How does exposure to overnutrition in utero lead to childhood adiposity? Testing the insulin hypersecretion hypothesis in the EPOCH cohort.
Adiposity
/ physiology
Adolescent
Blood Glucose
/ metabolism
Body Composition
Body Mass Index
Child
Diabetes Mellitus, Type 2
/ physiopathology
Female
Follow-Up Studies
Humans
Hyperinsulinism
/ physiopathology
Insulin
/ blood
Insulin Resistance
/ physiology
Intra-Abdominal Fat
/ metabolism
Male
Overnutrition
/ physiopathology
Pregnancy
Prenatal Exposure Delayed Effects
/ physiopathology
Beta cell dysfunction
Beta cell hypersecretion
Fasting insulin
Longitudinal cohort
Type 2 diabetes
Youth
Journal
Diabetologia
ISSN: 1432-0428
Titre abrégé: Diabetologia
Pays: Germany
ID NLM: 0006777
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
11
03
2021
accepted:
05
05
2021
pubmed:
18
7
2021
medline:
19
3
2022
entrez:
17
7
2021
Statut:
ppublish
Résumé
Our aim was to explore metabolic pathways linking overnutrition in utero to development of adiposity in normal-weight children. We included 312 normal-weight youth exposed or unexposed to overnutrition in utero (maternal BMI ≥25 kg/m >All participants were normal weight at baseline (BMIZ -0.32 ± 0.88), with no difference in BMIZ for exposed vs unexposed youth (p = 0.14). Of the study population, 47.8% were female sex and 47.4% were of white ethnicity. Overnutrition in utero corresponded with 14% higher baseline fasting insulin (geometric mean ratio 1.14 [95% CI 1.01, 1.29]), even after controlling for VAT/SAT ratio. Higher baseline fasting insulin corresponded with higher BMIZ (0.41 [95% CI 0.26, 0.55]), SAT (13.9 [95% CI 2.4, 25.4] mm Overnutrition in utero may result in hyperinsulinaemia during childhood, preceding development of adiposity. However, our study started at age 10 years, so earlier metabolic changes in response to overnutrition were not taken into account. Longitudinal studies in normal-weight youth starting earlier in life, and with repeated measurements of body weight, fat distribution, insulin sensitivity, beta cell function and blood glucose levels, are needed to clarify the sequence of metabolic changes linking early-life exposures to adiposity and dysglycaemia.
Identifiants
pubmed: 34272965
doi: 10.1007/s00125-021-05515-2
pii: 10.1007/s00125-021-05515-2
doi:
Substances chimiques
Blood Glucose
0
Insulin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2237-2246Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK068001
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR002534
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Mayer-Davis EJ, Lawrence JM, Dabelea D et al (2017) Incidence trends of type 1 and type 2 diabetes among youths, 2002-2012. N Engl J Med 376(15):1419–1429. https://doi.org/10.1056/NEJMoa1610187
doi: 10.1056/NEJMoa1610187
pubmed: 28402773
pmcid: 5592722
D’Adamo E, Caprio S (2011) Type 2 diabetes in youth: epidemiology and pathophysiology. Diabetes Care 34(Supplement 2):S161–S165. https://doi.org/10.2337/dc11-s212
doi: 10.2337/dc11-s212
pubmed: 21525449
pmcid: 3632155
Bianco ME, Kuang A, Josefson JL et al (2021) Hyperglycemia and adverse pregnancy outcome follow-up study: newborn anthropometrics and childhood glucose metabolism. Diabetologia 64(3):561–570. https://doi.org/10.1007/s00125-020-05331-0
doi: 10.1007/s00125-020-05331-0
pubmed: 33191479
Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC (1994) Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 17(9):961–969. https://doi.org/10.2337/diacare.17.9.961
doi: 10.2337/diacare.17.9.961
pubmed: 7988316
Carey VJ, Walters EE, Colditz GA et al (1997) Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women. The Nurses’ Health Study. Am J Epidemiol 145(7):614–619. https://doi.org/10.1093/oxfordjournals.aje.a009158
doi: 10.1093/oxfordjournals.aje.a009158
pubmed: 9098178
Oken E, Gillman MW (2003) Fetal origins of obesity. Obes Res 11(4):496–506. https://doi.org/10.1038/oby.2003.69
doi: 10.1038/oby.2003.69
pubmed: 12690076
Dabelea D, Harrod CS (2013) Role of developmental overnutrition in pediatric obesity and type 2 diabetes. Nutr Rev 71(Suppl 1):S62–S67. https://doi.org/10.1111/nure.12061
doi: 10.1111/nure.12061
pubmed: 24147926
Dabelea D, Crume T (2011) Maternal environment and the transgenerational cycle of obesity and diabetes. Diabetes 60(7):1849–1855. https://doi.org/10.2337/db11-0400
doi: 10.2337/db11-0400
pubmed: 21709280
pmcid: 3121421
Scholtens DM, Kuang A, Lowe LP et al (2019) Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): maternal glycemia and childhood glucose metabolism. Diabetes Care 42(3):381–392. https://doi.org/10.2337/dc18-2021
doi: 10.2337/dc18-2021
pubmed: 30617141
pmcid: 6385697
Ahlqvist E, Storm P, Käräjämäki A et al (2018) Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol 6(5):361–369. https://doi.org/10.1016/s2213-8587(18)30051-2
doi: 10.1016/s2213-8587(18)30051-2
pubmed: 29503172
Esser N, Utzschneider KM, Kahn SE (2020) Early beta cell dysfunction vs insulin hypersecretion as the primary event in the pathogenesis of dysglycaemia. Diabetologia 63(10):2007–2021. https://doi.org/10.1007/s00125-020-05245-x
doi: 10.1007/s00125-020-05245-x
pubmed: 32894311
Erion K, Corkey BE (2018) β-Cell failure or β-cell abuse? Front Endocrinol (Lausanne) 9:532–532. https://doi.org/10.3389/fendo.2018.00532
doi: 10.3389/fendo.2018.00532
Corkey BE (2012) Banting lecture 2011: hyperinsulinemia: cause or consequence? Diabetes 61(1):4–13. https://doi.org/10.2337/db11-1483
doi: 10.2337/db11-1483
pubmed: 22187369
Nolan CJ, Prentki M (2019) Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: time for a conceptual framework shift. Diab Vasc Dis Res 16(2):118–127. https://doi.org/10.1177/1479164119827611
doi: 10.1177/1479164119827611
pubmed: 30770030
RISE Consortium (2018) Metabolic contrasts between youth and adults with impaired glucose tolerance or recently diagnosed type 2 diabetes: I. observations using the hyperglycemic clamp. Diabetes Care 41(8):1696. https://doi.org/10.2337/dc18-0244
Rowley KG, Best JD, McDermott R, Green EA, Piers LS, O'Dea K (1997) Insulin resistance syndrome in Australian aboriginal people. Clin Exp Pharmacol Physiol 24(9–10):776–781. https://doi.org/10.1111/j.1440-1681.1997.tb02131.x
doi: 10.1111/j.1440-1681.1997.tb02131.x
pubmed: 9315388
Pontiroli AE, Alberetto M, Capra F, Pozza G (1990) The glucose clamp technique for the study of patients with hypoglycemia: insulin resistance as a feature of insulinoma. J Endocrinol Investig 13(3):241–245. https://doi.org/10.1007/bf03349549
doi: 10.1007/bf03349549
Del Prato S, Riccio A, Vigili de Kreutzenberg S et al (1993) Mechanisms of fasting hypoglycemia and concomitant insulin resistance in insulinoma patients. Metabolism 42(1):24–29. https://doi.org/10.1016/0026-0495(93)90167-m
doi: 10.1016/0026-0495(93)90167-m
pubmed: 8446044
Battezzati A, Terruzzi I, Perseghin G et al (1995) Defective insulin action on protein and glucose metabolism during chronic hyperinsulinemia in subjects with benign insulinoma. Diabetes 44(7):837–844. https://doi.org/10.2337/diab.44.7.837
doi: 10.2337/diab.44.7.837
pubmed: 7789652
Del Prato S, Leonetti F, Simonson DC, Sheehan P, Matsuda M, DeFronzo RA (1994) Effect of sustained physiologic hyperinsulinaemia and hyperglycaemia on insulin secretion and insulin sensitivity in man. Diabetologia 37(10):1025–1035. https://doi.org/10.1007/bf00400466
doi: 10.1007/bf00400466
pubmed: 7851681
Crume TL, Ogden L, West NA et al (2011) Association of exposure to diabetes in utero with adiposity and fat distribution in a multiethnic population of youth: the Exploring Perinatal Outcomes among Children (EPOCH) Study. Diabetologia 54(1):87–92. https://doi.org/10.1007/s00125-010-1925-3
doi: 10.1007/s00125-010-1925-3
pubmed: 20953862
Freedman DS, Sherry B (2009) The validity of BMI as an indicator of body fatness and risk among children. Pediatrics 124(Suppl 1):S23–S34. https://doi.org/10.1542/peds.2008-3586E
doi: 10.1542/peds.2008-3586E
pubmed: 19720664
Perng WOE, Dabelea D (2019) Developmental overnutrition and obesity and type 2 diabetes in offspring. Diabetologia 62(10):1779–2788. https://doi.org/10.1007/s00125-019-4914-1
National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28(12):1039–1057. https://doi.org/10.2337/diab.28.12.1039
doi: 10.2337/diab.28.12.1039
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419. https://doi.org/10.1007/bf00280883
doi: 10.1007/bf00280883
pubmed: 3899825
Centers for Disease Control and Prevention (2007) National Health and Nutrition Examination Survey (NHANES): Anthropometry Procedures Manual. Available from https://www.cdc.gov/nchs/data/nhanes/nhanes_07_08/manual_an.pdf
Perng W, Hockett CW, Sauder KA, Dabelea D (2020) In utero exposure to gestational diabetes mellitus and cardiovascular risk factors in youth: a longitudinal analysis in the EPOCH cohort. Pediatr Obes 15(5):e12611. https://doi.org/10.1111/ijpo.12611
doi: 10.1111/ijpo.12611
pubmed: 31920001
pmcid: 8311655
Marshall WA, Tanner JM (1968) Growth and physiological development during adolescence. Annu Rev Med 19:283–300. https://doi.org/10.1146/annurev.me.19.020168.001435
doi: 10.1146/annurev.me.19.020168.001435
pubmed: 4297619
Chavarro JE, Watkins DJ, Afeiche MC et al (2017) Validity of self-assessed sexual maturation against physician assessments and hormone levels. J Pediatr 186:172–178.e173. https://doi.org/10.1016/j.jpeds.2017.03.050
doi: 10.1016/j.jpeds.2017.03.050
pubmed: 28438374
pmcid: 5492944
Weston AT, Petosa R, Pate RR (1997) Validation of an instrument for measurement of physical activity in youth. Med Sci Sports Exerc 29(1):138–143. https://doi.org/10.1097/00005768-199701000-00020
doi: 10.1097/00005768-199701000-00020
pubmed: 9000167
Cullen KW, Watson K, Zakeri I (2008) Relative reliability and validity of the Block Kids Questionnaire among youth aged 10 to 17 years. J Am Diet Assoc 108(5):862–866. https://doi.org/10.1016/j.jada.2008.02.015
doi: 10.1016/j.jada.2008.02.015
pubmed: 18442512
Kaess BM, Pedley A, Massaro JM, Murabito J, Hoffmann U, Fox CS (2012) The ratio of visceral to subcutaneous fat, a metric of body fat distribution, is a unique correlate of cardiometabolic risk. Diabetologia 55(10):2622–2630. https://doi.org/10.1007/s00125-012-2639-5
doi: 10.1007/s00125-012-2639-5
pubmed: 22898763
pmcid: 22898763
Tu YK, West R, Ellison GT, Gilthorpe MS (2005) Why evidence for the fetal origins of adult disease might be a statistical artifact: the “reversal paradox” for the relation between birth weight and blood pressure in later life. Am J Epidemiol 161(1):27–32. https://doi.org/10.1093/aje/kwi002
doi: 10.1093/aje/kwi002
pubmed: 15615910
Tam WH, Ma RCW, Ozaki R et al (2017) In utero exposure to maternal hyperglycemia increases childhood cardiometabolic risk in offspring. Diabetes Care 40(5):679–686. https://doi.org/10.2337/dc16-2397
doi: 10.2337/dc16-2397
pubmed: 28279981
pmcid: 5399651
Sauder KA, Hockett CW, Ringham BM, Glueck DH, Dabelea D (2017) Fetal overnutrition and offspring insulin resistance and β-cell function: the Exploring Perinatal Outcomes among Children (EPOCH) study. Diabet Med 34(10):1392–1399. https://doi.org/10.1111/dme.13417
doi: 10.1111/dme.13417
pubmed: 28636758
pmcid: 5603388
Chen YY, Wang JP, Jiang YY et al (2015) Fasting plasma insulin at 5 years of age predicted subsequent weight increase in early childhood over a 5-year period—the Da Qing children cohort study. PLoS One 10(6):e0127389. https://doi.org/10.1371/journal.pone.0127389
doi: 10.1371/journal.pone.0127389
pubmed: 26047327
pmcid: 4457927
Schooling CM (2015) Life course epidemiology: recognising the importance of puberty. J Epidemiol Community Health 69(8):820. https://doi.org/10.1136/jech-2015-205607
doi: 10.1136/jech-2015-205607
pubmed: 25855123