Application of DIGE and mass spectrometry in the study of type 2 Diabetes Mellitus (T2DM) mouse models

Knowledge of the differences between the amounts and types of protein that are expressed in diseased compared to healthy subjects may give an understanding of the biological pathways that cause disease. This is the reasoning behind the presented protocol, which uses difference gel electrophoresis to discover up‐ or down‐regulated proteins between mice of different genotypes, or of those fed on different diets, that may thus be prone to develop diabetes‐like phenotypes. Subsequent analysis of these proteins by tandem mass spectrometry typically facilitates their identification with a high degree of confidence.

Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population

Peroxisome proliferator-activated receptor-gamma2 (PPARG2) is a nuclear hormone receptor of ligand-dependent transcription factor involved in adipogenesis and a molecular target of the insulin sensitizers thiazolidinediones. We addressed the question of whether the 3 variants (-1279G/A, Pro12Ala, and His478His) in the PPARG2 gene are associated with type 2 diabetes mellitus and its related traits in a South Indian population. The study subjects (1000 type 2 diabetes mellitus and 1000 normal-glucose-tolerant subjects) were chosen randomly from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The variants were screened by single-stranded conformational variant, direct sequencing, and restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. The -1279G/A, Pro12Ala, and His478His variants of the PPARG2 gene were not associated with type 2 diabetes mellitus. However, the 2-loci analyses showed that, in the presence of Pro/Pro genotype of the Pro12Ala variant, the -1279G/A promoter variant showed increased susceptibility to type 2 diabetes mellitus (odds ratio, 2.092; 95% confidence interval, 1.22-3.59; P = .008), whereas in the presence of 12Ala allele, the -1279G/A showed a protective effect against type 2 diabetes mellitus (odds ratio, 0.270; 95% confidence interval, 0.15-0.49; P < .0001). The 3-loci haplotype analysis showed that the A-Ala-T (-1279G/A-Pro12Ala-His478His) haplotype was associated with a reduced risk of type 2 diabetes mellitus (P < .0001). Although our data indicate that the PPARG2 gene variants, independently, have no association with type 2 diabetes mellitus, the 2-loci genotype analysis involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have shown a significant association with type 2 diabetes mellitus in this South Indian population.

The genetics of diabetes mellitus

Genes play an important role in the development of diabetes mellitus. Putative susceptibility genes could be the key to the development of diabetes. Type 1 diabetes mellitus is one of the most common chronic diseases of childhood. A combination of genetic and environmental factors is most likely the cause of Type 1 diabetes. The pathogenetic sequence leading to the selective autoimmune destruction of islet beta-cells and development of Type 1 diabetes involves genetic factors, environmental factors, immune regulation and chemical mediators. Unlike Type 1 diabetes mellitus, Type 2 diabetes is often considered a polygenic disorder with multiple genes located on different chromosomes being associated with this condition. This is further complicated by numerous environmental factors which also contribute to the clinical manifestation of the disorder in genetically predisposed persons. Only a minority of cases of type 2 diabetes are caused by single gene defects such as maturity onset diabetes of the young (MODY), syndrome of insulin resistance (insulin receptor defect) and maternally inherited diabetes and deafness (mitochondrial gene defect). Although Type 2 diabetes mellitus appears in almost epidemic proportions our knowledge of the mechanism of this disease is limited. More information about insulin secretion and action and the genetic variability of the various factors involved will contribute to better understanding and classification of this group of diseases. This article discusses the results of various genetic studies on diabetes with special reference to Indian population.

The effects of lipoic acid and alpha-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled trial

Antioxidants probably play an important role in the etiology of type 2 diabetes (DM2). This study evaluated the effects of supplementation with lipoic acid (LA) and alpha-tocopherol on the lipid profile and insulin sensitivity of DM2 patients. A randomized, double-blind, placebo-controlled trial involving 102 DM2 patients divided into four groups to receive daily supplementation for 4 months with: 600 mg LA (n = 26); 800 mg alpha-tocopherol (n = 25); 800 mg alpha-tocopherol + 600 mg LA (n = 25); placebo (n = 26). Plasma alpha-tocopherol, lipid profile, glucose, insulin, and the HOMA index were determined before and after supplementation. Differences within and between groups were compared by ANOVA using Bonferroni correction. Student`s t-test was used to compare means of two independent variables. The vitamin E/total cholesterol ratio improved significantly in patients supplemented with vitamin E + LA and vitamin E alone (p <= 0.001). There were improvements of the lipid fractions in the groups receiving LA and vitamin E alone or in combination, and on the HOMA index in the LA group, but not significant. The results suggest that LA and vitamin E supplementation alone or in combination did not affect the lipid profile or insulin sensitivity of DM2 patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Diabetes mellitus-related morphoquantitative changes in the celiac ganglion neurons of the dog

Diabetes mellitus is the most common endocrine disturbance of domestic carnivores and can cause autonomic neurological disorders, although these are still poorly understood in veterinary medicine. There is little information available on the quantitative adaptation mechanisms of the sympathetic ganglia during diabetes mellitus in domestic mammals. By combining morphometric methods and NADPH-diaphorase staining (as a possible marker for nitric oxide producing neurons), type I diabetes mellitus-related morphoquantitative changes were investigated in the celiac ganglion neurons in dogs. Twelve left celiac ganglia from adult female German shepherd dogs were examined: six ganglia were from non-diabetic and six from diabetic subjects. Consistent hypertrophy of the ganglia was noted in diabetic animals with increase of 55% in length, 53% in width, and 61.5% in thickness. The ordinary microstructure of the ganglia was modified leading to an uneven distribution of the ganglionic units and a more evident distribution of axon fascicles. In contrast to non-diabetic dogs, there was a lack of NADPH-diaphorase perikarial labelling in the celiac ganglion neurons of diabetic animals. The morphometric study showed that both the neuronal and nuclear sizes were significantly larger in diabetic dogs (1.3 and 1.39 times, respectively). The profile density and area fraction of NADPH-diaphorase-reactive celiac ganglion neurons were significantly larger (1.35 and 1.48 times, respectively) in non-diabetic dogs compared to NADPH-diaphorase-non-reactive celiac ganglion neurons in diabetic dogs. Although this study suggests that diabetic neuropathy is associated with neuronal hypertrophy, controversy remains over the possibility of ongoing neuronal loss and the functional interrelationship between them. It is unclear whether neuronal hypertrophy could be a compensation mechanism for a putative neuronal loss during the diabetes mellitus. (C) 2007 Elsevier Ltd. All rights reserved.

Biodritin microencapsulated human islets of langerhans and their potential for type 1 diabetes mellitus therapy

Background. Microencapsulation of pancreatic islets with polymeric compounds constitutes an attractive alternative therapy for type 1 diabetes mellitus. The major limiting factor is the availability of a biocompatible and mechanically stable polymer. We investigated the potential of Biodritin, a novel polymer constituted of alginate and chondroitin sulfate, for islet microencapsulation. Methods. Biodritin microcapsules were obtained using an air jet droplet generator and gelated with barium or calcium chloride. Microencapsulated rat insulinoma RINm5F cells were tested for viability using the [3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide] [MTT] colorimetric assay. Microencapsulated rat pancreatic islets were coincubated with macrophages derived from mouse peritoneal liquid to assess the immunomodulatory potential of the microcapsules, using quantitative real time-PCR (qPCR). Biodritin biocompatibility was demonstrated by subcutaneous injection of empty microcapsules into immunocompetent Wistar rats. Insulin secretion by microencapsulated human pancreatic islets was evaluated using an electrochemoluminescent assay. Microencapsulated human islets transplanted into chemically induced diabetic mice were monitored for reversal of hyperglycemia. Results. The metabolic activity of microencapsulated RINm5F cells persisted for at least 15 days. Interleukin-1 beta expression by macrophages was observed during coculture with islets microencapsulated with Biodritin-CaCl2, but not with Biodritin-BaCl2. No statistical difference in glucose-stimulated insulin secretion was observed between nonencapsulated and microencapsulated islets. Upon microencapsulated islet transplantation, the blood glucose level of diabetic mice normalized; they remained euglycemic for at least 60 days, displaying normal oral glucose tolerance tests. Conclusion. This study demonstrated that Biodritin can be used for islet microencapsulation and reversal of diabetes; however, further investigations are required to assess its potential for long-term transplantation.

Barns upplevelser av att leva med diabetes mellitus typ 1 : samt sjuksköterskans betydelse i deras omvårdnad

Syftet med denna studie har varit att beskriva hur barn med diagnosen diabetes mellitus typ 1 upplever sin sjukdom samt vilken betydelse sjuksköterskan kunde ha i omvårdnaden av dessa barn. Studien har utförts som en systematisk litteraturstudie och tillvägagångssättet har varit att systematiskt söka, kritiskt granska och sammanställa resultat inom det valda ämnesområdet från olika studier. Sökningen har skett i databaserna Elin@Dalarna, Cinahl och Blackwell Synergy. Sökorden som har använts var: diabetes mellitus type 1, diabetes mellitus, children, adolescents, experiences, perspective, nurs* och care i olika kombinationer. Sammanställningen från resultatet visade att barn med diagnosen diabetes mellitus typ 1 upplever sin sjukdom olika utifrån sina egna förutsättningar, kön eller ålder. Det framkom även att sjuksköterskan hade en viktig roll när det gällde att fånga upp barnens upplevelser kring den förändrade livssituationen som uppstått och utifrån detta kartlägga barnens resurser att hantera denna situation. Att då kunna bemöta barnen och deras familjer utifrån egna förutsättningar och att motivera dessa till att sköta den livslånga behandlingen, kan vara avgörande för att få en bra kontroll över diabetes och på så sätt en ökad livskvalité och ett gott välbefinnande.

Patienters upplevelser samt sjuksköterskans roll i undervisningen till patienter med Diabetes mellitus typ 2

Syfte: Syftet med denna studie var att undersöka hur patienter upplevde patient-undervisningen samt hur sjuksköterskans roll såg ut i patientundervisningen. Metod: Uppsatsen har genomförts som en systematisk litteraturstudie. Artiklar har sökts i databaserna ELIN samt Cinahl. Artiklar publicerade mellan 1999-2009 och som var tillgängliga i fulltext inkluderades i resultatdelen som omfattade 14 kvalitativa studier samt en litteraturstudie. Resultat: I resultatet framgick att patienterna upplevde att gruppundervisning var ett bra alternativ till enskild undervisning då de kunde ta del av andras erfarenheter och på det sättet få mer kunskap om sjukdomen. Dessutom upplevde de att det var givande att träffa personer med samma sjukdom. I studien framgick att enskild undervisning var önskvärt från både patienter och sjuksköterskor då det kunde upplevas lättare att ta upp de frågor de hade där. Sjuksköterskan kunde vara ett stort stöd för patienten. Förutom att förmedla sina kunskaper och undervisa patienten var lyssna, uppmuntra och stötta något som sjuksköterskorna ansåg vara viktigt i mötet med patienten. Något som togs upp av patienter och sjuksköterskorna var att de ansåg att det vore bra om patienterna under besöken träffade samma personer då det skulle underlätta uppföljningarna.

Icke-följsamhet vid diabetes mellitus : en litteraturstudie

Syftet med föreliggande studie var att beskriva vad personer med diabetes anser inverka på deras möjlighet och vilja att följa egenvårdsråd (patientperspektivet) och att beskriva omvård-nad som stöder följsamhet (sjukvårdsperspektivet). Studien har genomförts som en litteratur-studie. Det visade sig att alla krav för att hålla sjukdomen under kontroll innebär livsstilsför-ändringar, som kan vara så utmanande för patienten, att han kanske inte kan eller vill vidta dessa. Bristande kunskap om sjukdomen och om dess egenvårdskrav kan göra honom dåligt emotionellt anpassad till denna, det vill säga han har inte accepterat att han har sjukdomen och han vill inte låta dess egenvårdskrav inkräkta på det sociala livet. Detta ger honom för-sämrade möjligheter att hantera sjukdomen på ett bra sätt. Barriärer av olika slag kan uppstå mellan patient och vårdgivare. Det kan röra sig om en upplevd brist på information och stöd när diabetes diagnosticerats eller en känsla av att vara utsatt för läkarens eller sjuksköterskans stereotypa föreställningar och/eller att bli paternalistiskt behandlad. Till barriärer räknas även klinisk misskötsel, det vill säga att läkare/sjuksköterska inte följer vedertagna riktlinjer för be-handling.Vad som kan inverka positivt på följsamheten är patientens stöd av anhöriga eller andra i det sociala nätverket. Omvårdnad som stöder följsamhet visade sig varapatientundervisning, främst om den inriktades på att öka patientens självständighet genom att låta undervisningen pågå under en längre tid, så att patienten hinner integrera sin nya kunskap med det dagliga livet. Med eller utan patientundervisning tar det tid att bygga upp ett socialt stöd och ett förtroende mellan patient och vårdare.

Lifestyle and health status in a sample of Swedish women four years after pregnancy : a comparison of women with a history of normal pregnancy and women with a history of gestational diabetes mellitus

Background: Despite the recommendations to continue the regime of healthy food and physical activity (PA) postpartum for women with previous gestational diabetes mellitus (GDM), the scientific evidence reveals that these recommendations may not be complied to. This study compared lifestyle and health status in women whose pregnancy was complicated by GDM with women who had a normal pregnancy and delivery. Methods: The inclusion criteria were women with GDM (ICD-10: O24.4 A and O24.4B) and women with uncomplicated pregnancy and delivery in 2005 (ICD-10: O80.0). A random sample of women fulfilling the criteria (n = 882) were identified from the Swedish Medical Birth Register. A questionnaire was sent by mail to eligible women approximately four years after the pregnancy. A total of 444 women (50.8%) agreed to participate, 111 diagnosed with GDM in their pregnancy and 333 with normal pregnancy/ delivery. Results: Women with previous GDM were significantly older, reported higher body weight and less PA before the index pregnancy. No major differences between the groups were noticed regarding lifestyle at the follow-up. Overall, few participants fulfilled the national recommendations of PA and diet. At the follow-up, 19 participants had developed diabetes, all with previous GDM. Women with previous GDM reported significantly poorer self-rated health (SRH), higher level of sick-leave and more often using medication on regular basis. However, a history of GDM or having overt diabetes mellitus showed no association with poorer SRH in the multivariate analysis. Irregular eating habits, no regular PA, overweight/obesity, and regular use of medication were associated with poorer SRH in all participants. Conclusions: Suboptimal levels of PA, and fruit and vegetable consumption were found in a sample of women with a history of GDM as well as for women with normal pregnancy approximately four years after index pregnancy. Women with previous GDM seem to increase their PA after childbirth, but still they perform their PA at lower intensity than women with a history of normal pregnancy. Having GDM at index pregnancy or being diagnosed with overt diabetes mellitus at follow-up did not demonstrate associations with poorer SRH four years after delivery.

Patienters upplevelser av livskvalitet vid nydiagnostiserad typ 2 Diabetes Mellitus : En intervjustudie

Syfte: Att undersöka patienters upplevelser av livskvalitet vid nydiagnostiserad typ 2 Diabetes Mellitus. Metod: En empirisk studie med en kvalitativ ansats som innefattade tio deltagare med nydiagnostiserad typ 2 Diabetes Mellitus. Semistrukturerade intervjuer genomfördes utifrån en intervjuguide där insamlad data analyserades med kvalitativ manifest innehållsanalys. Resultat: Studien resulterade i fyra huvudkategorier och tio subkategorier. Upplevelsen av att få ett diagnosbesked varierade mellan deltagarna, för vissa deltagarna var beskedet inte förvånande medan andra upplevde känslor av chock och förnekelse. Deltagarna upplevde positiva förändringar, exempelvis viktnedgång och förbättrad hälsa men även negativa förändringar, exempelvis att vara beroende av läkemedel. Vissa upplevde ingen förändring alls. Typ 2 Diabetes Mellitus påverkade inte deltagarnas fysiska eller psykiska hälsa i de flesta fall. Deltagarna ansåg det som viktig att få stöd från både omgivningen och hälso- och sjukvården. Konklusion: Känslorna över ett diagnosbesked kunde variera men upplevelsen av livskvalitet påverkades inte av Typ 2 Diabetes Mellitus i de flesta fall i studien. Patientens inställning till att leva med Typ 2 Diabetes Mellitus inverkade på förmågan till att utföra egenvård, och distriktsköterskans stöd och engagemang ansågs vara betydelsefullt i sjukdomsprocessen.

No consensus on gestational diabetes mellitus screening regimes in Sweden : pregnancy outcomes in relation to different screening regimes 2011 to 2012, a cross-sectional study

Background: Although associated adverse pregnancy outcomes, no international or Swedish consensus exists that identifies a cut-off value or what screening method to use for definition of gestational diabetes mellitus. This study investigates the following: i) guidelines for screening of GDM; ii) background and risk factors for GDM and selection to OGTT; and iii) pregnancy outcomes in relation to GDM, screening regimes and levels of OGTT 2 hour glucose values. Methods: This cross-sectional and population-based study uses data from the Swedish Maternal Health Care Register (MHCR) (2011 and 2012) combined with guidelines for GDM screening (2011-2012) from each Maternal Health Care Area (MHCA) in Sweden. The sample consisted of 184, 183 women: 88, 140 in 2011 and 96,043 in 2012. Chi-square and two independent samples t-tests were used. Univariate and multivariate logistic regression analyses were performed. Results: Four screening regimes of oral glucose tolerance test (OGTT) (75 g of glucose) were used: A) universal screening with a 2-hour cut-off value of 10.0 mmol/L; B) selective screening with a 2-hour cut-off value of 8.9 mmol/L; C) selective screening with a 2-hour cut-off value of 10.0 mmol/L; and D) selective screening with a 2-hour cut-off value of 12.2 mmol/L. The highest prevalence of GDM (2.9%) was found with a 2-hour cut-off value of 8.9 mmol/L when selective screening was applied. Unemployment and low educational level were associated with an increased risk of GDM. The OR was 4.14 (CI 95%: 3.81-4.50) for GDM in obese women compared to women with BMI <30 kg/m(2). Women with non-Nordic origin presented a more than doubled risk for GDM compared to women with Nordic origin (OR = 2.24; CI 95%: 2.06-2.43). Increasing OGTT values were associated with increasing risks of adverse pregnancy outcomes. Conclusions: There was no consensus regarding screening regimes for GDM from 2011 through 2012 when four different regimes were applied in Sweden. Increasing levels of OGTT 2-hour glucose values were strongly associated with adverse pregnancy outcomes. Based on these findings, we suggest that Sweden adopts the recent recommendations of the International Association of Diabetes and Pregnancy Study Group (IADPSG) concerning the performance of OGTT and the diagnostic criteria for GDM.