Diabetes Chronic Complications - part 8 pdf

ogy of diabetic gut symptoms. Recent functional imaging studies have looked at brain structure and function in patients with type I diabetes. It is known that acute hypoglycaemia has an acute detrimental effect on brain function, 38 although a recent study suggests that recurrent exposure to severe hypoglycaemia in young people with type I diabetes mellitus has no detrimental effects on brain structure or function. 39 Chronic hyperglycaemia (inferred by the presence of diabetic retino- pathy), however, does appear to have an effect on brain structure and function, in that it is associated with small focal white matter changes in the basal ganglia and significant cognitive disadvantage. 39 8.4 Oesophageal Complications Oesophageal abnormalities in patients with diabetes are common, but what is clear from studies is that, despite the high prevalence of disorders of oesophageal motility in diabetes, there is not a clear increase in oesophageal symptoms. It is possible that this is due to a possible visceral afferent neuropathy in these patients. Motor abnormalities Oesophageal manometric and scintigraphic studies show that oesophageal transit is delayed in 40–60 per cent of diabetic patients, with a decrease in amplitude and number of peristaltic waves and an increase in simultaneous and non-propagated waves. 40 Rarely, marked abnormalities of motility, such as diffuse oesophageal spasm, are seen in diabetic patients. Additionally, lower oesophageal sphincter pressure is reduced compared with controls, suggesting a predisposition to gastro- oesophageal reflux. 41 It has been hypothesized that these effects are secondary to vagal neuropathy, since the vagus is the major efferent supply to the oesophagus. In support of this there is demyelination and loss of Schwann cells in the parasympathetic fibres of long standing type I diabetic patients. 42 Sensory abnormalities Decreased oesophageal sensory perception has been described in diabetic patients and may explain why, despite the high prevalence of motor dysfunction, this group remain relatively asymptomatic. Conversely, Rayner et al. 43 have demonstrated increased cortical evoked perception to low-pressure balloon distension in the oesophagus during acute hyperglycaemia, suggesting that under these conditions there is either increased peripheral perception or increased central processing. In essence, chronicity of diabetes may result in impairment of sensation, whilst acute hyperglycaemia enhances sensory awareness. OESOPHAGEAL COMPLICATIONS 173 Gastro-oesophageal reflux Perhaps unsurprisingly, given the prevalence of ineffective oesophageal peristalsis and decreased lower oesophageal pressure, gastro-oesophageal reflux (GORD) is more common in diabetic patients than matched controls. Even in asymptomatic patients, studies suggest that up to 40 per cent of diabetic patients have significant GORD, 44 although there is no evidence that the prevalence of oesophagitis is higher. Dysphagia Dysphagia describes the inability to swallow a solid or liquid bolus and is associated with a feeling of the bolus becoming ‘stuck’ before reaching the stomach. It is often described as being retrosternal, although localization by symptoms is notoriously imprecise. It is more common for dysphagia to be secondary to a mechanical obstruction such as peptic stricture or tumour than to be secondary to oesophageal dysmotility, and investigations should be tailored to rule out these organic causes before any functional studies are pursued. There is no evidence for an increase in oesophageal malignancy in diabetics per se, but there should be a low threshold for endoscopic investigation in the presence of dysphagia, especially in type II diabetics who are obese and more theoretically at risk of malignancy. Candidal oesophagitis This condition is not uncommon in diabetic patients and should be suspected in any diabetic patient who presents with painful swallowing (odynophagia). When severe it can present as dysphagia and in these circumstances prompt endoscopic evaluation is required. Endoscopic appearances are diagnostic with fluffy white exudates on the oesophageal mucosa. If there is doubt, brushings can be taken at the time of endoscopy, with microscopy revealing the fungal hyphae. Treatment with oral antifungals will often have a dramatic effect on symptoms and can be commenced empirically prior to endoscopy if there is any delay. Previously this condition was diagnosed frequently on double contrast barium swallow (which also gave a subjective view of motility), but endoscopy would now be the investigation of choice. Psychological effects The prevalence of anxiety and depression in diabetic patients with oesophageal contraction abnormailities (87 per cent) is significantly greater than in those 174 DIABETES AND THE GASTROINTESTINAL SYSTEM without (21 per cent). 45 This suggests that there may be a psychiatric association with oesophageal motor abnormalities in at least some diabetic patients. It has been postulated that this may arise from abnormalities of arousal and secondary activation of autonomic outflow from the higher centres. Investigations Oesophageal symptoms include heartburn, acid regurgitation, odynophagia and dysphagia. In a diabetic population there will be a higher prevalence of GORD and in the setting of severe heartburn an early endoscopy is warranted to confirm the presence or absence of oesophagitis or Barrett’s oesophagus (pre-malignant dysplastic change in the distal oesophagus related to chronic acid exposure). In the absence of inflammation or in the setting of continuing symptoms despite adequate acid suppression, oesophageal manometry and ambulatory 24 h pH studies should be considered. In addition to defining the amount of acid refluxed into the oesophagus, ambulatory pH studies reveal whether or not symptoms coincide with acid exposure, implying a significant relationship between observed acid exposure and symptoms. Odynophagia may be present in the absence of any mucosal inflammation, but its presence in a diabetic patient suggests possible candidiasis and the patient should be referred for endoscopy with empirical therapy if there is a delay. Dysphagia, as with non-diabetic patients, requires urgent investigation with endoscopy to rule out a mechanical cause. Some gastroenterologists will perform a contrast swallow prior to this to define the anatomy first. In the absence of mechanical blockage further investigations such as manometry or scintigraphy will define motility abnormalities. However, since these investigations are invasive and not widely available, it is reasonable to consider empirical therapy (see below) without testing. Treatment Symptoms of heartburn should be treated conventionally with acid suppression. Odynophagia secondary to candidiasis is treated with a one week course of an antifungal such as Nystatin 1–3 million units 6 hourly or fluconazole 100 mg daily. Treating motility disturbances is more problematic. There is limited evidence of efficacy of prokinetic medication on oesophageal symptoms in diabetics. Cisapride, a 5HT 4 agonist which has now been withdrawn for the market due to its potential cardiotoxicity, has acute effects on oesophageal transit but does not appear to improve symptoms with chronic use. 46 Domperidone has been shown to increase oesophageal emptying in those with delayed transit, but has a variable effect on symptoms. There is also little evidence for the use of metoclopramide or erythromycin in this setting. OESOPHAGEAL COMPLICATIONS 175 [...]... and low-lipid diets, and as with other complications advised to keep as good a glycaemic control as possible The cumulative incidence of chronic non-alcoholic liver disease is significantly higher in patients with diabetes9 6 (Figure 8. 4) 1.40% Diabetes Cumulative incidence 1.20% 1.00% 0 .80 % No diabetes 0.60% 0.40% 0.20% 0.00% 0 2 4 6 8 Follow-up (years) 10 12 14 Figure 8. 4 The cumulative risk of chronic. .. Ann Intern Med 19 58; 48: 797 81 2 3 Bytzer P, Talley NJ, Leemon M, Young LJ, Jones MP, Horowitz M Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults Arch Intern Med 2001; 161(16): 1 989 –1996 4 Schvarcz E, Palmer M, Ingberg CM, Aman J, Berne C Increased prevalence of upper gastrointestinal symptoms in long-term type 1 diabetes mellitus... Follow-up (years) 10 12 14 Figure 8. 4 The cumulative risk of chronic non-alcoholic disease including cirrhosis among veteran patients hospitalized between 1 985 and 1990 and a follow-up period that ended in 2002 Chronic non-alcoholic liver disease was significantly higher in patients with diabetes (p < 0.0001) Reproduced from El-Serag et al., Gastroenterology 2004; 126: 463 with kind permission from... patient group .81 8. 9 Pancreatic The pancreas obviously has a central role in the pathophysiology of diabetes Hence it is no surprise that other pancreatic diseases can lead to a diabetic state, in particular acute and chronic pancreatitis The former probably initially via increased levels of glucagon and epinephrine rather than a decrease in insulin production In the chronic situation, chronic fibrosis... pressures and action potentials Am J Dig Dis 1971; 16(7): 6 28 634 11 Whalen GE, Soergel KH, Geenen JE Diabetic diarrhea A clinical and pathophysiological study Gastroenterology 1969; 56(6): 1021–1032 12 Clouse RE, Lustman PJ Gastrointestinal symptoms in diabetic patients: lack of association with neuropathy Am J Gastroenterol 1 989 ; 84 (8) : 86 8 87 2 13 de Boer SY, Masclee AA, Lamers CB Effect of hyperglycemia... but there is at this time little other data to suggest their use as first-line therapy Coeliac disease As well as the effect of diabetes itself on the small intestine, adult patients with type I diabetes have a six times greater prevalence of coeliac disease, and in 186 DIABETES AND THE GASTROINTESTINAL SYSTEM children with type I diabetes this prevalence is 15 times greater, suggesting a genetic linkage...SMALL INTESTINE 183 increase stomach contractility in animal models, and may form a putative target for future drug innovation. 68, 69 8. 6 Small Intestine Abnormalities in small intestinal motility have been found to be present in up to 80 per cent of patients with long-standing diabetes. 31 The commonest abnormality is small intestinal transit delay... 1): A232 18 Talley NJ, Young L, Bytzer P, Hammer J, Leemon M, Jones M, Horowitz M Impact of chronic gastrointestinal symptoms in diabetes mellitus on health-related quality of life Am J Gastroenterol 2001; 96(1): 71–76 19 Jermendy G, Toth L, Voros P, Koltai MZ, Pogatsa G Cardiac autonomic neuropathy and QT interval length A follow-up study in diabetic patients Acta Cardiol 1991; 46(2): 189 –200 20 Vinik... Invest 2000; 106(3): 373– 384 30 Buysschaert M, Donckier J, Dive A, Ketelslegers JM, Lambert AE Gastric acid and pancreatic polypeptide responses to sham feeding are impaired in diabetic subjects with autonomic neuropathy Diabetes 1 985 ; 34(11): 1 181 –1 185 31 Camilleri M and Malagelada JR Abnormal intestinal motility in diabetics with the gastroparesis syndrome Eur J Clin Invest 1 984 ; 14(6): 420–427 32 Battle... non-diabetics patients Initially lifestyle advice can be helpful, including an increase in dietary fibre in the diet and taking adequate oral fluid each day The use of laxatives can then be in the form of an osmotic agent (especially if transit is slow) or stimulant laxatives for occasional on-demand use There is no evidence supporting the use of one type of laxative over another, but a trial of 188 DIABETES . processing. In essence, chronicity of diabetes may result in impairment of sensation, whilst acute hyperglycaemia enhances sensory awareness. OESOPHAGEAL COMPLICATIONS 173 Gastro-oesophageal reflux Perhaps. the basal ganglia and significant cognitive disadvantage. 39 8. 4 Oesophageal Complications Oesophageal abnormalities in patients with diabetes are common, but what is clear from studies is that,. young people with type I diabetes mellitus has no detrimental effects on brain structure or function. 39 Chronic hyperglycaemia (inferred by the presence of diabetic retino- pathy), however, does