Chronic Diarrhea in Diabetes Mellitus: Mechanisms and an Approach to Diagnosis and Treatment
1993; Elsevier BV; Volume: 68; Issue: 7 Linguagem: Inglês
10.1016/s0025-6196(12)60606-5
ISSN1942-5546
AutoresMiguel A. Valdovinos, Michael Camilleri, Bruce R. Zimmerman,
Tópico(s)Clostridium difficile and Clostridium perfringens research
ResumoIn this study, our aim was to develop a practical strategy to facilitate the management of patients with diabetes mellitus and chronic diarrhea in a tertiary referral practice. We reviewed the pertinent English-language literature of the past 30 years that described the pathophysiologic mechanisms and treatment of patients with diabetic diarrhea and retrospectively reviewed the medical records of all patients with diabetic diarrhea examined at the Mayo Clinic during 1990. Three typical case studies are described to illustrate the diverse mechanisms that lead to chronic diarrhea in patients with diabetes. No report in the literature has systematically evaluated all the putative mechanisms of chronic diarrhea in any group of patients with diabetes. In our tertiary referral practice, diabetic diarrhea was frequently due to celiac sprue, bacterial overgrowth in the small bowel, or fecal incontinence in conjunction with anorectal dysfunction; however, in almost 50% of the patients, these causes were excluded, and abnormal intestinal motility or secretion was postulated to be one of the likely causes of the diarrhea. These data suggest a practical algorithm based on three sequential assessments: first, tests of blood and stool specimens and flexible sigmoidoscopy to detect evidence of malabsorption or disease in the distal colon; second, small bowel aspirate and biopsy if the results of initial blood or stool tests are abnormal or anorectal function tests if those test results are normal; and, finally, measurement of gastrointestinal transit or therapeutic trials with opioids, clonidine hydrochloride, and, rarely, cholestyramine resin or octreotide acetate (or both methods). The mechanisms whereby abnormal neural function due to diabetes results in altered digestive, secretory, absorptive, or motor function necessitate further elucidation. The management of chronic diarrhea in patients in a tertiary referral practice, however, can be based on a practical algorithm to determine the cause and to adopt specific treatment to correct it. In this study, our aim was to develop a practical strategy to facilitate the management of patients with diabetes mellitus and chronic diarrhea in a tertiary referral practice. We reviewed the pertinent English-language literature of the past 30 years that described the pathophysiologic mechanisms and treatment of patients with diabetic diarrhea and retrospectively reviewed the medical records of all patients with diabetic diarrhea examined at the Mayo Clinic during 1990. Three typical case studies are described to illustrate the diverse mechanisms that lead to chronic diarrhea in patients with diabetes. No report in the literature has systematically evaluated all the putative mechanisms of chronic diarrhea in any group of patients with diabetes. In our tertiary referral practice, diabetic diarrhea was frequently due to celiac sprue, bacterial overgrowth in the small bowel, or fecal incontinence in conjunction with anorectal dysfunction; however, in almost 50% of the patients, these causes were excluded, and abnormal intestinal motility or secretion was postulated to be one of the likely causes of the diarrhea. These data suggest a practical algorithm based on three sequential assessments: first, tests of blood and stool specimens and flexible sigmoidoscopy to detect evidence of malabsorption or disease in the distal colon; second, small bowel aspirate and biopsy if the results of initial blood or stool tests are abnormal or anorectal function tests if those test results are normal; and, finally, measurement of gastrointestinal transit or therapeutic trials with opioids, clonidine hydrochloride, and, rarely, cholestyramine resin or octreotide acetate (or both methods). The mechanisms whereby abnormal neural function due to diabetes results in altered digestive, secretory, absorptive, or motor function necessitate further elucidation. The management of chronic diarrhea in patients in a tertiary referral practice, however, can be based on a practical algorithm to determine the cause and to adopt specific treatment to correct it. Gastrointestinal symptoms are common and varied in patients with diabetes mellitus who are examined in tertiary referral practices.1Feldman M Schiller LR Disorders of gastrointestinal motility associated with diabetes mellitus.Ann Intern Med. 1983; 98: 378-384Crossref PubMed Scopus (619) Google Scholar Diarrhea has been known to be associated with diabetes mellitus for more than 50 years,2Bargen JA Bollman JL Kepler EJ The “diarrhea of diabetes” and steatorrhea of pancreatic insufficiency.Mayo Clin Proc. 1936; 11: 737-742Google Scholar and its overall prevalence in patients with diabetes has been reported to vary from 8 to 22%.1Feldman M Schiller LR Disorders of gastrointestinal motility associated with diabetes mellitus.Ann Intern Med. 1983; 98: 378-384Crossref PubMed Scopus (619) Google Scholar, 3Dandona P Fonseca V Mier A Beckett AG Diarrhea and metformin in a diabetic clinic.Diabetes Care. 1983; 6: 472-474Crossref PubMed Scopus (83) Google Scholar These data may be influenced by selection (referral) bias; moreover, because no prospective epidemiologic studies are available from a random sample of patients with diabetes, these figures may not reflect the actual prevalence of diarrhea. The pathogenesis of chronic diarrhea in patients with diabetes is incompletely known. Several mechanisms may contribute to the development of this condition: anorectal dysfunction,4Schiller LR Santa Ana CA Schmulen AC Hendler RS Harford WV Fordtran JS Pathogenesis of fecal incontinence in diabetes mellitus: evidence for internal-anal-sphincter dysfunction.N Engl J Med. 1982; 307: 1666-1671Crossref PubMed Scopus (171) Google Scholar abnormalities in intestinal motility1Feldman M Schiller LR Disorders of gastrointestinal motility associated with diabetes mellitus.Ann Intern Med. 1983; 98: 378-384Crossref PubMed Scopus (619) Google Scholar and secretion,5Chang EB Bergenstal RM Field M Diarrhea in streptozocin-treated rats: loss of adrenergic regulation of intestinal fluid and electrolyte transport.J Clin Invest. 1985; 75: 1666-1670Crossref PubMed Scopus (61) Google Scholar bacterial overgrowth in the small bowel,6Goldstein F Wirts CW Kowlessar OD Diabetic diarrhea and steatorrhea: microbiologic and clinical observations.Ann Intern Med. 1970; 72: 215-218Crossref PubMed Scopus (67) Google Scholar bile acid catharsis,7Molloy AM Tomkin GH Altered bile in diabetic diarrhoea.BMJ. 1978; 2: 1462-1463Crossref PubMed Scopus (41) Google Scholar exocrine pancreatic insufficiency,8Vacca JB Henke WJ Knight Jr, WA The exocrine pancreas in diabetes mellitus.Ann Intern Med. 1964; 61: 242-247Crossref PubMed Scopus (101) Google Scholar, 9Frier BM Saunders JHB Wormsley KG Bouchier IAD Exocrine pancreatic function in juvenile-onset diabetes mellitus.Gut. 1976; 17: 685-691Crossref PubMed Scopus (143) Google Scholar and celiac disease.10Walsh CH Cooper BT Wright AD Malins JM Cooke WT Diabetes mellitus and coeliac disease: a clinical study.Q J Med. 1978; 47: 89-100PubMed Google Scholar The relative frequencies of these mechanisms in unselected patients with diabetes are unclear, however. In this article, we review the literature on mechanisms of chronic diarrhea in patients with diabetes, provide examples of clinical cases, retrospectively review the causes in all patients with an indexed diagnosis of diabetes mellitus and diarrhea examined at the Mayo Clinic during 1990, and propose an algorithm for the diagnosis and treatment of such patients. Among patients with diabetes in whom chronic diarrhea develops, one subgroup has “diabetic diarrhea”; this term was first used in 1936 by Bargen and associates2Bargen JA Bollman JL Kepler EJ The “diarrhea of diabetes” and steatorrhea of pancreatic insufficiency.Mayo Clin Proc. 1936; 11: 737-742Google Scholar at the Mayo Clinic to describe the unexplained diarrhea associated with severe diabetes. Subsequent reports emphasized that patients with diabetic diarrhea usually have poorly controlled diabetes and evidence of a generalized neuropathy.11Rundles RW Diabetic neuropathy: general review with report of 125 cases.Medicine. 1945; 24: 111-160Crossref Scopus (337) Google Scholar, 12Sheridan EP Bailey CC Diabetic nocturnal diarrhea.JAMA. 1946; 130: 632-634Crossref PubMed Scopus (19) Google Scholar, 13Berge KG Wollaeger EE Scholz DA Rooke ED Sprague RG Steatorrhea complicating diabetes mellitus with neuropathy: report of cases without apparent external pancreatic insufficiency.Diabetes. 1956; 5: 25-31PubMed Google Scholar Typically, diabetic diarrhea is chronic and occurs in patients with a long-standing history of insulin-dependent diabetes mellitus;14Katz LA Spiro HM Gastrointestinal manifestations of diabetes.N Engl J Med. 1966; 275: 1350-1361Crossref PubMed Scopus (134) Google Scholar generally, it begins a mean of 8 years (range, from a few months to several decades) after onset of diabetes. The male-to-female preponderance is 3 to 2.15Miller LJ Small intestinal manifestations of diabetes mellitus.Yale J Biol Med. 1983; 56: 189-193PubMed Google Scholar Peripheral neuropathy is present in most patients, and autonomic neuropathy, including abnormal pupillary responses, anhidrosis, gustatory sweating, orthostatic hypotension, impotence, retrograde ejaculation, and dysfunction of the urinary bladder, is common.11Rundles RW Diabetic neuropathy: general review with report of 125 cases.Medicine. 1945; 24: 111-160Crossref Scopus (337) Google Scholar Some patients have early satiety, nausea, and vomiting, factors that suggest impaired gastric emptying.16Yang R Arem R Chan L Gastrointestinal tract complications of diabetes mellitus: pathophysiology and management.Arch Intern Med. 1984; 144: 1251-1256Crossref PubMed Scopus (77) Google Scholar The diarrhea is often severe; the stools are usually brown, watery, voluminous, and, occasionally, accompanied with tenesmus.14Katz LA Spiro HM Gastrointestinal manifestations of diabetes.N Engl J Med. 1966; 275: 1350-1361Crossref PubMed Scopus (134) Google Scholar, 17Goyal RK Spiro HM Gastrointestinal manifestations of diabetes mellitus.Med Clin North Am. 1971 Jul; 55: 1031-1044PubMed Google Scholar Diarrhea can occur at any time but is often nocturnal12Sheridan EP Bailey CC Diabetic nocturnal diarrhea.JAMA. 1946; 130: 632-634Crossref PubMed Scopus (19) Google Scholar and may be associated with anal incontinence.17Goyal RK Spiro HM Gastrointestinal manifestations of diabetes mellitus.Med Clin North Am. 1971 Jul; 55: 1031-1044PubMed Google Scholar The bouts of diarrhea are usually episodic with interposed normal bowel movements or even constipation.16Yang R Arem R Chan L Gastrointestinal tract complications of diabetes mellitus: pathophysiology and management.Arch Intern Med. 1984; 144: 1251-1256Crossref PubMed Scopus (77) Google Scholar Diabetic diarrhea, however, is only one of the possible causes of chronic diarrhea in patients with diabetes. The following three typical cases illustrate the various mechanisms that result in chronic diarrhea in patients with diabetes mellitus. A 28-year-old woman with insulin-dependent diabetes mellitus of 12 years' duration and gastroparesis for the previous 6 years came to our institution because of chronic diarrhea, lack of sensation of stool in the rectum, and fecal incontinence, especially at night. The pupils reacted to accommodation but not to light; she had postural hypotension (120/80 mm Hg to 90/60 mm Hg). The anal sphincter tone was decreased. Anorectal manometry revealed mostly low resting pressures in the anal canal (proximal, 10 mm Hg [normal, 40 to 60]; middle, 38 mm Hg [normal, 50 to 80]; and distal, 50 mm Hg [normal, 30 to 50]). In contrast, maximal voluntary squeeze pressures were essentially normal (proximal, 93 mm Hg [normal, 115 to 150]; middle, 103 mm Hg [normal, 100 to 150]; and distal, 120 mm Hg [normal, 80 to 120]). The rectosphincteric reflex was elicited normally with a threshold of 15 ml of air (normal, less than 10). A distended balloon in the rectum was first sensed at a volume of 30 ml (normal, less than 20). Rectal capacity and compliance as well as rectoanal angle measurements at rest, during squeeze, and during defecation were normal. A 50-ml balloon placed into the rectum was expelled normally. In summary, the patient had autonomic neuropathy, decreased rectal sensation, and dysfunction of the internal anal sphincter that caused fecal incontinence. A 23-year-old woman with a 17-year history of insulin-dependent diabetes mellitus sought medical attention because of chronic diarrhea, abdominal bloating, and nocturnal fecal incontinence. In the past, she had experienced urinary tract infections, tingling in her feet, and dizziness on changing posture. Six years before the current assessment, watery, explosive diarrhea developed, which was worse postprandially. A physical examination revealed postural hypotension, distal sensory neuropathy in both lower limbs, and abdominal distention but no succussion splash or tenderness. The rectal mucosa and anal sphincter tone at rest and during squeeze were normal. The abnormal results of laboratory studies were as follows: total protein, 5.6 g/dl; albumin, 3.3 g/dl; urinary protein, 564 mg/24 h (normal, 27 to 93); and stool weight, 990 g with 7 g fat/24 h. Sympathetic adrenergic, sympathetic cholinergic, and vagal dysfunction were noted on autonomic reflex tests.18Camilleri M Disorders of gastrointestinal motility in neurologic diseases.Mayo Clin Proc. 1990; 65: 825-846Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar Gastrointestinal manometry18Camilleri M Disorders of gastrointestinal motility in neurologic diseases.Mayo Clin Proc. 1990; 65: 825-846Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 19Camilleri M Phillips SF Disorders of small intestinal motility.Gastroenterol Clin North Am. 1989 Jun; 18: 405-424PubMed Google Scholar showed periodic high-amplitude bursts of phasic pressure activity alternating with quiescence during the postprandial period. By scintigraphy, gastric emptying of solids was delayed; transit of both solid and liquid markers through the small bowel was rapid. In summary, this patient's diarrhea was due to abnormal motility of the small bowel in association with peripheral and autonomic neuropathy. A 27-year-old woman with a 6-month history of chronic intermittent diarrhea came to our institution. She had had insulin-dependent diabetes mellitus since the age of 6 years; retinopathy, autonomic and peripheral neuropathy, and nephropathy were diagnosed when she was 19 years old. She would have two to three bouts of profuse watery diarrhea associated with abdominal cramps and distention for 1 day and then no stools for 2 to 3 days. On physical examination, the patient's pupils did not react to light, but the accommodation response was normal. Patellar and ankle jerk responses were decreased. The abdomen was distended and tympanitic. Results of an anorectal examination and of proctoscopy were normal. The abnormal results of laboratory studies were as follows: mean corpuscular volume, 77.3 fl; albumin, 2.9 g/dl; and fecal fat, 39.2 g/24 h. No pancreatic calcification was noted on roentgenography; a barium examination showed a hypotonic, moderately dilated small intestine and coarsening of the mucosa. A biopsy specimen of the small bowel revealed subtotal villous atrophy and mononuclear cell infiltration of the lamina propria, findings compatible with celiac sprue. Small bowel aspirates were negative for Giardia and bacteria. Thus, this patient's chronic diarrhea was attributable to celiac sprue. Patients with diabetes in whom chronic diarrhea develops may have incidental diseases that occur in the general population. Several mechanisms (Table 1) that result in chronic diarrhea, however, are induced either by the autonomic dysfunction attributed to diabetes or by a disease more prevalent in patients with diabetes than in nondiabetic persons.Table 1Mechanisms of Chronic Diarrhea in Patients With DiabetesCauses associated with autonomic neuropathy Abnormal motility of the small bowel Bacterial overgrowth in the small bowel Abnormal colonic motility Anorectal dysfunction Exocrine pancreatic insufficiency Intestinal secretionFactors associated with diabetes mellitus Celiac sprue Bile acid catharsis Dietetic foodsIncidental causes Open table in a new tab Mechanisms Associated With Autonomic Neuropathy. Motility Disorders of the Small Bowel.—Intestinal motility is the end result of an intricately balanced series of control mechanisms: the electrical properties of the smooth muscle cell, the intrinsic nervous system, the extrinsic neural pathways (sympathetic and parasympathetic), the peptidergic transmitters, and the hormonal mediators.19Camilleri M Phillips SF Disorders of small intestinal motility.Gastroenterol Clin North Am. 1989 Jun; 18: 405-424PubMed Google Scholar Although the digestive tract can function fairly normally without extrinsic nerves, they modulate intrinsic neural reflexes and integrate activity in various regions. Thus, derangements of the extrinsic nerves at any level may result in abnormal gastrointestinal motility.18Camilleri M Disorders of gastrointestinal motility in neurologic diseases.Mayo Clin Proc. 1990; 65: 825-846Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 19Camilleri M Phillips SF Disorders of small intestinal motility.Gastroenterol Clin North Am. 1989 Jun; 18: 405-424PubMed Google Scholar Certain evidence supports a role of visceral autonomic neuropathy in diabetic diarrhea. First, diarrhea is commonly associated with symptoms of autonomic dysfunction in patients with diabetes,1Feldman M Schiller LR Disorders of gastrointestinal motility associated with diabetes mellitus.Ann Intern Med. 1983; 98: 378-384Crossref PubMed Scopus (619) Google Scholar, 20Dudl RJ Anderson DS Forsythe AB Ziegler MG O'Dorisio TM Treatment of diabetic diarrhea and orthostatic hypotension with somatostatin analogue SMS 201–995.Am J Med. 1987; 83: 584-588Abstract Full Text PDF PubMed Scopus (45) Google Scholar and it occurs in other conditions and situations that affect autonomic nervous function, such as vagotomy, sympathectomy, administration of ganglionic blocking agents, amyloidosis, and primary visceral neuropathies.18Camilleri M Disorders of gastrointestinal motility in neurologic diseases.Mayo Clin Proc. 1990; 65: 825-846Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 21French JM Hall G Parish DJ Smith WT Peripheral and autonomic nerve involvement in primary amyloidosis associated with uncontrollable diarrhoea and steatorrhoea.Am J Med. 1965; 39: 277-284Abstract Full Text PDF PubMed Scopus (53) Google Scholar Second, the density of unmyelinated axons is severely decreased, and the surviving axons in the abdominal vagus nerves of patients with diabetes are of small caliber.22Guy RJC Dawson JL Garrett JR Laws JW Thomas PK Sharma AK et al.Diabetic gastroparesis from autonomic neuropathy: surgical considerations and changes in vagus nerve morphology.J Neurol Neurosurg Psychiatry. 1984; 47: 686-691Crossref PubMed Scopus (98) Google Scholar Similarly, in patients with diabetic diarrhea, the sympathetic nervous system demonstrates two types of lesions: a hydropic neural change that produces giant neurons and dendritic swelling of postganglionic neurons in prevertebral and paravertebral ganglia23Hensley GT Soergel KH Neuropathologic findings in diabetic diarrhea.Arch Pathol. 1968; 85: 587-597PubMed Google Scholar, 24Duchen LW Anjorin A Watkins PJ Mackay JD Pathology of autonomic neuropathy in diabetes mellitus.Ann Intern Med. 1980; 92: 301-303Crossref PubMed Scopus (232) Google Scholar and decreased fiber density in the splanchnic nerves.25Low PA Walsh JC Huang CY McLeod JG The sympathetic nervous system in diabetic neuropathy: a clinical and pathological study.Brain. 1975; 98: 341-356Crossref PubMed Scopus (211) Google Scholar, 26Appenzeller O Richardson Jr, EP The sympathetic chain in patients with diabetic and alcoholic polyneuropathy.Neurology. 1966; 16: 1205-1209Crossref PubMed Google Scholar Third, although histologic studies of the myenteric plexus in the esophagus and stomach of humans with diabetes demonstrated no abnormalities,27Smith B Neuropathology of the oesophagus in diabetes mellitus.J Neurol Neurosurg Psychiatry. 1974; 37: 1151-1154Crossref PubMed Scopus (74) Google Scholar, 28Yoshida MM Schuffler MD Sumi M There are no morphologic abnormalities of the gastric wall or abdominal vagus in patients with diabetic gastroparesis [abstract].Gastroenterology. 1987; 92: 1705Google Scholar streptozotocin-treated rats have decreased sympathetic fibers in the myenteric plexus.29Lincoln J Bokor JT Crowe R Griffith SG Haven AJ Burnstock G Myenteric plexus in streptozotocin-treated rats: neurochemical and histochemical evidence for diabetic neuropathy in the gut.Gastroenterology. 1984; 86: 654-661PubMed Scopus (143) Google Scholar Patients with diabetic diarrhea have abnormal motility of the small bowel during fasting and postprandially; migrating motor complexes develop prematurely during the postprandial period.30Camilleri M Malagelada J-R Abnormal intestinal motility in diabetics with the gastroparesis syndrome.Eur J Clin Invest. 1984; 14: 420-427Crossref PubMed Scopus (295) Google Scholar In their study of 12 patients with non-insulin-dependent diabetes, autonomic neuropathy, and diarrhea, Dooley and associates31Dooley CP El Newihi HM Zeidler A Valenzuela JE Abnormalities of the migrating motor complex in diabetics with autonomic neuropathy and diarrhea.Scand J Gastroenterol. 1988; 23: 217-223Crossref PubMed Scopus (75) Google Scholar found that the duration or propagation velocity of the interdigestive migrating motor complexes was abnormal. Small intestinal transit in patients with diabetes has been studied by several groups; the results have been conflicting. One group of investigators32Keshavarzian A Iber FL Intestinal transit in insulin-requiring diabetics.Am J Gastroenterol. 1986; 81: 257-260PubMed Google Scholar found no significant difference in orocecal transit between control subjects and 25 unselected male patients with insulin-dependent diabetes. A third of these patients, however, had abnormal intestinal transit of the liquid test meal (four had rapid and four had delayed transit); one patient with diarrhea had rapid intestinal transit. Other investigators33Spengler U Stellaard F Ruckdeschel G Scheurlen C Kruis W Small intestinal transit, bacterial growth, and bowel habits in diabetes mellitus.Pancreas. 1989; 4: 65-70Crossref PubMed Scopus (32) Google Scholar measured duodenocecal transit in 19 patients with chronic diabetes: those without gastrointestinal symptoms had prolonged transit times in comparison with patients who had diabetes and constipation or diarrhea and healthy control subjects. Another group of investigators34Wegener M Börsch G Schaffstein J Luerweg C Leverkus F Gastrointestinal transit disorders in patients with insulin-treated diabetes mellitus.Dig Dis. 1990; 8: 23-36Crossref PubMed Scopus (126) Google Scholar found no significant overall difference in orocecal transit between 43 patients with insulin-dependent diabetes and gastrointestinal symptoms and 30 normal control subjects. The proportion of subjects with prolonged transit was substantially higher, however, in the group with diabetes. In another study, 12 patients with non-insulin-dependent diabetes and diarrhea had prolonged orocecal transit time in comparison with control subjects.31Dooley CP El Newihi HM Zeidler A Valenzuela JE Abnormalities of the migrating motor complex in diabetics with autonomic neuropathy and diarrhea.Scand J Gastroenterol. 1988; 23: 217-223Crossref PubMed Scopus (75) Google Scholar Overall, no convincing evidence supports abnormal transit in studies in which orocecal transit time was used. Nevertheless, two types of abnormal intestinal transit among patients with diabetes and altered bowel habits are conceivable—slow intestinal transit in some and rapid transit in others. Whether diarrhea develops in patients with slow small bowel transit because of bacterial overgrowth or another mechanism, such as intestinal secretion, is unclear. Systematic studies are needed; the availability of novel, separate scintigraphic measurement of gastric emptying and small bowel transit (see subsequent discussion) may provide further insights into this issue. Bacterial Overgrowth in the Small Bowel.—In conditions such as systemic sclerosis, the absence of interdigestive migrating motor complexes and delayed intestinal transit are associated with bacterial overgrowth in the small bowel35Vantrappen G Janssens J Hellemans J Ghoos Y The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine.J Clin Invest. 1977; 59: 1158-1166Crossref PubMed Scopus (674) Google Scholar, 36Scott LD Cahall DL Influence of the interdigestive myoelectric complex on enteric flora in the rat.Gastroenterology. 1982; 82: 737-745PubMed Scopus (94) Google Scholar that results in deconjugation of bile salts, fat malabsorption, and diarrhea. Increased concentrations of colonic bile acids induce colonic secretion. This sequence of events may pertain to patients with diabetes whose diarrhea frequently responds to broad-spectrum antibiotics.37Malins JM French JM Diabetic diarrhoea.Q J Med. 1957; 26: 467-480PubMed Google Scholar, 38Scarpello JHB Hague RV Cullen DR Sladen GE The 14C-glycocholate test in diabetic diarrhoea.BMJ. 1976; 2: 673-675Crossref PubMed Scopus (33) Google Scholar, 39Green PA Berge KG Sprague RG Control of diabetic diarrhea with antibiotic therapy.Diabetes. 1968; 17: 385-387PubMed Google Scholar This sequence, however, has rarely been proved, and steatorrhea and bacterial overgrowth have been reported infrequently in previous studies. Whalen and colleagues40Whalen GE Soergel KH Geenen JE Diabetic diarrhea: a clinical and pathophysiological study.Gastroenterology. 1969; 56: 1021-1032PubMed Scopus (86) Google Scholar found evidence of bacterial overgrowth in the upper part of the digestive tract in 1 of 13 patients with diabetes and diarrhea; however, it was verified only in the stomach of this patient, and a decrease in bacterial counts after 10 days of tetracycline therapy was not associated with diminished diarrhea. Goldstein and coworkers6Goldstein F Wirts CW Kowlessar OD Diabetic diarrhea and steatorrhea: microbiologic and clinical observations.Ann Intern Med. 1970; 72: 215-218Crossref PubMed Scopus (67) Google Scholar analyzed aerobic cultures of small bowel aspirates in seven patients with diabetic diarrhea; only two had more than 105 colony-forming units/ml. Dooley and associates31Dooley CP El Newihi HM Zeidler A Valenzuela JE Abnormalities of the migrating motor complex in diabetics with autonomic neuropathy and diarrhea.Scand J Gastroenterol. 1988; 23: 217-223Crossref PubMed Scopus (75) Google Scholar reported bacterial overgrowth in 3 of 12 patients (25%) with diabetes and diarrhea. Abnormal Colonic Motility.—Colonic motility has not been measured in patients with diabetes and diarrhea, but colonic dilatation has been reported in patients with nocturnal diarrhea associated with diabetes mellitus.41Paley RG Mitchell W Watkinson G Terminal colonic dilation following intractable diarrhea in a diabetic.Gastroenterology. 1961; 41: 401-407PubMed Google Scholar Some patients with diabetes mellitus have myoelectrical and motor abnormalities in the colon. Battle and colleagues42Battle WM Snape Jr, WJ Alavi A Cohen S Braunstein S Colonic dysfunction in diabetes mellitus.Gastroenterology. 1980; 79: 1217-1221PubMed Scopus (164) Google Scholar demonstrated that the colonic motor response to eating is absent or extremely delayed in patients with diabetes and constipation in comparison with normal subjects. More systematic studies of colonic motility are awaited, however, to evaluate the role of colonic dysmotility in the pathogenesis of diarrhea in patients with diabetes. Anorectal Dysfunction.—Anorectal dysfunction is relatively common in patients with diabetes assessed at tertiary referral centers. Fecal incontinence is experienced by approximately 20% of patients with chronic diabetes mellitus.1Feldman M Schiller LR Disorders of gastrointestinal motility associated with diabetes mellitus.Ann Intern Med. 1983; 98: 378-384Crossref PubMed Scopus (619) Google Scholar Patients with fecal incontinence frequently complain of “diarrhea,” even though stool volume or consistency may be unaltered. In an outpatient survey conducted in a Veterans Administration and university medical center,1Feldman M Schiller LR Disorders of gastrointestinal motility associated with diabetes mellitus.Ann Intern Med. 1983; 98: 378-384Crossref PubMed Scopus (619) Google Scholar almost half the patients with diabetes and diarrhea had incontinence; 10% of these patients had episodes of fecal incontinence without chronic diarrhea. Factors that maintain fecal continence are the high-pressure zone in the anal canal (internal and external sphincters); angulation at the junction between the rectum and the anal canal; anorectal sensory and reflex mechanisms; distensibility, tone, and capacity of the rectum; rectal motility and evacuation; and stool volume and consistency. Wald and Tunuguntla43Wald A Tunuguntla AK Anorectal sensorimotor dysfunction in fecal incontinence and diabetes mellitus: modification with biofeedback therapy.N Engl J Med. 1984; 310: 1282-1287Crossref PubMed Scopus (234) Google Scholar compared anorectal sensation in 14 patients with diabetes and incontinence with three patient control groups: patients with diabetes and continence, nondiabetic patients, and nondi
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