No abstract

Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T cells toward macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1β and a decrease of tumor necrosis factor-α. IL-10, PCNA, and insulin expression were increased in the LADA situation, whereas caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results, allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.

Emptying of the gastric substitute and small bowel transit time of a 99mTc-labeled solid test meal were measured in 20 tumor-free patients 13 to 63 (median, 35) months after total gastrectomy with Roux-y (n = 11) and jejunal interposition (n = 9) reconstruction. The emptying half-times ranged from 2 minutes to greater than 20 minutes. Rapid emptying was associated with dumping symptoms (p less than 0.03) and shorter orocoecal transit-time (p less than 0.05). Serum glucose concentrations rose more quickly in jejunal interposition, but the areas under the curve were identical in both groups. The median insulin-to-glucose ratio (areas under the curve) during the 20 minutes after the meal was 11.4 in jejunal interposition and 7.1 in Roux-y esophagojejunostomy (NS). Interposition cases had regained a significantly higher percentage (89%) of their premorbid weight than patients with Roux-y (78%; p less than 0.05). The weight/height2 ratio was above the 50th centile in 45% of interpositions, but below the 50th centile in all patients after the Roux-y mode of reconstruction (p less than 0.05). It is concluded that the emptying velocity of the gastric substitute has no impact on postoperative weight gain. The authors contend that the concept of a gastric substitute pouch is not supported by the findings of this study.

1. Mucosally added synthetic guanylin and Escherichia coli heat‐stable enterotoxin (STa) increased short‐circuit current (ISC) across isolated muscle‐stripped human intestine in vitro. 2. Serosal bumetanide inhibited ISC responses indicating that guanylin and STa stimulate electrogenic chloride secretion. 3. ISC responses were markedly greater in the colon than in the jejunum. 4. Pretreatment with indomethacin did not significantly alter the effects of guanylin and STa. 5. Both peptides induced concentration‐dependent increases in the cyclic GMP content of human intestinal mucosa in vitro; cyclic AMP levels remained unchanged. 6. In contrast to ISC responses, increases in cyclic GMP content induced by guanylin and STa were markedly greater in the jejunum than in the colon. 7. Sodium nitroprusside (SNP) but not human alpha‐atrial natriuratic peptide (CDD/ANP(99‐126)) increased chloride secretion in human intestine; both agents induced small increases in intestinal cyclic GMP content. 8. Guanylin, STa and the nitric oxide (NO) donor SNP increased electrogenic chloride secretion across human intestinal mucosa in vitro by stimulation of cyclic GMP. The discrepancy between the effects on chloride secretion and intracellular cyclic GMP content suggest different cellular action sites of guanylin and STa in human small and large intestine.