Plasminogen activator inhibitor-1 and type 2 diabetes: a systematic review and meta-analysis of observational studies

An emerging body of evidence has implicated plasminogen activator inhibitor-1 (PAI-1) in the development of type 2 diabetes (T2D), though findings have not always been consistent. We systematically reviewed epidemiological studies examining the association of PAI-1 with T2D. EMBASE, PubMed, Web of Science, and the Cochrane Library were searched to identify studies for inclusion. Fifty-two studies (44 cross-sectional with 47 unique analytical comparisons and 8 prospective) were included. In pooled random-effects analyses of prospective studies, a comparison of the top third vs. bottom third of baseline PAI-1 values generated a RR of T2D of 1.67 (95% CI 1.28-2.18) with moderate heterogeneity (I-2 = 38%). Additionally, of 47 cross-sectional comparisons, 34(72%) reported significantly elevated PAI-1 among diabetes cases versus controls, 2(4%) reported significantly elevated PAI-1 among controls, and 11(24%) reported null effects. Results from pooled analyses of prospective studies did not differ substantially by study design, length of follow-up, adjustment for various putative confounding factors, or study quality, and were robust to sensitivity analyses. Findings from this systematic review of the available epidemiological literature support a link between PAI-1 and T2D, independent of established diabetes risk factors. Given the moderate size of the association and heterogeneity across studies, future prospective studies are warranted

Idade no primeiro parto e diabetes recentemente diagnosticada em mulheres pós-menopáusicas : uma análise transversal do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil)

CONTEXT AND OBJECTIVE: It has been reported that earlier age at first childbirth may increase the risk of adult-onset diabetes among postmenopausal women, a novel finding with important public health implications. To date, however, no known studies have attempted to replicate this finding. We aimed to test the hypothesis that age at first childbirth is associated with the risk of adult-onset diabetes among postmenopausal women. DESIGN AND SETTING: Cross-sectional analysis using baseline data from 2919 middle-aged and elderly postmenopausal women in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: Age at first childbirth was determined from self-reporting and newly diagnosed diabetes through a 2-hour 75-g oral glucose tolerance test and/or glycated hemoglobin. Logistic regression was performed to examine associations between age at first childbirth and newly diagnosed diabetes among postmenopausal women. RESULTS: We did not find any association between age at first childbirth and diabetes, either when minimally adjusted for age, race and study center (odds ratio, OR [95% confidence interval, CI]: ≤ 19 years: 1.15 [0.82-1.59], 20-24 years: 0.90 [0.66-1.23] and ≥ 30 years: 0.86 [0.63-1.17] versus 25-29 years; P = 0.36) or when fully adjusted for childhood and adult factors (OR [95% CI]: ≤ 19 years: 0.95 [0.67-1.34], 20-24 years: 0.78 [0.56-1.07] and ≥ 30 years: 0.84 [0.61-1.16] versus 25-29 years; P = 0.40). CONCLUSION: Our current analysis does not support the existence of an association between age at first childbirth and adult-onset diabetes among postmenopausal women, which had been reported previously.CONTEXTO E OBJETIVO: Foi relatado que idade mais precoce no primeiro parto pode aumentar o risco do diabetes de início adulto entre mulheres na menopausa, um novo achado com implicações de saúde pública importantes. Até então, no entanto, nenhum estudo conhecido tentou replicar esta descoberta. Objetivou-se testar a hipótese de que a idade no primeiro parto está associada ao risco de diabetes de início na vida adulta em mulheres pós-menopáusicas. DESENHO DE ESTUDO E LOCAL: Análise transversal utilizando dados de base de 2.919 mulheres pós-menopáusicas de meia-idade e idosas no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). MÉTODOS: A idade no primeiro parto foi determinada por autorrelato e diabetes recentemente diagnosticado por um teste de tolerância à glicose oral de 2 horas com 75 g e/ou hemoglobina glicada. A regressão logística foi realizada para examinar associações entre idade no primeiro parto e diabetes recentemente diagnosticada entre mulheres pós-menopáusicas. RESULTADOS: Não encontramos associação entre idade no primeiro parto e diabetes, quando ajustados minimamente para idade, raça e centro de estudo (odds ratio, OR [intervalo de confiança, IC 95%]: ≤ 19 anos: 1,15 [0,82-1,59], 20-24 anos: 0,90 [0,66-1,23], ≥ 30 anos: 0,86 [0,63-1,17] versus 25-29 anos, P = 0,36) ou quando totalmente ajustados para fatores infantis e adultos (OR [IC 95%]: ≤ 19 anos: 0,95 [0,67-1,34], 20-24 anos: 0,78 [0,56-1,07], ≥ 30 anos: 0,84 [0,61-1,16] versus 25-29 anos, P = 0,40). CONCLUSÃO: Nossa análise atual não apoia uma associação entre a idade no primeiro parto e o diabetes de início na vida adulta entre mulheres pós-menopáusicas, como relatado anteriormente

Circulating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis.

In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 μg/L increase in circulating selenium) did not lower overall prostate cancer risk, but increased risk of high-grade prostate cancer and type 2 diabetes. Mendelian randomization analysis uses genetic variants to proxy modifiable risk factors and can strengthen causal inference in observational studies. We constructed a genetic instrument comprising 11 single nucleotide polymorphisms robustly (P < 5 × 10-8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72 729 men in the PRACTICAL Consortium (44 825 case subjects, 27 904 control subjects), 114 μg/L higher genetically elevated circulating selenium was not associated with prostate cancer (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.89 to 1.13). In concordance with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR = 1.21, 95% CI = 0.98 to 1.49) and type 2 diabetes (OR = 1.18, 95% CI = 0.97 to 1.43; in a type 2 diabetes genome-wide association study meta-analysis with up to 49 266 case subjects and 249 906 control subjects). Our Mendelian randomization analyses do not support a role for selenium supplementation in prostate cancer prevention and suggest that supplementation could have adverse effects on risks of advanced prostate cancer and type 2 diabetes

Investigating the transparency of reporting in two-sample summary data Mendelian randomization studies using the MR-Base platform.

BACKGROUND Two-sample Mendelian randomization (2SMR) is an increasingly popular epidemiological method that uses genetic variants as instruments for making causal inferences. Clear reporting of methods employed in such studies is important for evaluating their underlying quality. However, the quality of methodological reporting of 2SMR studies is currently unclear. We aimed to assess the reporting quality of studies that used MR-Base, one of the most popular platforms for implementing 2SMR analysis. METHODS We created a bespoke reporting checklist to evaluate reporting quality of 2SMR studies. We then searched Web of Science Core Collection, PsycInfo, MEDLINE, EMBASE and Google Scholar citations of the MR-Base descriptor paper to identify published MR studies that used MR-Base for any component of the MR analysis. Study screening and data extraction were performed by at least two independent reviewers. RESULTS In the primary analysis, 87 studies were included. Reporting quality was generally poor across studies, with a mean of 53% (SD = 14%) of items reported in each study. Many items required for evaluating the validity of key assumptions made in MR were poorly reported: only 44% of studies provided sufficient details for assessing if the genetic variant associates with the exposure ('relevance' assumption), 31% for assessing if there are any variant-outcome confounders ('independence' assumption), 89% for the assessing if the variant causes the outcome independently of the exposure ('exclusion restriction' assumption) and 32% for assumptions of falsification tests. We did not find evidence of a change in reporting quality over time or a difference in reporting quality between studies that used MR-Base and a random sample of MR studies that did not use this platform. CONCLUSIONS The quality of reporting of two-sample Mendelian randomization studies in our sample was generally poor. Journals and researchers should consider using the STROBE-MR guidelines to improve reporting quality