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Development and progression of diabetic retinopathy and associated risk factors in type 1 diabetic patients: a 15-year follow-up study

Background and aims. Diabetic retinopathy (DR) is an important cause of visual impairment in developed countries, especially in working age adults. The aim of this study was to evaluate the 15-year incidence of development and progression of retinopathy in a sample of type 1 diabetic patients and determine the associated risk factors in these patients. Materials and methods. 123 type 1 diabetic patients (62 male / 61 female) were enrolled in this study and followed for 15 years. Basic and anthropometric parameters assessed were age, gender, diabetes duration and body mass index (BMI). Glycated hemoglobin (HbA1c), total cholesterol, HDL and LDL cholesterol, triglycerides (TG), C-reactive protein (CRP), homocysteine (HCY), fibrinogen (FIB), plasma viscosity and serum creatinine were determined using routine laboratory methods. Urinary albumin excretion rate (UAE) was measured from a 24-hr urine sample. Blood pressure was measured with a mercury sphygmomanometer after a 10-min resting period. Ophthalmologic examination included binocular indirect slit lamp fundoscopy, color fundus photography after mydriasis according to the EURODIAB retinal photography methodology and optical coherence tomography of the macula. Possible risk factors for the development and progression of DR were examined in backward stepwise Cox's multiple regression analysis. Results: At the beginning of the study patients were 24.60 ± 4.45 years old with mean diabetes duration of 9.64 ± 4.42 years. Mean/median values of BMI (23 ± 2.43 kg/m2), total cholesterol (4.92 ± 1.11 mmol/L), HDL cholesterol (1.57 ± 0.36 mmol/L), LDL cholesterol (2.73 ± 0.77 mmol/L), TG (0.82 ± 0.43 mmol/L), CRP (0.8 (0.1 - 5.1) mg/L), HCY (10.5 (7.5 -14.2) µmol/L), FIB (2.9 (1.9 - 4.1) mg/L), plasma viscosity (1.55 ± 0.10 mPa.s), serum creatinine (81.59 ± 15.05 µmol/L), systolic (113 (95 - 130) mmHg) and diastolic blood pressure (75 (60 - 85) mmHg) were within normal range for diabetic patients, whereas HbA1c (7.72 ± 1.48 %) and UAE (10.05 (3.18 - 8036.07) mg/24h) were elevated. At baseline, 87 (71%) patients had no retinopathy and 36 (29%) had nonproliferative diabetic retinopathy (NPDR). After 15 years, 54 patients (43.9% ; 29.3/1000 person-years) developed NPDR or progressed to proliferative diabetic retinopathy (PDR). None of the patients had diabetic macular edema (DME) at baseline, nor has it developed after 15 years. From the 87 patients with no retinopathy at baseline 24 (27.6% ; 18.4/1000 person-years) developed NPDR, while from the 36 patients with NPDR at baseline 30 (83.3% ; 55.5/1000 person-years) progressed to PDR. Higher HbA1c (HR=2.276, P=0.006), lower HDL cholesterol (HR=0.161, P=0.025) and higher UAE (HR=0.388, p=0.045) were significant risk factors for development and progression of retinopathy, whereas the presence of DR at baseline (HR=2.319, p=0.023) was significant factor for its progression to PDR. Diabetes duration, BMI, inflammatory and hemostatic disturbance markers showed no significant values in the statistical analysis. Conclusions: The results of this study suggest that 15-year incidence of development and especially progression of retinopathy in type 1 diabetic patients is still very high. This points to the need for close monitoring of type 1 diabetic patients aimed at early detection, prevention or limitation the progression of retinopathy, especially those with higher HbA1c, lower HDL cholesterol, higher UAE and the initial presence of DR.

Type 1 diabetes, diabetic retinopathy, risk factors

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