Building up resistance to insulin you have used for a long time?

Curious what others’ experiences have been with this. I have taken Humalog exclusively since I was diagnosed about 20 years ago (well, there was a short period of about a year right after diagnosis where I was on MDI so took long acting as well, but after that was switched to the pump and only humalog) and it seems like it takes an increasing amount to get the same results. It also doesn’t work nearly as fast as it is supposed to (sometimes more than an hour to start working even on a fresh site in a rarely used location). My endo and most people say that all rapid acting insulins are pretty much the same, and that one shouldn’t build up a tolerance/resistance to it, but I sure seem to have.

Now this said, I have only tried one other recently which was Apidra which seemed to be a bit better the first day maybe, but ended up with the common crystallization problem so the second day wasn’t so great and not a great example for comparison. Has anyone had this issue and tried Novolog, or the newer FIASP and had better results?

My bolus ratio is about 1u:2g or 1u:3g in the morning till about lunch, and 1u:3-4g the rest of the day. My correction ratio is about 1:20 in the morning and 1:25 after lunch, though I feel like it has actually decreased (increased?) and is probably more like 1:10-15 in the morning and 1:15-20 in the afternoon and night. My basals aren’t horribly high, most are around 1u/hr. I don’t know if those requirements are higher than usual or not, though they seem much higher than most people I have heard from elsewhere. I have heard of some people using u200 concentrations, but I don’t know how beneficial that would be in my case. I also question if higher concentrations would lead to more weight gain, though there seems to be some disagreement on whether insulin actually causes weight gain. I do have issues with site longevity, and many people say large boluses can contribute to that, so I’m not sure if the higher concentration would help or hurt with that. My endo seems to feel that I would have to be doing much larger boluses for that to be a problem.

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Your post resonates with me because I went through a similar experience 6-10 years ago. My insulin just seemed to lose its horsepower and I had to deliver more and more of it and my BG results did not improve.

What I learned from my experience is that excessive insulin causes insulin resistance. I did not think that insulin resistance is something that affected people with T1D. I did affect me, however, and I’ve read of many other cases here.

What finally broke the back of my insulin resistance is simple enough on the face of it: take less insulin!

But how can you do that and not go sky-high BG-wise? For me, I used a lower-carbohydrate diet. Fewer carbs means taking less insulin which also means smaller dosing errors. I was astounded at the effect my changed way of eating had on my overall BG control. BG variability went down and so did my BG average. Most importantly, my total dose of insulin went down from about 80 units/day to under 40 units/day. I also lost 25 pounds without much expenditure of willpower.

I don’t think the brand of insulin matters here. I really think you are taking more insulin than you actually need. Larger insulin doses creates larger insulin resistance while blood glucose averages and variability climb.

I am not a doctor, just a fellow person with diabetes who has lived with diabetes 24/7 for decades. In my case, I went to several endos to try to get the answer for my out-of-control diabetes. I saw three endos in five years. Never once did we have a discussion of my ever-escalating rise in total daily insulin along with a related rise in my weight. I found my answer on this forum from other members.

I may be totally off on what is giving you problems right now, but I don’t think so. I do know one thing, however. Following up on some of my suggestions will cause you no harm. Good luck!

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This is an interesting subject and there have been numerous studies in this area. Even simple testing shows this. Here is one done in 40 hours. https://link.springer.com/article/10.1007/BF00279918

One group was given a higher and higher dose of insulin, the other was given saline (control group). The blood sugar was kept stable by infusions of glucose.

Those that had insulin infusion showed a significant 15% lower ability to use glucose compared to those that did not receive insulin. The insulin group developed 15% greater insulin resistance in only 40 hours.

Whats interesting is that this happened when the insulin level was high for a very long time compared to what you would have with a natural first phase release. This prolonged high level of insulin would be the same effect produced by the long tail of the RAAs.

I haven’t seen this reported with afrezza. In fact with the T2s some are reporting improving BG numbers taking the same level. Some of the early adopters who have been using since approval are not talking about needing more but its only been 3 years. http://afrezzauser.com/update-on-afrezza-users/

Now you have me thinking the increased insulin level with the long tail may be the issue. Does the resistance get worse as the day goes on? Is it less in the morning and worse for dinner?

I don’t know if Al Mann did any studies on this but I bet he did and it wouldn’t surprise me if its part of the private studies Dr. Kendall has been talking about. I am going to see if I can find some interesting research on the correlation between the tail and resistance…

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I also have the problem of insulin resistance, ever increasing doses and weight gain even though I do not over eat and eat low carb.

I just went on a low dose of thyroid medication about three weeks ago for hypothyroid. I have noticed a huge difference in the amount of insulin I’m needing. It’s only been three weeks so I haven’t see a big weight loss yet but I’m hoping to drop a few pounds from it.

I have been taking insulin for 32 years. I started out with regular and NPH. Switched over to Lantus and Humalog about 12 years ago.

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This is a good point. There are other important factors that influence insulin resistance.

@Cinderfella, I wish you continuing success with your new thyroid med.

@Terry IMHO is on to something. My TDD early last year was ~180u/day, with basal accounting for 85u. I changed my eating habits, transitioned to a pump, and changed my exercise regime and now use ~68u/day with basals accounting for 38u. My carb ratios have also changed from 1:2.25 to 1:5 during this process. My greatest IR is overnight and still a challenge for me.

That’s interesting. I don’t know very much about this condition but this thread has me looking at research done in this area. My initial thought is the long tail on the RAA’s have the liver messed up which is affecting the thyroid but thats a wild guess.

You saying going on the thyroid medicine is making a huge difference would make sense. Did you have a CT of your liver done?

No CT of liver. Just going by thyroid readings of blood work.

A lot has been written about insulin resistance in type 1 diabetes, sometimes called ‘double diabetes’ because of its similarities to type 2 diabetes. Some suggested explanations for the phenomenon are that continuing administration of insulin over the years causes the body to become less responsive to it, or that strict control regimens, which may require excess eating to combat the frequent hypoglycemic episodes associated with it, may also be increasing weight, which in turn leads to insulin resistance. A theory increasing in popularity lately is that the inflammatory condition which diabetics suffer from, and which is associated with the complications of the disease, may also cause insulin resistance:

Minerva Endocrinol. 2014 Jun;39(2):119-26.
Association of hematological parameters with insulin resistance in type 1 diabetes.
Bulum T1, Kolarić B, Duvnjak L, Vrhovac R.
Author information
Vuk Vrhovac Clinic for Diabetes Endocrinology and Metabolic Diseases University Hospital Merkur, School of Medicine University of Zagreb, Croatia - tbulum@idb.hr.
Abstract
AIM:
Previous studies reported independent associations of hematological parameters with insulin resistance. The aim of this study was to explore the associations of hematological parameters, including red blood cell count (RBC), hemoglobin (Hgb), white blood cell count (WBC), and platelets with insulin resistance in type 1 diabetes.
METHODS:
Study included 353 patients with type 1 diabetes. None showed signs of acute or chronic inflammatory, renal and cardiovascular diseases. Insulin sensitivity was measured with estimated glucose disposal rate (eGDR) calculated with the equation: eGDR=24.31-(12.22xWHR)-(3.29xAHT)-(0.57xHbA1c). The units were mg.kg-1min-1; WHR=waist to hip ratio; AHT=hypertension.
RESULTS:
RBC, Hgb, and WBC significantly correlated with insulin resistance measured by eGDR (r=-0.12, -0.21, and -0.14, respectively, all P≤0.01), and its components disorders, most notably WHR (r=0.38, 0.44, and 0.16, respectively, all P≤0.001). In a multiple logistic regression analysis after adjustment for age, sex, duration of diabetes and BMI, the presence of insulin resistance was independently associated with WBC count (odds ratio=1.28, P<0.01). The risk of insulin resistance increases by a factor of 4.41 for those in the 4th quartile of WBC, compared to those in 1st quartile.
CONCLUSION:
The significant independent association of WBC with the presence of insulin resistance suggests a role of subclinical inflammation in its pathogenesis.

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I saw this was presented on Sunday an thought maybe related-
https://www.endocrine.org/awards/student-and-early-career-awards/presidential-poster-competition

Swashti Agarwal: SUN-087 (Diabetes and Glucose Metabolism) – Subcutaneous Insulin Resistance Syndrome (SIRS) and Use of Inhaled Insulin

The paper says “with no increase in circulating insulin antibodies. Not much is known about its patho-physiology, but it has been suggested to occur due to rapid subcutaneous degradation of insulin” . It sounds like the presence of an insulin degrading enzyme, maybe?

Here is the study which won the award www.abstractsonline.com/pp8/#!/4482/presentation/7197

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Including age. And we are always getting older. Age also changes our metabolism and how we digest and the distribution and type of body fat, and often even how or what we eat. But it is frequently overlooked when we puzzle over our changing insulin needs.

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Has anyone switched insulin because of this? OP in mind. If yes, did you notice any difference? IC ratio, ISF, Duration, and most important TDD?

I remember reading that some users switch insulin because they suspect becoming resistant to the current insulin that they are using.


As you can see, in the molecular structure of the three fast acting insulin, each have their own slight molecular differrences from each other. Hence the different effects to each and everyone of our body’s endocrinological biological system. So, theoretically, one or the other insulin could be better suited to our own personal BG control. I tried Novolog, Humalog and Apidra. Each one tested for more than 6 months. Novolog gave me edema and muscle cramps. Humalog and Apidra were Ok. Apidra seems to be the fastest acting for me. Oh, I also tried FIASP. Since it is the same as Novolog mostly, with some other ingredients, I STILL EXPERIENCED THE EDEMA AND MUSCLE PAIN. I used it for 3 months. In the end, the onset was the same as Apidra but I needed more FIASP to lower my blood sugar. Hence TDD was 10-20% more with FIASP. I am currently using Apidra and has been for the last 10 years aprox. I was hoping FIASP was my new insulin but… NOT!

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I have T1D for 50+ years, but have not experienced insulin resistance. In past 20+ years I have used Novolog or Humalog in pump, based on insurance company coverage switching between them as preferred brand. Both worked about the same, with slightly lower dose for Novolog, around 18-23 units per day.

However, this past year I started metformin for reasons not related to diabetes. I had to decrease my insulin by about 10%. More likely due to less glucose dump from liver rather than change in resistance. But it is becoming more common for T1s to use metformin.

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I experienced something like this just a few years after diagnosis. I was diagnosed type 1 when I was 8 and started on injections of novolog and lantus. Over time, I somehow developed a resistance to Lantus because we had to keep increasing the dose and my normal BG levels just went higher and higher. At one point I was taking 22 units a day of Lantus! My doctor ended up convincing me to switch to a pump, which solved the problem.
For me, it may have been because I was just hitting puberty at that age (I was 12 or 13 by that time) and the extra hormones and such were messing with the Lantus, but who knows? Hopefully they can get more studies in on this phenomenon in Type 1!

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This is really interesting. Thanks for posting it.

I am glad I could provide some info for you. I thought it was interesting too and if they are correct and its due to rapid subcutaneous degradation of insulin due to an enzyme that would make sense since there is no increase in circulating insulin antibodies.

Whats interesting too is afrezza worked great since it goes directly through the pulmonary and into the blood.

I also saw something the other day which reminded me of a study done 10 years ago at John Hopkins about PWDs having greater decreases in lung function. In the study they raised the concern that inhaled insulin may in theory make things significantly worse. However the three year lung tests from afrezza users are being done and in general none are seeing a decrease in lung function and some are seeing an increase. Maybe afrezza is solving not only the degradation issue but also the lung issue.

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@arpida_seru your post speaks to me, because I get edema and muscle cramps from Humalog. I find I have e to take several potassium and magnesium capsules during the week to negate the cramps and edema.

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When I was on MDI I had the same problem. We had to keep switching the type of Long acting insulin to keep up its sensitivity. When I started on a different long acting, the dosage amount was almost always half of what it was on the previous long acting, but it would gradually increase up again as I seemed to build up resistance. So, we would then switch to another long acting and go through the whole process all over again. The long actings also never lasted as long as they promised - 24 hours never happened; I always had to take 2 or 3 times a day of a long acting to ensure basic background coverage.

This is a bit of an older topic but I had to chime in because YES! A couple years ago I had to drop Apidra because it just was NOT working for me in my pump anymore. I switched to Humalog and took a pump break, which worked much better for a while, but recently my (boundary-pushing) endo recalculated my basal and bolus rates for me to use the U-200 in my Omnipod and that has been a lifesaver!

I think a lot of other factors contributed to my insulin resistance and pump site irritation, but switching to the U-200 kwik pens (ugh, more expensive) has really helped. I’m in my third trimester of pregnancy and maintaining a 5.2 a1c using this method. I was eating low carb/keto last fall before we got pregnant and was finally starting to lose weight, so I’m hopeful that with this new trick up my sleeve, I’ll be able to shed some extra pounds once baby arrives.
I think I heard Humalog was releasing U-200 in a vial soon, maybe end of 2018, early 2019? But don’t quote me on that.
I also saw one of those sample/demo bottles of a different brand of insulin in my doctor’s office that was actually U-500! I wish I remembered the name of it.

Hi. I am new to this community but registered this evening after discovering information on this topic online. I’m 56 and have been type-1 for 23 years. I’ve been using Apidra for a few years now and in the last couple of months my insulin does not seem to working effectively at all. I’m on the Dexcom G5 and so I am able to monitor my levels on on CGM basis. Notwithstanding exercise and a low carb diet, my levels continue to be high as if I have not taken insulin at all. I saw the article about Subcutaneous Insulin Resistance Syndrome and will be contacting my doctor tomorrow to look at options. I guess I should first try changing insulin types but my concern is that this might not make much of a difference.

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