1. Diabetic Gastroparesis
내분비 대사 내과
R3 송 란

2. Introduction
Pathophysiology
Pathogenesis
Clinical Features
Differential Diagnosis
Diagnostic Test
Treatment
Summary

3. Introduction Delay of gastric emptying without any gastric outlet
obstruction.
Longstanding, poorly controlled DM, autonomic failure
First describtion : Rundles, 1945
part of a generalized autonomic neuropathy
Gastroparesis diabeticorum : Kassander,1954
prospective study of asymtomatic diabetic patients
where 22% had radiologic evidence of gastric retention
- Rundles,Medicine,1945 :24
- Kassander P, Ann Intern Med, 1954 :48

4. Pathophysiology - Interdigestive motor activiey –
Alterd gastric electrical activity
tachygastria
Decreased fundic motor activity
 Delayed emptying of solids from
the proximal
 Late filling of the antrum
Reduced antral motor activity
Impaired antroduodenal coordination
Dysfunction of interdigestive motor
activity phase three (the MMC)
 overnight retention of large
indigestible food
Pyloric motility: prolonged intense
contraction
- Nilsson PH. J Diab Comp,1996:10
- Atlas of Clinical Endocrinology
- Interdigestive motor activiey –
: Third phase – Migrating Motor
Complex (MMC)
- Gastric Neuromuscular Function -

5. and duodenum from a patient with diabetic gastroparesis >
< Simultaneous recording of motor activity from the antrum, pylorus,
and duodenum from a patient with diabetic gastroparesis >
“pylorospasm”
- Mearin F et al.Gastroenterology, 1986: 90

6. Pathogenesis 1 Autonomic neuropathy
Gastric vagal denervation
Altered secretion of various hormones
Motilin : Cholinegic dificiency  lack of motilin action
on gastric smooth muscle
Pancreatic polypeptide, Somatostatin : decreased
Gastrin : vagal denervation  increased
Cholecystokinin : increased  inhibition gastric motility
Glucagon : increased  inhibition gastric motility
( opposed to insulin )

7. Pathogenesis 2 Diabetic microangiopathy Hyperglycemia
Acute hyperglycemia in normal subjec  slows gastric emptying
Blood glucose > 400 mg/dL
Tachygastria
Inhibition of the interdigestive myoelectric complex

8. Clinical Features 1 Symptoms Exacerbation of gastroparesis Nausea
Intercurrent acute disease
Hyperglycemia
Medication causing delay of
gastric emptying
Nausea
Vomiting
Epigastric burning
Easy satiety
Belching
Regurgitation
Postprandial fullness
Brittle diabetes
Malnutrition
Weight loss
Opiates
Tranquilizers
Anticholinergic agents
Antidipressants
Apomorphine
Levodopa
β-adrenergic agonists
vincristine
Ganglion-blocking agents

9. Clinical Features 2 Generalized autonomic neuropathy
Postural hypotension, abnormal heart-rate response, bladder
dysfunction, impotence
< Prevalence of different intestinal symptoms in diabetic patients without of with peripheral (PNP) and autonomic neuropathy (ANP) >
Paul E.et al.Diabetes, 1997:46

10. Clinical Features 3
S:symptom
- Nowak TV et al. Gut, 1995: 37
Symptoms correlated poorly with actual delay in gastric emptying
Symptoms in normal gastric transit Iber FL et al. Dig Dis,1993:38
Patients with delayed gastric emptying are without dyspeptic
symptoms Nowak TV et al. Gut,1995:37

11. Differential Diagnosis
Acute gastroparesis
Administration of various drug
Metabolic disorder
Uremia, hypercalcemia, hypokalemia
Cold, pain, labyrinthine stimulation through CNS
Endogenous opiates, catecholamine
Chronic gastroparesis
Myogenic and nervous disease
Myotonia dystrofica, familial dysautonomia, multiple sclerosis,
spinal cord injury

12. Diagnosis 1 History and physical examination Laboratory testing
Character of the abdominal pain
localized to the upper abdomen , burning, vague, crampy
Underlying disease
Abdominal examination : not guarding or rigidity
Other signs of autonomic dysfunction
Laboratory testing
hemoglobin, fasting plasma glucose, serum total
protein, albumin, TSH concentrations, ANA titer,
chest x-ray, plain film of the abdomen
nutritional state, degree of bowel dilatation, screen for lung Ca.

13. Diagnosis 2 Radiologic test Scintigraphic gastric emptying
most cost-effective, simple, widely available technique
Normal < 50% of solid residual gastric activity after min
4 hours : most accurate (sensitivity-100%, specificity-70%)
Stable isotope breath testing
Expiratory 13-CO2 concentration
Indirect test
Sensitivity 60%–80% of scintigraphy
Esophagogastroduodenoscopy (EGD)
Evaluation for structural pathologies
Patients remains symptomatic despite treatment

14. Diagnosis 3 Barium swallow with upper gastrointestinal series
structural abnormalities (esp.mechanical obstruction)
poor correlation between barium transit and scintigraphy
Electrogastrography (EGG)
measures gastric myoelectrical activity
gastric dysrhythmias
not measure gastric contractile activity
Antroduodenal manometry
direct recording of gastroduodenal pressure
MRI
Simultaneous measurement of gastric emptying,
gastroduodenal motility, gastric secretion

15. Treatment 1 Supportive measure Optimizing glycemic control
Hydration & Nutrition
Dehydration, electrolyte control
Dietary modification
Low-fat diet (without nondigestible fiber)
frequent & small meals
Severe case: homogenized or liquid meals with vitamin
Optimizing glycemic control
Imprevement of gastric motor function

16. Medication : prokinetics and antiemetics
Treatment 2
Medication : prokinetics and antiemetics
- Lorenzo C. gastroenterology and hepatology ,1997

17. Treatment 3 Cisapride Metoclopramide Domperidone Erythromycin
Stimulate 5HT4 receptor  release of acetylcholine
Gastrointestinal motility & antroduodenal coordination
Metoclopramide
Stimulation cholinergic fiber & antagonizing dopaminergic fiber
Increase gastric emptying
Side effect :extrapyramidal symptom, hyperprolactinemia
Domperidone
Potent peripheral dopamine antagonist
Long term effect : not proven
Erythromycin
Bind to motilin receptor  motilin agonist
Acute exacerbation : IV erythromycine
Side effect : GI toxicity, ototoxicity, PMC, long QT syndrome
Bethacholine (acetylcholine analogue)
Increase gastric motor activity & gastric emptying
Cholinergic side effect  clinical effect :disappointing

18. Treatment 4 Decompression Surgery
Cannot maintain nutritional status or adequate hydration orally
Gastrostomy, jejunostomy
Surgery
Patients with intractable nausea, vomiting or malnutrition
Pyloroplasty, Billroth I gastrectomy, gastrojejunostomy
Side effect: post gastrectomy gastric stasis
Roux-en-Y stasis syndrome
Poor correlation between gastric symptoms and gastric emptying delay, another mechanism of symptom generation, visceral hyperalgesia,
Prokinetic agent : not helpful
Serotoninergic (5-HT-3) antagonists

19. Treatment 5 Botulinum toxin Eight type 1 diabetic subjects
- Brian EL et al.Diabetes care, 2004:27
Botulinum toxin
inhibits the release of acetylcholine
transient paralysis when injected into smooth muscle
Eight type 1 diabetic subjects
(six women and two men; mean age 41 years)
Safe and improvement of symptoms

20. Treatment 6 - GASTROENTEROLOGY 2003;125
Thirty-three patients with chronic
gastroparesis 17 diabetic and 16 idiopathic)
Continuous high-frequency/low-energy
gastric electrical stimulation
Significantly decreased vomiting frequency,
gastrointestinal symptoms and improved
quality of life

21. Summary
- Current treatment
options in
gastroenterology 4: 21