Diabetic kidney disease (DKD) is a major complication of diabetes mellitus. One third of patients with advanced diabetes mellitus can develop to uremia, which seriously endangers people’s health. In recent years, with the improvement of people’s living standards and the increasing incidence of diabetes, it has become the main cause of end stage renal disease in China. Over the past two decades, the understanding of diagnosis and treatment of DKD has been improved, such as putting forward the new concept of normoalbuminuric DKD and developing a variety of new anti-diabetic drugs. However, at present, the basic strategies of DKD treatment are still lifestyle modification, glucose control, blood pressure control and lipid control.
Purpose To study changes of cell cycle of vascular endothelial cell in non-proliferative diabetic retinopathy. Methods Alloxan induced Wistar-rats were employed and immunohistochemistry,Western blotting methods were used. Results The vascular endothelial cells of retinas of 8～20 weeks diabetic rats were observe to be cyclinD1,cyclinD3,cyclinB1,p21 and p27 positive stained with light and electronmicroscopies.CyclinE immuno-stained vascular endothelial cells was observed occasionally.Meanwhile,the evidences of morphologic changes of the vascular en dothelial cells were proved:less plasma,thinner cell,more bubble organelles than those of controls.But,the ultra-structures of pericytes and other type of retinal cells did not change and they also immunostain negative.Komas blue and Western blotting methods also proved that the vascular endothelial cells of retina of 20th week diabetic rats expressed cyclinD1,cyclinB1,p21 and p27 protein. Conclusion Glucose induced retinal vascular endothelial cells of 8～20th weeks diabetic rats enter cell cycle and were arrested at G1/S restriction point.This study also suggested that retinal vascular endothelial cells may possess the ability to resist glucose damage and mechanism of selfstability during very early stage of diabetes. (Chin J Ocul Fundus Dis,2000,16:173-176)
Objective To observe the effect of diabetic retinopathy on endothelial progenitor cells (EPCs) from peripheral blood. Methods Sixty male Wistar rats were divided into control group and diabetes group. The rats in diabetes group were induced with streptozotocin (STZ) injection for diabetic retinopathy model. Flow cytometry was used to identify and count the number of EPCs from peripheral blood at 1 week, 1, 3 and 6 months after injection. All eyeballs were examined by hematoxylin and eosin (HE) staining, periodic acidSchiff's (PAS) staining of trypsin-digested retinal vessels flat preparation and transmission electron microscope. EPCs count, and the relationship between DR morphological changes and EPCs count were compared and analyzed. Results The quantity of EPCs from peripheral blood at 1 week, 1, 3 and 6 months after STZ injection were 25plusmn;7, 28plusmn;8, 39plusmn;7, 43plusmn;7 cells per 200 000 monocytes respectively, which decreased compared with the control group 45plusmn;4 cells per 200 000 monocytes (F=8.933，Plt;0.01). The quantity of EPCs was gradually increased at 1 week, 1, 3 and 6 months after STZ injection, accompanied with responsive pathological changes of retinal structure and vessels. The thickness of retina at 1 week and 1 month after injection were reduced slightly. The number of retinal ganglion cells reduced, with the time passing by. Endothelial cells were edema, mitochondrial was swollen, capillary basement membrane was thicken, lumen was significant stenosis, lumen occlusion and retinal artery aneurysm were observed at 6 months after STZ injection. Conclusion The number of EPCs increases gradually throughout the development of DR.
Objective To analyze the causes of missed diagnosis of sleep apnea hypopnea syndrome ( SAHS) . Methods 42 missed diagnosed cases with SAHS from May 2009 to May 2011 were retrospectively analyzed and related literatures were reviewed. Results The SAHS patients often visited the doctors for complications of SAHS such as hypertension, diabetes mellitus, metabolic syndrome, etc. Clinical misdiagnosis rate was very high. Lack of specific symptoms during the day, complicated morbidities, and insufficient knowledge of SAHS led to the high misdiagnosis rate and the poor treatment effect of patients with SAHS. Conclusion Strengthening the educational propaganda of SAHS, detail medical history collection, and polysomnography monitoring ( PSG) as early as possible can help diagnose SAHS more accurately and reduce missed diagnosis.
Objective To evaluate and select essential medicine for diabetes mellitus based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Six guidelines were included, three of which were evidence-based and published from 2006 to 2011. (2) Five recommended medicines were included according to recommendations and evidence of WHOEML (2011), NEML (2009), CNF (2010) and other guidelines. They were metformin, glibenclamide, glipizide, rosiglitazone and pioglitazone. Domestic evidence of the first three drugs was evaluated. (3) The first three have been marketed with the specifications and dosage forms corresponding to guidelines in China. The FBG cost-effectiveness ratios of metformin with different dosage forms as immediate release compressed tablet, enteric-coated tablet and sustained release capsule were 3.37, 3.76 and 3.50 respectively. 2-hour BG cost-effectiveness ratios of metformin were 3.74, 4.00 and 3.71 respectively. The cost-effectiveness ratio of glibenclamide and glimepiride were 11.23 and 13.81 respectively. Conclusion We offer a recommendation for: (1) Metformin (immediate release tablet/capsule for oral use, 0.25 g), contraindicated in patients with renal insufficiency. (2) Glibenclamide (tablet, 2.5 mg; capsule, 1.75 mg) and glipizide (tablet, 2.5 or 5mg; dispersible tablet, 5 mg), contraindicated in children, women during pregnancy or lactation, patients in the perioperative period of major operation, patients after total pancreatectomy, and patients allergic or adversely reacted to sulfa drug. (3) Evidence-based and standardized primary healthcare guidelines as well as clinical and pharmacoeconomic studies on diabetes mellitus (large-scale, multi-centre, randomized and double-blinded) are needed to produce high-quality local evidence.
ObjectiveTo investigate the clinical symptom and risk factors of diabetic seizures. MethodsThe clinical data of 44 patients with diabetes related seizures were analyzed with the clinical classification, blood glucose, Na+, Plasma Osmotic Pressure, HbA1c, EEG, brain MR, and the antiepileptic drugs. Results① Diabetic hyperglycemia (DH) related seizures: among the 28 patients, 17 cases were male patients, 11 cases were female patients. The mean age was 51.3 years old. Simple partial seizure without secondary generalized seizures (12/28, 42.8%) was the most common, 8 patients (8/28, 28.6%) showed complex partial seizure, 8 patients (8/28, 28.6%) showed no obvious focal origin generalized tonic-closure seizures. Patients with poor glycemic control (HbA1c > 9%) had significantly higher risk of generalized seizures (46.7% vs. 7.7 %, P < 0.05) (P < 0.05). ② Diabetic ketoa-cidosis or hypertonic state associated seizures: among the 7 patients, 6 cases were male patients, 1case was female patients. The mean age was 45.7 years old, 2 patients (2/7, 28.6%) had generalized tonic-clonic seizure, 2 patients (2/7, 28.6%) showed status epilepticus, 2 patients (2/7, 28.6%) showed local motor seizure, 1 patient (1/7, 14.2%) showed Jackson seizure. ③ Diabetic hypoglycemia related seizures: among the 9 patients, 7 cases were male patients, 2 cases were female patients. The mean age was 45.3 years old.5 patients showed generalized tonic-clonic seizure (5/9, 55.6%), 3 patients had complex partial seizure (3/9, 33.3%), 1 patients had generalized tonic-closure seizures (1/9, 11.1%). ConclusionSimple partial seizure is the most common in patients with diabetic hyperglycemia related seizures; so as to diabetic hypoglycemia and keto-acidosis, generalized seizures are relatively common. HbA1c can be an important risk factor of seizures for patients with hyperglycemia.
Objective To determine the clinical efficacy of probucol in patients with diabetic macular edema (DME) and elevated serum lipids after focal/grid laser photocoagulation. Methods A prospective randomized controlled study included 48 type 2 diabetic patients with DME and dyslipidemia which were randomly divided into three groups. For patients with bilateral disease only the more severe eye was included. All patients were subjected to strict metabolic and blood pressure control during enrollment. All cases received macular laser photocoagulation. Besides, sixteen patients in group A were treated with probucol, 16 members in group B with atorvastatin and 16 members in group C were not treated with any lipid-lowering therapy for about three months. The outcome measurements were status of macular edema and hard exudates, visual acuity, foveal thickness, serum lipids and urine 8-hydroxydeoxyguanosine (8-OHdG) during the three months. Results The study included 20 men and 28 women with noninsulin dependent diabetes mellitus who could achieve good metabolic and blood pressure control within three months of inclusion in the study. Thirteen of 16 patients in group A, twelve of 16 patients in group B and five of 16 patients in group C showed reduction in hard exudates. Regression of macular edema was seen in twelve patients in group A, 11 in group B and eight in group C (χ2=2.368,P＞0.05). The difference of foveal thickness in group A, B and C was statistically significant (t=4.929, 4.669; P=0.000). Nine patients in group A, eight in group B and six in group C showed improving of visual acuity (χ2=1.169,P＞0.05). Three months after treatment, triglycerides (TG) (t=7.954, 6.832; P＜0.05), total cholesterol (TC) (t=6.643, 5.368; P＜0.05) and low-density lipoprotein cholesterol (LDLC) (t=3.279, 3.835; P＜0.05) decreased in group A and group B but not in group C, and high-density lipoprotein cholesterol showed no significant difference in the three groups. 8-OHdG decreased gradually during the first and third month in group A and group B but not in group C. In the first month post treatment, 8-OHdG showed no difference between group A and group B. In the third month, the 8-OHdG was lower in group A than group B, and the difference was statistically significant (t=2.947,P＜0.05). ConclusionsIn type 2 diabetes patients with DME and dyslipidemia, oral probucol can reduce the severity of hard exudates and macular edema, improve the visual acuity, and inhibit the levels of TG, TC, LDLC and 5-OHdG. The effect of probucol was similar to atorvastatin. Probucol could be an adjunct treatment of those patients.
ObjectiveTo systematically review the efficacy of amlodipine versus valsartan in the treatment of diabetes mellitus combined with hypertension and renal impairment. MethodsAll relevant randomized controlled trials (RCTs) were retrieved in WanFang Data, CNKI, VIP, CBM, The Cochrane Library (Issue 10, 2013), PubMed, EMbase and Ovid up to October 2013. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2. ResultsNine RCTs were finally included involving 794 cases. The results of meta-analysis showed that amlodipine was better than valsartan in improving 24-hour proteinuria (basic level < 1 000 mg:WMD=-10.24, 95%CI-18.52 to-1.95, P=0.02; basic level > 1 000 mg:WMD=-575.69, 95%CI-781.02 to-370.36, P < 0.000 01). However, there was no significant difference between two groups in lowing urine albumin excretion rates (UAER), serum creatinine (Scr), systolic blood pressure (SBP), diastolic blood pressure (DBP), and incidences of adverse events (UAER:WMD=-11.29, 95%CI-27.93 to 5.36, P=0.18; Scr:WMD=1.05, 95%CI-3.89 to 5.99, P=0.68; SBP:WMD=0.52, 95%CI-0.83 to 1.87, P=0.45; DBP:WMD=-0.40, 95%CI-1.41 to 0.62, P=0.44; ADR:WMD=1.00, 95%CI 0.3 to 3.34, P=1.00). ConclusionCurrent evidence shows that, compared with valsartan, amlodipine has the same efficacy in treatment of diabetes mellitus combined with hypertension and renal impairment, and it is even better in improving 24-hour proteinuria.
Objective To investigate the relationship between expression of retinal intercellular adhesion molecule-1 (ICAM-1) and blood-retinal barrier (BRB) rupture and therapeutic effect of intravitreous injection with triamcinolone acetonide (TA) on blood-retinal barrier rupture in rats with diabetes mellitus (DM). Methods Diabetic model of Wistar rats was induced and were divided into normal control group, DM-4-month group and DM-6-month group. Each group was subdivided into immunohistochemcial staining and BRB measurement groups. BRB measurement group was further divided into non-TA treatment group, 1-week-TA treatment group, and 2-week-TA treatment group. The rats were intravitreously injected with 5 mu;l TA. The digested retinal preparation was stained by immunohistochemcial method to observe the expression of retinal ICAM-1 and morphological changes. The mean optic density (A) value of endothelial cells was measured by image-analyzing software to quantify the expression of ICAM-1. BRB changes were measured by content test of retinal Evans blue (EB). Results In the immunohistochemcial staining groups, there was no significant positive expression of ICAM-1 in retinal capillary in control group. Compared with the control, there was significant positive expression of ICAM-1 in DM-4-month group (P＜0.001) with some morphological changes such as irregular width of capillary caliber, and there was enhanced positive expression of ICAM-1 in DM-6-month group (P＜0.001) with aggravated morphological changes and even acellular capillary. In the BRB measurement groups, there was no significant difference of EB content(P＞0.05) among control groups. The EB content in two DM groups significantly increased compared with that in the controls (Plt;0.001), and higher in DM-6-month group than that in DM-4-month group (Plt;0.01). In TA treatment groups, the EB content in all the DM groups significantly decreased (Plt;0.001) but with no significant difference among the groups(P＞0.05). EB content in DM-4-month group after 2-week treatment almost reached to normal value (P＞0.05) while was higher in the rest of TA treatment groups than that in the control group (Plt;0.05). Rectilinear correlation between A value of endothelial cells and the retinal EB content(r=－0.959)was found. Conclusion There is a positive relation between the expression of ICAM-1 and BRB rupture in retina of DM rats, and intravitreous injection with TA can effectively alleviate BRB rupture. (Chin J Ocul Fundus Dis, 2006, 22: 24-27)
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)