Diabetic Gastroparesis

Abstract

This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.

Figure 1.

Schematic representation of enteric and extrinsic mechanisms that control GI motility. Antegrade peristalsis, the motor pattern resulting in aborad propulsion, results from proximal contraction mediated by excitatory neurotransmitters, coordinated with distal relaxation mediated by inhibitory neurotransmitters. The sympathetic neural input, which is primarily mediated by presynaptic and prejunctional inhibition of acetylcholine release via adrenergic α₂ receptors, can tonically inhibit antegrade peristalsis in the viscus and stimulates tonic contraction of the sphincters (not shown).

Figure 2.

Assessment of GE by scintigraphy. Liquids empty from the stomach in an exponential manner whereas the emptying of solids is characterized by a biphasic profile that includes an initial lag phase, followed by a more rapid, linear emptying. Liquids with higher caloric content are more likely to evoke duodenogastric feedback mechanisms that inhibit GE and hence take longer to empty from the stomach than do noncaloric liquids. For solids, the lag period is prolonged by adding 10% or 25% dextrose to the meal. However, the slope of the linear phase is comparable for water and 10% and 25% dextrose. [Adapted with permission from Collins PJ, Horowitz M, Cook DJ, et al. Gastric emptying in normal subjects—a reproducible technique using a single scintillation camera and computer system. Gut 1983;24:1117–1125.]

Figure 3.

Stepwise approach to the management of gastroparesis. [From Adil E. Bharucha, MBBS, MD; Yogish C. Kudva, MBBS; and David O. Prichard, MB, BCh, PhD. Used with permission of the Mayo Foundation for Medical Education and Research. All rights reserved.]