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Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study

BMJ 2000; 321 doi: https://doi.org/10.1136/bmj.321.7258.405 (Published 12 August 2000) Cite this as: BMJ 2000;321:405

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Association of glycaemia with complications of type 2 diabetes: Is glycaemic treatment important?

Stratton, et. al. have documented that as glycaemic exposure
increases, diabetic complications increase.(1) They conclude that
treatment of hyperglycemia will have substantial benefit, a conclusion
reiterated by Dr. Tuomilehto.(2) Yet reduction of glycaemic exposure
failed to have such benefit in the UKPDS randomized trial (3, 4) For
example, Stratton's data would suggest that reducing mean HgA1C by 1%
would reduce diabetes related deaths by 21%. Intensive treatment of
hyperglycaemia for 10 year in UKPDS reduced HgA1C by nearly 1% (from 7.9
to 7.0%), yet failed to reduce diabetes-related deaths significantly. The
conventionally treated group, with greater glycaemic exposure, suffered
diabetes-related deaths at a rate of 11.5 deaths/1,000 person-years.
Based on Stratton's data, the intensively treated group should have
experienced diabetes-related death at a rate of 9.0 deaths/1,000 person-
years. However, intensive treatment was associated with only a non-
significant decrease in diabetes-related mortality.(4) Similarly,
Stratton's data suggests that intensive treatment would result in
significant reductions in adverse outcomes that include all-cause
mortality, stroke, myocardial infarction, and amputation. Reducing HgA1C
by nearly 1% in the UKPDS, however, was not associated with significant
reductions in any of these adverse outcomes.

Thus, treatment that significantly improves glycaemic control does
not achieve the predicted benefit. Does this mean that greater glycaemic
exposure is a marker for adverse outcomes--but not a cause? This would
imply that the higher the HgA1C, the more one needs to pay attention to
non-glycemic treatment of diabetic patients--such as controlling blood
pressure. Or does it mean that the treatments currently available to
lower glucose harm diabetic patients as much as the lowering of blood
glucose helps them?

I wonder if McCormack and Greenhalgh are correct when they suggest
that metformin treatment improves outcomes in diabetic patients, not
necessarily resulting from its glucose lowering effect, but that lowering
glucose per se is of little to no value in type 2 diabetes.(3)

(1)Stratton IM, Adler AI, Neil AW, et. al. Association of glycaemia with
macrovascular and microvascular complications
of type 2 diabetes (UKPDS 35): prospective observational study. BMJ
2000;321:405-412.

(2)Tuomilehto, J. Controlling glucose and blood pressure in type 2
diabetes. BMJ 2000;321: 394-395.

(3)McCormack J, Greenhalgh T. Seeing what you want to see in randomised
controlled trials: versions and perversions of UKPDS data. BMJ
2000;320:1720-1723.

(4)UKPDS Group. Intensive blood glucose control with sulphonylureas or
insulin compared with conventional treatment and risk of complications in
patients with type 2 diabetes Lancet 1998;352:837-853.

Competing interests: No competing interests

12 August 2000
Brian Budenholzer
Group Health Cooperative; Spokane, WA; USA