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Cited by 4Gestational Diabetes Research and ManagementDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes Management and Research

Hypoglycemia in Oral Glucose Tolerance Test during Pregnancy and Risk for Type 2 Diabetes—A Five-Year Cohort Study

Open access
Haggiag, Noa, Rotman, Moran, Hallak, Mordechai, Toledano, Yoel, Gabbay-Benziv, Rinat, Maor-Sagie, Esther·2024·Journal of Clinical Medicine
DOI 10.3390/jcm13133806PMC PMC11242525
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Abstract

Objective: To evaluate the risk of progression to type 2 diabetes (T2D) following reactive hypoglycemia in 100 g oral glucose tolerance test (oGTT). Methods: A retrospective analysis of parturients with up to 5-year follow-up postpartum. Data were extracted from the computerized laboratory system of Meuhedet, an Israeli HMO and cross-linked with the Israeli National Registry of Diabetes. Included were parturients with no prior diabetesand available oGTT values during pregnancy. Reactive hypoglycemia was defined as glucose levels lower than 60 mg/dL in at least one of 3 post-glucose load values in oGTT. The cohort was divided into 3 groups: normal glucose status, reactive hypoglycemia, and GDM. Maternal characteristics, laboratory data, and progression to T2D over 5 years were compared. Univariate and survival analyses assessed the adjusted hazard ratio for T2D, stratified by obesity Results: Among 14,122 parturients, 16.8% had reactive hypoglycemia, 71% had normal glucose status, and 12.2% had GDM. Adjusted for age, obesity, and hypertension, Parturients with reactive hypoglycemia had similar T2D risk compared to normal glucose status and a lower risk compared to GDM patients, regardless of obesity status. Conclusions: Reactive hypoglycemia during oGTT does not increase the risk of progressing to T2D.

AI snapshot

Written from the paper’s full text.

TL;DR

In this retrospective cohort of 14,122 pregnant individuals, reactive hypoglycemia on 100-g oGTT was not associated with increased risk of progression to type 2 diabetes over up to 5 years compared with normal glucose status, and was associated with lower risk than GDM. After adjustment, the hazard ratio for T2D versus normal glucose status was 0.988 (95% CI 0.659–1.483).

Key findings

  • Among 14,122 parturients, 2367 (16.8%) had reactive hypoglycemia, 11,025 (71%) had normal glucose status, and 1730 (12.2%) had GDM.
  • Reactive hypoglycemia occurred mostly at the 3-h post-load value (2263/2367; 1 h 20/2367; 2 h 84/2367).
  • Adjusted for confounders, reactive hypoglycemia had similar T2D risk to normal glucose status (HR 0.988, 95% CI 0.659–1.483, p > 0.05) and lower incidence/risk than GDM; no association was seen regardless of obesity status.
  • Maternal age, BMI ≥ 30 kg/m², and GDM were independent risk factors for T2D (p < 0.001 for all); median follow-up was 4.24 years (IQR 3.25–5.04).

Methods

  • Retrospective cohort using laboratory data from Meuhedet HMO cross-linked with the Israeli National Registry of Diabetes; included parturients without prior diabetes and available oGTT values, excluded fasting glucose >125 mg/dL and missing oGTT values, and included only the first pregnancy during the study period.
  • Reactive hypoglycemia was defined as glucose <60 mg/dL in at least one of 3 post-glucose load oGTT values; groups were normal glucose status, reactive hypoglycemia, and GDM.
  • Categorical variables were compared with χ² tests and continuous variables with Kruskal-Wallis tests; Kaplan-Meier and Cox proportional hazard models estimated HRs and 95% CIs for incident T2D using normal oGTT as the reference group, with stratification by obesity.

Limitations

  • The authors state the study is limited by its retrospective nature, a limited 5-year follow-up with a relatively young population and therefore low overall diabetes risk, missing data on family history of T2D and possible postpartum interventions such as weight reduction/lifestyle modification, and an INDR not designed to identify patients with PCOS.
  • The text also makes evident that the observational design leaves potential residual confounding, and the authors note that distinguishing proposed mechanisms would require real-time measurement of insulin and glucose levels, which this study did not perform.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/jcm13133806

Cites

21 of 21 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

3 of 17 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Findingown data

    Among patients with reactive hypoglycemia, most had hypoglycemia at the 3-h blood evaluation (2263/2367).

    “As shown in Table 1—among patients with reactive hypoglycemia, most had hypoglycemia at the 3-h blood evaluation (1 h—20/2367; 2 h 84/2367; and 3 h 2263/2367).”
    • Also stated in: § 4. Discussion · plain
      “(2) Hypoglycemia was mainly noted 3 h following the sugar load.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Maternal age was a statistically significant independent risk factor for T2D (p < 0.001).

    “Maternal age, BMI ≥ 30 kg/m2, and GDM were all statistically significant independent risk factors for T2D (p < 0.001 for all).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Among 14,122 parturients with available oGTT and INDR data, 16.8% (2367) had reactive hypoglycemia.

    “Among 14,122 parturients, 16.8% had reactive hypoglycemia”
    • Also stated in: § 3. Results · plain
      “Stratified to study groups, 2367 (16.8%) patients had reactive hypoglycemia oGTT (study group)”
    • Also stated in: § 4. Discussion · plain
      “(1) Prevalence of hypoglycemia in oGTT was 16.8% (2367/14,122).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Among the same cohort, 12.2% (1730) had GDM.

    “12.2% had GDM”
    • Also stated in: § 3. Results · plain
      “1730 (12.2%) had GDM (2nd control group)”
    Quote in the paperNot a substantial claim
  • Findingown data

    After adjustment for maternal age and BMI, pregnant individuals with reactive hypoglycemia had a similar risk for progression to T2D as compared to pregnant individuals with normal glucose status (HR 0.988, 95% CI 0.659-1.483, p > 0.05).

    “After adjustment to confounders, pregnant individuals with reactive hypoglycemia had a similar risk for progression to T2D as compared to pregnant individuals with normal glucose status (HR 0.988 (95% CI 0.659–1.483), p > 0.05), Table 2.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 12
  • May combine two claims. 9

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

    Premisecitation

    The prevalence of hypoglycemia during oGTT in pregnancy ranges between 3.6% and 11.3% in different reports.

    “Accordingly, the prevalence of hypoglycemia during oGTT in pregnancy ranges between 3.6% and 11.3% in different reports [4,5,6,7].”
    Quote in the paperNot a substantial claim1 of 4 sources checked
    • cites [4] Delibas, 2018, Does reactive hypoglycemia during the 100 g oral glucose tolerance test adversely affect perinatal outcomes?, Ginekol. Pol. source
    • cites [5] Raviv, 2022, Hypoglycemia during the oral glucose tolerance test in pregnancy-maternal characteristics and neonatal outcomes, Int. J. Gynaecol. Obstet. Off. Organ Int. Fed. Gynaecol. Obstet. source
    • cites [6] Bayraktar, 2020, Pregnancy outcomes of women with hypoglycemia in the oral glucose tolerance test, J. Gynecol. Obstet. Hum. Reprod. source
    • cites [7] Weissman, 2005, Hypoglycemia during the 100-g oral glucose tolerance test: Incidence and perinatal significance, Obstet. Gynecol. source

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

    Premisecitation

    Previous studies investigating the association between reactive hypoglycemia and pregnancy outcomes have conflicting results.

    “Previous studies investigated the association between reactive hypoglycemia and pregnancy outcomes with conflicting results [4,5,6,7].”
    Quote in the paperNot a substantial claim1 of 4 sources checked
    • cites [4] Delibas, 2018, Does reactive hypoglycemia during the 100 g oral glucose tolerance test adversely affect perinatal outcomes?, Ginekol. Pol. source
    • cites [5] Raviv, 2022, Hypoglycemia during the oral glucose tolerance test in pregnancy-maternal characteristics and neonatal outcomes, Int. J. Gynaecol. Obstet. Off. Organ Int. Fed. Gynaecol. Obstet. source
    • cites [6] Bayraktar, 2020, Pregnancy outcomes of women with hypoglycemia in the oral glucose tolerance test, J. Gynecol. Obstet. Hum. Reprod. source
    • cites [7] Weissman, 2005, Hypoglycemia during the 100-g oral glucose tolerance test: Incidence and perinatal significance, Obstet. Gynecol. source

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

    Premisecitation

    The exact definition of hypoglycemia is not uniform in the literature and varies according to glucose values (45-60 mg/dL) and accompanying symptoms.

    “The exact definition of hypoglycemia is not uniform in the literature and varies according to the glucose values (45–60 mg/dL) and accompanying symptoms [3,4].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [3] Hofeldt, 1989, Reactive hypoglycemia, Endocrinol. Metab. Clin. N. Am. source
    • cites [4] Delibas, 2018, Does reactive hypoglycemia during the 100 g oral glucose tolerance test adversely affect perinatal outcomes?, Ginekol. Pol. source

      The Introduction says there is no precise glucose cut-off that predicts hypoglycemic symptoms and that reports use 45–50 mg/dL as indicative of reactive hypoglycemia. This supports variation in thresholds and the relevance of symptoms, but not the claimed upper value of 60 mg/dL. The Study groups section uses a 45 mg/dL cut-off; page numbers were unavailable in our copy. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Compared to pregnant individuals with normal glucose status, patients with reactive hypoglycemia were older, leaner, and had lower glucose values (p < 0.001 for all).

    “Compared to pregnant individuals with normal glucose status during pregnancy, patients with reactive hypoglycemia were older, leaner, and had lower glucose values (p < 0.001 for all).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Among the same cohort, 71% (11,025) had normal glucose status.

    “71% had normal glucose status”
    • Also stated in: § 3. Results · plain
      “11,025 (71%) patients had normal oGTT (1st control group)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Pregnant individuals with reactive hypoglycemia in oGTT were younger and had lower BMI compared to patients with GDM.

    “Pregnant individuals with reactive hypoglycemia in oGTT were younger and had lower BMI compared to patients with GDM.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Reactive hypoglycemia at oGTT was not associated with risk for T2D both for patients with and without obesity as compared to patients with normal glucose tolerance.

    “Reactive hypoglycemia at oGTT was not associated with risk for T2D both for patients with and without obesity as compared to patients with normal glucose tolerance (Figure 2).”
    • Also stated in: § 4. Discussion · plain
      “(4) Regardless of obesity status, the risk of progressing to T2D was like that of pregnant individuals with normal OGTT.”
    Quote in the paperSubstantial claim

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

    Findingown data

    Median follow-up time for the entire cohort was 4.24 years (IQR 3.25-5.04).

    “As for risk for T2D, for the entire cohort, the median follow-up time was 4.24 years (IQR 3.25–5.04).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Short-term outcomes of reactive hypoglycemia range between no adverse maternal or neonatal outcome to association with low APGAR scores, lower birth weight, small head circumference and short body length, and perinatal admission to the NICU.

    “Short term outcome of reactive hypoglycemia have been described, ranging between no adverse maternal or neonatal outcome to association with low APGAR scores, lower birth weight, small head circumference and short body length, and perinatal admission to the NICU [5,6].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Raviv, 2022, Hypoglycemia during the oral glucose tolerance test in pregnancy-maternal characteristics and neonatal outcomes, Int. J. Gynaecol. Obstet. Off. Organ Int. Fed. Gynaecol. Obstet. source
    • cites [6] Bayraktar, 2020, Pregnancy outcomes of women with hypoglycemia in the oral glucose tolerance test, J. Gynecol. Obstet. Hum. Reprod. source

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

    Study design and conductnone given

    The Israeli National Registry of Diabetes is not designed to identify patients with PCOS.

    “Lastly, the INDR isn’t designed to identify patients with PCOS that might represent a unique group of reaction to oGTT.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    The Israeli National Registry of Diabetes has a sensitivity of 95% and a positive predictive value of 93%.

    “The registry has a sensitivity of 95% and the positive predictive value is 93% [10].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Twig, 2020, Adolescent Obesity and Early-Onset Type 2 Diabetes, Diabetes Care source

  • May combine two claims.

    Study design and conductreasoning

    The study had a limited 5-year follow-up and the overall risk of developing diabetes is relatively low because most pregnant patients are younger than 40 years old.

    “Most pregnant patients are younger than 40 years old and since we had a limited 5-year follow-up the overall risk of developing diabetes is relatively low.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    One of the earliest changes in T2D is loss of first-phase insulin release, resulting in increased second-phase insulin release followed by reactive hypoglycemia.

    “as one of the earliest changes in T2D is first-phase insulin release loss, resulting in increased second-phase insulin release followed by reactive hypoglycemia.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [8] Brun, 2000, Postprandial reactive hypoglycemia, Diabetes Metab.
    • cites [9] Altuntas, 2005, Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function, Eur. J. Obstet. Gynecol. Reprod. Biol. source

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

    Study design and conductnone given

    The study was based on a large cohort of pregnant individuals with high-quality data automatically generated from the laboratory cross-tabulated with the Israeli National Registry of Diabetes.

    “The study was based on a large cohort of pregnant individuals with high-quality data automatically generated from the laboratory cross-tabulated with INDR.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Missing data that could not be obtained included family history of T2D and possible after-pregnancy interventions such as weight reduction/lifestyle modifications that might have changed the risk for T2D.

    “Missing data that could not be obtained, such as a family history of T2D or possible after-pregnancy interventions such as weight reduction /lifestyle modifications that might have changed the risk for T2D.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The study was retrospective.

    “Nevertheless, the study has several limitations mainly due to its retrospective nature.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Hypoglycemia may result from hyperinsulinism that may precede T2D.

    “Alternatively, hypoglycemia may result from hyperinsulinism that may precede T2D [8,9]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [8] Brun, 2000, Postprandial reactive hypoglycemia, Diabetes Metab.
    • cites [9] Altuntas, 2005, Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function, Eur. J. Obstet. Gynecol. Reprod. Biol. source

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

    Study design and conductnone given

    The study benefits from a heterogenous population, with a distinction between individuals with and without obesity, and a validated statistic.

    “Moreover, it benefits from a heterogenous population, with a distinction between individuals with and without obesity, and a validated statistic.”
    Quote in the paperNot a substantial claim
18 of 18

  • The authors state this as an assumption.

    Variability in short-term outcomes of reactive hypoglycemia indicates abnormal glucose metabolism during pregnancy.

    “This variability might indicate abnormal glucose metabolism during pregnancy. Assuming that is true, we expect that pregnant individuals with reactive hypoglycemia during oGTT will have higher progression rates to T2D years after pregnancy.”

  • The paper relies on this without support.

    Data about the risk of developing future T2D after reactive hypoglycemia in oGTT during pregnancy is scarce.

    “However, data about the risk of developing future T2D after reactive hypoglycemia in oGTT during pregnancy is scarce.”

  • The paper relies on this without support.

    Gestational diabetes mellitus is a significant risk factor for type 2 diabetes.

    “Gestational diabetes mellitus (GDM) is a significant risk factor for T2D.”

  • The paper relies on this without support.

    The mechanism of reactive hypoglycemia during oGTT in pregnancy is not well understood.

    “The mechanism of reactive hypoglycemia during oGTT in pregnancy is not well understood and can be attributed to either dumping syndrome, gastrointestinal dysfunction, or idiopathic.”

  • The paper relies on this without support.

    Obesity is a significant risk factor for type 2 diabetes and insulin resistance.

    “Given that obesity stands as a significant risk factor for T2D and insulin resistance, it’s reasonable to anticipate that the subgroup analysis conducted based on maternal obesity status would at least partially distinguish between the groups.”
5 of 5

Self-check

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

  • Normal-glucose group count does not match its reported percentage

    Major

    A count of 11,025 out of 14,122 is approximately 78.07%, not 71%.

    Reported 71 · recomputed 78.069679

  • Study-group counts exceed the stated cohort size

    Major

    The three reported group counts sum to 15,122, which is 1,000 more than the stated cohort of 14,122.

    Reported 14122 · recomputed 15122

2 of 2

Cites

Flagged first, then by citations

1 of the 22 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Haggiag, N., Rotman, M., Hallak, M., Toledano, Y., Gabbay-Benziv, R., & Maor-Sagie, E.
Affiliations
  • Hillel Yaffe Medical Center (IL)
  • Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera 3820302, Israel
  • Technion – Israel Institute of Technology (IL)
  • Kupat Holim Meuchedet
ORCID
Venue
Journal of Clinical Medicine
Publisher
MDPI AG
Published
2024-06-28
Volume
13
Issue
13
Pages
3806
ISSN
2077-0383 (ISSN-L)
DOI
10.3390/jcm13133806
PMC
PMC11242525
OpenAlex
W4400198515
Semantic Scholar
09e43c8e4453a6078cea90502c8c7baba11225ed
Cited by
4
References
22
Citations by year
2026: 3 · 2025: 1
FWCI
1.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Medicine (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
reactive hypoglycemia, oral glucose tolerance test, pregnancy, type 2 diabetes risk, gestational diabetes mellitus, postpartum follow-up, obesity, diabetes progression

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