Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis.

Aims/hypothesis Glomerular hyperfiltration is a well established phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding whether hyperfiltration predicts later development of nephropathy. We performed a systematic review and meta-analysis of observational studies that compared the risk of developing diabetic nephropathy in patients with and without glomerular hyperfiltration and also explored the impact of baseline GFR.<br/><br/>Methods A systematic review and meta-analysis was carried out. Cohort studies in type 1 diabetic participants were included if they contained data on the development of incipient or overt nephropathy with baseline measurement<br/>of GFR and presence or absence of hyperfiltration. <br/><br/>Results We included ten cohort studies following 780 patients. After a study median follow-up of 11.2 years, 130 patients had developed nephropathy. Using a random effects model, the pooled odds of progression to a minimum<br/>of microalbuminuria in patients with hyperfiltration was 2.71 (95% CI 1.20–6.11) times that of patients with normofiltration. There was moderate heterogeneity (heterogeneity test p=0.05, measure of degree of inconsistency=48%) and some evidence of funnel plot asymmetry, possibly due to publication bias. The pooled weighted mean difference in baseline GFR was 13.8 ml min-1 1.73 m-2 (95% CI 5.0–22.7) greater in the group progressing to nephropathy than in those not progressing (heterogeneity test p&lt;0.01).<br/><br/>Conclusions/interpretation In published studies, individuals with glomerular hyperfiltration were at increased risk of progression to diabetic nephropathy using study level data. Further larger studies are required to explore this relationship and the role of potential confounding variables.

Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data

Aims/hypothesis: We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. Methods: Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. Results: Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p=0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p=0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p=0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. Conclusions/interpretation: Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes. © 2010 Springer-Verlag. <br/> <br/> <br/>-------------------------------------------------------------------------------- <br/> <br/>Reaxys Database Information| <br/> <br/>-------------------------------------------------------------------------------- <br/>

Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes: A meta-analysis of observational studies

Aims/hypothesis: The aim of this study was to investigate the evidence of an increased risk of childhood-onset type 1 diabetes in children born by Caesarean section by systematically reviewing the published literature and performing a meta-analysis with adjustment for recognised confounders. <br/>Methods: After MEDLINE, Web of Science and EMBASE searches, crude ORs and 95% CIs for type 1 diabetes in children born by Caesarean section were calculated from the data reported in each study. Authors were contacted to facilitate adjustments for potential confounders, either by supplying raw data or calculating adjusted estimates. Meta-analysis techniques were then used to derive combined ORs and to investigate heterogeneity between studies. <br/>Results: Twenty studies were identified. Overall, there was a significant increase in the risk of type 1 diabetes in children born by Caesarean section (OR 1.23, 95% CI 1.15-1.32, p&lt;0.001). There was little evidence of heterogeneity between studies (p=0.54). Seventeen authors provided raw data or adjusted estimates to facilitate adjustments for potential confounders. In these studies, there was evidence of an increase in diabetes risk with greater birthweight, shorter gestation and greater maternal age. The increased risk of type 1 diabetes after Caesarean section was little altered after adjustment for gestational age, birth weight, maternal age, birth order, breast-feeding and maternal diabetes (adjusted OR 1.19, 95% CI 1.04-1.36, p=0.01). <br/>Conclusions/interpretation: This analysis demonstrates a 20% increase in the risk of childhood-onset type 1 diabetes after Caesarean section delivery that cannot be explained by known confounders.

A Posteriori Dietary Patterns Are Related to Risk of Type 2 Diabetes: Findings from a Systematic Review and Meta-Analysis

Our review and meta-analysis examined the association between a posteriori–derived dietary patterns (DPs) and risk of type 2 diabetes mellitus. MEDLINE and EMBASE were searched for articles published up to July 2012 and data were extracted by two independent reviewers. Overall, 19 cross-sectional, 12 prospective cohort, and two nested case-control studies were eligible for inclusion. Results from cross-sectional studies reported an inconsistent association between DPs and measures of insulin resistance and/or glucose abnormalities, or prevalence of type 2 diabetes. A meta-analysis was carried out on nine prospective cohort studies that had examined DPs derived by principle component/factor analysis and incidence of type 2 diabetes risk (totaling 309,430 participants and 16,644 incident cases). Multivariate-adjusted odds ratios were combined using a random-effects meta-analysis. Two broad DPs (Healthy/Prudent and Unhealthy/Western) were identified based on food factor loadings published in original studies. Pooled results indicated a 15% lower type 2 diabetes risk for those in the highest category of Healthy/Prudent pattern compared with those in the lowest category (95% CI 0.80 to 0.91; P&lt;0.0001). Compared with the lowest category of Unhealthy/Western DP, those in the highest category had a 41% increased risk of type 2 diabetes (95% CI 1.32 to 1.52; P&lt;0.0001). These results provide evidence that DPs are consistently associated with risk of type 2 diabetes even when other lifestyle factors are controlled for. Thus, greater adherence to a DP characterized by high intakes of fruit, vegetables, and complex carbohydrate and low intakes of refined carbohydrate, processed meat, and fried food may be one strategy that could have a positive influence on the global public health burden of type 2 diabetes.

Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies

<p><em>Aims/hypothesisem> The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible.p><p><em>Methods em>A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis.p><p><em>Resultsem> In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors’ adjustments for potential confounding made a substantial difference to the pooled ORs.p><p><em>Conclusions/interpretationem> This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.p>

Homocysteine, Methylenetetrahydrofolate Reductase C677T Polymorphism, and Risk of Retnal Vein Occlusion: A Meta-analysis

Objective: To assess the role of plasma total homocysteine (tHcy) concentrations and homozygosity for the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) C677T gene as risk factors for retinal vascular occlusive disease. <br/> <br/>Design: Retinal vein occlusion (RVO) is an important cause of vision loss. Early meta-analyses showed that tHcy was associated with an increased risk of RVO, but a significant number of new studies have been published. Participants and/or Controls: RVO patients and controls. <br/> <br/>Methods: Data sources included MEDLINE, Web of Science, and PubMed searches and searching reference lists of relevant articles and reviews. Reviewers searched the databases, selected the studies, and then extracted data. Results were pooled quantitatively using meta-analytic methods. <br/> <br/>Main Outcome Measures: tHcy concentrations and MTHFR genotype. <br/> <br/>Results: There were 25 case-control studies for tHcy (1533 cases and 1708 controls) and 18 case-control studies for MTHFR (1082 cases and 4706 controls). The mean tHcy was on average 2.8 mol/L (95% confidence <br/>interval [CI], 1.8 –3.7) greater in the RVO cases compared with controls, but there was evidence of between-study heterogeneity (P0.001, I2 93%). There was funnel plot asymmetry suggesting publication bias. There was no evidence of association between homozygosity for the MTHFR C677T genotype and RVO (odds ratio [OR] 1.20; 95% CI, 0.84–1.71), but again marked heterogeneity (P 0.004, I2 53%) was observed. <br/> <br/>Conclusions: There was some evidence that elevated tHcy was associated with RVO, but not homozygosity for the MTHFR C677T genotype. Both analyses should be interpreted cautiously because of marked heterogeneity between the study estimates and possible effect of publication bias on the tHcy findings. <br/> <br/>Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Gene Expression Meta-Analysis Identifies VDAC1 as a Predictor of Poor Outcome in Early Stage Non-Small Cell Lung Cancer

Background: The bioenergetic status of non-small cell lung cancer correlates with tumour aggressiveness. The voltage dependent anion channel type 1 (VDAC1) is a component of the mitochondrial permeability transition pore, regulates mitochondrial ATP/ADP exchange suggesting that its over-expression could be associated with energy dependent processes including increased proliferation and invasiveness. To test this hypothesis, we conducted an in vivo gene-expression meta-analysis of surgically resected non-small cell lung cancer (NSCLC) using 602 individual expression profiles, to examine the impact of VDAC1 on survival.

Drivers of sales performance: a contemporary meta-analysis. Have salespeople become knowledge brokers?

It has been 25 years since the publication of a comprehensive review of the full spectrum of salesperformance drivers. This study takes stock of the contemporary field and synthesizes empirical evidence from the period 1982–2008. The authors revise the classification scheme for sales performance determinants devised by Walker et al. (1977) and estimate both the predictive validity of its sub-categories and the impact of a range of moderators on determinant-sales performance relationships. Based on multivariate causal model analysis, the results make two major observations: (1) Five sub-categories demonstrate significant relationships with sales performance: selling-related knowledge (ß=.28), degree of adaptiveness (ß=.27), role ambiguity (ß=-.25), cognitive aptitude (ß=.23) and work engagement (ß=.23). (2) These sub-categories are moderated by measurement method, research context, and salestype variables. The authors identify managerial implications of the results and offer suggestions for further research, including the conjecture that as the world is moving toward a knowledge-intensive economy, salespeople could be functioning as knowledge-brokers. The results seem to back this supposition and indicate how it might inspire future research in the field of personal selling.

Genetic Polymorphisms in Nitric Oxide Synthase 3 Gene and Implications for Kidney Disease: A Meta-Analysis

Background/Aims: The NOS3 gene is a biological and positional candidate for diabetic nephropathy. However, the relationship between NOS3 polymorphisms and renal disease is inconclusive. This study aimed to clarify the association of NOS3 variants with nephropathy in individuals with type 1 diabetes. Methods: We conducted a case-control study examining all common SNPs in the NOS3 gene by a tag SNP approach. Individuals with type 1 diabetes and persistent proteinuria (cases, n = 718) were compared with individuals with type 1 diabetes but no evidence of renal disease (controls, n = 749). Our replication collection comprised 1,105 individuals with type 1 diabetes recruited to a nephropathy case group and 862 control individuals with normal urinary albumin excretion rates. Meta-analysis was conducted for SNPs where more than three genotype datasets were available. Results: A novel association was identified in the discovery collection (rs1800783, p(genotype) = 0.006, p(allele) = 0.002, OR = 1.26, 95% CI: 1.08-1.47) and supported by independent replication using a tag SNP (rs4496877, pairwise r(2) = 0.96 with rs1800783) in the replication collection (p(genotype) = 0.002, p(allele) = 0.0006, OR = 1.27, 95% CI: 1.10-1.45). Conclusion: The A allele of rs1800783 is a significant risk factor for nephropathy in individuals with type 1 diabetes, and further comprehensive studies are warranted to confirm the definitive functional variant in the NOS3 gene. Copyright (C) 2010 S. Karger AG, Basel