Isolation of neonatal porcine islet tissue and transplantation into diabetic mice. A methodological evaluation

Diabetes mellitus type I can be a disabling disease with a high risk of complications (i.e. neuropathy, atherosclerosis and nephropathy). Furthermore, the treatment with insulin can be complicated with severe episodes of hypoglycaemia.As diabetes type 1 is caused by an autoimmune destruction of the islets of Langerhans, replacement of these islets could be the treatment of choice for this disease provided the immunological process is halted. Centres world wide perform islet allotransplantation (i.e. transplantation within species) as an experimental treatment of diabetes (Ricordi et al. 1992, Secchi et al. 1997, Warnock et al. 1992, Birkeland et al. 1995). However the results are poor with only 8 % of cases having more than one year of insulin independence after transplantation (international islet transplant registry, 1999).Islet transplantation faces two major obstacles : rejection and shortage of human donors. Rejection is avoided by immunosuppression and in experimental models by immunoprotection of the grafts with micro-encapsulation or larger encapsulating devices (Lanza et al. 1995, Lacy et al. 1991, Monaco et al. 1991). Shortage of human donors has necessitated the search for alternative donors, and in this context the pig has drawn most attention, because the physiology of the pig is comparable to that of humans. Indeed, pig insulin has been successfully used for decades in the treatment of human diabetics. Pigs breed fast, have large litters and can be bred under standardised conditions, which is important, as factors such as strain and age influence the outcome of porcine islet isolations (Socci et al. 1990, Heiser et al. 1994).By small modifications of the automated method developed for human islet isolation, it is possible to isolate large numbers of adult porcine islets (Ricordi et al. 1990). These islets are well functioning in vivo after transplantation to rodents. However, unlike human islets, the adult porcine islets have a very thin peri-insular capsule and are therefore very fragile disintegrating easily in overnight culture (van Deijnen et al. 1992, Warnock G.L. et al. 1995). Islet tissue from foetuses possess a potential for growth, and has been extensively examined in the rat (Yderstraede et al. 1995), pig (Korsgren et al. 1988) and humans (Tuch et al. 1991). Foetal porcine islet tissue has even been transplanted to eight diabetic humans with histological signs of graft survival after three weeks, and porcine C-peptide production detectable up to eight months after transplantation, but without any detectable metabolic improvement in the patients (Groth et al. 1993).Recently, a method has been developed for the isolation of islet tissue from neonatal pigs (Korbutt et al. 1996). The neonatal islet-like cell clusters (NICC’s) can be isolated in large numbers, and are able to differentiate and maybe even proliferate in vitro and in vivo.The purpose of this study is to describe the methods for isolation, transplantation and in vivo evaluation of porcine neonatal islet-like cell clusters. Focus is on the transplantation procedure, but aspects of isolation and functional outcome in vitro and in vivo are also included

Metabolic syndrome and subsequent risk of type 2 diabetes and cardiovascular disease in elderly women:Challenging the current definition

The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD) in elderly Caucasian women. We further investigated if stratification of individuals not defined with MetS would add predictive power in defining future disease prevalence of individuals with MetS. The Prospective Epidemiological Risk Factor Study, a community-based cohort study, followed 3905 Danish women since 2000 (age: 70.1 ± 6.5) with no previous diagnosis of T2DM or CVD, holding all measurements used for MetS definition; central obesity, hypertension, hyperlipidemia, and hyperglycemia combined with register-based follow-up information. Elderly women with defined MetS presented a 6.3-fold increased risk of T2DM (95% confidence interval: [3.74–10.50]) and 1.7-fold increased risk of CVD (1.44–2.05) compared to women with no MetS risk factors. Subdividing the control group without defined MetS revealed that both centrally obese controls and controls holding other MetS risk factors also had increased risk of T2DM (hazard ratio (HR) = 2.21 [1.25–3.93] and HR = 1.75 [1.04–2.96]) and CVD (HR = 1.51 [1.25–1.83] and HR = 1.36 [1.15–1.60]) when compared to controls with no MetS risk factors. MetS in elderly Caucasian women increased risk of future T2DM and CVD. While not defined with MetS, women holding only some risk factors for MetS were also at increased risk of T2DM or CVD compared to women with no MetS risk factors

Self-Management Support to People with Type 2 Diabetes - A comparative study of Kaiser Permanente and the Danish Healthcare System

BACKGROUND: Self-management support is considered to be an essential part of diabetes care. However, the implementation of self-management support within healthcare settings has appeared to be challenging and there is increased interest in “real world” best practice examples to guide policy efforts. In order to explore how different approaches to diabetes care and differences in management structure influence the provision of SMS we selected two healthcare systems that have shown to be comparable in terms of budget, benefits and entitlements. We compared the extent of SMS provided and the self-management behaviors of people living with diabetes in Kaiser Permanente (KP) and the Danish Healthcare System (DHS). METHODS: Self-administered questionnaires were used to collect data from a random sample of 2,536 individuals with DM from KP and the DHS in 2006–2007 to compare the level of SMS provided in the two systems and identify disparities associated with educational attainment. The response rates were 75 % in the DHS and 56 % in KP. After adjusting for gender, age, educational level, and HbA1c level, multiple linear regression analyses determined the level of SMS provided and identified disparities associated with educational attainment. RESULTS: Receipt of SMS varied substantially between the two systems. More people with diabetes in KP reported receiving all types of SMS and use of SMS tools compared to the DHS (p < .0001). Less than half of all respondents reported taking diabetes medication as prescribed and following national guidelines for exercise. CONCLUSIONS: Despite better SMS support in KP compared to the DHS, self-management remains an under-supported area of care for people receiving care for diabetes in the two health systems. Our study thereby suggests opportunity for improvements especially within the Danish healthcare system and systems adopting similar SMS support strategies

Effect of the addition of rosiglitazone to metformin or sulfonylureas versus metformin/sulfonylurea combination therapy on ambulatory blood pressure in people with type 2 diabetes: A randomized controlled trial (the RECORD study)

BACKGROUND: Hypertension and type 2 diabetes are common co-morbidities. Preliminary studies suggest that thiazolidinediones reduce blood pressure (BP). We therefore used ambulatory BP to quantify BP lowering at 6-12 months with rosiglitazone used in combination with metformin or sulfonylureas compared to metformin and sulfonylureas in people with type 2 diabetes. METHODS: Participants (n = 759) in the multicentre RECORD study were studied. Those taking metformin were randomized (open label) to add-on rosiglitazone or sulfonylureas, and those on sulfonylurea to add-on rosiglitazone or metformin. RESULTS: 24-Hour ambulatory BP was measured at baseline, 6 months and 12 months. At 6 and 12 months, reductions in 24-hour ambulatory systolic BP (sBP) were greater with rosiglitazone versus metformin (difference at 6 months 2.7 [95% CI 0.5-4.9] mmHg, p = 0.015; 12 months 2.5 [95% CI 0.2-4.8] mmHg, p = 0.031). Corresponding changes for ambulatory diastolic BP (dBP) were comparable (6 months 2.7 [95% CI 1.4-4.0] mmHg, p < 0.001; 12 months 3.1 [95% CI 1.8-4.5] mmHg, p < 0.001). Similar differences were observed for rosiglitazone versus sulfonylureas at 12 months (sBP 2.7 [95% CI 0.5-4.9] mmHg, p = 0.016; dBP 2.1 [95% CI 0.7-3.4] mmHg, p = 0.003), but differences were smaller and/or not statistically significant at 6 months (sBP 1.5 [95% CI -0.6 to 3.6] mmHg, p = NS; dBP 1.3 [95% CI 0.0-2.5] mmHg, p = 0.049). Changes in BP were not accompanied by compensatory increases in heart rate, did not correlate with basal insulin sensitivity estimates and were not explained by changes in antihypertensive therapy between the various strata. CONCLUSION: When added to metformin or a sulfonylurea, 12-month treatment with rosiglitazone reduces ambulatory BP to a greater extent than when metformin and a sulfonylurea are combined. TRIAL REGISTRATION: NCT00379769 http://clinicaltrials.gov