Exercise and Type 1 Diabetes: part 2

A picture I found on the Interwebs that amused me

In part 1 I tried to set out the problem of exercising with Type 1 Diabetes (T1D) - in brief, keeping blood glucose levels within reasonable bounds while hormones stimulated by activity are doing their best to frustrate your efforts. Here is part 2, which contains a few things that might help to manage the situation.

Managing blood glucose and insulin

Let’s start with the basic theory. Usually, with low or moderate intensity exercise and some active insulin on board, blood glucose will fall steadily and relatively predictably, and insulin will work more effectively. In order to avoid a hypo then, you would need either to reduce your mealtime insulin at the meal beforehand, or consume carbohydrate during the activity, or both. It is estimated that between 30g and 60g of carbohydrate is needed per hour to fuel moderate exercise.

So you could measure your blood glucose level before and after your activity and see how much it drops – say, from 11 to 6 mmol/L over 30 minutes fast walking 2 hours after a meal containing 60g carbohydrate for which you took half your usual dose of rapid insulin. If on another occasion your blood glucose was only 8 mmol/L before the same activity in the same circumstances, you could predict that carbohydrate would probably be needed to prevent a hypo.

To be able to reduce your rapid insulin dose at the previous meal, the activity needs to be planned or anticipated. Often activity is not planned, in which case there is no option but to eat or drink carbohydrate, unless your blood glucose happens to be high anyway. You can see that this makes it much more difficult to lose weight by exercising than for someone without diabetes. So another tactic that was suggested to help weight loss was to do the activity when insulin levels are at their lowest, usually first thing in the morning, although clearly this also requires an element of planning. But I can’t see how that would work if blood glucose is also at its lowest, because that’s just asking for a hypo, so maybe you’d have to reduce your overnight background insulin so that fasting blood glucose levels are a bit higher than usual. I’m not a fan of messing with background insulin on a day-to-day basis, which I will outline later on in this huge essay.

Blood glucose doesn’t always drop with exercise. If the activity is anaerobic (sprint, weight lifting, resistance exercise at the gym) then blood glucose tends to rise because those other hormones (especially adrenaline) stimulate the release of glucose and increase insulin resistance. In this situation extra insulin may be needed to take blood glucose levels down rather than extra carbohydrate to prevent hypos. A stressful or competitive situation like a football match where adrenaline is a factor may have a different impact on blood glucose compared with regular football training, and may need a different insulin dosing strategy.

This effect can be used to your advantage. If blood glucose before an exercise session is between 4 and 7 mmol/L, then starting with anaerobic or high intensity/stressful exercise may raise blood glucose enough to allow you to carry out some aerobic exercise without the need for insulin or carbohydrate adjustment ahead of time.

So we can start to imagine types and duration of activity and the likelihood of blood glucose rising and falling so that insulin and carbohydrate can be managed before and during exercise. Then comes the aftermath.

There are two effects of exercise on blood glucose after the activity is completed. The first is that glycogen stores in muscles and the liver have been depleted and need to be restocked, which makes blood glucose drop in the hours following the exercise. The other is that activity makes muscles more sensitive to insulin (less resistant) particularly in the period between 7 and 11 hours after exercise – the stress hormones released during activity induce insulin resistance for about 7 hours afterwards. For exercise in the afternoon or evening, this period of greatest hypo potential occurs during the night. Exercising first thing in the morning means the period of maximum hypo risk occurs during the day rather than overnight, which may be helpful.

Ways to manage this hypo risk after exercise include taking carbs on board immediately after exercising, and/or reducing the amount of insulin given for subsequent meals and corrections by about 50%, and possibly also reducing overnight basal insulin (but see below). Another option uses adrenaline to raise blood glucose levels by incorporating a 10-second sprint at maximum exertion level at the end of the period of exercise.

Blood glucose monitoring is the key to managing the amount of carb/insulin to maintain good control after exercise. Some experimentation is likely to be needed, while bearing in mind the poor reproducibility mentioned earlier. Perfection is unlikely to be achieved.

Background insulin adjustment

So far, all the insulin adjustment has been with the rapid insulin that works with carbohydrates that are eaten or drunk. But it is possible to adjust the background (basal) insulin too, and it was at this point that our practice and the recommendations within the study day diverged.

Background insulin works over long periods – from 12 to 72 hours depending on the type. Reducing the long-acting insulin will reduce the hypo risk overnight, so the advice on the course included routinely reducing this insulin both before and particularly after exercise. Doing this will certainly reduce the hypo risk, but on the other hand calculations of rapid insulin will be thrown out of kilter if background insulin is being adjusted day to day, especially if you exercise some days but not others. We didn’t reach any consensus on this point, so I suppose I’d have to look in the research literature to see if there’s anything relevant there.

I can, however, see the point of a basal adjustment for a short continuous period of daily exercise like an activity holiday – skiing, watersports or walking holidays being the most common examples. And I had not considered the pros and cons of different background insulins before – the newer, very long lasting insulins being less flexible if background insulin is to be adjusted. It’s also true that adopting a more active lifestyle will probably reduce the need for total background (and rapid) insulin, but injecting different amounts of long-acting insulin on a daily basis might be problematic.

What about insulin pumps?

So far all the discussion has been based on multiple daily injections of rapid-acting and long-acting insulin. Pumps are a bit different, because they only use rapid-acting insulin, and basal rates can be adjusted hour by hour. So with a pump there’s no problem about reducing background insulin as well as rapid mealtime insulin to avoid the need for extra carbs or to reduce the risk of hypos. This raises the chances of better control as well as being an advantage if weight loss is one of the aims of doing the activity. Reducing insulin is usually preferable to increasing carbohydrate for the ‘ordinary’ person. Proper athletes will want the carbohydrate, though.

The reduction suggested on the course was to set a temporary basal rate (TBR) of 50% for an hour before and up to an hour after aerobic exercise. If extra insulin is needed for anaerobic exercise, the course recommended raising the basal rate by only 10% starting 30 minutes before and lasting until 60 minutes after the activity. The TBR might be reduced again by 10% in that crucial period 7 to 12 hours after the exercise. There are more complicated formulae for calculating TBRs but I will leave those to the serious competitors.

The main downside to a pump is that it needs to be attached to you, and most types are not waterproof. So the pump would need to be disconnected completely for contact sports or watersports, which is really only safe to do for an hour or so. Some pumps can’t be disconnected temporarily, like the tubeless pumps which are actually attached to the skin. This type is usually waterproof for bathing or swimming up to an hour or so, although it clearly wouldn’t be suitable for scuba diving, and might be dislodged in a rugby scrum or during martial arts.

For situations where the pump has to be disconnected for longer than an hour, competitive athletes sometimes connect up with the pump from time to time to give themselves a quick bolus, or revert to the use of basal and bolus injections from a pen to maintain insulin levels on those occasions. When the pump is reconnected then there may be a need for a correction, which could take one of several forms. You could increase the basal rate by 50% for up to an hour, or give 50% of a correction bolus, or even work out how much basal insulin was missed and bolus half this amount. Then, of course, be a bit more rigorous about monitoring and correcting blood glucose levels.

What else?

There are a whole lot more factors that affect management of T1D with exercise, some of which I haven’t mentioned up to now because they are routine, like the need for fluids. Dehydration not only affects athletic performance but can make the blood glucose level appear higher than it really is.

Heat and cold also affect the uptake of insulin from the injection site as they do at any time. The location of the injection site matters because if you’ve injected near a muscle that will be used for the exercise (usually leg or buttock/lower back) then the insulin will reach your bloodstream faster than if you injected in a non-exercising part of the body.

Keen exercisers may use Continuous Glucose Monitoring (CGM) either standalone or in conjunction with an insulin pump. The main point to highlight with CGM is that there is a delay between the readings they give for the glucose in interstitial fluid and the level of blood glucose, which may not matter if you’re in an office and it’s coming up to lunchtime, but may be critical if you’re just reaching the summit of a mountain.

Carb intake: it has been established that the requirement for carbohydrate during moderate intensity exercise is around 1g per kg body weight per hour, i.e. for a 70kg person that would be around 70g per hour. It has also been established that the gut can only absorb dietary carbohydrates at the rate of 60g per hour, so there is no point trying to increase intake beyond this as it will just cause gastro-intestinal discomfort. The difference is made up by the use of stored glucose and fat as fuel.

All foods are not equal, but the question of which carbs to have at what time was not covered in the course. Of course hypos associated with exercise have to be treated with fast-acting carbohydrate as at any other time, and it would make sense to have slow-acting carbohydrate to sustain any prolonged period of activity. Beyond that, I suppose it has to be trial and error with plenty of blood glucose monitoring to find out which foods before, during and after exercise have the best effect on blood glucose levels. Aside from diabetes, the prevailing view is that a mixture of protein and carbohydrate such as cereal+milk, yogurt or meat/cheese sandwich is a good idea post-exercise to replenish glycogen stores and supply material for muscle regeneration and repair.

The overall message I took away from the study day was that exercising with Type 1 Diabetes is very, very complicated if you want to do anything more exciting than up to an hour of moderate intensity exercise in a regular controlled environment like road cycling, a run around the park or an hour in the gym. Competitive athletes need much more insight into their own physiology, but it is possible to compete at the highest level, and one of the diabetes pharmaceutical companies sponsors competitive cycling with the Team Novo Nordisk.

I have had a couple of patients asking me questions about serious exercise, and we have very quickly reached the limits of my knowledge. I don't see that changing much as a result of this course, but perhaps over time I will absorb more on this subject alongside my greater experience in diabetes as a whole.

Exercise and Type 1 Diabetes: part 1

View from the conference centre, May 2016

The recent study day I attended was about exercise and Type 1 diabetes (T1D), which is a truly difficult topic to write about, and even more difficult to manage.

Many hormones are involved in keeping blood glucose levels stable with exercise, including insulin, glucagon, growth hormone, cortisol and adrenaline. For someone with T1D, insulin is delivered in a very non-physiological way via subcutaneous fat rather than into the hepatic bloodstream from the pancreas. It is also thought that glucagon production by the pancreas becomes less efficient over time following a diagnosis of T1D. Each of these hormones has multiple effects at different organs (brain, muscles, liver, pancreas etc.) and all interact with each other. This complex situation means that the tight regulation of blood glucose with exercise that happens automatically when the pancreas is working properly is almost impossible to achieve with a broken pancreas.

The study day

The course was a single day, but they packed a great deal into it. Speakers presented slides with graphs and evidence and whizzed through topics at such a pace that I could barely keep up let alone take comprehensible notes. The slides were supposed to be available after the event, but I don’t think they have appeared yet, a month later. My scribbled note “good slide explains this bit” will have to wait for interpretation later.

The first speaker talked about ‘normal’ exercise metabolism, the second introduced T1D into the metabolic picture, and the third session was presented by paediatric and adult Dietitians. After a break there was more detail about managing blood glucose before, during and after exercise. The workshops after lunch gave us the chance to think about case studies and individual scenarios.

Overall I think everything was included that needed to be included, but much too fast, and the main focus was on serious athletes and people who were going to be running or cycling or weight lifting or at least going to the gym regularly. There was very little about the unfit or overweight person who might be starting with walking up a flight of stairs rather than taking the lift, or trying to increase their level of activity for weight loss or fitness rather than competing for an Olympic medal. Gardening, DIY, housework and shopping are the more common types of activity that I encounter in my caseload.

I did a little brainstorm for this blog entry just listing all the issues that pertain to the subject – the list was 2 pages long. So what shall I include here? Of course, this particular blog post probably isn’t going to be of much interest to you unless you have Type 1 Diabetes and you want to know about managing your blood glucose while exercising, and I think I may have fewer than one reader in that particular category. No, this blog post is for me, to enable me to assemble my thoughts and produce a reference point for that future day when I might have to advise a patient on this subject.

Fuel for activity

So, first to recap the basics. Dietary carbohydrate is digested into glucose which moves into the blood to be transported around the body. Insulin allows blood glucose to be taken up by cells in the body where it is metabolised into energy or stored as glycogen in muscle and liver. Excess glucose is converted into fat in the form of triglycerides (a triplet of linked fatty acids) and stored in the liver, muscle and in fat cells. High levels of insulin promote this storage process and inhibit the release of glucose or fat into the blood from fat and liver cells.

When energy is needed for activity, the most accessible sources are muscle glycogen and blood glucose. The hormone glucagon prompts the liver to very quickly start converting its stored glycogen into glucose (glycolysis) and send it out into the blood. Triglycerides in the muscles are also easily accessible and are used as fuel (fat oxidation). It takes a bit longer for new glucose to be manufactured in the liver (gluconeogenesis) and for the liver to break down triglycerides into free fatty acids and send them out to be used as fuel (fat oxidation). Insulin levels need to be low for all these processes to work efficiently.

If exercise is more intense (anaerobic) there is more reliance on carbohydrate as fuel; if exercise is less intense but goes on for longer (aerobic) there is a shift towards fat as the main fuel. Obviously exercise drains glycogen stores in muscles and liver, and these are ‘topped up’ afterwards using dietary glucose (fat stores don’t need to be topped up!) Non-diabetic metabolism manages all the hormone levels so all this takes place with blood glucose maintained between 4 and 7 mmol/L at all times.

The main difference that makes things difficult for someone with T1D is that insulin cannot be regulated up and down in a physiological way. It is certainly possible to adjust insulin levels according to various ‘rules’, but adjustment is crude and doesn’t reflect the metabolic state minute by minute.

There are also a couple of scenarios when it is not advisable to exercise. If your blood glucose is high (over 14 mmol/L) then it is possible that you don’t have enough insulin on board, and the official advice is that you need to check for ketones. If blood glucose is high without ketones then a small correction dose of insulin might be all that is needed, but if ketones are present then the full correction dose should be given and exercise postponed until ketones have gone. The majority of people with T1D don't have a meter that will measure blood ketones, however, so this advice is moot.

The other situation when you might choose not to exercise is if you have had a hypo in the last 24 hours, because this makes a hypo with exercise even more likely. If it wasn’t a serious hypo needing third party assistance then you might go ahead bearing in mind the need to be extra vigilant. If the hypo was within an hour before planned activity you would be advised to wait for 45-60 minutes after your blood glucose level has stabilised before exercising.

Changes in blood glucose and insulin

The level of your blood glucose will fluctuate according to:

• the duration, intensity and type of activity
• the type and amount of food and snacks eaten or drunk before, during and after the exercise
• the level of stress and competitiveness
• your level of fitness or previous training
• hydration status
• the time of day

and probably more.

The level of your blood insulin will fluctuate according to:

• the timing of insulin injections/infusion
• the amount and type of insulin injected/infused
• the site of the injection or cannula
• the ambient and body temperature.

Poor ‘reproducibility’ was highlighted in the study day, meaning that the same exercise for different people or even for the same person on different days may have very different effects on blood glucose levels. With all these variables it’s not surprising that matching blood glucose levels and blood insulin levels in order to manage T1D and exercise is a minefield.

So this is the landscape we're working in, with different sources of fuel and the action of hormones all interacting, and we have to try to maintain blood glucose levels without going low or high using tools (carbohydrate and insulin) that are about as precise as trying to steer a car at full speed with just your elbows on the steering wheel. At some point you're probably going to crash.

So having set out the scale of the problem, how can it be managed? Look out for part 2 in the series, coming soon!

I like my job

National Botanic Garden of Wales, May 2013

So far, I like my job.

I like the small team, the fact that we are mainly unsupervised and can do mostly what we like. I like the building, I like my office, I especially like the way that everybody comes together for lunch in the largest room. I can adjust 'my' heating, open 'my' window, and arrange 'my' furniture. I can always find somewhere to park on the site, even if not immediately outside the building. I can ask all sorts of people for all sorts of support, and so far they have not hesitated to do whatever they can to help.

Of course there are things that aren't so good. On Wednesday mornings I have to give up 'my' room to a renal Dietitian, but there are plenty of other places I can sit. We don't have any access to colour printing or copying in the building, but I believe we can go elsewhere if we really need it. These are small issues.

I have started to see more patients, and feel very pleased that I am almost keeping within the time limits allocated. One patient returned for a second appointment, and was extremely positive about how my advice had allowed him to make useful changes. There have been other patients who have not welcomed my input, but I have been content to leave them alone, and they may return for advice if they ever want it in future.

I've been given the job of reviewing the patient information leaflet that we offer on hypoglycaemia, and have included some of the great pictures that I produced last year. The draft leaflet is out with the rest of the team for comments at the moment; we'll see what they think.

A quick update on stuff outside work: no, there's nothing of any interest at all. I stupidly cut my finger on a tin can. I have a hurty arm, probably a result of the last wipe-out of the ski holiday and then exacerbated by badminton. My newest badminton club is very enthusiastic about the fact that I am eligible to play in matches; I am less enthusiastic, although I have said I will play if they are absolutely desperate. Mr A and I went dancing on Friday night; this is his latest plan to introduce some non-sedentary activity into his life. It was fun, but with two nights of badminton per week I'm not sure I will be accompanying him every time he wants to go dancing. The falconry centre has reopened after the 3-month winter break; it was interesting to see how the birds need reminding that they are expected to work for their living again. That's about it.

And it hasn't rained for two days!

Hypoglycaemia treatments

Hypoglycaemia, or a 'hypo', happens when the level of glucose in the blood falls too low. It is not caused by diabetes, because the effect of diabetes is the opposite: high blood glucose levels, or hyperglycaemia. Hypos in people with diabetes are caused by the treatment of hyperglycaemia, not by the diabetes itself.

Very few people who are not diabetic will ever experience hypoglycaemia, because the systems that manage glucose homeostasis are very sensitive to blood glucose level, and keep the concentration very steady between about 4 and 7 mmol/L. But in diabetes, these systems are pretty much messed up along with the pancreatic beta cells. Not only is the insulin response defective, but responses to other hormones that regulate glucose can be blunted too.

In someone with a fully functioning pancreas, receptors in the beta cells of the pancreas islets respond to rising levels of blood glucose with a corresponding and synchronous release of insulin. This facilitates the transport of glucose out of the bloodstream and into cells around the body for use in generation of energy, or into storage in the form of glycogen or fat. As the level of blood glucose falls, the secretion of insulin tails off but a different hormone, glucagon, is released from alpha cells in the same islets. Glucagon stimulates the secretion of glucose into the blood by the liver, either from stores or by the creation of new glucose from scratch.

In someone with diabetes, the matching of blood glucose and insulin is no longer finely tuned and synchronous, but rough and ready and very much asynchronous. When the blood glucose level falls too far or too fast, the level of insulin cannot be unconsciously adjusted down because it is coming from subcutaneous fat depots or an insulin pump rather than the minutely adjustable pancreatic beta cells. Due to the presence of insulin, the glucagon response is not as effective as it should be, and glucose may continue to be removed from the circulation rather than pumped into it.

This is a gross simplification of the many complex hormonal pathways involved in glucose metabolism, but it will do. People with diabetes who inject insulin or use medications that stimulate the pancreas to secrete insulin can't turn their insulin off automatically when they don't need it any more, and are therefore at risk of hypoglycaemia.

Most systems in the body can use glucose or fatty acids to supply their energy, but the brain depends on glucose, although it can utilise ketone bodies (a by-product of fat metabolism) if necessary. When blood glucose concentration falls, the brain signals its displeasure by provoking the nervous system to put out a series of escalating warnings, culminating in stress hormones such as adrenaline and cortisol, in order to generate a flood of glucose to fuel 'fight or flight'. This is what is responsible for the hypo warning signals such as sweating, tingling of the lips or extremities, irritability, dizziness or unsteadiness, which help a person with diabetes to realise that blood glucose is dropping. Hypo unawareness, which I referred to in the post about islet transplantation, is so dangerous because the diabetic person is unable to detect low blood sugar until it is too late.

If untreated, hypoglycaemia can lead to impairment of cerebral function (confusion, drowsiness, inattention), convulsions and unconsciousness. In most cases the glucagon response kicks in and the liver eventually secretes a load of glucose into the blood. A hypo is not pleasant to experience, and there is always an underlying fear of more serious consequences.

The generally accepted definition of a hypo is a blood glucose level less than 4 mmol/L ('Make 4 the floor'), and if this happens, then treatment is advised. If the person is using an insulin pump, then it also makes sense to suspend insulin delivery until blood glucose has stabilised.

First line treatment is to eat or drink something that contains 10-20g of fast-acting carbohydrate, ideally in the form of easily accessible glucose. Energy drinks such as Lucozade are very handy, as are sweets such as jelly babies, fruit pastilles, jelly beans, wine gums or Haribo - these all contain glucose or glucose syrup in their ingredients. Sucrose takes a little longer to be broken down and converted into glucose, but sugary fizzy drinks such as cola still work. There is some argument about whether fruit juice is suitable as a first-line treatment because its sugar is in the form of fructose, which has a longer metabolic pathway than sucrose, but real-life trials suggest that it works just fine. There are also dextrose tablets that are designed to provide fast-acting glucose, but these are fairly unappetising, which can be a good thing - you may fancy a quick snack of jelly beans, but you are unlikely to eat dextrose tablets for fun.

The quantity of carbohydrate is important, because too much will send blood glucose too high, potentially leading to a need for correction downwards and a roller-coaster ride for the next few hours, or even days. The aim is to raise the blood glucose level back above 4 mmol/L very quickly, but ideally not above 7 or 8 mmol/L. To find out if this is the case, the second stage of hypo treatment is to wait about 15 minutes and test again. If the blood glucose level is still below 4 then it's a good idea to repeat the dose of fast-acting carbohydrate, wait another 15 minutes, test again, and repeat a third time if necessary. If blood glucose is still too low after three attempts, it's time to call the paramedics.

In most cases, one treatment will be enough to bring blood glucose back up again. At this point, the game is not over, because whatever caused the hypo in the first place may still be present, so the second line treatment is to eat or drink something that contains 10-20g of medium- or long-acting carbohydrate. If it's a mealtime then the meal would do, but otherwise it could be a starchy snack such as toast, biscuits, crisps, chocolate, fruit, popcorn or yogurt. Milk falls into this category because lactose follows an even longer pathway than fructose or sucrose before being converted to glucose.

The above paragraphs presuppose that the individual is conscious and alert enough to eat or drink. If the person is conscious but not alert and there is someone to assist, there are glucose gels that can be squirted into the mouth as first-line treatment. If the individual is not conscious then nothing should ever be put into the mouth - time to call the paramedics.

There is one other self-help option: an injection of glucagon, which can be administered by a partner or family member who has been shown how to do it. It is not as straightforward as, say, an insulin injection, because glucagon is not stable in solution so has to be prepared by mixing two components on the spot - not easy to manage when your loved one is unconscious or convulsing. But you should have called the paramedics before starting on the path to the glucagon injection, so they should be there to help very soon.

Part of the support and information we give to people with diabetes is how to deal with hypos. We may cover the many and varied reasons why hypos might occur, discuss the law as it applies to diabetes and driving, and I have even given advice about what to do about hypos underwater when scuba diving. But we were especially challenged by one patient with Type 1 Diabetes who does not read, write or speak English.

When I asked colleagues if we had anything that might help, I was sent some fairly crappy illustrations of hypo treatments, and I wanted to do better. 'Crowd-sourcing' using Facebook turned up a photographically oriented friend who volunteered his daughter to help out. I produced a specification for the items and quantities that I wanted photographed, and after some prompting, a terrific set of pictures were the eventual result. I have had them printed and laminated, and plan to use them either with those who need visual rather than written information, or as a teaching aid. I think they're great!