ReviewDiabetologia2021
Two decades since the fetal insulin hypothesis: what have we learned from genetics?
Review in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Maternal obesity and offspring cardiovascular remodelling - the effect of preconception and antenatal lifestyle interventions: a systematic review.International journal of obesity (2005) · 2024Pooled it
- The Potential Physiologic Mechanisms by Which Early-Life Nutrition May Influence Type 2 Diabetes Pathophysiology in Humans.Annual review of nutrition · 2026Review
- Maternal and fetal genetic predispositions to insulin deficiency and resistance affect fetal growth through distinct pathways.Diabetologia · 2026Article
- Permanent Neonatal Diabetes with High Insulin Requirements due to a New Variant in theJournal of clinical research in pediatric endocrinology · 2026Article
- Prenatal Exposure to Artificial Light at Night and the Offspring's First 1000-Day Growth: A Prospective Metabolomic and Gene-Environment Interaction Study.Environmental science & technology · 2026Article
- Life-course influence of birthweight and subsequent pathways on healthy aging: a Mendelian randomization study.BMC medicine · 2026Article
- Incidence of gestational diabetes and inequalities in adverse pregnancy outcomes in England: contemporary, cross sectional observational study of 2.7 million births.BMJ medicine · 2026Article
- Birth weight and prematurity for predicting type 2 diabetes mellitus: a prognostic review.The Cochrane database of systematic reviews · 2025Article
- Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.Nature communications · 2025Article
- The causal effects of placental weight on atherosclerotic cardiovascular disease: a Mendelian randomization and mediation analysis.Archives of medical science : AMS · 2025Article
- Genetic associations of birthweight, childhood, and adult BMI with metabolic dysfunction-associated steatotic liver disease: a Mendelian randomization.BMC gastroenterology · 2024Article
- The interplay between birth weight and obesity in determining childhood and adolescent cardiometabolic risk.EBioMedicine · 2024Article
- Potential pathogenetic role of a novel ABCC8 missense variant on both transient neonatal diabetes mellitus and fetal growth restriction: a case report.Molecular biology reports · 2024Article
- Interaction effect between low birthweight and resistin gene rs1862513 variant on insulin resistance and type 2 diabetes mellitus in adulthood: Toon Genome Study.Journal of diabetes investigation · 2024Article
- Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.medRxiv : the preprint server for health sciences · 2024Article
- Disentangling the link between maternal influences on birth weight and disease risk in 36,211 genotyped mother-child pairs.Communications biology · 2024Article
- Reconsidering the developmental origins of adult disease paradigm: The 'metabolic coordination of childbirth' hypothesis.Evolution, medicine, and public health · 2024Review
- Opposite causal effects of birthweight on myocardial infarction and atrial fibrillation and the distinct mediating pathways: a Mendelian randomization study.Cardiovascular diabetology · 2023Article
- The influence of insulin-related genetic variants on fetal growth, fetal blood flow, and placental weight in a prospective pregnancy cohort.Scientific reports · 2023Article
- Insulin signaling in development.Development (Cambridge, England) · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In 1998 the fetal insulin hypothesis proposed that lower birthweight and adult-onset type 2 diabetes are two phenotypes of the same genotype. Since then, advances in research investigating the role of genetics affecting insulin secretion and action have furthered knowledge of fetal insulin-mediated growth and the biology of type 2 diabetes. In this review, we discuss the historical research context from which the fetal insulin hypothesis originated and consider the position of the hypothesis in light of recent evidence. In summary, there is now ample evidence to support the idea that variants of certain genes which result in impaired pancreatic beta cell function and reduced insulin secretion contribute to both lower birthweight and higher type 2 diabetes risk in later life when inherited by the fetus. There is also evidence to support genetic links between type 2 diabetes secondary to reduced insulin action and lower birthweight but this applies only to loci implicated in body fat distribution and not those influencing insulin resistance via obesity or lipid metabolism by the liver. Finally, we also consider how advances in genetics are being used to explore alternative hypotheses, namely the role of the maternal intrauterine environment, in the relationship between lower birthweight and adult cardiometabolic disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.