joint meeting gismad-fismad disturbi della motilita’ g i nelle patologie sistemiche diabete...

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

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Page 1: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Joint Meeting GISMAD-FISMAD

DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE

SISTEMICHE

DIABETE

STRUTTURA COMPLESSA GASTROENTEROLOGIA, CagliariSTRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari

Paolo Usai Satta

Verona, 9 Marzo 2010

Page 2: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Gastro-intestinal symptoms and diabetes

Page 3: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Arch Intern Med. 2000

Page 4: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Arch Intern Med. 2001

Page 5: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

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.

Page 6: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Autonomic neuropathy

Pathophysiology

Page 7: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

010203040506070

AN (%)

Bharucha, Gut 1993

Cardiovascular autonomic tests: extrinsec AN

Page 8: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

010203040506070

AN (%)

Usai Satta, Ital J Gastroenterol 1997

Cardiovascular autonomic tests: extrinsec AN

Page 9: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Diabetic autonomic neuropathy (DAN)

Page 10: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA
Page 11: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

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

Page 12: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Diabetic GastroparesisEpidemiology

• 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

Page 13: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Diabetic GastroparesisPathophysiology

• 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

Page 14: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Diabetic GastroparesisMotor 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

Page 15: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

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)

Page 16: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA
Page 17: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

AGA/ANMS review: Neuro-Gastroenterol Mot 2010

Diagnosis

Page 18: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Kloetzer L, Neuro-Gastroenterol Mot 2010, in press

Wireless motility capsuleSmart Pill

Page 19: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

Treatment: correction of glycemia…….

Page 20: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

J Clin Endocrinol Metab 2006

New treatments

Mitemcinal

Ghrelin

Prucalopride (5HT4 agonist)

Acotiamide (M1, M2 antagonist)

Iberogastr

Enterra gastric electric

stimulation

Page 21: Joint Meeting GISMAD-FISMAD DISTURBI DELLA MOTILITA’ G I NELLE PATOLOGIE SISTEMICHE DIABETE STRUTTURA COMPLESSA GASTROENTEROLOGIA, Cagliari STRUTTURA COMPLESSA

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