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recent insulin study

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noblehead said:
I'm not too sure about whether it's just relevant to HCHF Smidge. I've long suspected the delayed rise in bg maay hours after eating (even with a low-carb high-fat meal) couldn't possibly be down just to the slow digestion of the protein, and this is why I suspect that some type 1's that do go down the low-carb high-fat route need to inject twice for one meal a few hours apart, as I said earlier I need to inject twice for bacon eggs without any visible carbs otherwise my pre-prandial bg levels would be high the next time I eat.
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I find it a very interesting topic, Noblehead. I completely agree that there is something more to it than slow-release protein. The best example I have of this phenomenum is that if I have a meal of mixed cheeses and olives (so very little carb or protein), I find it almost impossible to get the right bolus - I'll either jab a unit and go low at about an hour or I'll not jab and be very high at 3 to 4 hours - so I have to go for a sort of delayed jab at around the two hour mark, but it is hit and miss. However, if I have one ryvita (about 6g carb) with the cheese, I can just jab a single unit for that and my BG remains stable throughout. So there is something going on in the interaction between carb, fat and insulin I think.

Smidge
 
To phoenix

“The thread has morphed ,it really hasn't a lot to do with the original post which was about a T2 study not a T1 one.” Perhaps it would be good to stay with the OPs original post-insulin and type two diabetics. You quoted me “Of course -it is how good control is achieved that makes all the difference” I stand by the comment. “I don't think that the original paper mentioned has actually been linked to” I posted the link on this thread today at 10.19. An analysis of the paper linked to.


Those on Metformin therapy had the lowest death rates, so that group was used as the reference.

In terms of primary outcome—that is, consideration of first adverse events only:

  • Sulfonylurea therapy resulted in patients being 1.4 times more likely to suffer one of these outcomes.

  • A combination of Metformin and Insulin resulted in 1.3 times greater risk.

  • Insulin therapy alone resulted in 1.8 times greater risk.

  • Those considered to be at greater risk because of glycosylated hemoglobin had as much as 2.2 times greater risk with Insulin therapy alone. When considering any of these events happening, whether they were the first event or a subsequent one, the results were even more dramatic:

  • Insulin monotherapy resulted in:
    • 2.0 times more myocardial infarctions.

    • 1.7 time more major adverse cardiac events

    • 1.4 time more strokes

    • 3.5 times more renal complications

    • 2.1 time more neuropathy

    • 1.2 times more eye complications

    • 1.4 times more cancer

    • 2.2 times more deaths
FB
 
Hi Fatbird,

Yes the paper you have given is the one I was referring to (I didn't have a link, only a hard copy so thanks to you and also Phoenix for putting up the link). Thank you also for putting up the outcomes again (I had done so, but they got a bit buried in my text, you have made the outcomes much clearer).
 
Thanks for thanking the thanks FB :-)
 
FB :I drafted my post last night and hadn't seen your later link. Sorry.

I think it's worth looking at the pre-existing health of the subjects. They had had diabetes for longer, and were far more likely to have vascular disease or renal disease before they started treatment. Those with renal problems could not take metformin.
Those on Met alone had been diagnosed with Diabetes for an average 1.5 (SD 2.3) years,
those on insulin alone 5.2 (SD 4.3) years.
11.1% of those on Met alone had large vessel disease before starting this treatment
22,3% of those on insulin alone had large vessel disease before starting this treatment.
2.2% of those on Met alone had raised creatinine levels before starting this treatment
21.1% of those on insulin alone had raised creatinine levels before starting this treatment.
The Charlston Index is a score that reflects multiple serious conditions
this was 1.6 for those on Met alone and 2.4 for those on insulin
(presumably, following normal UK protocols the people using insulin had previously used 1 then 2 or more oral medications but HbA1c had continued to rise )

It's also interesting to look at the link given by Catherine earlier. This was from the same researchers, using t similar UK ,GP data (though it appears from a different data base) This pointed to worse outcomes in those who took insulin and were deemed to be non compliant
'Medication noncompliance and clinic nonattendance, assessed during routine care by primary care physicians or their staff, were independently associated with increased all-cause mortality in patients with type 2 diabetes receiving insulin'
In the body of the paper they say
'patients defined as noncompliant by either metric were more likely to smoke and have higher BMI, HbA1c, and morbidity at index date, the association of treatment noncompliance with subsequent mortality was independent of these risk factors. Furthermore, there was a dose-response relationship between level of missed appointments and mortality risk.'
I think that there are very many more factors than simply suggesting that insulin is causative in the increased morbidity/mortality for this group,
 
academicdiabetic said:
I don't believe the authors of the 'insulin increased mortality' study controlled for diet... that would certainly have been a useful add-on. I don't know if the data are available, but I would have thought also that a group of comparable Type 2s given no medication and controlling diabetes by diet and exercise alone would have made even more interesting reading than the actual comparator of metformin alone.
! ;)
Click to expand...

Yes there is an important caveat at the end of the abstract of the article in question , viz -
"Differences in baseline characteristics between treatment groups should be considered when interpreting these results."

In other words they have not taken into consideration the age of the diabetic, the duration of diabetes, diet, socio-economic class, level of education, ethnicity, compliance with the regime etc etc. Nor have they taken into consideration the HbA1c of the various groups.

I'm a Type 2 of 22 years standing on insulin aged 66, it would be absurd to compare me with a T2 in their 40s of two years standing, on metformin and say I am more likely to die than them - of course I am !
 
smidge said:
I find it a very interesting topic, Noblehead. I completely agree that there is something more to it than slow-release protein. The best example I have of this phenomenum is that if I have a meal of mixed cheeses and olives (so very little carb or protein), I find it almost impossible to get the right bolus - I'll either jab a unit and go low at about an hour or I'll not jab and be very high at 3 to 4 hours - so I have to go for a sort of delayed jab at around the two hour mark, but it is hit and miss. However, if I have one ryvita (about 6g carb) with the cheese, I can just jab a single unit for that and my BG remains stable throughout. So there is something going on in the interaction between carb, fat and insulin I think.

Smidge
Click to expand...

Yes there certainly is and the more we know the better for all.

I find the same that a small amount of carbs with a meal makes it much easier to bolus for than when no carbs are present, if I'm having say a cheese omelette or eggs & bacon as above I'll have around 20g of carbs (toast or banana afterwards) and my insulin seems to work much better. Thanks again for the feedback Smidge:)

Apologies to the OP for going off topic in the thread.
 
To get the thread back on topic-type two diabetics and insulin.

Insulin: Potential Negative Consequences of Early Routine Use in Patients With Type 2 Diabetes

Some extracts from the full paper.

It would seem logical that the ideal treatment for type 2 diabetes should be early and continuing insulin therapy. Unfortunately, there are several characteristics of insulin treatment and insulin action in type 2 diabetes that limit the usefulness of insulin treatment and that suggest that chronic insulin therapy is best used in the later stages of diabetes when there is an absolute deficiency of insulin.

Starting insulin therapy early in the course of chronic treatment of patients with type 2 diabetes would imply that there are unique benefits to insulin treatment. As addressed above, there is little evidence to support such a view. Insulin treatment is neither durable in maintaining glycemic control nor is unique in preserving β-cells. Better clinical outcomes than those that occur with other antihyperglycemic regimens have not been shown. The downside of insulin therapy is the need to increase the dose and the regimen complexity with time, the increase in severe hypoglycemia, and the potential increase in mortality as well as the potential increased risk for specific cancers.

Weight gain accompanies insulin treatment. The magnitude of the weight gain is influenced by the level of the initial glycemic control, the treatment glycemic control achieved, the duration of insulin therapy, the insulin regimen used, and which combination of oral agents are concomitantly used For example, in a study normalizing the HbA1c during 6 months of intensive multiple-dose insulin therapy, the mean weight gain was 8.7 kg

For the vast majority of patients with type 2 diabetes, insulin therapy is best reserved until other therapies can no longer maintain the target glycemic goals.

http://care.diabetesjournals.org/content/34/Supplement_2/S225.full

FB
 
Good move Thommo

Cancer Incidence and Mortality in Patients with Type 2 Diabetes Treated with Human Insulin: A Cohort Study in Shanghai.

Aim
The aim was to investigate the association between human insulin and cancer incidence and mortality in Chinese patients with type 2 diabetes.

Methods
We recruited 8,774 insulin-naïve diabetes patients from the Shanghai Diabetes Registry (SDR). The follow-up rate was 85.4%. All subjects were divided into the insulin use cohort (n = 3,639) and the non-insulin use cohort (n = 5,135). The primary outcome was the first diagnosis of any cancer. The secondary outcome was all-cause mortality. Cox proportional hazards model was used to estimate the relative risk (RR) of cancer and mortality.

-insulin users, respectively. No significant difference in cancer risk was observed between the two cohorts (adjusted RR = 1.20, 95% CI 0.89–1.62, P = 0.228). Regarding site-specific cancers, only the risk of liver cancer was significantly higher in the insulin users compared to that in the non-insulin users (adjusted RR = 2.84, 95% CI 1.12–7.17, P = 0.028). The risks of overall mortality (adjusted RR = 1.89, 95% CI 1.47–2.43, P<0.0001) and death from cancer (adjusted RR = 2.16, 95% CI 1.39–3.35, P = 0.001) were all significantly higher in the insulin users than in the non-insulin users.

Conclusion
There was no excess risk of overall cancer in patients with type 2 diabetes who were treated with human insulin. However, a significantly higher risk of liver cancer was found in these patients. Moreover, insulin users showed higher risks of overall and cancer mortality. Considering that individuals treated with insulin were more likely to be advanced diabetic patients, caution should be used in interpreting these results.

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053411

FB
 
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Hi Phoenix,

If you refer to one of my earlier posts on this thread, in response to a similar point raised: the authors controlled for all those factors and the people in the study were selected to be recently diagnosed (and then 'followed up' for three years - albeit retrospectively) not to be people at the 'last chance saloon' in terms of medication. The authors' intent in the way they structured and analysed their study was to analyse the impact of insulin as such on mortality and morbidity, controlling for factors such as co-morbidity, HBA1C and so on.

Thanks for posting the additional study from Shanghai Fatbird, that's interesting. I think this may be one of those 'elephant in the room' scenarios, none of us want to believe that insulin can harm us, but I suspect the evidence is mounting and, realistically, it would be optimistic to think otherwise given that insulin is such a major hormone and also that analogue insulins, at least, differ from natural human insulin genetically and also in terms of mechanism of action.

The promising thing about the study I posted is that the authors found the adverse impact to be 'dose dependent' so if the study outcomes are valid (no study is perfect and all studies therefore should be replicated) those of us who 'have' to take insulin can lessen the risk of any potential damage by doing anything we can to keep our daily dose as low as possible.
 
Brett said:
Patch said:
This thread couldn't have come at a worse time for me...
Click to expand...

Whats up patch?
Click to expand...

I been "advised to start an insulin regime - Basal & Bolus insulin.

But my C-Peptide results came in at 18'ish - so I AM producing LOTS OF insulin... I don't like th eidea of taking MORE insulin, especially with reports like this turning up...
 
Reading slowly through this but a query ... is there no way to measure insulin, or have l not found the post yet. A home check like our glucometers so those on insulin know how much is in their body's at certain times would surely be useful especially given someone said "artificial" works differently. I am not on insulin but would it not be as useful as a glucometer is. Shouldn't be hard to make as it would be external of the body just based on prick you did for BG.

MID
 
Patch
This is part of the draft I wrote lost night. I've revised it but put my conclusion first.
I'm very afraid that some people will interpret this thread as meaning that being put onto insulin is the last nail ( many people already think this )and frighten them away from a necessary medication that may lengthen their lives and reduce the risks of complications. Individuals have great success on insulin and this includes many T2s (have a look at some of the US forums , some have regular T2 posters who have been on insulin for 20+ years)
This was not a controlled trial, it cannot establish any causality merely suggest hypotheses.

If we took a group of newly diagnosed T2diabetics and randomly put one group onto insulin and the other on metformin for 3 years (the time looked at in this analysis ) would the insulin users develop more complications or die more frequently than those using metformin ?
I suggest that there would be a difference in glucose levels and that would depend on the nature of the subjects diabetes. (after all the medications work in different ways and address different problems. I suspect that individual results would depend upon how much glucose was produced from the liver.(met treats this, insulin doesn't, that's a reason they work together)

A medscape reviewer suggests that there are three possible reasons for this pattern of results: http://www.medscape.com/viewarticle/804103
  • Residual confounding
  • that the co-morbidities are interrelated (well I certainly think they are)
  • There is one precipitating event. The researchers consider this to be the case ie insulin use .
The researchers have tried to eliminate confounders but include the caveat
these results must be considered with the caveat of residual confounding both within the candidate covariates and those factors that could not be represented within our models
Click to expand...

Here's just a couple of caveats I have .

They haven't taken into account the prior effects of longer term higher glucose levels
They acknowledge progression and the late use of insulin in many cases they don't seem to control for this aspect ( I can't see how they can)
Metabolic 'memory' may be important, just as prior good control seems to have a lasting beneficial effect when control deteriorates the opposite is also true.
T1s who omit insulin and run intermittent high glucose levels often don't see problems until later. These frequently occur when they have developed better control. It isn't the insulin that causes the problems but the damage done earlier. (early worsening of retinopathy is slightly different example)

When considering an outcome, they excluded people who already had markers for this problem ; so for kidney disease they removed those with known poor results on kidney tests but they could only do this accurately if there was a test on record, we don't actually know the state of the kidneys in those with no test. ie the missing data problem ( This is GP data and we also know from the diabetes audit that at least 30% of people with D in the UK don't receive this test. In some areas and GP practices it is considerably more)

Excluding those with known large vessel disease from CVD outcomes doesn't account for the interelationship between various microvascular and macrovascular complications , those who have kidney disease may well die from a heart attack or stroke.

The only long time trial of insulin use is the DCCT (so T1) This did look at insulin doses and future complications. Those who took higher doses had similar problems to those often associated with T2 . They had higher BMI and the various markers of the metabolic syndrome.
Weight, symptoms of the metabolic syndrome or subsequent higher insulin doses were not predictive of future complications, however lowered kidney function was predictive of both micro and macrovascular complications. (back to that interrelationship again)
http://www.ncbi.nlm.nih.gov/pubmed/17327345

Finally, Prof Currie, the lead researcher also said
"The vast majority of people who take insulin will experience no adverse effects and it remains a reliable and common form of treatment worldwide, but this study shows that we need to investigate this matter urgently and the drug regulatory authorities should take interest in this issue"
http://www.bbc.co.uk/news/uk-wales-21319226
and that is exactly what needs to be done ie further research because this study can only delve into possibilities and not establish anything.
 
I'm genuinely interested in this and have a question...If for example,a type 2 with less than perfect control,has an insulin resistance problem BUT tests reveal that they have plenty of their own insulin being produced-how does injecting synthetic insulin help that individual in any way if the insulin resistance is the issue?
 
Some T2's with insulin resistance have to inject huge amounts of insulin to overcome this.


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Paul said

“I'm genuinely interested in this and have a question...If for example,a type 2 with less than perfect control,has an insulin resistance problem BUT tests reveal that they have plenty of their own insulin being produced-how does injecting synthetic insulin help that individual in any way if the insulin resistance is the issue?”

More insulin will only increase insulin resistance. It’s a well known vicious circle.

Mo said

“Some T2's with insulin resistance have to inject huge amounts of insulin to overcome this.”

Huge amounts of insulin doesn't sound a good option-why not reduce the insulin resistance?

FB
 
I didn't say it was a good option ! Just stating what happens. I agree, inject as little as possible whilst keeping BG readings in line. Some people believe insulin is a ticket to eating whatever you like and DAFNE doesn't help. Eat a donut and take 4 units for example.


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Phoenix, I agree that it is important that more and better studies are carried out in this area, prospective long term studies in particular. The curious thing about the diabetes literature (which as you know is huge), is that pretty much all the insulin trials to date have focussed solely on lowering blood glucose as the outcome, it is only very recently that people have started to look at morbidity and mortality, which is, frankly, quite odd, since blood glucose levels, as such, are irrelevant unless linked with morbidity and mortality (if keeping blood glucose low mattered independently of any impact on mortality and morbidity we could all just slug back a bottle of neat gin every day, it would certainly lower the BGs ;)).

Out of curiosity, if, as studies progress, it becomes clear that insulin is damaging, what would your response be to that situation?

MID: Exactly - why not measure insulin, it seems obvious really. I can only assume that its more difficult to measure than blood glucose. I know that there are lab tests which can be done, so its not impossible. The consultant I see seems to have given me every test under the sun at his own instigation but whenever I've asked to have the amount of insulin I'm producing measured (which is understood to be the key problem for a T1 after all!) he has refused.

Does anyone know what the issues are with measuring insulin production and/or has anyone had a test for insulin production done under the NHS?
 
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