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Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes

Law GR, Gilthorpe MS, Secher AL, Temple R, Bilous R, Mathiesen ER, et al.

Diabetologia, 2017 04;60(4):618-624.
PMID: 28105519 DOI: 10.1007/s00125-017-4205-7

AIMS/HYPOTHESIS: This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA1clevels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA1c measurements are applicable to pregnant women with diabetes.
METHODS: CGM data from 117 pregnant women (89 women with type 1 diabetes; 28 women with type 2 diabetes) were analysed. Average glucose levels were calculated from 5-7 day CGM profiles (mean 1275 glucose values per profile) and paired with a corresponding (±1 week) HbA1c measure. In total, 688 average glucose-HbA1c pairs were obtained across pregnancy (mean six pairs per participant). Average glucose level was used as the dependent variable in a regression model. Covariates were gestational week, study centre and HbA1c.
RESULTS: There was a strong association between HbA1c and average glucose values in pregnancy (coefficient 0.67 [95% CI 0.57, 0.78]), i.e. a 1% (11 mmol/mol) difference in HbA1c corresponded to a 0.67 mmol/l difference in average glucose. The random effects model that included gestational week as a curvilinear (quadratic) covariate fitted best, allowing calculation of a pregnancy-specific eAG (PeAG). This showed that an HbA1c of 8.0% (64 mmol/mol) gave a PeAG of 7.4-7.7 mmol/l (depending on gestational week), compared with a standard eAG of 10.2 mmol/l. The PeAG associated with maintaining an HbA1c level of 6.0% (42 mmol/mol) during pregnancy was between 6.4 and 6.7 mmol/l, depending on gestational week.
CONCLUSIONS/INTERPRETATION: The HbA1c-average glucose relationship is altered by pregnancy. Routinely generated standard eAG values do not account for this difference between pregnant and non-pregnant individuals and, thus, should not be used during pregnancy. Instead, the PeAG values deduced in the current study are recommended for antenatal clinical care.
Fulltext The 'analysis of gene expression and biomarkers for point-of-care decision support in Sepsis' study; temporal clinical parameter analysis and validation of early diagnostic biomarker signatures for severe inflammation andsepsis-SIRS discrimination

Szakmany T, Fitzgerald E, Garlant HN, Whitehouse T, Molnar T, Shah S, et al.

Front Immunol, 2023;14:1308530.
PMID: 38332914 DOI: 10.3389/fimmu.2023.1308530

INTRODUCTION: Early diagnosis of sepsis and discrimination from SIRS is crucial for clinicians to provide appropriate care, management and treatment to critically ill patients. We describe identification of mRNA biomarkers from peripheral blood leukocytes, able to identify severe, systemic inflammation (irrespective of origin) and differentiate Sepsis from SIRS, in adult patients within a multi-center clinical study.
METHODS: Participants were recruited in Intensive Care Units (ICUs) from multiple UK hospitals, including fifty-nine patients with abdominal sepsis, eighty-four patients with pulmonary sepsis, forty-two SIRS patients with Out-of-Hospital Cardiac Arrest (OOHCA), sampled at four time points, in addition to thirty healthy control donors. Multiple clinical parameters were measured, including SOFA score, with many differences observed between SIRS and sepsis groups. Differential gene expression analyses were performed using microarray hybridization and data analyzed using a combination of parametric and non-parametric statistical tools.
RESULTS: Nineteen high-performance, differentially expressed mRNA biomarkers were identified between control and combined SIRS/Sepsis groups (FC>20.0, p<0.05), termed 'indicators of inflammation' (I°I), including CD177, FAM20A and OLAH. Best-performing minimal signatures e.g. FAM20A/OLAH showed good accuracy for determination of severe, systemic inflammation (AUC>0.99). Twenty entities, termed 'SIRS or Sepsis' (S°S) biomarkers, were differentially expressed between sepsis and SIRS (FC>2·0, p-value<0.05).
DISCUSSION: The best performing signature for discriminating sepsis from SIRS was CMTM5/CETP/PLA2G7/MIA/MPP3 (AUC=0.9758). The I°I and S°S signatures performed variably in other independent gene expression datasets, this may be due to technical variation in the study/assay platform.
Global status and conservation potential of reef sharks

MacNeil MA, Chapman DD, Heupel M, Simpfendorfer CA, Heithaus M, Meekan M, et al.

Nature, 2020 07;583(7818):801-806.
PMID: 32699418 DOI: 10.1038/s41586-020-2519-y

Decades of overexploitation have devastated shark populations, leaving considerable doubt as to their ecological status1,2. Yet much of what is known about sharks has been inferred from catch records in industrial fisheries, whereas far less information is available about sharks that live in coastal habitats3. Here we address this knowledge gap using data from more than 15,000 standardized baited remote underwater video stations that were deployed on 371 reefs in 58 nations to estimate the conservation status of reef sharks globally. Our results reveal the profound impact that fishing has had on reef shark populations: we observed no sharks on almost 20% of the surveyed reefs. Reef sharks were almost completely absent from reefs in several nations, and shark depletion was strongly related to socio-economic conditions such as the size and proximity of the nearest market, poor governance and the density of the human population. However, opportunities for the conservation of reef sharks remain: shark sanctuaries, closed areas, catch limits and an absence of gillnets and longlines were associated with a substantially higher relative abundance of reef sharks. These results reveal several policy pathways for the restoration and management of reef shark populations, from direct top-down management of fishing to indirect improvement of governance conditions. Reef shark populations will only have a high chance of recovery by engaging key socio-economic aspects of tropical fisheries.
Author Correction: Global status and conservation potential of reef sharks

MacNeil MA, Chapman DD, Heupel M, Simpfendorfer CA, Heithaus M, Meekan M, et al.

Nature, 2020 09;585(7825):E11.
PMID: 32848253 DOI: 10.1038/s41586-020-2692-z

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
Widespread diversity deficits of coral reef sharks and rays

Simpfendorfer CA, Heithaus MR, Heupel MR, MacNeil MA, Meekan M, Harvey E, et al.

Science, 2023 Jun 16;380(6650):1155-1160.
PMID: 37319199 DOI: 10.1126/science.ade4884

A global survey of coral reefs reveals that overfishing is driving resident shark species toward extinction, causing diversity deficits in reef elasmobranch (shark and ray) assemblages. Our species-level analysis revealed global declines of 60 to 73% for five common resident reef shark species and that individual shark species were not detected at 34 to 47% of surveyed reefs. As reefs become more shark-depleted, rays begin to dominate assemblages. Shark-dominated assemblages persist in wealthy nations with strong governance and in highly protected areas, whereas poverty, weak governance, and a lack of shark management are associated with depauperate assemblages mainly composed of rays. Without action to address these diversity deficits, loss of ecological function and ecosystem services will increasingly affect human communities.