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.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Objective: The objective of this study was to characterize the composition of the gut microbiota in type 2 Diabetes Mellitus (T2DM) patients with adequate and inadequate metabolic control, and its relationship with fiber consumption. Results: A total of 26 patients with type 2 diabetes mellitus (T2DM) were enrolled, of which 7 (26.9%) cases had adequate metabolic control (HbA1c < 7%) and 19 (73.1%) inadequate metabolic control (HbA1c ≥ 7%). It was observed that among patients with controlled T2DM, 2 (28.6%) cases presented good intake of fiber and 5 (71.4%) cases a regular intake. In contrast, in patients with uncontrolled T2DM, 13 (68.4%) patients reported a regular intake and 6 (31.6%) a poor intake. In relation to the identification of the gut microbiota, both groups presented a similar characterization. There were differences in the population of bacteria identified in both groups, however, the results were not statistically significant. The most frequently identified bacteria in controlled and uncontrolled T2DM patients were Prevotella (71.4% vs 52.6%), followed by Firmicutes (71.4% vs 42.1%), Proteobacteria (71.4% vs 36.8%) and Bacteroidetes (57.1% vs 37.8%). On the other hand, Fusobacterium, Actinobacteria were not identified in either of the two groups of study. / Revisión por pares

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Typ 2-diabetes är en folkhälsosjukdom som ökar drastiskt på både en nationell och global nivå. Behandlingen av typ-2 diabetes utgår till stor del utifrån att patienten genomför en god egenvård. För att stötta patienter i sin egenvård har användandet av E-hälsa ökat i hälso- och sjukvården. Genom rätt anpassad information och samråd med sjuksköterskan gällande egenvård vid typ-2 diabetes kan E-hälsa vara en möjlighet till att stärka patienten i sin egenvård. Litteraturöversiktens syfte är att belysa patienters upplevelser av E-hälsa som stöd i egenvård vid typ 2-diabetes. Metoden som valdes var en litteraturöversikt baserat på 16 vetenskapliga artiklar. I resultatet framkom två teman; E-hälsans inverkan på egenvård och utformning av teknik. E-hälsans inverkan på egenvård framställdes ur tre underteman; Patienter upplevde en ökad kontroll, E-hälsa påverkade patienters engagemang och kunskap skapar förutsättningar. Utformning av teknik framställdes ur två underteman; Personcentrerad E-hälsa och avsaknad av mänskliga möten. För att E-hälsa ska utvecklas och uppnå vision E-hälsa 2025, är det av vikt att ta del av patienters upplevelser för att sjuksköterskan ska kunna tillmötesgå patienters vårdbehov.

Immigrants are at elevated risk for not having their diabetes treatment appropriately intensified, likely resulting in poorly-controlled diabetes and increased morbidity and mortality. Immigrant status is a powerful sociodemographic cue, yet its influence on providers' diabetes treatment decisions remains unknown. The study objective was to determine the effect of patient immigrant status on provider decisions to (1) take no action, (2) add an oral hypoglycemic agent (OHA), (3) add/switch to insulin, or (4) refer the patient to an endocrinologist. Participants were 140 medical students/professionals ('providers'). Providers viewed profiles (videos+vignettes) for virtual patients different in immigrant status (born in Mexico or U.S.; other characteristics held constant). Analyses were completed at the group and individual levels. Group levels indicated providers were less likely to refer foreign-born patients to endocrinology than U.S.-born patients (p=0.03). No differences were detected for the other three treatment likelihood ratings. Individual results indicated that about half of provider decisions were influenced by patient immigrant status (i.e., Cohen's d≥0.50) across all four decisions. Effect size data show an almost even split between higher treatment ratings for foreign-born vs. U.S.-born patients for three decisions (take no action, add an OHA, add/switch to insulin), explaining why group-level differences for these ratings did not emerge. This study found that providers are less likely to refer foreign-born patients to endocrinology, potentially leading to therapeutic inertia. In addition, half of individual-level provider decisions were meaningfully influenced by patient immigrant status. However, traditional group-level analyses mask these important individual-level differences. These systematic differences in treatment based on non-relevant factors could lead to unintended adverse outcomes for the foreign-born population.

>Magister Scientiae - MSc / Current research classifies Type 2 diabetes as most prevalent non-communicable diseases in South Africa. Approximately 285 million people are affected globally with an expected increase to 595 million by the year 2035. Synthetic first-line drugs in the treatment of Type 2 diabetes, have been shown to have an efficacy rate of approximately 43% as a result of poor drug uptake and metabolism. Furthermore, given South Africa’s uniquely diverse botanical heritage, herbs commonly used traditional medicine have shown promise in the treatment of Type 2 diabetes.

Obesity, a major risk factor in the development of Type 2 Diabetes (T2D), is commonly associated with insulin resistance and hyperinsulinemia. The long accepted view has been that insulin resistance drives hyperinsulinemia; however, there are multiple lines of evidence that hyperinsulinemia can precede and drive insulin resistance. The signals and mechanisms by which chronic excess nutrients promote pancreatic β-cell dysfunction remain poorly understood. This prompted us to define the signaling events that contribute to basal insulin hypersecretion induced by excess glucose. Of particular interest is signaling through mechanistic target of rapamycin complex 1 (mTORC1), a nutrient sensitive kinase complex whose hyperactivation has been shown to promote hyperinsulinemia. Clonal ß-cells (INS-1 cells) with and without mTORC1 inhibition were pre-exposed to physiological (5mM) or excess (11mM) glucose for 4 to 24 hrs. Basal insulin secretion, respiration and metabolites were measured. Pre-exposure to excess glucose resulted in sustained mTORC1 hyperactivation, basal insulin secretion, higher basal respiration and increased maximal respiratory capacity, due to accelerated mitochondrial pyruvate metabolism. Inhibition of mTORC1 reduced basal insulin secretion, basal respiration and maximal respiratory capacity. Moreover, cells challenged with excess glucose had increased levels of glycolysis and TCA cycle intermediates. Our results suggest that hyperactivation of mTORC1 induced by excess glucose results in increased energy demand and in the generation of metabolic factors that can lead to basal insulin hypersecretion. Therefore, targeting mitochondrial pyruvate metabolism and /or mTORC1 signaling could potentially lead to specific therapies to control hyperinsulinemia and diabetes progression.

Bakgrund: Diabetes är en kronisk sjukdom som uppskattas att ca 19 % av all jordens befolkning över 65 år har. Typ 2 diabetes brukar oftast upptäckas vid en komplikation såsom fotsår. Fotsår kan förebyggas tidigt och sjuksköterskan kan ha en stor betydelse i denna process. Kunskapsutvecklingen inom hälso- och sjukvården går snabbt och därför är det av betydelse att se över de senaste årens forskning om hur sjuksköterskan bäst kan bidra till att förebygga diabetsfotsår. Syfte: Att beskriva hur sjuksköterskan kan förebygga diabetesfotsår hos patienter med typ 2 diabetes. Metod: Studien genomfördes som en allmän litteraturöversikt. Sökningarna utfördes i databaserna PubMed och Cinahl. Nio artiklar sorterades ut till resultatet. Analysen genomfördes enligt Fribergs (2017) definition.  Resultat: Studien resulterade i tre kategorier, att informera och utbilda, att screena fördiabetesfotsår och att samarbeta mellan professioner. Slutsats: Sjuksköterskan har en viktig roll i att informera och utbilda patienterna om diabetes för att förebygga komplikationer av diabetesfotsår hos patienter med typ 2 diabetes. Tidig upptäckt av neuropati och perifer artärsjukdom med hjälp av screeningsverktyg kan vara essentiell för att förebygga diabetesfotsår. Det är av betydelse att sjuksköterskan har ett gott samarbete med multidisciplinära team för att förebygga diabetesfotsår hos patienter med typ 2 diabetes.

Bakgrund: En viktig del av diabetessjuksköterskans arbete innefattar att stödja och utbilda patienten angående diabetesegenvård. Att stödja patienten i egenvården kan medföra förbättrad glykemisk och metabol kontroll med bibehållen livskvalitet. Det finns viss evidens för att en skriftlig individuell behandlingsplan kan vara en personcentrerad metod för att främja god egenvård hos patienter med diabetes typ 2 i primärvården. Det finns idag ingen sådan nationellt framtagen behandlingsplan. Syfte: Syftet med studien var att utvärdera om en skriftlig individuell behandlingsplan kan påverka HbA1c eller empowerment hos patienter med typ 2 diabetes. Metod: 50 patienter deltog i en kvantitativ randomiserad kontrollerad studie. Hälften av patienterna randomiserades till interventionsgrupp och erhöll en skriftlig individuell behandlingsplan i samband med besöket. Patienterna fick besvara frågeformuläret Swe-DES 23 samt lämna HbA1c. Uppföljande data samlades in efter tre månader (n=36). Data analyserades med icke-parametriska metoder. Resultat: Patienterna som erhöll en skiftlig individuell behandlingsplan sänkte sitt HbA1c, mätt efter tre månader. Det fanns dock inga signifikanta skillnader gällande HbA1c-förändring mellan interventions och kontrollgrupp. Inga förändringar gällande empowerment kunde uppmätas. Slutsats: Sjukvården behöver utveckla enkla kostnadseffektiva arbetsmetoder för att kunna erbjuda personcentrerad vård till det ökande antalet patienter med diabetes som behandlas i primärvården. Studiens urval var för litet för att kunna dra några signifikanta slutsatser. Vidare studier behövs för att undersöka om den individuella skriftliga behandlingsplanen kan påverka HbA1c samt empowerment. / Background: An important part of the work as a diabetes nurse is to support and educate the patient in diabetes self-care. This can lead to improved glycemic and metabolic control,without affecting the quality of life. There is evidence supporting that an written care-plan can be a person-centered method that promote good self-care through increased empowerment, within the group of patients diagnosed with diabetes type 2. There is currently no such nationally developed care-plan. Aim: The aim of this study was to evaluate if a written care-plan can affect HbA1c or empowerment in a group of patients diagnosed with diabetes type 2. Method: A quantitative randomized controlled trial. A total of 50 patients participated, of with 25 were randomized to the interventions group and received the written care-plan. Empowerment was measured with Swe-DES 23 and the participating patients HbA1c were collected. This data was then compared with data after three months (n=36). Non-parametric methods were used for the analysis.Results: The participating patients in the intervention group had a significant decrease in HbA1c after three months. There were no significant differences in HbA1c decrease in-between the groups. No significant differences were found regarding empowerment. Conclusion: The healthcare need to develop simple and cost effective work methods to be able to offer person-centered care to the increasing number of patients with diabetes in the primary care. The sample size was small and no significant conclusions could be drawn. Further studies are required to evaluate if the written care plan can have an effect on HbA1c or empowerment in patients with diabetes type 2.

MMed, Internal Medicine, Faculty of Health Sciences,University of the Witwatersrand / Aims: To determine whether impairment of the executive functioning domain of cognition could be detected by a battery of simple bedside cognitive tests of executive function associated with inadequate glycaemic control. Methods: People with type 2 diabetes attending a tertiary referral diabetic clinic who consented to participate in the study underwent a brief battery of cognitive testing (the Bedside Executive Screening Test) designed to detect executive function impairment. Glycaemic control was determined using glycated haemoglobin levels (HbA1c). Inadequate glycaemic control was defined as HbA1c ≥ 7.0%. Results: Executive function impairment was detected in 51 (52%) of the 98 study participants. The presence of executive function impairment was significantly associated with poor glycaemic control (HbA1c ≥ 7.0%) (odds ratio 4.9, 95% confidence interval 1.3 – 18.8, p=0.019). There were no significant differences between patients with and without executive function impairment with regard to age, target organ damage, patient reported adherence, and hypoglycaemic therapy. Patients with a lower level of education were more likely to demonstrate executive impairment when glycaemic control was poor (p=0.013). Conclusion: Executive function impairment is common in a population of people with difficult-to-manage type 2 diabetes. The presence of executive impairment is significantly associated with poor glycaemic control.