Diabetic retinopathy (DR) is one of the most common and serious complication of diabetes mellitus, which is the main cause of vision loss in adults. Biological clock genes produce circadian rhythms and control its operation, while the disorder of the expression causes the occurrence and development of a series of diseases. It has been demonstrated that biological clock genes might take effects in the development and progression of DR. On the one hand, circadian rhythm disorder-related behavior disrupts the circadian oscillation of clock genes, and the change in its expression level is prone to unbalanced regulation of glucose metabolism, ultimately increasing the risk of type 2 diabetes mellitus and DR pathogenesis. On the other hand, DR patients exhibit symptoms of circadian rhythm disorders, and it has been suggested that the clock genes may control the development and progression of DR by affecting a variety of retinal pathophysiological processes. Therefore, maintaining normal circadian rhythm can be used as a disease prevention strategy, and studying the molecular mechanism of clock genes in DR can provide new ideas for more comprehensive elaboration of the pathogenesis of DR and search for new therapeutic targets.
Objective To observe the effect of intravitreal injection of mouse nerve growth factor (NGF) on interphotoreceptor retinoid-binding protein (IRBP) in the vitreous of diabetic rats at early stages. Methods Ninety-six male Sprague Dawley (SD) rats were divided into control group (group A, 24 rats) and experimental group (72 rats). The rats in experimental group were induced with streptozotocin injection for diabetic retinopathy model, and then randomly divided into positive control group (group B), normal saline group (group C) and NGF group (group D), 24 rats in each group. The rats in the group A and B were not intervened. The rats were received intravitreal injection with 4mu;l normal saline (group C) or 4 mu;l (0.5 mu;g/mu;l) NGF (group D). At 2, 4, 6 and 8 weeks after injection, IRBP levels were detected by enzymelinked immunosorbent assay (ELISA); hematoxylin-eosin (HE) staining and light microscope were used to observe the morphological changes of the retina; transmission electron microscope was used to observe the retinal ultrastructure.Results At 2 weeks after injection, there was no significant difference in IRBP expression between group A,B,C and D (F=2.833，P=0.052). At 4, 6, 8 weeks after injection, the differences of IRBP expression between group A, B, C and D were significant (F=22.252, 108.459, 105.726; P=0.000). At different time points after injection, there was no significant difference in IRBP expression of group A (F=1.462, P=0.241), but there were significant differences in IRBP expression of group B, C and D (F=150.98, 63.519, 64.604; P=0.000). Light microscope found that the retinal structure was clear in group A and in group B, C, D at 2, 4 weeks after injection; the retinal thickness were thinner in group B, C, D at 8 weeks after injection. Transmission electron microscope displayed that the structure of rod outer segments was clear in group A and in group B, C, D at 2 weeks after injection; partly unclear structure of rod outer segments and slightly enlarged gap were observed in group B, C, D at 4, 8 weeks after injection. Conclusion Intravitreal injection with NGF can stabilize the IRBP expression in the vitreous of diabetic rats at early stages effectively.
ObjectiveTo investigate the effect of behavior intervention through diets and exercises on blood glucose controlling in patients with gestational diabetes mellitus (GDM), and to provide the basis for GDM therapy. MethodsA total of 116 patients with GDM diagnosed and treated in the Sixth Affiliated Hospital of Sun Yat-sen University between March 2011 and December 2012 were taken as our study objects, including 72 patients in the study group and 44 patients in the control group, based on their will. For patients in the study group, we carried out behavior interventions through diets and exercises, including dietary guidance, giving pamphlet and formulating exercise plan, while for patients in the control group, we only gave them oral guidance and publicity materials. The same questionnaire was used to collect all the patients' information. Follow-up was done once in every 3 days, and rechecking was performed 2 weeks later. The results of oral glucose tolerance test and the rate of pathoglycemia were compared in these groups before and after intervention. ResultsThe fasting blood glucose, 1- and 2-hour blood glucose were lowered after the behavior intervention in the study group (P<0.05), which were also significantly lower than the control group (P<0.05). Fasting blood glucose, 1- and 2-hour pathoglycemia was significantly lower in the study group than that in the control group and that before intervention (P<0.05). ConclusionCombination of diets and exercises can control levels of blood glucose in GDM patients, and is an important therapy for GDM.
Objective To observe the serum betatrophin levels in patients with type 2 diabetes mellitus (T2DM) and to explore the role of betatrophin in the pathogenesis of diabetic retinopathy (DR). Methods A total of 59 patients with T2DM (DM group) and 14 healthy controls (NC group) were enrolled in the study. Vision, slit lamp microscope, indirect ophthalmoscope, fluorescein fundus angiography were performed on all the subjects. According to the results of the examination combined with the international DR clinical staging criteria, the patients were divided into no DR (Non-DR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group, with 30, 20 and 9 patients in each, respectively. The fasting blood glucose (FPG), insulin (FIN), C-peptide, glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipid Protein (LDL-C) levels were detected. The level of betatrophin in serum was determined by enzyme-linked immunosorbent assay. The correlation between betatrophin and other indicators was analyzed by Spearman correlation. The influencing factors of PDR were analyzed by logistic regression. Results Compared with subjects in the NC group, the level of FPG (F=-4.316, P＜0.001), FIN (F=2.142, P=0.001), HbA1c (F=-5.726, P＜0.001), TC (t=3.609, P=0.010), LDL-C (t=0.000, P=0.003), and betatrophin (F=-2.263, P=0.024) were significantly increased and HDL-C level (F=-3.924, P＜0.001) was decreases in the DM group. The difference of TG level between two groups was not statistically significant (F= -1.422, P=0.155). Compared with the Non-DR group and the NPDR group, the serum C-peptide (F=7.818, P=0.020) and betatrophin levels (F=12.141, P=0.002) were significantly increased in the PDR group. Spearman correlation analysis showed that the levels of betatrophin in the DM group was positively correlated to TC (r=0.304, P=0.019). The serum levels of betatrophin was positively correlated to body mass index in the Non-DR group (r=0.513, P=0.004). Furthermore, in the PDR group, a significant positive correlation was observed between the serum betatrophin levels and diastolic blood pressure (r=0.685, P=0.042). Logistic regression analysis showed that the duration of diabetes, serum C-peptide and betatrophin levels were risk factors for PDR. After controlling for the duration and serum C-peptide, the PDR risk for betatrophin levels great than or equal to 1.0 ng/ml was 12 times as much as betatrophin levels less than 1.0 ng/ml in T2DM patients. Conclusions The serum betatrophin content of patients with T2DM is abnormal. Betatrophin may be involved in the occurrence and development of PDR.
OBJECTIVE To investigate clinical effects and possible mechanisms of various growth factors on impaired healing ulcers of patients with diabetic disease. METHODS Seventy-eight patients were divided into three groups; saline control, epidermal growth factor(EGF) experimental group, and platelet-derived wound healing factor (PDWHF) experimental group. General healing conditions, wound closing index, healing rates and histological changes of the patient’s ulcer wound were observed during 1-8 weeks after treatment. RESULTS The wound closing index and healing rate of ulcers were significantly increased in the EGF and PDWHF experimental groups compared with the control group, while the angiogenesis, fibroblast hyperplasia, and collagen deposit were more obvious in EGF and PDWHF experimental groups than that of control group. The promoting effects on wound healing in PDWHF experimental group were better than in EGF group. CONCLUSION It suggests that local application of certain growth factor alone or various growth factors together is an effective method to improve the condition of impaired healing of diabetic ulcers.
【Abstract】ObjectiveTo investigate the effects of cholecystokinin （CCK） on diabetes mellitus with cholecystolithiasis. MethodsRelevant literatures of recent years were reviewed. ResultsCCK exists widely in human body．On the one hand, CCK enhances cholecystolithiasis by causing diabetes. On the other hand, its pathological changes can also lead to cholecystolithiasis. Besides, it is possibility that the CCKrelated gene abnormality is the common cause of diabetes and cholecystolithiasis. ConclusionCCK plays an important role in diabetes mellitus complicated with cholecystolithiasis. However, there is much yet to be known about CCK．
Objective To investigate the amounts of endothelial progenitor cells (EPCs) in peripheral blood of patients with proliferative diabetic retinopathy (PDR). Methods Forty patients with PDR (PDR group), thirty patients with type 2 diabetes mellitus (DM) without DR (DM group), and twenty age-matched normal subjects (control group) were enrolled in this study. Blood samples were treated by repeated centrifugation and stained with monoclonal antibodies. At least 2times;105 cells were analyzed by flow cytometry. EPCs were identified by CD34 and CD133 antibody. The correlation between EPCs numbers and DR duration, glycosylated hemoglobin, serum lipids was analyzed. Results The number of EPCs in PDR, DM and control group were (49plusmn;12)、(35plusmn;11)、(90plusmn;25) cells/ml respectively, the difference was statistically significant (F=56.260, P=0.000). There was a positive correlation between EPCs numbers and DR duration (r=0.564, P＜0.05). However there was no correlation between EPCs numbers and glycosylated hemoglobin (r=-0.170, P＞0.05) or triglyceride levels (r=0.261, Pgt;0.05). Conclusions The number of EPCs in peripheral blood of PDR patients was decreased. EPCs might play an important role in the pathogenesis of PDR.
Objective To observe the morphological changes of dendrite and soma in retinal ganglion cells (RGCs) which subsisted in early diabetic rats. Methods The RGCs of 3-months-course diabetic rats and coeval normal rats were marked by gene gun techniques. To collect RGCs photographs by Leica microscope with Z axis and CCD camera；to observe the changes of diameter, variance of structural features in dendritic field and somata after classification which according to the size and morphology. Thy-1 antibody marks on the retinal RGCs, taking a photograph under fluorescent microscope, counting the changes of retinal RGCs density in early diabetic rat. Results In three-month diabetic rats,the density of retinal RGCs was decreased obviously. Morphological changes of RGCs in the dendritic fields were observed with gene gun technique. There was no severe variation in all kinds of the bole of cell dendrite, in which some only showed crispation partially and sparseness also twisting in the dendritic ramus. The mean diameter of dendritic field and soma in class A of diabetic rats was (401plusmn;86) mu;m, the mean diameter of dendritic field in control group was (315plusmn;72) mu;m,compared with each other, there is statistically significant differences (t=21.249，Plt;0.001); the mean diameter of soma in class A of diabetic rats was (24plusmn;6) mu;m, the mean diameter of soma in control group was (22plusmn;5) mu;m, compared with each other, there is no statistically significant differences (t=0.927，Pgt;0.05); the mean diameter of dendritic field and soma in class B of diabetic rats were (170plusmn;36)、(14plusmn;2) mu;m respectively, in control group were (165plusmn;36)、(16plusmn;2) mu;m, the mean diameter of dendritic field and soma in class C of diabetic group were(265plusmn;78)、(17plusmn;5) mu;m respectively, in control group were (251plusmn;57)、(17plusmn;4) mu;m , compared with each other, there are on statistically significant differences(t=1.357，0.798，0.835，1.104，Pgt;0.05). Conclusions In short-term diabetes, the survived RGCs show good plasticity in adult diabetic rats, especially in class A. The changes of dendrites were more sensitive than the soma, which could be the leading index of the morphologic changes of RGCs in the early stage. The good plasticity showed by the RGCs and the time window from changing in dendrite to cell death provide us many evidences not only for the research but also for the nerve protection in clinic. (Chin J Ocul Fundus Dis,2008,24:249-254)
Objective To explore the related risk factors for diabetic retinopathy (DR) in type 2 diabetes. Methods The clinical data of 412 type 2 diabetes patients, diagnosed between 2003 and 2010, were analyzed retrospectively. The diagnosis of DR and proliferative diabetic retinopathy (PDR) was confirmed by ophthalmoloscopy and fundus fluorescein angiography. Glycated hemoglobin A1c, glucose, insulin, and Cpeptide of fasting plasma, and 1, 2 and 3 hours postprandial plasma were measured. According to the abovementioned data, get the fluctuation of glucose, insulin and C-peptide of 1, 2 and 3 hour postprandial plasma. Results The morbidity of DR and PDR increased following the longer disease duration. Age, diabetic duration，body mass index (BMI), hypertension grade, HbA1C, fasting plasma insulin and C-peptide, 2 and 3 hours postprandial plasma glucose, 1 and 2 hours postprandial plasma insulin, 1, 2 and 3 hour postprandial plasma C-peptide, 1, 2 and 3 hours postprandial plasma glucose, insulin and C-peptide fluctuation are different statistically among non-DR group, non-PDR group and PDR group (P＜0.05). 3 hours postprandial plasma glucose and fasting plasma insulin were risk factors of DR (P＜0.05). Conclusions Postprandial plasma glucose and fasting plasma insulin were risk factors of DR. Nevertheless, postprandial insulin, fasting and postprandial C-peptide, postprandial plasma glucose, insulin and C-peptide fluctuation were useful for DR diagnosis.