Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.
OBJECTIVE
To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.


METHODS
Prospective observational study.


METHODS
23 hospital based clinics in England, Scotland, and Northern Ireland.


METHODS
4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk.


METHODS
Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA(1c) adjusted for possible confounders at diagnosis of diabetes.


RESULTS
The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA(1c) was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%, P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). No threshold of risk was observed for any end point.


CONCLUSIONS
In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA(1c) is likely to reduce the risk of complications, with the lowest risk being in those with HbA(1c) values in the normal range (<6.0%).
Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE. irene.stratton@dtu.ox.ac.uk
I M
IM
Stratton
A I
AI
Adler
H A
HA
Neil
D R
DR
Matthews
S E
SE
Manley
C A
CA
Cull
D
D
Hadden
R C
RC
Turner
R R
RR
Holman
D002387:Cataract Extraction; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000097:blood* / Q000401:mortality; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis / Q000378:metabolism*; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000401:mortality; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D013997:Time Factors
D006442:Glycated Hemoglobin