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Cited by 311Gestational Diabetes Research and ManagementBirth, Development, and HealthPancreatic function and diabetes

Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism

Open access
Scholtens, Denise M., Kuang, Alan, Lowe, Lynn P., Hamilton, Jill, Lawrence, Jean M., Lebenthal, Yael, Brickman, Wendy J., Clayton, Peter +83 more·2019·Diabetes Care
DOI 10.2337/dc18-2021PMC PMC6385697
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Abstract

OBJECTIVE: This study examined associations of maternal glycemia during pregnancy with childhood glucose outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. RESEARCH DESIGN AND METHODS: HAPO was an observational international investigation that established associations of maternal glucose with adverse perinatal outcomes. The HAPO Follow-up Study included 4,832 children ages 10–14 years whose mothers had a 75-g oral glucose tolerance test (OGTT) at ∼28 weeks of gestation. Of these, 4,160 children were evaluated for glucose outcomes. Primary outcomes were child impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Additional outcomes were glucose-related measures using plasma glucose (PG), A1C, and C-peptide from the child OGTT. RESULTS: Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1C; maternal 1-h and 2-h PG were positively associated with child fasting, 30 min, 1-h, and 2-h PG, and A1C. Maternal FPG, 1-h, and 2-h PG were inversely associated with insulin sensitivity, whereas 1-h and 2-h PG were inversely associated with disposition index. Maternal FPG, but not 1-h or 2-h PG, was associated with child IFG, and maternal 1-h and 2-h PG, but not FPG, were associated with child IGT. All associations were independent of maternal and child BMI. Across increasing categories of maternal glucose, frequencies of child IFG and IGT, and timed PG measures and A1C were higher, whereas insulin sensitivity and disposition index decreased. CONCLUSIONS: Across the maternal glucose spectrum, exposure to higher levels in utero is significantly associated with childhood glucose and insulin resistance independent of maternal and childhood BMI and family history of diabetes.

Integrity signals

Registry

Crossref · 10.2337/dc18-2021

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 23 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Maternal 1-h plasma glucose during pregnancy is positively associated with child fasting plasma glucose.

    “Maternal 1-h and 2-h PG were positively associated with child fasting, 30 min, 1-h, and 2-h PG, and A1C.”
    • Also stated in: § Associations Between Continuous Maternal Glycemia and Continuous Child Glucose Outcomes · plain
      “Maternal 1-h and 2-h PG during the pregnancy OGTT and maternal sum of glucose z scores were positively associated with all child glucose measures and A1C in all models”
    Quote in the paperSubstantial claim
  • Findingown data

    Maternal fasting plasma glucose during pregnancy is positively associated with child A1C.

    “Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1C”
    • Also stated in: § Associations Between Continuous Maternal Glycemia and Continuous Child Glucose Outcomes · plain
      “Maternal FPG was positively associated with child FPG, 30-min PG, the sum of glucose z scores, and A1C.”
    Quote in the paperSubstantial claim
  • Findingown data

    Maternal sum of glucose z scores was inversely associated with the child insulinogenic index only after adjustment for maternal BMI alone or together with child BMI z score in models 2 and 4.

    “Maternal sum of glucose z scores was inversely associated with child insulinogenic index only after adjusting for maternal BMI alone or together with child BMI z score (models 2 and 4).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Interaction terms between maternal glucose levels and Tanner stage were not statistically significant.

    “Although interaction terms between maternal glucose levels and Tanner stage were not statistically significant”
    Quote in the paperNot a substantial claim
  • Findingown data

    Maternal 2-h plasma glucose during pregnancy is inversely associated with child disposition index.

    “Maternal FPG, 1-h, and 2-h PG were inversely associated with insulin sensitivity, whereas 1-h and 2-h PG were inversely associated with disposition index.”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • Classified as probably not a substantial claim. 19

  • May combine two claims.

    Findingown data

    Adjustment for maternal BMI or child BMI z score weakened the associations between maternal glucose measures and child Matsuda index, but those associations remained statistically significant.

    “Adjusting for maternal BMI or child BMI z score in models 2–4 attenuated associations with the Matsuda index, but all associations remained significant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neither maternal 1-h nor 2-h plasma glucose was associated with child IFG.

    “Neither maternal 1-h nor 2-h PG was associated with child IFG.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Exploratory analyses within Tanner stage suggested that some associations may be strongest after the onset of puberty.

    “exploratory analyses within the Tanner stage suggested some associations may be strongest after onset of puberty (Supplementary Table 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the HAPO FUS cohort, higher continuous maternal fasting, 1-h, and 2-h plasma glucose and higher sum of glucose z scores during pregnancy were each associated with a lower child Matsuda index, indicating greater child insulin resistance.

    “Regarding child insulin resistance, continuous maternal FPG, 1-h and 2-h PG, and the sum of glucose z scores were inversely associated with child Matsuda index (i.e., associated with greater insulin resistance) (Table 1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Exploratory analyses within Tanner stage suggested that associations with IGT may be strongest after the onset of puberty.

    “but exploratory analyses within Tanner stage again suggested associations may be strongest for IGT after onset of puberty (Supplementary Table 4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Maternal fasting plasma glucose and the sum of glucose z scores during pregnancy were associated with child IFG.

    “Maternal FPG and maternal sum of glucose z scores during pregnancy were associated with child IFG.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Mothers of children who participated and those who did not had mean ages and gestational diabetes frequencies of 30.0 years and 14.9% versus 29.1 years and 16.9%, respectively.

    “The mean age and frequency of GDM were 30.0 years and 14.9% and 29.1 years and 16.9% in mothers of children who did and did not participate, respectively.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted).

    Findingown data

    Maternal fasting plasma glucose during pregnancy is not associated with child impaired glucose tolerance.

    “Maternal FPG, but not 1-h or 2-h PG, was associated with child IFG, and maternal 1-h and 2-h PG, but not FPG, were associated with child IGT.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mean BMI, fasting plasma glucose, 1-h, and 2-h plasma glucose during the HAPO OGTT and race/ethnicity were similar between participants and nonparticipants.

    “Mean BMI, FPG, 1-h, and 2-h PG during the HAPO OGTT and race/ethnicity were similar between groups.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Adjustment for maternal BMI and/or child BMI z score did not weaken associations of maternal glucose with child glucose outcomes, except for insulin sensitivity, which remained significant after adjustment.

    “However, adjustment for maternal BMI and/or child BMI z score did not attenuate associations of maternal glucose levels with child glucose outcomes, except for insulin sensitivity, although this association also remained significant after adjustment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Class C comprised 3.2% (132 of 4,160) of HAPO OGTTs and was characterized by high 1-h plasma glucose and a marked decline at 2 h.

    “Class C included 3.2% (132 of 4,160) of HAPO OGTTs with high 1-h PG and marked decline at 2-h.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Trajectory analyses indicated that the best-fitting model used quadratic trajectories adjusted for maternal BMI at the OGTT and estimated three latent classes.

    “Analyses indicated best fit of quadratic trajectories adjusted for maternal BMI at OGTT with three estimated latent classes (Fig. 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Class B comprised 9.0% (376 of 4,160) of HAPO OGTTs and was characterized by high 1-h and 2-h plasma glucose values.

    “A second class, class B, included 9.0% (376 of 4,160) of HAPO OGTTs with high 1-h and 2-h PG values.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The current study demonstrates that maternal glucose levels during pregnancy across the spectrum are associated with higher glucose levels and insulin resistance during childhood independent of maternal and child BMI and family history of diabetes, and that this relationship is continuous.

    “In summary, the current study demonstrates that maternal glucose levels during pregnancy across the spectrum are associated with higher glucose levels and insulin resistance during childhood independent of maternal and child BMI and family history of diabetes and that this relationship is continuous.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Maternal fasting plasma glucose and the sum of glucose z scores during the pregnancy OGTT had a positive relationship with child fasting plasma glucose and IFG.

    “This included a positive relationship of maternal FPG and the sum of glucose z scores during the pregnancy OGTT with child FPG and IFG”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The frequency of child IGT was higher across increasing categories of maternal glucose, consistent with linear associations confirmed in logistic regression models.

    “The frequency of child IGT was higher across increasing categories of maternal glucose, consistent with the linear associations confirmed in logistic regression models (Fig. 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For maternal 2-h plasma glucose, the middle three categories differed significantly from the lowest reference category with similar odds ratios for child IFG.

    “For maternal 2-h PG, the middle three categories were significantly different from the lowest reference category with similar odds ratios (ORs).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A prior HAPO FUS analysis demonstrated an inverse association of gestational diabetes by IADPSG criteria with insulin sensitivity and disposition index and a positive association with impaired glucose tolerance in children ages 10-14 years.

    “We recently demonstrated an inverse association of GDM, using IADPSG criteria, with insulin sensitivity and the disposition index and positive association with impaired glucose tolerance (IGT) in HAPO FUS children at ages 10–14 years (11).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Lowe, 2019, HAPO Follow-up Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): maternal gestational diabetes mellitus and childhood glucose metabolism, Diabetes Care source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The recruitment target was 7,000 mother-child pairs, based on the primary childhood outcome of overweight/obesity.

    “The recruitment target was 7,000 pairs, based on the primary childhood outcome of overweight/obesity (14).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Lowe, 2018, Association of gestational diabetes with maternal disorders of glucose metabolism and childhood adiposity, JAMA source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Colinearity was not a concern, with pairwise correlations ranging from 0 to 0.20 for model covariates.

    “Colinearity was not a concern, with pairwise correlations ranging from 0 to 0.20 for model covariates.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Hosmer-Lemeshow P values ranged 0.53-0.96 for all outcomes, indicating reasonable model fit.

    “Hosmer-Lemeshow P values for logistic regression models ranged 0.53–0.96 for all outcomes, indicating reasonable model fit.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    DFBETA statistics indicated no observations of undue influence.

    “DFBETA statistics indicated no observations of undue influence.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Mean coefficients of variation for C-peptide measurements ranged from 2.8% to 3.2%.

    “Mean CVs were 2.8% for fasting, 2.9% for 30-min, 3.0% for 1-h, and 3.2% for 2-h C-peptide.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Residual plots indicated reasonable linearity, and P values for quadratic terms and restricted cubic splines ranged 0.05-0.99, indicating no significant departure from linearity.

    “Residual plots indicated reasonable linearity. Confirming this, P values for quadratic terms and restricted cubic splines ranged 0.05–0.99, indicating no significant departure from linearity for all analyses.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Blinded participants were untreated.

    “Blinded participants were untreated.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Blinded duplicate samples were assayed several weeks apart.

    “Blinded duplicate samples were assayed several weeks apart.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    HAPO OGTT results were blinded to caregivers and participants except under specified criteria.

    “OGTT results remained blinded to caregivers and participants unless FPG >5.8 mmol/L and/or 2-h PG >11.1 mmol/L, either was <2.5 mmol/L, or random PG at 34–37 weeks of gestation was ≥8.9 mmol/L (12).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Metzger, 2008, Hyperglycemia and adverse pregnancy outcomes, N Engl J Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    C statistics for logistic regression models ranged 0.69-0.78, and R2 values ranged 0.05-0.39 for linear models.

    “C statistics for logistic regression models ranged 0.69–0.78, and R2 values ranged 0.05–0.39 for linear models.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Mean coefficients of variation for glucose and A1C measurements were low: 1.5% for fasting, 1-h, and 2-h plasma glucose, 1.3% for 30-min plasma glucose, and 3.1% for A1C.

    “mean CV was 1.5% for fasting, 1-h, and 2-h PG, 1.3% for 30-min PG, and 3.1% for A1C.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study was not powered to evaluate Tanner stage-specific associations.

    “Although the study was not powered to evaluate Tanner stage–specific associations, interaction terms between maternal glucose measures and Tanner stage were evaluated to explore potential variability in associations according to pubertal status.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    427 participants (1.8%) had OGTT results unblinded based on fasting and/or 2-h plasma glucose.

    “Using these criteria, the results of 427 participants (1.8%) were unblinded based on FPG and/or 2-h PG.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The long-term type 2 diabetes risk associated with a pattern similar to class C and the risk for child IGT with high 1-h plasma glucose observed in the current study demonstrate the importance of maternal 1-h glucose level separate from other values and provide a rationale for its inclusion during the pregnancy OGTT.

    “The long-term type 2 diabetes risk associated with a pattern similar to class C and risk for child IGT with high 1-h PG observed in the current study demonstrate the importance of the maternal 1-h glucose level separate from other values and provide a rationale for its inclusion during the pregnancy OGTT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    The HAPO and HAPO FUS cohorts included participants from multiple races and ethnicities around the world, making the results broadly applicable.

    “Third, the HAPO and HAPO FUS cohorts included participants from multiple races and ethnicities around the world, making the results broadly applicable.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Paternal BMI data were not available, and paternal diabetes data were limited to family history.

    “Fourth, paternal BMI data were not available, and paternal diabetes data were limited to family history.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A second study of nonpregnant adults showed that those with a curve similar to class C had a higher risk of future type 2 diabetes compared with class A, while those with a curve similar to class B had an even higher risk of type 2 diabetes and future cardiovascular disease.

    “A second study of nonpregnant adults showed that those with a curve similar to class C had a higher risk of future type 2 diabetes compared with those with a curve similar to class A (40), whereas those with a curve similar to class B had an even higher risk of type 2 diabetes as well as future cardiovascular disease.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Hulman, 2018, Glucose patterns during an oral glucose tolerance test and associations with future diabetes, cardiovascular disease and all-cause mortality rate, Diabetologia source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Although the confidence intervals for classes B and C relative to class A overlapped, the odds ratio estimates suggested a possible trend of higher IGT risk for children whose mothers had class C trajectories.

    “Although the CIs for classes B and C relative to class A overlapped, OR estimates indicated a possible trend of higher risk of IGT for children with maternal pregnancy OGTT trajectories in class C.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    HAPO was a blinded observational study in which caregivers and mothers were unaware of maternal glucose levels, so child outcomes were not confounded by treatment of maternal hyperglycemia.

    “First, HAPO was a blinded observational study in which both caregivers and mothers were not aware of maternal glucose levels, and thus, child outcomes were not confounded by treatment of maternal hyperglycemia.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study was not powered to examine Tanner stage-specific associations.

    “Finally, the study was not powered to examine Tanner stage–specific associations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In nonpregnant adults, individuals with a curve similar to class B were most insulin resistant and had impaired insulin secretion.

    “Individuals with a curve similar to class B were most insulin resistant and had impaired insulin secretion.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] Hulman, 2018, Pathophysiological characteristics underlying different glucose response curves: a latent class trajectory analysis from the prospective EGIR-RISC study, Diabetes Care source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    Participants missing a 2-h plasma glucose value who had normal fasting plasma glucose were defined as normal, so the number of individuals with IGT may have been underestimated.

    “Participants missing a 2-h PG value who had a normal FPG were defined as normal; thus, the number of individuals with IGT may have been underestimated.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Participants missing a 2-h plasma glucose value who had normal fasting plasma glucose are normal with respect to IGT status.

  • May combine two claims.

    Premisecitation

    Child adiposity is partly dependent on maternal adiposity and affects insulin sensitivity and glucose metabolism.

    “Child adiposity, which is partly dependent on maternal adiposity (28,29), affects insulin sensitivity and glucose metabolism (30).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [28] Philipps, 2011, The diabetic pregnancy and offspring BMI in childhood: a systematic review and meta-analysis, Diabetologia source

      Not checked in the free run.

    • cites [29] Zhao, 2016, Maternal gestational diabetes and childhood obesity at age 9-11: results of a multinational study, Diabetologia source

      Not checked in the free run.

    • cites [30] Weiss, 2008, Metabolic complications of childhood obesity: identifying and mitigating the risk, Diabetes Care source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In nonpregnant adults, individuals with curves similar to class C had lower first-phase insulin secretion and insulin sensitivity but greater overall insulin secretion.

    “Individuals with curves similar to class C had lower first-phase insulin secretion and insulin sensitivity but greater insulin secretion overall.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] Hulman, 2018, Pathophysiological characteristics underlying different glucose response curves: a latent class trajectory analysis from the prospective EGIR-RISC study, Diabetes Care source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The excluded subgroup, 1.8% of the HAPO cohort, would likely include children at highest risk of altered glucose metabolism.

    “This subgroup (1.8% of the HAPO cohort) would likely include children at highest risk of altered glucose metabolism.”
    Quote in the paperNot a substantial claim
43 of 43

  • The paper relies on this without support.

    The relationship between maternal glucose levels across the spectrum and childhood glucose metabolism was not known before this study.

    “However, the relationship between maternal glucose levels across the spectrum of glucose values and childhood glucose metabolism is not known.”
    “Whether similar relationships exist between maternal glucose levels during pregnancy across the continuum and childhood metabolic outcomes is unknown.”

  • The authors state this as an assumption.

    Missing Tanner stage data were missing at random.

    “A “missing at random” assumption was used after confirming findings varied little under “missing not at random” (14).”

  • The paper relies on this without support.

    Participants missing a 2-h plasma glucose value who had normal fasting plasma glucose are normal with respect to IGT status.

    “Participants missing a 2-h PG value who had a normal FPG were defined as normal; thus, the number of individuals with IGT may have been underestimated.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Offspring glucose levels from the 75 g oral glucose tolerance test and glycosylated hemoglobin were linearly associated with maternal glucose levels during pregnancy independent of maternal and child BMI.

    “Consistent with obesity parameters, offspring glucose levels from the 75 g OGTT and glycosylated hemoglobin were linearly associated with maternal glucose levels during pregnancy independent of maternal and child BMI [34,35].”

    From Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications (2022) · cites this paper as [35]

    The Results sections on continuous and categorical outcomes report generally linear associations between maternal pregnancy glucose and child glucose and A1C, persisting after adjustment for maternal BMI and child BMI z score. The Study Visit section specifies that children received 1.75 g/kg of glucose, capped at 75 g—not uniformly a 75 g dose. The associations also varied by measure: maternal fasting glucose was not associated with child 1-hour or 2-hour glucose. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • GDM is characterized by an increased risk of large-for-gestational-age birth weight and neonatal and pregnancy complications and an increased risk of long-term maternal type 2 diabetes and abnormal glucose metabolism of offspring in childhood.

    “GDM is characterized by an increased risk of large-for-gestational-age birth weight and neonatal and pregnancy complications and an increased risk of long-term maternal type 2 diabetes and abnormal glucose metabolism of offspring in childhood.”

    From 15. Management of Diabetes in Pregnancy: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [56]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Post hoc GDM in individuals diagnosed with the one-step method in the HAPO cohort was associated with higher prevalence of IGT; higher 30-min, 1-h, and 2-h glucose levels during the OGTT; and reduced insulin sensitivity and oral disposition index in their offspring at 10-14 years of age compared with offspring of mothers without GDM.

    “Post hoc GDM in individuals diagnosed with this method in the HAPO cohort was associated with higher prevalence of IGT; higher 30-min, 1-h, and 2-h glucose levels during the OGTT; and reduced insulin sensitivity and oral disposition index in their offspring at 10-14 years of age compared with offspring of mothers without GDM.”

    From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [199]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Associations of mother's fasting, 1-h, and 2-h values on the 75-g OGTT were continuous with a comprehensive panel of offspring metabolic outcomes.

    “Associations of mother's fasting, 1-h, and 2-h values on the 75-g OGTT were continuous with a comprehensive panel of offspring metabolic outcomes (198,199).”

    From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [199]

    The Results section, under “Associations Between Continuous Maternal Glycemia and Continuous Child Glucose Outcomes,” examines maternal fasting, 1-h, and 2-h OGTT values against a broad panel of child outcomes. But the associations were not present for every value–outcome pair: maternal fasting glucose was not associated with child 1-h or 2-h glucose, and it was not significantly associated with disposition index. The cited passages provide no page numbers. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • HAPO-FUS found persistent metabolic consequences of maternal hyperglycemia on long-term offspring glucose homeostasis, extending to glycemic levels below current GDM diagnostic thresholds.

    “Findings revealed persistent metabolic consequences of maternal hyperglycemia on long-term offspring glucose homeostasis, notably extending to glycemic levels below current GDM diagnostic thresholds.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [61]

    The Results (Associations Between Categorical Maternal Glycemia and Child Glucose Outcomes; page unavailable) report a continuous relationship between maternal glucose and child glucose measures at ages 10–14, including maternal glucose categories below the GDM diagnostic thresholds. But the study reports associations, not established persistent metabolic consequences caused by maternal hyperglycemia; the Conclusions describe fetal programming only as a potential contribution. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Significant insulinogenic result has an interval crossing zero

    Major

    For the model 4 maternal glucose-sum result, the reported P value is below 0.05, but its 95% confidence interval includes zero. These disagree on significance for the same estimate.

  • Maternal 1-hour Matsuda estimate falls outside its reported interval

    Minor

    The model 2 interval endpoints have a midpoint of 22.4, whereas the reported coefficient is −67.1. That coefficient is outside the interval even if the endpoints are reordered.

    Reported -67.1 · recomputed 22.4

  • Narrative omits a significant model 2 insulinogenic association

    Minor

    The text says the maternal 2-hour glucose association with the insulinogenic index appears only in models 3 and 4, but Table 1 also reports a significant model 2 result (P = 0.046).

  • Glucose-sum insulinogenic estimate falls outside its interval

    Minor

    The model 3 coefficient is −0.089, outside its reported interval of −0.019 to 0.0012. The interval's midpoint is −0.0089.

    Reported -0.089 · recomputed -0.0089

  • Maternal 1-hour insulinogenic estimate is inconsistent with its interval

    Minor

    The model 1 confidence interval is centered at −0.295, far from its reported coefficient of −0.034.

    Reported -0.034 · recomputed -0.295

  • Glucose-sum disposition interval has reversed bounds

    Minor

    The model 1 interval runs from −0.03 to −0.2, placing its reported coefficient of −0.02 outside both endpoints. Its endpoints also have a midpoint of −0.115.

    Reported -0.02 · recomputed -0.115

6 of 6

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Silverman, 1998, Long-term effects of the intrauterine environment, Diabetes Care, 21, B142
  2. R Core Team, 2016, A Language and Environment for Statistical Computing

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Authors
Scholtens, D. M., Kuang, A., Lowe, L. P., Hamilton, J., Lawrence, J. M., Lebenthal, Y., Brickman, W. J., Clayton, P., Ma, R. C., McCance, D., Tam, W. H., Catalano, P. M., Linder, B., Dyer, A. R., Lowe, W. L., Metzger, B. E., HAPO Follow-Up Study Cooperative Research Group, Deerochanawong, C., Tanaphonpoonsuk, T., Chotigeat, S. B. U., Manyam, W., Forde, M., Greenidge, A., Neblett, K., Lashley, P. M., Walcott, D., Corry, K., Francis, L., Irwin, J.-A., Langan, A., McCance, D. R., Mousavi, M., Young, I., Gutierrez, J., Jimenez, J., Lawrence, J. M., Sacks, D. A., Takhar, H. S., Tanton, E., Brickman, W. J., Howard, J., Josefson, J. L., Miller, L., Bjaloncik, J., Catalano, P. M., Davis, A., Koontz, M., Presley, L., Smith, S., Tyhulski, A., Li, A. M., Ma, R. C., Ozaki, R., Tam, W. H., Wong, M., Yuen, C. S. M., Clayton, P. E., Khan, A., Vyas, A., Maresh, M., Benzaquen, H., Glickman, N., Hamou, A., Hermon, O., Horesh, O., Keren, Y., Lebenthal, Y., Shalitin, S., Cordeiro, K., Hamilton, J., Nguyen, H. Y., Steele, S., Chen, F., Dyer, A. R., Huang, W., Kuang, A., Jimenez, M., Lowe, L. P., Lowe, W. L., Metzger, B. E., Nodzenski, M., Reisetter, A., Scholtens, D., Talbot, O., Yim, P., Dunger, D., Thomas, A., Horlick, M., Linder, B., Unalp-Arida, A., & Grave, G.
Affiliations
  • Northwestern University Feinberg School of Medicine, Chicago, IL
  • Royal Manchester Children’s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Healthy Sciences Centre, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, U.K.
  • Royal Victoria Hospital, Belfast, U.K.
  • Royal Victoria Hospital (GB)
  • National Institutes of Health (US)
  • Northwestern University (US)
  • Tel Aviv University (IL)
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2019-01-07
Volume
42
Issue
3
Pages
381-392
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc18-2021
PMC
PMC6385697
OpenAlex
W2908159319
Cited by
310
References
41
Citations by year
2026: 41 · 2025: 46 · 2024: 49 · 2023: 37 · 2022: 46 · 2021: 37 · 2020: 32 · 2019: 22
FWCI
37.24
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/content/license (vor, 44 d)
Locations
  • Diabetes Care (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion, other-oa)
Funders
  • National Institute for Health and Care Research (NF-SI-0513-10012)
  • National Institutes of Health (UL1TR001422, UL1TR002548)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U01DK094830)
  • National Center for Advancing Translational Sciences
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD034242, R01HD034243)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
maternal glycemia, hyperglycemia in pregnancy, impaired fasting glucose, impaired glucose tolerance, insulin resistance, insulin sensitivity, disposition index, HbA1c, fasting blood glucose, oral glucose tolerance test, prenatal exposure, offspring diabetes risk
MeSH terms
Adolescent, Adult, Blood Glucose, Child, Diabetes Mellitus, Female, Follow-Up Studies, Glucose Tolerance Test, Humans, Hyperglycemia, Insulin Resistance, Male, Middle Aged, Prediabetic State, Pregnancy, Pregnancy Complications, Pregnancy in Diabetics, Pregnancy Outcome, Prenatal Exposure Delayed Effects, Cohort Studies, Child of Impaired Parents, Glucose Intolerance

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