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recent insulin study

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academicdiabetic

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A few days ago, the email 'newsletter' from Diabetes.co.uk flagged a very recent study which showed that Type 2 Diabetics taking insulin had 3 x the mortality rate of Type 2s taking, for example, metformin. The authors also flagged the mechanisms bu which the higher mortality rates were induced by the action of insulin (i.e. they were linking the higher risk of death directly with taking insulin not with, for example, any differences in risk due to the existing health profile of people likely to be offered insulin).

Has this given anyone else on the forum 'pause for thought'?
 
My take on this would be that Type 2's on insulin tend to be people who have been through the raft of other medications and still failed to control their blood sugar levels due to a failing pancreas or insufficient dietary carb control. They would have had higher blood sugar levels in the intervening years which would have exposed them to a higher likelihood of complications. Maybe the researchers have got their conclusions wrong?
 
I agree, majority of T2's do not go straight onto insulin. It is a long progression of struggling BG levels generally before having to inject.
 
Yes but if there's no history of complications prior to going on insulin why would mortality rate increase
 
Well, I am only guessing but I think for most, certainly not all T2's, insulin is a slow progression from steadily rising BG levels. However, I'm certainly no scientist !


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I haven't read the study so these are just my thoughts as to what might cause the death rates:

1. Insulin is final treatment for poorly controlled Type 2s

2. Insulin resistance is a big factor in Type 2 so injected insulin will be at high doses which can increase weight and make insulin resistance worse.

3. Those with insulin resistance have high levels of insulin as well as high levels of glucose in their blood. Adding more insulin can surely only add to risk factors.

Just my thoughts and not based on any evidence!

Smidge
 
academicdiabetic said:
A few days ago, the email 'newsletter' from Diabetes.co.uk flagged a very recent study which showed that Type 2 Diabetics taking insulin had 3 x the mortality rate of Type 2s taking, for example, metformin. The authors also flagged the mechanisms bu which the higher mortality rates were induced by the action of insulin (i.e. they were linking the higher risk of death directly with taking insulin not with, for example, any differences in risk due to the existing health profile of people likely to be offered insulin).

Has this given anyone else on the forum 'pause for thought'?
Click to expand...
 
Hi,

Thanks for your thoughts all.

So, two ideas so far then:

1) its because they were already 'worse off' healthwise than others (I don't think this is likely in the case of this study - the authors controlled for all such in great detail, including HbA1C...)

2) (from Smidge) that insulin adds to the fact that T2s may already have 'too much' insulin, that's a possibility the authors mentioned also, but still suggests that insulin is definately a bad idea....

The study seems pretty good and certainly has a large sample size (something like 83,000), obviously there may be caveats not given in the paper, but taken at face value why are T2s not running screaming away from insulin (and/or suing their doctors) assuming that they are aware of this study (and its now been flagged on this forum at least twice)?

It also seems highly likely that the same adverse effects are likely to be relevant to T1s as well and whilst it may be that we 'cannot avoid' insulin, the higher mortality rates, renal failure (nearly 4x higher) etc. were found to be dose dependent, so cutting down insulin as far as possible came across as a very good idea.

Assuming the study outcomes are valid, do you (anyone on the forum that is!) think that insulin is just seen as a 'magic bullet' or 'only solution', or are people just not aware that it can, apparently, do a great deal of damage? :(
 
The authors may well have controlled HbA1C but the fact remains that the majority of T2's do not use insulin. It's generally those who have erratic control or have struggled with diabetes for a long time who end up insulin dependant. There will always be exceptions but I think because of this the results are hardly surprising.


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Do you have a link to the study academicdiabetic?
 
academicdiabetic said:
Hi,

Assuming the study outcomes are valid, do you (anyone on the forum that is!) think that insulin is just seen as a 'magic bullet' or 'only solution', or are people just not aware that it can, apparently, do a great deal of damage? :(
Click to expand...

having been in the system for a long time, (as a T1) I am aware that insulin is best minimised. When first diagnosed I ate a restricted carbohydrate diet as instructed in order to keep my sugar levels low. These days I eat a restricted carbohydrate diet to keep my required insulin levels lower.
 
Well, I don't believe that any medication is a magic bullet. All drugs, however beneficial will have unwanted side effects. Insulin is no exception.

One of the things I do know about injected insulin is that it travels through many area of the body that natural insulin does not go into. Natural insulin is contained within only a few area of the body and doesn't leak into places it is not required. We know this is believed to be one of the reasons insulin users have a tendency to put weight on. Maybe insulin being where it shouldn't be is one of the risk factors to mortality in using insulin?

We also know that insulin should not accumulate in the blood - for normal functioning humans, it is produced and used relatively quickly because of the body's amazing balancing act in producing insulin and glucose to keep BG within VERY tight limits. This would tend to suggest that insulin accumulating in the blood isn't very good for you.

Insulin is an amazing drug and it saved my life - and continues to do so every day - but it isn't the correct treatment for everybody and even where it is the correct treatment, I believe that it is a sensible precaution to use it wisely and not abuse it by eating junk and jabbing to cover it.

Smidge
 
Absolutely agree with Smidge, the main reason I went for the exercise and diet regime is to put off having to take insulin, which one of my doctors assured me I will need before too long.


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Thommothebear said:
Absolutely agree with Smidge, the main reason I went for the exercise and diet regime is to put off having to take insulin, which one of my doctors assured me I will need before too long.


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Click to expand...
Hi All,

Thank you very much for these really interesting replies. I certainly agree that keeping insulin doses as low as possible would seem to be the sensible thing to do. Thanks for the link to the 'mortality and compliance' paper Catherine, it is by the same authors, so should make interesting reading. I'm afraid I don't have a link to the two papers (reporting on the same study) that I have been talking about Denise, I got paper copies from the library. However the citations are as follows and at least the main article says it is online at the publishers address (also given below:)

1. CJ Currie, CD Poole, M Evans, JR Peters, CL Morgan 2013 'Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes J. Clin. Endocrinol Metab February 2013 98(2) 668-677 (online at jcem.endojournals.org)

2. CJ Currie & JA Johnson 2012 'The safety profile of exogenous insulin in people with type 2 diabetes: justification for concern' Diabetes, Obesity and Metabolism 14 1-4

Smidge - its the first time I've heard anything about how exogenous insulin differs from our normal insulin in terms of its action - do you have any links/citations for papers discussing the difference you mention? That sounds fascinating, I know that current analogue insulins are different genetically to natural insulin, so it follows that action or mechanisms of actions are different (and this nearly always spells trouble in relation to medicines) but I would love to read something more specific about this issue.

Thanks all :)
 
This is the report http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612791/

It makes interesting reading, not taking into account their final analysis about insulin, but that the overall average HbA1c of all people in the study was 8.7% (it wasn't a small study ether). No wonder my GP thinks I'm unusual with one of 5.4%.

So what is behind such terrible HbA1c's for the population of the UK Type 2 diabetics?
  1. Head in the sand and not changing their diet
  2. Poor dietary advice from HCP
  3. People who think meds are going to do all the work
  4. Sweetie eating old people
  5. Being told by their GP that a HbA1c of 7% is fine
  6. Non-compliance
  7. Not getting informed by joining forums such as this
The NICE pathway has medication recommendations for HbA1c of over 6.5% http://pathways.nice.org.uk/pathway...therapy-for-type-2-diabetes.xml&content=close are they not being taken any notice of?

According to the State of the Nation 2013 Diabetes UK report http://www.diabetes.org.uk/Documents/About Us/What we say/0160b-state-nation-2013-england-1213.pdf only 65.9% of Type 2 diabetics have a HbA1c of 7.5% or under, goodness only knows what the rest have.
 
Does it say what the weight of the people were? Obesity results in higher mortality rates whether someone is diabetic or not, with the added complication of being diabetic I would imagine that would just make it even more likely.... The result may not have been solely to do with insulin.....I haven't read the study though so I'm just coming up with ideas here nothing more


Diagnosed with GD in 2010, Completely disappeared postpartum. Re-diagnosed December 2012 with type 1.5 diabetes, age 26, BMI 22 currently controlled by only Metformin, 500mg twice a day.
 
academicdiabetic said:
Smidge - its the first time I've heard anything about how exogenous insulin differs from our normal insulin in terms of its action - do you have any links/citations for papers discussing the difference you mention? That sounds fascinating, I know that current analogue insulins are different genetically to natural insulin, so it follows that action or mechanisms of actions are different (and this nearly always spells trouble in relation to medicines) but I would love to read something more specific about this issue.

Thanks all :)
Click to expand...

I'll try to find the reference. It was a reference posted a few months ago either on this forum by Phoenix or another forum I use by Catza, so I'll have a look and see if I can dig it out.

Talking of the differences between natural and injected insulin, the obvious difference is that there is no c-peptide molecule attached to injected insulin - so those of us who do not produce enough insulin also do not produce c-peptide I guess. The researchers are only just starting to uncover the purpose of c-peptide in the human body, but it must have a purpose. And presumably, insulin resistant Type 2s have an excess of this too. So a very big difference there between Type 2s and Type 1s/1.5s maybe?

Smidge
 
Have read a bit on the differences. Main one of topic is the c~peptide thingy produced as smidge said. I believe it is possible to have that injected also but, as they are undecided exactly its function, probably due to cost and uncertainty not usual practice.
Injected insulin goes directly into fatty tissue so, injected areas are more prone to weight gain as it does something to the fat cells and also has a longer action period than if naturally produced . The other thing I remember is that the body fails to recognise the drop in sugar levels from injected insulin which is why diabetics are at risk of hypos, because the body does not react to the drop In sugar levels till at crisis point.
Those are a few things I remember reading about, sorry no studies.

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Thanks again all,

I think this is one of the most productive discussions I've had about insulin (forget most doctors!).

Denise, thanks very much for identifying the link to the paper we are discussing, and also for the links to the two guideline documents. Regarding HBA1C and type 2s, one question is whether we actually know what BG levels are in the 'normal' population, the NICE guidelines (for Types 1 and 2) cite frequently quoted figures, but not any research citation supporting these. Your options 1-5 all look to me like plausible reasons why people might not attain ideal targets (whatever those may be), I'm not sure about 'non-compliance' , I've always found this a rather derogatory term, since it implies, for example, that the medics giving the advice are definately right in some objective sense, and I feel this is in practice unlikely to be true, also, a study on some of the oldest living type 1 diabetics found that one of the main factors which made them stand out from diabetics who had pre-deceased them was that they were 'non-compliant' with medication... (sorry, again I don't have a link, I can dig out the reference if you're interested, it is a study comparing the US diabetic 'gold medallists' with diabetics who died younger having similar general profiles) given the study we are discussing here maybe there's a reason for that! I'm not sure about the joining a forum option, I think its 'horses for courses', I have found this discussion has turned up a lot of stuff I didn't know about and which looks like it could be quite important, but in the main I find that the threads are more about looking for/providing emotional support (which is fine of course!!) so I think in terms of the value of a forum it just depends what you are looking for, rather than about necessarily finding an evidence base or some concrete and objectively valid advice. .

Elaine77, regarding your query: the average weight at baseline for the sample was given as follows: Males: 93.8kg females; 82.2 kg. I'm not sure how this compares with the general population and the table suggests that this is an average which measures some people more than once (the details focus on weight at 'glucose relevant exposure periods' (N=105,123) rather than people (N=84,622) as such.

Smidge: Thank you again for some novel insights. I had never heard of the C-peptide issue either. I would really appreciate any of the papers you are able to track down with reference to the mode/mechanism of action of exogenous vs natural insulin. Really interesting.

Brett: Likewise, thank you for the novel insights. I had suspected that fat distribution became a little odd with insulin, but had not heard that referred to before as any kind of accepted fact.

Much 'food' for thought!
 
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