Lowering glucose concentrations may not be of any value in itself

EDITOR—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 Tuomilehto.2 Yet reduction of glycaemic exposure did not have such benefit in the UK prospective diabetes study (UKPDS) randomised trial. 3 4 The data by Stratton et al suggest that reducing mean haemoglobin A_1C concentration by 1% would reduce diabetes related deaths by 21%. Intensive treatment of hyperglycaemia for 10 years in UKPDS reduced haemoglobin A_1C by nearly 1% (from 7.9% to 7.0%) yet did not reduce diabetes related deaths significantly.

The conventionally treated group, with greater glycaemic exposure, experienced diabetes related death at a rate of 11.5 deaths per 1000 person years. On the basis of the data by Stratton et al, the intensively treated group should have experienced diabetes related death at a rate of 9.0 deaths per 1000 person years. Intensive treatment was, however, associated with only a non-significant decrease in diabetes related mortality.4 Similarly, the data by Stratton et al suggest that intensive treatment would result in significant reductions in adverse outcomes that include all cause mortality, stroke, myocardial infarction, and amputation. Reducing haemoglobin A_1C by nearly 1% in the UKPDS, however, was not associated with significant reductions in any of these adverse outcomes.

Treatment that significantly improves glycaemic control therefore 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 haemoglobin A_1C concentration the more attention needs to be paid to non-glycaemic 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 …