Physiological subtypes of gestational glucose intolerance and risk of adverse pregnancy outcomes

Selen, Daryl J.; Edelson, P. Kaitlyn; James, Kaitlyn; Corelli, Kathryn; Hivert, Marie‐France; Meigs, James B.; Thadhani, Ravi; Ecker, Jeffrey L.; Powe, Camille E.

doi:10.1016/j.ajog.2021.08.016

Cited by 13 publications

(8 citation statements)

References 46 publications

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“…It was surprising to see such lower rates of LGA in the GDM‐resistance group; however, rates of any adverse outcomes including C‐section and neonatal hypoglycaemia were highest in the GDM‐mix group (63.3%), followed by the GDM‐insulin resistant group (54.3%), and the authors surmised that this could be due to small sample size. More recently, a US‐based hospital cohort study examined gestational glucose intolerance based on the presence of insulin resistance, deficiency, or mixed pathophysiology based on homeostasis model assessment of fasting glucose and insulin levels between 16 and 20 weeks gestation, and consistent with our findings, found insulin‐resistant women had a higher BMI with excess insulin production, decreased insulin sensitivity, and highest rates of LGA infants, NICU admissions, and pregnancy‐related hypertension 27 …”

Section: Discussionsupporting

confidence: 84%

“…More recently, a US-based hospital cohort study examined gestational glucose intolerance based on the presence of insulin resistance, deficiency, or mixed pathophysiology based on homeostasis model assessment of fasting glucose and insulin levels between 16 and 20 weeks gestation, and consistent with our findings, found insulin-resistant women had a higher BMI with excess insulin production, decreased insulin sensitivity, and highest rates of LGA infants, NICU admissions, and pregnancy-related hypertension. 27 Limitations to our data include its observational nature, limiting causal inference. The Alberta Pregnancy Birth cohort was lacking BMI data, but this was addressed in the well-characterized biochemical cohort.…”

Section: Discussionmentioning

confidence: 99%

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Gestational diabetes: One size does not fit all—an observational study of maternal and neonatal outcomes by maternal glucose profile

Yeung,

Retnakaran,

Savu

et al. 2023

Diabet Med

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ObjectivesTo examine obstetrical and neonatal outcomes across maternal glucose profiles at the population‐level and to explore insulin sensitivity and beta‐cell function across profiles in an independent, well‐phenotyped cohort for potential pathophysiologic explanation.Research Design and MethodsObservational cohort study of all pregnancies with gestational diabetes screening between Oct 2008– Dec 2018 resulting in live singleton birth in Alberta, Canada (n= 436,773) were categorized into 7 maternal glucose profiles: 1) normal 50g‐glucose challenge test (nGCT) 2) normal 75‐g OGTT (nOGTT) 3) isolated elevated 1h post‐load glucose (ePLPG1) 4) isolated elevated 2h post‐load glucose (ePLPG2), 5) elevated 1 and 2 hr post‐load glucose (ePLPG12) 6) isolated elevated FPG (eFPG), and 7) elevated FPG + elevated 1‐h and/or 2‐h PLG (Combined). Primary outcomes were large‐for‐gestational‐age (LGA) and neonatal intensive care unit (NICU) admission rates. An independent observational cohort of 1451 females was examined for measures of beta cell function (ISSI‐2, insulinogenic index/HOMA‐IR) and insulin sensitivity/resistance (Matsuda index, HOMA‐IR) by similar maternal glucose profiles.ResultsPregnancies with elevated FPG, either isolated or combined, had higher adverse events and lower insulin sensitivity. The combination of elevated FPG +elevated 1‐h and/or 2‐h PLG had the highest rates of LGA(20.9%), NICU admissions(14.7%), and lowest insulin sensitivity as measured by Matsuda index and HOMA‐IR, and beta cell function as measured by ISSI‐2 and Insulinogenic index/HOMA‐IR.ConclusionsElevated fasting plasma glucose, either alone or combined with post‐load glucose elevation is associated with worse outcomes than isolated post‐load glucose elevation, possibly due to higher degrees of insulin resistance. Future work is needed to better understand these differences, and explore whether tailored treatment of GDM can improve neonatal outcomes.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Gestational diabetes: One size does not fit all—an observational study of maternal and neonatal outcomes by maternal glucose profile

Yeung,

Retnakaran,

Savu

et al. 2023

Diabet Med

View full text Add to dashboard Cite

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“…In contrast, obese GDM is associated with continuing insulin resistance and hyperinsulinemia [ 39 ]. Recently, Selen et al showed that of women diagnosed with gestational glucose intolerance, 48% were insulin resistant, 27% were insulin deficient and 17% were both insulin resistant and insulin deficient [ 49 ]. These studies in women highlight the spectrum of GDM pathophysiology and the utility of our non-obese mouse model with both insulin resistance and insulin deficiency.…”

Section: Discussionmentioning

confidence: 99%

A novel model of gestational diabetes: Acute high fat high sugar diet results in insulin resistance and beta cell dysfunction during pregnancy in mice

Mishra

Ruano²,

Saha³

et al. 2022

PLoS ONE

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Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic hyperinsulinemic clamp experiments were performed on day 13.5 of pregnancy to assess insulin resistance. Beta cell function was assessed by glucose stimulated insulin secretion (GSIS) assay performed on day 0, 13.5 and 17.5 of pregnancy. At day 0, insulin tolerance and beta cell numbers were not different. At day 13.5, glucose infusion and disposal rates were significantly decreased (p<0.05) in Pregnant (P) HFHS animals (p<0.05) suggesting development of insulin resistance in P HFHS dams. Placental and fetal glucose uptake was significantly increased (p<0.01) in P HFHS dams at day 13.5 of pregnancy and by day 17.5 of pregnancy fetal weights were increased (p<0.05) in P HFHS dams compared to P CD dams. Basal and secreted insulin levels were increased in HFHS fed females at day 0, however at day 13.5 and 17.5 GSIS was decreased (p<0.05) in P HFHS dams. In conclusion, this animal model results in insulin resistance and beta cell dysfunction by mid-pregnancy further validating its relevance in studying the pathophysiology GDM.

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“…It has been reported gestational glucose intolerance can be classified into two subgroups as insulin resistant group and insulin sensitive group, which are at differential risk for adverse outcomes [ 28 ]. Similarly, from our research, it can be postulated that preeclampsia may be stratified into two subgroups: normal blood lipid group and dyslipidemia group.…”

Section: Discussionmentioning

confidence: 99%

Elevated mid-trimester 4-h postprandial triglycerides for predicting late-onset preeclampsia: a prospective screening study

et al. 2022

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Background Abnormal maternal lipid concentrations are associated with increased risk of preeclampsia. However, previous studies mainly focused on fasting lipid concentrations, scarce data have been published on the relationship between postprandial triglyceride (TG) concentrations in the second trimester and the risk of preeclampsia. Our aim is to evaluate the potential of triglyceride (TG) concentrations at the time of oral lipid tolerance test (OLTT) measurement in the second trimester to predict preeclampsia and to elucidate the lipid metabolic changes related to these diseases. Methods This is a prospective cohort study of Pregnant women at 12–24 weeks of gestation undergone an OLTT in a university affiliated hospital between May 2019 and January 2020. Data were stratified into binaries according to the OLTT results. The receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off points of TG, HDL-C, LDL-C, sd-LDL, FFA, and BG for predicting preeclampsia. Results 438 pregnant women were recruited to undergo an OLTT at 12–24 weeks of gestation. Among these, 24 women developed preeclampsia and 414 women remained normotensive. Women who subsequently developed preeclampsia had higher concentrations of 4-h postprandial TG than those who remained normotensive. In the linear logistic regression analyses of potential confounding factors, mid-trimester 4-h postprandial TG concentrations at the time of OLTT measurement were significantly higher in preeclamptic cases than in controls. Conclusions Dyslipidemia in the second trimester of pregnancy, particularly postprandial hypertriglyceridemia, appears to be associated with an increased risk of preeclampsia. Mid-trimester 4-h postprandial TG concentration at the time of OLTT measurement may be a potential predictive marker of preeclampsia. Trial registration Data of registration: 2018/10/15. Date of initial participant enrollment: 2019/05/01. Clinical trial identification number: chiCTR1800018884. URL of the registration site: http://www.chictr.org.cn/showproj.aspx?proj=25526. Data sharing information: The data including individual participant data, detailed study protocols, statistical analysis plans will be shared upon request to the corresponding author.

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Physiological subtypes of gestational glucose intolerance and risk of adverse pregnancy outcomes

Cited by 13 publications

References 46 publications

Gestational diabetes: One size does not fit all—an observational study of maternal and neonatal outcomes by maternal glucose profile

Gestational diabetes: One size does not fit all—an observational study of maternal and neonatal outcomes by maternal glucose profile

A novel model of gestational diabetes: Acute high fat high sugar diet results in insulin resistance and beta cell dysfunction during pregnancy in mice

Elevated mid-trimester 4-h postprandial triglycerides for predicting late-onset preeclampsia: a prospective screening study

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