| BackgroundThe prevalence of diabetes has increased dramatically in recent years, and the prevalence of diabetic chronic complications also increased simultaneously. Diabetes and its complications have become the major public health problem. Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the two common chronic diabetic microangiopathy. Chronic hyperglycemia is an important factor in the development and progression of DN and DR. Despite the implementation of intensive glucose control in patients with diabetes,20%-40% of diabetic patients will develop DN, the main clinical manifestation of early DN is urinary albumin excretion increased slightly, and gradually progress to macroalbuminuria and increase serum creatinine with the extension of duration of diabetes, and eventually develop to end-stage renal disease, most of diabetic patients require dialysis or kidney transplant. The all cause mortality of DN is 20-40 times more than non-DN patients. DR is a highly specific diabetic microangiopathy, the pathological performance of DR are hemangioma, lipid exudation and hemorrhage for vascular permeability increasing, vascular occlusion and neovascularization. The prevalence of diabetic patients with DR is 15.5%-46.9%, DR is the most common cause of visual and blindness. As the disease progressed to proliferative retinopathy, about 50% of patients will be blind if effective treatments are not taken.Chronic hyperglycemia is the major risk factor for the development and progressed of diabetic nephropathy and retinopathy. The formation of advanced glycation end products, activation of protein kinase C, polyol pathway and hexosamine pathyway, and oxidative stress, the release of pro-inflammatory cytokines induced by chronic hyperglycemia can lead to microvascular injury. Capillary basement membrane thickening, capillary became narrow progressively, and occlusion, causing organ hypoperfusion. Duration of diabetes, glucose and blood pressure are the common risk factors for nephropathy and retinopathy, some researches indicated that part of patients with good glucose and blood pressure, but they still developed nephropathy and retinopathy, suggesting that there were other risk factors. For some T2DM patients, DN and DR had existed at the time of diagnosis of T2DM. Therefore, ADA guidelines suggested that patients should be screened for DN and DR shortly after the diagnosis of T2DM, and needed for annual quantitative assessment of albumin excretion and fundus examination after diagnosis of T2DM. In fact, Only a few patients screened for diabetic complication. The clinical manifestation of DN and DR are not obvious, and often ignored by patients, until the emergence of decline in renal function and visual defect, attention would be taken by patients. There is no effective method to completely cure the DN and DR, clinical studies also found that the emergence of DN and DR had increased the incidence of cardiovascular disease in diabetic patients, causing the quality of life to reduce seriously and increasing the financial burden of diabetic patients. Taking effective treatment at the early stage of DN and DR can slow down the rate of development of end-stage renal failure and visual impairment. Therefore, we should detect the risk factors of DN and DR at the early time for early diagnosis and taking intervention measures so that prevent and delay the occurrence and progression of diabetic complication effectively.The occurrence of DR is earlier than DN, more than 95% type 1 diabetic nephropathy with diabetic retinopathy, and researches also suggested that DR could predict the development of diabetic nephropathy in type 2 diabetic patients. DR has been recommended as one of standard for diagnosis of type 2 diabetic nephropathy by NKF/KDOQI guidelines. However, part of T2DM patients with DN diagnosed by pathological without DR. The relationship between DN and DR is still controversial in T2DM patients. Some researches found that there was no relationship between DN and DR. At the same time, studies also showed that the relationship between DN and DR was different among different races. Based on this background, a further investigate the risk factors of DN and DR, as well as the relationship between DN and DR in Chinese patients with type 2 diabetes mellitus is necessary, and it is helpful for clinicians to manage and educate diabetic patients. This study is divided into two part to discuss the risk factors of DN and DR, and the relationship between DN and DR, respectively.Part 1. Risk factors of diabetic nephropathy and diabetic retinopathyObjectiveTo investigate the relative risk factors associated with diabetic nephropathy and diabetic retinopathy so as to detect and diagnose DN and DR, and to provide theoretical evidence for prevention and treatment of DN and DR.Methods1. Research subjects:Retrospective analysis type 2 diabetic patients hospitalized in the Endocrinology and Metabolism Department at Nanfang Hospital between January 2011 to December 2013.1.1 Included criteria:(1)18 to 75-year-old;(2) Patients were accorded with the diagnostic criteria of diabetes mellitus of World Health Organization(WHO) 1999;(3) Classification criteria:according to family history* age of onset, the presence of spontaneous ketosis, insulin and C-peptide release test and antibody assay to diagnose T2DM;(4) All patients included in the study had 2 times 24-hour urinary albumin quantitative examination at least in 3-6 months.1.2 Exclusion criteria:(1) Other types of diabetes;(2) Acute complications of diabetes such as diabetes ketoacidosis and hyperosmolar coma;(3) Systemic infectious disease, sever edema and chronic heart failure;(4) Renal transplants or primary glomerular diasease proven by the renal biopsy, renal transplantation, dialysis? urinary tract infection and urinary tract obstruction, symptoms of acute or chronic congestive heart failure;(5) Unclear images of fundus for cataract and blind.2. Research method:2.1 Definition and grouping of diabetic nephropathy (DN):2 of 3 specimens collected within a 3- to 6-month period should be abnormal before considering DN diagnosis. Patients with infection or other glomerular diseases were excluded. Patients were grouped according to the urinary albumin excretion. Urinary albumin excretion (UAE)< 30 mg/24h was defined as normoalbuminuria,30-299 mg/24h as microalbuminuria and> 300 mg/24h as macroalbuminuria.2.2 Definition of diabetic retinopathy(DR):The severity of DR was graded according to the International Clinical Diabetic Retinopathy. DR-0 non-diabetic retinopathy; DR-1 mild non-proliferative retinopathy:microaneurysms only; DR-2 moderate non-proliferative retinopathy:more than microaneurysms but less than severe non-proliferative retinopathy; DR-3 severe non-proliferative retinopathy: more than 20 intraretinal hemorrhage in each of 4 quadrants, or definite venous beading in 2+quadrants, or prominent intraretinal microvascular abnormalities in 1+ quadrant, and no signs of proliferative retinopathy; DR-4 proliferative retinopathy: neovascularization or vitreous/preretinal hemorrhage.2.3 Gender, age, duration of diabetic and a history of medication were recorded. Blood pressure, height and weight were measured, Body-mass index(BMI) was calculated by the equation:BMI=weight (kg)/height2 (m2). A history of cardio-and cerebro-vascular disease, peripheral artery disease, hypertension, diabetic peripheral neuropathy were collected. Blood biochemical indexes were collected such as fasting blood glucose (FBG), glycosylated hemoglobin Alc (HbAlc), hemoglobin (Hb), triglyceride (TG), total cholesterol (CHOL), high density lipoprotein (HDL), low density lipoprotein (LDL), serum creatinine(sCr), uric acid (UA). Estimate glomerular filtration rate (eGFR) was caculaed with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.3. Statistical analysis:Statistical analyses were undertaken using SPSS version 13.0 (SPSS Inc, Chicago, IL, USA) software Package. Data conformed to a normal distribution were represented as mean±SD, data in skewness distribution were reported as medians (interquartile range), prevalence of DN and DR were presented as percentages. Comparison of rate was performed with Chi-square (Ⅹ2) test. Comparisons among groups of DN and DR were analyzed by One-way ANOVA or Kruskal-Wallis H test. Multivariate binary logistic regression was used to investigate the independent risk factors for DN and DR. DN or DR was used as the dependent variable, different risk factors which were identified in univariate logistic regression analysis entered the multivariate stepwise logistic regression. P< 0.05 (two-tailed) was recognized as statistically significant.Result1. A total of 935 T2DM patients were included in this study.649 (69.4%) patients with normalbuminuria,286 (30.6%) patients with DN consists of 173 (18.5%) microalbuminuria and 113 (12.1%) macroalbuminuria.1.1 Duration of diabetes, SBP, UA, sCr, UAE increased gradually in patients with normoalbuminuria, micro-and macro-albuminuria, Hb, eGFR were decreased gradually, there were significant differences, all P<0.05. There was no difference in age, sex, TG, CHOL, HDL, LDL, FBG among normoalbuminuria, micro-and macro-albuminuria, all P>0.05. The value of HbAlc declined with the increase in urinary albumin excretion, and HbAlc was significantly lower in macroalbuminuria.1.2 Compared with normalbuminuria group, the prevalence of cardio-and cerebro-vascular disease, hypertension, peripheral artery disease, diabetic peripheral neuropathy, diabetic retinopathy was significantly higher in DN group (14.3% vs 7.4%,44.4% vs 22.3%,8.4% V53.5%,59.8% vs 40.4%,65.4% vs 21.0%, respectively, all P＜0.05).1.3 Logistic analysis showed that duration of diabetic(OR=1.084,95%CI: 1.050-1.119), SBP(OR=1.025,95%CI:1.016-1.034), Hb(OR=0.986,95%CI: 0.977-0.996), UA(OR=1.005,95%CI:1.003-1.006), TG(OR=1.075,95%CI: 1.003-1.153), DR(OR=4.623,95%CI:3.254-6.567), cardio-and cerebro-vascular disease(OR=2.152,95%CI:1.256-3.688) were independent risk factors for albuminuria, and the severity of albuminuria increased with the longer duration, the higher SBP, TG and UA, the lower Hb, as well as the occurrence of DR and cardio-and cerebro-vascular diseases, all P＜0.05.2. T2DM patients with DR were 323(34.5%), NPDR 283(30.3%), PDR 40(4.2%).2.1 Duration of diabetes, SBP, UA, sCr, UAE increased gradually in patients withNDR, NPDR and PDR, there were significant differences, all P＜0.05. Hb, eGFR were decreased gradually, there were significant differences, all P＜0.05. There was no difference in sex, BMI, DBP, FBG, CHOL, HDL, LDL, TG among NDR, NPDR and PDR, all P>0.05. HbAlc was significantly lower in PDR than NDR and NPDR.2.2 Compared with NDR group, the prevalence of peripheral artery disease, hypertension, diabetic nephropathy, diabetic peripheral neuropathy were significantly higher in DN group(7.5% vs 3.8%,39.3% vs 23.7%,57.9% vs 16.2%, 64.1% vs 36.9%, respectively, all P＜0.05). There was no signifigant defference in the prevalence of cardio-and cerebro-vascular disease(10.8% vs 8.8%, P=0.319).2.3 Logistic regression analysis showed that duration of diabetic(OR= 1.067, 95% CI:1.035-1.100), SBP(OR=1.013,95%CI:1.005-1.021), Hb(OR=0.978, 95%CI:0.969-0.987), albuminuria(OR=4.400,95%CI:3.128-6.189), diabetic peripheral neuropathy (OR=1.860,95% CI:1.341-2.580) were independent risk factors for DR, and the severity of DR increased with the longer duration, the higher SBP, the lower Hb, and the occurrence of DN, diabetic peripheral neuropathy, all P<0.05.Conclusion1. A total of 935 T2DM patients were included in this study, the prevalence of DN(albuminuria) was 30.6%, microalbuminuria was 18.5% and macroalbuminuria was 12.1%. Duration, SBP, Hb, UA, TG, DR and cardio-and cerebro-vascular diseases were the independent risk factors of albuminuria, and Hb was a protective factor. The level of UAE increased with the longer duration, the higher SBP, TG and UA, the lower Hb, as well as the occurrence of DR and cardio-and cerebro-vascular diseases.2. The prevalence of DR, NPDR and PDR were 34.5%,30.3% and 4.2%, respectively. Duration, SBP, Hb, albuminruia and diabetic peripheral neuropathy were the independent risk factors of DR. The prevalence and severity of DR increased with the longer duration, the higher SBP, the lower Hb, and the occurrence of DN, diabetic peripheral neuropathy.Patients with longer duration should pay attention to screen for complication. Actively intervention measure should be taken for SBP, UA, TG, Hb, albuminuria, and as early as possible to diagnose, so as to prevent and delay the occurrence and progression of DN and DR.Part 2. Association between urinary albumin excretion and diabetic retinopathyObjectiveTo evaluate the association between 24 hour urinary albumin excretion (UAE) and diabetic retinopathy (DR), and analyze if UAE can predict the development of DR.Method1. Subjects, inclusion and exclusion standards were the same as the first part.2. The definition and staging of DR and DN were the same as the first part.3. Statistical analysis:The association between DN and DR was analysis by Spearman correlation. Patients were divided into UAE deciles, Odds ratios (ORs) and 95% confidence interval of DR for patients in UAE decile were calculated with logistic regression analyses; a potential cutoff value of UAE to predict the development of DR was calculated with Receiver operation characteristic curve (ROC). P< 0.05 (two-tailed) was recognized as statistically significant.Result1. Among 173 cases of microalbuminuria, patients with DR were 96 cases (55.5%),13 of them (7.5%) were mild NPDR,49 of them (28.3%) were moderate NPDR,26 of them (15.0%) were severe NPDR,8 of them (4.6%) were PDR. Among 113 cases of macroalbuminuria, patients with DR were 91 cases(80.5%),4 of them (3.5%) were mild NPDR,20 of them (17.7%) were moderate NPDR,37 of them (32.7%) were severe NPDR,30 of them (26.5%) were PDR. Among 649 cases of normalbuminuria, patients with DR were 136 cases(21.0%), and DR. was mainly composed of mild-and moderate-NPDR. The prevalence of DR among normalbuminuria, microalbuminuria and macroalbuminuria were significant difference, P=0.000. However, there were 34.6% patients with albuminuria without DR.2. The value of UAE in NDR, mild and moderate NPDR, severe NPDR, PDR were 9.9(6.0-20.0),26.0(10.0-117.4),143.5(14.0-908.0),888.5(296.5-3031.5), respectively, there were significant defference among groups, all P<0.05。3. Microalbuminuria and macroalbuminuria were independent risk factors of DR, and the OR of DR was 3.448 (2.325-5.115),7.833 (4.251-14.435), all P=0.000. Spearman correlation analysis showed the correlation coefficient of DN and DR was 0.489,?=0.000.4. Patients were divided into UAE deciles, compared with patients in the first decile UAE, the risk of DR for patients in the 6th decile UAE levels (14.0-19.2 mg/24h) was increased significantly, and the OR(95%CI) was 2.13 (1.04-4.39), P=0.04.5. The area under the ROC was 0.76. when microalbuminuria was 18.58 mg/24h, the sensitivity and specificity of the diagnosis of DR were 67.5%,72.6%, respectively. And the positive and negative predictive values of this cutoff were 56.0% and 80.8%, respectively.Conclusion1. The prevalence and severity of DR increased with the increasing of UAE. UAE was significantly positively correlated with diabetic retinopathy in T2DM patients, and the relationship independent of diabetic duration, serum lipid, SBP, Hb, UA and other risk factors.2. A UAE level in 18.58 mg/24h can be a potential predictor of the risk for DR development. Patients with UAE level above 18.58mg/24h should be deemed to be at high risk of DR, and they should undergo fundus examination closely, attention should pay to the patient’s condition. |
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