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Cited by 826Gestational Diabetes Research and ManagementDiabetes, Cardiovascular Risks, and LipoproteinsPancreatic function and diabetes

Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus

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Butte, Nancy F·2000·The American Journal of Clinical Nutrition
DOI 10.1093/ajcn/71.5.1256s
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Abstract

This article reviews maternal metabolic strategies for accommodating fetal nutrient requirements in normal pregnancy and in gestational diabetes mellitus (GDM). Pregnancy is characterized by a progressive increase in nutrient-stimulated insulin responses despite an only minor deterioration in glucose tolerance, consistent with progressive insulin resistance. The hyperinsulinemic-euglycemic glucose clamp technique and intravenous-glucose-tolerance test have indicated that insulin action in late normal pregnancy is 50-70% lower than in nonpregnant women. Metabolic adaptations do not fully compensate in GDM and glucose intolerance ensues. GDM may reflect a predisposition to type 2 diabetes or may be an extreme manifestation of metabolic alterations that normally occur in pregnancy. In normal pregnant women, basal endogenous hepatic glucose production (R(a)) was shown to increase by 16-30% to meet the increasing needs of the placenta and fetus. Total gluconeogenesis is increased in late gestation, although the fractional contribution of total gluconeogenesis to R(a), quantified from (2)H enrichment on carbon 5 of glucose (65-85%), does not differ in pregnant women after a 16-h fast. Endogenous hepatic glucose production was shown to remain sensitive to increased insulin concentration in normal pregnancy (96% suppression), but is less sensitive in GDM (80%). Commensurate with the increased rate of glucose appearance, an increased contribution of carbohydrate to oxidative metabolism has been observed in late pregnancy compared with pregravid states. The 24-h respiratory quotient is significantly higher in late pregnancy than postpartum. Recent advances in carbohydrate metabolism during pregnancy suggest that preventive measures should be aimed at improving insulin sensitivity in women predisposed to GDM. Further research is needed to elucidate the mechanisms and consequences of alterations in lipid metabolism during pregnancy.

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  • Elevated plasma insulin may inhibit fatty acid oxidation, and impaired triglyceride oxidation may contribute to macrosomia.

    “Elevated plasma insulin may inhibit fatty acid oxidation, and impaired triglyceride oxidation triglycerides may contribute to macrosomia [18,26].”

    From Medical Nutrition Therapy for Women with Gestational Diabetes: Current Practice and Future Perspectives (2025) · cites this paper as [18]

  • As pregnancy progresses, basal glucose concentrations decrease by 0.56 to 0.83 mmol/L by the third trimester, while both first- and second-phase insulin secretion rise by up to 3.5-fold to accommodate the increase in insulin resistance.

    “As pregnancy progresses, basal glucose concentrations decrease by 0.56 to 0.83 mmol/L by the third trimester, while both first- and second-phase insulin secretion rise by up to 3.5-fold to accommodate the increase in insulin resistance [18,19,20].”

    From Medical Nutrition Therapy for Women with Gestational Diabetes: Current Practice and Future Perspectives (2025) · cites this paper as [18]

  • Insulin secretion in response to oral glucose increases by at least 120% in the first trimester.

    “However, insulin secretion in response to oral glucose increases by at least 120% in the first trimester [16,17,18].”

    From Medical Nutrition Therapy for Women with Gestational Diabetes: Current Practice and Future Perspectives (2025) · cites this paper as [18]

  • Normal pregnancy is associated with a progressive increase in insulin resistance predominantly due to increased circulating placental hormones including growth hormone, corticotrophin-releasing hormone, human placental lactogen, prolactin, estrogen, and progesterone.

    “There is a progressive increase in insulin resistance, predominantly due to increased circulating placental hormones, including growth hormone, corticotrophin-releasing hormone, human placental lactogen, prolactin, estrogen, and progesterone.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [38]

  • In late gestation, insulin sensitivity is reduced by 40-80% in gravidae with normal or elevated body mass index.

    “Evidence from late-gestation studies demonstrates that insulin sensitivity is reduced by 40–80% in gravidae with normal or elevated body mass index.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [38]

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Authors
Butte, N. F.
Affiliations
Agricultural Research Service (US)
Corresponding author
Butte, Nancy F
ORCID
Butte, Nancy F
Venue
The American Journal of Clinical Nutrition
Publisher
Elsevier BV
Published
2000-05
Volume
71
Issue
5
Pages
1256S-1261S
ISSN
0002-9165 (ISSN-L)
DOI
10.1093/ajcn/71.5.1256s
OpenAlex
W2262338962
Cited by
826
References
5
Citations by year
2026: 29 · 2025: 33 · 2024: 34 · 2023: 59 · 2022: 48 · 2021: 68 · 2020: 56 · 2019: 38 · 2018: 47 · 2017: 48 · 2016: 52 · 2015: 43 · 2014: 29 · 2013: 36 · 2012: 33
FWCI
9.40
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Clinical Nutrition (publishedVersion)
  • PubMed (publishedVersion)
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 › Surgery › Pancreatic function and diabetes
Keywords
gestational diabetes mellitus, normal pregnancy, carbohydrate metabolism, lipid metabolism, insulin resistance, insulin sensitivity, hepatic glucose production, gluconeogenesis, glucose tolerance, respiratory quotient, oxidative metabolism, type 2 diabetes risk, maternal-fetal nutrient transfer
MeSH terms
Dietary Carbohydrates, Dietary Fats, Female, Humans, Insulin Resistance, Pregnancy, Diabetes, Gestational, Lipid Metabolism

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