Diabetes mellitus
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).
Progressive systemic sclerosis
The peak incidence of progressive systemic sclerosis is in the fifth and sixth decades. Gastrointestinal involvement occurs in a majority, affecting multiple regions of the gut, although the correlation between histological involvement and symptoms may be weak.71 Oesophageal dysmotility has a prevalence of about 80%, with diminished amplitude of pressure waves and sometimes a lack of peristalsis in the distal (smooth muscle) oesophagus, leading to impaired acid clearance and severe reflux disease. LOS resting pressure also tends to be extremely low. Furthermore, the stomach, small and large intestines, and anorectum may be involved, with clinical manifestations of gastroparesis, pseudo‐obstruction, bacterial overgrowth (sometimes associated with small‐intestinal diverticula), malnutrition, and constipation or faecal incontinence. While smooth muscle atrophy and fibrosis underlie some of these disturbances,72 inhibition of cholinergic transmission in the enteric nervous system by antibodies to M3 muscarinic receptors may be important in the pathogenesis. Similar effects on gastrointestinal motility may be seen in other connective tissue disorders and amyloidosis. PPIs are effective in the treatment of GORD, although high‐dose therapy may be needed. The role of surgery in refractory reflux symptoms is controversial, but good results can be achieved.73 Prokinetic drugs have a role when gastrointestinal transit is delayed.
Functional disorders
Functional gastrointestinal diseases are often overlooked in the elderly.74 They are characterised by recurrent or persistent symptoms referable to the gut, occurring in the absence of demonstrable organic disease. This group of disorders includes functional dyspepsia (upper abdominal pain, bloating, or nausea) and irritable bowel syndrome (IBS) (abdominal discomfort, which may be relieved by defecation, associated with abnormal bowel habit), as well as other syndromes related to the oesophagus, anorectum, and biliary tract, defined most recently by the Rome IV criteria.75
The prevalence of IBS appears to be less in the elderly than the middle‐aged in the United States; nevertheless, 10–15% of people over 70 had IBS based on a large community survey,76 so the condition is still common in the older age group. At all ages, the prevalence is greater in women than men. Somewhat surprisingly, the incidence, as opposed to prevalence, of IBS has been reported to increase with age, in at least one US population.77 This may potentially reflect an increase in healthcare‐seeking behaviour in the elderly, although no information regarding consulting behaviour in IBS is available specifically for this age group. As in younger patients with functional gastrointestinal disorders, it is common for different symptoms to be gained or lost over time so that the overall prevalence remains relatively constant.78 In the general population, around 10% of functional gut disorders follow a bout of infectious gastroenteritis, but there is evidence to suggest that the elderly are less prone to developing chronic post‐infective symptoms than the young. In contrast to IBS, there is little information regarding the prevalence of functional dyspepsia in older populations.
While, as discussed, visceral sensitivity seems to decline in healthy ageing, patients with functional dyspepsia or IBS have, as a group, increased sensitivity to gastric and rectal distension. Nevertheless, chronic gastrointestinal symptoms consistent with IBS are common in the elderly, although not markedly greater than in the young, with the possible exception of constipation. Visceral sensitivity has not been studied in the elderly with gut symptoms; nor has tolerance to visceral pain (the lowest level of stimulation at which a subject withdraws or asks for the stimulus to cease).