The performance of a diabetic retinopathy risk score for screening for diabetic retinopathy in Chinese overweight/obese patients with type 2 diabetes mellitus.

INTRODUCTION: Diabetic retinopathy (DR) is a common chronic microvascular diabetic complication. The presence of DR may indicate microcirculatory dysfunction in other organ systems besides visual morbidity. The objective of this study was to develop a simple diabetic retinopathy risk score to identify DR in Chinese overweight/obese patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: A multicentre hospital-based cross-sectional study was carried out in Guangdong Province between August 2011 and March 2012. The evaluated 2699 patients included 1263 males and 1436 females, with an average age of 59.4 ± 13.0 years. RESULTS: The diabetic retinopathy risk score was conducted by age, duration of DM, history of antihypertensive drug treatment, and waist circumference. The area under the receiver operating characteristics curve for DR was 0.700 (95% CI 0.671-0.729). Comparing Youden's index of different values, the optimal cut-off point was 20 to predict DR. The odds ratio for one unit increase in the diabetic retinopathy risk score associated with the risk of DR was 1.104 (95% CI 1.089-1.120). CONCLUSIONS: Our data suggest that the diabetic retinopathy risk score could be a reliable primary screening tool for the presence of DR in Chinese overweight/obese patients with T2DM.

Folic acid attenuates cognitive dysfunction in streptozotocin-induced diabetic rats.

Diabetic cognitive dysfunction is common in patients with diabetes but its pathogenesis is not clear. The aim of the present study is to investigate the role of 5', 10' methylene tetrahydrofolate reductase (MTHFR) in the development of diabetic cognitive impairment and test whether folic acid (FA) supplementation prevents cognitive dysfunction in diabetic rats. In the current study, three months after streptozotocin-induced diabetes onset, rats showed cognitive dysfunction including the prolonged escape latency, the decreased time spent in the target quadrant and the declined number of crossing the platform in Morris water maze test. Diabetic rats also presented elevated plasma homocysteine level and downregulation of MTHFR in hippocampus revealed by Western blotting. The diabetic cognitive dysfunction was attenuated by 30-day dietary FA treatment with a significantly decreased homocysteine level. In conclusion, these results suggest that MTHFR plays a crucial role in diabetic cognitive dysfunction and folate fortification might become a potent therapeutic strategy against diabetic cognitive impairment.

[Prevalence and risk factors for dyslipidemia in diabetics with overweight or obesity].

OBJECTIVE: To explore the prevalence and risk factors for dyslipidemia in diabetics with overweight or obesity. METHODS: Diabetics with overweight or obesity were recruited from 62 tertiary and secondary hospitals in Guangdong Province between August 2011 and March 2012. Dyslipidemia was diagnosed as total cholesterol (TC) ≥ 5.7 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density-lipoprotein cholesterol (LDL-C) ≥ 3.6 mmol/L or high-density-lipoprotein cholesterol (HDL-C) < 1.29 mmol/L in females or HDL-C < 1.03 mmol/L in males. Binary Logistic regression was used to assess the associations between dyslipidemia and associated risk factors. RESULTS: Dyslipidemia was detected in 3160/3593 (87.9%) diabetics with overweight or obesity. And the prevalence of hypertriglyceridemia, low blood HDL-C, hypercholesterolemia and high blood LDL-C was 52.5% (1888/3593) , 54.1% (1945/3593), 33.1% (1188/3593) and 27.4% (985/3593) respectively. Among those with dyslipidemia, patients with simple and mixed dyslipidemia accounted for 34.1% and 53.9% respectively. In binary Logistic regression analysis, the presence of dyslipidemia were associated with female gender (OR = 1.593, 95%CI 1.233-2.057), hemoglobinA1c(HbA1c) (OR = 1.120, 95%CI 1.054-1.191), body mass index (OR = 1.084, 95%CI 1.022-1.150), hypertension (OR = 1.331, 95%CI 1.033-1.714), history of diabetes (OR = 1.586, 95%CI 1.186-2.120) and hyperuricacidemia (OR = 2.270, 95%CI 1.642-3.138). CONCLUSIONS: The prevalence of dyslipidemia is quite high in diabetics with overweight or obesity. The controls of blood pressure, serum uric acid level, blood glucose and body weight may reduce the prevalence of dyslipidemia, prevent and delay the development of cardiovascular complications and reduce the mortality of diabetics with overweight or obesity.

Prevalence and determinants of hyperuricemia in type 2 diabetes mellitus patients with central obesity in Guangdong Province in China.

This study investigated the prevalence and determinants of hyperuricemia in Chinese type 2 diabetes mellitus (T2DM) patients with central obesity. A multicentric hospital-based cross-sectional study was carried out in Guangdong Province between August 2011 and March 2012. At each hospital, Chinese T2DM patients with central obesity who were aged over 20 years, whose serum uric acid levels were measured, and who had lived in Guangdong Province for >=1 year, were recruited. Hyperuricemia was defined as serum uric acid >420 µmol/L in men and >360 µmol/L in women. Binary logistic regression was used to assess associated risk factors for hyperu-ricemia. A total of 2,917 T2DM patients with central obesity took part. The overall prevalence of hyperuricemia was 32.6% (36.1% for women, 28.4% for men). Binary logistic regression analyses demonstrated that women (OR: 1.576; 95% confidence interval (CI): 1.231, 2.018), high BMI (OR: 1.228; 95% CI: 1.094, 1.379), waist cir-cumference (OR: 1.135; 95% CI: 1.009, 1.276), hypertension (OR: 1.603; 95% CI: 1.263, 2.035), high total cho-lesterol (OR: 1.133; 95% CI: 1.002, 1.281), triglycerides (OR: 1.134; 95% CI: 1.069, 1.203), low HDL-cholesterol (OR: 0.820; 95% CI: 0.677, 0.995) and low estimated glomerular filtration rate (OR: 0.840; 95% CI: 0.815, 0.866) were risk factors associated with hyperuricemia. Hyperuricemia is prevalent in Chinese T2DM patients with central obesity and is significantly positively associated with women, cardiovascular risk factors such as obesity, hypertension and dyslipidemia, and low eGFR.

[A cross-sectional survey of blood pressure control in overweight or obese type 2 diabetic patients in Guangdong province].

OBJECTIVE: To investigate the current situation and influential factors of blood pressure (BP) control in type 2 diabetic patients with overweight or obesity in Guangdong province. METHODS: From August 2011 to March 2012, type 2 diabetic patients with overweight or obesity were recruited from 60 hospitals in 20 cities of Guangdong province, and received standard questionnaires. The conditions of demographic data, clinical examinations, the most recent laboratory assessment, history of disease and drug therapy were recorded. RESULTS: A total of 4029 patients were collected with age of (58.9 ± 12.9) years, and body mass index (BMI) of (27.28 ± 2.76) kg/m². Among the participants, controlled BP was achieved in 23.8% patients. Multiple logistic regression analysis showed that older age, obesity, previous history of hypertension and inadequate glycemic control were the independent factors related to unsatisfactory blood pressure control rate. Among the patients with hypertension, 53.5% took 1 kind of antihypertensive drug, 32.5% took two, and 11.3% took three or more. CONCLUSIONS: Type 2 diabetic patients with overweight or obesity in Guangdong province have poor BP control. Thus, active lifestyle interventions and drug therapy as a comprehensive management way should be taken for the population so as to reduce their cardiovascular events.

Prevalence and risk factors for diabetic retinopathy in a high-risk Chinese population.

BACKGROUND: Lifestyle plays an important role in the development of diabetic retinopathy. The lifestyle in Guangzhou is different from other cities in China as the Cantonese prefer eating rice porridge, but not spicy foods. The objectives of this study were to investigate the prevalence and determinants of diabetic retinopathy in a high-risk population of Guangzhou. METHODS: Subjects (619 totals) aged over 45 years old, without known diabetes were recruited from five randomly selected Guangzhou communities in 2009-2010. All participants were invited to complete the Finnish Diabetes Risk Score (FINDRISC) questionnaire. Subjects with FINDRISC score ≥ 9 were included in the study, and underwent an investigation of demographic data, a standardized physical examination, ocular fundus examination, and laboratory analyses. The minimum criterion for diagnosis of diabetic retinopathy was the presence of at least one microaneurysm. RESULTS: Of 619 subjects, 208 eligible subjects (122 women) with FINDRISC score ≥ 9 were included in the study. The mean age was 69.2 ± 8.5 years. Diabetic retinopathy was detected in 31 subjects, and the prevalence of diabetic retinopathy in subjects with high risk for diabetes was 14.9%. In binary logistic regression analysis, risk factors associated with diabetic retinopathy were history of impaired glucose regulation [odds ratio (OR), 7.194; 95% confidence interval (CI): 1.083, 47.810], higher hemoglobin A1c (HbA1c; OR, 2.912; 95% CI: 1.009, 8.402), higher two-hour postprandial plasma glucose level (OR, 1.014; 95% CI: 1.003, 1.025), and presence of microalbuminuria (OR, 5.387; 95% CI: 1.255, 23.129). CONCLUSIONS: Diabetic retinopathy was prevalent in a high-risk Chinese population from Guangzhou. Histories of impaired glucose regulation and microalbuminuria were strong risk factors for diabetic retinopathy.

[A cross-sectional survey on current status of type 2 diabetes mellitus with overweight or obesity in Guangdong province].

OBJECTIVE: To explore the glycemic control status and related risk factors of overweight or obesity patients with type 2 diabetes mellitus (T2DM) in Guangdong province. METHODS: The medical records of overweight or obesity patients with T2DM from 60 tertiary and secondary hospitals in Guangdong Province were collected by questionnaire and physical examination. And the clinical data were analyzed to explore the influencing factors of glycemic control. The HbA1c level was used to assess glycemic control. HbA1c < 7.0% indicated that glycemic control was up to standard. RESULTS: From August 2011 to March 2012, 5241 T2DM patients were recruited. The scope of current analysis was restricted to 4768 subjects with true data and deficiency no more than 5%. There were 2252 males and 2516 females. The age range was from 16 to 90 years, a median age 59.0 (50.0 - 69.0) years, onset age of diabetes 52.0 (44.0 - 60.0) years; a range of disease duration from 1 day to 42 years and a median of 5.0 (2.0 - 11.0) years. The median body mass index was 26.33(24.88 - 28.34) kg/m(2) and median waist circumference 93.0 (88.0 - 100.0) cm. Median HbA1c was 8.1% (6.9% - 10.1%) and only 26.2% patients reached the target level of HbA1c < 7.0%. Influencing factors of poor glycemic control were central obesity, high levels of resting heart rate, concurrent fatty liver and high intensity of treatment. And influencing factors of good glycemic control were regular exercises, smoking cessation, regular glycemic monitoring and good control of total cholesterol/triglyceride. CONCLUSION: A majority of Guangdong type 2 diabetics fail to achieve target values for glycemic control. There is an urgent need for comprehensive management for improving glycemic control.

[A cross-sectional survey on prevalence and risk factors for abnormal plasma liver enzymes in overweight or obese patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the prevalence and risk factors for abnormal plasma liver enzymes in patients with type 2 diabetes mellitus. METHODS: Overweight or obese patients with type 2 diabetes were recruited from 60 tertiary and secondary hospitals in Guangdong Province between August 2011 and March 2012. The abnormal plasma liver enzymes was diagnosed as alanine aminotransferase >40 U/L and/or aspartate aminotransferase >40 U/L. Binary Logistic regression was used to assess the associations between abnormal plasma liver enzymes and associated risk factors. RESULTS: The abnormal plasma liver enzymes were detected in 709/3543 diabetics with overweight or obesity. And the prevalence of abnormal plasma liver enzymes was 20.0%. According to binary Logistic regression analysis, the presence of abnormal plasma liver enzymes was associated with male gender (OR = 1.603, 95%CI: 1.247-2.061), higher HbA1c(OR = 1.049, 95%CI: 1.005-1.096), higher body mass index (OR = 1.058, 95%CI: 1.014-1.103), higher waist circumference (OR = 1.019, 95%CI: 1.006-1.032), higher triglyceride level (OR = 1.053, 95%CI: 1.008-1.100), adiposis hepatica (OR = 1.543; 95%CI: 1.244-1.914), regular exercises (OR = 0.591, 95%CI: 0.472-0.740) and diet control (OR = 0.794, 95%CI: 0.635-0.993). CONCLUSIONS: There is a high prevalence of abnormal plasma liver enzymes in overweight/obese with diabetics. And decreasing the levels of HbA1c, body mass index, waist circumference and triglycerides, regular exercises and diet control may decrease its prevalence.

Glucagon-like peptide-1 (GLP-1) protects vascular endothelial cells against advanced glycation end products (AGEs)-induced apoptosis.

BACKGROUND: The peptide glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal L cells in response to food intake. GLP-1 has been proposed as the basis of emerging therapy for patients with type 2 diabetes. However, the effects of GLP-1 on vascular injury in diabetes have not been identified. Advanced glycation end products (AGEs) induce endothelial cell apoptosis and have been implicated in the process of vascular complications from diabetes. MATERIAL/METHODS: The aim of this work was to investigate whether and how GLP-1 protects endothelial cells from apoptosis induced by AGEs. Human umbilical vein endothelial cells (HUVECs) were treated with AGEs (200 µg/mL) for 48 h in the presence or absence of GLP-1. Cell morphology, viability, apoptosis, ratio of Bcl-2 protein to Bax protein, cytochrome c release, and activity of caspase-9 and -3 were determined. RESULTS: Treatment of cells with AGEs led to cell morphology changes and decreased cell viability, resulting in apoptosis. GLP-1 alone increased cell viability in a concentration-dependent manner. GLP-1 partially inhibited AGEs-induced apoptosis in HUVECs. GLP-1 increased Bcl-2/Bax ratio, reduced cytochrome c levels in the cytoplasm, and reduced the activity of caspase-9 and -3 in AGEs-treated HUVECs. CONCLUSIONS: AGEs induces apoptosis via the mitochondrion-cytochrome c-caspase protease pathway, and GLP-1 protects endothelial cells by interfering with this mechanism. GLP-1 may represent an anti-apoptotic agent in the treatment of vascular complications arising from diabetes.

[Clinical significance of glycosylated serum protein in patients with diabetic nephropathy].

OBJECTIVE: To explore the relations between fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c) and glycosylated serum protein (GSP). METHODS: FBG, HbA1c and GSP were measured in 303 patients with diabetic nephropathy and in 167 non-diabetic patients with comparable baseline data, and the correlations between FBG, HbA1c and GSP were analyzed. RESULTS: GSP levels were significantly higher in patients with diabetic nephropathy than in the non-diabetic patients (P<0.01). In patients with diabetic nephropathy, GSP levels were found to positively correlate to FBG (r=0.606) and HbA1c (r=0.733). CONCLUSION: Patients with diabetic nephropathy show strong correlations between FBG, HbA1c and GSP. GSP detection is convenient, stable, and practical in evaluating the average FBG over a short term, which reduces the interference by FBG fluctuations in conventional blood glucose monitoring.

[Relations between serum adipocyte fatty acid-binding protein and type 2 diabetes in a community population].

OBJECTIVE: To study the relationship between the serum levels of adipocyte fatty acid-binding protein (A-FABP) level and type 2 diabetes mellitus in a community population. METHODS: A total of 255 residents (aged 45-85 years) were randomly selected from 4 communities in Guangzhou to examine the fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), blood pressure (BP), triglyceride (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). The insulin resistance index (HOMA-IR) was calculated and enzyme-linked immunosorbent assay (ELISA) was used to determine serum A-FABP and fasting insulin (FINs) levels. The cases were divided into 3 groups according to blood glucose level, namely the normal group (group A, n=90), impaired glucose tolerance group (group B, n=85), and diabetic group (group C, n=80), and the A-FABP levels were compared between them. RESULTS: Compared with group A, the subjects in groups B and C showed significantly increased FPG, 2hPGh, HbA1C, HOMA-IR, systolic blood pressure (SBP), and waist circumference (P=0.000) as well as FINs, WHR, diastolic blood pressure (DBP) , TG, and HDL-C (P=0.038, 0.047, 0.01, and 0.046, respectively). Compared with group B, group C showed significantly higher FPG, 2hPG, HbA1c, TG, and SBP (P=0.00), with also higher levels of FINs, BMI, WC, DBP, and HDL-C (P=0.012, 0.006, 0.03, 0.019, and 0.029, respectively). A-FABP increased significantly in the order of group A, B, and C (P=0.00), and this result was not affected by the differences in age between the 3 groups (P>0.05). A-FABP level was positively correlated to FPB, 2hPG, FINS, WHR, BMI, WC, SBP, and HOMA-IR, but inversely to TG and HDL-C (P=0.00). CONCLUSION: Elevated serum A-FABP is closely related to glucose metabolism disorder, and A-FABP may serve as a useful marker for the occurrence and development of type 2 diabetes in the community population.

[Cross-sectional study of current situation of glycemic control with type 1 diabetes in Guangdong Province].

OBJECTIVE: To investigate the glycemic control and the related factors of type 1 diabetic patients in Guangdong Province. METHODS: Medical records and blood samples of type 1 diabetic patients were collected in 89 tertiary and secondary hospitals from all of the 21 cities in Guangdong Province. The clinical data were analyzed to explore the correlates of glycemic control. HbA1c levels, measured in Guangdong Diabetes Center, were used to assess glycemic control. RESULTS: 851 patients were enrolled from August 6, 2010 to May 25, 2011. There were 408 males and 443 females. The median (interquartile range) age was 29.6 years (20.3 - 41.3 years). The onset age of diabetes was 25.3 years (15.7 - 35.5 years). The disease duration was 3.3 years (1.0 - 7.3 years). The BMI was 19.9 kg/m(2) (17.9 - 21.8 kg/m(2)). HbA1c levels were 8.6% (6.9% - 11.0%) and only 234 (27.50%) patients reached the age-specific target levels. Correlates with poorer glycemic control were 13 - 19 years old (vs 7 - 12 and ≥ 20 years old), lower household income, not on dietary intervention, never accepting diabetic education and shorter diabetic duration. CONCLUSION: The majority of Guangdong type 1 diabetic patients did not achieve target values for glycemic control, indicating an urgent need for comprehensive management to improve glycemic control.

[Analysis of glucose levels and the risk for coronary heart disease in elderly patients in Guangzhou Haizhu district].

OBJECTIVE: To investigate the prevalence of diabetes and prediabetes and their association with the risk for coronary heart disease (CHD) in elderly residents in Haizhu District of Guangzhou. METHODS: Stratified random sampling was employed to select a total of 1800 resident aged 50 years or older in the region. The fasting fingertip blood glucose>5.6 mmol/L was used as the criterion for the initial screening. The data were collected from qualified subjects via scheduled questionnaire surveys, blood collection and testing, and physical examination. The subjects were divided into the 3 groups, namely normal blood glucose, prediabetes, and diabetes groups. The combination rates of the relevant risk factors (hypertension, hyperlipemia, obesity, and central obesity) were compared among the groups by Framingham Heart Study to predict the occurrence of CHD in 10 years. RESULTS: The incidence was 11.00% for prediabetes and 7.56% for diabetes in the elderly residents in Haizhu District. The occurrence of hypertension, hyperlipemia, obesity, and central obesity was significant higher in the prediabetes and diabetes group than in the normal blood glucose group, and showed no significant differences between the former two groups. The 10-year risks for CHD were markedly higher in both the prediabetes and diabetes groups than in the normal blood glucose group, but similar between the former two groups. CONCLUSION: Elderly patients with prediabetes and diabetes have significantly increased 10-year risk for CHD in comparison with those with normal blood glucose, but the risk is similar between the former two groups, indicating a close association of IGR (impaired fasting glucose+ impaired fasting glucose) with CHD. Early control of blood glucose is essential to the prevention and control of CHD.

[Preventive and therapeutic effect of strontium ranelate on osteoporosis in rats subjected to simulated weightlessness].

OBJECTIVE: To study the effects of strontium ranelate on osteoporosis induced by simulated weightlessness in male rats. METHODS: Twenty-seven male SD rats were randomly divided into 3 groups, namely the normal control group (group A) and two groups of weightlessness simulated by tail suspension (groups B and C). The rats in group C were treated with strontium ranelate, and those in the other two groups were given the same dose of normal saline for 28 consecutive days. RESULTS: The rats in group B showed significantly lower levels of alkaline phosphatase (ALP), bone mineral density (BMD) and bone mineral content (BMC) than those in group A (P<0.05), but serum calcium and phosphonium concentrations underwent no significant changes in the 3 groups (P>0.05). In the rats of group B, the trabeculae of the femur became thinner, fragile, and discontinuous with reduced quantity as compared with those in group A. The rats in group C had greater number of the trabeculae than those in group B with decreased resorption surface and more regular arrangement of the collagen fibers. CONCLUSION: Strontium ranelate may produce beneficial effect on the bone microstructure, reduce bone loss and stimulate bone formation in male rats subjected to simulated weightlessness.

[Transcription and promoter hypermethylation of thyroid stimulating hormone receptor gene in human papillary thyroid carcinoma].

OBJECTIVE: To study the mRNA expression of the tumor suppressor gene thyroid stimulating hormone receptor (TSHR) gene in papillary thyroid carcinoma (PTC) and the correlation between aberrant promoter methylation of TSHR gene and the tumorigenesis of PTC. METHODS: RT-PCR was used to detect the mRNA expression of TSHR gene in 50 PTC cases, 20 cases of nodular goiter and 12 cases of thyroid adenoma tissue. The status of TSHR gene promoter methylation was determined using methylation-specific PCR technique. RESULTS: Of the 50 PTC patients, 34 (68%) were found to have hypermethylation of TSHR gene promoter region, as compared to 7 out of the 32 control patients (21.9%) positive for TSHR gene promoter hypermethylation, suggesting a significantly higher rate of TSHR promoter methylation of in PTC patients than in the control patients (chi(2) = 16.61, P<0.05). Of the 34 PTC patients with TSHR promoter methylation, 14 (41.2%) showed the absence of TSHR mRNA expression; in the 16 PTC patients without TSHR promoter methylation, only 2 (12.5%) were negative for TSHR mRNA expression, showing a significant difference in the rate of negative TSHR mRNA expression with regard to TSHR promoter methylation. The PTC patients had a significantly lower TSHR mRNA expression than the control patients (chi(2) = 4.02, P<0.05). CONCLUSION: Methylation of TSHR gene in the promoter region is a common molecular event, which might be associated with the tumorigenesis and progression of human PTC.

[Protective effect of losartan on insulin secretion function of RIN-m cells against angiotensin II-induced injury and the mechanism].

OBJECTIVE: To investigate the protective effect of losartan against angiotensin II (AngII)-induced beta cell (RIN-m) impairment and explore its mechanism. METHODS: In vitro cultured RIN-m cells were divided into control group, 100 nmol/L AngII group and losartan pretreatment group. After cell incubation with the corresponding agents for 24 h, the amount of basal (3.3 mmol/L) and glucose-stimulated (16.7 mmol/L) insulin secretion (GSIS) was detected by radioimmunoassay, and the cellular reactive oxygen species (ROS) was assayed by flow cytometry with DCFH-DA staining; the mRNA and protein expressions of uncoupling protein 2 (UCP2) were determined by RT-PCR and Western blotting, respectively. RESULTS: The basal insulin secretion showed no significant differences between the 3 groups (P>0.05). The GSIS in 100 nmol/L AngII group was significantly lower than that of the control group (P<0.001), but losartan pretreatment markedly restored the insulin secretion function to a level comparable to that of the control group (P<0.05). Compared with the control group, 100 nmol/L AngII significantly increased the cellular ROS level and the mRNA and protein expressions of UCP2 (P<0.05), and these changes were eliminated by losartan pretreatment. CONCLUSIONS: Losartan pretreatment offers protective effect against AngII-induced impairment of the GSIS of beta cells possibly by antagonizing the effects of AngII that causes increased ROS level and UCP2 expressions in beta-cells.

[Effects of small interfering RNA targeting connective tissue growth factor on high glucose-induced human tubular epithelial hypertrophy].

OBJECTIVE: To observe the effect of transfection with small interfering RNA (siRNA) targeting connective tissue growth factor (CTGF) on human tubular epithelial hypertrophy induced by high glucose. METHODS: HK-2 cells were cultured in DMEM/F12 medium containing 1 g/L glucose (normal control group), 4.5 g/L glucose (high glucose group), or 1 g/L glucose+3.5 g/L mannitol (iso-osmolar control group). The cells were transfected with pGenesil-1, pGenesil/neg, or pGenesil/siRNA-CTGF and then cultured in DMEM/F12 medium containing 4.5 g/L glucose as the high glucose+blank control group, high glucose+negative control group and high glucose+interference group, respectively. After cell culture for 24, 48 and 96 h, the cells were collected to detect the mRNA and protein levels of CTGF by real-time PCR and Western blotting, respectively. The proliferative activities of the cells were evaluated with MTT assay, and the total cellular protein contents were determined with Bradford method. Flow cytometry was employed to analyzed the cell cycle changes. RESULTS: High-glucose significantly up-regulated the CTGF mRNA and protein levels in HK-2 cells. The cell proliferation was inhibited after high-glucose exposure with increased cell percentage in G1 phase and total cellular protein content suggesting cellular hypertrophy. Transfection with siRNA targeting CTGF significantly inhibited high glucose-induced up-regulation of CTGF mRNA and protein and promoted the cell proliferation, resulting also increased cells in S phase and lowered total cellular protein contents. CONCLUSION: CTGF is an important mediator of high glucose-induced tubular epithelial hypertrophy, and transfection with siRNA targeting CTGF can alleviate the hypertrophy, suggesting the potential value of CTGF-targeted treatment in the management of diabetic nephropathy.

[Isolation, purification and functional identification of Syrian golden hamster islets].

OBJECTIVE: To establish the methods for isolation, purification and function identification of Syrian golden hamster islets. METHODS: The Langerhans islets were isolated and purified from golden hamster pancreas by intra-ductal collagenase V perfusion and discontinuous Ficoll density gradient centrifugation. After isolation, the islet yield and purity were evaluated with DTZ staining. The islet function was assessed using glucose-stimulated insulin secretion test. RESULTS: The total number of purified islets from one donor hamster was 359-/+35 islet equivalent (IEQ), with the purity and viability of the isolated islets of more than 90%. In response to glucose stimulations at 5.8 and 16.7 mmol/L, the secretion of insulin by the islets was 3.29-/+0.3 and 11.12-/+0.57 mU/L, respectively, showing a 2.28-fold higher insulin release by high-concentration than by low- concentration glucose stimulation (P<0.01). CONCLUSION: The methods of collagenase V digestion and gradient centrifugation result in high yield and high purity of the isolated hamster islets.

[A survey of glucose and lipid metabolism and concomitant diseases among inpatients in Guangdong province].

OBJECTIVES: To investigate the epidemiological and clinical characteristics of dyslipidemia as well as its treatment and influence on accompanying diseases in impaired glucose status among inpatients. METHODS: A cross-sectional survey was conducted among the inpatients registered in ten university hospitals of Guangdong, China during the week before the Diabetes Day in 2004. The fasting blood glucose (FBG), lipid profiles, BMI, waist to hip ratio (WHR) and concomitant disorders of the first screen during the hospitalization period were recorded. Those who had FBG level from 5.6 to 6.9 mmol/L and not been previously diagnosed diabetes (PDM) underwent oral glucose tolerance test (OGTT). RESULTS: Of the 8753 inpatients investigated, 1067 cases had complete medical records (CMR case) including PDM cases and previously non-diagnosed diabetes ones with FBG > or = 5.6 mmol/L. Of the previously non-diagnosed diabetes cases with FBG levels from 5.6 to 6.9 mmol/L, 65.8% accepted OGTT. Of the CMR cases, 41.9% had PDM, 21.7% was newly diagnosed diabetes mellitus (NDM), 29.1% had impaired glucose regulation (IGR) and only 7.3% had normal glucose tolerance (NGT). The TG levels in NDM and PDM group were higher than those in IGR and NGT group (P < 0.05, respectively). The HDL-C levels in IGR, NDM and PDM group were lower than those in NGT group (P < 0.05, respectively). Sixty-nine point six percent of the diabetes mellitus (DM) inpatients was accompanied with dyslipidemia and the rate was higher than those in NGT (56.4%) and IGR inpatients (52.5%, P < 0.05, respectively). Only 22.8% of the PDM inpatients underwent treatment of dyslipidaemia and just 3.4% achieved the target suggested by the guideline of ATP-III. BMI was higher and waistline longer in the PDM and NDM inpatients than those in the NGT cases (P < 0.05, respectively). Seventy-two point eight percent of the PDM inpatients was complicated with more than one type of vascular diseases. Nine point seven percent and 0.2% of the NDM inpatients were tormented by diabetic nephropathy and diabetic retinopathy respectively. CONCLUSIONS: More inpatients with accompany DM or IGR had concomitant dyslipidemia than those with NGT, which included hypertriglyceridemia, hypo-high-density lipoproteinemia and metabolic syndrome. Concomitant vascular diseases were more frequently found in PDM inpatients than in the others. Some of the NDM and IGT inpatients were complicated with microvascular diseases.

[Effect of high glucose exposure on connective tissue growth factor expression in cultured human renal tubular epithelial cells and the role of p38MAPK pathway].

OBJECTIVE: To observe the effect of high glucose exposure on connective tissue growth factor (CTGF) expression in cultured human renal tubular epithelial cells and investigate the role of p38MAPK pathway in this process. METHODS: Human renal tubular epithelial cells (HKC) with and without SB203580 pretreatment were cultured in the presence of high glucose levels for 24, 48, 72, 96 h and 20 days. RT-PCR, immunohistochemical staining, indirect fluorescence staining and Western blotting were used to detect the changes in CTGF mRNA and protein expressions in the cells after the treatment. RESULTS: Low levels of CTGF mRNA and protein were detected in cultured HKC cells, and after high glucose treatment, the mRNA expression increased gradually and reached the peak level at 48 h, then followed by gradual decrease till recovering the baseline level at 96 h. Prolonged high glucose treatment for 20 days resulted in persisted high CTGF mRNA expression twice the level in the control group. The expression level of CTGF protein also increased progressively as the treatment time then prolonged, and long-term (20 days) treatment increased the expression by 4 folds in comparison with the expression in the control cells. SB203580 significantly inhibited the increase in the expressions of CTGF mRNA and protein stimulated by high glucose treatment. CONCLUSION: High glucose treatment can increase CTGF mRNA and protein expressions in cultured human renal tubular epithelial cells, suggesting that increased CTGF levels is a key event in the pathogenesis of renal tubulo-interstitial fibrosis in patients with diabetic nephropathy. p38MAPK pathway may also participate in this process.