Type 2 diabetes mellitus (T2DM) is one of the fastest growing diseases in China and has become a major public health challenge. The most common complication of T2DM is diabetic retinopathy (DR), which is a leading cause of preventable blindness in working-aged people. It has been estimated that diabetic individuals are 25 times more likely than their nondiabetic counterparts to suffer severe, permanent vision loss [
A retrospective, cross-sectional analysis was performed in T2DM patients who had been admitted to the Endocrinology Department of Shanghai Jiaotong University Affiliated Sixth People’s Hospital from January 2008 to December 2009. All of the patients had been admitted specifically for management of their diabetes. Diagnosis of diabetes was performed according to the 1999 World Health Organization criteria. Patients were excluded according to the presence of type 1 diabetes mellitus, any other non-type 2 diabetes (such as gestational diabetes), poor general condition, severe infection, acute cerebrovascular disease, recent surgery, impaired cardiac function (III-IV degree according to NYHA classification), or severely impaired hepatic or renal function.
Clinical data was extracted from the departments medical records for each patient and included age, gender, duration of diabetes, and previous history of hypertension and dyslipidemia. Patients’ medical examinations on the day of admission had included measurements of height, body weight, and blood pressure. BMI was calculated as kg/m2. Hypertension was defined as diastolic blood pressure (DBP) ≥ 90 mmHg, SBP ≥ 140 mmHg, or self-reported use of antihypertensive medication. Dyslipidemia was defined as an elevation of total cholesterol (TC) ≥ 6.1 mmol/L and/or of triacylglycerol (TG) ≥ 2.26 mmol/L, or an elevated low-density lipoprotein cholesterol (LDL-C) ≥ 4.14 mmol/L or a decreased high-density lipoprotein cholesterol (HDL-C) < 1.0 mmol/L, according to the American National Cholesterol Education Program (Adult Treatment Panel III) [
Fasting blood samples were drawn before breakfast on the second day of hospitalization for measurements of fasting plasma glucose (FPG), HbA1c, glycated albumin (GA), C-peptide, Ua, TC, TG, LDL-C, and HDL-C. The 2 h postprandial glucose (2 h PG) levels were drawn after a mixed meal. The plasma glucose concentration was measured using a glucose oxidase method (Automatic Biochemistry Analyzer; Beckman Coulter, USA). Serum lipids and renal function indices were determined by enzymatic procedures using an autoanalyzer (7600-020; Hitachi, Tokyo, Japan). Serum C-peptide was determined by radioimmunoassay (Linco, USA). HbA1c was estimated by high-performance liquid chromatography using the HLC-723G7 analyzer (Tosoh Corporation, Japan). GA was measured by a liquid enzymatic assay kit (Lucica GA-L; Asahi Kasei Pharma, Japan). The 24 h urinary albumin concentration was determined by nephelometry using an N antiserum to Human Albumin Assay and BN II analyzer (Dade-Behring, USA). Hb was measured using an automated blood analyzer (XE-5000; Sysmex Corp., Japan).
Fundus photographic imaging was carried out by following a standardized protocol. Both eyes of each participant were photographed with a 45-degree 6.3-megapixel digital nonmydriatic camera (Canon CR6-45NM, Lake Success, NY, USA). According to the International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease Severity Scales [
All statistical analyses were carried out using the Statistical Package for the Social Sciences software version 16.0 (SPSS Inc., Chicago, IL). Numerical variables of normal distribution were expressed as mean ± SD, while those of nonnormal distribution were expressed as median (quartile). One-way ANOVA and
In this study, binary logistic regression was primarily used to estimate the association of independent factors and DR by Wald and
According to the inclusion and exclusion criteria mentioned above, a total of 2009 T2DM patients were included in this analysis. There were 1145 (57%) males and 864 (43%) females, with mean age of 59.69 ± 12.28 years and diabetic duration of 8.05 ± 6.71 years. Of all the subjects, 597 (29.7%) were diagnosed with DR, of which 548 (27.3%) had NPDR and 49 (2.4%) had PDR. Comparisons between the two groups (NDR versus DR) revealed a significantly higher prevalence of anemia, hypertension, DN, DPN, and PA in the DR group. In contrast, no differences were found between the two groups for dyslipidemia, CHD, CVD, and hyperuricemia/gout. PA, DN, DPN, hypertension, and anemia were positively correlated with DR (Table
Comparison of clinical characteristics and comorbidities among DR groups:
Total | NDR | DR |
|
| |
---|---|---|---|---|---|
|
2009 (100) | 1412 (100) | 597 (100) | ||
Male | 1145 (57) | 832 (58.9) | 313 (52.4) | 0.007 | −0.060 |
Female | 864 (43) | 580 (41.1) | 284 (47.6) | ||
Dyslipidemia | 1503 (74.8) | 1063 (75.3) | 440 (73.7) | 0.564 | −0.017 |
Hypertension | 1166 (58) | 778 (55.1) | 388 (65) | 0.000 | 0.092‡ |
Anemia | 164 (8.2) | 86 (6.1) | 78 (13.1) | 0.000 | 0.116‡ |
CHD | 122 (6.1) | 90 (6.4) | 32 (5.4) | 0.385 | −0.019 |
CVD | 108 (5.4) | 78 (5.5) | 30 (5.0) | 0.650 | −0.100 |
PA | 1334 (66.4) | 912 (64.6) | 422 (70.7) | 0.008 | 0.059‡ |
DN | 497 (24.7) | 283 (20.0) | 214 (35.8) | 0.000 | 0.167‡ |
DPN | 866 (43.1) | 541 (38.3) | 325 (54.4) | 0.000 | 0.149‡ |
Hyperuricemia/ |
208 (10.4) | 151 (10.7) | 57 (9.5) | 0.441 | −0.017 |
* Univariate relation of DR with clinical comorbidities was determined using Spearman’s correlation coefficient.
Comparisons of clinical parameters according to the retinopathy status are shown in Table
Comparison of clinical parameters between DR groups.
Total | NDR | DR |
|
| |
---|---|---|---|---|---|
Age, years | 59.69 ± 12.28 | 59.89 ± 12.81 | 59.21 ± 10.93 | 0.227 | −0.032 |
Duration, years | 8.05 ± 6.71 | 6.99 ± 6.29 | 10.58 ± 6.98 | <0.001 | 0.255‡ |
BMI, kg/m2 | 24.77 ± 3.51 | 24.84 ± 3.53 | 24.61 ± 3.45 | 0.174 | −0.028 |
SBP, mmHg | 131.40 ± 17.39 | 129.53 ± 16.55 | 135.79 ± 18.51 | <0.001 | 0.164‡ |
DBP, mmHg | 79.61 ± 9.68 | 79.18 ± 9.48 | 80.62 ± 10.08 | 0.002 | 0.068‡ |
Hb, g/L | 135 (125~145) | 136 (126~146) | 132 (122~143) | <0.001 | −0.105‡ |
TC, mmol/L | 4.75 ± 1.13 | 4.72 ± 1.10 | 4.81 ± 1.20 | 0.149 | 0.034 |
TG, mmol/L | 1.86 ± 1.65 | 1.88 ± 1.76 | 1.79 ± 1.36 | 0.269 | −0.035 |
HDL-C, mmol/L | 1.11 ± 0.32 | 1.10 ± 0.32 | 1.13 ± 0.31 | 0.056 | 0.052† |
LDL-C, mmol/L | 3.22 ± 1.0 | 3.21 ± 0.98 | 3.25 ± 1.03 | 0.515 | 0.008 |
FPG, mmol/L | 8.32 ± 2.84 | 8.29 ± 2.73 | 8.39 ± 3.09 | 0.480 | −0.007 |
2 hPG, mmol/L | 14.06 ± 4.67 | 14.05 ± 4.64 | 14.09 ± 4.76 | 0.827 | 0.005 |
HbA1c, % | 8.7 (7.2~10.5) | 8.5 (7.1~10.4) | 9.1 (7.5~10.7) | 0.003 | 0.068‡ |
GA, % | 24 (19~30) | 24 (19~30) | 25 (20~31) | <0.001 | 0.09‡ |
C-peptide, ng/mL | 1.59 (1.0~2.28) | 1.70 (1.11~2.41) | 1.35 (0.85~2.04) | <0.001 | −0.157‡ |
IMT, mm | 0.94 ± 0.71 | 0.92 ± 0.62 | 0.99 ± 0.87 | 0.047 | 0.049† |
24 h-urinary albumin, mg | 10.92 (5.72~30.62) | 9.37 (5.32~23.15) | 18.66 (7.25~77.60) | <0.001 | 0.213‡ |
GFR, mL/min | 92.47 ± 25.28 | 93.60 ± 25.17 | 89.66 ± 25.37 | 0.003 | −0.069‡ |
Data are mean ± SD or mean (quartile).
* Univariate relation of DR with clinical parameters were determined using Spearman’s correlation coefficient.
Age, gender, duration of diabetes, BMI, dyslipidemia, HbA1c, SBP, DBP, C-peptide, anemia, DN, DPN, and PA were entered into a logistic regression model. The results of the logistic regression analyses are displayed in Table
Logistic-regression-identified factors associated with DR.
Items |
|
S.E. | Wald |
|
OR | 95% CI of OR | |
---|---|---|---|---|---|---|---|
Lower boundary | Upper boundary | ||||||
Duration | 0.080 | 0.011 | 56.809 | 0.000 | 1.083 | 1.061 | 1.105 |
SBP | 0.013 | 0.004 | 12.848 | 0.000 | 1.013 | 1.006 | 1.021 |
DN | 0.479 | 0.144 | 11.041 | 0.001 | 1.614 | 1.217 | 2.142 |
Anemia | 0.619 | 0.218 | 8.509 | 0.004 | 1.857 | 1.225 | 2.815 |
PA | 0.463 | 0.160 | 8.360 | 0.004 | 1.589 | 1.161 | 2.176 |
C-peptide | −0.273 | 0.066 | 17.018 | 0.000 | 0.761 | 0.669 | 0.867 |
The relationship between each independent factor associated with DR and the severity of retinopathy was examined. The prevalence of NPDR and PDR was much higher in patients with longer duration of diabetes, higher level of SBP, increased severity of DN, more severe anemia, presence of PA, and lower serum C-peptide quartile (all
Prevalence of NDR, NPDR, and PDR for the related risk factors. All had
The results of this clinic-based study suggest that independent factors associated with DR in Chinese patients include duration of diabetes, SBP, C-peptide, DN, PA, and anemia. In particular, the severity of DR was found to be increased in conditions of lower C-peptide levels and elevated levels of the other independent factors.
In our study, the duration of diabetes was found to be significantly higher in patients with DR than in those without, and the longer the duration of diabetes the higher the prevalence of retinopathy. Our findings agree with those from previously published studies in populations of other ethnic groups that also identified duration of diabetes to be an independent risk factor for retinopathy [
HbA1c and GA were found to be significantly higher in DR patients from our Chinese study population. However, they did not retain significance in the final logistic regression analysis. This was different from the results of previous studies [
The current study in Chinese patients showed that the prevalence of hypertension was higher in subjects with DR than in those without, and the study found that SBP was positively associated with DR. The UKPDS also found that the incidence of retinopathy was associated with SBP in their largely Caucasian population; specifically, the relative risk for DR was found in the UKPDS to be 1.5 for systolic pressures between 125 and 139 mmHg and 2.8 for systolic pressures higher than 140 mmHg [
Dyslipidemia was not shown in our study population to be associated with retinopathy, which was consistent with the reported results from some of the other studies in the literature [
Albuminuria excretion was significantly higher in our patient population with DR than in those without, and GFR was negatively correlated to DR. Further analysis showed that DN was observed to be an independent risk factor for the development of DR, with odds of 1.614 times. Moreover, the severity of DR in patients with T2DM appeared to be aggravated with an increasing severity of DN. Higher risk of concomitant DR might be predicted in patients with DN or renal dysfunction. This could be explained by the fact that both nephropathy and retinopathy are related to endothelial dysfunction-mediated microvascular complications of diabetes mellitus (DM). A number of previous studies have published evidence to support the suggestion that DR and DN progress in a parallel manner; thus, the presence of one is believed to predict the development of the other [
C-peptide was negatively correlated with DR in our study, indicating it as a protective factor against DR. Our results were consistent with a previous study that also found reduced serum C-peptide to be associated with a higher prevalence of retinopathy in T2DM [
In agreement with findings of previous studies [
Anemia was found in our study to be another risk factor of DR in Chinese patients, perhaps because of anemia-induced retinal hypoxia. Individuals with anemia were 1.857 times more likely to develop DR than individuals without anemia. Moreover, the prevalence of PDR was significantly increased in patients with moderate-severe anemia than those with absolutely no detectable anemia. These results are consistent with those reported in the ETDRS, in which low hematocrit was identified as an independent risk factor for the development of high-risk PDR and visual impairment [
There were several limitations to the present study that should be noted here, as they may affect the generalization of our findings. Because this was a cross-sectional study, the results do not provide definite information on a cause-and-effect relationship. In addition, because our study population was composed solely of patients from a single center, there was unavoidable bias of selection, information, and confounding variables. Prospective and larger studies are required to overcome these limitations.
The authers would like to express their appreciation to the study participants and research associates who made it possible to complete this research project. This work was funded by Grants from the National Natural Science Foundation of China (no. 30670989) and the National 973 Program (no. 2011CB504001).