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.

Improved skeletal muscle oxidative enzyme activity and restoration of PGC-1α and PPARß/δ gene expression upon rosiglitazone treatment in obese patients with type 2 diabetes mellitus

Objective: To examine whether rosiglitazone alters gene expression of some key genes involved in mitochondrial biogenesis and oxidative capacity in skeletal muscle of type 2 diabetic patients, and whether this is associated with alterations in skeletal muscle oxidative capacity and lipid content.

Design: Skeletal muscle gene expression, mitochondrial protein content, oxidative capacity and lipid accumulation were measured in muscle biopsies obtained from diabetic patients, before and after 8 weeks of rosiglitazone treatment, and matched controls. Furthermore, whole-body insulin sensitivity and substrate utilization were assessed.

Subjects: Ten obese type 2 diabetic patients and 10 obese normoglycemic controls matched for age and BMI.

Methods: Gene expression and mitochondrial protein content of complexes I–V of the respiratory chain were measured by quantitative polymerase chain reaction and Western blotting, respectively. Histochemical staining was used to quantify lipid accumulation and complex II succinate dehydrogenase (SDH) activity. Insulin sensitivity and substrate utilization were measured during a hyperinsulinemic–euglycemic clamp with indirect calorimetry.

Results: Skeletal-muscle mRNA of PGC-1a and PPARb/d – but not of other genes involved in glucose, fat and oxidative metabolism – was significantly lower in diabetic patients (Po0.01). Rosiglitazone significantly increased PGC-1a (B2.2-fold, Po0.01) and PPARb/d (B2.6-fold, Po0.01), in parallel with an increase in insulin sensitivity, SDH activity and metabolic flexibility (Po0.01). Surprisingly, none of the measured mitochondrial proteins was reduced in type 2 diabetic patients, nor affected by rosiglitazone treatment. No alterations were seen in muscular fat accumulation upon treatment.

Conclusion: These results suggest that the insulin-sensitizing effect of rosiglitazone may involve an effect on muscular oxidative capacity, via PGC-1a and PPARb/d, independent of mitochondrial protein content and/or changes in intramyocellular lipid.

Aerobic exercise and resistance training for the management of type 2 diabetes mellitus

BACKGROUND
Implementation of a structured physical exercise program can improve glycemic control in patients with type 2 diabetes mellitus.

OBJECTIVE
To evaluate the efficacy of aerobic exercise and resistance training (either alone or in combination) in the management of type 2 diabetes mellitus.

DESIGN AND INTERVENTION
DARE (Diabetes Aerobic and Resistance Exercise) was a 26-week, single-center, parallel-group, randomized, controlled trial of patients with type 2 diabetes mellitus of >6 months' duration. Participants were aged 39-70 years with a baseline [HbA.sub.1c] level 6.6-9.9%. Exclusion criteria included current insulin therapy, regular exercise regime and blood pressure >160/95 mmHg. All participants underwent a 4-week run-in period that comprised 12 sessions of combined aerobic exercise and resistance training; participants who attended [greater than or equal to] 10 sessions were eligible to enter the study. Eligible participants were randomly allocated to one of four groups: aerobic exercise alone; resistance training alone; combined aerobic exercise and resistance training; and no intervention (control group). Exercise was performed three times weekly. The aerobic exercise group progressed from 15-20 min on a treadmill or bicycle ergometer per session at 60% of the maximum heart rate to 45 min per session at 75% of the maximum heart rate. The resistance training group performed 7 different exercises on weight machines per 45 min session, and progressed to 2-3 sets of each exercise at the maximum weight that could be lifted 7-9 times. The combined exercise group performed the full aerobic exercise program plus the full resistance training program. Participants in the control group reverted to their pre-study exercise levels.

OUTCOME MEASURES
The primary outcome measure was the change in [HbA.sub.1c] from baseline. Secondary outcome measures included changes in blood pressure, lipid profile, and body composition.

RESULTS
A total of 251 participants were eligible for intervention. The median session attendance was 80% (aerobic exercise), 85% (resistance training) and 86% (combined exercise). When compared with the control group, the HbA1c levels were reduced by 0.50% in the aerobic exercise group (P = 0.007) and by 0.38% in the resistance training group (P = 0.038). The combined exercise group had an additional reduction of 0.46% when compared with the aerobic exercise group (P = 0.014) and of 0.59% when compared with the resistance training group (P = 0.001). Decreases in [HbA.sub.1c] levels were greatest for participants with a baseline [HbA.sub.1c] level = 7.5% (P <0.001). For participants with a baseline level [HbA.sub.1c] <7.5%, significant improvements in glycemic control were observed in the combined exercise group only (P = 0.002). Changes in blood pressure and lipid profiles did not differ between the groups. By contrast, participation in a structured exercise program improved body composition.

CONCLUSION
Although aerobic exercise or resistance training alone improved glycemic control, additional improvements were observed with the combined exercise regimen.

Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance. The Australian Diabetes, Obesity and Lifestyle Study (AusDiab)

Background--Diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. The relationship between milder elevations of blood glucose and mortality is less clear. This study investigated whether impaired fasting glucose and impaired glucose tolerance, as well as diabetes mellitus, increase the risk of all-cause and CVD mortality.

Methods and Results--In 1999 to 2000, glucose tolerance status was determined in 10 428 participants of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). After a median follow-up of 5.2 years, 298 deaths occurred (88 CVD deaths). Compared with those with normal glucose tolerance, the adjusted all-cause mortality hazard ratios (HRs) and 95% confidence intervals (CIs) for known diabetes mellitus and newly diagnosed diabetes mellitus were 2.3 (1.6 to 3.2) and 1.3 (0.9 to 2.0), respectively. The risk of death was also increased in those with impaired fasting glucose (HR 1.6, 95% CI 1.0 to 2.4) and impaired glucose tolerance (HR 1.5, 95% CI 1.1 to 2.0). Sixty-five percent of all those who died of CVD had known diabetes mellitus, newly diagnosed diabetes mellitus, impaired fasting glucose, or impaired glucose tolerance at baseline. Known diabetes mellitus (HR 2.6, 95% CI 1.4 to 4.7) and impaired fasting glucose (HR 2.5, 95% CI 1.2 to 5.1) were independent predictors for CVD mortality after adjustment for age, sex, and other traditional CVD risk factors, but impaired glucose tolerance was not (HR 1.2, 95% CI 0.7 to 2.2).

Conclusions--This study emphasizes the strong association between abnormal glucose metabolism and mortality, and it suggests that this condition contributes to a large number of CVD deaths in the general population. CVD prevention may be warranted in people with all categories of abnormal glucose metabolism.

The metabolic syndrome as a predictor of incident diabetes mellitus in Mauritius

Aims : To assess the utility of the metabolic syndrome (MetS) and a Diabetes Predicting Model as predictors of incident diabetes.

Methods : A longitudinal survey was conducted in Mauritius in 1987 (n = 4972; response 80%) and 1992 (n = 3685; follow-up 74.2%). Diabetes status was retrospectively determined using 1999 World Health Organization (WHO) criteria. MetS was determined according to four definitions and sensitivity, positive predictive value (PPV), specificity and the association with incident diabetes before and after adjustment for MetS components calculated.

Results : Of the 3198 at risk, 297 (9.2%) developed diabetes between 1987 and 1992. The WHO MetS definition had the highest prevalence (20.3%), sensitivity (42.1%) and PPV (26.8%) for prediction of incident diabetes, the strongest association with incident diabetes after adjustment for age and sex [odds ratio 4.6 (3.5–6.0)] and was the only definition to show a significant association after adjustment for its component parts (in men only). The low prevalence and sensitivity of the International Diabetes Federation (IDF) and ATPIII MetS definitions resulted from waist circumference cut-points that were high for this population, particularly in men, and both were not superior to a diabetes predicting model on receiver operating characteristic analysis.

Conclusions : Of the MetS definitions tested, the WHO definition best identifies those who go on to develop diabetes, but is not often used in clinical practice. If cut-points or measures of obesity appropriate for this population were used, the IDF and ATPIII MetS definitions could be recommended as useful tools for prediction of diabetes, given their relative simplicity.

Sociodemographic correlates of the increasing trend in prevalence of gestational diabetes mellitus in a large population of women between 1995 and 2005

OBJECTIVE—Gestational diabetes mellitus (GDM) is an increasingly prevalent risk factor for the development of type 2 diabetes in the mother and is  responsible for morbidity in the child. To better identify women at risk of developing GDM we examined sociodemographic correlates and changes in the prevalence of GDM among all births between 1995 and 2005 in Australia's largest state.
RESEARCH DESIGN AND METHODS—A computerized database of all births (n = 956,738) between 1995 and 2005 in New South Wales, Australia, was used in a multivariate logistic regression that examined the association between sociodemographic characteristics and the occurrence of GDM.
RESULTS—Between 1995 and 2005, the prevalence of GDM increased by 45%, from 3.0 to 4.4%. Women born in South Asia had the highest adjusted odds ratio (OR) of any region (4.33 [95% CI 4.12–4.55]) relative to women born in Australia. Women living in the three lowest socioeconomic quartiles had higher adjusted ORs for GDM relative to women in the highest quartile (1.54 [1.50–1.59], 1.74 [1.69–1.8], and 1.65 [1.60–1.70] for decreasing socioeconomic status quartiles). Increasing age was strongly associated with GDM, with women aged >40 years having an adjusted OR of 6.13 (95% CI 5.79–6.49) relative to women in their early 20s. Parity was associated with a small reduced risk. There was no association between smoking and GDM.
CONCLUSIONS—Maternal age, socioeconomic position, and ethnicity are important correlates of GDM. Future culturally specific interventions should target prevention of GDM in these high-risk groups.

Vitamin C and the risk of gestational diabetes mellitus: a case-control study

OBJECTIVE: To examine whether low maternal dietary intake of vitamin C and low maternal plasma ascorbic acid (AA) concentrations are associated with an increased risk of gestational diabetes mellitus (GDM).
METHODS: Cases were 67 women with GDM meeting National Diabetes Data Group criteria. Controls were 260 women without such a diagnosis. Maternal dietary vitamin C consumption during the periconceptional period and during pregnancy was assessed using a 121-item, semiquantitative food frequency questionnaire. Maternal plasma AA concentrations were determined using automated enzymatic procedures on specimens collected during the intrapartum period.
RESULTS: Mean maternal daily consumption of vitamin C and plasma AA concentrations were 10% and 31% lower, respectively, among GDM cases as compared with controls (130.7 +/- 10.2 vs. 145 +/- 4.9 mg/d, P = .190; 36 +/- 2.0 vs. 53 +/- 1.0 micromol/L, P <.001). After controlling for maternal age, race, prepregnancy adiposity, family history of type 2 diabetes, energy intake and income, women reporting low daily vitamin C intake (< 70 mg/d), as compared with the other women, experienced a 3.7-fold increased risk of GDM (odds ratio [OR] = 3.7, 95% confidence interval [CI] 1.7-8.2). There was a linear relation in risk of GDM with decreasing concentrations of plasma AA (P for linear trend <.001). After adjusting for confounders, women in the lowest quartile (< 42.6 micromol/L), as compared with women in the highest quartile (> 63.3 micromol/L), experienced > 12-fold increased risk of GDM (OR = 12.8, 95% CI 3.5-46.2). CONCLUSION: Low maternal dietary vitamin C intake and low plasma AA concentrations are associated with an increased risk of GDM. Large, prospective, cohort studies are needed to further evaluate the potential beneficial role of vitamin C and other antioxidants in the prevention of impaired glucose tolerance in pregnancy.