Islet transplantation is a potential treatment for type 1 diabetes, but the shortage of donor organs limits its routine application. As potential donor animals, we generated transgenic pigs expressing LEA29Y, a high-affinity variant of the T-cell costimulation inhibitor CTLA-4Ig, under the control of the porcine insulin gene promoter. Neonatal islet cell clusters (ICCs) from INSLEA29Y transgenic (LEA-tg) pigs and wild-type controls were transplanted into streptozotocin-induced hyperglycemic NOD-scid IL2Rγ^null mice. Cloned LEA-tg pigs are healthy and exhibit a strong β-cell–specific transgene expression. LEA-tg ICCs displayed the same potential to normalize glucose homeostasis as wild-type ICCs after transplantation. After adoptive transfer of human peripheral blood mononuclear cells, transplanted LEA-tg ICCs were completely protected from rejection, whereas reoccurrence of hyperglycemia was observed in 80% of mice transplanted with wild-type ICCs. In the current study, we provide the first proof-of-principle report on transgenic pigs with β-cell–specific expression of LEA29Y and their successful application as donors in a xenotransplantation model. This approach may represent a major step toward the development of a novel strategy for pig-to-human islet transplantation without side effects of systemic immunosuppression.

To explore the association between knowledge on diabetes and glycemic control among patients with type 2 diabetes in Bangladesh. A cross-sectional study was conducted among 515 patients with type 2 diabetes attending a tertiary hospital in Dhaka, Bangladesh. Trained interviewers were used to collect data on socioeconomic status, time since the onset of diabetes, co-morbidities, anthropometric measurements, blood tests, knowledge and perceptions about the causes, management, and complications of diabetes through face to face interviewers based on a structured questionnaire. Diabetes knowledge was reported using a composite score. Chi square tests and correlation analysis were performed to measure the association between knowledge on diabetes and glycemic control. Overall, 45.6% participants had good, 37.7% moderate and 16.7% poor knowledge on diabetes. The mean composite score was 0.75 ± 0.28 and the proportion of participants with a score of ≤50% was 16.7%. Only 24.3% participants identified physical inactivity as a risk factor for diabetes. Knowledge on diabetes was significantly associated with education, gender, monthly income, duration of diabetes, body mass index, family history of diabetes, and marital status but not with glycated hemoglobin (HbA1c). Correlation matrix showed weak negative association between diabetes knowledge score and glycemic control (p < 0.001). Patients with type 2 diabetes in Bangladesh have limited knowledge on the causes, management and risk factors for diabetes, despite receiving professional health education and care in a tertiary diabetic hospital. Strategies to improve the quality of diabetes education and identifying other potential factors for glycemic control are important for ensuring optimum management of diabetes in Bangladesh.

Aims/hypothesis: Many individuals who develop type 2 diabetes also display increased glucagon levels (hyperglucagonaemia), which we have previously found to be associated with the metabolic syndrome. The concept of a liver–alpha cell axis provides a possible link between hyperglucagonaemia and elevated liver fat content, a typical finding in the metabolic syndrome. However, this association has only been studied in individuals with non-alcoholic fatty liver disease. Hence, we searched for a link between the liver and the alpha cells in individuals with non-steatotic levels of liver fat content. We hypothesised that the glucagon–alanine index, an indicator of the functional integrity of the liver–alpha cell axis, would associate with liver fat and insulin resistance in our cohort of women with low levels of liver fat. Methods: We analysed data from 79 individuals participating in the Prediction, Prevention and Subclassification of Type 2 Diabetes (PPSDiab) study, a prospective observational study of young women at low to high risk for the development of type 2 diabetes. Liver fat content was determined by MRI. Insulin resistance was calculated as HOMA-IR. We conducted Spearman correlation analyses of liver fat content and HOMA-IR with the glucagon–alanine index (the product of fasting plasma levels of glucagon and alanine). The prediction of the glucagon–alanine index by liver fat or HOMA-IR was tested in multivariate linear regression analyses in the whole cohort as well as after stratification for liver fat content ≤0.5% (n = 39) or >0.5% (n = 40). Results: The glucagon–alanine index significantly correlated with liver fat and HOMA-IR in the entire cohort (ρ = 0.484, p < 0.001 and ρ = 0.417, p < 0.001, respectively). These associations resulted from significant correlations in participants with a liver fat content >0.5% (liver fat, ρ = 0.550, p < 0.001; HOMA-IR, ρ = 0.429, p = 0.006). In linear regression analyses, the association of the glucagon–alanine index with liver fat remained significant after adjustment for age and HOMA-IR in all participants and in those with liver fat >0.5% (β = 0.246, p = 0.0.23 and β = 0.430, p = 0.007, respectively) but not in participants with liver fat ≤0.5% (β = −0.184, p = 0.286). Conclusions/interpretation: We reproduced the previously reported association of liver fat content and HOMA-IR with the glucagon–alanine index in an independent study cohort of young women with low to high risk for type 2 diabetes. Furthermore, our data indicates an insulin-resistance-independent association of liver fat content with the glucagon–alanine index. In summary, our study supports the concept that even lower levels of liver fat (from 0.5%) are connected to relative hyperglucagonaemia, reflecting an imminent impairment of the liver–alpha cell axis.

Mobile phone technologies including SMS (short message service) have been used to improve the delivery of health services in many countries. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. The aim of this study therefore is to measure the impact of a mobile phone SMS service on treatment success of newly diagnosed type 2 diabetes in an urban area of Bangladesh. This is a single-centred randomized controlled intervention trial (prospective) comparing standard-of-care with standard-of-care plus a mobile phone-based SMS intervention for 6 months. A total of 216 participants with newly diagnosed type 2 diabetes will be recruited. Data will be collected at the outpatient department of Bangladesh Institute of Health Science (BIHS) hospital at baseline and after 6 months. The primary outcome measure will be change in HbA1c between baseline and 6 months. The secondary outcome measures are self-reported medication adherence, clinic attendance, self-reported adoption of healthy behaviours, diabetes knowledge, quality of life and cost effectiveness of the SMS intervention. The inclusion criteria will be as follows: diagnosed as patients with type 2 diabetes by the BIHS physician, using oral medication therapy, living in Dhaka city, registered with the BIHS hospital, using a mobile phone, willing to return for follow up after 6 months and providing written informed consent. Participants will be allocated to control and intervention arms after recruitment using a randomization software. Data will be collected on socio-demographic and economic information, mobile phone use and habits, knowledge of prevention, management and complications of diabetes, self-perceived quality of life assessment, self-reported diseases, medical history, family history of diseases, medication history, medication adherence, health seeking behaviour, tobacco use, physical activity, diet, mental health status, life events and disability, anthropometric measurements of weight, height, blood pressure and blood tests for HbA1c. Mobile phone SMS services have the potential to communicate with diabetes patients and to build awareness about the disease, improve self-management and avoid complications also in resource-limited setting. If this intervention proves to be efficient and cost-effective in the current trial, large-scale implementation could be undertaken. DRKS00005188 .

Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ^−/− (NSG) mice stably reconstituted with a human immune system. Transplantation of INSLEA29Y expressing NPICCs resulted in development of normal glucose tolerance (70.4%) and long-term maintenance of normoglycemia without administration of immunosuppressive drugs. All animals transplanted with wild-type NPICCs remained diabetic. Immunohistological examinations revealed a strong peri- and intragraft infiltration of wild-type NPICCs with human CD45⁺ immune cells consisting of predominantly CD4⁺ and CD8⁺ lymphocytes and some CD68⁺ macrophages and FoxP3⁺ regulatory T cells. Significantly less infiltrating lymphocytes and only few macrophages were observed in animals transplanted with INSLEA29Y transgenic NPICCs. This is the first study providing evidence that beta cell-specific LEA29Y expression is effective for NPICC engraftment in the presence of a humanized immune system and it has a long-lasting protective effect on inhibition of human anti-pig xenoimmunity. Our findings may have important implications for the development of a low-toxic protocol for porcine islet transplantation in patients with type 1 diabetes.

Background: Metabolic alterations and endothelial dysfunction are interrelated processes in type 2 diabetes (T2D) and metabolic syndrome (MetS) that often develop in parallel. We assessed the association of vasoactive precursor peptides (VPPs) with MetS and T2D.Design and methods: Plasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and midregional pro-adrenomedullin (MR-proADM) were measured by novel sensitive assays in 1590 participants of the population-based KORA F4 study. The association of the VPPs with T2D, MetS defined by IDF criteria, the components of MetS, and insulin resistance (IR) was assessed in logistic regression models.Results: Elevated levels of CT-proET-1 and MR-proADM were associated with T2D, MetS, and IR in age- and sex-adjusted models. After adjustment for age, sex, former vascular complications, lifestyle factors, high-sensitive C-reactive protein, and serum creatinine, significant associations with MetS were found for MR-proADM (OR=5.94, 95% CI 3.78–9.33) and CT-proET-1 (OR=5.18, 95% CI 3.48–7.71) (top quartile vs bottom quartile). CT-proET-1 and MR-proADM were strongly associated with all components of MetS as defined by IDF criteria. After multivariable adjustment, association of CT-proET-1 and MR-proADM with pathological glucose tolerance and T2D disappeared and a borderline association with IR was found only for CT-proET-1 (OR=1.34, 95% CI 0.96–1.87).Conclusions: We here demonstrate for the first time that plasma levels of both MR-proADM and CT-proET-1 levels are related to MetS and its components, thus suggesting that they possibly have a role as a surrogate biomarker for the disease and its complications.