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Thursday, 28 April 2016

UNDIGESTED MUSCLE FIBERS AND STARCH GRANULES IN A STOOL SAMPLE OF A DIABETIC PATIENT SUFFERING FROM DIARRHEA

Written by Iñaki Vallés Díez | Miren Vallejo Ruiz | Naiara Tirapu Fernández de la Cuesta, Posted in Volumen 2

Gastrointestinal symptoms are found in up to 76% of patients diagnosed with diabetes mellitus, and diarrhea is one of the most common clinical manifestations1. Diarrhea episodes in diabetic patients are usually watery, intermittent, mild and occur mostly during nights. Moreover, they can be long lasting and resistant to several treatments2.

Gastrointestinal symptoms are found in up to 76% of patients diagnosed with diabetes mellitus, and diarrhea is one of the most common clinical manifestations1. Diarrhea episodes in diabetic patients are usually watery, intermittent, mild and occur mostly during nights. Moreover, they can be long lasting and resistant to several treatments2.
Articulo3 imagen1 500x498Figure . Patient stool sample (optical microscopy, 400X). Undigested muscle fibers (A) and cells containing starch granules (B) are observed in fresh sample. Incubation with lugol’s solution changes starch colour into blue/black (C).

Those episodes are not linked to any particular food, apart from fat consumption, since reducing the fat intake improves the symptoms. The patient has lost more that 10 kg in the last few months. Lost of appetite, fever or skin/articular damage are not reported. The patient has not taken any antibiotics and has not travelled recently.
Serology for celiac disease is negative. Stool microbiological tests are also negative. No parasite is found under optical microscopy. However, numerous undigested muscle fibers are found, on which part of the longitudinal and transversal striations can still be distinguished. Also, cells containing many starch granules are detected in fresh sample, as well as after incubation with lugol´s solution (Figure 1, A-C). No fat drops are found, consistent with the absence of fat intake in the days before the stool sample collection.

Clinical chemistry tests show reduced levels of liposoluble vitamins A (0.27 mg/L), D (<7 ng/mL) and E (0.5 mg/dL), biochemical parameters reflecting caloric and protein malnutrition (cholesterol: 98 mg/dL; prealbumin: 18 mg/dL), slight increase of livertransaminases (AST: 101 U/L; ALT: 170 U/L) and very poor glycemic control (glucose: 307 mg/dL; Haemoglobin A1c: 10.5%). Faecal calprotectin values are normal.

Several imaging tests are performed, including gastroscopy, colonoscopy with colon biopsy and endoscopies. Such tests allow the detection of food remaining in the stomach and duodenum. A small-sized pancreas and a hemangioma in the liver are also found.

A special diet, consisting of low-fat food, no alcohol and no intestine irritating substances is recommended as treatment for the patient. Vitamin A, D and E supplements, as well as amylase, lipase and protease supplements are prescribed. Ongoing insulin treatment must be continued. After following these recommendations, a slight improvement is reported in the number and type of stools. However, diarrhea still occurs, since the insulin treatment scheme is not followed by the patient.

Diabetic diarrhea etiology is diverse. One of the causes of diarrhea is the autonomic diabetic neuropathy, which induces intestinal dysfunction with an increase in the motility (reduced colonic transit)3. Diarrhea in diabetic patients can also arise from overgrowth of intraluminal bacteria, as well as from some of the drugs intended for glycemic control, such as biguanides or sulfonylureas, all of them with known gastrointestinal consequences. Finally, other factors such microscopic colitis, celiac disease or C. difficile infection are less frequent causes of diarrhea in diabetic patients4-5.

Treatment is based in strict control of blood glucose and glycated haemoglobin levels, by administration of clonidine, somatostatin analogues, rifaximin and, of course, antidiabetic drugs, for which careful monitoring of adverse effects is essential4, 6-7.

In the case presented, laboratory tests played a fundamental role in identifying the diabetic etiology of the diarrhea. First, by helping in the visualization of undigested food (muscle fibers and starch granules) by optical microscopy. Secondly, by detecting alteration of nutritional markers. Incorrect glycemic control by the patient, due to the fact that he did not follow the insulin treatment, could have caused an autonomic neuropathy, probably explaining the abnormally fast intestinal transit, leading to nutrient malabsorption and continuous diarrhea episodes.

Therefore, when undigested food is found in a stool sample from a patient suffering from diarrhea, the laboratory specialist should consider the following options, in order to guide a diagnosis:

Pancreatic o liver insufficiency: steatorrhea and intact muscle fibers. Measure pancreatic and liver enzymes.
Food intolerances: gluten (celiac disease), lactose, fructose... HLA typing, autoantibodies, intestine biopsy, certain food-free diet...
Digestive tract infections: bacteria, virus, parasites... Microbiological cultures and specific antigen detection.
Diabetes: glycemia, glycated hemoglobin...
In any case: laboratory measurement of nutrient profile parameters (albumin, cholesterol, vitamins...)
References

  • Feldman M, Chiller L. Disorders of Gastrointestinal Motility Associated with Diabetes Mellitus. Ann Intern Med.1983;98(3):378-84.
  • Farthing MJ. The patient with refractory diarrhea. Best Pract Res Clin Gastroenterol. 2007;21(3):485-501.
  • Werth B, Meyer-Wyss B, Spinas GA, Drewe J, Beglinger C. Non-invasive assessment of gastrointestinal motility disorders in diabetic patients with and without cardiovascular signs of autonomic neuropathy. Gut. 1992;33(9):1199-203.
  • Méndez-Flórez J, García-Muñoz L. Diarrea en el paciente con diabetes mellitus. Rev Fac Med. 2015; 63(4):727-32.
  • Virally-Monod M, Tielmans D, Kevorkian JP, Bouhnik Y, Flourie B, Porokhov B, et al. Chronic diarrhoea and diabetes mellitus: prevalence of small intestinal bacterial overgrowth. Diabetes Metab. 1998;24(6):530-6.
  • Fedorak RN, Field M, Chang EB. Treatment of diabetic diarrhea with clonidine. Ann Intern Med. 1985;102(2):197-9.
  • Mourad FH, Gorard D, Thillainayagam AV, Colin-Jones D, Farthing MJ. Effective treatment of diabetic diarrhoea with somatostatin analogue, octreotide. Gut. 1992;33(11):1578-80.

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