Tighter blood glucose control through medication linked to higher death risk

[DCUK NewsBot]

A new study looking at the relationship between death rate and blood glucose management has found that tighter blood sugar control may raise the risk of death. Research increasingly suggests that there is an increased risk of developing health problems with both very loose and tighter blood glucose control, as a result of medication, in type 2 diabetes. We know that diabetes complications can be reduced by tighter blood glucose control but concerns were raised that this may adversely affect all-cause mortality. The study, released this week, adds new knowledge by finding that tighter blood glucose control, or lower HbA1c levels, can raise the risk of death among people on intensive blood glucose-lowering therapy. However, the findings won't apply to those achieving excellent HbA1c levels, and experiencing other health benefits, through positive lifestyle change which inevitably influences mortality risk. People following a low carb lifestyle without hypo-causing medication, for example, should not be affected. Researchers from Cardiff University investigated whether tight blood glucose control significantly increased the risk of death for over 300,000 patients with type 2 diabetes living in the UK. They analysed data collected between 2004 and 2015 on their level of blood glucose control determined through measuring HbA1c. According to their findings, lower HbA1c levels were associated with increased mortality risk, compared to moderate levels. Here, lower HbA1c levels are regarded as obtaining values lower than 53 mmol/mol (7%), while moderate HbA1c levels are defined as having values between 53 and 69 mmol/mol (7 and 8.5%). There was another layer of complexity in interpreting evidence as it was found that the risk of death differed according to the treatment regimen followed by participants. The researchers reported that lower HbA1c levels were associated with increased mortality especially in those receiving treatments that can cause hypoglycemia, such as sulfonylureas. It is important to note that this research only provides preliminary evidence, therefore people with 2 diabetes who are well-controlled on these types of medications should not stop them unless otherwise indicated by their doctor. The study also found that high HbA1c levels were associated with an elevated mortality risk, but only among patients taking diabetes drugs associated with a low risk of hypoglycemia. In light of this information, further investigation is warranted on the interplay between different glucose-lowering medications, blood glucose control and mortality. For now, this association between higher mortality and tighter blood glucose control has implications for our understanding of good blood glucose control in type 2 diabetes and overall suggests that blood sugar balance is key - particularly for those on intensive glucose-lowering medications. The findings were published in the journal Diabetes, Obesity and Metabolism.

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[paulus1]

we just cant win.

 

[Art Of Flowers]

This corresponds to what Jason Fung was saying in the video in the following forum topic ... http://www.diabetes.co.uk/forum/threads/dr-jason-fung-insulin-toxicity.129431

High levels of glucose are dangerous, but high levels of insulin is also toxic, especially for those type 2 people who have insulin resistance. Having a HBA1C below 6% using insulin or insulin stimulating drugs is associated with a higher mortality risk. The ideal treatment for type 2 diabetes is one which lowers glucose levels without raising insulin.

 

[Grateful]

It is sobering, for those who need drugs (in particular, sulfonylureas) to control their T2D. It does validate tight BG control done solely with lifestyle modifications, for those who are candidates for doing it that way.

Then there is this: "It is important to note that this research only provides preliminary evidence, therefore people with 2 diabetes who are well-controlled on these types of medications hould not stop them unless otherwise indicated by their doctor." (My boldface.)

Finally ... it is only a single study.

 

[ringi]

Did you miss:

However, the findings won't apply to those achieving excellent HbA1c levels, and experiencing other health benefits, through positive lifestyle change which inevitably influences mortality risk. People following a low carb lifestyle without hypo-causing medication, for example, should not be affected.
​

I see nothing new in this study compared to ACCORD, but it is worthwhile to confirm the name results from a different dataset. But why do the researchers think it is due to the risk of hypoglycemia, when it is becoming clear it due to very high insulin levels destroying the body.

 

[ringi]

It is sobering, for those who need drugs to control their T2D. It does validate BG control done solely with lifestyle modifications, for those who are candidates for doing it that way.

Note that both Netformin and SGLT2 inhibitors have been shown to increase length of life. They both lower glucose levels without raising insulin. Metformin seems to increase length of life more than getting the same reduction in AC1 by diet. But you can get a much larger reduction in AC1 by diet, and also combine diet with Metformin and/or SGLT2 inhibitors.

With the way this research is going, I expect that the NHS will soon have a large bill for SGLT2 inhibitors......

 

[Grateful]

Not being able to read the whole study, it is a bit frustrating not to know the causes of the extra mortality. They say that those were linked with taking meds that can cause hypos, but do they mean that the hypos caused the deaths? (Sorry if that sounds like a naïve reading, but the phrasing is vague.)

 

[ringi]

I expect they are not saying, as it was a study just looking at data from GP records etc. But remember that for a drug to cause hypos it must increase insulin levels....

Given the cut off date (2013) for the people who they included, I expect that few people were on drugs other than Metformin that reduce BG without increasing insulin.

 

[Oldvatr]

It is sobering, for those who need drugs (in particular, sulfonylureas) to control their T2D. It does validate tight BG control done solely with lifestyle modifications, for those who are candidates for doing it that way.

Then there is this: "It is important to note that this research only provides preliminary evidence, therefore people with 2 diabetes who are well-controlled on these types of medications hould not stop them unless otherwise indicated by their doctor." (My boldface.)

Finally ... it is only a single study.

It echoes a study published last year that found the same thing. Lower bgl = higher risk. (Note: all cause mortality includes other causes which have no direct diabetic link, but may be influenced by lack of concentration or depression etc that diabetes contributes to. Neither study seems to provide any clarity as to which causes were increased over others,)

 

[Grateful]

One part that really gives food for thought is that those taking sulfonylreas fared best on "moderate" control. Both the tight-controllers and (unsurprisingly) the loose-controllers fared worse.

 

[Oldvatr]

One part that really gives food for thought is that those taking sulfonylreas fared best on "moderate" control. Both the tight-controllers and (unsurprisingly) the loose-controllers fared worse.

Here is another way of looking at it
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747722/

Edit to add note: Most studies so far seem to be on intensive care or critically ill patients. The study above seems to be only looking at exogenic insulin treatments in ICU, so is not quite the same as the Cardiff study.

 

[Grateful]

"However, the findings won't apply to those achieving excellent HbA1c levels, and experiencing other health benefits, through positive lifestyle change which inevitably influences mortality risk. People following a low carb lifestyle without hypo-causing medication, for example, should not be affected."

How do they know? The wording ("should") suggests that they did not study lifestyle-controlled T2Ds. Otherwise the summary written by DCUK would presumably have used the word "were not" or "are not" affected.

It just sounds like jumping to conclusions. "Positive lifestyle changes" = "reduction in mortality risk." This might be common sense, but it doesn't sound like it was explicitly studied/tested in the report.

 

[ringi]

They compared people who were only on Martformin, with people who where taking the other drugs. It was only the other drugs that gave the problems..... Without the other drugs a lower AC1 was always better.

 

[Dark Horse]

Not being able to read the whole study, it is a bit frustrating not to know the causes of the extra mortality. They say that those were linked with taking meds that can cause hypos, but do they mean that the hypos caused the deaths? (Sorry if that sounds like a naïve reading, but the phrasing is vague.)

Yes, you have to be very careful about the DCUK write-ups of research, it's not always clear which parts are DCUK's own speculation. As you surmised, diet control was not studied in the original research:- http://onlinelibrary.wiley.com/doi/10.1111/dom.13155/full

 

[ringi]

Are there enough people with Type2 in the UK with good diet control who are not on Metformin to get a meaningful result..... Remember it needs at least a few years of records for each person for this sort of study, so it will be the number of people with diet control a few years ago we care about.

 

[ickihun]

This corresponds to what Jason Fung was saying in the video in the following forum topic ... http://www.diabetes.co.uk/forum/threads/dr-jason-fung-insulin-toxicity.129431

High levels of glucose are dangerous, but high levels of insulin is also toxic, especially for those type 2 people who have insulin resistance. Having a HBA1C below 6% using insulin or insulin stimulating drugs is associated with a higher mortality risk. The ideal treatment for type 2 diabetes is one which lowers glucose levels without raising insulin.

But what happens to people where low carb and all type2 drugs don't work or intolerant?
I'm such person. Low carb helps but not solves high bgs totally. I am highly insulin resistant. Only insulin stops me rotting away. I cannot do heavy exercise, walking is in pain. Many others have other health problems too.

 

[ickihun]

They compared people who were only on Martformin, with people who where taking the other drugs. It was only the other drugs that gave the problems..... Without the other drugs a lower AC1 was always better.

I thought everyone was clear about that anyway. Common sense. Always better without insulin if control can be found. Or other drugs , other than metformin.
Wouldnt everyone rather get good control without drugs or insulin?

 

[ickihun]

Well I only lose weight when my bgs are in excellent control longterm so I'd never lose weight if I wasn't on insulin therapy. Trust me to be different!

 

[Oldvatr]

Yes, you have to be very careful about the DCUK write-ups of research, it's not always clear which parts are DCUK's own speculation. As you surmised, diet control was not studied in the original research:- http://onlinelibrary.wiley.com/doi/10.1111/dom.13155/full

Thanks for posting the abstract here. One thing that jumps out on me is the dichotomy on the wording. On one hand the results show that using a hypogenic drug increases mortality, but in the next sentence they say that therapies that do not involve hypoglycmia episodes is also raising the risk. So in other words whatever drug we use seems to be shortening our lives. Which some here would say is erflinger obvious.

So the obvious conclusion I would draw is that if normal HbA1c is achieved by lifestyle changes only (i.e. as if we were normals) then thats the best remedy, Doctor. But my question echoes the thought made above - is diet change considered a lifestyle regime, or not if it is only transitory? So binge dieting would not be effective?

 

[ickihun]

Not being able to read the whole study, it is a bit frustrating not to know the causes of the extra mortality. They say that those were linked with taking meds that can cause hypos, but do they mean that the hypos caused the deaths? (Sorry if that sounds like a naïve reading, but the phrasing is vague.)

I agree. It must be hypo comas causing death if good control on meds and insulin reduce inflammation and infections etc.
Unless organ failure?