Diagnostic Assessment of Diabetic Gastroparesis

Gastroparesis is characterized by a constellation of upper gastrointestinal (GI) symptoms in association with delayed gastric emptying (GE) in the absence of mechanical outlet obstruction from the stomach. Cardinal symptoms are nausea, vomiting, early satiety or postprandial fullness, bloating, and abdominal or epigastric pain (1). Gastric retention may be asymptomatic in some, possibly due to afferent dysfunction in the setting of vagal denervation (2,3), and delayed GE may be associated with recurrent hypoglycemia in patients without upper GI symptoms (4,5). In these individuals, the term “delayed GE” is preferred to gastroparesis (1), although others have used terms such as “gastric hypoglycemia” (6). Thus, clinical manifestations of impaired GE may include anorexia, weight loss, malnutrition, phytobezoar formation, poorer quality-of-life, or impaired glycemic control due to erratic delivery of nutrients to the small bowel for absorption, and these may occur independent of factors such as age, gender, alcohol consumption, tobacco use, and diabetes type (7–9). Upper GI symptoms in diabetic patients may result from accelerated GE, often in association with vagal neuropathy and impaired proximal gastric accommodation (10). In addition, upper GI symptoms in diabetic patients were not significantly different in those with delayed compared with rapid GE, except possibly for postprandial distress (P = 0.076 on univariate analysis) (11). Hence, it is essential to measure GE in patients with upper GI symptoms if the right treatment is to be selected, such as choice of a prokinetic agent in those with delayed GE. Similarly, one cannot assume that patients with known vagal neuropathy and upper GI symptoms have gastroparesis, because the measured GE may be normal, fast, or slow in such patients. The magnitude of GE delay may also influence diagnosis; there is overlap in the clinical diagnosis of functional dyspepsia and gastroparesis in patients with mild GE delay and upper GI symptoms, whereas those with marked GE delay (greater than 35% retention at 4 h using a standard low-fat meal) should be diagnosed with gastroparesis (12,13). The cumulative 10-year incidence of gastroparesis has been estimated at 5.2% in type 1 diabetes and 1% in type 2 diabetes among community patients with diabetes (14). However, the estimated incidence of gastroparesis is critically dependent on definition and previous higher estimates of diabetic gastroparesis on symptom surveys rather than the use of quantitative tests (14). Studies of the natural history of GE and upper GI symptoms in patients with diabetes suggest that delayed GE and symptoms are both relatively stable over 12 years or 25 years (15,16). Abnormalities, such as accelerated GE, visceral hypersensitivity, and impaired accommodation, may contribute to symptom generation in patients with diabetes (10,17). Mechanisms associated with abnormal gastric motor functions include impaired glycemic control (18), extrinsic (e.g., vagal) and intrinsic neuropathy, abnormalities of interstitial cells of Cajal (19–21), loss of nitric oxide synthase (22), and, possibly, myopathy (1,23). The nonspecific nature of GI symptoms, multiple contributing pathophysiological mechanisms, diverse methods used to assess GE, varying degree of accuracy in assessment of GE of solids, and differences in patient selection across studies may all contribute to explaining the relatively weak association between symptoms and abnormal GE (3,24). Thus, careful evaluation of symptomatic patients through the use of validated techniques to document delayed GE is essential to diagnose and manage patients with suspected diabetic gastroparesis. GE assessment is also prognostically relevant, as it is associated with long-term morbidity due to diabetes (25). The gold standard for the evaluation of GE is GE scintigraphy (GES), a noninvasive, physiologic, and quantitative assessment of GE (13). Alternative methods include stable-isotope GE breath testing (GEBT), a wireless motility capsule (WMC), and functional ultrasonography (Table 1). Additional data on gastric motor functions may also be obtained by tests such as antroduodenal manometry and electrogastrography, but these are regarded as secondary or research methods. The aim of this review is to discuss available techniques for the diagnostic evaluation of diabetic gastroparesis and their relative advantages, limitations, and clinical and research applicabilities.