Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 456

Diabetes mellitus, particularly type 2 diabetes, is increasing dramatically in prevalence worldwide and frequently occurs in older individuals. Disordered motor function involving all segments of the gastrointestinal tract is common in longstanding diabetes, and there is a high prevalence of gut symptoms,⁶⁶ although little information specific to elderly patients with diabetes.⁶⁷ Although both disordered motility and gut sensation have been attributed to irreversible autonomic neuropathy, it is now recognised that acute changes in the blood glucose concentration have a significant influence on gut function.⁶⁸ Studies in a limited number of patients with gastroparesis refractory to medical treatment have revealed loss of both interstitial cells of Cajal, which are responsible for generating the electrical rhythm of the stomach, and myenteric neurons, while staining for inhibitory neurotransmitters is reduced, and a few have evidence of gastric myopathy.⁶⁶

In the oesophagus, manometric abnormalities observed in diabetes include a reduction in the amplitude of pressure waves, abnormal wave forms, and failure of peristalsis, all of which are associated with delayed oesophageal transit. LOS pressure may be diminished, and the prevalence of GORD is increased.

Up to 50% of patients with longstanding diabetes and poor blood glucose control attending tertiary referral clinics have delayed gastric emptying for solids, liquids, or both. By contrast, gastroparesis appears to be much less common in uncomplicated patients with type 2 diabetes treated with diet or metformin alone.⁶⁹ Motor correlates of abnormally slow gastric emptying include diminished antral motility and impaired coordination of antroduodenal pressure wave sequences, together with reduced fundic tone. Both the delay in gastric emptying and the underlying motor mechanisms are more marked during acute hyperglycaemia when compared to euglycemia. Disordered gastric emptying potentially contributes to upper gut symptoms, can impair absorption of nutrients and orally administered medications, and may result in, as well as arise from, poor glycaemic control. While a delay in gastric emptying may actually reduce the postprandial blood glucose profile in non‐insulin‐requiring type 2 patients due to slower release of carbohydrate to the small intestine, it also has the potential to result in a mismatch between the absorption of glucose and the onset of insulin action in patients receiving exogenous insulin. Patients with upper gut symptoms referable to the stomach should be investigated with endoscopy to exclude mucosal lesions or obstruction, and consideration can then be given to evaluating the rate of gastric emptying, ideally with scintigraphy. Diabetic gastroparesis is usually treated with a prokinetic drug, such as metoclopramide, domperidone, or erythromycin (a motilin agonist). The previous agent of choice, cisapride, was withdrawn in many markets due to a risk of cardiac arrhythmia. The role of pyloric injections of botulinum toxin in refractory patients is unclear; a recent retrospective analysis suggested that older patients (50 years or greater) are less likely to benefit than the young,⁷⁰ while two trials involving this therapy did not demonstrate a benefit compared to sham injections. Similarly, the benefit of implantable gastric electrical stimulators has yet to be adequately demonstrated in controlled trials, and no subgroup analyses of outcomes specifically address their efficacy in older patients.⁶⁶

Small‐intestinal motility is also frequently abnormal in diabetes, and up to 80% of patients with diabetic gastroparesis have abnormal small‐intestinal motility.⁶⁶ During fasting, the duration of the phases of the migrating motor complex is reduced, while postprandially, bursts of non‐propagated pressure waves may occur, together with disordered flow patterns of chyme. Small‐bowel transit is widely variable in patients with diabetes, and its relationship to gastrointestinal symptoms and glycaemic control remains to be clarified. Diarrhoea and constipation are common in diabetes; small‐bowel bacterial overgrowth, coeliac disease, and pancreatic exocrine insufficiency should be specifically excluded when patients with diabetes present with diarrhoea. Loperamide and clonidine (an α‐adrenergic agonist) may be of benefit when no specific cause for diarrhoea is uncovered, although older patients may be particularly susceptible to adverse effects (constipation, urinary retention, and glaucoma for loperamide; hypotension, bradycardia, sedation, and dry mouth for clonidine).