theprofsblog

[theprofsblog]

Fast acting insulin Are we ready for this?

Fast acting aspart insulin is an ultra fast form of insulin aspart to which is added niacinamide.  This promotes more rapid absorption into the blood stream, a higher peak insulin concentration and greater insulin action within 30 minutes compared to standard aspart.  

Two publications in the July issue of Diabetes Care have assessed efficacy in randomised studies in type 1 and 2 diabetes.  In both studies fast acting aspart was compared with standard aspart when incorporated in basal bolus treatment regimens.  In the type 1 study fast acting aspart 2 hour post mealtime glucose was reduced by 0.7 mmol/l compared to standard aspart and a significant reduction was also noted at 1 hour.  Over a 26-week period fast acting aspart led to a 0.1% greater reduction in HbA1c compared to standard aspart.  However, the odds of achieving an HbA1c less than 7% was 1.47 higher with fast acting aspart compared to standard aspart.

In the study of patients with type 2 diabetes who had slightly higher HbA1c than the type 1 patients there was no difference between the different insulins over the 26-week period despite significantly less glucose excursions 1 hour after meals but not after 2-4 hours.  However, both types of insulin did reduce HbA1c by 1.5%.

In both studies there was no difference in hypoglycaemia rates.

These studies suggest that fasting acting aspart would be useful to use as a bolus insulin 20 minutes before food intake with closer matching of insulin delivery to glucose excursion.  Of interest is the greater number of patients attaining HBA1c below 7%.  As HbA1c did not change much in these studies the question remains what the overall effect on long term problems might be.  We also need to know how fast acting aspart will perform as part of pump therapy. Persuading commissioners and ultimately NICE that this new medication is of value will require firmer data on long term benefits.

Russell-Jones D, Bode BW, De Block C et al. Fast-acting insulin aspart improves glycemic controlin basal-bolus treatment for Type 1 diabetes: Results of a 26 week multicentre, active-controlled, treat-to-target, randomised parallel group trial (Onset 1).  Diabetes Care 2017; 40: 943-50

Bowering K, Case C, Harvey J et al.  Faster aspart versus insulin aspart as part of a basal-bolus regimen in inadequately controlled Type 2 diabetes: The Onset 2 trial. Diabetes Care 2017; 40: 951-7

[theprofsblog]

Is each child different? Of course they are

When we are thinking about Diabetes Care it is important that we recognise that we are all different and have different values and beliefs.  The aim of care should be to fit diabetes into the family life style and not the other way round. This means that within the constraints of what we have for therapy we should be as flexible as possible.  

Even within our insulin regimens,  we recognise that sensitivity to insulin varies between individuals, at different times of day and at different ages.  We have to factor in what the individual’s make up is and how they will respond to what we advise should be done.  

It is true that there are certain broad principles such as carbohydrate counting, correction factors and what to do for exercise but all these will need some modification to fit the individual.  

Blood testing is another although here the case for testing 7 times per day or more is clearer.  The more information the better the control is likely to be.  

Similarly when we discuss tightening blood glucose values to improve HbA1c we have to balance against risk of hypoglycaemia.  Is reducing HbA1c from 7% to 6.7% worth it (probably not in terms of long term complications risk) when hypoglycaemia rates will increase?  Answer – probably not.  

The important message from Adult Diabetology is that individualising diabetes care is important.   The same applies to paediatrics.  This can cause problems with different care plans at school but all these issues are surmountable.

[theprofsblog]

FAT and PROTEIN  - again !

There has been considerable interest over the last few years on the role of fat and protein in determining insulin dosing for food.  We are all comfortable with the idea of dosing for carbohydrate content so should we be doing something about fat and protein?

Postprandial hyperglycaemia is a major factor in not being able to achieve target glycosylated haemoglobin values.  Dietary fat and protein do lead to postprandial hyperglycaemia in patients with type 1 diabetes.  How to adjust for this remains unclear.  

This study in Diabetes Care assessed the impact of high-fat, high-protein (HFHP) or a low-fat, low-protein (LFLP) meal with identical carbohydrate content on postprandial hyperglycaemia and from this determined how insulin doses should be adjusted to cover a HFHP meal.

This is a very specific study focussed on pizza!!  Adults with type 1 diabetes ate LFLP (273 calories, 4 g of fat, 9 g of protein) and HFHP (764 calories, 44 g of fat, 36 g of protein) meals with an identical carbohydrate content of 50g covered with identical insulin doses. Interestingly their standard insulin bolus delivered by an insulin pump used a mixed or dual bolus set with a 50:50 ratio over 2 hours.  

With the same insulin dose, the HFHP increased postprandial blood glucose by almost double.  To achieve target glucose control following the HFHP, 65% more insulin was required with a 30/70 split over 2.4 hours.

So this is a start at least for pizzas!!  The insulin needs varied between patients indicating that individualisation is required of the dosing schedule.  For patients on injection therapy the combination bolus can be mimicked by a preprandial injection of regular rapid-acting analog insulin followed by an additional injection 60–90 min later.  

This study was done in adults, in younger children the amount of protein or fat needed to impact on blood glucose levels depends on age or size. The insulin to carbohydrate ratio actually covers some protein and fat, so lower carbohydrate meals with high fat/protein contents may have more of an effect on blood glucose levels than expected.  

Now all we have to do is work out what is needed for all other meal fat, protein and carbohydrate combinations!!  It is going to vary between people so this is the kind of information that you can best share through CWD Facebook sites, that way we can rapidly build up a library of meals.  Patients and families are the best ones to do this so get out there and share your experiences

Diabetes Care 2016; 39: 1631-4

Tips & tricks by parents who do something about bolusing for fat and protein

(please note these have not been recommended by medical professionals but what the parents have found works for their child/teen)

“We use increased temp basal rate for 8 hours after eating high fat foods, usually 160%.  Think I got that advice from other parents.  If he eats a bacon and cheese omelette that needs a 25g carb bolus for the eggs and bacon.  Its trial and error for that though.”

“We add on for fat, but we base ours on the Dexcom CGM sensor/Nightscout arrows too.  We bolus anything up to 4 to 6 hours after eating the fatty meal and get pretty good results doing it this way.”

“We do extended boluses for any meal containing fat.  We overestimate the carbs if a lot of fat and protein is involved.  Summer BBQ food means some meals are virtually carb free except for ketchup but I estimate we bolus 20% of the protein weight as they raise levels over a few hours.  It helps having the 640G and sensors to monitor.”

“We use higher temp basals for fatty stuff, mainly fast food which says a lot ! Pizza, chippy and Chinese all get it, for a good 4 to 6 ours unless he has been really exercising hard that day.  He doesn’t eat any meals where there is not a shed load of carbs so we don’t need to bolus for protein.”

“We increase the temp basal rate to between 150% to 170% for 4 hours after pizza.”

“If my daughter has eaten no carbs with her meal we always bolus for the protein and bolus between 15 and 25 carbs for it.   For high fat take aways ie Chinese, fish and chips, pizza we over bolus by about 10 to 20 carbs and then after a few hours we start to see a rise so whack on a higher temp basal of around 150 to 160% for 2 to 4 hours.  It means we test blood sugar levels more or look at the Medtronic CGM sensor more, to see what’s going on.”

[theprofsblog]

Better Long Term Outcomes in Type 1 Diabetes

We are used to hearing that diabetes shortens life expectancy although sometimes it is difficult to separate Type 1 and Type 2 diabetes outcomes.

Historically, mortality in type 1 diabetes has exceeded that in the general population. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study cohort was set up in the 1980s to compare intensive insulin therapies with conventional approaches.  

In the short term intensive insulin therapy reduced complications such as kidney disease.  EDIC is the long term follow up of this study.  

In the August edition of Diabetes Care mortality, in the intensive treated arm of DCCT, was slightly but not significantly lower than that observed in the United States population.  In the conventional group it was higher than expected. Mortality risk compared to the general population increased with increasing mean HbA1c with a significant step up over HbA1c of 9% especially amongst females.

This tells us that not only is better control associated with a reduction in complications but we can now say that life expectancy with good control is no different to the general population.  Good news for all with Type 1 Diabetes and especially our youngsters with the condition.

Diabetes Care 2016; 39: 1378–1383

[theprofsblog]

Sunny days

Hi everyone

Hope that you are enjoying the sun and heat!!  Just one thing though these are very high temperatures.  If you are using a pump then you might find that the insulin is not working as well.  At temperatures over 30 degrees there is the chance that the insulin will go off so unless you have a Frio pouch to keep the pump in then best to change the insulin daily.  Also try and keep it out of direct sunlight.  Yes I know it is a pain but this way it makes sure that it is less likely that the insulin will go off.

Pens are less of a problem unless you carry them around with you all the time when same cooling idea applies.

[theprofsblog]

Test Strips

Just about every year we get a note from families that their GP is being bit stingy on blood glucose strips.  This is partly because they look at Type 2 Diabetes where not much blood glucose testing takes place and then question why Type 1 diabetes might be different.

What we know is that blood testing is of paramount importance in the management of Type 1 Diabetes.   Tests are required on a daily basis in order to determine dose adjustments for eating, correction of high blood glucose values and prevention or handling of hypoglycaemia.  Research data show a clear relationship between the frequency of blood glucose control and diabetes control as measured by glycosylated haemoglobin.

The graph is the data for pump therapy showing that there is still benefit out there at 10-12 tests per day.

The minimum number of tests per day that resulted in improving control was 8 with an average of 10 per day.  This would suggest that children and young people with type 1 diabetes require a regular prescription of a minimum of 300 test strips per month.  Just out of interest this costs £150.

There is also a disturbing tendency for local Commissioners to advise certain meters and not others.  This is particularly so with those systems that link to the pumps.  This can be simply deflected on safety issue as the linking is important for schools where it avoids wrong glucose entry when requested into the pump.

[theprofsblog]

Glucagon - the mini dose

LOW DOSE GLUCAGON FOR HYPOGLYCAEMIA

There has been a lot on interest in this topic recently and a recent paper in Diabetes Care this month has opened up the topic for a broader discussion.

  In people who do not have diabetes when blood glucose starts to fall a series of responses start to operate.  At a blood glucose of about 3.6-3.8 mmol/l insulin secretion by the beta cells switches off.  This switch off in insulin leads to an increase in glucagon release from the alpha cells in the pancreas and the increase in glucagon tells the liver to break down glycogen (the liver stores glucose as glycogen) and release glucose into the blood stream.  If the blood glucose falls down to about 3.2 mmol/l then other hormones are released such as adrenaline, cortisol and growth hormone which will all act to increase blood glucose.  Cortisol and growth hormone take some time to act which is why you often get a rebound high after a hypoglycaemic episode.

  In Type 1 diabetes the usual reason for going hypo is that there is a bit too much insulin around for the situation eg doing exercise after lunch when you have bolused normal amount for the food.  As there are no beta cells working, insulin cannot be switched off and because insulin cannot be switched that natural rise in glucagon cannot take place. 

  Normally we get round this by taking rapidly available glucose and going through the “15 rule.”  Occasionally this does not work and a glucagon injection might be needed.  The dose recommended is 0.5mg for those under 12 years of age and 1.0mg for those above 12 years of age. 

  More recent thinking has questioned this and raised the idea of low dosing with glucagon.  This has been in part stimulated by the use of insulin and glucagon in a pump delivery system as part of the artificial pancreas project.  We mentioned this in an earlier article about the closed loop.

  The Diabetes Care study looked at how much glucose was produced (mg/kg) when different doses of glucagon were given on the background of different insulin infusion rates.  The results are summarised in the graph.

So for a child weighing 20kg the insulin infusion rates would be 0.3 units/hr (blue line), 0.6 units/hr (red line) and 1.0 units/hr (black line). 

  These doses are a fraction of the standard suggested dose.  What is important to note is that if the insulin infusion rate is high (black line) then the mini-doses are likely to be less effective in raising the blood glucose.  This will mean that higher more conventional doses may be needed.

  What this means is that if the basal insulin infusion rate is less than 0.05 units/kg body weight/hour then mini-doses would seem to be good way of getting the blood glucose up without overshooting but if rates are higher than this then they may be less effective.

  If you want to read the article which is quite technical then have a look at:

Diabetes Care 2014; 37: 3054-60.

[theprofsblog]

Getting HbA1c Right

We all know that one of the important things about type 1 diabetes is getting a good HbA1c.  This is because large studies have shown that long term complications of diabetes relate to HbA1c.  So the graph below shows the risk compared to the general population of developing eye (retinopathy), kidney (nephropathy) and nerve (neuropathy) problems if your HbA1c runs at high values for more than 10 years.

In this graph anything less than 7.5% carries a risk similar to the general population without diabetes as the risk is nearly 1.  Even up to 8% the risk only gets close to 2.  Remember that the risk in the general population is quite small anyway.

  HbA1c is a measure of how much glucose sticks to the Haemoglobin in the red blood cells.  It is quite useful as red blood cells have a life of about 120 days so the HbA1c gives us an idea of average blood glucose concentrations over that time.

Unfortunately HbA1c is measured either as a percentage eg 7.5% or in newer units eg 58 mmol/mol.

Day to day diabetes management uses blood glucose measurements which are in mmol/l so how do I relate what I measure on a day to day basis to the HbA1c that I want to achieve?

Over the last 2-3 years several studies have shown how to do this by relating the results of continuous blood glucose monitoring over long periods of time to a HbA1c measurement.

We can now use a graph to translate our blood glucose measurement into what the HbA1c is likely to be.

  So what you can do is to each week check the average blood glucose for that week and then read off what your HbA1c is likely to be as a result if you kept up that average for the next 3 months.  So if your blood glucose average for the week is 7 mmol/l then you are likely to have an HbA1c of 6%, if 8.6 mmol/l then the HbA1c will be 7% and to get HbA1c of 7.5% your weekly average needs to be about 9.5 mmol/l. 

This means that you can then start to change things to get your blood glucose looking better and you can then almost predict what your HbA1c will be at the next clinic !!

[theprofsblog]

Closed Loop System - getting better all the time

    Insulin pump therapy has become well established as a way to improving blood glucose control in type 1 diabetes.  Now researchers are seeking to improve this with closed loop systems that monitor and automatically adjust the insulin infusion rate depending on the tissue glucose recorded.

In the medical journals over the last three months here have been a series of reports from several research groups on mainly overnight glucose control using the closed loop system.

Essentially the closed loop uses a glucose sensor to track tissue glucose levels.  These values are fed into a lap-top computer that determines from the glucose level and a series of other parameters the amount of insulin the pump needs to deliver to maintain a normal glucose level.

The closed loop system certainly can achieve overnight normal blood glucose values at least in the hospital setting.  In all the studies to date only insulin has been given.  What is novel about the New England Journal of Medicine article is that insulin is administered as usual using the sensor and pump.  The difference is that at a preset glucose level glucagon is also pumped in as insulin is switched off to avoid hypoglycaemia.

You will remember that normally in the pancreas if our blood glucose falls insulin is switched off and the fall in insulin levels in the pancreas triggers the release of glucagon from the alpha cells in the pancreas and this raises the blood glucose.

So this pump mimics this process.  Not only were 24 hour glucose levels better 7.7 mmol/l on the “bionic” pump there were less hypoglycaemic episodes.

As always the limitations of the closed loop are how good the sensor system is.  This was evident in this study.  Reliable sensors remain the goal if this technology approach is to be of value to patients with type 1 diabetes.  Things are looking good for this kind of technology in the coming 2-3 years.

Check out the paper 

Outpatient Glycemic Control with a Bionic Pancreas in Type 1 Diabetes

New England Journal of Medicine 2014; 371:313-325

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1314474

[theprofsblog]

Ketones : the first blog by Professor Peter Hindmarsh

What are ketones and what do they mean is a common question asked by parents of children with Type 1 Diabetes Mellitus (T1DM).  Ketones are by-products of the breakdown of fat by the body.  There is a balance between us building up fat stores and breaking them down and one of the key factors that stops us breaking fat down is insulin.  Whenever insulin is around then the system works to store glucose as fat.  When insulin is not around in the blood then fat can be broken down to release energy and the by-product of this is the formation of ketone bodies.

In fact ketones are very weak acids and there are two forms beta-hydroxybutyric acid and acetoacetate.  These are what gives you the pear drop smell. Ketones come as result of four possibilities

1. Lack of insulin

2. Ingestion of alcohol

3. Break down of fruit juices in the large bowel.

4. Starvation

 For people with T1DM the most common cause is Number 1.  This is because insulin is required to switch off the breakdown of fat.  When you fast insulin is almost switched off so that you can liberate energy from fat stores. This happens in everyone whether they have diabetes or not.  So in children without diabetes if you test them for ketones first thing in the morning there will some say 0.2-0.6 mmol/l.   These are called starvation ketones.  They are not dangerous as long as the blood glucose is not elevated above 14 mmol/l. They will clear once food is taken in with insulin.

Alcohol when it breaks down forms ketone bodies and certain fruit juices when broken down in the large bowel release ketone bodies which can be absorbed.  The main point about Numbers 2, 3 and 4 are that ketones form when blood glucose is normal.

The important and more worrying situation is when there are ketones present and blood glucose is high.  This can happen when a person with diabetes is unwell and needs action. 

To look at this further check out the website

www.uclh.nhs.uk/T1

and look under Managing Diabetes, Sick day rules for those on insulin pumps or multiple daily injections of insulin.  This gives you tables of what to do if you have a certain blood glucose measurement with a corresponding blood ketone value