Overweight and obesity are associated with Type 2 Diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictorexpress mature adipocyte markers but develop a striking lipid storage defect. In vivo,this results in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes transcriptional upregulation of select lipid metabolism genes controlled by PPARgand ChREBP. These include genes that control lipid uptake, synthesis, and degradation pathways as well as Akt2, the gene encoding its substrate and insulin effector. Finally, we reveal a potential novel mTORC2 target, ACSS2, which might control intracellular acetyl-CoA availability and regulate metabolic gene expression by altering histone modification in white adipocytes. Exploring this pathway may uncover strategies to promote safe lipid storage and improve insulin sensitivity.

Bakgrund: Typ 2 diabetes mellitus är en av de stora folksjukdomarna och förekomsten av sjukdomen ökar i hela världen. Typ 2 diabetes mellitus kan medföra allvarliga komplikationer om sjukdomen inte behandlas korrekt. Det går inte att bli frisk från sjukdomen, men genom livsstilsförändringar kan blodsockret sänkas till normala nivåer. Detta innebär att vården har en stor uppgift att hantera för att främja hälsan hos dessa patienter. För att stödja patienten i att hantera sin situation kan sjuksköterskan använda sig av motiverande samtal. Syfte: Beskriva effekten av motiverande samtal hos patienter med typ 2 diabetes mellitus gällande levnadsvanor. Metod: En kvantitativ litteraturöversikt med 14 vetenskapliga artiklar. Resultat: Motiverande samtal visar en varierad effekt. Positiv effekt kunde ses på egenvård, midjemått samt fysisk aktivitet. Ingen effekt kunde påvisas gällande övriga utfallsmått. Vid summering av samtliga utfallsmått från artiklarna visade motiverande samtal endast ha 35% signifikant effekt. Konklusion: Trots varierande effekt av motiverande samtal kan det vara en möjlig metod för sjuksköterskor i mötet med patienter med typ 2 diabetes mellitus för att minska risken för komplikationer.Sjuksköterskan kan med hjälp av motiverande samtal främja motivation, men för att detta ska ha effekt krävs att patienten själv har motivationen att förändra sin livsstil. / Background: Type 2 diabetes mellitus is one of our primary public diseases, and the incidence of the disease is increasing worldwide. Type 2 diabetes mellitus can lead to severe complications if the disease is not controlled. It is not possible to cure the disease, but blood sugar can be lowered to normal levels through lifestyle changes. This means that healthcare has a major task to handle to promote the health of these patients. To support the patient in managing their situation, the nurse can use motivational interviewing. Aim:To describe the effect of motivational interviewing in patients with type 2 diabetes mellitus regarding lifestyle. Method: A quantitative review with 14 scientific articles. Result: Motivational interviewing showed a varying effect. The positive effects could be seen onself-care, waist measurements, and physical activity. No effect is shown regarding other outcome measures. When summarizing all outcome measures from the articles, motivational interviewing showed only a 35% significant effect. Conclusion: Despite the varying effect of motivational interviewing, it may be possible for nurses to use in care for patients with type 2 diabetes mellitus to reduce the risk of complications. With the help of motivational interviewing, the nurse can promote motivation, but for this to have an effect,the patient himself must have the motivation to change his lifestyle.

ABSTRACTThe prevalence of diabetes is increasing dramatically, incurring a major health and socioeconomic burden. Type 2 diabetes (T2D), the most prevalent form of diabetes, results from a variable combination of insulin resistance and insulin deficiency, secondary to pancreatic β-cell failure. These defects are caused by a complex interplay between genetic and environmental/ lifestyle factors. Among the latter, poor dietary quality is a crucial driver of T2D development. Although adopting healthy dietary habits is considered as a mainstay for T2D prevention, what constitutes a healthy diet remains controversial. Epidemiological studies examining the association of dietary fat quality with T2D incidence have yielded equivocal results and may suffer from confounding. On the other hand, randomized trials assessing the impact of dietary fat saturation on glucose homeostasis have major methodological shortcomings, precluding reliable conclusions. In order to elucidate this question, we compared the effects of palm oil vs olive oil on glucose homeostasis and other relevant metabolic parameters, in a mouse model of high-fat diet-induced obesity. The saturated fatty acid-rich palm oil is the most abundantly used oil worldwide. Olive oil is a staple food of the Mediterranean diet, rich in monounsaturated fatty acids and widely regarded as healthful. In this model, palm oil was not more harmful than olive oil with regard to glucose/insulin homeostasis. However, palm oil was associated with increased visceral adiposity and triglyceridemia compared to olive oil. Circulating and tissue free fatty acid (FFA) concentration and composition are determined by dietary factors, as well as genetic and metabolic factors. There is accumulating evidence indicating that increased FFA levels and/or an unbalanced FFA composition with excess palmitate, induce β-cell dysfunction and apoptosis (lipotoxicity). To characterize the mechanisms underlying lipotoxicity, we combined RNA-sequencing with proteomics of β-cells exposed to palmitate, the most prevalent SFA in humans. This cross-omics study showed that palmitate altered lipid and amino-acid metabolism, and affected amplifying pathways of insulin secretion and exocytosis. Furthermore, palmitate induced stress pathways, including mitochondrial dysfunction, oxidative stress and endoplasmic reticulum (ER) stress. ER stress is triggered when protein folding demand exceeds ER folding capacity. This response aims to restore ER homeostasis but if unresolved, it can become deleterious. Islets from T2D patients display signs of ER stress, pointing to a potentially pathogenic role of the latter.Monogenic and neonatal diabetes are rare forms of diabetes caused by single gene mutations. These forms are of particular interest, as they can serve as ‘human knockout’ models of diabetes. Recent evidence shows that there is overlap in the genetic basis of monogenic diabetes and T2D, suggesting that they may be part of a pathologic continuum. To explore the role of ER stress in diabetes pathogenesis, we studied two different genetic syndromes involving neonatal or early-onset diabetes, caused by mutations in genes related to ER function (DNAJC3 and YIPF5). Using in vitro knockdown models, we showed that ER stress elicited by impaired chaperone function (DNAJC3) or by impaired ER-to-Golgi protein transport (YIFP5) causes β-cell apoptosis. Altogether, our findings support that lipotoxic and genetic ER stress contribute to diabetes pathogenesis. Preventing or modulating ER stress thus holds anti-diabetic therapeutic potential. Future research should focus on defining optimal strategies to restore a balanced FFA profile and enhance ER function, aiming to prevent ER-stress induced β-cell failure. RésuméLa prévalence du diabète progresse constamment, posant un défi sanitaire et socioéconomique majeur. Le diabète de type 2 (DT2), la forme la plus courante de diabète, résulte de la résistance à l’insuline, en association avec un déficit insulinique dû à la défaillance des cellules β pancréatiques. Ces anomalies découlent d’une interaction complexe entre des facteurs génétiques et des facteurs liés au mode de vie. Parmi ces derniers, la qualité du régime alimentaire est un facteur crucial pour le développement du DT2. Bien que le suivi d’un régime alimentaire sain est considéré comme le pilier pour la prévention du DT2, ce qui constitue un régime sain demeure un sujet de controverse.Les études épidémiologiques examinant l’association entre la qualité de la graisse alimentaire et l’incidence du DT2 ont donné des résultats équivoques, affectés éventuellement par des facteurs confondants. En outre, les études randomisées évaluant l’impact du degré de saturation de la graisse alimentaire sur l’homéostasie du glucose comportent des limitations méthodologiques majeures. Afin d’élucider cette question, on a comparé les effets de l’huile de palme aux effets de l’huile d’olive sur l’homéostasie du glucose et d’autres paramètres métaboliques pertinents. Dans ce but, on a utilisé un modèle murin d’obésité induite par un régime riche en graisse. L’huile de palme est riche en acides gras saturés et elle est l’huile la plus utilisée globalement. L’huile d’olive est un aliment phare du régime Méditerranéen, riche en acides gras monoinsaturés et généralement reconnu comme un aliment sain. Dans notre modèle murin, la consommation d’huile de palme n’était pas plus néfaste que celle de l’huile d’olive sur l’homéostasie du glucose, la sensibilité à l’insuline et l’insulinosécrétion. Par contre, l’huile de palme était associée à une adiposité viscérale et une triglycéridémie plus élevée comparée à l’huile d’olive.La concentration et la composition des acides gras libres (AGL) sont déterminées par des facteurs alimentaires, génétiques et métaboliques. Des données abondantes démontrent que la présence des niveaux élevés d’AGL et/ou d’une composition déséquilibrée d’AGL induit la dysfonction et l’apoptose des cellules β (lipotoxicité). Pour caractériser les mécanismes sous-jacents de la lipotoxicité, on a combiné un séquençage ARN à une étude protéomique des cellules β exposées au palmitate, l’AGL saturé le plus courant chez l’homme. Cette étude conjointe a montré que le palmitate altère le métabolisme des lipides et des acides aminés, les voies d’amplification de la sécrétion d’insuline et l’exocytose. Le palmitate induit également des voies de stress cellulaires, telles que la dysfonction mitochondriale, le stress oxydatif et le stress du réticulum endoplasmique (RE). Le stress du RE est activé quand les besoins en sécrétion protéique dépassent les capacités de l’organite. Cette réponse a pour but de rétablir l’homéostasie du RE mais si le stress reste non résolu, ceci peut s’avérer délétère. Des îlots des patients avec un DT2 montrent des signes de stress du RE, évoquant un rôle potentiellement pathogénique de ce dernier.Le diabète monogénique et néonatal sont des formes rares de diabète causées par des mutations d’un seul gène. Ces formes sont particulièrement intéressantes sur le plan physiopathologique car elles représentent des ‘knockout’ humains. Des données récentes montrent que la base génétique du diabète monogénique n’est pas complètement distincte de celle du diabète de type 2 et les deux entités pourraient faire partie d’un continuum. Afin d’explorer le rôle du stress du RE dans la pathogénèse du diabète, on a étudié deux syndromes génétiques entraînant un diabète néonatal ou à début très précoce. Ces syndromes sont causés par des mutations dans des gènes impliqués dans la fonction du RE (DNAJC3 et YIPF5). En silençant ces gènes in vitro, on a montré que le stress du RE, déclenché soit par une dysfonction des chaperones (DNAJC3), soit par un retard du trafic de protéines du RE vers le Golgi (YIPF5), induit l’apoptose des cellules β.Ces résultats suggèrent que le stress du RE génétique et lipotoxique contribuent à la pathogénèse du diabète. La prévention ou modulation du stress du RE présente donc un potentiel thérapeutique anti-diabétique. Des études futures pourraient permettre de définir des stratégies optimales pour rétablir un profil d’AGL équilibré ou renforcer la fonction du RE, en vue de prévenir la défaillance des cellules β. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

African American women (AAW) are at a high risk for type 2 diabetes, a debilitating and potentially fatal disease for which there is no cure. The purpose of this study was to extend the research of Mosca et al. (2012) by examining the relationship between caregiver status and self-reported health status for AAW 18 years or older diagnosed with type 2 diabetes. The chronic care model (CCM) provided the theoretical framework for this study. The CCM promoted routine care for patients with chronic illnesses to migrate from acute care to proactive, planned, and risk-based protocols. A binomial logistic regression investigated the relationship between caregiver status, categorized as paid or unpaid, and self-reported health status, which was dichotomized as either good to excellent health or poor to fair health. There was a statistically significant relationship between primary caregiver status and self-reported health status among AAW diagnosed with Type 2 diabetes after controlling for age, education, and marital status (p < .004). Based on the fitted binomial logistic regression model, there were 186 cases of AAW with type 2 diabetes; having a paid caregiver was associated with a lower odds of having good to excellent health (OR = 0.294). About 12.3% of the variance in self-report health status was attributable to caregiver status. Overall, 82.6% of predictions were accurate. Nearly all participants required frequent assistance from a caregiver in the preceding 12 months. These findings suggest a critical need for healthcare service providers to educate caregivers as a means to deliver post-acute care to AAW diagnosed with type 2 diabetes, consistent with the CCM.

Adventists following a plant-based diet have half the prevalence and incidence of type 2 diabetes than nonvegetarian Adventists. This study used a quantitative, correlational study design to assess if there was a significant difference in type 2 diabetes prevalence rate between Adventists and non-Adventists preprogram, and if there were significant differences in biometrics between Adventists and non-Adventists with diabetes pre- and post-Complete Health Improvement Program (CHIP). This study incorporated the social ecological model for its conceptual framework and examined pre- and postprogram changes among Adventists (n=210; 20.1%) and non-Adventists (n=836; 79.9%) with type 2 diabetes. It used secondary data from participants in the volunteer-delivered CHIP intervention from 2006 to 2012 (n=7,172), a whole foods, plant-based, vegan health program. Analysis showed a significant difference in the pre-CHIP diabetic state between the two groups in step one, but not after controlling for covariates in step two (OR=0.96 and 0.91; CI=1.21 and 1.24). A repeated measures MANOVA analysis indicated that religious affiliation (Adventist or non-Adventist) was the determining factor in improved biometric outcomes pre- and post-CHIP for TC (F(1) = 5.65; p = 0.02), and LDL (F(1) = 5.76; p = 0.02) but not for HDL (F(1) = 0.00; p = 0.99), TG (F(1) = 0.19, p = 0.67), FPG (F(1) = 2.71, p = 0.10), SBP (F(1) = 2.25; p = 0.13), DBP (F(1) = 1.20; p = 0.27), and BMI (F(1) = 1.65; p = 0.20). However, both groups improved post-CHIP in all biometrics. The implications for positive social change from this study showed that CHIP is an effective lifestyle model for improving type 2 diabetes outcomes for both Adventists and non-Adventists, a model that does not involve the use of pharmaceuticals.

Abstract Type 2 Diabetes Mellitus (T2DM) is the seventh leading cause of death in the United States with a projected increase of 552 million people worldwide who will be affected with this illness by 2030. The need to address this issue is vital to prevent complications and reduce healthcare spending. The DNP project is aimed at planning and designing a nutritional education program tailored toward specific ethnic groups in order to increase knowledge in making healthy food choices. This project is intended to educate Registered Nurses (RNs) on nutrition so that they can offer dietary knowledge to T2DM patients. Additional patients can be reached by educating the RNs rather than patients being limited to consultations with a Certified Diabetes Educator or Registered Dietician. This project focused on whether healthy nutrition tailored toward the individual's own ethnic foods helps to stabilize glycemic values for patients with Type 2 diabetes. A toolkit was utilized to aid with the RNs' learning on healthy nutrition and its impact on the management of blood glucose. It addressed areas such as food groups and calories, grocery shopping, preparation methods, and portion control. The framework for design utilized the basic concepts associated with the systems theory with an intended goal to prevent further complications and improve patients' glycemic value through consuming nutritious foods. The logic model will be used to evaluate the impact of healthy nutrition on blood glucose through pre- and post-program tests of the RNs' nutritional knowledge on healthy eating. The continuation of this program will promote positive social change by helping patients to achieve a healthier lifestyle and reduce healthcare expenditures.

Indiana University-Purdue University Indianapolis (IUPUI) / Type 2 diabetes, a chronic condition affecting millions, continues to rise in epidemic proportions. Type 2 diabetes, managed through lifestyle changes, affects the entire family. Family caregivers provide vital support to these individuals; however, little research has been conducted surrounding the perceived difficulty or ease of caregiver activity and supportive behaviors. The purpose of this dissertation was to develop and psychometrically test a scale that measures this difficulty or ease of activities and behaviors. This was accomplished through the compilation of three distinct manuscripts. First, an integrative review was conducted to identify what is known regarding needs and concerns of family caregivers of persons with type 2 diabetes; findings revealed a need for more research. Then, based on these recommendations, a qualitative study was conducted that explored the needs and concerns identified by 33 American Indian, African American, and White family caregivers. All these caregivers had similar concerns related to needing general diabetes information, providing support to the family member, and taking care of their own health. Study themes were used to develop items for a new instrument, the Diabetes Caregiver Activity and Support Scale (D-CASS) that was psychometrically tested with 101 American Indian, African American, and White family caregivers of persons with type 2 diabetes. This study used a cross-sectional, descriptive-correlational design and provided evidence of internal consistency reliability (α = .82) and two-week test-retest reliability (intraclass correlation coefficient = .70) for the D-CASS. Criterion-related validity was established using a single-item criterion measuring overall how easy or difficult it was for caregivers to provide care for their loved ones (r = .65, p < .01). Unidimensionality was supported by factor analysis, with loadings ranging from .45 to .70, with 32% of the variance explained by the first factor (eigenvalue = 4.02). Model testing through a series of three hierarchical multiple regressions guided by a conceptual model provided further evidence of construct validity for the D-CASS. This dissertation provided better understanding of needs and concerns of family caregivers of persons with type 2 diabetes and led to the development of a psychometrically sound diabetes-specific instrument for future research.

Purpose: This qualitative descriptive study was undertaken to describe Eastern Woodlands Native adult perspectives, health care beliefs and type 2 diabetes management experiences. Specific Aims: The specific aims were to 1) explore and describe perceptions of type 2 diabetes among Eastern Woodland Native adults and how they relate to their understandings about the cause and treatment approaches to the disease, 2) describe how family, friends, and community intersect with type 2 diabetes management, 3) describe relationships with health care providers and 4) determine resources that would help diabetes-self management within their community. Framework: The PEN-3 Model by Airhihenbuwa was the initial framework used for the study. Methods: A qualitative descriptive design with maximum variation and snowball sampling was used and data was analyzed using qualitative content analysis. Results: The overarching theme of Together We Can Return To Balance comprised five sub-themes: Coming to Know Life Paths with T2DM, Negotiating My Way Forward, Making Important Connections, Acknowledging the Imbalance, and Sticking Closer to Mother Earth illustrating physical, spiritual, and environmental health factors influencing DSM capacities. Conclusion: Native perspectives should be viewed as a crucial contextual variation for type 2 diabetes care when developing DSMES and for improving DSM capacities in these populations.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19892号 / 医博第4141号 / 新制||医||1016(附属図書館) / 32969 / 京都大学大学院医学研究科医学専攻 / (主査)教授 川村 孝, 教授 横出 正之, 教授 妹尾 浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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