Diabetes and the gut: Part 2

Complications D C Colin-Jones MD FRCP Consu Ita n t Physician Queen Alexandra Hospital, Cosham, Portsmouth, Hants, PO6 3LY

In the first article in this two-part series, I looked at the diseases associated with diabetes, particularly disease of the ex- ocrine pancreas and cancer. Not only associations of diabetes, however, but also diabetic complications may affect the gastrointestinal tract.

Acute Diabetic ketoacidosis

Nausea and vomiting frequently are early symptoms of impending diabetic ketoacidosis. This is particlarly troublesome to the patient, who feels unable to eat or drink properly; this ag- gravates the tendency to dehydration. The poor intake of food often suggests to the patient incorrectly that he/she should not take so much insulin; thus a twist in the spiral towards ketoacidosis is established. The mechanism is unknown. It is thought sometimes to be associated with gastric atony - many patients with severe ill- nesses will experience delay in gastric emp- tying and it may be this rather than a direct consequence of the diabetes which causes the nausea and vomiting. Early in the development of hyperglycaemia and before full ketoacidosis has developed, the patient must try to avoid dehydration and control the blood sugar carefully, with ad- ditional short-acting insulin if needed. Because of the usual delay in gastric emp- tying, small frequent drinks are essential and much better than irregular large drinks.

Occasionally in severe ketoacidosis, an acute abdomen is mimicked by the diabetes. The patient complains of severe pain and there is often generalised tenderness, with some abdominal guar- ding and rigidity. Bowel sounds are quiet and infrequent but are usually present. The patient requires careful observation in hospital and early correction of the diabetic ketoacidosis. The patient should under no circumstances be operated upon during this phase, unless there is demonstrably an abnormality on in- vestigation, such as air under the diaphragm indicating a perforation. It is dangerous to operate during ketoacidosis. The patient’s symptoms will remit as his metabolic control is restored.

Chronic For convenience, most chronic condi-

tions will be dealt with by organ.

Oesophagus (a) Oesophageal motility: It has been established that there is a disorder of

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oesophageal motility in long-standing diabetics. This seems to be increased in frequency and severity in patients who have an autonomic neuropathy. For- tunately, however, it rarely causes symp- toms and it is usually a finding on a barium meal, which is done for reasons other than dysphagia or chest pain. The motility disorder is that of abnormal ter- tiary contractions, and a tendency for dif- fuse spasm to occur. If this is found, the patient should be investigated for an autonomic neuropathy. Treatment of the spasm, if needed, is with antispasmodics such as isosorbide or nifedipine, instituted after full investigation.

(b) Candidiasis: Diabetics, as is well known, are particularly susceptible to can- didiasis. The oesophagus is frequently af- fected and the patient who has been ill and requires antibiotics is especially at risk. The condition may take two forms. The more common, acute form is associated with severe dysphagia and retrosternal discomfort on swallowing. It comes on swiftly after the illness or antibiotics and may be so painful that the patient is quite unable to swallow anything. Response to frequently-administered nystatin suspen- sion or amphotericin lozenges is usually dramatic, the patient feeling very much better within 48 hours. The other form is chronic and seems to cause minor dyspep- tic symptoms. It is increasingly frequent- ly recognised at endoscopy, when cytology and culture of the lower oesophagus can be undertaken. It is usually treated, although chronic candidiasis of the lower oesophagus only causes minor symptoms - if indeed any.

Stomach (a) Gastric secretion: In the vast majori-

ty of patients with diabetes, gastric secre- tion and gastric emptying are normal, but in the older diabetic there seems to be an increased frequency of hypochlorhydria and an increased frequency of antibodies to parietal cells and intrinsic factor. This means that diabetics are at a greater-than- average risk of developing pernicious anaemia, but the frequency of this is still low. It has been claimed that diabetics are at increased risk from peptic ulceration, but this is very doubtful and more com- prehensive studies are needed.

(b) Gastroparesis: Gastroparesis is one of the more important and difficult com- plications of diabetes to treat. There is great variation in the rate of gastric emp- tying in normal and diabetic individuals,

both within the patient from day to day and also in response to different foods. For example, an attack of migraine may cause a dramatic but temporary delay in gastric emptying, and fatty foods or meals that are too salty or too sweet will cause a physiological reduction in the rate of gastric emptying. In long-standing insulin- dependent diabetics, especially those with an autonomic neuropathy, persistent delay in gastric emptying seems to occur. A rather atonic stomach with excessive fluid content may be demonstrated on a barium meal (Figure. opposite). Sometimes this may increase substantially, causing pain and vomiting.

The prognosis from gastroparesis is very poor - in one study (Zitomer et al, 1968), one-third of 35 patients had died within 3 years of the diagnosis being made, but this was chiefly from vascular disease rather than the gastric problem - the gastroparesis was a sign of the severity of the diabetes. It is difficult to treat. The poor motility is thought to be due to denervation and should be responsive, in theory, to cholinergic drugs such as bethanechol, metoclopramide and domperidone. All these have been tried with reported, though variable, success. The author has had success using metoclopramide and bethanechol. The drugs are given in liquid form before meals and the patient encouraged to drink plenty of fluids with the meal, as the li- quid phase of gastric emptying is less dependent upon motility than is the solid phase. Fatty, salty, sweet and rich meals should be avoided, as these cause a physiological slowing of gastric emptying.

It is important to investigate carefully. By definition, there is no mucosal abnor- mality (other than sometimes gastritis due to stasis). Particular care must be taken to ensure this is not an organic pyloric stenosis due to previous ulceration or car- cinoma. A barium meal and, in most cases, an endoscopy should be done to ex- clude pyloric canal disease. Gastric surgery is seldom helpful; treatment must be medical.

Colon (a) Constipation: Constipation has been

reported as occurring more commonly in diabetics. For the majority of diabetics, this is a result of inadequate fibre in the diet and chronic dehydration. Mild and sustained dehydration is underrated as a cause of persistent constipation, so poor diabetic control with glucosuria, or the

Practical DIABETES MarchIApril 1986 Vol 3 No 2

mBeu€ewm Diabetes and the gut, part 2. Complications

Figure. Barium follow-through showing delay in gastric emptying and coeliac disease in a diabetic of 1.5 years sfanding. There is residual food (white arrow) in stomach despite fasting. Black arrow shows oedema of jejunal mucosa which, on investigation, proved to be due to coeliac disease

diuretic action of caffeine in excessive cups of tea or coffee, may well aggravate a tendency to constipation - one which can be corrected readily. More severe cases of constipation are usually associated with a n autonomic neuropathy, when a megacolon may be demonstrated on a barium enema. Although some patients need regular enemas to achieve defaeca- tion, most can be controlled with bulking agents, magnesium salts (if no renal failure) and stimulant purgatives.

(b) Diabetic diarrhoea: Diarrhoea is associated with long-standing diabetes and occurs more commonly in diabetics than in a control population (7% v 2%). The vast majority of patients presenting with this diarrhoea have an autonomic neuropathy and a retinopathy. About one- third of patients also have gastroparesis. A patient may present with watery diar- rhoea, alternating initially with constipa- tion but progressively becoming more

frequent and more watery. There is seldom pain, but urgency of defaecation is com- mon. Characteristically, the patient ex- periences nocturnal diarrhoea, often with soiling or even incontinence. There is usually some degree of weight-loss and malaise. Investigation with barium enema may show disordered motility but usual- ly barium enema is normal and a barium follow-through unhelpful.

(c) Diabetic steatorrhoea: The diabetic with diarrhoea usually has watery stools, whereas the patient with steatorrhoea will have a bulky, offensive stool, sometimes watery but much more frequently rather clay-coloured and putty-like in nature. it is very important to remember that diabetes is associated with coeliac disease. Any patient presenting with malabsorp- tion should have a duodenal/jejunal biop- sy undertaken. If there is gastroparesis, this should be done by means of an en- doscope, because of the very slow transit

of a Crosby capsule through the poorly- emptying stomach.

lnvestigafion of diabetic diarrhoea/stea torrhoea

The first requirement is to separate the patient who has simple diarrhoea from the one with diarrhoea due to malabsorption. A faecal fat test and possibly a vitamin A absorption test (which will detect a mucosal abnormality of absorption) will separate the two groups. The patient with steatorrhoea may well have chronic pan- creatitis, which will need to be diagnosed by means of a Lundh test meal (usually) or a non-invasive test of pancreatic func- tion, such as a p-aminobenzoic acid (PABA) absorption test. An ERCP gives information on the structure of the pan- creas (see previous article). Coeliac disease has already been mentioned and it is essential to take a small bowel biopsy. If the pancreas is exonerated and the patient does not have coeliac disease, the diagnosis is likely to be diabetic steatorrhoea.

The cause of diabetic steatorrhoea is unknown. The most plausible explanation is that there is bacterial overgrowth in the gut, possibly due to the delay in gastric emptying (one-third have gastroparesis), allowing colonisation, or possibly due to poor immune mechanisms. There is an altered motility of the whole gut, which may be responsible for the problem direct- ly or possibly by failing to clear bacteria from the lumen. Another mechanism may be the result of bile salt malabsorption, reducing the bile salt pool. Detailed in- vestigation needs to be done, looking at the absorption of vitamin Blz and serum levels of iron and folate. Checks should be made on the serum albumin and potassium. Urinary indicans may provide evidence of bacterial colonisation of the small gut, and a hydrogen breath test or 14C labelled bile salt test may provide in- formation on possible bacterial activity in the small gut. The diagnosis of diabetic diarrhoea is largely by exclusion.

Treatment (a) Diarrhoea: Simple anti-diarrhoea1

remedies can be tried first, such as codeine phosphate, Lomotil or loperamide (Im- odium). These are often of some help, although they seldom return the patient’s bowel action to normal. There has been increasing interest in the bile salt malab- sorption in these patients. It is postulated that an abnormal absorption of bile salts in the ileum, possibly due to bacterial growth, may cause loss of bile salts into the colon, where the detergent action of the bile on the colonic mucosa causes the watery diarrhoea. Abnormality of the enterohepatic recycling of bile salts has been demonstrated in a number of con- ditions. Although it has never been demonstrated formally in diabetes, it is certainly worth trying cholestyramine as a binding agent for bile salts, to reduce

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their irritant effect on the colonic epithelium. Half to one sachet of Questran (a palatable form o f cholestyramine) with each meal is often strikingly beneficial. A course of an- tibiotics might be tried, although it is not usually as helpful as in steatorrhoea. Metronidazole is probably the antibiotic of choice.

(b) Diabetic steatorrhoea: Very full in- vestigation of the cause of steatorrhoea in the diabetic patient is needed and treat- ment must be started appropriately. If the patient has diabetic steatorrhoea - which is probably caused by bacterial colonisa- tion of the small gut - antibiotics should be tried first. A course of metronidazole, or if that is unsuccessful metronidazole plus amoxycillin by mouth, given for, say, 10 days, will often dramatically improve the situation, particularly if the patient has his gastroparesis (if present) corrected. If the steatorrhoea continues, then the substitution of medium-chain triglycerides (MCT) for the more naturally occurring longer-chain triglycerides and fatty acids will often reduce strikingly the bulk of the stool and aid absorption, as the MCTs do not require digestion by lipase or solubilisation by bile salts for absorption. Unfortunately, cholestyramine often ag- gravates the steatorrhoea but, if no im- provements occur with MCT dieting, a small dose, such as half a sachet of Questran BD or TDS should be tried. In both these situations, very careful control of the diabetes is important. Replacement of any deficiencies is of course essential, eg vitamin Blz folate, zinc, potassium.

Diabetic radiculopathy Very rarely, diabetic radiculopathy may

affect the thoracic and upper lumbar nerve roots, causing excruciating ab- dominal pain. There is alteration of sen- sation of the abdominal wall and loss of abdominal reflexes. These usually give the necessary clinical clue as to the basis of the severe and excruciating pain. One side is usually more affected than the other. Careful control of the diabetes is needed. Remission usually occurs over a number of months.

Complications of oral hypoglycaemic drugs

Biguanides frequently cause anorexia, nausea and occasionally abdominal pain and vomiting. This is particularly true of metformin, if high doses are used, and the dose should be reduced if at all possible. Sulphonylureas also cause nausea sometimes and in particular a bitter taste in the mouth. An explanation to the pa- tient is sufficient to reassure. Metformin is said to increase the frequency of vitamin BI2 absorption, although the mechanism is not understood.

The Liver (a) Fatty Liver: The liver may be af-

fected by diabetes most commonly in pa-

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Diabetes and the gut, part 2. Complications

tients whose control is poor. This does not cause symptoms of itself. The patient may complain of tiredness, which is con- tributed to by poor diabetic control. It is usually detected by hepatic enlargement on examination and by changes in the liver enzymes (but not bilirubin) on routine testing. Typically, the alkaline phosphatase and aminotransferase are both elevated to about 20% to 30% above normal. Higher levels than these demand investigation. The echo pattern is abnormal on ultra- sound scan. An experienced radiologist may be able to confirm the clinical diagnosis. Liver biopsy is needed when there is clinical doubt. The liver looks pale and yellow, and the biopsy often floats in the fixative. Histologically, there are numerous fat globules throughout the liver parenchyma.

Both excess alcohol and diabetes can cause a fatty liver by altering glucose metabolism. A careful history is needed in the diabetic who drinks fairly heavily. An elevated MCV points to alcohol, but the gamma-glutamyltransferase is not usually helpful, as it can be elevated in a fatty liver from either cause. Careful diabetic control is needed, and abstinence seems sensible. However, the diabetic liver does not progress to cirrhosis and ag- gressive measures to treat are not in- dicated. On the other hand, a fatty alcoholic liver frequently does progress to permanent liver damage and so needs positive management to control alcohol intake.

(b) Chronic active hepatitis: there is an association between diabetes and the auto- immune type of chronic active hepatitis (CAH) (see first article). However, the association is not very common and in most patients diabetes occurring in con- junction with CAH is as a result of steroid treatment, which is often needed in moderately high doses for several years. Many other conditions needing steroids for long-term treatment, eg inflammatory bowel disease, collagen diseases, nephrotic syndrome, are at risk of developing diabetes and these patients should have periodic checks for glycosuria.

Summary The two most important chronic com-

plications of diabetes affecting the gastro- intestinal tract are the delay in gastric emptying (gastroparesis) and diabetic diarrhoea. Gastrointestinal disease in the diabetic is not uncommon and ap- propriate treatment can often help great- ly, but it is important to remember that prevention is better than cure. Although this is not yet proven, there are reasonable grounds for hoping that good diabetic control over the years will prevent autonomic neuropathy and its associated sequelae from developing.

Further Reading Bank S, Marks I N, Vinik A I. Clinical and hormonal aspects of pancreatic diabetes. Amer J Gastroent, 1975; 64: 13-22. Gorelick F S. Diabetes mellitus and the exocrine pancreas. Yale J Biol Med, 1983; 56: 271-5. Karmody A J, and Kyle J. The association between carcinoma of the pancreas and diabetes mellitus. Brit J Surg, 1969; 56: 362-4. h u n g J W C, Bowen-Wright M, Aveling W, Shorvon P J, Cotton P B. Coeliac plexus blocks for pain in pancreatic cancer and chronic pancreatitis. Brit J Surg, 1982; 7 0 730-2. Levin D L, Connelly R R, Devesa S S. Demographic characteristics of cancer of the pancreas: mortality, incidence and survival. Cancer, 1981; 47: 1456-68. Russell J G B, Vallon A G, Braganza J M, Howat H T. Ultrasonic scanning in pancreatic disease.

Sarles H, Laugier R. Alcoholic pancreatitis. Clinics in Gastroent, 1981; 10: 401-15. Walsh C H, Cooper B T, Wright A D et al. Diabetes mellitus and coeliac disease, : a clinical study. Q J Med, 1978; 47: 89-100. Merrick M V, Eastwood M A, Ford M J. Is bile acid malabsorption underdiagnosed? An evaluation of accuracy of diagnosis by measurement of SeHCAT retention. Br Med J, 1985; 290 665-8. Zitomer B R, Gramm H F, Kozak G P. Gastric neuropathy in diabetes mellitus : clinical and radiologic observations. Metabolism, 1968; 17: 199-211. Ricci D A, Saltzman M B, Meyer C, Callachan C, McCallum R W. Effect of metoclopramide in diabetic gastroparesis. J Clin, Gastroent, 1985; 7: 25-32. Fox S, Behar J. Pathogenesis of diabetic gastroparesis: a pharmacologic study. Gastroenterology, 1980; 78: 757-63. Malagelada J R, Rees W D, Mazzotta L J, Go V L W. Gastric motor abnormalities in diabetic and post vagotomy gastroparesis: effect of metoclopramide and bethanechol. Gastroenterology, 1980; 78: 286-93. Walsh C H, Cooper B T, Wright A D et al. Diabetes mellitus and coeliac disease: a clinical study. Q J Med, 1978; 47: 89-100. Scarpello J H B, Hague R V, Cullen D R, Sladen G E. The ''C-glycocholate test in diabetic diarrhoea. Br Med J, 1976; 2: 673-5. Molloy A M, Tomkin G H. Altered bile in diabetic diarrhoea. Br Med J, 1978; 2: 1462-3. Scarpello J H B, Greaves M, Sladen G E. Small intestinal transit in diabetes. Br Med J, 1976; 2: 1225-6. Editorial. Diabetic autonomic neuropathy. Br Med J, 1974; 3: 2-3.

Gut, 1981; 19: 1027-33.

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