Gastroparesis (part 2)

Groombridge Place, June 2013

In part 1, I described the symptoms of gastroparesis, what might be causing it in someone with diabetes, and the problems that arise - gastrointestinal symptoms, poor glycaemic control, malnutrition and weight loss, and depression. Now I'm going to write about possible treatments.

Nerve damage, if that's what is causing the problem, is irreversible. We can't (yet) mend nerves: once they're gone, they're gone. There doesn't seem to be an option to fix the faulty pacemaker cells either. But it is always useful to run through a list of things that will definitely not be helping. For example, opiate drugs are known for their constipating effects, and should be replaced with alternative painkillers if pain relief is necessary. Cigarette smoking has been shown to delay the gastric emptying of solids. Unfortunately, high blood sugar has also been shown to significantly delay gastric emptying, which is of no comfort to the person with diabetes who has been trying unsuccessfully to manage wild swings in blood sugar in the face of unyielding opposition from the gastroparesis itself. So I wouldn't bother opening that particular can of worms.

There are three methods used to help improve gastric emptying: pharmacotherapy (i.e. drugs), diet and surgical approaches. Two types of drugs can help with symptoms: prokinetics, which help to speed the intestinal contents on their way, and anti-emetics, which are used to prevent nausea and vomiting. These are routinely used, but changes to diet can be more effective than the medicines.

The Glycaemic Index (GI) is often used to assist with blood glucose control and weight management, and describes the speed at which carbohydrates are digested. High GI foods e.g. foods containing large proportions of monosaccharides and disaccharides (sugars) are digested quickly, and their glucose payload can reach the bloodstream before subcutaneous insulin has had time to get there, causing blood glucose to rise beyond the desired range. Low GI foods (complex starchy carbohydrates) such as oats and pulses are digested more slowly, and therefore deliver glucose to the blood slowly and more controllably, and keep you feeling fuller for longer. Unlike the majority of people with diabetes, high GI foods may help someone with diagnosed gastroparesis. These foods tend to contain simple sugars or processed carbohydrate and little fat and fibre - sweets, white bread, mashed potato.

Another good reason to avoid fibre, apart from its role in slowing gastric emptying, is that as it hangs around in the stomach it can contribute to the formation of unwanted fibrous masses called bezoars. The disadvantage of avoiding fat, however, is that someone with chronic gastroparesis is at risk of malnutrition, and could do with the calories supplied by energy-dense fatty food.

The diabetologist who referred the patient with gastroparesis to me suggested that a low carbohydrate diet might help reduce the volatility in blood glucose levels. The problem with this approach is that taking out the carbs leaves an energy deficit that can either be filled by protein or fat. Protein increases feelings of satiety, which is certainly not what we want, and fat slows gastric emptying. Blood glucose levels may be better managed with a greater proportion of high GI carbohydrate, which might actually be released from the stomach in a more predictable manner.

Research suggests other dietary recommendations, both to relieve symptoms and to maintain nutritional status. Small frequent meals are digested better than three large meals a day, and 'particle size' makes a difference - food should be chewed well, and liquids seem to leave the stomach more easily than solids. A patient might be prescribed three liquid supplements a day, adding a much needed 900 calories. Positioning during a meal, and sitting up and/or walking post-meal can promote gastric emptying; alcohol and carbonated drinks tend to exacerbate symptoms of bloating.

Placing a feeding tube below the stomach and pylorus in the jejunum (upper small intestine) allows nutrition to bypass the problem area, but brings with it the risk of infections and the inconvenience of having to be hooked up to a feed pump for hours at a time - jejunal feeding has to be much slower than feeding into the stomach. If nutritional status continues to decline, intravenous (parenteral) feeding is a possibility, but brings a whole new range of potential complications.

As well as addressing symptoms and nutrition, there are those pesky blood sugars to consider as well. Eating a meal containing carbohydrate requires a matching dose of insulin in order to maintain blood glucose within the desirable range, but we have seen that giving the insulin at the usual time (before, during or immediately after the meal) doesn't work if the glucose hits the bloodstream over a period greater than the lifetime of the insulin. So we could try splitting the insulin dose, perhaps giving 30% of the total dose just after eating, and the remaining 70% after an hour, or two, or whenever we think blood glucose is rising.

If you don't want to end up as a pincushion, this type of insulin regimen can be managed much more comfortably and conveniently with an insulin pump, which can be programmed to deliver insulin at whatever rate you desire. Delivering 6 units of insulin at one-tenth of a unit every five minutes over five hours can't be done with conventional insulin injection devices, but is a piece of cake with a pump.

Unfortunately the NHS doesn't fund Continuous Glucose Monitoring (CGM) systems, which have a subcutaneous sensor that samples interstitial fluid every five minutes linked to a device that translates the reading into an estimated blood glucose level. We lend these systems to patients to wear for just seven days at a time when we can't work out what their blood glucose is doing. Otherwise, users have to buy the kit and consumables themselves, which works out rather expensive. Although not mentioned in the research papers I have read about this condition, I think that CGM in combination with an insulin pump would be a valuable and effective approach to managing blood glucose with gastroparesis.

Finally, there are more technical and innovative options to try.

• Gastric electrical stimulation (GES) was approved in 2000 in the USA. Similar to a heart pacemaker, the GES device is implanted next to the stomach and mimics the role of the gastric pacemaker cells, stimulating and enhancing vagal function and muscle tone. 
• Botox (Clostridium botulinum toxin) is a muscle relaxant used cosmetically to reduce facial wrinkles, but will relax muscles elsewhere to therapeutic effect. Injecting Botox into the pyloric sphincter may cause it to relax sufficiently to allow better gastric emptying, but trials have shown this effect to be short-lived. 
• In future, that universally-cited panacea 'stem cell therapy' may be relevant, providing a way to replace or rejuvenate those faulty pacemaker cells of Cajal.

Gastroparesis (part 1)

Berlin, March 2013 - no idea about the Star Wars characters...

I saw a patient recently who is suffering with gastroparesis, and I say 'suffering' for a good reason. Gastroparesis is 'a chronic disorder of gastric motility that is characterized by delayed emptying of either solids or liquids from the stomach in the absence of any mechanical obstruction.'

Food is normally chewed and mixed with saliva to form the bolus that you swallow. The bolus passes down the oesophagus into the stomach, where it is mechanically, chemically and enzymatically digested to form chyme: an acidic slurry of food, fluid and enzymes. The pyloric sphincter at the bottom of the stomach is prompted to release chyme from the stomach into the small intestine in small bursts, where the acid is neutralized and further digestion takes place by enzymes released from the intestinal wall and the pancreas. [The release of digestive enzymes into the intestine is the exocrine function of the pancreas, and is usually unaffected by diabetes, which is a disorder of the endocrine system.]

Food normally starts to leave the stomach within minutes of ingestion. After one hour 10% or more will have passed through to the small bowel, after two hours at least 40% should have gone, and four hours post-meal more than 90% of the meal should have left the stomach heading for the intestines. The final products of digestion are nutrients - fatty acids, amino acids, sugars, vitamins and minerals - that are absorbed through the wall of the gut into the body, and the indigestible fraction passes on through to be excreted as faeces.

The symptoms of gastroparesis include nausea, reflux, bloating, early satiety and post-prandial fullness, abdominal discomfort and pain. Putting a camera down into and beyond the stomach, which is usually the first line of investigation in most disorders of the gastrointestinal tract, is done to see if there's mechanical obstruction (from a tumour, for example), and in the patient that I saw, showed the remains of a meal that had been eaten the day before.

So the symptoms of gastroparesis simply arise because the stomach is not emptying - the pyloric sphincter is not being prompted appropriately to allow the chyme through to the small bowel. The next diagnostic test might be to follow a radioactive meal through the GI tract. Using this technique, delayed gastric emptying has been found in 25-55% of people with Type 1 diabetes, and in 30% of people with Type 2 diabetes.

Hyperglycaemia, or high blood glucose, is pretty toxic to the smallest blood vessels in the body, found in the retina and the kidneys, and also damages nerves. Often the nerves that are damaged are the smallest ones furthest from the brain, which is why foot care is so important. For some very unlucky people, the nerve that is affected is the vagus nerve, which transmits the signals that manage the extremely complex processes going on in the intestinal tract. But it turns out that hyperglycaemia affecting the vagus nerve is not usually the culprit in diabetes, but more often it is due to destruction of the pacemaker cells ('cells of Cajal') that link the vagus nerve with the smooth muscle of the stomach, and the result is the absence of peristalsis and atrophy of gastric smooth muscle.

Let's look next at what happens to the food once it has been digested, and glucose from carbohydrate in food has been transferred from the gut to the bloodstream. Insulin is secreted from the pancreas in order to allow the glucose to enter cells of the body where it is used for energy. In someone without diabetes, the pancreas simply responds to the level of glucose in the blood: lots of glucose leads to lots of insulin, little glucose means little insulin. It's automatic, and maintains tight control of blood glucose levels very effectively, to prevent those toxic effects of hyperglycaemia (or the unpleasant and potentially dangerous effects of hypoglycaemia, low blood sugar).

Now, we'll throw Type 1 Diabetes into the mix. Insulin secretion by the pancreas is non-existent, so the diabetic patient has to supply the insulin by injection. Usually it takes about the same time for glucose to reach the bloodstream from digested food as it takes for rapid-acting insulin to reach the bloodstream from the injection site. This type of insulin is effective over about 4 to 6 hours, which is about the time it usually takes for the whole meal to leave the stomach, be digested, and all the glucose to be delivered to the bloodstream.

With gastroparesis, there is a delay. Some glucose may turn up in the bloodstream straight away, but there is no way of knowing how much, or how long it will take for the whole lot to come through, and at what rate. So you can calculate the insulin that is needed to match the carbohydrate in the meal, but if you inject it all at once, it will arrive in the bloodstream before the glucose, and your blood glucose level will drop. The way to deal with low blood glucose from too much insulin is to consume some sugary carbohydrate that should be quickly digested, but - will it reach the bloodstream in time, given that the pyloric sphincter is mostly stuck shut? Later, when the rest of the carbohydrate from the meal finally gets through to the bloodstream, the insulin will no longer be there to deal with it, and your blood glucose level will rise. And there is no reliable way to predict how long this will take. The insulin and blood glucose graphs look like roller coasters.

Meanwhile, you feel uncomfortably full all the time and find it difficult to eat even a small amount of food. Eating is no longer pleasurable, you're losing weight, your family are initially sympathetic but you keep vomiting after a trivial amount of food, your breath smells terrible and with the constipation alternating with diarrhoea, the bathroom is never free. The diabetes team give the impression that your terrible glycaemic control is because of something you're doing wrong with the carb counting or insulin dosage, but you're doing everything you can think of to try and avoid high or low blood sugar, it's just that nothing's working. The high and low blood sugars make you feel awful too. Depression is a well-documented side effect of diabetes, and if you have gastroparesis too, well, there aren't many happy days.

Although part 1 ends on a low note, part 2 should provide some reassurance that treatments are available and can help.

Outpatients, interpreters and FODMAPS

Leamington Spa's 'Justice Centre' Jan 2011

I am starting to enjoy my outpatient clinics. One of the main reasons for this is that I am no longer scared of them, no longer worried that I won't know the answer, or won't know what to say. They are still difficult and tiring: three and a half hours on a Tuesday morning, with slots for up to three new and eight follow-up appointments. I would be very surprised if any Dietitian has actually managed to see eleven patients, though, because usually fewer are booked in, or at least one patient doesn't turn up. This is actually the only thing that makes a clinic manageable - I don't quite know how I could possibly cope if all the scheduled patients did turn up. Last week one of my colleagues had ten patients, and she had a student with her. She deserves a medal.

I have also had an unusual number of patients who require interpreters. Neither of the other junior Dietitians have needed any interpreters at all, but so far, in about ten clinics, I have needed interpreters for Punjabi (twice), Persian, Kurdish, French (North African), and English (Sign Language for a deaf patient).

Up to now the system has worked in that nobody has turned up without an interpreter, and I have been given extra time for a consultation that includes an interpreter - except last week when I had only fifteen minutes for what was effectively a first appointment, which should have been allocated thirty minutes, even without the need for interpretation. Luckily, the patient didn't turn up. Unluckily, the interpreter did.

Using an interpreter is slow and difficult, especially when there is something complicated or sensitive to discuss, such the foods that do or don't contain gluten (how do you say 'rye' or 'buckwheat'?) or the workings of the bowels. Talking about the consistency of poo with a stranger is difficult enough without having someone else you've never met and who has no health qualification involved in the conversation as well.

Irritable Bowel Syndrome, or IBS, is one of the most frequent conditions that I see in my outpatient clinic. It's not really a disease, it's what's left when all the other likely diseases have been eliminated. If you have chronic bloating, wind, diarrhoea or constipation and you don't have a malignancy or tumour, or coeliac disease, or inflammatory bowel diseases like Crohn's Disease or Ulcerative Colitis, then IBS is what's left.

Treatment: well, there isn't really any treatment other than trying to identify what's causing the symptoms and eliminating that. It could be stress rather than anything physiological, or an intolerance to a food or ingredient, or not enough fluid or fibre, or the wrong type of fibre. A recent innovation is the FODMAP diet, where foods are eliminated that contain Fermentable Oligo-, Di-, Mono-saccharides and Polyols. These are short and medium chain length carbohydrates (compared with the long chain polysaccharides that comprise starch and cellulose), and it is thought that trying to digest them may cause some of the symptoms of IBS for some people.

Digestion takes place mostly in the small intestine, where transit time is relatively brief and enzymes excreted by the pancreas, liver, gall bladder and the gut chop up the food into its constituent parts so they can be absorbed through the wall of the intestine into the bloodstream or lymphatic system. A lot of fluid is needed for this task, so when the undigested remainder of our meals passes into the large intestine, the main job is to recover all that fluid so we don't dehydrate (which is the main problem with diarrhoeal diseases like dysentery and cholera).

But quite a lot of potentially digestible material still remains, such as these FODMAPs. The huge number of bacteria that colonise the lower intestines can perform this function on our behalf, chopping up the FODMAPs, allowing us to absorb potentially useful molecules, but generating gas as they do so. Eliminating FODMAPs from the diet might bring relief to someone who suffers with wind, bloating or diarrhoea.

Unfortunately, it's no easy thing to eliminate FODMAPs, which are present in many different foods. It takes a lot of effort and creativity as well as time to remember lists of foods, read food labels and avoid many social situations that include eating, for six to eight weeks. If there is no relief, then either FODMAPs are not to blame, or else the task of achieving their exclusion is too hard. If excluding FODMAPs is of benefit, then there is a protracted period of re-introduction, to try and ensure that foods are not unnecessarily excluded from the diet.

If all this doesn't work, then there is the Exclusion diet, where you cut down to a very few foods and gradually reintroduce things one at a time. This is almost as hard as the low FODMAP option, and takes just as long. In the end, IBS is not like Crohn's or coeliac disease, because eating foods that cause symptoms does no underlying damage to the body, it's just a matter of deciding how much effort you're prepared to put in to identify troublesome foods compared with the pain or discomfort of the symptoms.