Insulin Resistance and Risk of Incident Cardiovascular Events in Adults without Diabetes: Meta-Analysis

Background

Glucose, insulin and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) are markers of insulin resistance. The objective of this study is to compare fasting glucose, fasting insulin concentrations and HOMA-IR in strength of association with incident cardiovascular disease.

Methods

We searched the PubMed, MEDLINE, EMBASE, Web of Science, ScienceDirect and Cochrane Library databases from inception to March, 2011, and screened reference lists. Cohort studies or nested case-control studies that investigated the association between fasting glucose, fasting insulin or HOMA-IR and incident cardiovascular disease, were eligible. Two investigators independently performed the article selection, data extraction and risk of bias assessment. Cardiovascular endpoints were coronary heart disease (CHD), stroke or combined cardiovascular disease. We used fixed and random-effect meta-analyses to calculate the pooled relative risk for CHD, stroke and combined cardiovascular disease, comparing high to low concentrations of glucose, insulin or HOMA-IR. Study heterogeneity was calculated with the I² statistic. To enable a comparison between cardiovascular disease risks for glucose, insulin and HOMA-IR, we calculated pooled relative risks per increase of one standard deviation.

Results

We included 65 studies (involving 516,325 participants) in this meta-analysis. In a random-effect meta-analysis the pooled relative risk of CHD (95% CI; I²) comparing high to low concentrations was 1.52 (1.31, 1.76; 62.4%) for glucose, 1.12 (0.92, 1.37; 41.0%) for insulin and 1.64 (1.35, 2.00; 0%) for HOMA-IR. The pooled relative risk of CHD per one standard deviation increase was 1.21 (1.13, 1.30; 64.9%) for glucose, 1.04 (0.96, 1.12; 43.0%) for insulin and 1.46 (1.26, 1.69; 0.0%) for HOMA-IR.

Conclusions

The relative risk of cardiovascular disease was higher for an increase of one standard deviation in HOMA-IR compared to an increase of one standard deviation in fasting glucose or fasting insulin concentration. It may be useful to add HOMA-IR to a cardiovascular risk prediction model.     

Statin Use and Risk of Prostate Cancer: A Meta-Analysis of Observational Studies

Background

Emerging evidence suggests that statins may decrease the risk of cancers. However, available evidence on prostate cancer (PCa) is conflicting. We therefore examined the association between statin use and risk of PCa by conducting a detailed meta-analysis of all observational studies published regarding this subject.

Methods

Literature search in PubMed database was undertaken through February 2012 looking for observational studies evaluating the association between statin use and risk of PCa. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects model (DerSimonian and Laird method). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed.

Results

A total of 27 (15 cohort and 12 case-control) studies contributed to the analysis. There was heterogeneity among the studies but no publication bias. Statin use significantly reduced the risk of both total PCa by 7% (RR 0.93, 95% CI 0.87–0.99, p = 0.03) and clinically important advanced PCa by 20% (RR 0.80, 95% CI 0.70–0.90, p<0.001). Long-term statin use did not significantly affect the risk of total PCa (RR 0.94, 95% CI 0.84–1.05, p = 0.31). Stratification by study design did not substantially influence the RR. Furthermore, sensitivity analysis confirmed the stability of results. Cumulative meta-analysis showed a change in trend of reporting risk from positive to negative in statin users between 1993 and 2011.

Conclusions

Our meta-analysis provides evidence supporting the hypothesis that statins reduce the risk of both total PCa and clinically important advanced PCa. Further research is needed to confirm these findings and to identify the underlying biological mechanisms.     

Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis

BackgroundStem cell therapy is a promising therapeutic modality for advanced diabetes mellitus (DM). This study presents a meta-analysis of relevant clinical trials to determine the efficacy of stem cell therapy in DM. We aim to critically evaluate and synthesize clinical evidence on the safety and efficiency of different types of stem cell therapy for both T1DM and T2DM.ConclusionsStem cell transplantation can represent a safe and effective treatment for selected patients with DM. In this cohort of trials, the best therapeutic outcome was achieved with CD34⁺ HSC therapy for T1DM, while the poorest outcome was observed with HUCB for T1DM. Diabetic ketoacidosis impedes therapeutic efficacy.     

Statin Use and the Risk of Parkinson's Disease: An Updated Meta-Analysis

Introduction

In response to the ongoing debate over the relationship between the use of statins and the risk of Parkinson''s disease (PD), we performed a systematic review and meta-analysis of observational studies to examine their association.

Methods

We conducted a review of the literature using electronic databases supplemented by a manual search to identify potentially relevant case-control or cohort studies. Summary relative risk (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Sensitivity and subgroup analyses were also conducted.

Results

Eleven studies (five case-control and six cohort) with a total of 3,513,209 participants and 21,011 PD cases were included. Statin use was associated with a lower risk of PD, with a summary RR of 0.81 (95% CI 0.71–0.92). Sensitivity analysis demonstrated the robustness of results. Subgroup analyses showed that neither study design nor study region significantly influenced the effect estimates. However, subgroup studies adjusted for age or sex had a greater inverse association than did unadjusted analyses (age-adjusted RR 0.75, 95% CI 0.60–0.95; age-unadjusted RR 0.86, 95% CI 0.75–0.99 and sex-adjusted RR 0.76, 95% CI 0.59–0.98; sex-unadjusted RR 0.85, 95% CI 0.79–0.92).

Conclusions

Results of this systematic review suggest that statin use is associated with a reduced PD risk. However, randomized controlled trials and more observational studies should be performed before strong conclusions are drawn.     

Insulin Glargine and Cancer Risk in Patients with Diabetes: A Meta-Analysis

Aim

The role of insulin glargine as a risk factor for cancer is controversial in human studies. The aim of this meta-analysis was to evaluate the relationship between insulin glargine and cancer incidence.

Methods

All observational studies and randomized controlled trials evaluating the relationship of insulin glargine and cancer risk were identified in PubMed, Embase, Web of Science, Cochrane Library and the Chinese Biomedical Medical Literature Database, through March 2012. Odds ratios (ORs) with corresponding 95% confidence interval (CI) were calculated with a random-effects model. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Results

A total of 11 studies including 448,928 study subjects and 19,128 cancer patients were finally identified for the meta-analysis. Insulin glargine use was associated with a lower odds of cancer compared with non-glargine insulin use (OR 0.81, 95% CI 0.68 to 0.98, P = 0.03; very low-quality evidence). Glargine did not increase the odds of breast cancer (OR 0.99, 95% CI 0.68 to 1.46, P = 0.966; very low-quality evidence). Compared with non-glargine insulin, no significant association was found between insulin glargine and prostate cancer, pancreatic cancer and respiratory tract cancer. Insulin glargine use was associated with lower odds of other site-specific cancer.

Conclusions

Results from the meta-analysis don''t support the link between insulin glargine and an increased risk of cancer and the confidence in the estimates of the effects is very low. Further studies are needed to examine the relation between insulin glargine and cancer risk, especially breast cancer.     

Statin Use Is Associated with Reduced Risk of Haematological Malignancies: Evidence from a Meta-Analysis

Background

Several observational studies have shown that statin use may modify the risk of haematological malignancies. To quantify the association between statin use and risk for haematological malignancies, we performed a detailed meta-analysis of published studies regarding this subject.

Methods

We conducted a systematic search of multiple databases including PubMed, Embase, and Cochrane Library Central database up to July 2013. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses and sensitivity analysis were also performed.

Results

A total of 20 eligible studies (ten case-control studies, four cohort studies, and six RCTs) reporting 1,139,584 subjects and 15,297 haematological malignancies cases were included. Meta-analysis showed that statin use was associated with a statistically significant 19% reduction in haematological malignancies incidence (RR = 0.81, 95% CI [0.70, 0.92]). During subgroup analyses, statin use was associated with a significantly reduced risk of haematological malignancies among observational studies (RR = 0.79, 95% CI [0.67, 0.93]), but not among RCTs (RR = 0.92, 95% CI [0.77, 1.09]).

Conclusions

Based on this comprehensive meta-analysis, statin use may have chemopreventive effects against haematological malignancies. More studies, especially definitive, randomized chemoprevention trials are needed to confirm this association.     

Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis

Objectives

Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and abdominal aortic aneurysm (AAA). We investigated this association between Hcy levels in patients with AAA and unaffected controls by conducting a meta-analysis and systematic review.

Methods

We conducted a systematic literature search (up to August 2013) of the PubMed database and Embase. We selected observational studies that evaluated Hcy levels in subjects with AAA compared to unaffected controls. Criteria for inclusion were the assessment of baseline Hcy and risk of AAA as an outcome. The results were presented as odd ratio (OR) and corresponding 95% confidence intervals (CI) comparing AAA patients to the control subjects.

Results

7 studies with 6,445 participants were identified and analyzed. Overall, elevated plasma Hcy was associated with an increased risk of AAA (3.29; 95% CI 1.66–6.51). The pooled adjusted OR from a random effect model of only men participants in the AAA compared with the control group was 2.36 (95% CI 0.63–8.82).

Conclusion

This meta-analysis and systematic review suggested that Hcy significantly increased the risk of AAA.     

Periodontal Therapy and Systemic Inflammation in Type 2 Diabetes Mellitus: A Meta-Analysis

Aim

The aim of this systematic review was to assess the effect of periodontal therapy (PT) on serum levels of inflammatory markers in people with type 2 diabetes mellitus (T2DM).

Methods of Study Selection

A literature search was carried out using MEDLINE via Pubmed, EMBASE, LILACS and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Randomized-controlled trials (RCTs) and controlled clinical trials (CCTs) evaluating the effect of PT on systemic inflammatory markers were deemed eligible. Case series (CS), reports and pilot trials were excluded. Study quality was assessed using the Cochrane Collaboration’s risk assessment tool. Meta-analysis was carried out using random effect methods.

Results

The search strategy identified 3,164 potential studies of which 61 were assessed for eligibility and 9 (6 RCTs and 3 CCTs) were included in this systematic review. Three RCTs were classified by the authors as being at low risk of bias and three were “unclear” and classified as uncertain risk of bias. All CCTs were considered to be at a high risk of bias. The meta-analysis showed a statistically significant mean difference (MD) for TNF- α (-1.33 pg/ml, 95% CI: -2.10; -0.56, p<0.001) and CRP (-1.28 mg/l, 95% CI: -2.07; - 0.48, p<0.001) favoring periodontal intervention versus control.

Conclusion

The results of this meta-analysis support the hypothesis that PT reduces serum levels of TNF- α and CRP in T2DM individuals. The decrease of inflammatory burden has important implications for metabolic control and can, in part, explain the mechanisms linking periodontitis and increased risk for complications in people with T2DM.     

TORC2:糖尿病治疗的新靶点

胰高血糖素等通过激活受体,使胞内cAMP浓度升高,激活异生或糖原分解与糖相关的基因,从而使血糖浓度升高。此过程由转录因子cAMP应答元件结合蛋白(CREB),在其他蛋白质尤其是TORC2辅助下完成的。TORC2磷酸化时处于细胞质,脱去磷酸而进入细胞核才能发挥与CREB的共激活效应。因此,抑制TORC2的脱磷酸或进入细胞核,可以实现减少肝脏中的糖生成,从而可望在糖尿病治疗中发挥作用。     

Hyperuricemia and Risk of Incident Hypertension: A Systematic Review and Meta-Analysis of Observational Studies

Background

Observational studies of the relationship between hyperuricemia and the incidence of hypertension are controversial. We conducted a systematic review and meta-analysis to assess the association and consistency between uric acid levels and the risk of hypertension development.

Methods

We searched MEDLINE, EMBASE, CBM (Chinese Biomedicine Database) through September 2013 and reference lists of retrieved studies to identify cohort studies and nested case-control studies with uric acid levels as exposure and incident hypertension as outcome variables. Two reviewers independently extracted data and assessed study quality using Newcastle-Ottawa Scale. Extracted information included study design, population, definition of hyperuricemia and hypertension, number of incident hypertension, effect sizes, and adjusted confounders. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) for the association between hyperuricemia and risk of hypertension were calculated using a random-effects model.

Results

We included 25 studies with 97,824 participants assessing the association between uric acid and incident hypertension in our meta-analysis. The quality of included studies is moderate to high. Random-effects meta-analysis showed that hyperuricemia was associated with a higher risk of incident hypertension, regardless of whether the effect size was adjusted or not, whether the data were categorical or continuous as 1 SD/1 mg/dl increase in uric acid level (unadjusted: RR = 1.73, 95% CI 1.46∼2.06 for categorical data, RR = 1.22, 95% CI 1.03∼1.45 for a 1 SD increase; adjusted: RR = 1.48, 95% CI 1.33∼1.65 for categorical data, RR = 1.15, 95% CI 1.06∼1.26 for a 1 mg/dl increase), and the risk is consistent in subgroup analyses and have a dose-response relationship.

Conclusions

Hyperuricemia may modestly increase the risk of hypertension incidence, consistent with a dose-response relationship.     

Gamma-Glutamyltransferase Level and Risk of Hypertension: A Systematic Review and Meta-Analysis

Background

Several prospective observational studies suggest that gamma-glutamyltransferase(GGT) level is positively associated with risk of hypertension. However, these studies draw inconsistent conclusions. Therefore, we conducted a systematic review and meta-analysis to evaluate the exact association between GGT level and subsequent development of hypertension.

Methods

We searched Pubmed, Embase, and Science Citation Index (ISI Web of Science) for prospective cohort studies examining the association between GGT level and hypertension. Then, pooled effect estimates (RRs) for the association between GGT level and hypertension were calculated.

Results

A total of 13 prospective cohort studies including 43314 participants and 5280 cases of hypertension were included. The pooled RR of hypertension was 1.94(95%CI: 1.55–2.43; P<0.001) when comparing the risk of hypertension between the highest versus lowest category of GGT levels. Moreover, the risk of hypertension increased by 23% (summary RR: 1.23; 95%CI: 1.13–1.32; P<0.001) per 1 SD logGGT increment. Subgroup analyses showed significant positive associations in each subgroup except in ≧160/95 subgroup (RR: 2.56, 95%CI: 0.87–7.54; P = 0.088) and nondrinkers subgroup (RR: 1.76, 95%CI: 0.88–3.53; P = 0.113). Sensitivity analyses showed no single study significantly affects the pooled RRs. No publication bias was found in our meta-analysis.

Conclusions

GGT level is positively associated with the development of hypertension. Further studies are needed to confirm our findings and elucidate the exact mechanisms between GGT level and the incidence of hypertension.     

Metabolic Syndrome Risk after Gestational Diabetes: A Systematic Review and Meta-Analysis

Background

A number of studies have been conducted to investigate the risk of metabolic syndrome (MS) after gestational diabetes mellitus (GDM), but the results are contradictory. Accordingly, we performed a systematic review and meta-analysis to assess the association between these two conditions. The aim was to better understand the risks of MS with prior gestational diabetes.

Methods

Pubmed, ISI Web of Science, and Cochrane databases from September 1, 1979 to July 11, 2013 were searched to identify relevant studies. 17 studies containing 5832 women and 1149 MS events were included. We calculated the odds ratio (OR) with 95% confidence interval (CI) in analysis for each study using a random-effect or fixed-effect model. We also determined heterogeneity among these 17 articles and their publication bias.

Results

Women with a history of gestational diabetes had a significantly higher risk of MS than those who had a normal pregnancy (OR, 3.96; 95% CI, 2.99 to 5.26), but had significant heterogeneity (I ² = 52.6%). The effect remained robust (OR, 4.54; 95% CI, 3.78–5.46) in the subgroup of Caucasians, but no association (OR, 1.28; 95% CI, 0.64–2.56) was found in Asians. Heterogeneity was reduced (body mass index (BMI) matched group I ² = 14.2%, BMI higher in the GDM group I ² = 13.2%) in the subgroup of BMI. In addition, mothers with higher BMI in the GDM group had higher risk of MS than those in the BMI matched group (BMI higher in GDM group OR, 5.39; 95% CI, 4.47–6.50, BMI matched group OR, 2.53; 95% CI, 1.88–3.41).

Conclusions

This meta-analysis demonstrated increased risk of MS after gestational diabetes. Therefore, attention should be given to preventing or delaying the onset of MS in GDM mothers, particularly in Caucasian and obese mothers.     

Diabetes Mellitus as a Risk Factor for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis

Objective

To determine the association between diabetes mellitus (DM) and primary open-angle glaucoma (POAG).

Methods

This is a systematic review and meta-analysis of case-control and cohort studies. The literature search included two databases (PubMed and Embase) and the reference lists of the retrieved studies. Separate meta-analyses for case-control studies and cohort studies were conducted using random-effects models, with results reported as adjusted odds ratios (ORs) and relative risks (RRs), respectively.

Results

Thirteen studies—seven case-control studies and six population-based cohort studies—were included in this meta-analysis. The pooled RR of the association between DM and POAG based on the risk estimates of the six cohort studies was 1.40 (95% CI, 1.25–1.57). The pooled OR of the association between DM and POAG based on the risk estimates of the seven case-control studies was 1.49 (95% CI, 1.17–1.88). There was considerable heterogeneity among the case-control studies that reported an association between DM mellitus and POAG (P<0.001) and no significant heterogeneity among the cohort studies (P = 0.377). After omitting the case-control study that contributed significantly to the heterogeneity, the pooled OR for the association between DM and POAG was 1.35 (95% CI, 1.06–1.74).

Conclusions

Individuals with DM have an increased risk of developing POAG.     

Diabetes Mellitus and Risk of Bladder Cancer: A Meta-Analysis of Cohort Studies

Background

Increasing evidence suggests that diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. To provide a quantitative assessment of this association, we evaluated the relation between DM and incidence and mortality of bladder cancer in an updated meta-analysis of cohort studies. Methods We identified cohort studies by searching the EMBASE and MEDLINE databases, through 31 March 2012. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random-effects models.

Results

A total of 29 cohort studies (27 articles) were included in this meta-analysis. DM was associated with an increased incidence of bladder cancer (RR 1.29, 95% CI: 1.08–1.54), with significant evidence of heterogeneity among these studies (p<0.001, I² = 94.9%). In stratified analysis, the RRs of bladder cancer were 1.36 (1.05–1.77) for diabetic men and 1.28 (0.75–2.19) for diabetic women, respectively. DM was also positively associated with bladder cancer mortality (RR 1.33, 95% CI: 1.14–1.55), with evident heterogeneity between studies (p = 0.002, I² = 63.3%). The positive association was observed for both men (RR 1.54, 95% CI: 1.30–1.82) and women (RR 1.50, 95% CI: 1.05–2.14).

Conclusion

These findings suggest that compared to non-diabetic individuals, diabetic individuals have an increased incidence and mortality of bladder cancer.     

Depression as a Risk Factor for Mortality in Individuals with Diabetes: A Meta-Analysis of Prospective Studies

Objective

To quantify the impact of depression measured by self-reports and depression measured by clinical interview on all-cause mortality in individuals with diabetes and to analyze the strength of both associations, the influence of covariates, and possible differences between studies assessing self-rated depressive symptoms and those using a clinical interview to measure depression as predictors of mortality.

Research Design and Methods

PUBMED and PsycINFO were searched up to July 2013 for prospective studies assessing depression, diabetes and mortality. The pooled hazard ratios were calculated using random-effects models.

Results

Sixteen studies met the inclusion criteria. After adjustment for demographic variables depression measured by self-reports was associated with an increased all-cause mortality risk (pooled HR = 2.56, 95% CI 1.89–3.47), and the mortality risk remained high after additional adjustment for diabetes complications (HR = 1.76, 95% CI 1.45–2.14,). Six studies reporting adjusted HRs for depression measured by clinical interviews supported the results of the other models (HR = 1.49, 95% CI 1.15–1.93).

Conclusions

Both depression measured by self-report and depression measured by clinical interview have an unfavorable impact on mortality in individuals with diabetes. The results, however, are limited by the heterogeneity of the primary studies. It remains unclear whether self-reports or clinical interviews for depression are the more precise predictor.     

Diabetes Mellitus and Risk of Bladder Cancer: A Meta-Analysis of Cohort Studies

Objective

Diabetes is associated with increased risk of cancer at several sites, but its association with risk of bladder cancer is still controversial. We examined this association by conducting a systematic review and meta-analysis of cohort studies.

Methods

Studies were identified by searching PubMed, EMBASE, Scopus, Web of Science, Cochrane register, and Chinese National Knowledge Infrastructure (CNKI) databases through April 29, 2012. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model.

Results

A total of fifteen cohort studies were included in this meta-analysis. Analysis of all studies showed that diabetes was associated with a borderline statistically significant increased risk of bladder cancer (RR 1.11, 95% CI 1.00–1.23; p<0.001 for heterogeneity; I² = 84%). When restricting the analysis to studies that had adjusted for cigarette smoking (n = 6) or more than three confounders (n = 7), the RRs were 1.32 (95% CI 1.18–1.49) and 1.20 (95% CI 1.02–1.42), respectively. There was no significant publication bias (p = 0.62 for Egger’s regression asymmetry test).

Conclusions

Our findings support that diabetes was associated with an increased risk of bladder cancer. More future studies are warranted to get a better understanding of the association and to provide convincing evidence for clinical practice in bladder cancer prevention.     

Statin Use and Risk of Lung Cancer: a Meta-Analysis of Observational Studies and Randomized Controlled Trials

Clinical studies have shown that statin use may alter the risk of lung cancer. However, these studies yielded different results. To quantify the association between statin use and risk of lung cancer, we performed a detailed meta-analysis. A literature search was carried out using MEDLINE, EMBASE and COCHRANE database between January 1966 and November 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to calculate the pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. A total of 20 (five randomized controlled trials, eight cohorts, and seven case–control) studies contributed to the analysis. Pooled results indicated a non-significant decrease of total lung cancer risk among all statin users (RR = 0.89, 95% CI [0.78, 1.02]). Further, long-term statin use did not significantly decrease the risk of total lung cancer (RR = 0.80, 95% CI [0.39 , 1.64]). In our subgroup analyses, the results were not substantially affected by study design, participant ethnicity, or confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of results. The findings of this meta-analysis suggested that there was no significant association between statin use and risk of lung cancer. More studies, especially randomized controlled trials and high quality cohort studies are warranted to confirm this association.     

Hematopoietically-Expressed Homeobox Gene Three Widely-Evaluated Polymorphisms and Risk for Diabetes: A Meta-Analysis

Background

The hematopoietically-expressed homeobox (HHEX) gene is identified as a promising candidate for type 2 diabetes by genome-wide association studies, triggering plenty of subsequent replications; however, the results are conflicting. We therefore conducted a meta-analysis of three widely-evaluated polymorphisms in HHEX gene and diabetes risk.

Methodology/Principal Findings

A random-effects model was adopted irrespective of heterogeneity. Data and study quality were assessed in duplicate. There were 49 studies (cases/controls: 57931/74658) for rs1111875, 18 studies (18227/30366) for rs5015480 and 26 studies (25725/30579) for rs7923837, respectively. Overall analyses indicated that rs1111875-C allele (odds ratio [OR] = 1.16; 95% confidence interval [CI]: 1.13–1.2; P<0.0005), rs5015480-C allele (OR = 1.16; 95% CI: 1.06–1.26; P = 0.001) and rs7923837-G allele (OR = 1.18; 95% CI: 1.12–1.24; P<0.0005) conferred significantly increased risk for type 2 diabetes, yet accompanying moderate to strong evidence of heterogeneity. Despite vast divergence in allele distributions, subgroup analyses by ethnicity showed comparable risk estimates between Asians and Caucasians for three examined polymorphisms. Moreover, results of studies with hospital-based controls deviated greatly from that of all qualified studies, especially for rs7923837-G allele carrying a doubled risk (OR = 1.37 versus 1.18). Furthermore, when only large studies (≥500 case-patients) were considered, risk effects were identical to the overall estimates for three examined polymorphisms. The Begg''s funnel plot and Egger''s test indicated low probability of publication bias.

Conclusions

Our results provide clarification to the significant association of rs1111875, rs5015480 and rs7923837 in HHEX gene with type 2 diabetes.     

Diabetes and the Risk of Multi-System Aging Phenotypes: A Systematic Review and Meta-Analysis

Background

Observational studies suggested an association between diabetes and the risk of various geriatric conditions (i.e., cognitive impairment, dementia, depression, mobility impairment, disability, falls, and urinary incontinence). However, the magnitude and impact of diabetes on older adults have not been reviewed.

Methodology/Principal Findings

MEDLINE and PSYCINFO databases were searched through November 2007 for published studies, supplemented by manual searches of bibliographies of key articles. Population-based, prospective cohort studies that reported risk of geriatric outcomes in relation to diabetes status at baseline were selected. Two authors independently extracted the data, including study population and follow-up duration, ascertainment of diabetes status at baseline, outcomes of interest and their ascertainment, adjusted covariates, measures of association, and brief results. Fifteen studies examined the association of DM with cognitive dysfunction. DM was associated with a faster decline in cognitive function among older adults. The pooled adjusted risk ratio (RR) for all dementia when persons with DM were compared to those without was 1.47 (95% CI, 1.25 to 1.73). Summary RRs for Alzheimer''s disease and vascular dementia comparing persons with DM to those without were 1.39 (CI, 1.16 to 1.66) and 2.38 (CI, 1.79 to 3.18), respectively. Four of 5 studies found significant association of DM with faster mobility decline and incident disability. Two studies examined the association of diabetes with falls in older women. Both found statistically significant associations. Insulin users had higher RR for recurrent falls. One study for urinary incontinence in older women found statistically significant associations. Two studies for depression did not suggest that DM was an independent predictor of incident depression.

Conclusions/Significance

Current evidence supports that DM is associated with increased risk for selected geriatric conditions. Clinicians should increase their awareness and provide appropriate care. Future research is required to elucidate the underlying pathological pathway.     

Diabetes Mellitus and Risk of Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00–1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00–1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44–1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13–1.49) and late AMD (OR, 1.16; 95% CI, 1.11–1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96–1.26), 1.48 (95% CI, 1.44–1.51), and 1.15 (95% CI, 1.11–1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association.