2型糖尿病肾脏损害与糖尿病视网膜病变相关性的临床和病理研究
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摘要
【研究背景】
糖尿病肾脏病变和糖尿病视网膜病变的发病机制尚不完全清楚,但一般倾向于认为高血糖及其异常代谢产物的形成是导致其血管损伤的病理基础。因此理论上说,这两者应该是平行发展的。然而,目前关于糖尿病肾脏病变与视网膜病变相关性的文献结果存在许多矛盾之处,尤其是2型糖尿病。另一方面,现有研究资料绝大多数均为国外文献,考虑到2型糖尿病的明显遗传异质性,我们认为有必要针对中国的2型糖尿病患者进行相应的临床和病理研究,以期了解中国2型糖尿病人群中视网膜病变与肾脏病变之间的可能关联。
【目的】
从临床以及病理两个方面探讨2型糖尿病患者糖尿病肾脏疾病与视网膜病变之间的相关性。
【方法】
(1)蛋白尿与DR的相关性分析:我们回顾性分析了2007年1月1日至2007年12月31日于北京协和医院内分泌科住院治疗且诊断明确的2型糖尿病患者的相关临床资料。比较DR组患者和NDR组患者在临床资料上的差异性,使用多元logistic回归分析尿蛋白与DR之间的相关性。
(2) DR与肾脏病理类型的相关性分析:我们回顾性分析了2001年1月至2007年12月期间于北京协和医院住院行肾活检且临床、病理资料保存完整、有明确眼底检查结果的2型糖尿病患者;回顾性分析各组病例的病理表现与视网膜病变之间的相关性。
【结果】
(1)尿蛋白组患者发生DR的比例明显高于正常白蛋白尿组,显性蛋白尿组合并PDR的概率明显高于正常白蛋白尿和微量白蛋白尿组。DR和NDR组患者在年龄、2型糖尿病病程、胰岛素使用率、DKD患病率、eGFR、SCr、SBP和合并代谢综合征概率等方面存在明显差异。白蛋白尿和糖尿病病程是DR的独立预测因素;显性白蛋白尿和病程则是PDR的独立预测因素;(2) DG组的29名患者有23名合并DR,明显高于ADRD组(1/18)和NDRD组(10/84)(p＜0.01);DR对于DG的阳性预测值为52.3%,阴性预测值为94.9%;PDR对于DG的阳性预测值为100.0%,阴性预测值为86.7%。(3) DG组和ADRD组分别有15名和10名患者的VEGF单抗染色强度较对照病例增强,但无组间差异。DG组内VEGF染色增强患者合并PDR的概率显著高于染色未增强组。
【结论】
(1)蛋白尿与DR之间存在明显相关性,在2型糖尿病患者中,糖尿病视网膜病变和糖尿病肾脏病变作为糖尿病的微血管组分病变有可能是在病变的某一个阶段同时或者先后出现。(2)对于具有显性白蛋白尿的2型糖尿病患者,DR在DG组的发病率显著高于ADRD组和NDRD组,DR与DG明显相关,PDR是DG的较强正性预测指标。DG患者的肾脏VEGF表达程度与PDR相关。对于DR阴性的显性白蛋白尿患者,建议行活检明确诊断。
Background
The underlying mechanism of diabetic kidney disease (DKD) and diabetic retinopathy (DR) remains unclear, but the hypothesis that persistent hyperglycemia and its abnormal metabolites play a vital role has never been ruled out. Based on this theory, it may be postulated that DKD and DR begin at the same time of disease course. Some reports say it is just the case, however, a remarkable discordance has been found between DKD and DR, especially in type 2 diabetic patients. Moreover, there has been little evidence in Chinese patients. Therefore, the present study will investigate the possible relationship between DR and DKD in Chinese type 2 diabetic patients.
Objective
To evaluate the potential relationship between diabetic kidney injuries and diabetic retinopathy in Chinese patients with type 2 diabetes , from the prospective of clinical findings as well as pathological results.
Methods
Part 1: We retrospectively analyzed 201 patients for whom a diagnosis of type 2 diabetes had been confirmed and had been hospitalized in the endocrine department in our hospital in the year of 2007. Part 2: 142 consecutive type 2 diabetic patients with persistent macroalbuminuria(> 300mg/24h), an ophthalmoscopy and an adequate renal biopsy were enrolled. The biopsy were evaluated by 2 masked nephrologists.
Results
(1) Patients with albuminuria were much more often complicated with DR than those without, while patients with macroalbuminuia were much more often complicated with PDR than those with microalbuminuria and normoalbuminuria. Patients with DR and without DR had significant differences in diabetes duration, insulin use, prevalence of DKD, eGFR, SCr concentration and SBP, among which albuminuria and duration of diabetes are independent predictors for diabetic retinopathy, while macroalbuminuria and duration of diabetes are independent predictors for proliferative diabetic retinopathy (PDR). (2) For the 29 patients with typical diabetic glomerulopathy (DG), 79. 3% (23/29) were complicated with DR, much more higher than patients in ADRD and NDRD group(p<0. 01). All 11 patients with PDR revealed typical DG. The negative predictive value of DR for DG is 94.9%, and a positive predictive value of PDR for DG is 100. 0%. (3) All patients in DG and ADRD groups had positive staining of VEGF antibody. 15 patients in DG group and 10 patients in ADRD group appeared to have stronger staining than control patients. For those patients in DG group who had stronger VEGF antibody staining than control patients, a higher prevalence of PDR was found.
Conclusion
1. Albuminuria and DR are strongly associated. We intend to believe that DR and DKD begins at the same time of disease course or one after another. For those with albuminuria, a close monitoring of the fundus is recommended, the vice versa. 2. For type 2 diabetic patients with macroalbuminuria, DR has a strong relation with DG.. For macroalbuminuric patients without DR, a renal biopsy should be performed if possible.
糖尿病肾脏病变和糖尿病视网膜病变的发病机制尚不完全清楚,但一般倾向于认为高血糖及其异常代谢产物的形成是导致其血管损伤的病理基础。因此理论上说,这两者应该是平行发展的。然而,目前关于糖尿病肾脏病变与视网膜病变相关性的文献结果存在许多矛盾之处,尤其是2型糖尿病。另一方面,现有研究资料绝大多数均为国外文献,考虑到2型糖尿病的明显遗传异质性,我们认为有必要针对中国的2型糖尿病患者进行相应的临床和病理研究,以期了解中国2型糖尿病人群中视网膜病变与肾脏病变之间的可能关联。
【目的】
从临床以及病理两个方面探讨2型糖尿病患者糖尿病肾脏疾病与视网膜病变之间的相关性。
【方法】
(1)蛋白尿与DR的相关性分析:我们回顾性分析了2007年1月1日至2007年12月31日于北京协和医院内分泌科住院治疗且诊断明确的2型糖尿病患者的相关临床资料。比较DR组患者和NDR组患者在临床资料上的差异性,使用多元logistic回归分析尿蛋白与DR之间的相关性。
(2) DR与肾脏病理类型的相关性分析:我们回顾性分析了2001年1月至2007年12月期间于北京协和医院住院行肾活检且临床、病理资料保存完整、有明确眼底检查结果的2型糖尿病患者;回顾性分析各组病例的病理表现与视网膜病变之间的相关性。
【结果】
(1)尿蛋白组患者发生DR的比例明显高于正常白蛋白尿组,显性蛋白尿组合并PDR的概率明显高于正常白蛋白尿和微量白蛋白尿组。DR和NDR组患者在年龄、2型糖尿病病程、胰岛素使用率、DKD患病率、eGFR、SCr、SBP和合并代谢综合征概率等方面存在明显差异。白蛋白尿和糖尿病病程是DR的独立预测因素;显性白蛋白尿和病程则是PDR的独立预测因素;(2) DG组的29名患者有23名合并DR,明显高于ADRD组(1/18)和NDRD组(10/84)(p＜0.01);DR对于DG的阳性预测值为52.3%,阴性预测值为94.9%;PDR对于DG的阳性预测值为100.0%,阴性预测值为86.7%。(3) DG组和ADRD组分别有15名和10名患者的VEGF单抗染色强度较对照病例增强,但无组间差异。DG组内VEGF染色增强患者合并PDR的概率显著高于染色未增强组。
【结论】
(1)蛋白尿与DR之间存在明显相关性,在2型糖尿病患者中,糖尿病视网膜病变和糖尿病肾脏病变作为糖尿病的微血管组分病变有可能是在病变的某一个阶段同时或者先后出现。(2)对于具有显性白蛋白尿的2型糖尿病患者,DR在DG组的发病率显著高于ADRD组和NDRD组,DR与DG明显相关,PDR是DG的较强正性预测指标。DG患者的肾脏VEGF表达程度与PDR相关。对于DR阴性的显性白蛋白尿患者,建议行活检明确诊断。
Background
The underlying mechanism of diabetic kidney disease (DKD) and diabetic retinopathy (DR) remains unclear, but the hypothesis that persistent hyperglycemia and its abnormal metabolites play a vital role has never been ruled out. Based on this theory, it may be postulated that DKD and DR begin at the same time of disease course. Some reports say it is just the case, however, a remarkable discordance has been found between DKD and DR, especially in type 2 diabetic patients. Moreover, there has been little evidence in Chinese patients. Therefore, the present study will investigate the possible relationship between DR and DKD in Chinese type 2 diabetic patients.
Objective
To evaluate the potential relationship between diabetic kidney injuries and diabetic retinopathy in Chinese patients with type 2 diabetes , from the prospective of clinical findings as well as pathological results.
Methods
Part 1: We retrospectively analyzed 201 patients for whom a diagnosis of type 2 diabetes had been confirmed and had been hospitalized in the endocrine department in our hospital in the year of 2007. Part 2: 142 consecutive type 2 diabetic patients with persistent macroalbuminuria(> 300mg/24h), an ophthalmoscopy and an adequate renal biopsy were enrolled. The biopsy were evaluated by 2 masked nephrologists.
Results
(1) Patients with albuminuria were much more often complicated with DR than those without, while patients with macroalbuminuia were much more often complicated with PDR than those with microalbuminuria and normoalbuminuria. Patients with DR and without DR had significant differences in diabetes duration, insulin use, prevalence of DKD, eGFR, SCr concentration and SBP, among which albuminuria and duration of diabetes are independent predictors for diabetic retinopathy, while macroalbuminuria and duration of diabetes are independent predictors for proliferative diabetic retinopathy (PDR). (2) For the 29 patients with typical diabetic glomerulopathy (DG), 79. 3% (23/29) were complicated with DR, much more higher than patients in ADRD and NDRD group(p<0. 01). All 11 patients with PDR revealed typical DG. The negative predictive value of DR for DG is 94.9%, and a positive predictive value of PDR for DG is 100. 0%. (3) All patients in DG and ADRD groups had positive staining of VEGF antibody. 15 patients in DG group and 10 patients in ADRD group appeared to have stronger staining than control patients. For those patients in DG group who had stronger VEGF antibody staining than control patients, a higher prevalence of PDR was found.
Conclusion
1. Albuminuria and DR are strongly associated. We intend to believe that DR and DKD begins at the same time of disease course or one after another. For those with albuminuria, a close monitoring of the fundus is recommended, the vice versa. 2. For type 2 diabetic patients with macroalbuminuria, DR has a strong relation with DG.. For macroalbuminuric patients without DR, a renal biopsy should be performed if possible.
引文
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8.中华医学会糖尿病分会协作组,中华医学会糖尿病分会关于代谢综合征的建议.中华糖尿病杂志,2004.12:p.156—191.
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17.Mohamed,Q.,M.C.Gillies,and T.Y.Wong,Management of diabetic retinopathy:a systematic review.Jama,2007.298(8):p.902-16.
18.Wolf,G.,et al.,Association of diabetic retinopathy and renal function in patients with types 1 and 2 diabetes mellitus.Clin Nephrol,2007.68(2):p.81-6.
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24.Cha,D.R.,et al.,Vascular endothelial growth factor is increased during early stage of diabetic nephropathy in type Ⅱ diabetic rats.J Endocrinol,2004.183(1):p.183-94.
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2.Hovind,P.,et al.,Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes:inception cohort study.Bmj,2004.328(7448):p.1105.
3.Klein,R.,et al.,The relationship of diabetic retinopathy to preclinical diabetic glomerulopathy lesions in type 1 diabetic patients:the Renin-Angiotensin System Study.Diabetes,2005.54(2):p.527-33.
4.Chavers,B.M.,et al.,Relationship between retinal and glomerular lesions in IDDM patients.Diabetes,1994.43(3):p.441-6.
5.Trevisan,R.,et al.,Concomitance of diabetic retinopathy and proteinuria accelerates the rate of decline of kidney function in type 2 diabetic patients.Diabetes Care,2002.25(11):p.2026-31.
6.Wolf,G.,et al.,Association of diabetic retinopathy and renal function in patients with types 1 and 2 diabetes mellitus.Clin Nephrol,2007.68(2):p.81-6.
7.Christensen,P.K.,et al.,Causes of albuminuria in patients with type 2diabetes without diabetic retinopathy.Kidney Int,2000.58(4):p.1719-31.
8.中华医学会糖尿病分会协作组,中华医学会糖尿病分会关于代谢综合征的建议.中华糖尿病杂志,2004.12:p.156—191.
9.Rigalleau,V.,et al.,Estimation of glomerular filtration rate in diabetic subjects:Cockcroft formula or modification of Diet in Renal Disease study equation? Diabetes Care,2005.28(4):p.838-43.
10.Gall,M.A.,et al.,Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus:prospective,observational study.Bmj,1997.314(7083):p.783-8.
11.Cignarelli,M.,et al.,High systolic blood pressure increases prevalence and severity of retinopathy in NIDDM patients.Diabetes Care,1992.15(8):p.1002-8.
12.Savage,S.,et al.,Urinary albumin excretion as a predictor of diabetic retinopathy,neuropathy,and cardiovascular disease in NIDDM.Diabetes Care,1996.19(11):p.1243-8.
13.Cruickshanks,K.J.,et al.,The association of microalbuminuria with diabetic retinopathy.The Wisconsin Epidemiologic Study of Diabetic Retinopathy.Ophthalmology,1993.100(6):p.862-7.
14.Squadrito,G.and D.Cucinotta,The late complications of diabetes mellitus.Ann Ital Med Int,1991.6(1 Pt 2):p.126-36.
15.Villar,G.,et al.,Determinants of development of microalbuminuria in normotensive patients with type 1 and type 2 diabetes.Diabetes Metab,1999.25(3):p.246-54.
16.Chihara,E.,et al.,Retinal nerve fiber layer defect as an early manifestation of diabetic retinopathy.Ophthalmology,1993.100(8):p.1147-51.
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