Forty-two diabetic patients on insulin once a day in the earlystage of diabetic retinopathy were randomly assigned to one of two kinds of insulin regimen, i.e., single or multiple daily injections. Retinal changes were quantitatively estimated by counting the microaneurysms (MAs) observed on fluorescein angiograms at the posterior pole of the more diseased eye. Baseline characteristics of the two groups were not significantly different. These included duration of diabetes, age at diagnosis, daily dose of insulin, amount of urinary sugar excreted in 24 hours, fasting Mood sugar (FBS), and number of MAs. During the follow-up (mean duration of three years) the mean yearly progression in the number of MAs was significantly less in the multiple-than in the single-injection group: 1.8 ± 0.7 versus 7.2 ± 1.9 (p<0.01; nonparametric test: p<0.02). Final values were, respectively, MAs: 15.2 ± 4.9; 33.0 ± 7.9; glycosuria (gm./24 hrs): 20.6 ± 2.5; 27.5 ± 4.3; FBS (mg./lOO ml.): 154 ± 15; 195 ± 11. P values comparing the two groups were <0.02, <0.02, and <0.05. Thus, in this clinical trial, made under routine treatment conditions, the use of divided daily insulin injections was effective in improving diabetic control and delaying retinal changes. DIABETES 25:463-69, May, 1976.Prospective studies on the effect of the treatment of diabetes on the course of microangiopathy are scarce but strongly suggest that insulin administration and/or the control of diabetes reduce and delay the development of retinal and glomerular changes in diabetic humans 1 -4 and animals. 5 " 8 Indirect arguments have also been given by biochemists. 9 " 11 Previously retrospective studies have claimed that the quality of diabetes control influences the course of

We demonstrate in Caucasians with Type 1 diabetes that (i) eNOS4a/a is associated with absent or non-severe DR, and (ii) eNOS4b/b is associated with severe DR.

Neovascularization plays a role in determining the severity of diabetic retinopathy (DR) due to the effects of several angiogenic and growth factors, including vascular endothelial growth factor (VEGF), plateletderived growth factor (PDGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-1) [1].Chronic hyperglycaemia induces non-severe diabetic retinopathy (DR) in most patients of long duration, but not severe DR in the majority of them, sug- Abstract Aims/hypothesis. Vitamin D, a molecule with antiproliferative, antiangiogenic, antioxidant and immunosuppressive effects, could play a role in the pathogenesis of severe diabetic retinopathy. We examined whether Taq I polymorphism of the vitamin D receptor is involved in the development of severe diabetic retinopathy. Methods. 200 unrelated C-peptide-negative French Type I diabetic patients were randomly selected (male:female, 103:97, age 44.4 12.4 years, diabetes duration: 27.7 10.0 years, BMI: 24.3 3.4 kg/m 2 , HbA 1 c : 8.6 1.3 %). The Taq I site was analysed by PCR followed by digestion with Taq I enzyme. Diabetic retinopathy was assessed by retinal angiography and classified as presence (n = 101) or absence (n = 99) of severe (preproliferative or proliferative) diabetic retinopathy. Results. Frequency of wild-type genotype TT was lower in patients with severe diabetic retinopathy (n = 27) when compared with control subjects (n = 42, OR = 0.5, p = 0.028). Allele frequencies were not different between patients (T: n = 112 and t: n = 90) and control subjects (T: n = 128, and t: n = 70, p = 0.075). Global c 2 (df = 2): p = 0.064. In subjects with diabetes duration of more than 25 years, TT was lower in severe diabetic retinopathy (n = 14) than control subjects (n = 18, OR = 0.3, p = 0.01). Allele frequencies were different between patients (T: n = 68 and t: n = 66) and control subjects (T: n = 52, OR = 0.5, and t: n = 26, OR = 1.9, p = 0.034). Global c 2 (df = 2): p = 0.024. In subjects with HbA 1 c over 9 %, Tt was higher in patients (n = 28) than control subjects (n = 15, OR = 3.1, p = 0.019). Allele frequencies were not different between patients (T: n = 52 and t: n = 38) and control subjects (T: n = 57, and t: n = 29, p = 0.31). Global c 2 (df = 2): p = 0.035. Conclusion/interpretation. In French Type I (insulindependent) diabetic patients, we demonstrate an association between TT form (VDR) and low risk for severe diabetic retinopathy, especially in patients with long duration, and between Tt variant and high risk for severe diabetic retinopathy in subjects with poor glycaemic control. [Diabetologia (2002) 45: 436±442]

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