diabetic gastroparesis

DEFINITION: Chronic motility disorder with objective delayed gastric emptying in the absence of mechanical gastric outlet obstruction. It occurs in a minority of patients with long-standing type 1 or type 2 diabetes and is usually accompanied by other microvascular complications (retinopathy, nephropathy, peripheral/autonomic neuropathy).

PATHOPHYSIOLOGY: - Vagal (autonomic) neuropathy: impaired vagal input reduces antral contractions and coordination between the antrum, pylorus, and duodenum (antropyloroduodenal dyscoordination), and impairs fundic accommodation. - Loss/dysfunction of interstitial cells of Cajal (gastric pacemaker cells), which causes gastric dysrhythmias (tachygastria, bradygastria). - Loss of nitric oxide synthase-containing inhibitory neurons in the enteric nervous system, leading to pylorospasm. - Acute hyperglycemia itself slows gastric emptying, which creates a vicious cycle. Hypoglycemia accelerates emptying. - Oxidative stress and enteric neuron/smooth muscle injury also contribute.

CLINICAL FEATURES: - Early satiety, postprandial fullness, nausea, vomiting of undigested food (often hours after eating), bloating, upper abdominal discomfort. Abdominal pain is less prominent than in other causes. - Erratic glycemic control: a mismatch between insulin action and delayed nutrient absorption causes postprandial hypoglycemia, followed by later hyperglycemia. Poor control can precipitate DKA. - Complications: weight loss, malnutrition, dehydration, electrolyte disturbances, bezoar formation (phytobezoar), and erratic absorption of oral medications. - Exam may show a succussion splash.

DIAGNOSIS: 1. Exclude mechanical obstruction first with upper endoscopy (or upper GI series/CT/MR enterography if needed). Residual food in the stomach after an overnight fast suggests gastroparesis. 2. Gastric emptying scintigraphy is the gold standard. It uses a solid meal (low-fat egg-white meal labeled with Tc-99m) with imaging at 0, 1, 2, and 4 hours. Retention of more than 60% at 2 hours or more than 10% at 4 hours is delayed. Stop medications that affect motility (opioids, GLP-1 agonists, anticholinergics, pramlintide) and control glucose (ideally <270 mg/dL) before testing. 3. Alternatives: wireless motility capsule and 13C-octanoate breath test. 4. Rule out other causes: medications (opioids, GLP-1 receptor agonists, anticholinergics, calcium channel blockers, TCAs), hypothyroidism, hypercalcemia, pregnancy, and scleroderma. Other causes include post-viral, post-surgical (vagotomy), and idiopathic gastroparesis.

MANAGEMENT: - Optimize glycemic control (continuous glucose monitoring, insulin timing adjustments, possibly postprandial insulin dosing). Review and stop offending medications. - Dietary: small, frequent, low-fat, low-fiber meals; liquid or pureed calories; avoid carbonated drinks. - Prokinetics: - Metoclopramide (D2 antagonist and 5-HT4 agonist) is the only FDA-approved drug. It carries a boxed warning for tardive dyskinesia, so limit use to 12 weeks or less. Other adverse effects include extrapyramidal symptoms, hyperprolactinemia, and neuroleptic malignant syndrome. - Erythromycin (motilin receptor agonist) works short term. Tachyphylaxis occurs, and it can cause QT prolongation and drug interactions via CYP3A4 inhibition. - Domperidone (peripheral D2 antagonist) is available only through an FDA investigational new drug program in the U.S. It can cause QT prolongation. - Antiemetics: ondansetron, prochlorperazine, promethazine. Low-dose TCAs or mirtazapine may help refractory nausea. - Refractory cases: jejunostomy tube feeding, gastric electrical stimulation (humanitarian device exemption), pyloric interventions (G-POEM, botulinum toxin with limited benefit), and venting gastrostomy.

BOARD PEARLS: - Classic vignette: a long-standing diabetic with other microvascular complications, early satiety, postprandial vomiting, and unexplained glucose swings. - Think "vagal neuropathy plus ICC loss, with delayed emptying but no obstruction." - First step is to exclude obstruction with EGD, then scintigraphy to confirm. - Treatment of choice: metoclopramide (watch for tardive dyskinesia). Erythromycin is a motilin agonist. - GLP-1 agonists and pramlintide slow gastric emptying and can mimic or worsen the condition. - Other diabetic GI/autonomic manifestations: diabetic diarrhea (often nocturnal), constipation, and esophageal dysmotility. Other autonomic effects include orthostatic hypotension, neurogenic bladder, and erectile dysfunction.