[priamus]

shows intensive glucose control reduces serious complications.

The George Institute for International Health

see also

NEJM -- Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes

Cheers,

[Coppernob]

Thank you for posting these links - I have bookmarked them to read more fully later. My initial scan tells me they are worth looking at in detail.

[jacobsam622]

Originally Posted by priamus

shows intensive glucose control reduces serious complications.

The George Institute for International Health

see also

NEJM -- Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes

Cheers,

This just confirms the results of the UKPDS done back in 1998


http://dermatology.jwatch.org/cgi/co...on/1999/101/25

"UK Prospective Diabetes Study (UKPDS), have been announced. As one might expect, based on the DCCT (which showed that tight control decreases complications in people with type 1 diabetes), the UKPDS shows that the risk of complications of diabetes can be reduced dramatically in people with type 2 diabetes. "

[REDLAN]

found this link here, with some more detail.

Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE)

the UKPDS shows that the risk of complications of diabetes can be reduced dramatically in people with type 2 diabetes. "

The UKPDS showed that tight glucose control made little difference to reduction in risk of complications. Strict BP control however did make a difference.

Everyone is aware of the ACCORD trial that showed excess mortality in the tight control arm. It's important to not get confused with mortality from cardiac events. I do not know (nor can I find any information) what the excess mortality was caused by. Nor how it breaks down.

This study is different to ACCORD in that tight glucose control is attained over a longer period. The short period in which tight control was attained was cited as a possible cause of the excess mortality.

There is an issue, that is detailed within the study paper but not reported.

The ADVANCE trial was originally designed to have a statistical power of 90% to detect a relative risk reduction of 16% or more for intensive control, as compared with standard control, for each of the primary outcomes, with the use of a two-tailed test with an alpha level of 5%. After a mean of approximately 3 years of follow-up, it became apparent that the event rates (in the two groups combined) were lower than expected. Thus, in a manner blinded to any results of the effects of intervention, two changes were made to the protocol to increase the power of the study: joint (as well as separate) analysis of the primary outcomes was prespecified, and the period of treatment and follow-up was extended by 12 months for the part of the study that evaluated the lowering of blood pressure and by 18 months for the part that evaluated the control of blood glucose.

They had to change the study protocols - whatever that means, but I assume it means adjusting how end-points are defined to generate more events, and increased follow up times, which would also generate more events. Now note the RR reduction that the study was designed to detect - 16% or more, and this is where we are going to diverge from the term dramatic and will now have to explain the use of signifcant.

And now for the results

overall mortality - no difference between the 2 groups.
Myocardial infarction - no difference between the 2 groups
Macrovascular events - no difference between the 2 groups
Retinopathy - no difference between the 2 groups.

so that's a lot of null results....

and what about the positives?

Significant reductions were attained for

Microvascular events, which was driven by a reduction in Nephropathy. Retinopathy we know was not affected by tight control.

So this study shows that <CUE FANFARE>

tight control reduces the risk of Nephropathy in Type 2 by 21%

and now for the downsides of tight control.

There was a significant trend for higher rates of hospitalisation amongst those on tight control, along with a higher risk of severe hypoglycemia.

So was this result dramatic?

and now for an explanation of significant...

significant in this case is used entirely in the context of whether the result is statistically significant. The result for nephropathy was significant in the sense that it was unlikely to have occured by chance, but was it significant in the sense that it was a large or dramatic?

well...

statins typically produce Relative Risk reductions of around 33%, which is deemed to be clinically significant. Most medical treatments produce RR reductions of between 33% and 50%.

Compare and contrast with DCCT for a type 1 on tight control.

Retinopthy - 76% reduction in risk
nephropathy - 50% reduction in risk
neuropathy - 60% reduction in risk

kinda speaks for itself doesn't it

[BlueSky]

Originally Posted by REDLAN

.... The UKPDS showed that tight glucose control made little difference to reduction in risk of complications. ...

As far as I can see, the UKPDS study showed a 25% microvascular relative risk reduction in the intensive control arm. But there was little change in macrovascular complication relative risk.

The relatively small risk reduction, when compared to DCCT results with type 1 diabetics begs the question of what else is going on. Blood glucose control can'r be the only factor here. Interestingly, the UKPDS study concluded that insulin is not atherogenic, but the biggest difference between T1 and T2 is the presence of insulin resistance....

[REDLAN]

As far as I can see, the UKPDS study showed a 25% microvascular relative risk reduction in the intensive control arm.

yep this is what they trumpeted. UKPDS managed to achieve around a 40% reduction in microvascular risk with tight BP control. I find it odd that they trumpeted the tight glucose control, when the BP results were much better.

The 25% RR reduction is not alot to shout about - it translates to an absolute risk reduction of around 1.5% over 7 years, around 0.2% per year.

The relatively small risk reduction, when compared to DCCT results with type 1 diabetics begs the question of what else is going on. Blood glucose control can'r be the only factor here.

I think the issue is that type 1 and type 2 are two entirely different disease processes.

type 1 is an autoimmune response which destroys pancreatic cells. Type 2 is primarily a metabolic disorder, in which there is misregulation of several key systems - lipids, cholesterol, BP systems are also affected along with insulin regulation.

The problem comes from the fact doctors and medical personnel, and even researchers treat the 2 diseases as though they are the same. So the results from the DCCT which looked solely at type 1, are then used as recommendations to treat type 2. Why?

What studies like UKPDS suggest (at least to me), is that the misregulation of BP systems are more important to long term health than the misregulation of the insulin/glucose system

We also get the reverse happening. The findings from UKPDS, that BP was important in controlling retinopathy in type 2, was then applied in the UK to type 1's. Tight BP control got recommended for type 1's on the basis of the UKPDS results. It was stated by my GP, when my BP was a bit borderline, that BP control was more important than good glucose control. Actually DCCT showed that tight glucose control was much more important. So again why are results derived from studying one disease process then used as recommendations of another disease process?

As long as type 2 is primarily thought of as an insulin/BG problem, rather than as a metabolic problem involving multiple body systems, then these "surprise" findings are likely to continue.

[xMenace]

Originally Posted by BlueSky

The relatively small risk reduction, when compared to DCCT results with type 1 diabetics begs the question of what else is going on. Blood glucose control can'r be the only factor here.

C-peptides?
Diabetes In Control - C-Peptides May Prevent Diabetes Complication

[BrianSCohen]

I find that these sorts of studies often are so improperly designed, that they almost were not worth running. The use of aggresive pharmaceutical treatment in the control arms itself is a confounding factor. I find it likely that this is what caused the problems with the ACCORD. In either case, I would agree, as has been suggested above, that diabetes complications come from broader dysfunction than just elevated blood sugars.