Gastroparesis is defined by objective delaying of gastric emptying without any evidence of mechanical obstruction. Diabetic gastroparesis is a potential complication that occurs in the setting of poorly controlled diabetes, resulting from dysfunction in the coordination and function of the autonomic nervous system, neurons and specialized pacemaker cells (interstitial cells of Cajal, ICC) of the stomach and intestine, and the smooth muscle cells of the gastrointestinal tract.
Hyperglycemia (blood glucose greater than 200 mg/dL), commonly seen in the setting of poorly controlled diabetes, has been associated with diabetic gastroparesis that occurs as a result of neuropathy in the setting of chronic hyperglycemia and does not resolve with improved glycemic control. Acute hyperglycemia, on the other hand, though it can also result in delayed gastric emptying, is often reversible with improved glycemic control.
Gastric emptying requires coordination of fundal tone and antral phasic contraction with simultaneous inhibition of pyloric and duodenal contractions. This coordination also requires interactions between the enteric and autonomic nervous systems, smooth muscle cells, and the specialized pacemaker cells (ICC) of the stomach. The gastric motor dysfunction that is encountered in the setting of diabetes may occur as a result of autonomic neuropathy (both sympathetic and parasympathetic), enteric neuropathy (both excitatory and inhibitory neurons), ICC abnormalities (intrinsic neuropathy), acute blood glucose fluctuations, use of incretin-based medications, or psychosomatic factors. As a result, most diabetic patients tend to have dysfunction at multiple points in the process of gastric emptying. This includes abnormal postprandial proximal gastric accommodation and contraction, as well as abnormalities in antral motor function.
Although idiopathic gastroparesis is the most common form of gastroparesis, diabetes is the most common disease associated with the condition. Upper gastrointestinal symptoms are reported in 11% to 18% of diabetic patients, the majority of which are associated with delayed gastric emptying. Gastroparesis is seen in approximately 4.8% of individuals with type 1 diabetes, 1% of those with type 2 diabetes, and 0.1% of those without diabetes. Although there is a stronger association between type 1 diabetes and gastroparesis, the incidence of type 2 diabetes is much greater, and therefore, gastroparesis associated with type 2 diabetes is seen more frequently. Additionally, incretin mimetics are used to treat type 2 diabetic patients, and these medications pose an additional risk factor for developing gastroparesis.
Signs and symptoms of delayed gastric emptying are seen more frequently in individuals with type 1 versus type 2 diabetes, and typically in those patients who have had the disorder for at least five years. It has been observed that gastroparesis typically occurs in patients with a diagnosis of diabetes of at least ten years, and therefore seen more commonly in older individuals (with type 2 diabetes).
Diabetic gastroparesis occurs as a result of dysfunction in the autonomic and enteric nervous systems. Chronically high levels of blood glucose (or inefficient glucose uptake) leads to neuronal damage resulting in abnormal myenteric neurotransmission (e.g., vagus nerve), impaired inhibitory (nitric oxide) neuronal function, and dysfunctional smooth muscle and pacemaker (interstitial cells of Cajal) cells. Altogether, this dysfunction results in a combination of fewer contractions of the antrum, uncoordinated antro-duodenal contractions, and pyloric spasms ultimately resulting in delayed gastric emptying (gastroparesis).
Delayed gastric emptying in diabetic patients, particularly of solids, may also occur in the setting of abnormal small bowel motility which is thought to occur by a similar mechanism as that which is described in the stomach. Some diabetic patients may additionally experience changes in gastric compliance, both increased or decreased, which may also contribute to delayed gastric emptying.
In addition to this, serum (postprandial) glucose levels have a direct relationship with gastric emptying. In the setting of diabetic autonomic neuropathy, acute hyperglycemia stimulates gastric electrical activity. In diabetic patients (without neuropathy) and healthy controls, acute hyperglycemia will instead relax the proximal stomach, and suppress gastric electrical activity (e.g., reduced the frequency, propagation, and contraction of the antrum) in both fasting and post-prandial conditions, thereby slowing gastric emptying.
Acute hyperglycemia has also been associated with increased sensitivity in the gastrointestinal tract. This may be responsible for the postprandial dyspepsia (e.g., early satiety, nausea, vomiting, heartburn, bloating and pain) frequently experienced by patients with diabetic gastroparesis.
Carbohydrate absorption is highly dependent on the speed of gastric emptying through the release of peptides such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in which slower gastric emptying results in higher level of carbohydrate absorption. Therefore, a higher serum glucose level as a result of delayed gastric emptying can itself lead to worsening of gastroparesis.
The most common symptoms associated with gastroparesis include nausea, vomiting of undigested food, early satiety, bloating of the abdomen, and abdominal pain. In some cases, gastroparesis may also be associated with heartburn, and in severe cases, weight loss.
Factors that may trigger an exacerbation of diabetic gastroparesis include uncontrolled blood glucose levels, medication noncompliance or intolerance, adrenal insufficiency, or infection.
Diabetic gastroparesis is usually suspected based on clinical signs and symptoms, once other potential causes of symptoms have been excluded. Diagnostic evaluation involves scintigraphy (e.g., measuring the rate of emptying of solids) showing delayed gastric emptying, with obstruction (e.g., in the stomach or small intestine) ruled out by endoscopy or imaging (e.g., computed tomography or magnetic resonance imaging).
Treatment of diabetic gastroparesis is aimed at alleviating the associated symptoms and replenishing electrolytes, nutrition, and hydration. Modalities typically include correction of blood glucose levels (in other words, improved glycemic control), treatment with antiemetics or prokinetics, and modifications to diet. If a patient is on a regimen of incretin-based diabetic therapy (for example, pramlintide or GLP-1 analogs). These medications should be discontinued as they are also known to slow gastric emptying.
Frequently used medications include erythromycin (macrolide antibiotic associated with increased gastrointestinal motility) and metoclopramide (antiemetic and prokinetic). Miralax (polyethylene glycol 3350) may additionally be used to provide relief from severe constipation. Pain relief should be achieved through the use of non-narcotic medications, as narcotics are also known to delay gastric emptying.
Patients who continue to experience symptoms of gastroparesis despite medical therapy may be candidates for gastric electrical stimulation (GES) wherein an electrical device is implanted into the abdomen. It functions to deliver electrical impulses to both the smooth muscles and the neurons innervating the lower stomach. Gastric electrical stimulation has been shown to decrease symptoms of nausea and vomiting in patients with a history of gastroparesis.