Pregnancy and postpartum dynamics revealed by an atlas of millions of lab tests

Bär, A.; Cohen, Netta Mendelson; Kohanim, Yael Korem; Mayo, Avi; Toledano, Yoel; Alon, Uri

doi:10.1101/2023.05.11.540359

Cited by 4 publications

(2 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To compare this to the model, we obtained data on the temporal dynamics of lymphocytes during pregnancy from the Clalit dataset on about 500,000 pregnancies. 49 This cross-sectional dataset includes 1.5 million lymphocyte counts averaged over each week of pregnancy and 80 weeks postpartum ( Figure 4 B). Mean lymphocyte counts decrease during pregnancy and increase after delivery, returning to baseline (pre-pregnancy) level after about 60 weeks.…”

Section: Resultsmentioning

confidence: 99%

Excitable dynamics of flares and relapses in autoimmune diseases

Lebel,

Milo,

Bar

et al. 2023

iScience

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Excitable dynamics of flares and relapses in autoimmune diseases

Lebel,

Milo,

Bar

et al. 2023

iScience

View full text Add to dashboard Cite

“…We analyzed glucose lab tests after delivery using an electronic medical record dataset from a large Israeli health service, Clalit (32,33) which includes 231260 glucose tests performed in the 20 months after delivery. Mean glucose drops below baseline after delivery by about 2%, a change that is accurately detected due to the large number of glucose tests in this dataset (Fig.…”

Section: Resultsmentioning

confidence: 99%

Quantification of beta cell carrying capacity in prediabetes

Woller,

Tamir,

Bar

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Prediabetes, a subclinical state of high glucose, carries a risk of transition to diabetes. One cause of prediabetes is insulin resistance, which impairs the ability of insulin to control blood glucose. However, many individuals with high insulin resistance retain normal glucose due to compensation by enhanced insulin secretion by beta cells. Individuals seem to differ in their maximum compensation level, termed beta cell carrying capacity, such that low carrying capacity is associated with a higher risk of prediabetes and diabetes. Carrying capacity has not been quantified using a mathematical model and cannot be estimated directly from measured glucose and insulin levels in patients, unlike insulin resistance and beta cell function which can be estimated using HOMA-IR and HOMA-B formula.Here we present a mathematical model of beta cell compensation and carrying capacity, and develop a new formula called HOMA-C to estimate it from glucose and insulin measurements. HOMA-C estimates the maximal potential beta cell function of an individual, rather than the current beta cell function. We test this approach using longitudinal cohorts of prediabetic people, finding 10-fold variation in carrying capacity. Low carrying capacity is associated with higher risk of transitioning to diabetes. We estimate the timescales of beta cell compensation and insulin resistance using large datasets, showing that, unlike previous mathematical models, the new model can explain the slow rise in glucose over decades. Our mathematical understanding of beta cell carrying capacity may help to assess the risk of prediabetes in each individual.

show abstract

Using PBPK modeling to supplement clinical data and support the safe and effective use of dolutegravir in pregnant and lactating women

Ning,

Pansari,

Rowland Yeo

et al. 2024

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

Optimal dosing in pregnant and lactating women requires an understanding of the pharmacokinetics in the mother, fetus, and breastfed infant. Physiologically‐based pharmacokinetic (PBPK) modeling can be used to simulate untested scenarios and hence supplement clinical data to support dosing decisions. A PBPK model for the antiretroviral dolutegravir (mainly metabolized by UGT1A1) was verified using reported exposures in non‐pregnant healthy volunteers, pregnant women, and the umbilical cord, lactating mothers, and breastfed neonates. The model was then applied to predict the impact of UGT1A1 phenotypes in extensive (EM), poor (PM), and ultra‐rapid metabolizers (UM). The predicted dolutegravir maternal plasma and umbilical cord AUC in UGT1A1 PMs was 1.6‐fold higher than in EMs. The predicted dolutegravir maternal plasma and umbilical cord AUC in UGT1A1 UMs mothers was 1.3‐fold lower than in EMs. The predicted mean systemic and umbilical vein concentrations were in excess of the dolutegravir IC90 at 17, 28, and 40 gestational weeks, regardless of UGT1A1 phenotype, indicating that the standard dose of dolutegravir (50 mg q.d., fed state) is generally appropriate in late pregnancy, across UGT1A1 phenotypes. Applying the model in breastfed infants, a 1.5‐, 1.7‐, and 2.2‐fold higher exposure in 2‐day‐old neonates, 10‐day‐old neonates, and infants who were UGT1A1 PMs, respectively, compared with EMs of the same age. However, it should be noted that the exposure in breastfed infants who were UGT1A1 PMs was still an order of magnitude lower than maternal exposure with a relative infant daily dose of <2%, suggesting safe use of dolutegravir in breastfeeding women.

show abstract

Pregnancy and postpartum dynamics revealed by an atlas of millions of lab tests

Cited by 4 publications

References 85 publications

Excitable dynamics of flares and relapses in autoimmune diseases

Excitable dynamics of flares and relapses in autoimmune diseases

Quantification of beta cell carrying capacity in prediabetes

Using PBPK modeling to supplement clinical data and support the safe and effective use of dolutegravir in pregnant and lactating women

Contact Info

Product

Resources

About