How to evaluate a patient with type 2 diabetes (T2D) presenting with chronic diarrhea and abdominal pain?

Evaluation of Chronic Diarrhea in Type 2 Diabetes

In a patient with type 2 diabetes presenting with chronic diarrhea and abdominal pain for 10 months, begin with targeted blood and stool testing to exclude inflammatory bowel disease, celiac disease, and medication-induced diarrhea, followed by colonoscopy with biopsies if alarm features are present or initial testing is abnormal. 1, 2

Initial Clinical Assessment

Critical Alarm Features to Identify

The presence of alarm features mandates urgent evaluation and changes the diagnostic approach:

• Weight loss is a critical alarm feature that excludes functional disorders and necessitates colonoscopy within 2-4 weeks 1, 2
• Nocturnal diarrhea suggests organic disease rather than functional bowel disorder 1
• Blood in stools or iron deficiency anemia requires immediate colonoscopy to exclude inflammatory bowel disease or colorectal cancer 1, 2
• Age >50 years warrants structural evaluation of the colon 3, 2
• Family history of inflammatory bowel disease, celiac disease, or colorectal cancer increases pretest probability of organic disease 1

Diabetes-Specific Considerations

Several factors unique to diabetic patients must be evaluated:

• Medication review is mandatory, as metformin causes chronic diarrhea in up to 53% of patients taking it and is the most common cause of non-diabetic diarrhea in type 2 diabetes 4, 5, 6
• Duration and control of diabetes should be documented, as poorly controlled diabetes with evidence of peripheral or autonomic neuropathy increases likelihood of diabetic enteropathy 7, 8
• Presence of autonomic neuropathy can cause anorectal dysfunction and fecal incontinence, mimicking diarrhea 7, 9

First-Line Laboratory Testing

Blood Tests

Order the following blood tests within 1-2 weeks:

• Complete blood count to assess for anemia, which may indicate celiac disease, inflammatory bowel disease, or malignancy 1, 2
• IgA tissue transglutaminase (tTG) with total IgA level to screen for celiac disease, which has higher prevalence in diabetic patients and presents with chronic diarrhea 1, 7, 5
• Hemoglobin A1c to assess glycemic control, as poor control is associated with diabetic enteropathy 7, 8

The AGA recommends against using ESR or CRP alone to screen for inflammatory bowel disease due to low diagnostic accuracy 1.

Stool Tests

Obtain the following stool studies:

• Fecal calprotectin or fecal lactoferrin to distinguish inflammatory from non-inflammatory causes of diarrhea, with sensitivity >90% for inflammatory bowel disease 1, 2
• Giardia antigen testing is strongly recommended, as Giardia is a common cause of chronic diarrhea with high diagnostic accuracy 1
• Stool culture if infectious etiology is suspected, though less likely after 10 months of symptoms 2

Testing for ova and parasites (other than Giardia) is not recommended without travel history to high-risk areas 1.

Endoscopic Evaluation

Indications for Colonoscopy with Biopsies

Colonoscopy with biopsies is mandatory in the following scenarios:

• Presence of any alarm features (weight loss, nocturnal symptoms, blood in stools, anemia) requires colonoscopy within 2-4 weeks 2
• Elevated fecal calprotectin (>50 mg/g) indicating inflammatory bowel disease 1
• Abnormal blood tests suggesting malabsorption or inflammation 1
• Age >50 years with change in bowel habits, even without other alarm features 3, 2

Critical pitfall: Do not perform flexible sigmoidoscopy alone, as approximately 50% of neoplasia may be proximal to the splenic flexure; full colonoscopy is required 3, 2. Always obtain biopsies even if mucosa appears normal, as microscopic colitis (15% of chronic diarrhea in older adults) can only be diagnosed histologically 2.

Upper Endoscopy Considerations

If initial workup is unrevealing or celiac serology is positive, proceed to upper endoscopy with duodenal biopsies to confirm celiac disease 1, 7.

Diabetes-Specific Diagnostic Considerations

Evaluate for Diabetic Enteropathy

If initial testing excludes inflammatory bowel disease, celiac disease, and medication effects:

• Assess for bacterial overgrowth with small bowel aspirate and culture, as this occurs frequently in diabetic patients with autonomic neuropathy 7, 8
• Consider pancreatic exocrine insufficiency, which is more common in diabetic patients and causes steatorrhea 7, 9
• Evaluate anorectal function if fecal incontinence is suspected, as autonomic neuropathy can cause sphincter dysfunction 7, 8

Test for Bile Acid Diarrhea

The AGA suggests testing for bile acid diarrhea in patients with chronic diarrhea, though specific tests (SeHCAT) are not available in North America 1. An empiric trial of bile acid binders (cholestyramine) is reasonable if bile acid diarrhea is suspected clinically 1.

Algorithmic Approach

Step 1 (Week 1-2): Complete blood count, IgA-tTG with total IgA, hemoglobin A1c, fecal calprotectin, and Giardia antigen testing 1, 2

Step 2 (Week 2-4): If alarm features present or abnormal initial tests, schedule colonoscopy with biopsies urgently 2

Step 3 (Week 4-6): If initial workup unrevealing, consider upper endoscopy if celiac serology positive, or evaluate for bacterial overgrowth and anorectal dysfunction 7

Step 4 (Week 6-8): If all testing negative, consider empiric trial of bile acid binders or antidiarrheal agents, or measure gastrointestinal transit 7, 8

Common Pitfalls to Avoid

• Do not diagnose irritable bowel syndrome in patients with weight loss, as this is an exclusion criterion for functional disorders 2
• Do not attribute symptoms to diabetes without excluding other common causes (metformin, celiac disease, microscopic colitis, inflammatory bowel disease) that have higher prevalence in diabetic patients 7, 5
• Do not skip colonic biopsies even with normal-appearing mucosa, as microscopic colitis requires histologic diagnosis 2
• Do not delay colonoscopy in patients >50 years with chronic diarrhea and abdominal pain, as colorectal cancer prevalence is 27% in patients with change in bowel habits 2