Diabetes
Pathogenesis and Clinical Manifestations Several population-based studies suggest an increased prevalence of upper and lower gastrointestinal symptoms among patients with diabetes, although epidemiologic data are inconsistent.
130,
131,
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133 Gastrointestinal symptoms in diabetics may be due to gastroparesis, altered intestinal motility/function, loss of sphincteric control, infection, or associated autoimmune disorders such as celiac disease and atrophic gastritis.
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Gastroparesis occurs in both type 1 and 2 diabetics but seems to be particularly prevalent in patients with long-standing type 1 diabetes.
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135 Symptoms of gastroparesis include nausea, vomiting, epigastric fullness, bloating, and abdominal discomfort. Bezoar formation may sometimes ensue, exacerbating the symptoms of gastroparesis or producing a palpable mass, ulceration, perforation, or small bowel obstruction
131,
135 (
Fig. 8-8). The cause of gastric dysmotility appears to be multifactorial with postulated mechanisms including autonomic dysfunction, impaired glycemic control (hyperglycemia disrupts antral motor complexes, delaying gastric emptying), hormonal imbalances (elevations in postprandial glucagon delays gastric emptying), loss of interstitial cells of Cajal, microangiopathy, and psychological distress.
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135
Diarrhea affects 4% to 22% of diabetics with up to 75% also having steatorrhea.
131,
134 Occasionally this is severe and intractable.
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137 Segments of bowel may undergo dilatation with secondary bacterial overgrowth, which may cause or exacerbate diarrhea.
138 Bacterial overgrowth is present in up to 43% of diabetics with chronic diarrhea.
139 As with gastroparesis the etiology of diabetic diarrhea appears to be multifactorial. A role of visceral autonomic neuropathy is supported by morphologic changes in both the parasympathetic and sympathetic nervous systems in diabetics (see below) and by the occurrence of diarrhea in other conditions affecting the autonomic nervous system including vagotomy.
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142 Other postulated mechanisms include pancreatic insufficiency, small bowel bacterial overgrowth, infections, drugs (e.g., metformin) or associated celiac disease or hyperthyroidism,
131,
134,
139,
143 and a decrease in interstitial cells of Cajal.
In the colon, dysmotility may result in severe constipation and even stercoral ulceration.
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145 Autonomic neuropathy is likely a major factor, but a deficiency of ICC
146 and decreased production of substance P (a stimulant of colonic motility and fluid secretion)
147 may also contribute. Sometimes, patients develop dysfunction of anal sphincters, resulting in fecal incontinence, often in association with diarrhea.
131 They may also develop severe, unexplained abdominal pain (diabetic radiculopathy).
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Although esophageal abnormalities are commonly demonstrated with manometry, esophageal symptoms are uncommon. Diabetics are known to be
susceptible to infections in the gut, especially esophageal candidiasis,
148 and in ketoacidosis there may be severe upper gastrointestinal bleeding from gastric erosions, presumably of the stress type. There is an increased incidence of atrophic gastritis with pernicious anemia and celiac sprue among type 1 diabetics. These cases are associated with significant titers of circulating parietal cell antibodies and often thyroid antibodies.
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152 The prevalence of autoimmune gastritis in type 1 diabetics is three- to fivefold higher than that of the general population. Celiac disease is reported in up to 5% to 10% of patients with type 1 diabetes
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154 compared to 0.55% to 1% in the general population in Europe and North America. In most cases the diagnosis of diabetes precedes that of celiac disease. One study found the prevalence of symptomatic celiac disease at diagnosis to be 0.7%, but this increased to 10% after 5 years of annual screening.
154 Many centers advocate routine annual screening for celiac disease in type 1 diabetics with a minimum of 2 years suggested.
154 (Celiac disease is further discussed in
Chapter 20.)
Most studies support an association between diabetes and colorectal carcinoma. A meta-analysis of 15 studies including over 2,500,000 patients confirmed this association, demonstrating a relative risk of 1.3 (95% CI = 1.2-1.4) in diabetic patients compared to nondiabetics. This relative risk was maintained when analysis was restricted to the seven studies, which controlled for body mass index and physical inactivity.
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Pathology Surgical pathologists encountering material from the gastrointestinal tract of diabetics are most likely to see esophageal candidiasis, the mucosal lesion of celiac disease, or autoimmune gastritis (see
Chapters 14 and
20). Other findings include erosive gastritis in diabetic ketoacidosis, SIBO, and stercoral ulceration. Resection specimens may show features of autonomic neuropathy, which are frequently patchy and may involve both the vagal and the sympathetic nervous systems. Such changes include a marked decrease in the density of unmyelinated axons, axonal degeneration, thickening of the basement membrane of Schwann cells, decreased caliber of vagal nerves, and decreased fiber density of sympathetic nerves.
131,
156 Myenteric ganglia may also show degenerative changes characterized by distended neurons; enlarged, club-shaped neuronal processes; and accompanying chronic inflammation. Secondary degenerative changes in the muscularis propria may be found.
157 A marked decrease in interstitial cells of Cajal has been reported both in the stomach and the colon of diabetics
146,
158,
159 as well as animal models of diabetic gastroparesis
143 and may be related to lack of Heme oxygenase 1.
159a Patients with diabetes are also at increased risk of atherosclerosis and its complications, such as acute mesenteric arterial ischemia. Microangiopathy is frequently mentioned in the literature, but it has not been conclusively demonstrated in the gut.
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