FUDiabetes

Levemir - giving me some real trouble here

Greetings all,
I am now a couple of months into Levemir use, which i switched to from Tresiba in an effort to better control for ‘unsual’ days of rest/exertion/late dinners, etc. I’m on MDI, and usually exercise every day.
After a pretty good start, things seem to be taking a relatively sharp turn for the worse of late.

Things i’m noticing and experiencing are as follows, and i would be most grateful if others could comment in case of resonance and/or suggested solutions:-

i) Basal dose is rising precipitously, particularly the night dose. I am 61-63kg, and typically took 16-18u (once daily) or Tresiba. I started on a total Levemir dose of 18u, and am now up to 37u (as of last night) - amid a steadily rising daily average BG. Night time dose rose from 10u, to 15u, to 18u, to 20u and now 22u, to try to curb a night time rise/dawn phenomenon. I will probably have to try 25u tonight (so 40u of basal in total). That’s a huge, alarming rise! What’s going on? This can’t continue, surely.

ii) Bolus doses are also rising sharply. My C/I ratio, amid raising the basal, has steadily dropped from c. 15 down to around 5 or 6 as of today, while i’m trying to maintain everything else steady (carbs, exercise, sleep, stress, etc). My total insulin dose has therefore risen from c. 30-35u to 50-60u…accompanied by a rise in daily BG. Weird, and unnerving… making any semblance of control utterly transitory.

iii) Night-time glycemic rises, no matter what dose i seem to take… so i get woken by xDrip alarms any time after c. 3am. 2u of bolus used to push down a 10 or 11mmol reading down to 4-5… now it does very little, and i’m woken again. Typucally end up taking 6-8u during the night on 1-3 separate occasions. This is patently ridiculous. Bolussing (even split doses) tend to result in hypos, likely due to the fat content slowing absorbtion and the insulin acting quicker than the dinner… so i am effectively trying to combat this by raising my nighttime basal, but i’m just chasing my tail.

iv) Correcting highs becoming increasingly challenging… i can go on injecting at night, hours apart, into muscle (hence ‘active’ time surely only a couple of hours) yet they have increasingly little effect… until ‘get-up’ time, when BANG. i shoot down. Does the body somehow ‘store up’ all the injected night time bolus that it did nothing with, and release them in one big load when i actually get up? Needless to say, it’s annoying.

So what do you think is going on here? Is the Levemir fundamentally disagreeing with me? 60u+ for someone of my mass seems over the top, particularly given it was around half that only a few months ago, with no obvious changes. A bad batch? Seems unlikely. Heat damaged? in 15yrs+, never experienced this. Overuse of injection sites? Trying to rotate as much as i can. I have no clue, but my stats are currently absolutely dreadful. Struggling to keep in 3.5-8 for 50% of the day.

Your comments, as always, are warmly welcomed.

Some typical nighttime excursions:




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All these things are most likely caused by the same issue. Same thing for all of them, you need more insulin across the board. So you can most likely rule out an issue with a type of insulin or a particular vial or pen of insulin. Also I assume at some point you have used a different vial or pen. If not, switch it out. Use new needles and everything and totally remove that possibility.

It might be an issue with the injection sites, but those problems usually reveals themselves over years not months.

Has anything changed in the past few months? Diet, exercise amount, total amount of carbs, stress level, sleep habits, total level of activity? Anything that might cause this?

If you can’t identify anything different in your habits or environment, it might be good to get a general wellness check. Get blood-work and so forth (not just A1C, but a complete blood panel, iron, vitamin levels, thyroid, lipids, etc.). See if there is an issue that can be identified that is causing this.

Total dose of insulin gives us great insight into our state. We can learn a lot from our total daily dose (TDD). We can use it to gauge a lot of things - activity and food consumption. It gives us insight that non-diabetics do not have. And it can also be a measure of other health issues.

When you go to an endocrinologist (or any doctor), be aware they might simply mask the issue by giving you U-200 or metformin or something else. Make sure you are clear that you want to identify the cause of the issue, not just take more insulin.

One other thing…

This one might be a little different than the others. This one might just be an issue with insulin profile and timing, and your changing basal needs in the middle of the night.

Since Levemir is somewhat flat, one thing that can help with a nighttime rise like that is a dose of NPH at bedtime. NPH has a peak around 6 hours. So if you took it around 9pm or 10pm, it can help with the middle of the night peak.

I use NPH when I am not using a pump. I’d jump on that one right away. It’s an easy thing to use to at least help address nighttime spikes.

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Thank you @Eric, this, as always, is a very helpful steer.

No - i have tried as best i can to keep the same. The only thing that has changed is my basal insulin: from Tresiba to Levemir, causing me to suspect this is the cause of the regime shift, after a honeymoon first 2/3 weeks. Has this happened to anyone else? Or does Levemir seem to be fairly universally ‘accepted’?

As ever, you are introducing new things to me where my endocrinologist (who i am starting to increasingly regard as useless) fails to. I had never even heard of NPH until today. No idea whether this can be obtained in the UK under the NHS, but i shall explore.

Thank you again.

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Oh, another thing to discuss. How are you doing the Levemir doses? A single dose or multiple doses?

Also, did we discuss the duration of Levemir as it relates to the dosage amount? The variable rate? As in, the more Levemir you take, the longer it lasts.

I am not sure if this was discussed before, I apologize if I forgot.

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We discussed a little, but i’m not sure i 100% followed it.

I have been experimenting. Always two daily doses… tried 12h apart, 10h and 14hr apart, 50/50 dose split, now it’s at around 70/30 night/day. I have been trying to get the ‘peak’ action (8-10hrs? or none at all?) to coincide with 3-6am, when i shoot high and don’t want to get up and bolus.

40u (daily) feels like a huge Levemir dose (vs my 16u of Tresiba), which surely should be lasting a good while (longer than 12hrs?) particularly given my slim 62kg body mass.

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Yes that is a huge amount.

Here is something else to consider. Levemir works differently than other basals in that it binds to the albumin in your blood and is slowly released. Other basals do not do that.

Would be good to ensure your blood panel is normal in that regard, just to rule out any underlying issues. Albumin is made by your liver, and the liver is involved in so much of the framework of blood sugar. It is involved in all the feedback loops - releasing glucose into your blood, taking up glucose, etc.

And it might also be of interest for you to compare your current state with tresiba again. I mean, if you returned to tresiba for a week, would 16 units still work for you? Or did your tresiba requirement also rise?!? That would certainly be a useful test. And an easy thing to test as well.

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I know I had an inflammatory response to Levemir, similar to what I developed in response to Lente after using it for a while back in the day. For me that showed up as a raised red mark around the injection site, which I now recognize as a mast cell reaction. I’ve tolerated NPH, Lantus, and Tresiba all fine. Just saying sometimes one formulation really just doesn’t work for a certain body, and you might not easily find out why, but if returning to Tresiba gives you better results after at least a week (I would give it that long to switch given how long acting Tresiba is), I’d just give up on Levemir if I were you. Inflammation is one sure thing to drive up blood sugars, so if your body is having some kind of inflammatory response, dramatic rises in insulin need could make sense.

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When I tried Tresiba, even at small doses (I was taking around 14 units and kept having to decrease it) it would be extremely potent for the first 12 hours. If I did not eat a high fat/protein dinner it would drive me low all night and even in the morning I couldn’t really dose for breakfast without going low. I had to keep decreasing it until I got to a point where I wasn’t taking enough for it to even last 18 hours, and so I gave up on it. What do you usually eat for dinner and how late? I wonder if it was giving you a similar effect and just helping to cover high fat/protein meals at low doses.

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I wonder if you are just not taking enough during the day and seeing the effect of this much later on. This might also explain why your carb ratio has changed so drastically - you may be short on basal all day and compensating for it with insulin. Also as @Eric said, its duration is dose-dependent, meaning a 70/30 split might give you trouble. A typical night dose is only going to last me 10-12 hours at best, and the last 2 hours aren’t very effective at curbing dawn phenomenon. So if I were to take significantly less in the morning, it would not come close to lasting till evening. I don’t think of it in terms of a proportional split (i.e. 70/30 or 50/50). I don’t know what my total daily basal dose is/should be, and don’t care. I think of it as how much Levemir I need to take to cover sleeping, and in the morning how much I need for my day ahead.
If 10 units at night covers me for 10-12 hours, I could not get away with taking 3-4 units at any time during the next day for example. That would only last a few hours and I would have no basal coverage for hours after.

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One last thing - how late are you eating and when do you take your nighttime Levemir dose? Remember it takes ~2 hours to kick in and peaks later than this, so if you are taking it at midnight and eating dinner late and/or foods that are spiking you around 1-2am, I doubt your Levemir dose is going to be able to handle this alone even if you have taken a large dose.

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Overall Levemir has been my favorite long-lasting insulin. There have been times when my number has gone up unexpectedly and it has usually been due to either the Levemir pen being old or getting warm. Even taking care of the pens sometimes it just seems to happen which in turn throws everything else off.

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Thanks @Eric. Over the last few days I have dialled things down again (since dialling up was making no difference, in fact, if anything driving me even higher) and am now on 12u morning and evening…and seeing my C/I ratio back up to a more ‘normal’ (for me) 10-12. 24u of basal is still 50% higher than my Tresiba dose, but i heard that it is less potent, and can’t be compared like-for-like.

So i’m not sure why adjusting my evening doses higher didn’t push my BG lower at night, and instead casues a ridiculous feedback loop causing ever-higher doses, to less and less effect…

At least the doses now look healthier again, but still have my original problem of rising every night from 1 or 2am (after being low at bedtime), so am still not sure how to avoid being woken up at 3 or 4am every morning.

NPH might be a possibility. I don’t want to give up on Levemir just yet since i’ve heard so much good stuff about it.

I have asked my nurses (and endo) about this and a blood test to check nothing untoward but still haven’t heard back as yet… the UK’s NHS can be really hit and miss at times.

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Interesting, and sounds like it could well be the cause…but i don’t see any reaction around my injection sites.

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Strange. It’s meant to be the flattest profile? I never noticed any profile as such, but did often rise from 3am, similar to my current problem, which is making me start to think it isn’t the basal change (to Levemir) that’s the causing this problem.

This is potentially a problem: i eat late. I finish work at 6 or 7, go for a run or ride, cook, and then it’s 9:30 or later by the time i eat. i try to keep carbs low, but therefore fat is high (e.g. steak and veg or casserole with pulses… nothing super-high GI), and this fat content likley slows everything down. would it really delay it until 3am or later? that strikes me as odd.
i tend to get a quick spike from whatever sugar is in there, so need bolus straight away (or before eating) but if i bolus again later, i’ll hypo…but then perhaps the gluconeogenesis kicks in later at night and starts me off on my rise.
I try to get to bed by 11:30, which is often soon after i’ve stopped eating, as i’ll often have cheese & biscuits (10-15g carb) after dinner.

This is revolutionary for me. So it varies every day for you? And ‘should’ (theoretically) for all Levermir users? Q is, how do you know how much your day or night needs? And how much does it vary? one night 5u, another night, 15u? or not as wild as that? with bolus, we have our C/I ratio to give us a rough guide, along with adjustments for exercise, current level, etc. what are the equivalent ‘rules’ for Levemir dosing?

As an aside, i’ve adjusted back to 50/50 now (12u/12u) as my sharply unequal doses (at the suggestion of someone else on the forum) unfortunately didn’t seem to work for me… perhaps for the very reasons you are suggesting.

I’ve tried taking at 8pm, 9pm and midnight, and they seem to have no effect. I start rising at around 1am and will continue all night (pretty much a straight 45degree line) if not addressed with a bolus shot (or 2 or 3)

should it really ‘kick in’ ? i thought it was meant to be a flat profile (or as near as can be)
i’ll try tonight now (ie. just after 11pm) but it seems to not to have made a noticable difference in the past. I guess you’re saying if i inject it at 8pm, it’ll ‘start working’ by 10pm and have ‘peak action’ around 1-3am, right when i need it.

are you suggesting 8pm should give a noticeable improvement? the trouble is, i don’t know how much i’ll be eating that evening (at 8pm), which i think you have suggested should effectively drive the evening dosage decision?

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Yeah doesn’t sound like the same thing exactly, but my point is more that bodies can be weird and idiosyncratic and sometimes they just react badly to something that works well for most others. You may or may not get answer, but if other things work better, stick with those. That said, if you haven’t switched out your pen, def do that first. While short acting insulins are pretty robust to time and heat and whatnot, I find that the long acting ones are less so and can go off now and then and become less potent.

That part sounds like an early dawn phenomenon maybe?

Or else if you eat late at night, maybe delayed absorption of food? I find if I eat later in the evening, it can hit my blood sugar much later than the same meal would during the day, presumably due to slowed digestion during sleep/states of parasympathetic dominance.

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Sorry you’re having a headache with it… but perhaps we shouldn’t simply discount the obvious…

You were doing well on Tresiba, you thought that levemir would offer additional benefits so you switched to it… your results were not what you hoped for and have been frustrating…

Maybe the most simple solution is also the most obvious, that it’s just not actually a better fit for you and tresiba worked better for you?

Yes, especially if you are eating red meat and then adding cheese and biscuits later - the effect can last hours. I think this is your culprit, regardless of what basal you are using or when you take it. You should consider using Actrapid insulin in addition to rapid-acting. It has a curve that is better suited for high fat/protein meals. Also remember if you exercise before, this can cause spikes later on even though exercise can lower blood sugar during it.

This is exactly what Actrapid is suited for. If you Google Dr. Richard Bernstein diabetes solution, the doctor has been advocating for years eating carb-free high protein meals and only using Regular (Actrapid) insulin to bolus for them.

It varies because everyone’s insulin needs are never truly the same every day and night. It does not vary wildly, lately I have been taking 9.5 u 12 h apart because my routine is consistent, but this can change. There is a baseline you can’t go below with Levemir, depending on how long it lasts for you. I really can’t go below 8.5 u, it will not last long enough to get me to the next dose.

I possibly suggested to you that doses don’t have to be equal or 12 h apart, which is true, but only to an extent. It’s not about being equal or unequal, but how much you need to get 10-12 hours out of a dose. That’s why I say total daily basal dose doesn’t matter - you can’t think that you’ve taken 75% of your basal dose at night, so you can just take the other 25% the next day. That likely won’t be enough to cover you during the day. You have to find out, through trial and error and using a Libre/CGM, how long doses last for you. Again, I can’t go below 8 units as this won’t last long enough - it makes no difference how much I took at night. Doses also don’t have to be 12 h apart, but you have to consider how long your doses last in scheduling them. If a night dose lasts you 12 hours, you can’t take your daytime dose 14 hours later without a gap.

Yes, every time you take a dose it takes about 2 hours to start working and there is a curve - it ramps up and ramps down. This is why overlap can be helpful and you can’t space your doses too far apart depending on how long you know they last. Again, you are not feeding a total daily basal dose with Levemir. Think of each dose as relatively independent from the next.

I don’t know, it’s all trial and error. It depends when you wake up too, if you are getting up at 6am that night work, but if you sleep till 8 or later you are likely to wake up with a rising BG. Just remember this - if you took your morning Levemir dose at 9am, for example, eat dinner at 9pm and take your evening dose at that time, you are eating right when your morning dose is likely fading away and your evening dose has not yet kicked in - you have the least amount of basal insulin possible in your system, and this can cause issues.

It’s trial and error and knowing from experience. Often I get it wrong too, but at least I can try again 12 hours later. If I know it will be a stressful day I will add 2-3 units in the morning. If I ate a big dinner with dessert I will add 3-4 units at night. It gives me a fighting chance to deal with these problems. It’s closer to the flexibility of a pump, where you can change basal patterns or set temporary basal rates. It’s all about finding a baseline and then adjusting based off experience, intuition, what your CGM/Libre is telling you and sometimes wild guesses. I do this with dosing for meals as well, instead of trying to follow rigid ratios which never work out anyway.