GASTROPARESIS

DIABETICORUM
4 JULY - 2019
BY : DR ABDELRAHMAN A MOUKHTAR
PROFESSOR OF INTERNAL MEDICINE MANSOURA UNIVERSITY
 GASTROPARESIS
Gastro = stomach
paresis = weakness/paralysis

Gastroparesis: A neuromuscular (motility) disorder of the

stomach characterized by delayed gastric emptying
without evidence of mechanical obstruction

Term used in 1958 by Kassander

”as “gastroparesis diabeticorum
.Kassander P. .Ann Intern Med 1958;48:797-812
DISTRIBUTION OF DIFFERENT ETIOLOGIES
FOR GASTROPARESIS IN PUBLISHED CASE
.SERIES

2012 Klaus Bielefeldt.

 GASTROPARESIS DIABETICORUM

Term used in 1958 by Kassander

.Kassander P. .Ann Intern Med 1958;48:797-812

 Definition
Gastroparesis Diabeticorum
is defined by the presence of dyspeptic symptoms and the documented delay in gastric emptying of ingested
nutrients in the absence of gastric outlet obstruction.

A third factor, (3 months or more ) duration of symptoms, is generally added, as many acute
illnesses or abdominal operations transiently impair stomach function, but typically resolve within a
relatively short-time.
Symptoms of gastroparesis usually include early satiety, nausea, vomiting, bloating, and upper abdominal
pain.
Diabetic gastroparesis can result in nutritional compromise, impaired glucose control and a poorer quality
of life, independent of other factors such as age, tobacco and alcohol use, or type of diabete
 EVEN IN THE ABSENCE OF SUBJECTIVE SYMPTOMS,
DELAYED GASTRIC EMPTYING MAY LEAD TO
.NUTRITIONAL AND METABOLIC CONSEQUENCES

If occurring in isolation (i.e., without other symptoms), these scenarios

do not meet the accepted definition criteria.

However, the detrimental nutritional and metabolic consequences may

be sufficient to consider the diagnosis of gastroparesis.
 THE DATA SUGGEST THAT INTENTIONAL AND REVERSIBLE
DELAY IN GASTRIC EMPTYING COULD PROVIDE AN
ALTERNATIVE MANAGEMENT OPTION IN OBESE PATIENTS

Postprandial discomfort or fullness and early satiation are the main mechanism of restrictive bariatric surgeries !!!.
• With the obesity epidemic in most developed countries, could a reversible induction of gastroparesis be beneficial???

• Exenatide and other GLP1 receptor agonists indeed trigger a delay in gastric emptying, which may be beneficial for
type II diabetics due to the blunted postprandial hyperglycemia .
• The associated anorexia contributes to weight loss, another beneficial effect in persons with metabolic syndrome.
Patho-physiology
Mechanical &
POSTPRANDIAL WORK OF THE NORMAL STOMACH
enzymatic
breakdown of
larger
particles into
smaller
particles (< 2
mm), known
as chyme.

Delivery of
chyme to the
duodenum at
a rate not to
exceed the
digestive and
absorptive
capacity of the
small
intestine.

Trituration & Emptying

 On a functional basis, The proximal stomach comprises the cardia, fundus, and

The stomach may be body—and is characterized by a thin layer of muscle that

produces relatively weak contractions. Upon the ingestion of
food, the proximal stomach exhibits receptive relaxation,
subdivided into two regions: with very little increase in intragastric pressure. This portion
of the stomach is responsible for storage.

The distal stomach consists of the antrum and pylorus

—and is characterized by a thick and powerful muscular
wall. This is the part of the stomach that controls
mechanical and enzymatic digestion. The pattern of
contraction in the distal stomach also regulates the rate
at which partially digested food is emptied into the
duodenum.
Normal gastric motility /
emptying requires an integrated ,
coordinated interplay between :

Extrinsic nervous system

( sympathetic & parasympathetic
), enteric nervous system,
interstitial cells of Cajal (ICCs),
smooth muscles and immune
cells.

Disturbance at any level has the

potential to alter the gastric
function.
ULTRASTRUCTURAL DIFFERENCES BETWEEN DIABETIC
AND IDIOPATHIC GASTROPARESIS
FAUSSAONE-PELLEGRINI ET AL GPCRC J CELL MOL MED;2011: 16;1573-1581
+GROVER ET AL NEUROGASTROENTEOL MOTIL 2012;24:531-E249
THE MIXING AND EMPTYING WORK OF THE STOMACH IS PACED.
SLOW WAVES + PLATEAU/ACTION POTENTIALS PROPAGATE FROM THE PACEMAKER REGION
THROUGH THE BODY-ANTRUM: GASTRIC PERISTALSIS
KLKOCH, SLEISINGER & FORDTRAN, 2015
RECORDING GASTRIC MYOELECTRICAL ACTIVITY
WITH SURFACE ELECTRODES:
ELECTROGASTROGRAMS (EGGS)

The use of EGG in patients with upper

gastrointestinal symptoms and those with
symptoms suggestive of gastroparesis is
limited to highly specialized centers.
Hence, there is currently no consensus on
the role of EGG in the work-up of such
patients.

In addition:
Gastric dysrhythmias may or may not be
associated with gastroparesis.
Tachygastria (6 cpm) and Bradygastria(1-2 cpm)
in a patient with Type 2 Diabetes Mellitus

60 sec.

500 µV

Water Load
60 sec.
500 µV
GASTRIC NEUROMUSCULAR
DISORDERS
. MODIFIED FROM KOCH KL. SLEISENGER AND FORDTRAN, 2015
Glucose-Gut–Incretins-Islet Cross-Talk impact on gastric Motility

THE LAST BUT NOT THE LEAST

To Summarize
PATHOPHYSIOLOGIC MECHANISMS OF DIABETIC
GASTROPARESIS Diabetes Ther (2018) 9 (Suppl 1):S1–S42
https://doi.org/10.1007/s13300-018-0454-9
GASTROENTEROLOGY, 141(4), OWYANG C, PHENOTYPIC SWITCHING IN DIABETIC GASTROPARESIS:
,MECHANISM DIRECTS THERAPY, 1134–1137, 2011
RETAINED, UNDIGESTED FOOD IN GASTROPARESIS
DIAGNOSIS
THE DIAGNOSIS OF GASTROPARESIS IS
:BASED ON THE COMBINATION OF
Symptoms of gastroparesis.

Absence of gastric outlet obstruction or ulceration

A delay in gastric emptying.

• Nausea
• Early Satiety
• Prolonged fullness (bloating)
• Vomiting undigested food
• Discomfort/pain in the epigastrium

Symptoms are non-specific , should consider D,.D

EXAM. SUCCUSSION SPLASH

1. Obstructive gastroparesis (pyloric spasm-dysfunction,
pyloric stenosis) (10-15%).

2. Ischemic gastroparesis (<1%).

3. Postsurgical gastroparesis (15%)

(antrectomy, vagotomy, fundectomy, fundoplication)
The conventional test for measurement of gastric emptying is scintigraphy

Gastric emptying scintigraphy of a solid-phase meal is considered as the standard for

diagnosis of gastroparesis, as it quantifies the emptying of a physiologic caloric meal.
The most reliable parameter to report gastric emptying is the gastric retention at 4 h.

Alternative approaches for assessment of gastric emptying include wireless

capsule motility testing and 13C breath testing using octanoate or spirulina
incorporated into a solid meal; they require further validation before they can be
considered as alternates to scintigraphy for the diagnosis of gastroparesis.

Am J Gastroenterol. 2013 January ; 108(1): 18–38. doi:10.1038/ajg.2012.373.

Gastric emptying scintigraphy of a solid-phase meal
MANAGEMENT
: TREATMENT APPROACHES INCLUDE
Dietary therapy

Accelerating Emptying

Targeting Accommodation
THE MOST IMPORTANT IS
Targeting Pyloric Function.

Targeting Symptoms.
DIET
Surgery and Gastroparesis.

Gastric Electrical Stimulation .

 NUTRITIONAL GOALS IN
:GASTROPARESIS
Easy to mix/mill/empty.

Ingest foods that are: Result in good nutrition.

modified from Koch KL. Sleisinger and Fordtran, 2015

Summary of nutritional interventions for diabetic gastroparesis Republished and modified .
Diabetes Ther (2018) 9 (Suppl 1):S1–S42
Summary of nutritional interventions for diabetic gastroparesis Republished and modified .
Diabetes Ther (2018) 9 (Suppl 1):S1–S42
ENTERAL FEEDING IN GP
INDICATIONS:
1. 5%-10% UNINTENTIONAL WEIGHT LOSS
2. INABILITY TO MEET DAILY CALORIC GOAL
3. FREQUENT NEED FOR GASTRIC DECOMPRESSION
4. FREQUENT HOSPITALIZATIONS FOR DEHYDRATION
IS IT TIME TO BYPASS THE PARALYZED STOMACH?
 ENTERAL FEEDINGS IN GP
GOALS
1. REGAIN WEIGHT-NUTRITION ITSELF CAN IMPROVE GI NEUROMUSCULAR
FUNCTION; STRIATED MUSCLE STRENGTH, ENERGY, ATTITUDE
2. STRESS AND WORK OF TRYING TO EAT IS GREATLY REDUCED; PATIENTS SNACK
AS DESIRED
3. REMOVE TUBES 3-6 MONTHS AFTER NUTRITION GOALS ACHIEVED - RELAPSE
RATES UNKNOWN.
4. AVOID TPN-LINE SEPSIS FREQUENT
INTUBATIONS FOR DECOMPRESSION AND FEEDING IN PATIENTS
WITH GASTROPARESIS
: OTHER TREATMENT APPROACHES INCLUDE

Accelerating Emptying

Targeting Accommodation
THE MOST IMPORTANT IS
Targeting Pyloric Function.

Targeting Symptoms.
DIET
Surgery and Gastroparesis.

Gastric Electrical Stimulation .

NOVEL POTENTIAL AGENTS

• There is considerable ongoing research aimed at identifying novel therapies for gastroparesis.
• Putative agents include:
• Sildenafil (potentiates nitric oxide) improves pyloric relaxation. Definitive improvement on gastroparesis has not been documented.
• Levosulpiride (Dopamine receptor D2-antagonist) is expected to reverse dopaminergic inhibition on gastric contraction. A randomized
trial has demonstrated effectiveness comparable to cisapride.
• Loxiglumide (CCK-A antagonist) was found to increase antral motility. It remains under investigation.
• Clonidine (a 2-receptor agonist), a commonly used anti-hypertensive, decreases antro-duodenal contractions. Although in studies
clonidine did not alter gastric emptying in healthy adults, it did improve emptying in diabetics. The exact mechanism remains unclear.
Further studies are needed.
• Tegaserod (5-HT4 partial agonist) increased gastric emptying in tested diabetic mice, but not in healthy volunteers. More studies are in
progress.
• Clarithromycin (a newer macrolide) has shown promise in improving gastric emptying. Further studies are awaited.
• Motilin agonists. Motilin agonists have been explored as a treatment for gastroparesis, but no current Relamorelin. The novel
pentapeptideselective
• Ghrelin agonist relamorelin (RM-131) has similar characteristics to native ghrelin, but with a 100-fold greater potency to reverse gastric
ileus in animal models and a longer plasma half-life. RM-131 (100 lg/day, subcutaneous) accelerated gastric emptying in patients with
type 1 or 2 diabetes who had upper gastrointestinal symptoms.compounds are available for investigational use .
 TAKE HOME MESSAGES
1. CONSIDER POSTPRANDIAL STOMACH PHYSIOLOGY: FUNDIC
RELAXATION, TRITURATION, GASTRIC EMPTYING.

2. GASTRIC NEUROPATHY/CAJALOPATHY AND PYLORIC

DYSFUNCTION RESULTS IN GASTROPARESIS IN DIABETICS.

3. USING GASTRIC EMPTYING PHYSIOLOGY FOR DIET THERAPY:

NUTRITIOUS FOOD CHOICES BASED ON EASE OF
MIXING/EMPTYING-THE GASTROPARESIS DIET
 TAKE HOME MESSAGES

SMALL NUMBERS OF PATIENTS NEED ENTERAL FEEDING, BUT .4

.MANY CAVEATS

DRUGS AND DEVICES IN DEVELOPMENT.5

THANK YOU