolism, directly or through the Sex Hormone Binding Protein (SHBG). Our main hypotheses were: 11 Vitamin D status and polymorphisms of genes involved in its metabolism may be associated with metabolic pammeters in Afro-Caribbean (AC). They could explain the importance of cardiometabolic diseases in Guadeloupe. 2/ SHBG may be associated with abnormal glucose metabolism, independently of sex steroids. Our research is presente<! in four studies. We have demonstrated a high prevalence of vitamin D deficiency in AC patients with type 2 diabetes. We found a significant association between vitamin D status and cardiometabolic risk in these subjects, but also in a population of patients undergoing in chronic hemodialysis. Polymorphisms in genes involved in vitam in D metabolism are also associated with this risk, In dysmetabolic patients, a relationship between SHBG, intmhepatic fat, hépatokines and metabolic parameters was demonstrated, independently of sex steroids hormones. In conclusion, vitamin D and SHBG may be markers of interest for screening patients at high cardiometabolic risk.

<p>In type 2 diabetes the concentration of glucose in the blood is increased, and tissues like fat and musclebecome less sensitive to insulin. These two phenomena are interrelated, but since the glucose-insulininterplay is highly complex, many aspects are still not understood. Here, a model-based approachmight help. Nevertheless, also a model-based approach has a limited impact, unless models for thesub-systems can be combined into a model for the whole-body regulation. Such a multi-level,module-based model is referred to as a hierarchical model, and this thesis is a proof-of-principle studyfor the future development of such models.</p><p>We have extended one of the best available models for the whole-body regulations, to include azoomable module for the fat tissue. The first step was to implement the whole-body model in thesoftware MathModelica, which support hierarchical modeling. Second, the originally mergedinsulin-responding module was sub-divided, so that a fat tissue was singled out. Third, a model for theinput-output profile for the fat tissue was developed by combining mechanistic knowledge withexisting and novel data from human fat cells. Finally, this detailed model was fitted to the profile of theoriginal fat model, and inserted in the whole-body model, with negligible effect on the whole-bodysimulations.</p><p>The resulting model has the ability to translate mechanistically oriented simulations on the biochemicallevel, which is the level were drugs act, to the whole-body level, which is of clinical interest. This is aquantum leap forward for modeling, and understanding, glucose homeostasis and type 2 diabetes.</p>

<p>Bakgrund: I dagens samhälle flödar information från många olika håll. Kunskap förmedlas till patienter och anhöriga av olika professioner utan samordning, vilket kan leda till missförstånd. För patienter med diabetes typ 2 är det viktigt att få information som kan förstås och som är relevant för deras sjukdom. Genom patientutbildning kan patienten sedan bedriva egenvård och ta kontroll över sjukdomen. Syfte: Syftet med studien var att se hur patienter med nydiagnostiserad typ 2 diabetes förstår egenvård efter besök hos diabetessköterskan. Metod: En empirisk, kvalitativ intervjustudie genomfördes och innehållet analyserades med kvalitativ innehållsanalys inspirerad av Graneheim och Lundman. Resultat: Det framkom under intervjuerna att ungefär hälften av deltagarna förväntade sig att drabbas av diabetes, då det fanns i släkten. Diabetes var naturligt att få vid en viss ålder, med eller utan egenvård. De flesta hade gjort förändring av kostvanor och rökning under de första månaderna efter diagnosen och fått bekräftat att egenvården gjort nytta. Många kände oro inför att inte orka fortsätta med de förändringar, men var ändå inte oroliga för framtiden. Andra hade fortsatt stor tillförsikt och visste att resultatet berodde på dem själv. Slutsats: Med eller utan tidig egenvård hade sjukdomen kommit ändå. Den första tiden efter diagnosen genomfördes förändringar och egenvården kändes viktig. När sedan känslan av att ”må bra” återkom, dalade motivationen. Med täta besök hos diabetessköterskan motiverades patienterna att fortsätta.</p> / <p>Background: In today's society, information flowing from many different directions. Knowledge communicated to patients and families of different professions, without coordination, which can lead to misunderstandings. For patients with diabetes type 2, it is important to get information that is understandable and relevant to their illness. Through patient education, the patient may then engage in self-care and take control of the disease. Aim: The purpose of this study was to see how patients with newly diagnosed type 2 diabetes understand self-care after visiting the nurse. Method: An empirical, qualitative interviews were carried out and contents were analyzed using qualitative content analysis inspired by Granheim and Lundman. Results: It emerged during the interviews that about half of the participants expected to suffer from diabetes, when there was a family history. Diabetes was natural to get at a certain age, with or without self-care. Most patients had made changes in diet and smoking during the first months after being diagnosed and confirmed that self-care was useful. Many felt concerned about not being able to continue with the changes, but was not worried about the future. Others had continued very confident and knew that the outcome depended on themselfs. Conclusion: With or without early self-care the disease would had come anyway. The first time after beeing diagnosed, change and self-care feelt important. When the sense of "feel good" reappeared, the motivation faded. With frequent visits to the nurse, the patients were motivated to continue.</p>

<p><strong>Background:</strong> Type 2-diabetes is now a public health problem, which constitutes 85-90 percent of diabetes care. The district nurse´s role in treating a diabetic (/person with diabetes) does not only comprise pure medical treatment but also support, advice and training to the individual. In our profession as nurses, we have found that medical knowledge in patients with Typ 2-diabetes is not always enough to obtain changes in lifestyles.</p><p><strong>A</strong><strong>im:</strong><strong> </strong>The purpose of this study was to investigate the illness perceptions in patients with Type 2-diabetes and their impact on health behavior.</p><p><strong>Method:</strong> This qualitative study used grounded theory as a method.<strong> </strong></p><p><strong>Results: </strong>The informants described in the interviews, their perceptions of living with Type 2-diabetes. The analysis revealed the main category <em>periodic health</em> <em>behavior </em>built up on and related to five categories developed in data: <em>preventive health awareness, guilt, confidence in medical treatment, motivational problems and periods of insight.</em></p><p><strong>Conclusion: </strong>This study contributes to understanding of patients with Type 2 - diabetes their beliefs about illness and how it affects everyday lives.<strong></strong></p><p><strong>Keywords: </strong>Believes, District nurses, Groundey Theory, Illness perception, Type 2-diabetes</p>

The cardiac sodium-calcium exchanger (NCX) is an important membrane protein which regulates cellular calcium necessary for the optimal contractile function of the heart. NCX has become a focal point in ischemic heart disease (IHD) research as evidence suggests that reactive oxygen species (ROS) produced during IHD can cause NCX to malfunction resulting in an intracellular calcium overload leading to cardiac contractile abnormalities. Therefore, I hypothesized that NCX function is mediated by ROS increasing NCX1 activity during cardiac ischemia-reperfusion. To research this hypothesis, I investigated cellular mechanisms which may play a role in NCX dysfunction and also examined methods to correct NCX function. I found that reactive oxygen species directly and irreversibly modify NCX protein, increasing its activity, thereby worsening the calcium overload which is deleterious to cardiac function. I also elucidated the molecular means by which NCX protein modification occurs. Exploring pharmacological means by which to decrease NCX function to relieve the calcium overload and reduce the damage to the heart, I discovered that ranolazine (Ranexa), indicated for the treatment of angina pectoris inhibits NCX activity directly, thereby further reducing the calcium overload-induced injury to the heart. Furthermore, many IHD patients are also co-morbid for type-2 diabetes. These patients are prescribed sulfonylurea (SU) agents which act at the ATP sensitive K+ channel (KATP). One agent such as glibenclamide is known to have cardiotoxic side effects. Therefore, SUs devoid of any cardiac side effects would beneficial. Interestingly, patients possessing the genetic variant E23K-S1369A KATP channel have improved blood glucose levels with the use of the SU gliclazide. Therefore, I determined the functional mechanism by which gliclazide has increased inhibition at the KATP channel. These findings have implications for type-2 diabetes therapy, in which 20% of the type-2 diabetic population carries the KATP channel variant. In summary, the findings presented in this thesis have implications on treatment strategies in the clinical setting, as a NCX inhibitor can be beneficial in IHD and possibly type-2 diabetes. Moreover, a pharmacogenomic approach in treating type-2 diabetes may also provide a positive outcome when considering co-morbid cardiac complications such as atrial fibrillation and heart failure.