Gastroparesis in diabetes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Synonyms and keywords:

Overview

Historical Perspective

Classification

Based on the rate of gastric emptying, abnormalities of gastric emptying in diabetes may be classified as:

  • Transient slow gastric emptying
  • Transient rapid gastric emptying
  • Persistent slow or delayed gastric emptying (gastroparesis)
  • Persistent rapid gastric emptying

Pathophysiology

Metabolic Changes That Affect Gastric Emptying in Diabetes

Transient Slow Gastric Emptying

  • It occurs as a result of a reduction in the proximal stomach muscle tone, inhibition of antral contractions, and inhibition of the powerful contractions of the interdigestive migrating motor complex.
  • Acute hyperglycemia causes a delay in gastric emptying of digestible food in the digestive period and indigestible food during the fasting period.
  • Delayed gastric emptying decreases postprandial hyperglycemia and acts as a negative feedback loop.
  • Hyperglycemia inhibits ATP-sensitive potassium (KATP) channels leading to activation of glucose-sensitive neurons in the vagal afferents. Activation of the gastric inhibitory vagal motor circuit can influence electrical slow waves and smooth muscle.
  • Acute hyperglycemia can cause dysfunction of myenteric interstitial cells of Cajal, resulting in isolated tachygastria (an increase in the cyclic electrical activity in the stomach, with a frequency of >3.6 cycles per minute [cpm]).[7]
  • Elevated blood glucose levels activates the gastric inhibitory vagal motor circuit, suppressing the stomach contractions and can overcome the hyperglycemia-mediated contraction of the smooth muscle.[8]
  • Transient slow gastric emptying as a result of acute hyperglycemia is considered a counter-regulatory phenomenon and does not need any treatment.
  • The transient effect is due to down-regulation of glucokinase.[9]

Transient Rapid Gastric Emptying


Persistent Rapid Gastric Emptying

Persistent Delayed Gastric Emptying (Gastroparesis)

Causes

Disease name] may be caused by [cause1], [cause2], or [cause3].

OR

Common causes of [disease] include [cause1], [cause2], and [cause3].

OR

The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].

OR

The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click here.

Differentiating ((Page name)) from other Diseases

[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].

OR

[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].

Epidemiology and Demographics



Risk Factors

There are no established risk factors for [disease name].

OR

The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.

Screening

There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].

Natural History, Complications, and Prognosis

If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].

OR

Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].

OR

Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.

Diagnosis

Diagnostic Study of Choice

Gastric scintigraphy or stable-isotope 13C breath test can detect different gastric emptying abnormalities

History and Symptoms

The most common symptoms "cardinal symptoms" of gastroparesis include early satiety, postprandial fullness, nausea, vomiting, and bloating.

Treatment

Medical Therapy

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

OR

The mainstay of treatment for [disease name] is [therapy].

OR   The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

OR

Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

OR

Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

OR

Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

OR

Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Surgery

Surgical intervention is not recommended for the management of [disease name].

OR

Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]

OR

The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].

OR

The feasibility of surgery depends on the stage of [malignancy] at diagnosis.

OR

Surgery is the mainstay of treatment for [disease or malignancy].

Primary Prevention

There are no established measures for the primary prevention of [disease name].

OR

There are no available vaccines against [disease name].

OR

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

OR

[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].

Secondary Prevention

There are no established measures for the secondary prevention of [disease name].

OR

Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].

References

  1. Camilleri M, Chedid V, Ford AC, Haruma K, Horowitz M, Jones KL; et al. (2018). "Gastroparesis". Nat Rev Dis Primers. 4 (1): 41. doi:10.1038/s41572-018-0038-z. PMID 30385743.
  2. Grover M, Farrugia G, Stanghellini V (2019). "Gastroparesis: a turning point in understanding and treatment". Gut. 68 (12): 2238–2250. doi:10.1136/gutjnl-2019-318712. PMC 6874806 Check |pmc= value (help). PMID 31563877.
  3. Varol C, Mildner A, Jung S (2015). "Macrophages: development and tissue specialization". Annu Rev Immunol. 33: 643–75. doi:10.1146/annurev-immunol-032414-112220. PMID 25861979.
  4. Joshi SR, Comer BS, McLendon JM, Gerthoffer WT (2012). "MicroRNA Regulation of Smooth Muscle Phenotype". Mol Cell Pharmacol. 4 (1): 1–16. PMC 4190587. PMID 25309675.
  5. Neshatian L, Gibbons SJ, Farrugia G (2015). "Macrophages in diabetic gastroparesis--the missing link?". Neurogastroenterol Motil. 27 (1): 7–18. doi:10.1111/nmo.12418. PMC 4409126. PMID 25168158.
  6. Cai Y, Yu X, Hu S, Yu J (2009). "A brief review on the mechanisms of miRNA regulation". Genomics Proteomics Bioinformatics. 7 (4): 147–54. doi:10.1016/S1672-0229(08)60044-3. PMC 5054406. PMID 20172487.
  7. Coleski R, Hasler WL (2009). "Coupling and propagation of normal and dysrhythmic gastric slow waves during acute hyperglycaemia in healthy humans". Neurogastroenterol Motil. 21 (5): 492–9, e1–2. doi:10.1111/j.1365-2982.2008.01235.x. PMID 19309443.
  8. Hien TT, Turczyńska KM, Dahan D, Ekman M, Grossi M, Sjögren J; et al. (2016). "Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization". J Biol Chem. 291 (7): 3552–68. doi:10.1074/jbc.M115.654384. PMC 4751395. PMID 26683376.
  9. Halmos KC, Gyarmati P, Xu H, Maimaiti S, Jancsó G, Benedek G; et al. (2015). "Molecular and functional changes in glucokinase expression in the brainstem dorsal vagal complex in a murine model of type 1 diabetes". Neuroscience. 306: 115–22. doi:10.1016/j.neuroscience.2015.08.023. PMC 4575893. PMID 26297899.
  10. Lamy CM, Sanno H, Labouèbe G, Picard A, Magnan C, Chatton JY; et al. (2014). "Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion". Cell Metab. 19 (3): 527–38. doi:10.1016/j.cmet.2014.02.003. PMID 24606905.
  11. Frank JW, Saslow SB, Camilleri M, Thomforde GM, Dinneen S, Rizza RA (1995). "Mechanism of accelerated gastric emptying of liquids and hyperglycemia in patients with type II diabetes mellitus". Gastroenterology. 109 (3): 755–65. doi:10.1016/0016-5085(95)90382-8. PMID 7657103.
  12. Singh J, Kumar S, Rattan S (2015). "Bimodal effect of oxidative stress in internal anal sphincter smooth muscle". Am J Physiol Gastrointest Liver Physiol. 309 (5): G292–300. doi:10.1152/ajpgi.00125.2015. PMC 4556951. PMID 26138467.
  13. Hayashi Y, Toyomasu Y, Saravanaperumal SA, Bardsley MR, Smestad JA, Lorincz A; et al. (2017). "Hyperglycemia Increases Interstitial Cells of Cajal via MAPK1 and MAPK3 Signaling to ETV1 and KIT, Leading to Rapid Gastric Emptying". Gastroenterology. 153 (2): 521–535.e20. doi:10.1053/j.gastro.2017.04.020. PMC 5526732. PMID 28438610.
  14. Frank JW, Saslow SB, Camilleri M, Thomforde GM, Dinneen S, Rizza RA (1995). "Mechanism of accelerated gastric emptying of liquids and hyperglycemia in patients with type II diabetes mellitus". Gastroenterology. 109 (3): 755–65. doi:10.1016/0016-5085(95)90382-8. PMID 7657103.
  15. Meier JJ, Rosenstock J, Hincelin-Méry A, Roy-Duval C, Delfolie A, Coester HV; et al. (2015). "Contrasting Effects of Lixisenatide and Liraglutide on Postprandial Glycemic Control, Gastric Emptying, and Safety Parameters in Patients With Type 2 Diabetes on Optimized Insulin Glargine With or Without Metformin: A Randomized, Open-Label Trial". Diabetes Care. 38 (7): 1263–73. doi:10.2337/dc14-1984. PMID 25887358.
  16. Goyal RK (2021). "Gastric Emptying Abnormalities in Diabetes Mellitus". N Engl J Med. 384 (18): 1742–1751. doi:10.1056/NEJMra2020927. PMID 33951363 Check |pmid= value (help).
  17. Singh J, Boopathi E, Addya S, Phillips B, Rigoutsos I, Penn RB; et al. (2016). "Aging-associated changes in microRNA expression profile of internal anal sphincter smooth muscle: Role of microRNA-133a". Am J Physiol Gastrointest Liver Physiol. 311 (5): G964–G973. doi:10.1152/ajpgi.00290.2016. PMC 5130548. PMID 27634012.
  18. Bhetwal BP, An C, Baker SA, Lyon KL, Perrino BA (2013). "Impaired contractile responses and altered expression and phosphorylation of Ca(2+) sensitization proteins in gastric antrum smooth muscles from ob/ob mice". J Muscle Res Cell Motil. 34 (2): 137–49. doi:10.1007/s10974-013-9341-1. PMC 3651903. PMID 23576331.
  19. Eisenman ST, Gibbons SJ, Verhulst PJ, Cipriani G, Saur D, Farrugia G (2017). "Tumor necrosis factor alpha derived from classically activated "M1" macrophages reduces interstitial cell of Cajal numbers". Neurogastroenterol Motil. 29 (4). doi:10.1111/nmo.12984. PMC 5367986. PMID 27781339.
  20. Feldman M, Smith HJ, Simon TR (1984). "Gastric emptying of solid radiopaque markers: studies in healthy subjects and diabetic patients". Gastroenterology. 87 (4): 895–902. PMID 6468877.
  21. Camilleri M, McCallum RW, Tack J, Spence SC, Gottesdiener K, Fiedorek FT (2017). "Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study". Gastroenterology. 153 (5): 1240–1250.e2. doi:10.1053/j.gastro.2017.07.035. PMC 5670003. PMID 28760384.
  22. Goyal RK (2021). "Gastric Emptying Abnormalities in Diabetes Mellitus". N Engl J Med. 384 (18): 1742–1751. doi:10.1056/NEJMra2020927. PMID 33951363 Check |pmid= value (help).
  23. Bharucha AE, Camilleri M, Forstrom LA, Zinsmeister AR (2009). "Relationship between clinical features and gastric emptying disturbances in diabetes mellitus". Clin Endocrinol (Oxf). 70 (3): 415–20. doi:10.1111/j.1365-2265.2008.03351.x. PMC 3899345. PMID 18727706.
  24. Goyal RK (2021). "Gastric Emptying Abnormalities in Diabetes Mellitus". N Engl J Med. 384 (18): 1742–1751. doi:10.1056/NEJMra2020927. PMID 33951363 Check |pmid= value (help).


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