OBJECTIVE: The aryl hydrocarbon receptor (AhR) translocates to the nucleus and binds to the aryl hydrocarbon receptor nuclear translocator (ARNT) to regulate biological responses upon ligand activation. The aim of this study was to measure the effects of activation or inhibition of AhR activity on basal and glucose-stimulated insulin secretion (GSIS) from clonal pancreatic β-cells (INS-1) cultured under normal and glucolipotoxic (GLT) conditions (high glucose and fatty acid). METHODS: Insulin content and secretion were measured utilizing homogenous time-resolved fluorescence (HTRF) insulin assay kit (cisbio). Cells cultured in RPMI media containing 5 mM and 11 mM glucose were pre-incubated with the receptor agonist FICZ or antagonist CH223191 for 96 hours. Insulin secretion over 2 hours was reported as ng/million cells. Intracellular lipid was measured by fluorescence after Nile red staining. RESULTS: Incubation of INS-1 cells with 11 mM glucose and fatty acid increased lipid droplets, basal insulin secretion and inhibited GSIS compared to cells cultured in 4 mM glucose, characteristic of GLT. Incubation of INS-1 cells with 11 mM glucose alone also exhibited GLT characteristics. INS-1 cells cultured at 11 mM glucose and treated with antagonist (1.25 - 10 μM) had decreased lipid content and improved insulin secretion compared to cells cultured in 11 mM glucose alone. INS-1 cells cultured in 5 mM glucose and treated with the AhR agonist (1.25 - 10 μM) exhibited increased intracellular lipid and impaired insulin secretion. CONCLUSION: The AhR may play a mediatory role in the development of GLT in pancreatic β-cells cultured in excess nutrients and β-cell specific activator or inhibitor ligands of this receptor could potentially be a targeted therapeutic treatment of diabetes.

Introduktion: Det beräknas att det finns över 350 000 personer med diabetes i Sverige (Diabetesförbundet, 2016). WHO (2015) förutspår att fram till år 2030 kommer dubbelt så många vara drabbade av diabetes. Viktigt är att distriktsköterskan kan tolka, förstå och ge det stöd som varje unik individ behöver för ett framgångsrikt arbete med egenvården. Dessutom är en ökad förståelse och kunskap om patientens möjligheter, hinder samt att förstå sammanhanget ur patientens synvinkel betydelsefullt. Syftet med studien var att beskriva patienters möjligheter och hinder för att uppnå för en god egenvård vid Diabetes Mellitus typ 2. Metod: För att svara på syftet gjordes en litteraturstudie som följde Statens beredning för medicinsk utvärderings SBU:s sju steg. Tretton vetenskapliga artiklar användes för att svara på syftet varav elva är kvalitativa samt två är kvantitativa. Resultat redovisas i en syntes med tre huvudteman: kommunikation/kunskap, socialt och kulturellt. Rätt information ger kunskap för att uppnå god egenvård. Socialt stöd från närstående och ekonomiska resurser är också en avgörande faktorer. Olika kulturer påverkar de val som personer med DM2 gör i vardagen. Kostförändringar upplevs av de flesta som det svåraste att genomför i egenvården. Konklusion: Att drabbas av DM2 ställer stora krav på patienterna. Hälsotillståndet är beroende av de val den enskilde patienten gör i vardagen.   En ökad förståelse för vad patienter med DM2 upplever som hinder och möjligheter vid egenvård kan gör det lättare för vårdpersonal att ge rätt stöd och hjälp för att uppnå deras egenvårdsmål. / Introduction: It is estimated that there are over 350,000 people with diabetes in Sweden (Diabetes Association, 2016). WHO (2015) predicts that in 2030 there will be twice as many who sufferers of diabetes. It is important that the district nurse can interpret, understand and provide the support that each unique individual needs for success with self-care. In addition, a greater understanding and knowledge of the patient's opportunities, barriers, and to understand the context of the patient's point of view is significant. Aim: The purpose of the study is to describe the patient's opportunities and obstacles to achieve a good self-care for Diabetes Mellitus type 2. Method: To answer the purpose of a literature review followed the Swedish Council for Medical Evaluation SBU's seven steps. Thirteen scientific papers were used to answer the purpose of which eleven are qualitative and two quantitative. Results are presented in a synthesis with three main themes: communication / knowledge, socially and culturally. Right information brings knowledge to achieve good self-care. Social support from family and financial resources is also crucial factors. Different cultures influence the choices that individuals with DM2 do in everyday life. Dietary changes are perceived by most as the most difficult to implement in your own care. Conclusion: To suffer from DM2 places great demands on the patients. The state of health is dependent on the choices that the individual patient does in everyday life. An improved understanding of what patients with DM2 perceive as obstacles and opportunities for self-care can make it easier for health professionals to provide the right help and support to achieve their goal of self care.

Background: Type 2-diabetes is a growing public health problem that cause suffering for people living with the disease and it is expensive for the Swedish healthcare system. The diabetes specialist nurse is often the person who stands for the continuity in the diabetes care and therefore has a big inpact on the outcome. The aim of this study was to describe the diabetes nurse’s experience of nursing care for adults with type 2-diabetes in primary care. The used method is qualitative. Eight diabetes nurses were interviewed with semi structured interviews and the content was analysed with qualitative content analysis. The result showed obstacles, dilemmas and possibilities experienced in diabetes care. Conclusion: There is a winning in knowing about obstacles, dilemmas and possibilities that can be experienced by diabetes specialist nurses in order to maintain a good diabetes care. The experienced obstacles and dilemmas needs to be continuously studied in order to keep evolving the diabetes care.

Type 2 Diabetes (T2D) affects over 415 million people globally and is characterised by cellular stresses including: poor glucose homeostasis, dyslipidaemia, inflammation, hypoxia and ER stress. Studies in mice have shown that exposure to these stresses influences beta cell differentiation status as well as cell survival and may explain the extent of beta cell mass loss that is seen in the disease. To date, studies of altered beta cell differentiation have largely been confined to murine models. I used the EndoC-bH1 human beta cell line, along with human pancreatic tissue sections, to better characterise this mechanism in human disease. To elucidate these mechanisms, I firstly established a humanised version of cell culture techniques for the EndoC βH1 cell model and assessed the influence on cell function. Secondly, I evaluated the effects of the diabetic microenvironment on beta cell differentiation and gene expression patterns. Finally, I investigated whether a diabetomimetic microenvironment induced differences in microRNA regulation in the cells. I found that the humanised EndoC-βH1 culture techniques improved glucose sensitive insulin release in the cell model. EndoC-βH1 cells exposed to a Diabetic microenvironment showed some degree of transdifferentiation and this may be due to dysregulation of splicing factor expression. These effects may be compounded by altered microRNA regulation in response to these cell stresses. These data suggest that altered gene regulation caused by a diabetic microenvironment may alter gene regulation to produce a reversible delta-like phenotype in human beta cells.

O diabetes mellitus tipo 2 (DM2) constitui um dos mais importantes problemas de saúde pública no mundo. A alta concentração plasmática de triglicérides e a baixa concentração do HDL-C são as principais alterações lipídicas no DM2. A hipertrigliceridemia, além de outros fatores, pode alterar a composição das lipoproteínas, ocasionando alterações funcionais das partículas. O efeito antiaterogênico da HDL se dá, sobretudo, devido à sua ação de promover o Transporte Reverso do Colesterol, sendo a troca lipídica entre as lipoproteínas uma das etapas desse processo. O objetivo deste trabalho foi avaliar o tamanho da partícula de HDL e sua capacidade em receber seus lípides constituintes de outras lipoproteínas. O método é baseado na troca lipídica ocorrida entre uma nanoemulsão artificial (LDE) marcada radioativamente com 14C-CL e 3H-TG ou 14CFL e 3H-CE que se assemelha à estrutura lipídica da LDL, usada como doador de lipídeos. Neste trabalho foram estudados 45 pacientes diabéticos (53±7 anos) e 45 indivíduos sem a doença (55±8 anos), como grupo controle. As taxas de transferência de colesterol livre e fosfolípides para a HDL foram maiores no grupo dos pacientes diabéticos quando comparados com o grupo controle (CL= 7,1±1,7 e 6,4±1,4%, p=0,0400; FL= 23,6±2,4 e 19,3±3,3%, p<0,0001, respectivamente). No entanto, não houve diferença na transferência de éster de colesterol e triglicérides entre os pacientes diabéticos e indivíduos controles. O tamanho da partícula de HDL também não foi diferente entre os grupos. As transferências de éster de colesterol, triglicérides e colesterol livre correlacionaram-se positivamente. Houve também correlação positiva entre a concentração plasmática do colesterol total e LDL-C com a taxa de transferência de triglicérides e entre a concentração plasmática da apoAI com a taxa de transferência de éster de colesterol e de colesterol livre. Em virtude da partícula de HDL ter importante papel antiaterogênico, a maior transferência de FL e CL para a HDL no DM2, podem ser relevantes para estabelecer mecanismos antiaterogêncios associados a alterações na lipoproteína relacionados com o DM2. / Type II diabetes mellitus has become one of the world\'s main public health issues. High triglyceride concentrations and low HDL-C concentrations are the main in the plasma lipids found in DM2. Hipertriglyceridemia is but one of the factors that cause lipoprotein composition, which in turn can cause alterations in particle function. The antiatherogenic effect of HDL is due primarily to its ability to promote Reverse Cholesterol Transport, in which lipid transfer between lipoproteins is one step in the process. The objective of this study was to evaluate HDL particle size and its capacity to accept lipid constituents from other lipoproteins. The methodology utilized is based on the lipid transfer between with an artificial cholesterol-rich nanoemulsion labeled with 3H-tryglicerides (TG) and 14C-free cholesterol (FC) or 3H-cholesteryl ester (CE) and 14C-phospholipids (PL), structurally similar to LDL, used as a radioactive lipid donator. After LDE and other lipoprotein precipitation, the capacity of HDL to receive lipids is quantified by measuring the radioactivity present in the lipoprotein. Forty-five diabetic individuals (53±7) and 45 non-diabetic individual (55±8) as a control group were studied. The free cholesterol (FC) and phospholipids (PL) transfer rate to HDL was higher for the diabetic group when compared with control group (FC= 7.1±1.7 e 6.4±1.4%, p=0.0400; PL= 23.6±2.4 e 19.3±3.3%, p<0.0001, respectively). However, there was no transfer difference of the cholesteryl ester and triglycerides between the two study groups. No difference in the HDL particle size was observed in either group. There was found correlations between the lipid transfer rates and between the transfer rates and the lipoprotein profile of the diabetic individuals were also analyzed. The transfer of cholesteryl ester, triglycerides and free cholesterol correlated positively. There was also a positive correlation between the plasmatic concentration of total cholesterol and LDL-C with the triglyceride transfer and between the plasmatic concentration of apoAI with the cholesteryl ester and free cholesterol. This pattern of greater PL and FC transfer to HDL associated with DM2 can be a marker related to functional alterations in HDL that may contribute to atherogenic in those patients.

The objectives of this study were to assess patient activation levels, to assess association between sociodemographic characteristics and patient activation, to assess association between health status characteristics and patient activation, and to assess association between patient activation and medication adherence among Medicare beneficiaries with type 2 diabetes. A retrospective cohort study was conducted using data from the 2009 through 2013 Medicare Current Beneficiary Survey (MCBS). Patient activation was measured with the Patient Activation Supplement in the MCBS and was categorized as low, moderate, and high levels based on activation scores. Medication adherence was assessed with proportion of days covered (PDC) using Medicare Part D administrative records from the MCBS within a period of six months after measurement of patient activation. The sample included Medicare beneficiaries who completed the MCBS Patient Activation questionnaire, who were diagnosed with type 2 diabetes, and who were 18 or older. Beneficiaries were excluded if they responded “Not ascertained,” “Not Applicable,” “Don’t know” or “Refused” to more than 50 percent of the Patient Activation questions, did not have continuous Medicare Part A and Part D coverage throughout the assessment period, had less than two Medicare Part D claims for an antidiabetic medication throughout the assessment period, used insulin during the assessment period, resided in long-term care facilities, or had Alzheimer’s disease, dementia, mental retardation or mental disorder. All analyses were conducted in SAS 9.4 for Unix environment. An <i>a priori</i> alpha level of 0.05 was used to determine significance. Bivariate and multivariable weighted ordinal logistic regression were applied for assessing associations. A total of 571 individuals met sample selection criteria. The mean age was 72.4 years. Of the 571 persons in the sample, 27.5 percent were at low activation level, 38.7 percent were at moderate activation level, and 33.7 percent were at high activation level. Approximately three-fourths of the sample persons were adherent to antidiabetic medications. Low activation was more likely to be found in males, less educated patients, and patients without arrhythmia. Ex-smokers as compared to non-smokers and overweight patients as compared to those with healthy weight were less likely to report low activation. In multivariable logistic analysis adjusting for race, gender, osteoporosis, Charlson Comorbidity Index score, and number of prescribed medications, patient activation level was not significantly associated with medication adherence. Non-Whites and patients with a Charlson Comorbidity Index score of 1 as compared to those with a score of 0 were more likely to be non-adherent. A lower number of prescribed medications was associated with higher odds of non-adherence.

Estudo descritivo transversal, cujo objetivo foi analisar a relação das variáveis sociodemográficas, de tratamento, hábitos de vida, clínicas e laboratoriais com as variáveis sintomas e fases do estresse, em pessoas com diabetes mellitus tipo 2, em unidade ambulatorial de hospital de nível terciário de atenção à saúde. A amostra foi constituída por 222 pessoas e os dados foram coletados no período de junho de 2011 a agosto de 2012. O instrumento utilizado foi o Inventário de Sintomas de Stress de Lipp, composto por três quadros de sintomas de estresse, que fornecem porcentagens para classifica-los em quatro fases: alerta, resistência, quase exaustão e exaustão. Entre as características sociodemográficas, de tratamento, hábitos de vida, dados clínicos e laboratoriais, destacam-se que 53,15% das pessoas eram do sexo feminino, 43,85% do masculino, com média de idade de 60,68 anos (DP=8,40), tempo médio de escolaridade de 5,07 anos (DP=4,15), 71,17% viviam com o companheiro, 57,66% procediam da região de Ribeirão Preto (SP), 50,9% eram aposentados/pensionistas, 87,38% referiu fazer uso de insulina, 78,82% antidiabético oral, 68,91% seguir a dieta recomendada e 46,85% não praticava exercícios físicos regulares. O tempo médio de diagnóstico foi de 15,15 (DP=8,03) anos, índice de massa corporal 32,10 (DP=5,75) Kg/m2 , pressão arterial sistólica 180,10 (DP=14,03) mmHg e diastólica 143,7 (DP=23,63) mmHg, taxa de hemoglobina glicada 9,446 (DP=2) %, colesterol total 74,9 (DP=41,95) mg/dl, lipoproteína de alta densidade 35,67 (DP=8,58) mg/dl, lipoproteína de baixa densidade 101,55 (34,52) mg/dl e triglicerídeos 203,60 (DP=147,72) mg/dl. Quanto às variáveis do estresse, destaca-se que a maior média das porcentagens obtidas ocorreu para os sintomas de estresse do quadro 2 (20,16%-DP=20,165). Para fins de análises estatísticas, excluiu-se a fase de alerta e aglutinou-se as de exaustão e quase exaustão. A frequência dos sintomas de estresse referidos pelos participantes nos três quadros distintos permitiu verificar a presença do estresse em 63,51% da amostra, bem como a frequência de 53,60% na fase de resistência ao estresse, e predomínio de sintomas físicos (61,53%). As fases do estresse associaram-se com a idade, procedência, uso de insulina e lipoproteína de baixa densidade; os sintomas do estresse com o uso de antidiabéticos orais, tabagismo, consumo de bebida alcoólica e lipoproteína de baixa densidade. Quanto à porcentagem média obtida nos três quadros, observou-se que houve associação dos sintomas do primeiro quadro com a ocupação; do segundo quadro com o seguimento da dieta, glicemia plasmática de jejum, o colesterol total e lipoproteína de baixa densidade; correlação do terceiro quadro com o índice de massa corporal, de modo positivo e com a renda familiar, de modo negativo. A idade e a hemoglobina glicada correlacionaram-se com o segundo e terceiro quadros, porém de forma negativa e positiva, respectivamente. O presente estudo permitiu conhecer as possíveis relações do estresse com as variáveis sociodemográficas, tratamento da doença, hábitos de vida, clínicas e laboratoriais da pessoa com diabetes mellitus tipo 2 e reitera a importância desse conhecimento na prática clínica para intervenções que desenvolvam habilidades pessoais para o enfrentamento de situações estressantes percebidas pelas pessoas durante o curso da doença / Cross-sectional study aimed to examine the relations of sociodemographic variables, disease treatment, lifestyle, clinical and laboratory variables with the symptoms and phases of stress in people with type 2 diabetes mellitus, in an outpatient unit of a tertiary level hospital of health care. The sample consisted of 222 individuals and the data were collected between June 2011 and August 2012. The instrument used was the Lipp Stress Symptom Inventory, composed of three frames of stress symptoms, which provide percentages for grades them into four phases: alarm, resistance, near exhaustion and exhaustion. Among the sociodemographic characteristics, treatment, lifestyle, clinical and laboratory data, it highlights that 53.15% of those were female, 43.85% male, with a mean age of 60.68 years (SD = 8.40), mean years of education 5.07 years (SD = 4.15), 71.17% lived with a partner, 57.66% were from Ribeirao Preto region (SP) and 50.9% were retired / pensioners, 87.38% reported use insulin, 78.82% oral antidiabetic, 68.91% followed the recommended diet and 46.85% did not practice regular physical exercise. The average time of diagnosis was 15.15 (SD = 8.03) years, mean body mass index 32.10 (SD = 5.75) kg/m2, mean systolic blood pressure 180.10 (SD = 14 03) and diastolic 143.7 mmHg (SD = 23.63) mmHg, glycated hemoglobin rate 9.446 (SD = 2)%, total cholesterol 74.9 (SD = 41.95) mg/dl, high density lipoproteins 35.67 (SD = 8.58) mg/dL, low density lipoproteins 101.55 (34.52) mg/dL and triglycerides rate of 203.60 (SD = 147.72) mg/dl. As for the variables of stress, there is that most average of these percentages occurred to the frame stress symptoms 2 (20.16% - SD = 20.165). For the purpose of statistical analysis, we excluded the alert phase and connect them of exhaustion and near exhaustion. The frequency of symptoms of stress reported by participants in three different frames demonstrated the presence of stress in 63.51% of the sample, and the frequency of 53.60% in stress resistance phase, and predominance of physical symptoms (61,53%). The phases of stress were associated with age, origin, use of insulin and low-density lipoprotein; symptoms of stress with the use of oral antidiabetic drugs, smoking, consumption of alcohol and low-density lipoprotein. The average percentage obtained in the three frames, it was noted that there was an association of the symptoms of the first frame with the occupation; the second frame with the following the diet, fasting plasma glucose, total cholesterol and low-density lipoprotein; the third frame correlation with body mass index in a positive way and to family income, negatively. The age and glycated hemoglobin correlated with the second and third frames, but negatively and positively, respectively. This study helped identify the possible relations of stress with sociodemographic variables, disease treatment, lifestyle, clinical and laboratory of the person with type 2 diabetes mellitus and reiterates the importance of this knowledge in clinical practice to interventions that develop personal skills for coping stressful situations perceived by the people during the course of the disease

Obesity can lead to a range of health problems including type 2 diabetes (T2DM), cardiovascular disease and non-alcoholic fatty liver disease (NAFLD), and causes an estimated 2.8 million deaths annually (2016). It is a growing epidemic affecting over 600 million people worldwide (in 2014), with 26.8% of the adult population in England alone being obese, an increase of 10% in the last decade, and 62.9% overweight or obese. This trend is predicted to continue, and is attributed to an increasingly sedentary lifestyle, coupled with a high calorie “western diet”, which is estimated to cost >£25billion/year in the UK (2015), which is predicted to rise to £49.9 billion by 2050. It is clear that both sex and genetics affect the extent to which individuals exposed to a high fat diet develop adiposity and its associated morbidities, although the mechanisms underlying these differences are not well understood. Here we explore this aetiology, focusing on poly(A)-binding protein 4 (PABP4), an RNA-binding protein in which polymorphisms associated with altered cholesterol levels and cardiovascular disease risk were identified in human GWAS studies. To this end, I take advantage of an unpublished Pabp4 knock-out mouse, maintained on either normal (ND) or high fat diet (HFD), to explore the role of PABP4 in determining the response to high fat diet. PABP4 is a poorly characterised member of the PABP family, which are multifunctional central regulators of global and mRNA-specific translation, and stability. In cell lines, PABP4 is predominantly cytoplasmic, consistent with such functions. However, analogously to PABP1, the prototypical PABP family member, PABP4 is relocalised to stress granules or the nucleus in response to specific cellular stresses and/or viral infections, suggesting a role in altering gene expression programs in responses to changing cellular conditions. Whilst the expression pattern of PABP4 within tissues has not been previously characterised, western blotting of adult mouse tissues revealed that PABP4 is highly expressed in tissues relevant to obesity, T2DM and NAFLD, such as adipose, pancreas, liver and muscle, consistent with the idea that it may play a role in regulating gene expression programs in response to HFD. Immunohistochemistry of tissue sections provided additional insight, revealing a distinct cellular distribution of PABP4 in some tissues, when compared to the well characterised PABP1. Birth weight and post-birth growth can affect adult metabolism. In particular, low birth weight and catch-up growth, characterised by preferentially putting down adipose over lean mass, increases the risk of metabolic conditions in adulthood, such as obesity, T2DM and cardiovascular disease. Therefore, Pabp4-/- and wildtype mice were weighed at birth and daily until weaning. Interestingly this revealed that Pabp4-/- mice have a reduced weight at birth that is exacerbated to weaning (21days (P21)) (5.7% and 18.3% reductions respectively). This analysis also uncovered a reduced survival to weaning, with both male and female Pabp4-/- mice being present at sub-Mendelian ratios by P21 (p=0.0056). Whilst most death occurred neonatally, Pabp4-/- mice showed an increased rate of attrition until weaning, preceded in some cases by an arrest of weight gain. Weight gain was also tracked from 4 weeks to 12 weeks of age on normal diet showing that Pabp4-/- mice had reduced weight into adulthood (12% reduction at 12wks). Analysis of weight gain by sex uncovered a sexually dimorphic effect of Pabp4-deficiency, with female, but not male, Pabp4-/- mice remaining reduced in weight compared to wildtype after 8 weeks on ND (13.4% reduction in female weight). Body composition analysis showed that fat mass was equivalent to wildtype at 12 weeks of age in both sexes but that female Pabp4-/- mice had a 14.3% reduction in lean mass. Neither the catch-up growth in males nor the reduced lean mass in females was sufficient to result in a change in glucose homeostasis. As the risk of developing metabolic disorders in adult life is a consequence of both genetic and environmental factors, such as diet, Pabp4-/- were placed on a HFD at 4 weeks of age for 8 weeks. HFD models the ‘western’ diet, and has been shown to induce obesity, insulin resistance and glucose intolerance in wildtype mice. Whereas Pabp4-/- mice were only distinguishable from wild-type in terms of female lean mass on normal diet, pronounced sexually dimorphic differences were observed in HFD fed mice. Male Pabp4-/- mice appeared to be partially protected from the negative effects of an 8 week HFD regimen, with a 44% decrease in adipose mass gain compared to wildtype despite equal lean mass. Pabp4-/- male mice also had significantly reduced ectopic lipid stores, with an 81% decrease in hepatic triglyceride concentration compared to wildtype, meaning that NAFLD has not developed. Furthermore, Pabp4- /- male mice did not develop hyperinsulinemia on HFD and retained insulin sensitisation (assessed via glucose tolerance test (GTT) and insulin tolerance test (ITT)), although they displayed wildtype-like elevated plasma glucose concentrations (compared to ND). Western blotting had detected high PABP4 levels in the pancreas, indicating a possible pancreatic origin of these alterations. However, immunofluorescence revealed that PABP4 was confined to the exocrine portion of the pancreas, and was undetectable in the insulin producing pancreatic beta cells, suggesting this phenotype may not be beta cell in origin. This is consistent with the fact that the Pabp4-/- male mice retained an appropriate glucose-induced burst of insulin secretion, and therefore insulin production appears unimpaired. Thus, the primary defect may reside in the exocrine pancreas, which aids digestion, or in other key metabolism related tissues (e.g. muscle, liver, adipose and brain), or a combination thereof. In HFD fed wildtype mice, insulin resistance is caused by increased adiposity and ectopic lipid depots, which blunt insulin stimulated signalling cascades, meaning that the normal responses to insulin (e.g. cellular up take of glucose in muscle and arrested glucose production in liver, to decrease plasma glucose concentrations), are impaired. Therefore, the absence of insulin resistance in HFD fed Pabp4-/- male mice may be a consequence of the reduced increase in adipose mass and ectopic lipid deposits detected in these mice, and their consequent lack of inhibition on insulin signalling pathways. The reduced adiposity was not a result of reduced food intake or dietary fat absorption as male Pabp4-/- mice did not eat less nor exhibit apparent steatorrhea (fatty stools). These results highlight that the Pabp4-/- male mice appear to have an alteration in energy use/storage, and the investigation of this will form the basis of future work. When fed HFD, female Pabp4-/- mice revealed a divergent phenotype to that of wildtype female mice and Pabp4-/- male mice. HFD fed Pabp4-/- female mice showed no difference to HFD-fed wildtype mice in terms of weight, but still exhibited the reduction in lean mass seen on ND, but now with a 22.8% increase in volume of adipose tissue. Together, this means that HFD fed Pabp4-/- females have a higher body fat percentage (32.6% compared to 25.9 % for wildtype females). In contrast to the males, there was no difference in terms of hepatic triglycerides in HFD fed Pabp4-/- female mice and they showed greater hyperglycaemia than wildtype (GTT), although like males they retained insulin sensitisation (ITT). These potentially conflicting results in terms of insulin sensitivity and plasma glucose concentrations may result from the alterations in body composition, which can confound results when lean mass is altered and total body weight is used for calculating doses for GTT/ITT. Interestingly, adiponectin, an adipokine normally found in inverse proportion to adipose mass, was increased in plasma from HFD fed Pabp4-/- female mice (21% increase from HFD fed wildtype mice). Whilst surprising given the increase fat mass of Pabp4-/- females, the insulin sensitising properties of adiponectin may help to explain the retained insulin sensitivity detected in the female Pabp4-/- mice. / The finding that HFD revealed metabolic differences in the Pabp4-/- mice lead to the question of whether Pabp4-/- mice have issues adapting to other situations which require modulation of energy storage and glucose homeostasis. One such event is pregnancy, when maternal regulation of insulin resistance is tightly modulated throughout gestation. We therefore characterised the maternal Pabp4-/- environment in late pregnancy (E18.5), when insulin sensitivity decreases to 40-60% lower than pre-pregnancy which results reduced maternal glucose uptake, freeing the glucose up for the rapidly developing foetus. Pregnant Pabp4-/- mice had elevated plasma insulin concentration post fasting (63.7% increase), however glucose homeostasis was wildtype-like, both in terms of plasma glucose and insulin concentrations, throughout a GTT. However, plasma glucose and insulin concentrations in E18.5 Pabp4-/- foetuses were significantly decreased (9% and 44.3% respectively). Pabp4-/- foetuses also had reduced foetal and placental weight/length parameters. This establishes that the differences in weight observed at birth were present by late gestation and secondly, that the reductions in both foetal glucose and insulin concentrations which may contribute to or underlie the reduced growth. It also suggests that the differences seen in adulthood on HFD may be a consequence of metabolic differences present during pregnancy. Taken together, these data support the hypothesis that PABP4 plays a key role in the regulation of mRNAs which are important in growth, post-natal survival and metabolic adaption to high fat diet.

Bakgrund: Typ 2 diabetes är en växande folksjukdom och är förenad med följdsjukdomar. Ökningen beror främst på ohälsosamma levnadsvanor. Behandlingen av typ 2 diabetes innebär att förändra livsstilen, vilket medför stora utmaningar för den enskilda personen. En bristande följsamhet till behandlings råd bidrar oftast till komplikationer och följdsjukdomar, vilket leder till ökade samhällskostnader och stora utmaningar för hälso- och sjukvården. Syfte: Syftet med denna litteraturöversikt är att beskriva patientens följsamhet till behandlingsråd hos personer med typ 2 diabetes. Metod: En litteraturöversikt baserad på 15 vetenskapliga artiklar där både kvalitativa och kvantitativa artiklar granskats. Artiklarna samlades in via databaserna Cinahl och Pubmed. Resultat: Viktiga beståndsdelar som framkom i resultatet och påverkade följsamheten av behandlings råd hos personer med typ 2-diabetes var information, kunskapsbrist, utbildning, självmedvetande, socialt stöd och personcentrering. Alla ovanstående faktorer var viktiga för att uppnå livsstilsförändring. Slutsats: Sjuksköterskan måste ha en förståelse för vilka behandlingsråd som påverkar följsamheten vid typ 2 diabetes. Sjuksköterskan måste få en bild av patientens tidigare erfarenheter, kunskap och personliga egenskaper för att sedan anpassa information och utbildning till patienten. Dessa faktorer ökar självmedvetenheten och motivation tillsammans med stöd av anhöriga vilket leder till god följsamhet till behandlingsråd vid typ 2 diabetes. / Background: Type 2 diabetes is a increasing and is associated with complications. The increase is mainly due to unhealthy living habits. The treatment of type 2 diabetes primarily involve changing of lifestyle, which poses great challenges for the individual. A lack of compliance to change lifestyle advice may contribute to complications which leads to increased cost and major challenges for healthcare. Aim: The purpose of this literature review is to describe factors that affect the adherence to treatment advice among persons with type 2 diabetes. Method: A Literature review based on 15 scientific publications with qualitative and quantitative design. Articles were collected from the databases Cinahl and Pubmed. Results: Factors that emerged that affected the adherence to treatment advice in people with type 2 diabetes were information, lack of knowledge, education, self-awareness, social support and person centred approach. All the above factors were important to achieve lifestyle changes. Conclusion: Nurses must have an understanding of the factors that affect the compliance to lifestyle advice of Type 2 diabetes. Nurses need to be aware of the patients previous experience, knowledge and personal characteristics. To make the information and education feasible to the patient these factors increase self-awareness and motivation together with support from relatives resulting in good adherence to lifestyle advice to patients with type 2 diabetes.

Objetivo: Avaliar a influência da terapia com tibolona no metabolismo dos carboidratos e lipídeos de pacientes na pós-menopausa portadoras de diabetes mellitus tipo 2. Método: estudo prospectivo, longitudinal, aberto e controlado envolvendo 24 mulheres na pós-menopausa portadoras de diabetes mellitus tipo 2, com média de idade de 57,5 ± 4,8 anos, tratadas seqüencialmente com placebo (6 meses) e tibolona-2,5 mg/dia (6 meses). Parâmetros clínicos, antropométricos, bioquímicos, hormonais e ultra-sonográficos foram avaliados no período basal, após 6 (tempo 1) e 12 meses de acompanhamento (tempo 2). Análise estatística foi realizada utilizando-se ANOVA para medidas repetidas, com nível de significância 5%. Resultados: com os 6 meses de uso da tibolona, evidenciamos reduções significativas nos sintomas climatéricos avaliados através do índice de Blatt-Kuperman, assim como no percentual de gordura corporal, circunferência abdominal, pressão arterial diastólica, e níveis séricos de transaminases, triglicerídeos e HDL-colesterol. Não houve variações significativas nos níveis de glicose e insulina de jejum, hemoglobinaglicada, área sobre a curva da glicose, área sobre a curva da insulina, índice QUICKI, colesterol total e LDL-colesterol. A avaliação ultra-sonográfica não revelou variações significativas do volume uterino e espessura endometrial. Efeitos colaterais surgiram apenas durante o primeiro mês de uso da tibolona (cefaléia e mastalgia em 8,3% e sangramento genital em 16,6%). Conclusão: o tratamento com tibolona em curto prazo mostrou-se uma alternativa viável para pacientes na pós-menopausa portadoras de diabetes mellitustipo 2. / Objective: to determine the effects of tibolone on the glycemic and lipid metabolism in postmenopausal women with Type 2 diabetes mellitus. Method: a prospective, longitudinal, open and controlledstudy involving 24 postmenopausal women with Type 2 diabetes mellitussequentially treated with placebo (6 months) and 2.5 mg/day tibolone (6 months). Clinical evaluation, anthropometric parameters, biochemical and hormonal measurements, and transvaginal ultrasonography were performed at baseline and after 6 (time 1) and 12 months of follow-up (time 2). Statistical analysis was performed by repeatedmeasures analysis of variance, with the level of significance set at 5 %. Results: After 6 months the tibolone use, we observed significant reductions in the climacteric symptoms evaluated by the Blatt-Kupperman index, % body fat, abdominal circumference, diastolic arterial pressure, and in the serum levels of aminotransferases, triglycerides and HDL-cholesterol. There were no significant variations in fasting glucose and insulin levels, glycosylated hemoglobin, glucose-area under the curve (AUC), insulin-AUC, quantitative insulin sensitivity check index (QUICKI), total cholesterol and LDL-cholesterol levels. Ultrasonographic evaluation showed no significant changes in uterine volume or endometrial thickness. Side effects were present only during first months of tibolone use (headache and mastalgia in 8.3% and genital bleeding in 16.6%). Conclusion: The short-term treatment with tibolone showed to be a good alternative for postmenopausal women with Type 2 diabetes mellitus.