Nonspecific inflammation is associated with primary graft nonfunction (PNF). Inflammatory islet damageis mediated at least partially by pro-inflammatory cytokines, such as interleukin-1b (IL-1b ) and tumor necrosis factor-a (TNF-a ) produced by resident islet macrophages. The p38 pathway is known to be involved in cytokine production in the cells of the monocyte-macrophage lineage. Therefore, inhibition of the p38 pathway may prevent pro-inflammatory cytokine production by resident islet macrophages and possibly reduce the incidence of PNF. Our present study has demonstrated that inhibition of the p38 pathway by a chemical p38 inhibitor, SB203580, suppresses IL-1b and TNF-a production in human islets exposed to lipopolysaccharide (LPS) and/or inflammatory cytokines. Although IL-1b is predominantly produced by resident macrophages, ductal cells and islet vascular endothelial cells were found to be another cellular source of IL-1b in isolated human islets. SB203580 also inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the treated islets. Furthermore, human islets treated with SB203580 for 1 h prior to transplantation showed significantly improved graft function. These results suggest that inhibition of the p38 pathway may become a new therapeutic strategy to improve graft survival in clinical islet transplantation.
Photovoice is a research method developed to help communities share images as a tool for discussion of key issues. Although this may be useful to promote healthy behavior, using Photovoice in adolescents has been logistically challenging. Given adolescents’ engagement in social media, our study explored the feasibility of using a photo-sharing mobile phone application, Instagram, to accomplish the principles of Photovoice. Twenty adolescents 14 to 18 years old with type 1 diabetes were asked to use Instagram to post any diabetes-related photo for 3 weeks. Individual interviews and a focus group were also offered, and recruitment and retention statistics were tracked. Of those approached (n = 47), 43% agreed to participate. Twelve were actively engaged. Shared photos were most likely to fall into the categories of diabetes care, humor, or food. Engaged participants universally reported the project to be a positive experience; however, there were technological and personal factors to consider for widespread implementation.
Our data indicate that Triple Stained cells may represent a quiescent population of SSCs, whereas SSEA-4 might be expressed on a subpopulation of actively dividing SSCs.
Using the specified culture methods, non-islet pancreas cells can generate cell clusters resembling islets. These ICCs, obtained from fractions of the pancreas that are otherwise discarded, continue to differentiate after transplantation to become mature islets.
Background.
One in three adolescents and young adults with type 1 diabetes have at least one early diabetes-related complication/comorbidity. However, the prevalence, patterning, and risk factors for co-occurring complications in this population are not well understood.
Methods.
The SEARCH for Diabetes in Youth observational cohort study includes 1327 individuals diagnosed with type 1 diabetes before 20 years of age from 5 United States locations. Sociodemographic and metabolic risk factors were assessed at baseline (mean diabetes duration = 0·8 years, mean age = 10·9 years) and follow-up (mean diabetes duration = 7.8 years, mean age = 18·0 years). Early diabetes complications (diabetic kidney disease, diabetic retinopathy, peripheral neuropathy, cardiovascular autonomic neuropathy, and arterial stiffness) were assessed at follow-up. We aimed to describe co-occurrence of complications and examine differences in co-occurrence within demographic and metabolic risk factor clusters identified using cluster analysis.
Findings.
Overall, co-occurrence of any ≥2 complications was observed in 5·9% of all participants, more frequently than expected by chance alone (4·4%, p=0·015). Specifically, retinopathy and diabetic kidney disease, retinopathy and arterial stiffness, and arterial stiffness and cardiac autonomic neuropathy all co-occurred more frequently than expected (all p<0·05). The cluster analysis produced four unique clusters characterized by progressively worsening metabolic risk factor profiles (longer duration; higher A1c, non-HDL cholesterol, and waist to height ratio) and differences in sociodemographic characteristics (race/ethnicity, household income, type of health insurance). Prevalence of ≥2 complications progressively increased with worsening metabolic profiles (from 2·3% to 20·8%, p<0·001).
Interpretation.
We report that early complications co-occur in adolescents and young adults with type 1 diabetes more frequently than expected after an average of less than eight years of diabetes duration. A cluster of high risk factors identifies groups that may benefit most from interventions to reduce complications.
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