KINGDOM PROSPECTIVE DIABETES STUDY: WHAT DOES IT TELL US?
The UKPDS is the largest and longest study
on type 2 diabetic patients that has ever been performed. It
recruited 5,102 patients with newly diagnosed type 2 diabetes in
23 centers within the U.K. between 1977 and 1991. Patients were
followed for an average of 10 years to determine 1) whether
intensive use of pharmacological therapy to lower blood glucose
levels would result in clinical benefits (i.e., reduced
cardiovascular and microvascular complications) and 2) whether
the use of various sulfonylurea drugs, the biguanide drug
metformin, or insulin have specific therapeutic advantages or
disadvantages. In addition, patients with type 2 diabetes who
were also hypertensive were randomized to "tight" or "less
tight" blood pressure control to ascertain the benefits of
lowering blood pressure and to ascertain whether the use of an
ACE inhibitor (captopril) or beta-blocker (atenolol) offered
particular therapeutic advantages or disadvantages.
The UKPDS results establish that
retinopathy, nephropathy, and possibly neuropathy are benefited
by lowering blood glucose levels in type 2 diabetes with
intensive therapy, which achieved a median HbA1c of 7.0%
compared with conventional therapy with a median HbA1c of 7.9%.
The overall microvascular complication rate was decreased by
Epidemiological analysis of the UKPDS data
showed a continuous relationship between the risks of
microvascular complications and glycemia, such that for every
percentage point decrease in HbA1c (e.g., 9 to 8%), there was a
35% reduction in the risk of complications.
The results demonstrate that the risks of
complications can be significantly lowered even in the range of
hyperglycemia where HbA1c levels are <8.0%. There was no
evidence of any glycemic threshold for any of the microvascular
complications above normal glucose levels (i.e., HbA1c >6.2%).
These results confirm previous conclusions
that lowering blood glucose would be beneficial based on
observational studies, pathological studies, and on three
randomized clinical trials: the DCCT, the Stockholm Diabetes
Intervention Study, and the Japanese study.
For every percentage point decrease in
HbA1c (e.g., 9 to 8%), there was a 25% reduction in
diabetes-related deaths, a 7% reduction in all-cause mortality,
and an 18% reduction in combined fatal and nonfatal myocardial
infarction. Again, no glycemic threshold for these complications
above normal glucose levels was evident.
The study showed that lowering blood
pressure to a mean of 144/82 mmHg significantly reduced strokes,
diabetes-related deaths, heart failure, microvascular
complications, and visual loss.