Type 1 diabetes: a disease of developmental origins.

The incidence of type 1 diabetes globally has increased dramatically over the last 50 years. Proposed environmental reasons for this increase mirror the modern lifestyle. Type 1 diabetes can be viewed as part of the non- communicable disease epidemic in our modern society. Meanwhile rapidly evolving new technologies are advancing our understanding of how human microbial communities interface with the immune system and metabolism, and how the modern pro-inflammatory environment is changing these communities and contributing to the rapid rise of non-communicable disease. The majority of children who present with clinical type 1 diabetes are of school age; however 80% of children who develop type 1 diabetes by 18 years of age will have detectable islet autoantibodies by 3 years of age. The evolving concept that type 1 diabetes in many children has developmental origins has directed research questions in search of prevention back to pregnancy and early life. To this end the world's first pregnancy to early childhood cohort study in at-risk children has commenced.

Interleukin 10 Restores Gastric Emptying, Electrical Activity, and Interstitial Cells of Cajal Networks in Diabetic Mice.

BACKGROUND & AIMS: Gastroparesis is a complication of diabetes characterized by delayed emptying of stomach contents and accompanied by early satiety, nausea, vomiting, and pain. No safe and reliable treatments are available. Interleukin 10 (IL10) activates the M2 cytoprotective phenotype of macrophages and induces expression of heme oxygenase 1 (HO1) protein. We investigated whether IL10 administration could improve gastric emptying and reverse the associated cellular and electrical abnormalities in diabetic mice. METHODS: Nonobese diabetic mice with delayed gastric emptying were given either IL10 (0.1-1 µg, twice/day) or vehicle (controls). Stomach tissues were isolated, and sharp microelectrode recordings were made of the electrical activity in the gastric muscle layers. Changes to interstitial cells of Cajal (ICC), reduced nicotinamide adenine dinucleotide phosphate diaphorase, and levels and distribution of HO1 protein were determined by histochemical and imaging analyses of the same tissues. RESULTS: Gastric emptying remained delayed in vehicle-treated diabetic mice but returned to normal in mice given IL10 (n = 10 mice; P < .05). In mice given IL10, normalization of gastric emptying was associated with a membrane potential difference between the proximal and distal stomach, and lower irregularity and higher frequency of slow-wave activity, particularly in the distal stomach. Levels of HO1 protein were higher in stomach tissues from mice given IL10, and ICC networks were more organized, better connected, and more evenly distributed compared with controls. CONCLUSIONS: IL10 increases gastric emptying in diabetic mice and has therapeutic potential for patients with diabetic gastroparesis. This response is associated with up-regulation of HO1 and repair of connectivity of ICC networks.