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1.
Nightingale CM Krishnaveni GV Rudnicka AR Owen CG Veena SR Hill JC Cook DG Fall CH Whincup PH 《PloS one》2012,7(4):e36236
Objective
UK Indian adults have higher risks of coronary heart disease and type 2 diabetes than Indian and UK European adults. With growing evidence that these diseases originate in early life, we compared cardiometabolic risk markers in Indian, UK Indian and white European children.Methods
Comparisons were based on the Mysore Parthenon Birth Cohort Study (MPBCS), India and the Child Heart Health Study in England (CHASE), which studied 9–10 year-old children (538 Indian, 483 UK Indian, 1375 white European) using similar methods. Analyses adjusted for study differences in age and sex.Results
Compared with Mysore Indians, UK Indians had markedly higher BMI (% difference 21%, 95%CI 18 to 24%), skinfold thickness (% difference 34%, 95%CI 26 to 42%), LDL-cholesterol (mean difference 0.48, 95%CI 0.38 to 0.57 mmol/L), systolic BP (mean difference 10.3, 95% CI 8.9 to 11.8 mmHg) and fasting insulin (% difference 145%, 95%CI 124 to 168%). These differences (similar in both sexes and little affected by adiposity adjustment) were larger than those between UK Indians and white Europeans. Compared with white Europeans, UK Indians had higher skinfold thickness (% difference 6.0%, 95%CI 1.5 to 10.7%), fasting insulin (% difference 31%, 95%CI 22 to 40%), triglyceride (% difference 13%, 95%CI 8 to 18%) and LDL-cholesterol (mean difference 0.12 mmol/L, 95%CI 0.04 to 0.19 mmol/L).Conclusions
UK Indian children have an adverse cardiometabolic risk profile, especially compared to Indian children. These differences, not simply reflecting greater adiposity, emphasize the need for prevention strategies starting in childhood or earlier. 相似文献2.
Thomas C Nightingale CM Donin AS Rudnicka AR Owen CG Sattar N Cook DG Whincup PH 《PloS one》2012,7(3):e32619
Background
Socio-economic position (SEP) and ethnicity influence type 2 diabetes mellitus (T2DM) risk in adults. However, the influence of SEP on emerging T2DM risks in different ethnic groups and the contribution of SEP to ethnic differences in T2DM risk in young people have been little studied. We examined the relationships between SEP and T2DM risk factors in UK children of South Asian, black African-Caribbean and white European origin, using the official UK National Statistics Socio-economic Classification (NS-SEC) and assessed the extent to which NS-SEC explained ethnic differences in T2DM risk factors.Methods and Findings
Cross-sectional school-based study of 4,804 UK children aged 9–10 years, including anthropometry and fasting blood analytes (response rates 70%, 68% and 58% for schools, individuals and blood measurements). Assessment of SEP was based on parental occupation defined using NS-SEC and ethnicity on parental self-report. Associations between NS-SEC and adiposity, insulin resistance (IR) and triglyceride differed between ethnic groups. In white Europeans, lower NS-SEC status was related to higher ponderal index (PI), fat mass index, IR and triglyceride (increases per NS-SEC decrement [95%CI] were 1.71% [0.75, 2.68], 4.32% [1.24, 7.48], 5.69% [2.01, 9.51] and 3.17% [0.96, 5.42], respectively). In black African-Caribbeans, lower NS-SEC was associated with lower PI (−1.12%; [−2.01, −0.21]), IR and triglyceride, while in South Asians there were no consistent associations between NS-SEC and T2DM risk factors. Adjustment for NS-SEC did not appear to explain ethnic differences in T2DM risk factors, which were particularly marked in high NS-SEC groups.Conclusions
SEP is associated with T2DM risk factors in children but patterns of association differ by ethnic groups. Consequently, ethnic differences (which tend to be largest in affluent socio-economic groups) are not explained by NS-SEC. This suggests that strategies aimed at reducing social inequalities in T2DM risk are unlikely to reduce emerging ethnic differences in T2DM risk. 相似文献3.
Jensen RA Agardh E Lernmark A Gudbjörnsdottir S Smith NL Siscovick DS Törn C;DISS Group 《PloS one》2011,6(3):e17569
Aims/Hypothesis
HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15–34 year old individuals.Methods
The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.Results
The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25th (GADA>233 WHO units/ml) and 5th percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA1c, treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.Conclusions
Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials. 相似文献4.
Peter H. Whincup Claire M. Nightingale Christopher G. Owen Alicja R. Rudnicka Ian Gibb Catherine M. McKay Angela S. Donin Naveed Sattar K. George M. M. Alberti Derek G. Cook 《PLoS medicine》2010,7(4)
Background
Adults of South Asian origin living in the United Kingdom have high risks of type 2 diabetes and central obesity; raised circulating insulin, triglyceride, and C-reactive protein concentrations; and low HDL-cholesterol when compared with white Europeans. Adults of African-Caribbean origin living in the UK have smaller increases in type 2 diabetes risk, raised circulating insulin and HDL-cholesterol, and low triglyceride and C-reactive protein concentrations. We examined whether corresponding ethnic differences were apparent in childhood.Methods and Findings
We performed a cross-sectional survey of 4,796 children aged 9–10 y in three UK cities who had anthropometric measurements (68% response) and provided blood samples (58% response); ethnicity was based on parental definition. In age-adjusted comparisons with white Europeans (n = 1,153), South Asian children (n = 1,306) had higher glycated haemoglobin (HbA1c) (% difference: 2.1, 95% CI 1.6 to 2.7), fasting insulin (% difference 30.0, 95% CI 23.4 to 36.9), triglyceride (% difference 12.9, 95% CI 9.4 to 16.5), and C-reactive protein (% difference 43.3, 95% CI 28.6 to 59.7), and lower HDL-cholesterol (% difference −2.9, 95% CI −4.5 to −1.3). Higher adiposity levels among South Asians (based on skinfolds and bioimpedance) did not account for these patterns. Black African-Caribbean children (n = 1,215) had higher levels of HbA1c, insulin, and C-reactive protein than white Europeans, though the ethnic differences were not as marked as in South Asians. Black African-Caribbean children had higher HDL-cholesterol and lower triglyceride levels than white Europeans; adiposity markers were not increased.Conclusions
Ethnic differences in type 2 diabetes precursors, mostly following adult patterns, are apparent in UK children in the first decade. Some key determinants operate before adult life and may provide scope for early prevention. Please see later in the article for the Editors'' Summary 相似文献5.
Background
Body mass index (BMI) and waist circumference (WC) are used to define cardiovascular and type 2 diabetes risk. We aimed to derive appropriate BMI and WC obesity cut-off points in a migrant South Asian population.Methods
4688 White Europeans and 1333 South Asians resident in the UK aged 40–75 years inclusive were screened for type 2 diabetes. Principal components analysis was used to derive a glycaemia, lipid, and a blood pressure factor. Regression models for each factor, adjusted for age and stratified by sex, were used to identify BMI and WC cut-off points in South Asians that correspond to those defined for White Europeans.Findings
For South Asian males, derived BMI obesity cut-off points equivalent to 30.0 kg/m2 in White Europeans were 22.6 kg/m2 (95% Confidence Interval (95% CI) 20.7 kg/m2 to 24.5 kg/m2) for the glycaemia factor, 26.0 kg/m2 (95% CI 24.7 kg/m2 to 27.3 kg/m2) for the lipid factor, and 28.4 kg/m2 (95% CI 26.5 kg/m2 to 30.4 kg/m2) for the blood pressure factor. For WC, derived cut-off points for South Asian males equivalent to 102 cm in White Europeans were 83.8 cm (95% CI 79.3 cm to 88.2 cm) for the glycaemia factor, 91.4 cm (95% CI 86.9 cm to 95.8 cm) for the lipid factor, and 99.3 cm (95% CI 93.3 cm to 105.2 cm) for the blood pressure factor. Lower ethnicity cut-off points were seen for females for both BMI and WC.Conclusions
Substantially lower obesity cut-off points are needed in South Asians to detect an equivalent level of dysglycemia and dyslipidemia as observed in White Europeans. South Asian ethnicity could be considered as a similar level of risk as obesity (in White Europeans) for the development of type 2 diabetes. 相似文献6.
Background
We aimed to determine whether family practices'' achievement of diabetes quality of care targets is associated with diabetic retinal disease in registered patients.Methods
Data for achievement of diabetes quality of care targets, including the proportion of patients with HbA1c≤7.5%, for 144 family practices in London UK, for the years 2004/5 to 2007/8, were linked to data from a population-based diabetes eye screening programme collected from September 2007 to February 2009. Analyses were adjusted for age, sex, duration and type of diabetes, unadjusted diabetes prevalence, ethnicity and deprivation category.Results
Data were analysed for 24,458 participants with one or more eye screening results in the period. There were 9,332 (38%) with any diabetic retinopathy and 2,819 (11.5%) with sight threatening diabetic retinopathy (STDR), including 2,654 (10.9%) with maculopathy. Among participants registered at 13 family practices that were in the highest quartile for achievement of the HbA1c quality of care target for all four years of study, the relative odds of any diabetic retinopathy were 0.78 (0.69 to 0.88) P<0.001. For participants at 12 practices consistently in the lowest quartile of HbA1c achievement, the relative odds of any diabetic retinopathy were 1.16 (1.03 to 1.30), P = 0.015. In the highest achieving practices, the relative odds of maculopathy were 0.74 (0.62 to 0.89), P = 0.001 and STDR 0.77 (0.65 to 0.92), P = 0.004.Conclusions
The risk of diabetic retinopathy might be lower at family practices that consistently achieve highly on diabetes quality of care targets for HbA1c. 相似文献7.
Zheng Y Lamoureux EL Ikram MK Mitchell P Wang JJ Younan C Anuar AR Tai ES Wong TY 《PloS one》2012,7(4):e34829
Background
Health of migrants is a major public health challenge faced by governments and policy makers. Asian Indians are among the fastest growing migration groups across Asia and the world, but the impact of migration and acculturation on diabetes and diabetes-related eye complications among Indians living in urban Asia remains unclear.Methodologies/Principal Findings
We evaluated the influence of migration and acculturation (i.e., migration status and length of residence) on the prevalence of type-2 diabetes mellitus (T2DM) and diabetes-related eye complications (diabetic retinopathy (DR) and cataract), among first-generation (defined as participant born in India with both parents born in India, n = 781) and second-generation (participants born in Singapore with both parents born in India, n = 1,112) Indian immigrants from a population-based study of Adult Indians in Singapore. Diabetes was defined as HbA1c≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal and lens photographs were graded for the presence of DR and cataract. Compared to first generation immigrants, second generation immigrants had a higher age- and gender-standardized prevalence of T2DM (34.4% versus 29.0%, p<0.001), and, in those with T2DM, higher age- and gender-standardized prevalence of DR (31.7% versus 24.8%, p<0.001), nuclear cataract (13.6% versus 11.6%, p<0.001), and posterior sub-capsular cataract (6.4% versus 4.6%, p<0.001). Among first generation migrants, longer length of residence was associated with significantly younger age of diagnosis of diabetes and greater likelihood of having T2DM and diabetes-related eye complications.Conclusion
Second generation immigrant Indians and longer length of residence are associated with higher prevalence of diabetes and diabetes-related complications (i.e., DR and cataract) among migrant Indians living in Singapore. These data highlight potential worldwide impacts of migration patterns on the risk and burden of diabetes. 相似文献8.
Background
Limited data exists on the prevalence of heart failure amongst minority groups in the UK. To document the community prevalence and severity of left ventricular systolic dysfunction, heart failure, and atrial fibrillation, amongst the South Asian and Black African -Caribbean groups in the UK.Methods and Results
We conducted a cross-sectional study recruiting from September 2006 to July 2009 from 20 primary care centres in Birmingham, UK. 10,902 eligible subjects invited, 5,408 participated (49.6%) and 5,354 had complete data (49.1%). Subjects had median age 58.2 years (interquartile range 51.0 to 70.0), and 2544 (47.5%) were male. Of these, 1933 (36.3%) had BMI>30 kg/m2, 1,563 (29.2%) had diabetes, 2676 (50.0%) had hypertension, 307 (5.7%) had a history of myocardial infarction, and 104 (1.9%) had history of arrhythmia. Overall, 59 (1.1%) had an Ejection Fraction<40%, and of these 40 (0.75%) were NYHA class ≥2; 51 subjects (0.95%) had atrial fibrillation. Of the remaining 19 patients with an EF<40%, only 4 patients were treated with furosemide. A further 54 subjects had heart failure with preserved ejection fraction.Conclusions
This is the largest study of the prevalence of left ventricular systolic dysfunction, heart failure and atrial fibrillation in under-researched minority communities in the UK. The prevalence of heart failure in these minority communities appears comparable to that of the general population but less than anticipated given the high rates of cardiovascular disease in these groups. Heart failure continues to be a major cause of morbidity in all ethnic groups and preventive strategies need to be identified and implemented. 相似文献9.
Aim
To assess the performance of automated disease detection in diabetic retinopathy screening using two field mydriatic photography.Methods
Images from 8,271 sequential patient screening episodes from a South London diabetic retinopathy screening service were processed by the Medalytix iGrading™ automated grading system. For each screening episode macular-centred and disc-centred images of both eyes were acquired and independently graded according to the English national grading scheme. Where discrepancies were found between the automated result and original manual grade, internal and external arbitration was used to determine the final study grades. Two versions of the software were used: one that detected microaneurysms alone, and one that detected blot haemorrhages and exudates in addition to microaneurysms. Results for each version were calculated once using both fields and once using the macula-centred field alone.Results
Of the 8,271 episodes, 346 (4.2%) were considered unassessable. Referable disease was detected in 587 episodes (7.1%). The sensitivity of the automated system for detecting unassessable images ranged from 97.4% to 99.1% depending on configuration. The sensitivity of the automated system for referable episodes ranged from 98.3% to 99.3%. All the episodes that included proliferative or pre-proliferative retinopathy were detected by the automated system regardless of configuration (192/192, 95% confidence interval 98.0% to 100%). If implemented as the first step in grading, the automated system would have reduced the manual grading effort by between 2,183 and 3,147 patient episodes (26.4% to 38.1%).Conclusion
Automated grading can safely reduce the workload of manual grading using two field, mydriatic photography in a routine screening service. 相似文献10.
Background
The UK introduced an ambitious national strategy to reduce population levels of salt intake in 2003. The aim of this study was to evaluate the impact of this strategy on salt intake in England, including potential effects on health inequalities.Methods
Secondary analysis of data from the Health Survey for England. Our main outcome measure was trends in estimated daily salt intake from 2003–2007, as measured by spot urine. Secondary outcome measures were knowledge of government guidance and voluntary use of salt in food preparation over this time period.Results
There were significant reductions in salt intake between 2003 and 2007 (−0.175grams per day per year, p<0.001). Intake decreased uniformly across all other groups but remained significantly higher in younger persons, men, ethnic minorities and lower social class groups and those without hypertension in 2007. Awareness of government guidance on salt use was lowest in those groups with the highest intake (semi-skilled manual v professional; 64.9% v 71.0% AOR 0.76 95% CI 0.58–0.99). Self reported use of salt added at the table reduced significantly during the study period (56.5% to 40.2% p<0.001). Respondents from ethnic minority groups remained significantly more likely to add salt during cooking (white 42.8%, black 74.1%, south Asian 88.3%) and those from lower social class groups (unskilled manual 46.6%, professional 35.2%) were more likely to add salt at the table.Conclusions
The introduction a national salt reduction strategy was associated with uniform but modest reductions in salt intake in England, although it is not clear precisely which aspects of the strategy contributed to this. Knowledge of government guidance was lower and voluntary salt use and total salt intake was higher among occupational and ethnic groups at greatest risk of cardiovascular disease. 相似文献11.
12.
Aims
To investigate the relationship between hyperuricemia (HUA) and the clinical backgrounds in Japanese patients with type 2 diabetes mellitus.Methods
After a cross-sectional study evaluating the association of HUA with the clinical characteristics in 1,213 patients with type 2 diabetes mellitus, the estimated glomerular filtration rate (eGFR) and the incidence of diabetic macroangiopathies was investigated in a prospective observational study in 1,073 patients during a 3.5 year period. HUA was defined by serum uric acid levels >327 μmol/L or as patients using allopurinol.Results
The frequency of HUA was significantly higher in the diabetic patients (32% in men and 15% in women) than in the normal controls (14% in men and 1% in women). In total, HUA was found in 299 (25%) of the patients during the cross-sectional study. Even after adjusting for sex, drinking status, treatment for diabetes mellitus, body mass index, hypertension, use of diuretics, hyperlipidemia, HbA1c and/or the eGFR, the HUA was independently associated with some diabetic complications. The eGFR was significantly reduced in HUA patients compared to those with normouricemia in the 12 months after observation was started. HUA was also an independent risk factor for coronary heart disease even after adjustment in the Cox proportional hazard model.Conclusions
HUA is a associated with diabetic micro- and macroangiopathies. HUA is a predictor of coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus. However, the influence of HUA is considered to be limited. 相似文献13.
Background
The glycemic thresholds for diabetes diagnosis have long been at the forefront of discussion. However, no information about glycemic cutoff points has been made available for the Chinese population. The aim of the present study was to examine the association of fasting plasma glucose (FPG), 2-h plasma glucose (2-h PG) and HbA1c levels with diabetic retinopathy (DR) and determine the associated cutoff levels in a Chinese population.Methodology and Principal Findings
In a cross-sectional population-based sample of 2551 Chinese (representing a population of 1,660,500 in a Beijing district) between 18–79 years of age, the three glycemic measures were measured in a 75 g oral glucose tolerance test, and DR was assessed by two 45° color digital retinal images. The prevalence of DR increased in the ninth decile of each variable, corresponding to an FPG of ≥7.2 mmol/l, a 2-h PG of ≥10.7 mmol/l, and HbA1c of ≥6.4%, according to the Joinpoint regression method. After excluding individuals receiving antihyperglycemic medication, the prevalence significantly increased at an FPG of ≥6.8 mmol/l, a 2-h PG of ≥12.0 mmol/l, and HbA1c of ≥6.7%. The area under the ROC curve for all three measures showed no significant differences for detecting DR. After excluding individuals receiving antihyperglycemic medication, the three measures also showed no significant differences.Conclusions and Significance
A significant increase in retinopathy prevalence occurs among individuals with FPG ≥7.2 mmol/l, 2-h PG ≥10.5 mmol/and HbA1c ≥6.4%; and measuring FPG or HbA1c are equally reliable methods as measuring 2-h PG for the diagnosis of diabetes in the Chinese population. 相似文献14.
Objective
To investigate whether the elevated liver enzymes gamma-glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate-oxalacetate transaminase (GOT) and alkaline phosphatase (AP) and non-alcoholic fatty liver disease (NAFLD) respectively are independently associated with pre-diabetic states, namely impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or known and newly diagnosed diabetes (NDD), in men and women from the general German population.Methods
The study was based on 3009 subjects (1556 females, 1453 males) aged 32 to 81 years who participated in the KORA-F4-Study in 2006/2008 in Augsburg, Southern Germany. All non-diabetic participants underwent an oral glucose tolerance test to assess disturbances in glucose metabolism. NAFLD was estimated by liver enzyme concentrations and the Bedogni Fatty Liver Index (FLI).Results
229 participants (7.6%) reported known diabetes, 106 had NDD (3.5%), 107 (3.6%) had IFG, 309 (10.3%) had IGT, 69 (2.3%) were affected with both metabolic disorders (IFG/IGT) and 74 (2.5%) could not be classified. GGT and GPT were significantly elevated in persons with pre-diabetes and diabetes (GGT in diabetic persons OR = 1.76, [1.47–2.09], in IFG OR = 1.79 [1.50–2.13], GPT in diabetic persons OR = 1.51, [1.30–1.74], in NDD OR = 1.77 [1.52–2.06]), GOT and AP only inconsistently in some pre-diabetes groups. The effects were sharpened in models using an increase of two or three out of three enzymes as an estimate of fatty liver and especially in models using the FLI. Overall frequency of NAFLD applying the index was 39.8% (women: 27.3% and men: 53.2%). In participants with fatty liver disease, the OR for NDD adjusted for sex and age was 8.48 [5.13–14.00], 6.70 [3.74–12.01] for combined IFG and IGT and 4.78 [3.47–6.59] for known diabetes respectively.Conclusions
Elevated GGT and GPT–values as well as estimates of fatty liver disease are significantly associated with pre-diabetes and diabetes and thus very useful first indicators of a disturbed glucose metabolism. 相似文献15.
Peiyao Jin Jinjuan Peng Haidong Zou Weiwei Wang Jiong Fu Binjie Shen Xuelin Bai Xun Xu Xi Zhang 《PloS one》2014,9(11)
Purpose
To determine the rate and risk factors of diabetic retinopathy (DR) onset and regression in Chinese type 2 diabetes mellitus patients.Methods
This is a 5-year community-based prospective study. The demographic information, systemic examination results and ophthalmological test results of each participant were collected. The study outcomes were DR incidence, defined as the onset of DR in at least one eye, and DR regression, defined as full regression from existing DR to no retinopathy without invasive treatments. The associations between each potential risk factor and the outcomes were studied.Results
In total, 778 participants were enrolled. There were 322 patients without DR at baseline, of which 151 participants developed DR during follow-up (DR incidence rate = 46.89%). Baseline hyperglycemia and high blood pressure were two independent risk factors associated with DR incidence. Among the 456 participants with existing DR at entry, 110 fully recovered after 5 years (DR regression rate = 24.12%). Low baseline glucose and low serum triglyceride were two independent factors associated with DR regression.Conclusions
DR incidence occurred more frequently in patients with hyperglycemia and high blood pressure. DR regression occurred mostly in patients with lower glucose and lower serum triglyceride levels among Chinese type 2 diabetes patients. 相似文献16.
Objective
VEGFR1 and 2 signaling have both been increasingly shown to mediate complications of ischemic retinopathies, including retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and diabetic retinopathy (DR). This study evaluates the effects of blocking VEGFR1 and 2 on pathological angiogenesis and vascular leakage in ischemic retinopathy in a model of ROP and in choroidal neovascularization (CNV) in a model of AMD.Materials and Methods
Neutralizing antibodies specific for mouse VEGFR1 (MF1) and VEGFR2 (DC101) were administrated systemically. CNV was induced by laser photocoagulation and assessed 14d after laser treatment. Retinal NV was generated in oxygen-induced ischemic retinopathy (OIR) and assessed at p17. NV quantification was determined by measuring NV tufts and vascular leakage was quantified by measuring [3H]-mannitol leakage from blood vessels into the retina. Gene expression was measured by real-time quantitative (Q)PCR.Results
VEGFR1 and VEGFR2 expressions were up-regulated during CNV pathogenesis. Both MF1 and DC101 significantly suppressed CNV at 50 mg/kg: DC101 suppressed CNV by 73±5% (p<0.0001) and MF1 by 64±6% (p = 0.0002) in a dosage-dependent manner. The combination of MF1 and DC101 enhanced the inhibitory efficacy and resulted in an accumulation of retinal microglia at the CNV lesion. Similarly, both MF1 and DC101 significantly suppressed retinal NV in OIR at 50 mg/kg: DC101 suppressed retinal NV by 54±8% (p = 0.013) and MF1 by 50±7% (p<0.0002). MF1 was even more effective at inhibiting ischemia-induced BRB breakdown than DC101: the retina/lung leakage ratio for MF1 was reduced by 73±24%, p = 0.001 and for DC101 by 12±4%, p = 0.003. The retina/renal leakage ratio for MF1 was reduced by 52±28%, p = 0.009 and for DC101 by 13±4%, p = 0.001.Conclusion
Our study provides further evidence that both VEGFR1 and 2 mediate pathological angiogenesis and vascular leakage in these models of ocular disease and suggests that antagonist antibodies to these receptor tyrosine kinases (RTKs) are potential therapeutic agents. 相似文献17.
Kim PS Woods C Dutcher L Georgoff P Rosenberg A Mican JA Kopp JB Smith MA Hadigan C 《PloS one》2011,6(9):e24610
Objective
HIV and type 2 diabetes are known risk factors for albuminuria, but no previous reports have characterized albuminuria in HIV-infected patients with diabetes.Research Design and Methods
We performed a cross-sectional study including 73 HIV-infected adults with type 2 diabetes, 82 HIV-infected non-diabetics, and 61 diabetic control subjects without HIV. Serum creatinine >1.5 mg/dL was exclusionary. Albuminuria was defined as urinary albumin/creatinine ratio >30 mg/g.Results
The prevalence of albuminuria was significantly increased among HIV-infected diabetics (34% vs. 13% of HIV non-diabetic vs. 16% diabetic control, p = 0.005). HIV status and diabetes remained significant predictors of albuminuria after adjusting for age, race, BMI, and blood pressure. Albumin/creatinine ratio correlated significantly with HIV viral load (r = 0.28, p = 0.0005) and HIV-infected subjects with albuminuria had significantly greater cumulative exposure to abacavir (p = 0.01). In an adjusted multivariate regression analysis of HIV-infected subjects, the diagnosis of diabetes (p = 0.003), higher HIV viral load (p = 0.03) and cumulative exposure to abacavir (p = 0.0009) were significant independent predictors of albuminuria.Conclusions
HIV and diabetes appear to have additive effects on albuminuria which is also independently associated with increased exposure to abacavir and HIV viral load. Future research on the persistence, progression and management of albuminuria in this unique at-risk population is needed. 相似文献18.
Anand SS Tarnopolsky MA Rashid S Schulze KM Desai D Mente A Rao S Yusuf S Gerstein HC Sharma AM 《PloS one》2011,6(7):e22112
Objective
We sought to determine if differences in the distribution and characteristics of adipose tissue between South Asians and white Caucasians account for differences in risk factors for cardiovascular disease.Research Design and Methods
We recruited 108 healthy South Asians (36.8 years) and white Caucasians (34.2 years) within three BMI strata. Body composition, adipocyte size, abdominal fat area, and hepatic adiposity were assessed and related to fasting glucose, insulin, lipids and adiponectin.Results
After adjustment for age, sex, and BMI, South Asians compared to white Caucasians had higher ln fasting insulin (mean difference (md): 0.44; 95% CI: 0.20–0.69), lower HDL cholesterol (md: −0.13; 95% CI:−0.26 to −0.01), and lower adiponectin (md: −2.38; 95% CI: −3.59 to −1.17). South Asians also had more body fat (md: 2.69; 95% CI: 0.70 to 4.69), lower lean muscle mass (md: −3.25; 95%CI: −5.35 to −1.14), increased waist to hip ratio (md: 0.03; 95% CI: 0.01–0.05), less superficial subcutaneous abdominal adipose tissue (md: −2.94; 95% CI: −5.56 to−0.32), more deep/visceral to superficial adipose tissue ratio (md 0.34; 95% CI: 0.02 to 0.65), and more liver fat (md: 7.43%; 95% CI: 2.30 to 12.55%). Adipocyte area was increased in South Asians compared to white Caucasians (md: 64.26; 95% CI: 24.3 to 104.1) units2. Adjustment for adipocyte area attenuated the ethnic differences in insulin (md: 0.22; 95% CI: −0.07 to 0.51), HDL (md: −0.01; 95% CI: −0.16 to 0.13) and adiponectin (md: −1.11; 95% CI: −2.61 to 0.39). Adjustment for differences in adipocyte area and fat distribution attenuated the ethnic difference in liver fat (md: 5.19; 95% CI: 0.31 to 10.06).Conclusion
South Asians have an increased adipocyte area compared to white Caucasians. This difference accounts for the ethnic differences in insulin, HDL cholesterol, adiponectin, and ectopic fat deposition in the liver. 相似文献19.
Burgdorf KS Grarup N Justesen JM Harder MN Witte DR Jørgensen T Sandbæk A Lauritzen T Madsbad S Hansen T;DIAGRAM Consortium Pedersen O 《PloS one》2011,6(1):e15813
Aims
A study of 222 candidate genes in type 2 diabetes reported association of variants in RAPGEF1, ENPP1, TP53, NRF1, SLC2A2, SLC2A4 and FOXC2 with type 2 diabetes in 4,805 Finnish individuals. We aimed to replicate these associations in a Danish case-control study and to substantiate any replicated associations in meta-analyses. Furthermore, we evaluated the impact on diabetes-related intermediate traits in a population-based sample of middle-aged Danes.Methods
We genotyped nine lead variants in the seven genes in 4,973 glucose-tolerant and 3,612 type 2 diabetes Danish individuals. In meta-analyses we combined case-control data from the DIAGRAM+ Consortium (n = 47,117) and the present genotyping results. The quantitative trait studies involved 5,882 treatment-naive individuals from the Danish Inter99 study.Results
None of the nine investigated variants were significantly associated with type 2 diabetes in the Danish samples. However, for all nine variants the estimate of increase in type 2 diabetes risk was observed for the same allele as previously reported. In a meta-analysis of published and online data including 55,521 Europeans the G-allele of rs1042522 in TP53 showed significant association with type 2 diabetes (OR = 1.06 95% CI 1.02–1.11, p = 0.0032). No substantial associations with diabetes-related intermediary phenotypes were found.Conclusion
The G-allele of TP53 rs1042522 is associated with an increased prevalence of type 2 diabetes in a combined analysis of 55,521 Europeans. 相似文献20.
Alkhalaf A Zürbig P Bakker SJ Bilo HJ Cerna M Fischer C Fuchs S Janssen B Medek K Mischak H Roob JM Rossing K Rossing P Rychlík I Sourij H Tiran B Winklhofer-Roob BM Navis GJ;PREDICTIONS Group 《PloS one》2010,5(10):e13421