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Diagnosing & Managing
Diabetic Gastroparesis
    Patricia L. Raymond MD FACP FACG

    • Assistant Professor of Clinical Internal
      Medicine, Eastern Virginia Medical
      School
    • Gastroenterology Consultants, a
      division of Gastrointestinal & Liver
      Specialists of Tidewater pllc
Recognize the evil that is
stalking your patients?
GI tract among many organ systems affected
by diabetic autonomic neuropathy
          • Cardiovascular
          • Genitourinary
          • Neuroendocrine

          • Gastrointestinal tract
             • Upper
             • Lower
How frequent are gastrointestinal
symptoms in diabetics?
• 1101 subjects from outpatient
  clinics and the community
• GI symptoms associated with
  autonomic or peripheral
  neuropathy (OR 1.62-2.39)
• Constipation 29%
• GERD 19%
• Dyspepsia 14%
• Abdominal pain 11%
• Fecal incontinence 9%
          Bytzer, P. Am J Gastroenterol 2002; 97:604.
ACG 2011 Abstract #468:
Economic Burden of Diabetic
Gastroparesis
• 3498 hospitalizations in 2006
• $2293 per hospitalization
• $76 million annually
Esophageal involvement
• GERD from autonomic neuropathy
  with decreased LES pressure,
  impaired peristaltic clearance of
  esophagus, delayed gastric
  emptying
• Normals with hypergycemia (15
  mm/l, 8 mm/l) with impaired transit
  and elevated TLESRs compared
  with euglycemia


           Rayner, CK. Diabetes Care 2001; 24:371.
Definition: Diabetic Gastroparesis
• Synonyms: Gastric stasis, delayed
  gastric emptying
• Symptoms: Nausea, vomiting, early
  satiety, bloating, weight loss,
  difficult glycemic control

• Gastroparesis types: Diabetic, post
  viral, electrolyte imbalance,
  hypothyroid,idiopathic
Diabetic Gastroparesis
• True prevalence unclear
• 20-40% of diabetics, especially long
  standing type I
• Magnitude of delay does not
  correlate with symptoms
  • Lack symptoms from neuropathy
    afferent sensory nerve fibers
  • Hyper-reactive symptoms
• Results in poor glycemic control
Blood glucose affects gastric
contractions
• Normal, non
  diabetic
  subjects
• Gastric
  contractions
  nearly absent at
  250 mg/dl
• Markedly
  reduced at 140
  and 175 mg/dl
        Barnett, JL. Gastroenterology 1988; 94:739.
Fast = Goes fast!
• Hypoglycemia
  leads to
  accelerated
  gastric
  emptying even
  in patients with
  delay in gastric
  emptying



      Russo, A. J Clin Endocrinol Metab 2005; 90:4489.
Just too sensitive?
• Increased sensitivity with elevated
  blood glucose within physiologic
  range
• Esophagus
  • Threshold for perception of balloon
    distension lowered
• Stomach
  • Nausea, fullness, epigastric pain


      Rayner, CK. Diabetes Care 2001; 24:371.
      Parkman, HP. Gastroenterology 2004; 127:1592.
Diagnosis of Gastroparesis
• EGD
• Scintigraphy
  • Solid
  • Liquid
  • Both
• Rare testing
  • EGG (Electrogastrogram), MRI,
    US, Isotope breath testing
  • (only done at some motility centers)
Diagnosis
Esophago-
Gastro-
Duodenoscopy
(EGD)

Exclude
obstruction at the
pylorus
Taking a peek!
Not Gastroparesis:
Pyloric Obstruction
• Pyloric stenosis   • Pyloric channel
  or stricture         ulcer
Pyloric Cancer
Suggestive of Gastroparesis
• Bezoar           • Limited
  • Trichobezoar     peristalsis
  • Pytobezoar     • Gastric pool
                     (saliva and
                     gastric juices)
Diagnosis
Scintigraphy GES

Measure actual
emptying time
• Oatmeal
• Egg Salad
• Beef Stew
  • Technetium-99
Scintillating Syntigraphy
Every hospital
has own
technique and
normal values

Cannot compare
between hospitals

Some do liquid
phase emptying
also
Treatment of Gastroparesis
Watch out!
• Poor correlation between
  magnitude of delay and symptoms

• No data to support improving
  assymptomatic gastroparesis
  • improves long term diabetes control
    or prevents diabetes complications


• Treat for symptom relief

     Stacher, G. J Clin Endocrinol Metab 1999; 84:2357.
Treatment of Gastroparesis
• Dietary maneuvers
    • Low residue
       • aka the Twinkie ® diet
•   Take a hike
•   Medications
•   Endoscopic treatment/Botox
•   Gastric pacemaker
•   Feeding tube
Low residue diet
                   You should avoid:
                   • Whole-grain
                     breads, cereals
                     and pasta
                   • Whole vegetables
                     and vegetable
                     sauces
                   • Whole fruits,
                     including canned
                     fruits
                   • Seeds and nuts
Take a hike
• Postprandial walking
• 50 patients with DM
• Emptying rates of 28
  patients (56%) were
  within normal range of
  controls
• 4 patients with
  accelerated emptying
  (8%).
• 18 patients with delayed
  emptying (36%)
Lipp, R. W. American Journal
of Gastroenterology 2000; 95(2), 419–424.
Postprandial walking
• Two variants of delayed gastric emptying
  (18 of 50 patients):

• Counteracted by postprandial walking in 7
  patients (39% of GP)

• Not influenced
  by postprandial
  walking in 11
  patients (61% of GP)
Medications
•   Erythromycin
•   Reglan/promethazine
•   Cisapride
•   Domperidone

• Antiemetics
Erythromycin
• Erythromycin
  • 3mg/kg IV over 45 min to ‘kick-start’
    stomach
     • High amplitude gastric propulsive
       contractions which dump solid residue out
       of stomach
  • Evidence for po Erythro weak
     • 35 trials, only 5 ‘fulfilled inclusion criteria’,
       all small #,all short (< 4 weeks)
     • Improvement in 26 of 60 patients (43%)


   Prather, CM. Am J Physiol 1993; 264:G928.
   Keshavarzian, A. Am J Gastroenterol 1993; 88:193.
   Maganti, K. Am J Gastroenterol 2003; 98:259.
Erythromycin potential side
effects
•   GI toxicity
•   Ototoxicity
•   Pseudomembranous colitis
•   Resistant bacterial strains
•   Sudden death due to
    prolonged QT interval
ACG 2011 Abstract # 875:
Azithromycin verses Erythromycin
• 13 patients,      • AZI may be
  crossover trial     better due to
• 100 mg AZI          • longer half life
• Breath-testing      • better SE
                        profile
  prior to
                      • lack P450
  crossover
                        interaction
• Findings:
  Bioequivalent
1-800-SoSueMe: Reglan
• PO or SQ
  • Tardive dyskinesia
  • Irritability, anxiety,
   depression, hyperprolactinemia



  • 2010 meta analysis UK &
    Sweden tardive dyskinesia
    <1%, may be reversible if
    caught early

      Rao, AS. Aliment Pharmacol Ther 2010; 31:11.
Reglan/Metaclopramide po:
Start low, give holidays
• 5mg 15 minutes    • Notify MD for
  AC and HS           any involuntary
• Titrate upward      movement
  (to 40 mg/day)    • Early
• Consider liquid     recognition and
  version, SQ         drug
• Drug holidays       discontinuation
  or occasional       may lead to
  dose reductions     resolution
Cisapride and Zelnorm:
Can’t Get No Satisfaction
• Cisapride: QT interval
  issues with cardiac
  arrhythmias and death
  • 5HT3 receptor agonist
  • Increased solid and liquid
    emptying in various gastric
    stasis conditions
  • More potent and better
    tolerated than reglan
• Zelnorm: Yanked by FDA
Oh Canada! Domperidone
• Not FDA approved for
  use in the US
  • Can be obtained through
    IND application
• May be compounded by
  local pharmacists or
  purchased overseas by
  internet
  • Efficacy similar to
    metaclopramide
  • Cardiac arrhythmias in
    animal studies
ACG 2011 Abstract #878:
Domperidone at Walter Reed
• 13 patients
• 54% improved on
  domperidone
• Dosage 20 to 80
  mg daily (median
  40 mg daily)
• No QT changes,
  no SE, no lab
  abnormalities
Antiemetics
• Antihistamine
  • Diphenhydramine (Benadryl)
     • Oral or rectal
• Phenothiazines
  • Compazine
     • IV or rectal
• HT3 Antagonists
  • Ondansetron (Zofan), granisitron
    (Kytril) no advantage over
    conventional agents
Endoscopy with botox
                • Pilot studies
                  injecting botox
                  into pylorus
                  helped gastric
                  emptying
Rethinking botox
• Controlled trial 32 patients
   • No difference in emptying or symptoms
     compared with placebo at 1 month
• Crossover trial 23 patients
   • No improvement symptoms or rate of
     gastric emptying


• “Larger, controlled trials are needed”


    Friedenberg, FK. Am J Gastroenterol 2008; 103:416.
    Arts, J. Aliment Pharmacol Ther 2007; 26:1251.
Abstract #467 ACG 2011:
Botox or Pyloric Balloon with
Normal 3 cpm EGG
• 18 patients with     • 15 improved after
  normal EGG slow        2 interventions, 3
  GES, normal EGD        no response
• 4 quadrant botox     • Symptom free for
  100 mcg or 20 mm       4 months average
  balloon x 2          • Retreatment at
  minutes                relapse
• If no symptom
  improvement,
  other intervention
  done
Gastric Pacemaker
The lure of gastric pacemakers
• Photo gastric          • Better
  pacemaker                symptoms, but
                           no improvement
                           in emptying
                         • Limited efficacy,
                           humanitarian
                           use device



        Abell, T. Gastroenterology 2003; 125:421.
        McCallum, R. Gastroenterology 2009; AB376.
ACG 2011 Abstract #877:
Mucosal Nerve Fiber Density
• 5 GP patients (1      • MNF density
  DM, 2 idiopathic, 2     reduced in
  post-op), 3 age         GP.0018 vs .0024
  matched controls        (p=.02)
• GP patients had       • MNF density
  full thickness          correlates with
  biopsies at pacer       symptom severity
  implant               • MNF density
                          correlates with
                          duration of
                          disease
Sometimes nothing works
Last ditch- the jejenostomy tube
or decompressive PEG
                  • Rarely needed
What evils are following your
patients?
Gastroparesis
• Symptoms don’t correlate with
  degree of emptying impairment
• EGD and scintigraphy to diagnose
• Lifestyle changes as mainstay of
  treatment
• Reglan not as evil as previously
  supposed, newer management
  continues to be a ‘wash out’
Diabetic gastroparesisv2011
Diabetic gastroparesisv2011

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Diabetic gastroparesisv2011

  • 1. Diagnosing & Managing Diabetic Gastroparesis Patricia L. Raymond MD FACP FACG • Assistant Professor of Clinical Internal Medicine, Eastern Virginia Medical School • Gastroenterology Consultants, a division of Gastrointestinal & Liver Specialists of Tidewater pllc
  • 2. Recognize the evil that is stalking your patients?
  • 3. GI tract among many organ systems affected by diabetic autonomic neuropathy • Cardiovascular • Genitourinary • Neuroendocrine • Gastrointestinal tract • Upper • Lower
  • 4. How frequent are gastrointestinal symptoms in diabetics? • 1101 subjects from outpatient clinics and the community • GI symptoms associated with autonomic or peripheral neuropathy (OR 1.62-2.39) • Constipation 29% • GERD 19% • Dyspepsia 14% • Abdominal pain 11% • Fecal incontinence 9% Bytzer, P. Am J Gastroenterol 2002; 97:604.
  • 5. ACG 2011 Abstract #468: Economic Burden of Diabetic Gastroparesis • 3498 hospitalizations in 2006 • $2293 per hospitalization • $76 million annually
  • 6. Esophageal involvement • GERD from autonomic neuropathy with decreased LES pressure, impaired peristaltic clearance of esophagus, delayed gastric emptying • Normals with hypergycemia (15 mm/l, 8 mm/l) with impaired transit and elevated TLESRs compared with euglycemia Rayner, CK. Diabetes Care 2001; 24:371.
  • 7. Definition: Diabetic Gastroparesis • Synonyms: Gastric stasis, delayed gastric emptying • Symptoms: Nausea, vomiting, early satiety, bloating, weight loss, difficult glycemic control • Gastroparesis types: Diabetic, post viral, electrolyte imbalance, hypothyroid,idiopathic
  • 8. Diabetic Gastroparesis • True prevalence unclear • 20-40% of diabetics, especially long standing type I • Magnitude of delay does not correlate with symptoms • Lack symptoms from neuropathy afferent sensory nerve fibers • Hyper-reactive symptoms • Results in poor glycemic control
  • 9.
  • 10.
  • 11. Blood glucose affects gastric contractions • Normal, non diabetic subjects • Gastric contractions nearly absent at 250 mg/dl • Markedly reduced at 140 and 175 mg/dl Barnett, JL. Gastroenterology 1988; 94:739.
  • 12. Fast = Goes fast! • Hypoglycemia leads to accelerated gastric emptying even in patients with delay in gastric emptying Russo, A. J Clin Endocrinol Metab 2005; 90:4489.
  • 13.
  • 14. Just too sensitive? • Increased sensitivity with elevated blood glucose within physiologic range • Esophagus • Threshold for perception of balloon distension lowered • Stomach • Nausea, fullness, epigastric pain Rayner, CK. Diabetes Care 2001; 24:371. Parkman, HP. Gastroenterology 2004; 127:1592.
  • 15.
  • 16. Diagnosis of Gastroparesis • EGD • Scintigraphy • Solid • Liquid • Both • Rare testing • EGG (Electrogastrogram), MRI, US, Isotope breath testing • (only done at some motility centers)
  • 19. Not Gastroparesis: Pyloric Obstruction • Pyloric stenosis • Pyloric channel or stricture ulcer
  • 21. Suggestive of Gastroparesis • Bezoar • Limited • Trichobezoar peristalsis • Pytobezoar • Gastric pool (saliva and gastric juices)
  • 22. Diagnosis Scintigraphy GES Measure actual emptying time • Oatmeal • Egg Salad • Beef Stew • Technetium-99
  • 23. Scintillating Syntigraphy Every hospital has own technique and normal values Cannot compare between hospitals Some do liquid phase emptying also
  • 25. Watch out! • Poor correlation between magnitude of delay and symptoms • No data to support improving assymptomatic gastroparesis • improves long term diabetes control or prevents diabetes complications • Treat for symptom relief Stacher, G. J Clin Endocrinol Metab 1999; 84:2357.
  • 26. Treatment of Gastroparesis • Dietary maneuvers • Low residue • aka the Twinkie ® diet • Take a hike • Medications • Endoscopic treatment/Botox • Gastric pacemaker • Feeding tube
  • 27.
  • 28. Low residue diet You should avoid: • Whole-grain breads, cereals and pasta • Whole vegetables and vegetable sauces • Whole fruits, including canned fruits • Seeds and nuts
  • 29.
  • 30. Take a hike • Postprandial walking • 50 patients with DM • Emptying rates of 28 patients (56%) were within normal range of controls • 4 patients with accelerated emptying (8%). • 18 patients with delayed emptying (36%) Lipp, R. W. American Journal of Gastroenterology 2000; 95(2), 419–424.
  • 31. Postprandial walking • Two variants of delayed gastric emptying (18 of 50 patients): • Counteracted by postprandial walking in 7 patients (39% of GP) • Not influenced by postprandial walking in 11 patients (61% of GP)
  • 32.
  • 33. Medications • Erythromycin • Reglan/promethazine • Cisapride • Domperidone • Antiemetics
  • 34. Erythromycin • Erythromycin • 3mg/kg IV over 45 min to ‘kick-start’ stomach • High amplitude gastric propulsive contractions which dump solid residue out of stomach • Evidence for po Erythro weak • 35 trials, only 5 ‘fulfilled inclusion criteria’, all small #,all short (< 4 weeks) • Improvement in 26 of 60 patients (43%) Prather, CM. Am J Physiol 1993; 264:G928. Keshavarzian, A. Am J Gastroenterol 1993; 88:193. Maganti, K. Am J Gastroenterol 2003; 98:259.
  • 35. Erythromycin potential side effects • GI toxicity • Ototoxicity • Pseudomembranous colitis • Resistant bacterial strains • Sudden death due to prolonged QT interval
  • 36. ACG 2011 Abstract # 875: Azithromycin verses Erythromycin • 13 patients, • AZI may be crossover trial better due to • 100 mg AZI • longer half life • Breath-testing • better SE profile prior to • lack P450 crossover interaction • Findings: Bioequivalent
  • 37. 1-800-SoSueMe: Reglan • PO or SQ • Tardive dyskinesia • Irritability, anxiety, depression, hyperprolactinemia • 2010 meta analysis UK & Sweden tardive dyskinesia <1%, may be reversible if caught early Rao, AS. Aliment Pharmacol Ther 2010; 31:11.
  • 38. Reglan/Metaclopramide po: Start low, give holidays • 5mg 15 minutes • Notify MD for AC and HS any involuntary • Titrate upward movement (to 40 mg/day) • Early • Consider liquid recognition and version, SQ drug • Drug holidays discontinuation or occasional may lead to dose reductions resolution
  • 39. Cisapride and Zelnorm: Can’t Get No Satisfaction • Cisapride: QT interval issues with cardiac arrhythmias and death • 5HT3 receptor agonist • Increased solid and liquid emptying in various gastric stasis conditions • More potent and better tolerated than reglan • Zelnorm: Yanked by FDA
  • 40. Oh Canada! Domperidone • Not FDA approved for use in the US • Can be obtained through IND application • May be compounded by local pharmacists or purchased overseas by internet • Efficacy similar to metaclopramide • Cardiac arrhythmias in animal studies
  • 41. ACG 2011 Abstract #878: Domperidone at Walter Reed • 13 patients • 54% improved on domperidone • Dosage 20 to 80 mg daily (median 40 mg daily) • No QT changes, no SE, no lab abnormalities
  • 42.
  • 43. Antiemetics • Antihistamine • Diphenhydramine (Benadryl) • Oral or rectal • Phenothiazines • Compazine • IV or rectal • HT3 Antagonists • Ondansetron (Zofan), granisitron (Kytril) no advantage over conventional agents
  • 44. Endoscopy with botox • Pilot studies injecting botox into pylorus helped gastric emptying
  • 45. Rethinking botox • Controlled trial 32 patients • No difference in emptying or symptoms compared with placebo at 1 month • Crossover trial 23 patients • No improvement symptoms or rate of gastric emptying • “Larger, controlled trials are needed” Friedenberg, FK. Am J Gastroenterol 2008; 103:416. Arts, J. Aliment Pharmacol Ther 2007; 26:1251.
  • 46. Abstract #467 ACG 2011: Botox or Pyloric Balloon with Normal 3 cpm EGG • 18 patients with • 15 improved after normal EGG slow 2 interventions, 3 GES, normal EGD no response • 4 quadrant botox • Symptom free for 100 mcg or 20 mm 4 months average balloon x 2 • Retreatment at minutes relapse • If no symptom improvement, other intervention done
  • 47.
  • 49. The lure of gastric pacemakers • Photo gastric • Better pacemaker symptoms, but no improvement in emptying • Limited efficacy, humanitarian use device Abell, T. Gastroenterology 2003; 125:421. McCallum, R. Gastroenterology 2009; AB376.
  • 50. ACG 2011 Abstract #877: Mucosal Nerve Fiber Density • 5 GP patients (1 • MNF density DM, 2 idiopathic, 2 reduced in post-op), 3 age GP.0018 vs .0024 matched controls (p=.02) • GP patients had • MNF density full thickness correlates with biopsies at pacer symptom severity implant • MNF density correlates with duration of disease
  • 52. Last ditch- the jejenostomy tube or decompressive PEG • Rarely needed
  • 53.
  • 54. What evils are following your patients?
  • 55. Gastroparesis • Symptoms don’t correlate with degree of emptying impairment • EGD and scintigraphy to diagnose • Lifestyle changes as mainstay of treatment • Reglan not as evil as previously supposed, newer management continues to be a ‘wash out’