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Introduction. The underlying pathophysiology of diabetes mellitus after acute pancreatitis is unknown and overall risk of developing diabetes postacute pancreatitis in children is understudied. The objective of our study was to describe the frequency of islet cell autoimmunity and abnormal glucose testing in pediatric patients in the year following their index case of acute pancreatitis. Materials and Methods. Data were obtained from a single-center observational cohort study of patients with their first episode of acute pancreatitis. Islet cell autoantibody titers were measured on stored plasma collected from acute pancreatitis diagnosis, at 3 months and at 12 months postacute pancreatitis attack. Abnormal glucose testing was defined as the presence of prediabetes or diabetes, as defined by American Diabetes Association criteria. Results. Eighty-four patients with acute pancreatitis and islet cell autoantibody data were included, 71 had available glucose measures. Median age at first acute pancreatitis attack was 14 years (IQR 8.7–16.3) and 45/84 (54%) were females. Twenty-four patients (29%) were positive for at least one of four islet cell autoantibodies (IAA, GADA, IA-2A, and ZnT8A) and 6 (7%) had two or more positive islet cell autoantibodies. Nineteen patients out of 71 (27%) had abnormal glucose testing at or postacute pancreatitis diagnosis. A higher proportion (37%, 7/19) with abnormal glucose testing had severe acute pancreatitis compared to those with normal glucose testing (13%, 7/52) (p = 0.04). Patients with normal glucose testing were more likely to be positive for one or more islet cell autoantibodies (31%, 16/52) compared to those with abnormal glucose testing (0%, 0/19) (p = 0.004). Conclusions. Islet cell autoimmunity is more common in children after their index acute pancreatitis attack (29%) than in the general population (7%–8%). While the frequency of prediabetes and diabetes postacute pancreatitis is high, other mechanisms besides islet cell autoimmunity are responsible. [ABSTRACT FROM AUTHOR]

Recent studies, albeit controversial, have suggested that the incretin exendin-4 (Ex-4) is capable of inducing β cell proliferation in vivo. Furthermore, this compound has been shown to enhance the ability of other agents (e.g., anti-CD3, antilymphocyte serum) to reverse type 1 diabetes (T1D) in NOD mice. However, the mechanisms underlying this beneficial action for disease reversal remain largely unclear. Herein, we tested the hypothesis that Ex-4 therapy may act as a stimulator of regulatory T cells (Tregs). We evaluated the effect of Ex-4 (Byetta®; 0.2 μg/mouse/day for 30 days) treatment on the frequency and function of Tregs and changes in the cytokine profile of NOD mice with recently diagnosed T1D. In comparison to that of saline-treated control NOD mice, the frequency of Tregs was increased in Ex-4-treated mice. Suppression assays demonstrated a trend towards increased Treg suppression after administration of Ex-4, but were limited by small sample size. Lastly, Ex-4 treatment induced production of IL-10, indicating a possible shift towards a more Th2-like phenotype. Taken collectively, these data suggest that in addition to its potential effects on β cell proliferation, Ex-4 may also act as a regulator of the immune response. [ABSTRACT FROM AUTHOR]

Abstract: Insulin production afforded by hepatic gene therapy (HGT) retains promise as a potential treatment for type 1 diabetes, but successful approaches have been limited. We employed a novel and previously untested promoter for this purpose, glucose transporter-2 (GLUT2) to drive insulin production via delivery by recombinant adeno-associated virus (rAAV). In vitro, the GLUT2 promoter was capable of robust glucose-responsive expression in transduced HepG2 human hepatoma cells. Therefore, rAAV constructs were designed to express the furin-cleavable human preproinsulin B10 gene, under the control of the murine GLUT2 promoter and packaged for delivery with rAAV expressing the type 5 capsid. Streptozotocin-induced diabetic mice were subjected to hepatic portal vein injection immediately followed by implantation of a sustained-release insulin pellet to allow time for transgenic expression. All mice injected with the rAAV5-GLUT2-fHPIB10 virus remained euglycemic for up to 35 days post-injection, with 50% euglycemic after 77 days post-injection. In contrast, mock-injected mice became hyperglycemic within 15 days post-injection following dissolution of the insulin pellet. Serum levels of both human insulin and C-peptide further confirmed successful transgenic delivery by the rAAV5-GLUT2-fHPIB10 virus. These findings indicate that the GLUT2 promoter may be a potential candidate for regulating transgenic insulin production for hepatic insulin gene therapy in the treatment of type I diabetes. [Copyright &y& Elsevier]

The author discusses the use of leptin in the treatment of type 1 diabetes mellitus. Leptin is a 167 amino acid cytokine-like hormone. The study on leptin here base itself and on alternative experiments to the view of Frederick Jezegou as 'Caution is the parent of safety.' The data on leptin in humans come from several studies linking elevated peripheral leptin with pelvic endometriosis and others. It mentions the need to be cautious about extrapolating animal data to human disease.