Risk factors of diabetic retinopathy in type 2 diabetic patients

Diabetic retinopathy (DR) represents a frequent complication of type 2 diabetes mellitus. Up until now, although advances in treatment have greatly reduced the risk of blindness from this disease, DR remains an important problem. Studies about development and risk factors of DR have been carried out internationally. Manariat et al¹ reported that urine albumin, body mass index (BMI), age, fast blood glucose and glycated hemoglobin (HbA1c) were related to DR. Tapp et al² concluded that duration of diabetes, HbA1c and systolic blood pressure were risk factors of DR. However, whether these factors are related with the onset and development of diabetic retinopathy in Chinese patients was not sure. Therefore, the present study was undertaken to investigate related risk factors of DR in Chinese type 2 diabetic patients.

Patients
A total of 746 in-patients (449 men and 297 women) with type 2 diabetes collected from March 2003 to August 2005 were enrolled. Their age were from 16 to 89 years old, with an average age 55.9 years. The average duration of diabetes was 91.41 months, between 0 and 480 months.

Measurements
Body mass index (BMI), waist hip ratio, systolic and diastolic blood pressure were measured. Blood HbA1c was measured by Bio-Rad Variant II and urine albumin was measured by COBAS INTEGRA400 plus (Roche, USA). Blood urine nitrogen (BUN), creatinine (CREA), cholesterol (CHO), triglyceride (TG), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), C-reaction peptide (CRP) and uric acid (UA) were measured using enzymatic methods by Hitachi 7170A auto-chemical analysis instrument, Japan. Fast insulin and C-peptide level were also performed by BYAER ACS180.

Assessment of DR
All these patients were examined by the TRC. NW100. camera (TOPCON, Japan), and were separated into three groups according to their degree of DR. Group 0: non diabetic retinopathy; Group 1: non proliferative diabetic retinopathy (NPDR), including microaneurysms, hard exudates, cotton wool spots, retinal haemorrhages; Group 2: proliferative diabetic retinopathy (PDR), including new vessels, extensive neovascularization, vitrous haemorrhages, fibrovascular proliferation with or without retinal detachment.

Statistical analyses
Descriptive data are given as mean±standard deviation (SD). Comparisons among subjects of group 0, 1 and 2 were performed by the ANOVA tests for continuous variables, whereas frequency of dichotomous variables was compared using χ² analysis. A P value of less than 0.05 was considered significant. The association of DR and the potential risk factors were tested by multiple Logistic regressions.

Of all these 746 patients, 526 (70.51%) patients were classified as non-diabetic retinopathy, 159 (21.31%) patients as non-proliferative-diabetic retinopathy and 61 (8.18%) patients as proliferative-diabetic retinopathy.

Significant differences were found in duration of diabetes, systolic blood pressure (SBP), urine albumin, HbA1c, CRP, HDL-C, UA, CREA, BUN among the three groups. No differences were found in BMI, W/H ratio, diastolic blood pressure (DBP), insulin level, c-peptide level, CHO, TG, LDL-C (Table 1).

Multiple Logistic regression analysis showed that from non-DR to DR, duration of diabetes and urine albumin were associated with odds ratio of 1.010, 1.003 respectively, adjusted for age, sex. And from NPDR to PDR, duration of diabetes, urine albumin, HDL-C and SBP were associated with odds ratio of 1.009, 1.002, 0.157 and 1.019 respectively, adjusted for age, sex. No other factor was significantly associated with DR (Table 2).

With the longitation of duration of diabetes, the prevalence of DR stepped up, shown as the morbidity was 8.95%, 13.75%, 28.4%, 57.93% and 60.32% respectively among the group of duration less than 1 year, 1－5 years, 6－10 years, 11－20 years and more than 20 years (Table 3).

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Table 3. Relationship between duration of diabetes and diabetic retinopathy

Of all these patients, 75.07% experienced non-albuminuria, 15.68% microalbuminuria and 9.25% macroalbuminuria. With the increasing of urine albumin, the prevalence of DR stepped up, shown as among the group of non-, micro- and macro-albuminuria, the prevalence of DR was 16.43%, 59.83% and 84.06% respectively. On the other hand, among the non-DR group, the prevalence of micro- and macro-albuminuria was 8.94% and 2.09%; among the NPDR group, the prevalence was 29.56% and 22.64%; among the PDR group, the prevalence was 37.70% and 36.07% separately (Table 4).

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Table 4. Relationship between albuminuria and diabetic retinopathy

DISCUSSION

Predictors of diabetic complications may be important in the prevention and the management of these complications.³ The present data demonstrated that duration of diabetes and urine albumin were independently related to diabetic retinopathy.

Mitchell et al⁴ reported that about 8% patients became DR for each year that duration of diabetes increased. From this study, it was demonstrated that with the extension of duration of diabetes, the prevalence of DR stepped up, and that it was an independent risk factor of DR. As duration of diabetes is a total reflection of blood glucose control and exposing to other risk factors, and the prevalence of DR is highly related with the increasing of HbA1c, duration of diabetes is an important factor for the incidence and development of DR. Similar conclusions were also found in several studies (including UKPDS⁵), which demonstrated that duration of diabetes and hyperglycemia contributed to the development of DR, and if excellent glycemic control was done at the beginning, DR can be controlled.^6-8

Furthermore, secretion of urine albumin was significantly different among the three groups according to this study, and with the incidence and aggregation of DR, the prevalence of micro- and macro-albuminuria stepped up. Logistic regression analysis showed that urine albumin was also an independent risk factor of DR, which had been reported in both type 1 and type 2 diabetes.^1,9,10 This could be explained as both retinopathy and nephropathy are typical changes of diabetes microvascular disease, and they share same pathogenic mechanisms, increasing of secretion of urine albumin accompanied with development of retinopathy, the incidence and development of DR may indicate the albuminuria level, on the other hand, the albuminuria level may indicate the degree of DR. The mechanisms involved dysfunction of metabolic pathway, nonenzymatic glycation of proteins and advanced glycation end products, the increased production of sorbitol, activation of protein kinase C, reactive oxygen species, inducible form of nitric oxide synthase which enhances free-radical production and apoptotic death of retinal capillary pericytes and endothelial cells which reduces function and increases hypoxia.¹¹ Lunctta et al¹² reported that urine albumin/creatinine had positive correlation with incidence of DR and development of DR, the degree of DR could be accelerated with the increasing of urine albumin, therefore, urine albumin/creatinin was considered to be a manifestation of vascular hyperpermeability which could intensify microvascular disease.

It was also found in this study that from NPDR to PDR, HDL-C and SBP were the other two independent risk factors, which suggested that the decreasing level of HDL-C and the increasing of SBP were significantly correlated with PDR. Several studies reported that serum lipids had the relationship with DR, but the kind of lipids was not same and reason for this relationship was not clear.^13-15 The relationship between blood pressure and DR was identified according to UKPDS,¹⁶ which concluded that high BP was detrimental to each aspect complications from diabetic eye disease.

Therefore, according to this study, in Chinese type 2 diabetic patients, two risk factors, duration of diabetes and urine albumin are independently related to DR, both from non-DR to DR and from NPDR to PDR.

REFERENCES

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