A little over a month ago I wrote how I was starting long-acting insulin at night and beginning the journey of finding the right level.
The good news is I have started to achieve gluco-normal levels in the morning and I am so excited I thought I would write about the path to get there.
A couple of years ago I did a literature review to work out at what blood glucose levels damage is being done to my body. The conclusions out of that were:
There is NO evidence that occasionally going over 140mg/dL (7.8 mmol/L) does damage. None, zero, zilch. So stop beating yourself up over a “bad day”. The damage to your mental health is not worth it. Win the war and do not focus on the odd battle that goes astray.
Keeping your HbA1c below 7.0% is good and, if you are at low risk of hypo, below 6.4% is better. Arguably, the lower you can go without exposure to serious hypos is a good thing
A fasting blood glucose below 120mg/dL (6.7mmol/L) is a good thing although the best predictor is HbA1c
My last blood results had an HbA1c of 6.6% and a fasting glucose of 7.2mmol/L so things had to change. This is where Levemir came in.
The Choice Of Treatment
I could shortcut to simply using a pump and continuous glucose monitor (CGM) which, in an ideal world, talk to each other to manage my blood glucose levels but, as I still do not require mealtime insulin, and that is a lot of equipment to manage (and pay for given CGMs are not yet subsidized for most people with Type 1 diabetes in Australia), I opted for a simpler solution of taking a long-acting insulin at night.
The insulin suggested by my endo was Levemir. While there are 24-hour insulins available (and weekly ones coming soon), the problem was overnight highs (confirmed by wearing a CGM a couple of weeks up to my endo appointment). We can see this in the excursions above 10 in the below plot which happen, almost exclusively, post dinner and continue until after midnight.
Levemir, with a roughly 12 hour action was a good choice.
Working Out The Dosage
The fact is there is no way to work out the right dosage without experimenting. Too little and blood sugars remain high, doing damage over time. Too much and you hypo which is dangerous and damaging. To quote a meme.
At my endo’s recommendation I started at 2 units and took measurements in the middle of the night and in the morning with a view of keeping the measurement in the middle of the night above 4.5mmol/L (80ish mg/dL) and between 4.5-5.5mmol/L (80-100mg/dL) in the morning. Each week I saw if I was in the goal range and, if not, incremented by 2 additional units.
This went on for a month but it was clear even 8 units was not doing much at all for my blood glucose levels. Clearly insulin resistance (which I knew I had) was working against me. My endo suggested jumping to 14 units and when this did not work, I went to 20 units.
This morning, for the first time in a long time, my morning blood glucose was in the set range.
Next is to fine tune the units to keep the average around 5.0mmol/L (90mg/dL) and minimise the variation. To measure this I will be looking at the 7-day average for the night and morning readings and the standard deviation. Both of these are readily calculable in Excel. My hope is adjusting the dosage and being reasonably strict on when I inject will keep these measures in check.
Conclusions/Things I Have Learned
Set your targets/goals early in your diagnosis: It is very easy to put off making a move to insulin, convincing yourself you will move more and eat less and it will all be better in 3-6 months time. I believe a better approach is have your past self set the goals for you when it is less likely emotion will influence the decision. It is also much harder arguing with your past self than it is with an endo who you can dismiss as not knowing your ‘lived experience’.
Tread carefully but purposefully: While it took a bit over a month to get near the right dosage, the approach was safe in the short term and set me up well for the long term
Continue to monitor, measure and improve: Getting my levels right now, and monitoring for change will set me up well for when I move to a pump and ensure I remain as healthy as possible. Injecting once a day and measuring twice a day seems like a small price to pay to minimise the risk of long term complications and short term hypos.
It may seem like a curious choice but there is method to it. In “Frio vs Breezy Packs” I mentioned that Breezy Packs use Phase Change Materials (PCMs) to maintain the internal temperature. For a rundown of the physics on how they work, head over to that post.
While the specific material used in Breezy Packs is a trade secret, one candidate substance is octadecane whose melting point is around 28C (82.5F). While not listed on the box, on eBay the listing for the breast pads had octadecane as one of the main ingredients. For $20 it was worth a shot.
Sure enough, on touching the pad there was a cooling sensation so things were promising.
For Breezy Packs, I used their smallest size and put one of my Ozempic pens inside with a digital temperature sensor embedded within it.
For the breast pads, I used a mesh pencil case I had picked up and layered the breast pads inside with another pen with a sensor between them.
In the image you only see the pads on one side but I did put eight on one side and eight on the other for the experiment.
A third sensor was used to track the oven temperature.
With the two containers on a rack on an oven tray (I did not want the tray to be in direct contact with the containers) I placed them in the oven and took the temperature around every five minutes until one of the containers went past 30C (86F).
Prior to entering the oven, the breast pads consistently measured a lower temperature than the Breezy Pack. I assume this was because of the higher area of contact between the pads and the insulin pen. However, things changed when the oven became involved.
While the breast pads initially showed a lower temperature, this soon changed. Both were pretty stable but, at 17:15, the temperature of the oven was continuing to fall and was heading towards 30C so I increased the dial by a small amount. The different response can be seen with the breast pads increasing temperature much faster than the Breezy Pack and eventually hitting 30C. In fact, over 40 minutes, the breast pad temperature went up by 7C (12F) compared to 2C (3F) for the Breezy Pack.
Breezy Packs wins again although I suspect if we used a similar volume/weight of breast pad PCM the result may have been different. This being said, the amount of breast pads needed to achieve this would be excessively expensive. As with previous experiments, the components were fully funded by myself without commercial sponsorship of any kind.
I had my six-monthly meeting with my Endocrinologist this week and it was clear the atmosphere was a little more formal than usual. Looking over my blood results he asked “Where do you want to start?”. Getting straight to the point I indicated the HbA1c number to which he replied “6.6%”.
This came as quite a shock as, for the five years since diagnosis, I had been 6.1% or less. The number had drifted up slightly in the last few results but this was quite the jump. “Well that’s it”, I concluded, “it is time to get onto the good stuff” which, in this case, meant insulin.
Set Your Goals and Limits Early
Back in November 2019 I had written a blog on what levels a person must maintain to limit damage and the risk of long term complications. My conclusion had been an HbA1c over 6.4% significantly increased the risk of complications and, once I reached this mark, it was time for insulin. That time had come.
I cannot recommend highly enough setting these kinds of personal limits early in your diabetes journey. Talk to your health team, review the literature as I did and create your own lines in the sand. When the time comes, they will serve you well because it is only natural to try and maintain the status quo when, in fact, change is necessary. Let your past self guide your present self so you can both look after your future self.
Grieving the Loss of Familiarity
I am a firm believer people go through grief when faced with significant changes in their life. The move to using insulin while not a big deal in itself, is such a change. While my other medications are to slow the progression of the disease and will no longer be needed in the future, the move to insulin is, in all likelihood, a permanent one.
In reviewing my HbA1c it was tempting to defend the result by considering the large error margin that is inherent in the HbA1c measurement (Denial) but, thanks to my regular reporting for my endo, I knew this result was consistent with the trend of my numbers heading upward and unlikely to be an outlier.
Without my line in the sand of 6.4% it would have also been tempting to give it another, say, six months, resisting my endo’s recommendation for insulin intervention and see where the numbers landed, doing my best to exercise more and eat less sugar in the interim (Pleading, Bargaining, and Desperation) but past Leon had prepared for this day allowing me to move past the second stage, reconciled by evidence over emotion.
There was a little Anger at myself for not doing more e.g. more exercise and less candy but, in reality, the immune system always wins. Five years of insulin independence was a remarkable achievement and it is mentally much healthier to focus on what was achieved than what was not.
There was also a little Depression that the inevitable had arrived along with small feelings of Loss of Self but, again, equipped with the knowledge that this was always going to happen helped me get past this. While there may still be some lingering feelings of this (while I write this it has been three days since I saw the endo), it is time to accept the next stage of my journey.
Acceptance and the Road Ahead
I had put on a sensor in the weeks leading up to the meeting with the endo so we had good information to guide us on where the high sugars were.
It is clear in the trace that from around 9pm at night my numbers go up and slowly drift down until morning. It is also clear that this drift sits around 7 mmol/L (126 mg/dL) and should probably be closer to 5 mmol/L. I remember when I was first diagnosed my blood sugars would sit in the 4s outside of meals but I have not been there for a very long time. This night-time elevation is where we decided to target the levels.
Long Acting Insulin
I spoke about the two main roles of insulin back in 2019. In short, if you are not eating, your levels should be reasonably flat and towards the bottom on the standard range e.g. 4.5-5.5 mmol/L (80-100 mg/dL). If the levels are not behaving like this, it is likely the body is struggling to keep the liver’s glucose release in check. For multiple daily injection, this is the role performed by long acting insulin.
As neither I nor my endo know exactly how much insulin is needed to flatten the overnight curve, we are starting conservatively: 2 units of Levemir taken at around 9pm and monitored once in the middle of the night (checking I am not too low), and once in the morning to see if I am between 4.5 and 5.5 mmol/L.
After one week I will see how it has gone and, if I am not getting down low enough, I will increase the dosage by another 2 units, monitor for another week, rinse and repeat.
There are a few long-acting insulins available but Levemir is useful for my specific purpose because it has peak activity for 12 or so hours which matches the period of time I need it for.
The New Normal
This is now my new normal; injecting once at night and for now, monitoring levels twice per day until I get the dosage right. My new goal is to reduce my HbA1c to a healthier level (sub-6% without hypos would be ideal) and if I can do this without the need for mealtime insulin, even better. Of course, if I continue to have an HbA1c above 6.4%, additional measures will be required. Again, the measures I have set for myself, informed by my own investigations and supported by discussions with my health care team, will guide me and allow me to keep a level head no matter what happens.
I thought I would go through the report I generate for my endo before every visit and the tools I use to create it.
Tool 1: Microsoft Word
All the graphs and tables I generate I put into Word and then save to PDF for emailing.
Tool 2: Nightscout (OOB Reports)
If you are unfamiliar with Nightscout it is, essentially, a web site which shows your CGM’s glucose readings. Very useful for allowing others to review your levels, and used in some looping setups.
For more details on Nightscout, go here. It all might sound technical but the automated scripts make things really easy and no coding knowledge is needed. Also, all the tools it uses are free.
It also comes with a report section which can generate a Glucose Distribution Graph. Generally I select three months for my graphs even if I have not been wearing a CGM for the whole time. This is what the graph looks like.
I am pretty happy with this. Using the conventional TIR range (3.8-10/70-180) I am 93% in range. Given I have not been particularly strict over the last three months, I am good with this. My predicted HbA1c is 6.0% which is creeping up but, given my pancreas is slowly being destroyed by my immune system, this is not overly surprising. Hopefully the blood tests will reflect a similar HbA1c when I get the results back.
Nightscout also has a Glucose Percentile report showing the spread of values over the day.
Looking at the highs, the areas of interest are night time (around 8pm – 1am) and lunchtime (2pm). In both cases it is likely poor food choices which are to blame. Maybe choosing less carby options at lunchtime will help and maybe I need to be more judicious in my late night snacking.
For this tool you will need Nightscout set up. Assuming you have Nightscout in place, you go to the Nightscout Reporter site, give it the web address of your Nightscout site and it does the rest. It also generates a table with similar information to the first graph.
To the casual observer, the “Lowest value in the period” at 1.7mmol/L (30mg/dL) may seem something of concern but this was simply a bad reading from my CGM; it is either a “compression low” (sensor giving a low reading by being squashed) or a worn out sensor giving nonsense readings. Being insulin independent it is impossible for me to go that low. The lowest I have ever been is around 3.5mmol/L (63mg/dL).
The Nightscout Reporter also has a Glucose Percentile Report but, as it is essentially a repeat of the same report from Nightscout reports, you only need one of them.
The next report I include in my report to my endo is the Comprehensive Glucose Pentagon. It is a spider graph of five parameters us people with diabetes need to keep an eye on and compares it to the typical values for a Muggle (non diabetic person).
For me, the outlier is the CV %, the variability in my glycaemic values. Again this suggests maybe less sweet treats and more lower GI options.
Finally, the Nightscout Reporter gives us a distribution graph of glucose values.
This also gives us a good indication of where our numbers sit.
Medications and Questions
Finally in my report to the endo I include a list of my medications and supplements, and any questions I have. Given my questions often involve new medications or protocols it seems fair to give my endo some notice before meeting them so they can do some research beforehand.
The other benefit of generating these reports is I can review the results over time. For example, here are the results of my glucose distribution for 13/08/20-13/11/20, 17/06/21-14/09/21, and 12/12/21-12/03/22
If we look at the “Values above 10.0mmol/L” (180mg/dL) we see this is slowly increasing but still substantially less than the 25-30% guideline.
While the standard deviation is the same, the GVI is increasing suggesting less blood glucose control, but still in the “good” range.
Average glucose is also rising over time.
All of this is consistent with a LADA’s slowly deteriorating pancreas. The question will be when do I start looking at additional interventions, such as insulin? As per my analysis on when damage starts to accumulate, I am happy to let things progress until my HbA1c gets closer to 6.5% but this is also a good subject to discuss with my endocrinologist at my appointment.
This week was my fifth diaversary. It is a word you will not find in the dictionary and is used exclusively in the diabetes community. In short, it is five years since I was diagnosed with Type 1 diabetes.
It may seem a strange thing to celebrate, the acquisition of a chronic, damaging, sometimes fatal disease but it is important, at least to me.
To celebrate I went all out with Italian:
Half of a 14″ meat-lovers pizza
4-inch square of lasagne
half a garlic bread roll
single serve of tiramisu
A nightmare to manage for most Type 1s. Being a honeymooning LADA, albeit an insulin-independent one, helped although I still spiked, peaking at around 12.2mmol/L (220mg/dl) and then headed down.
So why subject my body to such a stress? Because sometimes it is the healthiest thing you can you do for yourself.
My Usual Eating Routine
I characterise my diet at “lowish carbohydrate”. Where there is an obvious, practical low/no carbohydrate alternative to a food, I will eat it. I do not drink sugary drinks, opting for the ‘diet’ alternatives. I am very comfortable with sugar substitutes such as phenylalanine and sucralose. As a general rule I try to make sure anything solid I eat has 10% net carb or less and, for liquids, zero carbs. That is it.
The result, when I stick to this, are blood glucose traces like this.
The thing is, even with these relatively light rules, it still requires commitment and effort to maintain. If I am eating out, I need to scan the menu for the friendliest options. I need to make sure, if I order a soft drink, that the diet version has been served and not its sugar-filled cousin and so on.
Other Common Eating Regimens
Other common eating regimens for people with diabetes are even stricter. If we consider Bernstein’s approach we are eating:
30g of net carb or less per day
Roughly the same amount of carb every day for breakfast, lunch, and dinner e.g. 6g, 12g, 12g
Eating at roughly the same time every day
That is a lot to keep on top of and while I am sure the ‘Gritters’ will say it is not a big deal and worth it because “we deserve normal blood sugar levels” there is no doubt it does require effort and will impact social interactions with those not complying with this routine.
The strictest of all is probably the zero-carb carnivore diet. This pretty much speaks for itself; if it was not once part of an animal (or is a drink with practically no calories) it is off the list.
At the other end of the spectrum we have the Forks Over Knives advocates, where eating involves a “plant-based diet”. In short a “small v” vegan diet where no foods are off-limits but some (those from animals) are to be avoided.
This one is relatively friendly and, for those looking to reduce insulin resistance the benefits of avoiding animal fats may outweigh the additional carb intake.
Whatever system that is followed, assuming a person with diabetes is adopting some kind of food management, rules mean conscious effort.
The Risk To Mental Health
Orthorexia nervosa is defined as “an unspecified feeding or eating disorder characterized by an exaggerated, unhealthy obsession with healthy eating”. “The affected individual might be driven by dietary asceticism, cherry-picked evidence, or even by evidence-based recommendations, leading to a restrictive dietary pattern in pursuit of improved health”. Overly strict diets which individuals religiously follow, and myths about the food we eat feed, reinforce this kind of unhealthy thinking.
Another aspect is willpower (also known as volition) is a finite resource. A person can only perform conscious actions for so long before they need to take a break. A person with diabetes is ‘on’ 24-7 (except possibly the closed loopers but they are still the exception rather than the rule). They know that maintaining their blood sugar is necessary to stay alive and stay healthy. So what happens when they run out of willpower to manage their disease? Diabetes Burnout. They simply stop managing the disease because they need to take a break.
Obviously there is a lot more to managing diabetes than food intake but it certainly contributes and can be overly burdensome when it becomes all-consuming.
Food Myths Which Contribute To Orthorexia And Diabetes Burnout
There are a few myths when it comes to blood sugars and food which focus on 140mg/dl (7.8mmol/L)
“Damage Starts Happening When Your Blood Sugar Goes Over 140mg/dl”
I tackled this in a previous blog. In short, there is no evidence that damage begins over 140mg/dl. There is literally no study which has examined people with blood sugars at 141mg/dl and observed cellular damage occurring. It is a myth used to sell books but has no basis in scientific fact. It is true that having a sustained high blood sugar will do damage in the long term but this is better measured through metrics such as the HbA1c or Time in Range (TIR).
“Muggles (Non-Diabetic Folk) Never Go Above 140mg/dl”
This is simply not true. A recent article gave a great summary of some of the research that has been done in this area. Here are quotes from the studies examined:
Muggle Study #1: “On average, their daily glucose levels stayed between 70–140 mg/dl for 93% of the day, with very small portions of the day spent above 140 mg/dl or below 70 mg/dl”
Muggle Study #2: “Levels were lower than 70 mg/dl for 1.7% of the time and greater than 140 mg/dl, only 0.4% of the time.”
Muggle Study #3: “Participants spent 93% of time between glucose values of 70-140 mg/dl, with 3% of the time below 70 mg/dL on average and 4% of the time above 140 mg/dl on average”
Muggle Study #4: “2.1% of glucose sensor values were >140 mg/dl”
Muggle Study #5: “Glucose was above 140 mg/dL for only 0.8% of the day”
Muggle Study #6: “Participants spent 1.6% of the time above 140 mg/dl”
Literally every study showed that while going above 140mg/dl was the exception, even Muggles do it for short periods of time every day.
In other words, not only are these myths untrue, anyone believing them is putting themselves under unnecessary mental stress for effectively no discernible gain.
Diaversary As A Mental Steam-Release Valve
This is why I celebrate my diaversary. My diaversary is a day when I give myself permission to not to be as concerned with my blood sugars, secure in the knowledge that one day of spiking is going to do little but give me a mental break and help me recharge for the other 364 days. I genuinely believe the one day of poor bloods is a small price for sustained mental wellbeing. While maintaining healthy blood glucose levels is important, so is managing my mental health. My diaversary is a key element in my approach.
My previous battle, Frio vs Gel, showed that while a gel pack slows down the transfer of heat, it has no power to stop that heat energy eventually reaching the contents of the pouch. In contrast, the evaporation of the water from the Frio pouch actively fights the heating of insulin by redirecting the heat energy to converting the water from a liquid to a gas.
In this battle, we have two related, but different technologies which both redirect the heat energy to perform other tasks than heating the pouch contents. As mentioned, for the Frio pouch, it is the conversion of water to steam and, for the Breezy Pack, it is the melting of a mysterious substance called a PCM (Phase Change Material).
What are PCMs?
We know from high school science that, in the everyday world, matter is in one of three states: solid, liquid, or gas. What we may not know is, to move from solid to liquid, or liquid to gas takes energy. The scientific term for the energy required to melt a substance is the “Heat of Fusion” or “Enthalpy of Fusion” and it is measured in energy per weight e.g. kJ/kg or energy per volume e.g. MJ/m^3.
The energy needed to evaporate a substance is called the “Heat of Vaporization”. It turns out the energy needed to evaporate water is really high. It literally takes five times the energy to get water to turn to steam once it reaches boiling temperature than it takes to take water from ice to that temperature. So, if you have a kettle or heater which can get your water to just under boiling temperature, and that serves your purposes, do so because you will save a LOT of money on energy bills.
So, in the case of our Frio pouch, the PCM at play is water going from a liquid to a gas. While water does boil at 100C (212F), even at 30-40C (86-104F) we get some cooling effect because the water molecules in the Frio pouch are at a range of energy levels so a little heat energy can tip some of these over to becoming a gas at these lower temperatures. This is why we may see a little steam, even before the water is boiling.
In the case of Breezy Packs, the makers do not reveal what the PCM substance is but we can make an educated guess.
What is the PCM in Breezy Packs?
This is what we know:
The substance is solid below 25C (77F) and turns to a liquid above this temperature. We know this from the instruction sheet.
From the Breezy Pack website, the substance begins to melt above 27C (80.6F)
Going to Wikipedia, we have a range of common PCMs. Assuming the manufacturers have gone for an inexpensive PCM whose melting point is somewhere above room temperature and below the fail temperature for insulin (around 30C/86F) the obvious choice is Sodium Sulfate, maybe with some salt added. At US5c/kg, it is the cheapest PCM in the table, after water. You will notice below that pure Sodium Sulfate melts at 32.4C (90.3F) but, adding a little salt brings this down to a lower temperature. I have bought some pure Sodium Sulfate to experiment with and see if I can replicate the Breezy Pack but that is for another post.
As with the Frio vs Gel experiment, I have enlisted the help of my oven to maintain an even temperature. While I used the middle shelf and the fan forced setting last time, I was finding the oven was going above 46C (115F) which I did not want so I put the Frio and Breezy pouches on the lower shelf with only the top element on. I also put a dishcloth on the middle shelf to act as a shield from the direct heat of the heating element. I also put the two pouches on two plastic cutting sheets to prevent contact with the metal bottom.
The wires were linked to digital sensors so I could monitor the temperature.
The blank one is the temperature of the oven.
The Breezy Packs, at the time of writing come in two versions: Breezy Basic and Breezy Plus. Both of these are the same physical size but the Breezy Plus contains more PCM so it can work for longer. This experiment used a Breezy Basic. The Frio pouch was the same one as I used in the Gel comparison and was soaked in water for the same amount of time prior to going into the oven i.e. 5 minutes. The only difference was the temperature of the water used which, in this case, was room temperature and not, as last time, from the cold tap.
So, for an oven where we the temperature is between 35-40C (95-104F), we see that the Frio took around 15 minutes to go from 25C (77F) to 30C (86F). In contrast, the Breezy Packs only moved 1.5 degrees Celsius over the same time period.
The rapid rise in the Frio surprised me as it took twice as long to move the temperature the same distance but, even if we use the Frio vs Gel pack results for considering the Frio pouch, we see that it is still out-performed by the Breezy Pack. My guess is the sensor in the Frio pouch was closer to the outside this time around and, therefore heated up quicker. An alternative explanation could be the difference in oven temperature from last time changing the performance of the Frio pouch i.e. the oven ran a little hotter, although more consistently this time around than last time.
To my initial surprise, the Breezy Pack strongly outperformed the Frio pouch. In hindsight, this makes sense. If we think about it considering the PCM in each case, for water, most of the water molecules are still too cold to transition to a gas state and, therefore the heat energy is simply used to warm the material. For the Breezy Pack though, the majority of the molecules are close to melting and will more heat energy can be redirected away from heating the pouch.
Given the Breezy Pack requires no soaking, is not damp and simply works and given the price point for both the Frio pouch and Breezy Pack are similar, it seems clear the Breezy Pack is the superior option between the two when carrying a couple of pens.
Please note: I bought all pouches with my own money and have received no financial benefit in this comparison. This being said, I am very, very open to receiving sample pouches if either Frio or Breezy Pack want me to compare different sized models in the future 😉
David Burren recently put me on to Breezy Packs which, if their claims are to be believed, offer a new way to keep insulin cool in the field. I have ordered a couple of Breezy Packs to put them through their paces but, first, I thought I would try out the existing methods commonly employed to show how they work.
Gel packs contain gel (no surprise there) which holds its temperature well and acts as an insulator. There is no actual cooling mechanism here other than the gel slows heat passing from one side to the other. So, to use a gel pack, you cool it down in the fridge (not the freezer as insulin does not like to be frozen) and put your insulin inside it to protect it from outside fluctuations in temperature. Outside heat is slow to heat up the gel pack which means the insulin stays cold.
Frio is, arguably, the most popular brand name for evaporative cooling pouches for keeping insulin cool. There are other brands out there (I even sell a version in my Etsy store) so feel free to shop around. They all work in the same way though. You immerse the pouch in water for, say, five minutes and it puffs up. You take it out of the water, wipe it down and put your insulin inside.
Not only are the pouch contents (generally silica gel beads or similar) an insulator but they are spectacular at absorbing and holding on to water. How Frio bags work is, when exposed to a warm temperature, the water in the beads begins to evaporate but evaporating water molecules takes energy so, instead of the external heat being used to raise the temperature of the water, some of it is used to turn the water to steam. This means the water temperature stays reasonably stable and, in turn, so does the temperature of the insulin inside the pouch. Our bodies use the same trick to stay cool when we sweat.
Breezy Packs offer a new way to keep insulin cool, which is similar to Frio bags but, instead of absorbing energy, turning water from liquid to a gas, it converts its active material from a solid to a liquid. No need to soak and wipe down. The physics of Breezy Packs is actually very smart so I will save it for when the pouches arrive and I will write another blog on the subject.
The Cooling Battleground: My Oven
It turns out that I can get my fan-forced oven down to around 30-40 degrees Celsius (104 degrees Fahrenheit) so this was my “controlled environment”. The contestants were a small Frio pouch capable of holding two insulin pens and a massive pillow gel insert.
The insert is 30x40cm with three panels. Both pouches went onto an oven tray with baking paper underneath to try and insulate from the metal bottom.
The gel pad was folded into three with two of the panels at the bottom and both pouches had a temperature probe put in the middle of them. As indicated above, the gel pad had been stored in the fridge whereas the Frio was soaked in tap water.
Once in the oven, I monitored their temperature and the temperature of the oven.
Here the gel pack is 10.7 degrees Celsius, the Frio pouch is 23.8 degrees Celsius, and the oven is 35.5 degrees celsius.
Thanks to the magic of Excel we can see how the two pouches fared. The oven temperature, which had previously reached the target temperature, was slowly dropping but remained above 30 degrees for the whole time. The Frio pouch, with the oven’s heat being used to turn the Frio’s water to steam, was holding a reasonably even temperature. The gel pouch, with nothing but insulation, slowly increased in temperature, catching up to the Frio after about 30 minutes, despite the 15 degree head start.
To be honest I was not sure the Frio pouch would work as well as it did as the oven was closed and, therefore, once the air inside the oven was saturated with moisture, the Frio would no longer be able to cool but for the 30 minutes it continued to work.
First of all I was really impressed the results came out as well as they did, showing the characteristics of the two pouches. For my money, if I was expecting to carry insulin for an extended period of time in high heat, I would likely look to a pouch that uses evaporative cooling. I would also invest in a MedAngel so I could check the temperature inside the pouch at any time and be alerted if things were going astray. Gel is a much cheaper option, of course, so, for short excursions, it will work fine. You could also, if you had a large enough pouch, put a cooled gel pouch inside a Frio pouch and gain a double benefit. As long as the Frio pouch is on the outside this should work fine.
Should someone diagnosed with LADA go onto insulin immediately?
Are there treatments for Type 1 other than insulin?
If I do use insulin what are the pros and cons of the various methods of delivery?
As usual, for those who want the short version, you can go to the tl;dr section at the end.
Where We Landed In Part 1
In Part 1, I concluded the diagnosis flow chart from the Type 1 report was the more detailed and effectively covered LADAs flow chart.
So, assuming someone has LADA or Type 1 diabetes means either:
We have some reason to suspect diabetes (unintentional weight loss, ketoacidosis, glucose > 20 mmol/L (>360 mg/DL) etc.)
Auto-antibody presence OR
Low C-peptide (less than 200 pmol/L (0.2 nmol/L) ) OR
No features of Type 2 diabetes (BMI >= 25 kg/m^2, no weight loss, no ketoacidosis, less severe hyperglycaemia etc.)
Treatment According to the LADA Report
The LADA report has a flow chart for treatment which looks like this:
The Type 1 C-peptide limit is different (0.2 nmol/L vs 0.3 nmol/L) but, given there are two other options available which do not consider the C-peptide level in the Type 1 report (auto-antibody presence and no Type 2 features), there is still the possibility that someone with Type 1 could have a C-peptide in any of the above three ranges.
I go through the LADA and Type 2 guidelines in detail in my “Gold Standard” LADA article. In short, if your C-peptide is over 0.7nmol/L (700 pmol/L) options include:
While part of the Type 2 algorithm, there is a notable exception of Sulfonylureas not being used with LADAs because “The panel concluded that sulfonylureas are not recommended for the treatment of LADA, as deterioration of b-cell function as a consequence of this treatment cannot be ruled out”.
For patients with a C-peptide below 0.7 nmol/L, there are two flow charts. The first is if heart (ASCVD/HF) or kidney (CKD) disease is present with the same medications as before except TZDs which may have been excluded because of the limited evidence of benefit and increased risk of bone fracture.
For patients without heart or kidney disease, we have this chart where the SUs are still not present but which does include TZDs.
What is good is this set of flow charts covers the entire Type 1 C-peptide spectrum which means, even when someone with LADA becomes a “classic” Type 1 because of declining C-peptide levels, we have a prescribed course of action. What is missing is a complete answer to the question “When should someone with LADA start using insulin?” The answer from the above flow charts is “If the HbA1c is above target” but no target is firmly established. Let us move to the Type 1 report.
Treatment According to the Type 1 Report
In fact, the Type 1 report immediately addresses the issue of targets for Type 1 in their first table.
Here the target HbA1c is 7.0% with the caveat that “all glycemic targets should be individualized and agreed with the person with diabetes.” So, unless we have discussed and agreed on a different target with our health care team, achieving an HbA1c equal to or below 7.0% is a good benchmark for considering moving to the use of insulin. This is in agreement in my post where I considered how high someone’s HbA1c could be before a significant risk of long term damage.
For the specific question of when someone with LADA should consider bolus insulin, we also have guidelines for post-prandial (after meal) insulin levels with the suggestion that 1-2 hours after a meal a person’s glucose level should be less than 10 mmol/L (180 mg/dL) and the option of pushing this to less than 7.8 mmol/L (140 mg/dL) if safe to do so.
In contrast to the LADA report, the Type 1 report takes an “insulin-first” approach saying “The cornerstone of type 1 diabetes therapy is insulin replacement” and providing the following summary of the multi-pronged approach suggested for the newly diagnosed.
Given how difficult it can be to manage insulin therapy in the newly diagnosed, it acknowledges the need to prepare for hyperglycemia (“highs”) and hypoglycemia (“lows”).
The Type 1 report also talks about the relative merits for the different ways of delivering insulin.
Where money is no object, clearly, closed-loop technology is the winner.
Eventually (page 27 out of 37 pages), the Type 1 report talks about “Adjunctive therapies”. In other words, treatments which can be used alongside insulin.
There is common ground between the two reports with both reports mentioning Metformin, GLP-1 RA, and SGLT-2i. It also mentions pramlintide which is an amylin analogue (another hormone produced by the beta cells and, therefore, compromised in Type 1 diabetes). It fails to mention DPP4i and TZD. TZD may be because of the limited evidence but I am not sure why DDP4i’s were left off the list. They affect the same hormone cycle as GLP-1 RAs and therefore have similar effects/benefits.
Reconciling the Two Reports
In contrast to Part 1 where I sided with the Type 1 flow chart for diagnosis, here I am siding with the LADA report for treatment. There are a few reasons for this:
It explicitly considers treatment in the presence of heart and kidney disease
It offers a more comprehensive range of non-insulin treatment options e.g. DPP4i and TZD (but should likely include Pramlintide as well)
It takes the approach that insulin may not be necessary in patients with high C-peptide levels and, given the inherent hypo/hyper risk that comes with using insulin, if target ranges can be maintained, this seems like a sensible approach to me
This being said, the Type 1 report is much more comprehensive in considering the various ways of delivering insulin to the body (injection, pumps etc.) and also has a lot to say about looking beyond medication for individualised treatment e.g. considering lifestyle factors and diabetes education.
One big takeaway for all people with Type 1 or LADA should be that treatment no longer begins and ends with insulin. There are a range of other medications which can help with managing long term blood glucose levels and have other benefits such as helping a patient lose weight or reduce blood pressure.
Arguably, the LADA report’s flow charts for the treatment of Type 1 diabetes are more detailed for treatment than what is presented in the Type 1 report. Not only, does the LADA report consider insulin independence for patients with high C-peptide levels, it considers which medications are appropriate in the presence of heart or kidney disease. However, the Type 1 report fills in a significant gap of providing target values to chase and which help inform decisions such as when to move to insulin therapy.
The Type 1 report also goes into more detail in the areas of:
The relative merits and costs of different insulin delivery methods
Treatment of Type 1 diabetes beyond medication e.g. lifestyle factors and education
Thanks to the generosity of #dedoc°, I recently had the privilege of virtually attending the world’s largest Diabetes conference: EASD 2021. Arguably the biggest news at the conference was an international consensus on the diagnosis, treatment, and management of Type 1 Diabetes. This is a comprehensive guide, backed by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), which should, in my opinion, be the bible for health care professionals and for guiding health-related government policy.
Interestingly, last year an international consensus was released for the diagnosis, treatment, and management of LADA. I wrote a blog on it at the time going through the details. While not the same authors, nor directly endorsed by ADA/EASD, one would hope the two reports are broadly aligned in their approach given LADA is usually considered a sub-group of Type 1. In fact they are but there are differences at the edges and I raised this during the conference.
Rather than wait for the academics I thought I would go through the reports and see if I could make some headway. I will split this up into at least two parts with this one covering the diagnosis of Type 1 and of LADA.
As usual, there is the tl;dr section at the end for those that want to cut to the chase.
The first problem is there is no simple categorical feature of LADA. At diagnosis it shares features with “classic” Type 1 and Type 2.
So, while we can make a good guess at diagnosis, there is room for error. The report goes on to weigh up the various factors which can be used for assessment and comes up with the following flow chart.
So, first we test for the auto-antibody GADA. If it is positive, the person has Type 1 (LADA) diabetes and their treatment is then determined by their C-peptide levels. The report is vague on whether the C-peptide test is fasting, random time, or post-prandial (after a meal).
If the GADA screening is negative, the report suggests it is likely the patient has Type 2 diabetes and, therefore not LADA (although Type 3c and MODY should be considered). However, if LADA is still suspected, other auto-antibodies such as IA-2A, ICA, and ZnT8A can be screened. If these are positive, we are back to a positive diagnosis of Type 1 with treatment being defined by C-peptide levels.
Diagnosing Type 1
The Type 1 report also weighs up the various factors in diagnosing Type 1 compared to other Types, such as Type 2 and MODY and comes up with this flow chart.
The first statement, like the LADA report, is that no one feature is categorical, not even auto-antibodies (which can be present in other conditions). So, assuming something, such as DKA, has triggered the investigation, testing for auto-antibodies is, like the LADA report, the first place to look. Also, similar to the LADA report, the Type 1 report considers GADA as the first auto-antibody to screen for, followed by the others. If the test is positive, the patient is considered to have Type 1 diabetes.
If the test is negative (as can be the case in 5-10% of people with Type 1), age is the next consideration. For patients over 35 years old, it is not obvious what Type of diabetes they have. The suggestion is assume Type 2 unless there is suspicion of a different Type e.g. Type 3c, but monitor closely for a rapid deterioration in insulin production. After 3 years, test their C-peptide levels (“a random C-peptide measurement (with concurrent glucose) within 5 hours of eating”) and if they are very low (less than 200pmol/L) then they are considered to have Type 1 diabetes. If the C-peptide levels are high (greater than 600pmol/L) the patient is considered to have Type 2 diabetes. If their C-peptide levels are between these two extremes, the recommendation is to re-test in 5 or more years.
For patients who test negative for auto-antibodies and are less than 35 years old, if MODY is suspected, test the C-peptide and if greater than 200pmol/L, perform genetic testing for MODY. If the C-peptide is less than 200pmol/L, the patient is considered to have Type 1 diabetes. Where MODY is not suspected, and there are no indications of “classic” Type 2, the patient is considered to have Type 1 diabetes. While not obvious what the conclusion is for patients with a C-peptide greater than 200pmol/L, one would assume they follow the same path as those over the age of 35.
Reconciling the Two Consensus Reports
The Type 1 flow chart is more complex so we will use this as the foundation and modify it, if required, to align with the LADA flow chart.
In both reports it is directly acknowledged there is no categorical feature to define Type 1 or LADA. For the purposes of diagnosis, this means there must be a reason we are testing for diabetes in the first place. The Type 1 report suggests “unintentional weight loss, ketoacidosis, and glucose >20 mmol/L (>360 mg/dL) at presentation…Other features classically associated with type 1 diabetes, such as ketosis without acidosis, osmotic symptoms, family history, or a history of autoimmune diseases are weak discriminators.”
Assuming some kind of indicator of diabetes is in place, both reports call for screening for the GADA auto-antibody. If this fails, following up with the other indicative auto-antibodies. If any of these are positive then we have a diagnosis of Type 1 and, depending on the C-peptide level, treatment may differ. Given we are dealing with diagnosis and not treatment in this post, let us move to the case of a negative auto-antibody test.
For the LADA consensus report, once all of the auto-antibody tests come back negative, the conclusion is the patient is Type 2. However, the Type 1 consensus report does not give up so easily. As mentioned in the previous section, if the person is under 35, and there is no indication of MODY or Type 2 (high BMI, no DKA and less severe hyperglycaemia), the conclusion is the patient is likely to have Type 1 diabetes.
This last part, where the patient is negative for auto-antibodies, is probably the biggest departure in diagnosis between the two flow charts. Given there is a far higher rate of misdiagnosis of Type 1/LADAs as Type 2 than the other way around, my preference would be to side with the Type 1 report’s process and conclusions. As we will see in my future post on the treatment recommendations of the two reports, the treatment for a person with Type 1 and high C-peptide levels (as can be the case for LADAs), and the treatment for people with Type 2 is quite similar with main difference being the exclusion of sulfonylureas which can accelerate a person with LADA’s progression to insulin dependence.
The two consensus reports are pretty similar with the Type 1 report being the more comprehensive. The main difference is for people who test negative for auto-antibodies. For the LADA consensus report, it is assumed they have Type 2 diabetes whereas the Type 1 consensus report assumes, if there are no indications of MODY or Type 2, the patient likely has Type 1 and should be treated accordingly.
Therefore, whether someone is suspected of having Type 1 diabetes or are part of the LADA sub-group, the Type 1 consensus report’s flow chart is a good guide for accurate diagnosis. The main steps of this flow are:
Determine there is a reason to suspect some form or diabetes e.g. unintentional weight loss, ketoacidosis, and glucose >20 mmol/L (>360 mg/dL) at presentation
Screen for GADA auto-antibodies
If positive, the patient has Type 1 diabetes
If negative and under 35
Consider the possibility of MODY and, for a sufficiently high C-peptide level, test if suspected. If negative for MODY (presumably) treat them as if they were negative and over 35 (see below)
Consider the possibility of Type 2. If the presentation is consistent with Type 2 (high BMI, no DKA and less severe hyperglycaemia) then diagnose them as if they were negative and over 35 (see below)
If the presentation is not consistent with “classic” Type 2 diabetes, assume they are Type 1 and treat accordingly
If negative and over 35
Consider the possibility of other Types but, if there are no other indicators, assume Type 2 diabetes but monitor closely for a rapid drop in insulin production. Test C-peptide levels in 3 years (“a random C-peptide measurement (with concurrent glucose) within 5 hours of eating”). If the C-peptide levels are high, the patient is considered to have Type 2 diabetes, otherwise re-test in 5 or more years
ATTD 2021 was held 2-5 June, 2021 and, thanks to dedoc, I had the privilege to attend and live tweet the presentations. However, with many sessions running in parallel, it was not possible to attend every session and many sessions covered similar topics. To address this, I watched the recordings of the sessions I missed and brought them together under common themes. Where the presentation called out that the results were confidential and/or not yet published and not for distribution I left them out of my blog but I can confirm there was nothing presented under confidence which contradicted what I am presenting in these summaries.
This is my second “distillation” which is on pregnancy and gestational diabetes. For my first “distillation” covering looping go here. Firstly, let me be clear in my intent: I am a male and never been pregnant. My aim is to present the research, as I understand it, from ATTD 2021. I am not a medical professional and nothing here should be considered medical advice or me telling you what to do with your body. If something I have written is of interest, I strongly encourage you to discuss it with your medical team to determine the best course of action for you. I will also call out that this post discusses the possible adverse outcomes of pregnancy for the baby. Not all pregnancies go to plan and if this subject is distressing for you, you may be triggered by the contents of this post.
A common observation of women with diabetes is their menstrual cycle has a significant impact on their blood glucose level management. It is known in that the fluctuation of hormone levels in the body directly impacts insulin resistance. The same happens in pregnancy with the thinking being that hormone levels increase in a woman’s body to increase insulin resistance so more glucose reaches the baby for growth and development.
For women with diabetes this amplifies an existing health condition and, for women who do not have diabetes, given the stresses this puts the body under, it can trigger diabetes during pregnancy in what is called Gestational Diabetes. ATTD 2021 looked at some of the latest research on diabetes and pregnancy which I present here.
Specific questions covered in the presentations were:
As usual there is a TL;DR section at the end if you want to read the summary of results without the details.
If I am a Woman with Diabetes, What are the Health Risks to my Baby?
Dr. Helen Murphy presented on the risks to the baby for women with Type 1 and Type 2 diabetes. Both Dr. Murphy and other presenters made it clear that there has not been a lot of improvement in adverse outcomes for pregnant women with diabetes (congenital abnormalities and deaths), for decades. As we will see later, there is potential for this to change with tools like continuous glucose monitoring devices (CGMs).
A result which surprised me was the risks to women with Type 1 and Type 2 diabetes was about the same and slightly higher for neonatal death in women with Type 2 diabetes. While there appears to be a trend upwards in some of these graphs, Dr. Murphy pointed out the tending was not statistically significant.
A question I had was how this compares to the general population. Dr. Robert Lindsay, covered this with some earlier data. Assuming the risk level has remained the same for the general population, for stillbirth, women with diabetes have a risk somewhere between 2-4 times higher than the general population.
For adverse outcomes (death and congenital defects), we also see similar risk profiles for women with Type 1 and Type 2 diabetes. Literally 1 in 10 women with diabetes, who do not prepare for pregnancy, have a serious complication with their pregnancy. The good news is, with planning and preparation, this number goes down to 1 in 50 which is close to the rate for the general population.
Planning and preparation in this case means taking folic acid before and during pregnancy and controlling blood sugar levels as well as possible. The guideline is to have an HbA1c below 48mmol/mol (6.5%) which, for many, is easier said than done. Many factors affect a woman’s ability to control their blood sugars beyond the usual diet and exercise. For Type 1 is was shown that other factors include:
Age (younger Type 1s often struggle to control their average blood glucose levels compared to their older counterparts)
Social disadvantage (Deprivation)
Time since diagnosis (while older Type 1s typically have a lower HbA1c, those diagnosed 5 or more years ago typically have a higher HbA1c)
BMI (the higher the body mass index, the lower likelihood of a woman with Type 1 having an HbA1c below 6.5%)
For Type 2, social disadvantage was a factor although it does not seem to be as pronounced, time signce diagnosis was a factor, and also BMI.
The only one of these factors which can be easily addressed by a woman looking to get pregnant is BMI but, as many of us know, shifting the needle on weight is not a simple task.
While important before getting pregnant and in the first trimester, HbA1c is also predictive of adverse outcomes as late as the third trimester. For both women with Type 1 and Type 2 diabetes, the risks significantly increase for an HbA1c above 75 mmol/mol (9.0%). Dr. Murphy also pointed out that this result removed confounders (contributing factors such as weight, age etc.) In other words, HbA1c is very predictive of risk.
She also presented details of the relative risks for Neonatal Intensive Care (NICU) admission, preterm birth, and having a “big baby” (LGA: Large for Gestational Age) showing HbA1c also predicts for these events as well.
Dr. Robert Lindsay also presented on factors associated with still birth, including those with Gestational Diabetes.
Not surprisingly, blood glucose levels are a factor here as well even for those diagnosed and treated for gestational diabetes. Given there were different results for the diagnosed and undiagnosed, it suggests there is a factor beyond fasting blood glucose affecting outcomes which treatment is addressing. My assumption is it is the non-fasting glucose levels and their fluctuations.
While the results may seem depressing, there is hope. As we will see in the next two sections, there are new technologies and treatments which can positively impact pregnancy outcomes for women with diabetes of all Types.
Health Benefits of Using a CGM During Pregnancy
Dr. Jennifer Yamamoto presented on the performance and benefits of Continuous Glucose Monitoring (CGMs) for pregnant women with diabetes.
For sensor performance, she spoke of a study looking at placement on the body of the CGM sensor covering women of all Types.
Overall, regardless of placement the accuracy as measured by MARD (Mean Absolute Relative Difference), where a lower number indicates better accuracy, performance was good but the arm was the best area for placement achieving 8.7% accuracy.
In terms of the benefit of using a CGM device, Dr Helen Murphy, presented results specific to Type 1 showing, especially in the third trimester, significantly better results for pregnant women who used a CGM; they literally gained an additional 100 minutes per day in range.
As to be expected, this had a knock-on effect on neonatal outcomes with a statistically significant lowering of risk for a larger baby (LGA), hypoglycaemia, and neonatal ICU admission.
Dr. Claire Meek presented on the predictive power of CGMs for adverse outcomes, using CGM measures such as mean glucose levels (MEAN), Time in Range (TIR), Time Above Range (TAR), Time Below Range (TBR), the coefficient of variation (CV, a measure of variability of levels), and standard deviation (SD, another measure of variability). These were compared to the effectiveness of biomarkers in the blood and the traditional HbA1c.
Even for me these graphs are hard to read but the key takeaway is to look at the rows with an asterisk on the end as these are the measures which were significantly predictive. So, for preterm birth, for 12 weeks, CGM and one of the biomarkers fared well and for 24 weeks, CGM, a different biomarker, and HbA1c fared well.
Looking at predictors for a “big baby” (LGA), Neonatal ICU (NICU) admission, and Neonatal Hypoglycaemia (NH) we see CGM and HbA1c are the constant performers for prediction.
Looking at just Time in Range (TIR) and the HbA1c, we see, for early pregnancy a CGM offers good predictability and the opportunity for early intervention. Later in the pregnancy, HbA1c provides stronger predictability.
In conclusion, CGMs not only offer the ability to predict adverse outcomes early on in the pregnancy but their use can also improve them. Yet again we have compelling evidence that CGMs offer tremendous benefit to people with diabetes.
Should Women with Diabetes Take Metformin?
The final presentation I will talk about was a debate on the benefits and risks of using metformin during pregnancy. This was discussed between Professor Denice Feig who argued the “pro” case and Dr. Yariv Yogev who argued against. However, discussions in the question and answer session at the end showed both agreed on many of the key points with little debate between them.
Typically a “Type 2 drug”, metformin has many effects on the body but is broadly known as a drug which reduces insulin resistance. It is known to cross over the placenta into the baby but it is well established that it does not cause birth defects.
It is understandable that the issue of metformin use needs to be discussed/debated because international consensus on whether metformin or insulin should be used as a first line treatment is still mixed.
Professor Feig presented a meta-analysis study showing the benefit of metformin over insulin although it was clear in the discussion that many women with diabetes often used insulin as well as metformin to help control blood glucose levels.
Factors of potential concern were a lower gestational age i.e. babies were born slightly earlier and a slightly higher incidence of “small babies” or what is referred to as SGA (Small for Gestational Age).
Professor Feig presented other studies comparing metformin to insulin with similar results finding:
Metformin helped with glucose levels after meals
There were less cases of hypoglycaemia with metformin
Metformin reduced the amount of weight gain in mothers and the need for c-sections
For women with Type 2 we, again, saw similar results and the potential for a “small baby”.
There was discussion on the long term effects on the baby of exposure to metformin but both presenters agreed the results are mixed and no strong conclusions can yet be drawn that there are detrimental effects.
Dr. Yogev presented a great table showing how metformin compared to a placebo for outcomes (a p-value of 0.05 or less indicates statistical significance) indicating:
Lower birthweights with metformin
Reduction in the rate of extremely large babies
Increase in small babies
Dr. Yogev did point out that in his own studies he could not confirm the increased risk of small babies as a result of using metformin. Both agreed that where there was a risk of babies being born small, metformin may not be advisable e.g. in the case of twins. Professor Feig also made the point that, if a pregnant woman with diabetes was taking metformin and there was indications that her baby was undersized, metformin could be stopped during pregnancy to minimise any problems.
Health risks to the baby for women with diabetes are:
Higher risk of stillbirth and neonatal death (death in the first few weeks of birth) compared to the general population
Higher risk of congenital defects
These risks can be reduced through taking folic acid both before and during pregnancy and reducing HbA1c. However many factors affect the ability to reduce HbA1c such as age, social disadvantage, time since diagnosis, and weight. While difficult, HbA1c is a strong predictor of outcomes at all stages of pregnancy so any intervention which can help reduce HbA1c is of significant interest.
One intervention which shows promise are CGMs whose measures are predictive of outcomes (especially in early pregnancy while HbA1c is good at predicting outcomes later in pregnancy) and, therefore CGMs can be used to advise early intervention. It was also shown that the use of CGMs for women of all Types saw a reduction in adverse outcome risk. For pregnant women using a CGM while accuracy was good wherever the sensor was placed, placement on the arm showed the most accurate results.
A second intervention which shows promise is metformin, a drug which lowers insulin resistance. While reducing risk across most measures, there was potentially an increased risk in a smaller baby for gestational age (SGA). It was agreed that, in most cases, the risk could be managed through active monitoring of the pregnancy (and taking the pregnant woman off metformin if needed) but for cases where there was an existing known risk of SGA (twin birth, for example) metformin would not be advised.