Easy-to-use, reproducible tests such as gastric scintigraphy and stable-isotope 13C breath tests have helped identify rapid gastric emptying, which may be an emerging target in postprandial hyperglycemia in patients with type 2 diabetes mellitus (T2DM), according to a review article published in The New England Journal of Medicine.
Although diabetes mellitus is linked with various gastric emptying abnormalities, rapid gastric emptying can affect the genesis and progression of T2DM. Emerging treatments for rapid gastric emptying may facilitate the management of postprandial hyperglycemia.
Cellular and molecular alterations due to oxidative stress can lead to disruptions in neuromuscular transmission, which increase the number of interstitial cells of Cajal, providing a hypercontractile phenotype to smooth muscle cells. However, macrophage polarization is promoted during moderate oxidative stress, leading to inflammatory response and loss of neurotransmission. This further leads to the loss of interstitial cells of Cajal, and therefore, the hypocontractile phenotype of smooth muscle cells.
Acute hyperglycemia leads to the activation of the gastric inhibitory vagal motor circuit via glucose-stimulated vagal afferent neurons. These neurons reduce smooth-muscle contractility, cause dysfunction of interstitial cells of Cajal, and lead to slow-wave abnormalities. “Transient slow gastric emptying due to acute hyperglycemia is a counterregulatory phenomenon and doesn’t require treatment,” the author of the review noted.
Acute hypoglycemia leads to fast gastric emptying, and is often a serious complication of insulin treatment. Activation of the gastric excitatory vagal motor circuit enhances contractility of smooth muscle cells, thereby leading to rapid gastric emptying. Transient rapid gastric emptying is also counterregulatory and should not be treated.
While study results suggest that there may not be a specific relation between upper abdominal symptoms and rapid gastric emptying, glucose intolerance is significantly affected by rapid gastric emptying and may lead to T2DM.
Rapid gastric emptying, often associated with amylin and leptin deficiencies, can be decelerated with dietary manipulation of pharmacologic interventions such as metformin, amylin analogs, and short-acting glucagon-like peptide 1 agonists.
Diabetic gastroparesis, categorized by abnormal initiation and conduction of slow waves on high-resolution mapping, is a frequent complication of diabetes mellitus. Therefore, a differential diagnosis must be considered, as mechanical outlet obstructions and other comorbidities may affect gastric emptying.
Motor abnormalities in diabetic gastroparesis can be caused by oxidative stresses that lead to loss of cholinergic excitatory neuromuscular transmission, leading to smooth muscle weakness. Impairment of pyloric and duodenal relaxation may also occur, causing obstructions in outflow. “The available studies do not support a causal relationship between motor abnormalities and symptoms in diabetic gastroparesis,” the author noted. “The most telling argument against gastric motor abnormalities in diabetic gastroparesis is the fact that patients with diabetes and upper abdominal symptoms have normal, delayed, or rapid gastric emptying.”
Upper gastrointestinal symptoms can also mark the presence of diabetic gastroparesis. Because cardinal symptoms of gastroparesis, such as postprandial fullness, early satiety, nausea, vomiting, and bloating, are not necessarily distinguished from functional dyspepsia, clinical gastroparesis is considered part of functional dyspepsia.
The use of invasive maneuvers to target symptom relief in gastric emptying has been discouraged and accelerating gastric emptying may exacerbate hyperglycemia. It is argued that parallel effects of oxidative stress and inflammation on nociceptors and afferent neurons – not motility changes – may lead to functional dyspepsia-like symptoms in gastroparesis.
“Recent concepts of the mechanism of functional dyspepsia suggest the involvement of low-grade inflammation and noxious mediators in symptoms related to functional dyspepsia,” the author wrote. Therefore, effective treatments for diabetic gastroparesis-related symptoms may be similar to treatments for functional dyspepsia.
Although rapid gastric emptying has a role in postprandial hyperglycemia mechanisms, the researcher concluded that “An understanding of the mechanisms of these complications may help to identify new targets for rational treatment.”
Goyal RK. Gastric emptying abnormalities in diabetes mellitus. N Engl J Med. 2021;384(18):1742-1751. doi: 10.1056/NEJMra2020927
This article originally appeared on Gastroenterology Advisor