Maternal diabetes affects specific extracellular matrix components during placentation

During embryo implantation, invasive trophoblast cells mediate embryo invasion into the decidualized stroma, forming a rich network of lacunae that connect the embryonic tissues to the maternal blood vessels. Placentation is probably guided by the composition and organization of the endometrial extracellular matrix. Certain pathological conditions that occur during pregnancy, including diabetes, have been linked to abnormal placental morphology and consequent fetal morbidity. We used immunoperoxidase techniques to identify members of the collagen, proteoglycan and glycoprotein families in the various compartments of the rat placenta and to determine whether experimentally induced diabetes affects placental morphology and alters the distribution of these molecules during pregnancy. Single injections of alloxan (40 mg kg(-1) i.v.) were used to induce diabetes on day 2 of pregnancy in Wistar rats. Placentas were collected on days 14, 17, and 20. Type I and III collagen, as well as the proteoglycans decorin and biglycan, were found to be distributed throughout the placentas of control and diabetic rats. In both groups, laminin expression decreased at the end of pregnancy. In contrast, fibronectin was detected in the labyrinth region of diabetic rats at all gestational stages studied, whereas it was detected only at term pregnancy in the placentas of control rats. These results show for the first time that some extracellular matrix molecules are modulated during placental development. However, as diabetic rats presented increased fibronectin deposition exclusively in the labyrinth region, we speculate that diabetes alters the microenvironment at the maternal-fetal interface, leading to developmental abnormalities in the offspring.

INSULIN REGULATES CYTOKINES AND INTERCELLULAR ADHESION MOLECULE-1 GENE EXPRESSION THROUGH NUCLEAR FACTOR-kappa B ACTIVATION IN LPS-INDUCED ACUTE LUNG INJURY IN RATS

Diabetic patients have increased susceptibility to infection, which may be related to impaired inflammatory response observed in experimental models of diabetes, and restored by insulin treatment. The goal of this study was to investigate whether insulin regulates transcription of cytokines and intercellular adhesion molecule 1 (ICAM-1) via nuclear factor-kappa B (NF-kappa B) signaling pathway in Escherichia coli LIPS-induced lung inflammation. Diabetic male Wistar rats (alloxan, 42 mg/kg, iv., 10 days) and controls were instilled intratracheally with saline containing LPS (750 mu g/0.4 mL) or saline only. Some diabetic rats were given neutral protamine Hagedorn insulin (4 IU, s.c.) 2 h before LIPS. Analyses performed 6 h after LPS included: (a) lung and mesenteric lymph node IL-1 beta, TNF-alpha, IL-10, and ICAM-1 messenger RNA (mRNA) were quantified by real-time reverse transcriptase-polymerase chain reaction; (b) number of neutrophils in the bronchoalveolar lavage (BAL) fluid, and concentrations of IL-1 beta, TNF-alpha, and IL-10 in the BAL were determined by the enzyme-linked immunosorbent assay; and (c) activation of NF-kappa B p65 subunit and phosphorylation of I-kappa B alpha were quantified by Western blot analysis. Relative to controls, diabetic rats exhibited a reduction in lung and mesenteric lymph node IL-1 beta (40%), TNF-alpha (similar to 30%), and IL-10 (similar to 40%) mRNA levels and reduced concentrations of IL-1 beta (52%), TNF-alpha (62%), IL-10 (43%), and neutrophil counts (72%) in the BAL. Activation of NF-kappa B p65 subunit and phosphorylation of I-kappa B alpha were almost suppressed in diabetic rats. Treatment of diabetic rats with insulin completely restored mRNA and protein levels of these cytokines and potentiated lung ICAM-1 mRNA levels (30%) and number of neutrophils (72%) in the BAL. Activation of NF-kappa B p65 subunit and phosphorylation of I-kappa B alpha were partially restored by insulin treatment. In conclusion, data presented suggest that insulin regulates transcription of proinflammatory (IL-1 beta, TNF-alpha) and anti-inflammatory (IL-10) cytokines, and expression of ICAM-1 via the NF-kappa B signaling pathway.

Egenvård vid typ 2 diabetesur ett sjuksköterske- och patientperspektiv

Syftet med litteraturstudien var att kartlägga sjuksköterskans och patientens syn på egenvård vid typ två diabetes. Studien genomfördes som en systematisk litteraturstudie. Materialsökningen har skett via facklitteratur, Internet samt databaserna Blackwell Synergy, EBSCO HOST, Elin@Dalarna och Ovid. Sökorden var diabetes, education, empowerment, management, nurse, nursing, patient, satisfaction, selfcare. Totalt användes 31 referenser till studien varav 16 empiriska artiklar låg till grund för resultatet. Artiklarna granskades med hjälp av Forsberg & Wengströms modifierade granskningsmall. Av resultatet framkom att sjuksköterskorna och patienterna önskade att de hade mer tid för att tillgodose patientens önskemål. Sjuksköterskorna hindrades av tidsbristen och det påverkade patienterna, vilket ledde till att patienterna inte kunde utveckla sig i hanteringen av sin egenvård. Patienterna önskade även att tillgängligheten av sjuksköterskor fanns kontinuerligt så att de kunde få svar på sina frågor och funderingar kring sin egenvård. Mer ansvar borde läggas på en sjuksköterska som arbetade självständig med diabetespatienter då detta tenderade till att patienterna fick empowerment och ökad kunskap om sin egenvård. Patienterna hade erfarenhet av olika utbildningar som ledde till att deras egenvård förbättrades. Sjuksköterskorna önskade sig mer utbildning som kunde hjälpa patienterna till en god egenvård.

Omvårdnadsbehov hospatienter med diabetesmellitus typ 2 : En systematisk litteraturstudie

Föreliggande systematiska litteraturstudie syftade till att klarlägga vilka omvårdnadsbehov som föreligger hos patienter med typ 2-diabetes. Sammanlagt 15 vetenskapliga artiklar valdes ut via sökmotorn Electronic Library Information Navigator (ELIN), databasen Cumulative Index of Nursing and Allied Health (CINAHL) samt sökmotorn och databasen för medicinska artiklar som drivs av United States National Library of Medicine (MEDLINE), för vidare granskning. Sökorden type 2 diabetes AND quality of life AND nurs* användes. Alla titlar lästes, om titeln verkade relevant för forskningsområdet lästes även abstraktet. Kvalitetsgranskning av artiklarna genomfördes efter granskningsmallar med 28 bedömningskriterier. Omvårdnadsbehoven hos patienter med typ 2-diabetes som framkom vid artikel granskningen evidensgraderades på basen av kvalitetsgranskningen med hjälp av graderingsskala. Resultatet visade att hjälp till förbättrad egenvård, önskan om utökad utbildning, information och kunskap, socialt stöd och kontinuerlig vårdkontakt var de omvårdnadsbehov som studien fann evidens för. Omvårdnadsbehov hos patienter med typ 2-diabetes som framkom var kända sedan tidigare men föreliggande studie säkrade evidensen för dessa. Resultatet diskuterades utifrån Virginia Hendersons omvårdnadsteori där omvårdnaden måste ha en utgångspunkt i individens egna upplevelser av sina behov och hur dessa behov på bästa sätt kan tillfredsställas. Med hjälp av studiens resultat sammanlänkat med Virginia Hendersons teori om individens omvårdnadsbehov kan sjuksköterskan få en bättre bild av vilka behov som föreligger hos patienter med typ 2-diabetes för att bevara deras livskvalité.

"Man måste ju typ lära sig, annars går det inte" : World of Warcraft och lärande av engelska

Det här examensarbetet har sin utgångspunkt i elevernas intresse av att spela onlinespelet Word of Warcraft (WoW) vilket har lett fram till en undersökning om spelets eventuella påverkan på elevernas färdigheter i engelska, och hur den i så fall ser ut. Eftersom spelet inte finns på svenska är de flesta spelarna beroende av sina färdigheter i engelska för att kunna förstå och göra sig förstådd i spelet. Arbetet utgår från tre huvudfrågeställningar:1. Finns det ett samband mellan elevernas resultat i engelska och deras spelande av World of Warcraft? Om det finns ett samband, hur kan det beskrivas?2. Hur upplever eleverna som spelar World of Warcraft att de lär sig engelska? Upplever eleverna att de lär sig engelska när de spelar, och i så fall vad/hur?3. Hur upplever eleverna att deras fritidsintressen skulle kunna tas tillvara mer i engelskundervisningen?För att få svar på frågeställningarna genomfördes två undersökningar. Dels en jämförande studie av resultat på det nationella provet i engelska för år 9, där resultat jämfördes mellan elever som spelar World of Warcraft och elever som inte spelar. För att söka svar på frågeställning 2 och 3 genomfördes fokussamtal med två elevgrupper, en grupp med elever som spelar World of Warcraft och en elevgrupp som inte spelar.Analysen av resultat på det nationella provet visar att eleverna som spelar World of Warcraft uppvisar ett högre medelvärde på samtliga delprov än de som inte spelar. Skillnaden mellan spelare och icke spelare var störst när det gällde delprov B som testar elevernas receptiva förmågor (läs- och hörförståelse) samt även delprov A som testar den muntliga färdigheten. Även av fokussamtalen framgår att elevernas upplever att spelet påverkar deras språkliga färdigheter på ett positivt sätt, särskilt då det ger goda tillfällen att kommunicera muntligt på engelska samt mycket övning i att läsa och lyssna.

Manoeuvring between anxiety and control : Patients experience of learning to live with diabetes: a lifeworld phenomenological study

Research shows that people with diabetes want their lives to proceed as normally as possible, but some patients experience difficulty in reaching their desired goals with treatment. The learning process is a complex phenomenon interwoven into every facet of life. Patients and healthcare providers often have different perspectives in care which gives different expectations on what the patients need to learn and cope with. The aim of this study, therefore, is to describe the experience of learning to live with diabetes. Interviews were conducted with 12 patients afflicted with type 1 or type 2 diabetes. The interviews were then analysed with reference to the reflective lifeworld research approach. The analysis shows that when the afflicted realize that their bodies undergo changes and that blood sugar levels are not always balanced as earlier in life, they can adjust to their new conditions early. The afflicted must take responsibility for balancing their blood sugar levels and incorporating the illness into their lives. Achieving such goals necessitates knowledge. The search for knowledge and sensitivity to changes are constant requirements for people with diabetes. Learning is driven by the tension caused by the need for and dependence on safe blood sugar control, the fear of losing such control, and the fear of future complications. The most important responsibilities for these patients are aspiring to understand their bodies as lived bodies, ensuring safety and security, and acquiring the knowledge essential to making conscious choices.

What is important for you? A qualitative interview study of living with diabetes and experiences of diabetes care to establish a basis for a tailored Patient-Reported Outcome Measure for the Swedish National Diabetes Register

OBJECTIVES: There is a growing emphasis on the perspective of individuals living with diabetes and the need for a more person-centred diabetes care. At present, the Swedish National Diabetes Register (NDR) lacks patient-reported outcome measures (PROMs) based on the perspective of the patient. As a basis for a new PROM, the aim of this study was to describe important aspects in life for adult individuals with diabetes. DESIGN: Semistructured qualitative interviews analysed using content analysis. SETTING: Hospital-based outpatient clinics and primary healthcare clinics in Sweden. PARTICIPANTS: 29 adults with type 1 diabetes mellitus (DM) (n=15) and type 2 DM (n=14). INCLUSION CRITERIA: Swedish adults (≥18 years) living with type 1 DM or type 2 DM (duration ≥5 years) able to describe their situation in Swedish. Purposive sampling generated heterogeneous characteristics. RESULTS: To live a good life with diabetes is demanding for the individual, but experienced barriers can be eased by support from others in the personal sphere, and by professional support from diabetes care. Diabetes care was a crucial resource to nurture the individual's ability and knowledge to manage diabetes, and to facilitate life with diabetes by supplying support, guidance, medical treatment and technical devices tailored to individual needs. The analysis resulted in the overarching theme 'To live a good life with diabetes' constituting the two main categories 'How I feel and how things are going with my diabetes' and 'Support from diabetes care in managing diabetes' including five different categories. CONCLUSIONS: Common aspects were identified including the experience of living with diabetes and support from diabetes care. These will be used to establish a basis for a tailored PROM for the NDR.

Tanis: a link between type 2 diabetes and inflammation?

Here we describe a novel protein, which we have named Tanis, that is implicated in type 2 diabetes and inflammation. In Psammomys obesus, a unique polygenic animal model of type 2 diabetes and the metabolic syndrome, Tanis is expressed in the liver in inverse proportion to circulating glucose (P = 0.010) and insulin levels (P = 0.004) and in direct proportion with plasma triglyceride concentrations (P = 0.007). Hepatic Tanis gene expression was markedly increased (3.1-fold) after a 24-h fast in diabetic but not in nondiabetic P. obesus. In addition, glucose inhibited Tanis gene expression in cultured hepatocytes (P = 0.006) as well as in several other cell types (P = 0.001–0.011). Thus, Tanis seems to be regulated by glucose and is dysregulated in the diabetic state. Yeast-2 hybrid screening identified serum amyloid A (SAA), an acute-phase inflammatory response protein, as an interacting protein of Tanis, and this was confirmed by Biacore experiments. SAA and other acute-phase proteins have been the focus of recent attention as risk factors for cardiovascular disease, and we contend that Tanis and its interaction with SAA may provide a mechanistic link among type 2 diabetes, inflammation, and cardiovascular disease.

Does high-intensity resistance training maintain bone mass during moderate weight loss in older overweight adults with type 2 diabetes?

The aim was to investigate whether the addition of supervised high intensity progressive resistance training to a moderate weight loss program (RT+WLoss) could maintain bone mineral density (BMD) and lean mass compared to moderate weight loss (WLoss) alone in older overweight adults with type 2 diabetes. We also investigated whether any benefits derived from a supervised RT program could be sustained through an additional home-based program. This was a 12-month trial in which 36 sedentary, overweight adults aged 60 to 80 years with type 2 diabetes were randomized to either a supervised gymnasium-based RT+WLoss or WLoss program for 6 months (phase 1). Thereafter, all participants completed an additional 6-month home-based training without further dietary modification (phase 2). Total body and regional BMD and bone mineral content (BMC), fat mass (FM) and lean mass (LM) were assessed by DXA every 6 months. Diet, muscle strength (1-RM) and serum total testosterone, estradiol, SHBG, insulin and IGF-1 were measured every 3 months. No between group differences were detected for changes in any of the hormonal parameters at any measurement point. In phase 1, after 6 months of gymnasium-based training, weight and FM decreased similarly in both groups (P<0.01), but LM tended to increase in the RT+WLoss (n=16) relative to the WLoss (n=13) group [net difference (95% CI), 1.8% (0.2, 3.5), P<0.05]. Total body BMD and BMC remained unchanged in the RT+WLoss group, but decreased by 0.9 and 1.5%, respectively, in the WLoss group (interaction, P<0.05). Similar, though non-significant, changes were detected at the femoral neck and lumbar spine (L2-L4). In phase 2, after a further 6 months of home-based training, weight and FM increased significantly in both the RT+WLoss (n=14) and WLoss (n=12) group, but there were no significant changes in LM or total body or regional BMD or BMC in either group from 6 to 12 months. These results indicate that in older, overweight adults with type 2 diabetes, dietary modification should be combined with progressive resistance training to optimize the effects on body composition without having a negative effect on bone health.

The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes

Aims/hypothesis This study aimed to identify genes that are expressed in skeletal muscle, encode proteins with functional significance in mitochondria, and are associated with type 2 diabetes.
Methods We screened for differentially expressed genes in skeletal muscle of Psammomys obesus (Israeli sand rats), and prioritised these on the basis of genomic localisation and bioinformatics analysis for proteins with likely mitochondrial functions.
Results We identified a mitochondrial intramembrane protease, known as presenilins-associated rhomboid-like protein (PSARL) that is associated with insulin resistance and type 2 diabetes. Expression of PSARL was reduced in skeletal muscle of diabetic Psammomys obesus, and restored after exercise training to successfully treat the diabetes. PSARL gene expression in human skeletal muscle was correlated with insulin sensitivity as assessed by glucose disposal during a hyperinsulinaemic–euglycaemic clamp. In 1,031 human subjects, an amino acid substitution (Leu262Val) in PSARL was associated with increased plasma insulin concentration, a key risk factor for diabetes. Furthermore, this variant interacted strongly with age to affect insulin levels, accounting for 5% of the variation in plasma insulin in elderly subjects.
Conclusions/interpretation Variation in PSARL sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome.

PGC-1α and exercise: important partners in combating insulin resistance

Diabetes and obesity are characterised by an impairment in mitochondrial function resulting in a decrease in glucose and fatty acid oxidation, respiration and an increase in intramuscular triglycerides (IMTG's) and insulin resistance. Peroxisome proliferator-activated receptor (PPAR)-ggr coactivator 1agr (PGC-1agr) is a nuclear transcriptional coactivator which regulates several important metabolic processes including, mitochondrial biogenesis, adaptive thermogenesis, respiration, insulin secretion and gluconeogenesis. In addition, PGC-1agr has been shown to increase the percentage of oxidative type I muscle fibres, with the latter responsible for the majority of insulin stimulated glucose uptake. PGC-1agr also co-activates PPAR's agr, bgr/dgr and ggr which are important transcription factors of genes regulating lipid and glucose metabolism. Exercise causes mitochondrial biogenesis, improves skeletal muscle fatty acid oxidation capacity and insulin sensitivity, therefore making it an important intervention for the treatment of insulin resistance. The expression of PGC-1agr mRNA is reduced in diabetic subjects, however, it is rapidly induced in response to interventions which signal alterations in metabolic requirements, such as exercise. Because of the important role of PGC-1agr in the control of energy metabolism and insulin sensitivity, it is seen as a candidate factor in the etiology of type 2 diabetes and a drug target for its therapeutic treatment.

Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor-[gamma] coactivator-1 and peroxisome proliferator-activated receptor-[alpha] in skeletal muscle

The peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 (PGC-1) can induce mitochondria biogenesis and has been implicated in the development of oxidative type I muscle fibers. The PPAR isoforms α, β/δ, and γ control the transcription of genes involved in fatty acid and glucose metabolism. As endurance training increases skeletal muscle mitochondria and type I fiber content and fatty acid oxidative capacity, our aim was to determine whether these increases could be mediated by possible effects on PGC-1 or PPAR-α, -β/δ, and -γ. Seven healthy men performed 6 weeks of endurance training and the expression levels of PGC-1 and PPAR-α, -β/δ, and -γ mRNA as well as the fiber type distribution of the PGC-1 and PPAR-α proteins were measured in biopsies from their vastus lateralis muscle. PGC-1 and PPAR-α mRNA expression increased by 2.7- and 2.2-fold (P < 0.01), respectively, after endurance training. PGC-1 expression was 2.2- and 6-fold greater in the type IIa than in the type I and IIx fibers, respectively. It increased by 2.8-fold in the type IIa fibers and by 1.5-fold in both the type I and IIx fibers after endurance training (P < 0.015). PPAR-α was 1.9-fold greater in type I than in the II fibers and increased by 3.0-fold and 1.5-fold in these respective fibers after endurance training (P < 0.001). The increases in PGC-1 and PPAR-α levels reported in this study may play an important role in the changes in muscle mitochondria content, oxidative phenotype, and sensitivity to insulin known to be induced by endurance training.

Decreased expression of adipogenic genes in obese subjects with type 2 diabetes

Objective: Our objective was to delineate the potential role of adipogenesis in insulin resistance and type 2 diabetes. Obesity is characterized by an increase in adipose tissue mass resulting from enlargement of existing fat cells (hypertrophy) and/or from increased number of adipocytes (hyperplasia). The inability of the adipose tissue to recruit new fat cells may cause ectopic fat deposition and insulin resistance.

Research Methods and Procedures: We examined the expression of candidate genes involved in adipocyte proliferation and/or differentiation [ CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPdelta, GATA domain-binding protein 3 (GATA3), C/EBPbeta, peroxisome proliferator-activated receptor (PPAR) gamma2, signal transducer and activator of transcription 5A (STAT5A), Wnt-10b, tumor necrosis factor alpha, sterol regulatory element-binding protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin-related protein (PGAR), insulin-like growth factor 1, PPARitalic gamma coactivator 1alpha, PPARitalic gamma coactivator 1beta, and PPARdelta] in subcutaneous adipose tissue from 42 obese individuals with type 2 diabetes and 25 non-diabetic subjects matched for age and obesity.

Results: Insulin sensitivity was measured by a 3-hour 80 mU/m2 per minute hyperinsulinemic glucose clamp (100 mg/dL). As expected, subjects with type 2 diabetes had lower glucose disposal (4.9 plusminus 1.9 vs. 7.5 plusminus 2.8 mg/min per kilogram fat-free mass; p < 0.001) and larger fat cells (0.90 plusminus 0.26 vs. 0.78 plusminus 0.17 mum; p = 0.04) as compared with obese control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and PPARitalic gamma2, p = 0.02) had significantly lower expression in obese type 2 diabetics, whereas C/EBPbeta only tended to be lower (p = 0.07).

Discussion: This cross-sectional study supports the hypothesis that impaired expression of adipogenic genes may result in impaired adipogenesis, potentially leading to larger fat cells in subcutaneous adipose tissue and insulin resistance.

High-intensity resistance training improves glycemic control in older patients with type 2 diabetes

OBJECTIVE -- To examine the effect of high-intensity progressive resistance training combined with moderate weight loss on glycemic control and body composition in older patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS -- Sedentary, overweight men and women with type 2 diabetes, aged 60-80 years (n = 36), were randomized to high-intensity progressive resistance training plus moderate weight loss (RT & WL group) or moderate weight loss plus a control program (WL group). Clinical and laboratory measurements were assessed at 0, 3, and 6 months.

RESULTS -- HbA._1c fell significantly more in RT & WL than WL at 3 months (0.6 ± or -] 0.7 vs. 0.07 ± 0.8%, P < 0.05) and 6 months (1.2 ±1.0 vs. 0.4 ±0.8, P < 0.05). Similar reductions in body weight (RT & WL 2.5 ±2.9 vs. WL 3.1±2.1 kg) and fat mass (RT & WL 2.4 ± 2.7 vs. WL 2.7±2.5 kg) were observed after 6 months. In contrast, lean body mass (LBM) increased in the RT & WL group (0.5 ±1.1 kg) and decreased in the WL group (0.4±1.0) after 6 months (P < 0.05). There were no between-group differences for fasting glucose, insulin, serum lipids and lipoproteins, or resting blood pressure.

CONCLUSIONS -- High-intensity progressive resistance training, in combination with moderate weight loss, was effective in improving glycemic control in older patients with type 2 diabetes. Additional benefits of improved muscular strength and LBM identify high-intensity resistance training as a feasible and effective component in the management program for older patients with type 2 diabetes.