The relation of glycaemia to the risk of development and progression of retinopathy in the Diabetic Control and Complications Trial

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Abstract
We have assessed the relation between the quarterly capillary glucose profile and the risk of the development and progression of retinopathy in the DCCT. Seven point (preprandial and 90-min postprandial for each meal and bedtime) capillary glucose data were analysed from volunteers whose collections were complete in 80 %, or more, of quarterly periods and who were in the study longer than 4 years (n = 296, conventional therapy; n = 269, intensive therapy). The study cohort differed from excluded patients in having more women and lower HbA1 c at baseline and fewer adolescents, older age and lower baseline mean blood glucose in the intensive therapy group. Univariate analysis showed significant (p < 0.01) associations to sustained 3-step change in retinopathy of each updated glycaemic parameter: mean blood glucose, mean preprandial glucose, mean postprandial glucose, each preprandial, postprandial and bedtime glucose; range glucose, standard deviation glucose; M-value of Schlichtkrull and mean amplitude of glycaemic excursions, albeit with relatively small hazard ratios. Multivariate analyses showed updated mean blood glucose to be the primary risk factor (p < 0.001) with a weak contribution of mean amplitude of glycaemic excursions at baseline (p < 0.005); no other variables added significantly to the model. The association between updated mean blood glucose and risk for retinopathy was nonlinear: risk progressively increased above updated mean blood glucose of 8.3 mmol/l. A gradient of risk could not be determined below this level because events were few. Within the limitations provided by quarterly 7-point capillary glucose measurements as an expression of overall glycaemic behaviour, the major risk for progression of retinopathy is conveyed by updated mean blood glucose especially above 8.3 mmol/l. [Diabetologia (2001) 44: 1215–1220]