Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy.

BACKGROUND: A high prevalence of diabetes mellitus (DM) coexisting with autoimmune pancreatitis (AIP) is observed. However, evidence on the circumstances under which corticosteroid therapy (CST) for AIP improves or worsens DM is scarce. This study aimed to demonstrate and identify predictors of DM control under the influence of CST. METHODS: Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed: pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM). The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as 'improvement' and 'non-improvement' (including 'no change' and 'exacerbation'). RESULTS: Among 101 patients with type 1 AIP, 52 (51.5%) patients were complicated with DM at the time of AIP diagnosis, with 36 patients in the cDM group and 16 patients in the pDM group. The incidences of diffuse pancreatic swelling (72.2%) and pancreatic body/tail involvement (91.7%) were significantly higher in the cDM group than in both the pDM and nDM groups. Of the 52 patients with DM, CST was administered in 48 cases. Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase (GGT) level at AIP diagnosis [odds ratio (OR) = 0.032, 95% confidence interval (CI): 0.003-0.412, P = 0.008] and pancreatic atrophy after CST (OR = 0.027, 95% CI: 0.003-0.295, P = 0.003) were negatively associated with DM control improvement. CONCLUSIONS: Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis. CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis, particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Gene therapy for diabetes mellitus in rats by intramuscular injection of lentivirus containing insulin gene.

We assessed therapeutic potential of intramuscular insulin gene delivery in a diabetic murine model. The human proinsulin gene cDNA engineered with concensus furin cleavage sequences was inserted into an advanced lentiviral vector that contained CMV early promoter. After injection of concentrated lentiviral vector (3.5 microg p24 Gag antigen) carrying the insulin gene into the thigh muscle, treated rats demonstrated an increase in body weight, increased survivability, attenuated the hyperglycemic response as well as prevented the formation of ketoacidosis. For these reasons, the intraparenchymal injection of lentiviral vectors into the skeletal muscle to ectopically produce insulin may be an easy and therapeutic treatment modality for type 1 diabetes mellitus.

Intracerebroventricular injection of stresscopin-related peptide enhances cardiovascular function in conscious rats.

Stresscopin-related peptide (SRP), which is a member of the corticotropin-releasing factor (CRF) family, is a high-affinity ligand for the type 2 corticotropin-releasing factor receptor (CRF-R2) and is involved in stress-coping responses. Central treatment with SRP suppresses food intake, delays gastric emptying and decreases heat-induced edema, but the effects of central administration of SRP on the cardiovascular system are unclear. Here we examined the effects of intracerebroventricular (i.c.v.) administration of SRP on cardiovascular function, and compared the cardiovascular effects of SRP and stresscopin (SCP). Our results showed that i.c.v. administration of SRP (0.5nmol) increased mean arterial blood pressure (MABP) and heart rate (HR), but failed to increase plasma norepinephrine and epinephrine levels. Compared with an equivalent dose of SCP, the area under the curve (AUC) values for the changes in MABP and HR were significantly smaller with SRP, indicating that the cardiovascular effects of SRP were weaker than those mediated by SCP. Pre-treatment with a selective CRF-R2 antagonist, antisauvagine-30 (4nmol, i.c.v.) abolished the SRP and SCP induced changes in MABP and HR. These results indicate that central administration of SRP induces a weaker enhancement of cardiovascular function through CRF-R2 than that induced by SCP and that these effects are mediated without increasing plasma norepinephrine and epinephrine levels.