1. Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari Paolo Usai Satta Verona, 9 Marzo 2010

2. Gastro-intestinal symptoms and diabetes

3. Arch Intern Med. 2000

4. Arch Intern Med. 2001

5. Am J Gastroenterol 2008 The turnover of GI symptoms in diabetic subjects was not associated with glycemic control but there was a positive association with change in depression.

6. Autonomic neuropathy Pathophysiology

7. Bharucha, Gut 1993 Cardiovascular autonomic tests: extrinsec AN

8. Usai Satta, Ital J Gastroenterol 1997 Cardiovascular autonomic tests: extrinsec AN

9. Diabetic autonomic neuropathy (DAN)

11. Esophageal enteropathy (disordered peristalsis, abnormal lower esophageal sphincter function) Gastroparesis diabeticorum (nonobstructive impairment of gastric propulsive activity; brady/tachygastria, pylorospasm) Diarrhea (impaired motility of the small bowel [bacterial overgrowth syndrome], increased motility and secretory activity [pseudocholeretic diarrhea]) Constipation (dysfunction of intrinsic and extrinsic intestinal neurons, decreased or absent gastrocolic reflex) Fecal incontinence (abnormal internal anal sphincter tone, impaired rectal sensation, abnormal external sphincter) Gallbladder atony and enlargement Gastro-intestinal DAN

12. Diabetic Gastroparesis Epidemiology 20-40% of diabetics female sex (4:1) similar frequence in DM1 e DM2 ? Nausea and vomiting (5-10%) AGA/ANMS review: Neuro-Gastroenterol Mot 2010

13. Diabetic Gastroparesis Pathophysiology Vagal autonomic neuropathy Acute Hyperglycemia Loss of expression of neuronal nitric oxide (nNOS) Disruption of interstitial cell of Cajal (ICC) networks. AGA/ANMS review: Neuro-Gastroenterol Mot 2010

14. Diabetic Gastroparesis Motor dysfunctions - impaired meal-induced relaxation of the gastric fundus - increased pyloric motor activity - fewer antral contractions - impaired antroduodenal coordination AGA/ANMS review: Neuro-Gastroenterol Mot 2010

15. Interstitial cells of Cajal were greatly reduced in the distal stomach, and the normally close associations between these cells and enteric nerve terminals were infrequent Diabetes 2000 Interstitial cell of Cajal (ICC)

17. AGA/ANMS review: Neuro-Gastroenterol Mot 2010 Diagnosis

18. Kloetzer L, Neuro-Gastroenterol Mot 2010, in press Wir eless motility capsule Smart Pill

19. Treatment: correction of glycemia…….

20. J Clin Endocrinol Metab 2006 New treatments Mitemcinal Ghrelin Prucalopride (5HT4 agonist) Acotiamide (M1, M2 antagonist) Iberogastr Enterra gastric electric stimulation

21. Diabetes: Conclusions Autonomic neuropathy is the most important pathophysiological mechanism Gastroparesis is the most frequent motor disorder Delayed gastric emptying is more frequent than symptoms Scintigrafy and BTs are the most standardized studies New therapies could be available