CLINICAL DIABETES
VOL. 17 NO. 4 1999


CASE STUDIES


Case Study: A 37-Year-Old Man With Type 1 Diabetes, Vomiting, and Diarrhea

William H. Herman, MD, MPH


Presentation
R.C. is a 37-year-old man with a 32-year history of type 1 diabetes. His diabetes is complicated by hypoglycemia unawareness. His last episode of hypoglycemia with loss of consciousness was at age 20. He also has proliferative diabetic retinopathy treated with laser in 1992, gastroparesis treated with a low-fat diet and cisapride (Propulsid), and painful peripheral polyneuropathy. He has had two cranial nerve palsies: a right sixth cranial nerve palsy that required ocular muscle surgery and a left Bell's palsy. He has also had bilateral carpal tunnel releases. There is no history of nephropathy, hypertension, dyslipidemia, tobacco abuse, or cardiovascular disease. Past medical history is remarkable for reflux esophagitis and a seizure disorder.

Since 1995, R.C. had been treated with an insulin infusion pump with buffered human insulin. More recently, he was switched to insulin lispro. Other medications include cisapride 10 mg four times daily and famotidine (Pepcid) 20 mg twice daily. The patient is allergic to sulfa and penicillin. He does not use ethanol.

In November 1996, R.C. presented with nausea, vomiting, abdominal pain, and watery diarrhea. His wife and two young children had similar symptoms that had lasted 4–5 days and resolved. Two weeks earlier, he had been treated with azithromycin (Zithromax) for sinusitis. He denied fevers, chills, hematochezia, and melana. Bowel sounds were present. Abdominal exam revealed a soft, flat abdomen with mild diffuse tenderness but no rebound or guarding. Stools for fecal leukocytes, ova and parasites, and c-difficile were all negative. Because of dehydration, the patient required 2 liters of intravenous normal saline. He was treated symptomatically with Imodium and promethazine with gradual resolution of his symptoms.

Over the subsequent year and a half, the patient had seven similar episodes. During these episodes, he was afebrile but had vomiting and liquid bowel movements with mucus. The episodes generally lasted for 2 weeks and resolved. Between episodes, he generally had one formed bowel movement per day but had alternating periods of constipation and diarrhea. He denied any problems with fecal incontinence.

Questions

1.  What is the differential diagnosis of vomiting and diarrhea?
2.  What diagnostic testing should be performed?
3. What is the best treatment strategy?

Commentary
This patient's history of exposure to a spouse and young children with similar symptoms certainly raises the possibility of viral gastroenteritis and bacterial and parasitic enteric pathogens. In addition, his previous treatment with a broad-spectrum antibiotic for sinusitis raises the possibility of pseudomembranous colitis. Appropriate testing ruled out these possibilities and the recurrence of symptoms made these diagnoses less likely.

Nausea and vomiting in a patient with long-standing type 1 diabetes may represent gastroparesis, a manifestation of diabetic autonomic neuropathy. Diarrhea in a diabetic patient with gastroparesis raises the possibilities of both bacterial overgrowth and diabetic diarrhea.

Diabetic diarrhea is an uncommon but troubling manifestation of diabetic autonomic neuropathy. Diabetic diarrhea may be preceded by abdominal cramps. It is often severe and watery but may occasionally be associated with steatorrhea. It is generally not associated with weight loss, but is often worse at night and may fluctuate from season to season. It is intermittent, and during remissions the individual may experience constipation, which characteristically lasts from a few hours to several weeks. It may also be associated with fecal incontinence.

Although gastroparesis, bacterial overgrowth, and diabetic diarrhea may occur in patients with diabetes, a thorough history, physical examination, and laboratory evaluation must be performed to rule out vomiting and diarrhea resulting from other causes. Diabetic gastroparesis is a diagnosis of exclusion. The most important considerations in the differential diagnosis include acute or chronic metabolic disturbances, such as diabetic ketoacidosis or uremia, and gastric or intestinal obstruction. The differential diagnosis of diarrhea includes medication-induced diarrhea, diarrhea associated with dietary sorbitol or lactose, enteric pathogens, pseudomembranous colitis, primary intestinal diseases, such as inflammatory bowel disease and celiac disease, and pancreatic exocrine insufficiency.

In this patient, hemoglobin A1c ranged between 6 and 7%. CBC, electrolytes, blood urine nitrogen, creatinine, liver function studies, and thyroid-stimulating hormone were all within normal limits. Treatment with metaclopramide (Reglan) and domperidone did not prevent the episodes, nor did treatment with tetracycline 250 mg 3 times per day for 14 days. A hydrogen breath test was negative. Colonoscopy was normal. Upper GI endoscopy revealed a normal esophagus, stomach, pylorus, and duodenum. Multiple biopsy specimens were obtained from the post-bulbar duodenum and sweep. Biopsies from the small intestine revealed blunting of the villae consistent with celiac disease. In addition, IgA anti-endomysial antibodies were performed. These were positive in a titer of 1 to 640. The patient began a gluten-free diet with complete resolution of his symptoms and a 10-lb weight gain within 2 months.

Celiac disease, or gluten-sensitive enteropathy, is a disease caused by damage to villus epithelial cells in response to the ingestion of dietary gluten. The clinical manifestations of celiac disease range from mild abdominal discomfort and diarrhea to severe diarrhea and signs of malabsorption including iron deficiency anemia, folate deficiency, and reduced bone mineral density. IgA endomysial antibody is the most sensitive and specific screening test for celiac disease. It has been estimated to be 90100% sensitive and 99–100% specific for celiac disease. The diagnosis is confirmed by small bowel biopsy.

Celiac disease and type 1 diabetes are autoimmune diseases with a common genetic predisposition. Both celiac disease and type 1 diabetes are associated with a high frequency of HLA-DR3 genotypes. As a result, celiac disease is more frequent in type 1 diabetes than in type 2 diabetes or in the general population. Studies that have screened patients with type 1 diabetes for celiac disease have found rates of celiac disease between 1% and 8%. These rates are 411 times higher than rates of celiac disease in the general population. Type 1 diabetic patients with celiac disease detected by screening have been predominately female and have had an earlier age of onset of type 1 diabetes. In many instances, gastrointestinal symptoms have been mild and appreciated only in retrospect. Most such patients have had few or no symptoms or signs of malabsorption.

Clinical Pearls

  • The simultaneous occurrence of type 1 diabetes and celiac disease is relatively common.
  • Serologic testing using IgA antiendomysial antibodies is the most sensitive and specific screening test for celiac disease.
  • Clinicians should be aware of the association between type 1 diabetes and celiac disease and should have a low threshold for testing type 1 diabetic patients with otherwise unexplained constitutional or gastrointestinal symptoms.

SUGGESTED READINGS

Herman WH, Greene DA: Microvascular complications of diabetes. In Management of Diabetes Mellitus: Perspectives of Care Across the Lifespan, 2nd edition. Haire-Joshu D, Ed. St. Louis, Mo., Mosby, 1996, p. 234-80.

Rensch MJ, Merenich JA, Lieberman M, Long BD, Davis DR, McNally PR: Gluten-sensitive enteropathy in patients with insulin-dependent diabetes mellitus. Ann Int Med 124:564-67, 1996.

Cronin CC, Shanahan F: Insulin-dependent diabetes mellitus and celiac disease. Lancet 349:1096-97, 1997.


William H. Herman, MD, MPH, is an associate professor of internal medicine in the Division of Endocrinology and Metabolism at the University of Michigan in Ann Arbor. He is an associate editor of Clinical Diabetes.


Copyright 1999 American Diabetes Association
Updated 11/99
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