The prevalence of both Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is increasing worldwide, and the trends are unfortunately expected to continue. AD has recently been tied with mitochondrial dysfunction and insulin resistance, creating a mechanistic tie between AD and T2DM. Unfortunately, insulin resistance is often increased with aging and therefore, all individuals are at risk of brain mitochondrial dysfunction. Without proper mitochondrial function, the brain will degenerate, causing impaired cognitive function and reduced quality of life. The purpose of this study is two-fold: first, to understand the role of ceramides in insulin-induced brain mitochondrial dysfunction, and; second, to understand how ketones can restore brain mitochondrial function in aged brains. To evaluate the role of insulin resistance and ceramides in brain mitochondrial function, we induced hyperinsulinemia in ApoE4 mice. In addition to insulin, one group received myriocin injections to inhibit ceramide biosynthesis. We observed significant increases in brain ceramides in the insulin-treated group, which correlated with disrupted brain mitochondrial function. However, the group receiving myriocin alone, and, importantly, myriocin with insulin, had normal lipid profiles and normal mitochondrial bioenergetics. Altogether, these findings support the hypothesis of the key role of ceramides in insulin resistance-induced mitochondrial dysfunction within the brain. Next, young adult (5 months old) and old (28 months old) rats were assigned to either standard chow diets or very-low-carbohydrate, high-fat, ketogenic diets for 4 weeks. Following the treatment period, we analyzed brain mitochondrial function and oxidative stress. We found that the old rats fed the ketogenic diet had improved mitochondrial function in comparison to the old rats consuming standard rodent chow. In addition, the old rats fed a standard diet had significantly higher levels of oxidative stress than the aged rats on the very-low-carbohydrate, high-fat diet. These findings revealed that ketones can protect brain mitochondrial function in aging. Collectively, these results suggest that insulin resistance has a role in the development of brain mitochondrial dysfunction due to ceramide accumulation, while ketones can help mitigate some of the negative consequences of aging, perhaps some due to insulin resistance, on brain mitochondrial function.

American Indian and Alaska Native adults are 2.6 times more likely to have adult onset diabetes resulting from higher weight at birth. Pregnant women, providers, and Indian Health Service administrators may benefit from timely information during pregnancy to intervene and prevent Type 2 diabetes. The purpose of this study was to examine the role of birth weight in the development of Type 2 diabetes among Southeast Alaska (SEA) Natives. Guided by the socioecological model, this study examined the extent to which birth weight and gestational age predict the incidence of Type 2 diabetes. The study used a quantitative research design with retrospective analysis of 540 Native children born in SEA whose data were abstracted from birth journals and electronic medical records at ages 43-53. A t test indicated a significant positive correlation between gestational birth weight and incidence of Type 2 diabetes (t(285) = 13.91, p < .001). Birth weight for gestational age was associated with frequency of Type 2 diabetes, where small for gestational age (SGA) had the lowest risk (1.42%), average for gestational age (AGA) at medium risk (8.76%), and large for gestational age (LGA) had the highest risk at 32.25% (x^2(12) = 63.29, p < .0005). Findings indicate that adult Type 2 diabetes among the SEA Native population is due to excess intrauterine fetal weight gain. The positive social change implications include preventing Type 2 diabetes in SEA Natives by controlling weight gain during pregnancy; the findings also suggest using diagnostic risk profiles for those who are LGA at birth for the management of diabetes and prevention of obesity and chronic disease.

A research report from the Centers for Disease Control and Prevention (CDC) indicated that more than 50% of people with diabetes mellitus (DM) in the United States (U.S.) also have arthritis. The diabetes population is disproportionately affected by arthritis, but there has been limited and inconsistent research to confirm the association between type 2 diabetes mellitus (T2DM) and rheumatoid arthritis (RA). The current study aimed to identify an association between T2DM and RA for noninstitutionalized U.S. adults between 1999 and 2012 using a nationally representative sample from the National Health and Nutrition Examination Survey (NHANES) database (n =31,488 ). A quantitative, cross-sectional investigation was conducted to determine if patients with T2DM had an increased prevalence of RA. The current study also sought to identify characteristics that could affect the association between both groups and the prevalence of cardiovascular disease (CVD) in this population. Prevalence and adjusted odds ratios (OR) using logistic regression were calculated. The results show evidence of a strong association between T2DM and concomitant RA. Prevalence of RA was significantly higher in participants with T2DM compare to those without T2DM. Important factors in this association were gender, ethnicity, education, disability, and work functioning. The prevalence of CVD and adjusted OR of association were doubled in participants with T2DM and RA when compared to participants who had just one of the conditions; the OR of association was quadrupled when compared to those without this comorbidity. This study may provide patients and health care providers with a better understanding of the need for management of both conditions in a interdisciplinary manner

The relationship between physicians' perceptions of Mexican American patients at risk for Type 2 diabetes and the subsequent care they provide was studied. Primary care providers responded to questionnaires about their health promotion practices. A 2x2 analysis of variance was used to identify differences in reported treatment of patients that accounted for both ethnicity and risk. Results indicated Hispanic patients received less time with their providers than Caucasian patients regardless of risk for Type 2 diabetes. Both groups received about the same reported care in terms of information gathered for diagnosis, diagnosis made, and treatment regimen prescribed. Data also suggested that providers' scores for treatment regimen and information gathered were disappointingly low, which may not only account for the lack of statistically significant findings, but may reflect a larger issue within the medical care field.

Emerging evidence suggests that an important mechanism for the negative feedback control of insulin signalling involves the inhibition of tyrosine phosphorylation of IRS-1 by its prior serine/threonine (ser/thr) phosphorylation. IRS-1 ser/thr phosphorylation has been linked to the dissociation of IRS-1 from the insulin receptor and PI3K, and its degradation via a proteasome-dependent pathway. Studies in animal models have shown that increases in plasma free fatty acids (FFAs) are associated with reduced IRS-1-signalling, and so it has been postulated that elevated FFA cause insulin resistance by activating pathways that negatively regulate insulin action, including hyper-phosphorylation of ser/thr residues in IRS-1. We have shown that in the case of linoleate-induced insulin resistance in L6 rat skeletal muscle cells, the inhibition of IRS-1-dependent signalling arises via effects on both the phosphorylation status and degradation of IRS-1, which are mediated, in part, by IKKb. In addition, the reduction of IRS-1 mRNA levels allude to transcriptional effects of linoleate treatment that also contribute to the observed reduction in the total levels of this protein. PtdOH, particularly dilinoleoyl PtdOH, was found to be significantly increased in linoleate treated L6 cells, and sufficient to induce at least some of the effects on insulin-signalling that are observed upon linoleate treatment. It is unlikely, however, that IKKb and PtdOH are components of the same inhibitory pathway, since inhibiting IKKb activity did not alleviate the effects of PtdOH on IRS-1 tyrosine (tyr) phosphorylation. Moreover, although an integral component of the mechanism by which linoleate induces insulin-resistance in L6 cells, it appears that restoring IRS-1 function in linoleate treated cells is not sufficient to reverse insulin resistance. Hence, we hypothesise that linoleate induces multiple inhibitory pathways in L6 cells, with at last two of these involving IKKb- and PtdOH-dependent inhibition of IRS-1 signalling, which act in parallel to reduce glucose disposal and cause insulin resistance in this model.

Patients with type 2 diabetes have reduced gene expression of Heat Shock Protein (HSP) 72 which correlates with reduced insulin sensitivity. Heat therapy, which activates HSP72, improves clinical parameters in these patients. Activation of several inflammatory signalling proteins such as c-jun amino terminal kinase (JNK) can induce insulin resistance but HSP72 can block the induction of these molecules in vitro. Whether up-regulation of HSP72 can protect against insulin resistance is not known. In experiments reported in this thesis we show that HSP72 protects against insulin resistance and blocks the activation of JNK in vivo. We first show that mice that underwent weekly heat shock therapy to increase intramuscular HSP72 protein expression were protected from high fat diet (HFD)-induced hyperinsulinemia, hyperglycemia and glucose intolerance, factors associated with reduced JNK phosphorylation. To determine whether the elevation in intramuscular HSP72 expressio n and protection from insulin resistance are causally linked, we studied muscle specific HSP72 overexpression mice (HSP72+/+). Compared with wild-type mice, HSP72+/+ mice were protected from hyperglycemia, hyperinsulinemia, glucose intolerance and insulin resistance when placed on a HFD, factors associated with a complete inhibition of HFD-induced JNK phosphorylation in skeletal muscle. Finally, we show that HSP72+/+ mice display greater mitochondrial enzyme activity in the liver, adipose tissue and skeletal muscle, corresponding to reduced plasma free fatty acid levels, white adipose tissue mass and alterations in circulating adipokines. These data identify HSP72 as being pivotal in protecting against obesity-induced insulin resistance possibly by blocking JNK and/or by up-regulation of mitochondrial oxidative capacity.

<p>Mellan tre och fyra procent av Sveriges befolkning har diabetes och antalet ökar stadigt. Av dessa har ca 80 % diagnosen typ 2-diabetes vilket kan leda till allvarliga följdsjukdomar och död om inte adekvat behandling och livsstilsförändring vidtas. Syftet med denna systematiska litteraturstudie var att identifiera omvårdnadsinterventioner som kan underlätta livsstilsförändringar för patienter med typ 2-diabetes. Studien baseras på tio vetenskapliga artiklar som analyserats med inspiration av kvalitativ innehållsanalys. Analysen resulterade i två huvudrubriker; stöd och utbildning samt fyra underrubriker; känslomässigt stöd, praktiskt stöd, utformning av utbildning samt innehåll i utbildning. Stöd och utbildning ges genom att erhålla patienterna tillräckligt med resurser som krävs, att skapa en positiv attityd som ger aktivt lärande, att upprätthålla medicinering och rutiner samt delta i undervisning som uppmuntrar till frågor och diskussion om känslor och rädslor. För att kunna utföra adekvata omvårdnadsinterventioner ställs det krav på sjuksköterskan och hennes kompetens. Kompetensen i det här fallet kan vara avgörande för om patienten lyckas med en livsstilsförändring eller inte. Vidare forskning bör fokusera på vilka attityder, kunskaper och färdigheter som sjuksköterskan bör inneha för att kunna utföra adekvata omvårdnadsinterventioner för patienter med typ 2-diabetes.</p>

Purpose: To examine the effectiveness of a community-based intensive multifactorial clinical intervention for patients with Type 2 diabetes, to evaluate the feasibility of achieving clinical targets for glycemic control in a community setting, and to identify factors that are predictive of glycemic control in this cohort (age, gender, disease duration, continuity of care, pharmacologic treatment, diabetes self-care and smoking status). Methods: Participants with Type 2 diabetes referred to the Diabetes Clinic following dissemination of the 2003 Clinical Practice Guidelines of Canadian Diabetes Association and who attended a minimum of two physician visits within a twelve month period were deemed eligible for participation. 70 patients were included in this retrospective study. Baseline and twelve month values for the following biomedical outcomes were collected via chart audit: BMI, hemoglobin A1c, blood pressure (systolic, diastolic) and lipid profile (HDL, LDL, triglycerides, total cholesterol, TC:HDL ratio). Data for identification of predictive factors for glycemic control were also retrieved by chart audit. Results: The results of the paired t-test yielded a significant improvement in hemoglobin A1c (p<0.05), systolic blood pressure (p<0.01), HDL-cholesterol (p<0.05), LDL-cholesterol (p<0.01), total cholesterol (p<0.05) and total cholesterol:HDL ratio (p<0.05) over twelve months. No significant difference in BMI, diastolic blood pressure or triglycerides was reported over twelve months. Over half the sample (52.9%) achieved clinical targets for glycemic control (hemoglobin A1c <7.0%) at twelve months. Logistic regression analysis identified disease duration (O.R. = 0.90, 95% CI Exp(B) = 0.079 - 0.773, p = 0.01) and continuity of care (O.R. = 0.25, 95% CI Exp(B) = 0.831 - 0.969, p = 0.02) as significant predictors of glycemic control at twelve months. Conclusions: These findings demonstrate the effectiveness of this community-based intensive multifactorial clinical intervention for patients with Type 2 diabetes and show that the implementation of CPGs related to glycemic control is feasible in a community-based setting. Additionally, patients in this cohort with increased disease duration and increased continuity of care were less likely to achieve clinical targets for glycemic control following a twelve month intensive multifactorial clinical intervention for Type 2 diabetes. In summary, health professionals should strive to implement similar intensive multifactorial interventions in community practice in order to decrease the likelihood of diabetes-related complications and improve the patients quality of life.

Diabetes är en utav Sveriges vanligaste folksjukdomar och idag lever 300 000 personer med denna kroniska sjukdom, och antalet ökar. I denna litteraturöversikt behandlas typ 2 diabetes vilken är den vanligast förekommande typen av diabetes. Något botemedel finns idag inte utan dagens behandling består av insulin, antidiabetika, god kosthållning samt fysisk aktivitet och är mer av ett preventivt syfte för att förebygga åtföljande komplikationer. Diabetes är vanligt förekommande inom vården och sjuksköterskan har ett stort ansvar i behandlingen, då den till stor del består av patientundervisning. I tidigare forskning har det framkommit att sjuksköterskor upplevt att de har brister i sin kunskap och undervisning. Syftet med denna litteraturöversikt består i att beskriva resurser och brister i sjuksköterskans undervisningsarbete av patienter med typ 2 diabetes. Totalt analyserades 15 vetenskapliga artiklar och sex teman framkom. Dessa är; Undervisning och information, Kunskap, Kommunikation, Motivation och engagemang, Psykisk påverkan och Förutsättningar. Resultatet visar att det finns både resurser och brister i sjusköterskans undervisningsarbete av patienter med typ 2 diabetes. Dessa påverkar sjuksköterskan i hennes undervisningsarbete och därmed även patienternas vårdkvalitet. / Diabetes is one of the most common diseases in Sweden today and 300 000 persons live with this chronic disease and the number is increasing. In this literature survey type 2 diabetes is processed which has the highest prevalence rate. No cure exists, instead treatment focuses on preventive measures consisting of insulin, antidiabetic, diet therapy and physical activity, which is found effective in preventing complications. The diabetes prevalence is high in all health care instances and the nurse has a great responsibility which to a large extent consists of patient education. Former surveys have shown that nurses experienced shortage in their knowledge and education skills. The aim of this literature survey is to describe resources and failures in nurse education of patients with type 2 diabetes. A total of 15 scientific articles where analysed and six themes emerged. The themes are; Education and information, Knowledge, Communication, Motivation and engagement, Psychical influence and Presumptions. The results show that there are both resources and failures in nurse education of patients with type 2 diabetes. These resources and short-comings affect the nurse in her education and consequently the patients quality of care.

<p>Globalization scholars have disagreed about the effects of globalization on the production and reproduction of difference: Do fundamental differences endure, do cultures converge, or is there hybridization? This dissertation analyzes the durability of distinct medical cultures in two technologically advanced healthcare systems that rely on an evidence-based, biomedical approach. Durability refers to the tendency to maintain or develop diverse, even idiosyncratic, practices and beliefs--even as the forces of globalization are perceived to be pressing health practices everywhere toward a single global standard. To do so, this dissertation offers a comparative, empirically based argument using the case of type 2 diabetes in the U.S. and Japan. As an inductive, theory-constructing project, the argument has at its foundation 11 months of ethnographic field work in Japanese hospitals and clinic exam rooms, 115 semi-structured interviews with patients and biomedical health practitioners in Japan, and 25 interviews with American health care providers and patients. I argue that physicians in both research sites, Okayama, Japan and North Carolina, USA, practice empirical biomedicine, but that empirical biomedicine is not all there is to biomedical practice. Practicing physicians in both contexts act not only on increasingly globalized professional standards, but also on local knowledge, on their own explanatory models for type 2 diabetes, and in reaction to local patient populations' explanatory models. Further, local knowledge and patient interactions shape the ways in which practicing physicians interpret global standards and best practices. Occasionally, they may even be reshaped beyond recognition without interfering with physicians' self-evaluation as participants in a universal, standardized scientific project. The interaction of globalizing standards of practice, local knowledge, and local explanatory models of illness can result in dramatically divergent medical practice across different social contexts--in this case, the U.S. and Japan.</p> / Dissertation