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Erschienen in: Current Diabetes Reports 9/2020

01.09.2020 | Pathogenesis of Type 2 Diabetes and Insulin Resistance (ME Patti, Section Editor)

Type 2 Diabetes in Youth: the Role of Early Life Exposures

verfasst von: Ankur Rughani, Jacob E. Friedman, Jeanie B. Tryggestad

Erschienen in: Current Diabetes Reports | Ausgabe 9/2020

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Abstract

Purpose of Review

This review examines the impact of early life exposures on glucose metabolism in the offspring and explores potential metabolic mechanisms leading to type 2 diabetes in childhood.

Recent Findings

One in five adolescents is diagnosed with prediabetes. Recent studies have elucidated the impact of early exposures such as maternal diabetes, but also hyperglycemia below the threshold of gestational diabetes, obesity, hyperlipidemia, and paternal obesity on the future metabolic health of the offspring. Mechanisms affecting the developmental programing of offspring toward type 2 diabetes include epigenetic modifications, alterations in stem cell differentiation, metabolome and microbiome variation, immune dysregulation, and neonatal nutrition.

Summary

The risk of type 2 diabetes in offspring is increased not only by diabetes exposure in utero but also by exposure to a heterogeneous milieu of factors that accompany maternal obesity that provoke a vicious cycle of metabolic disease. The key period for intervention to prevent type 2 diabetes is within the first 1000 days of life.
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Zurück zum Zitat Dani C, Bresci C, Berti E, Ottanelli S, Mello G, Mecacci F, et al. Metabolomic profile of term infants of gestational diabetic mothers. The Journal of Maternal-Fetal & Neonatal Medicine : the official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2014;27(6):537–42. Dani C, Bresci C, Berti E, Ottanelli S, Mello G, Mecacci F, et al. Metabolomic profile of term infants of gestational diabetic mothers. The Journal of Maternal-Fetal & Neonatal Medicine : the official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2014;27(6):537–42.
49•.
Zurück zum Zitat Schlueter RJ, Alakwaa FM, Benny PA, Gurary A, Xie G, Jia W, et al. Pre-pregnant obesity of mothers in a multi-ethnic cohort is associated with cord blood metabolomic changes in offspring. J Proteome Res. 2020. A case-control study investigated the metabolomic changes in cord blood from infants exposed to obese vs. normal weight mothers and identified several cord blood metabolites associated with maternal obesity. Schlueter RJ, Alakwaa FM, Benny PA, Gurary A, Xie G, Jia W, et al. Pre-pregnant obesity of mothers in a multi-ethnic cohort is associated with cord blood metabolomic changes in offspring. J Proteome Res. 2020. A case-control study investigated the metabolomic changes in cord blood from infants exposed to obese vs. normal weight mothers and identified several cord blood metabolites associated with maternal obesity.
50•.
Zurück zum Zitat Shokry E, Marchioro L, Uhl O, Bermudez MG, Garcia-Santos JA, Segura MT, et al. Impact of maternal BMI and gestational diabetes mellitus on maternal and cord blood metabolome: results from the PREOBE cohort study. Acta Diabetol. 2019;56(4):421–30. A German study that examines metabolites in maternal and fetal blood with associations noted between BMI and branched chain amino acids, as well as inflammation and beta oxidation with GDM. Shokry E, Marchioro L, Uhl O, Bermudez MG, Garcia-Santos JA, Segura MT, et al. Impact of maternal BMI and gestational diabetes mellitus on maternal and cord blood metabolome: results from the PREOBE cohort study. Acta Diabetol. 2019;56(4):421–30. A German study that examines metabolites in maternal and fetal blood with associations noted between BMI and branched chain amino acids, as well as inflammation and beta oxidation with GDM.
51.
Zurück zum Zitat Lowe WL Jr, Bain JR, Nodzenski M, Reisetter AC, Muehlbauer MJ, Stevens RD, et al. Maternal BMI and Glycemia impact the fetal metabolome. Diabetes Care. 2017;40(7):902–10.PubMedPubMedCentral Lowe WL Jr, Bain JR, Nodzenski M, Reisetter AC, Muehlbauer MJ, Stevens RD, et al. Maternal BMI and Glycemia impact the fetal metabolome. Diabetes Care. 2017;40(7):902–10.PubMedPubMedCentral
52•.
Zurück zum Zitat Perng W, Ringham BM, Smith HA, Michelotti G, Kechris KM, Dabelea D. A prospective study of associations between in utero exposure to gestational diabetes mellitus and metabolomic profiles during late childhood and adolescence. Diabetologia. 2020;63(2):296–312. This prospective study performed investigated the impact of exposure to GDM on metabolite patterns from childhood through adolescence and found higher circulating phospholipids in offspring exposed to GDM which were associated with higher adiposity and worse metabolic profile in females. Perng W, Ringham BM, Smith HA, Michelotti G, Kechris KM, Dabelea D. A prospective study of associations between in utero exposure to gestational diabetes mellitus and metabolomic profiles during late childhood and adolescence. Diabetologia. 2020;63(2):296–312. This prospective study performed investigated the impact of exposure to GDM on metabolite patterns from childhood through adolescence and found higher circulating phospholipids in offspring exposed to GDM which were associated with higher adiposity and worse metabolic profile in females.
53.
Zurück zum Zitat Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. 2014;10(12):723–36.PubMedPubMedCentral Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. 2014;10(12):723–36.PubMedPubMedCentral
54•.
Zurück zum Zitat Broadney MM, Chahal N, Michels KA, McLain AC, Ghassabian A, Lawrence DA, et al. Impact of parental obesity on neonatal markers of inflammation and immune response. Int J Obes. 2017;41(1):30–7. This study examined the association between parental BMI and gestational weight gain and markers of inflammation and immune function in the offspring identifying an association between maternal (but not paternal) BMI and systemic inflammation in newborns. Broadney MM, Chahal N, Michels KA, McLain AC, Ghassabian A, Lawrence DA, et al. Impact of parental obesity on neonatal markers of inflammation and immune response. Int J Obes. 2017;41(1):30–7. This study examined the association between parental BMI and gestational weight gain and markers of inflammation and immune function in the offspring identifying an association between maternal (but not paternal) BMI and systemic inflammation in newborns.
55.
Zurück zum Zitat Sureshchandra S, Wilson RM, Rais M, Marshall NE, Purnell JQ, Thornburg KL, et al. Maternal Pregravid obesity remodels the DNA methylation landscape of cord blood monocytes disrupting their inflammatory program. J Immunol. 2017;199(8):2729–44.PubMedPubMedCentral Sureshchandra S, Wilson RM, Rais M, Marshall NE, Purnell JQ, Thornburg KL, et al. Maternal Pregravid obesity remodels the DNA methylation landscape of cord blood monocytes disrupting their inflammatory program. J Immunol. 2017;199(8):2729–44.PubMedPubMedCentral
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Zurück zum Zitat Segovia SA, Vickers MH, Gray C, Reynolds CM. Maternal obesity, inflammation, and developmental programming. Biomed Res Int. 2014;2014:418975.PubMedPubMedCentral Segovia SA, Vickers MH, Gray C, Reynolds CM. Maternal obesity, inflammation, and developmental programming. Biomed Res Int. 2014;2014:418975.PubMedPubMedCentral
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Zurück zum Zitat Marques AH, Bjorke-Monsen AL, Teixeira AL, Silverman MN. Maternal stress, nutrition and physical activity: impact on immune function, CNS Development and Psychopathology. Brain Res. 1617;2015:28–46. Marques AH, Bjorke-Monsen AL, Teixeira AL, Silverman MN. Maternal stress, nutrition and physical activity: impact on immune function, CNS Development and Psychopathology. Brain Res. 1617;2015:28–46.
58.
Zurück zum Zitat Teague AM, Fields DA, Aston CE, Short KR, Lyons TJ, Chernausek SD. Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and native American women with diabetes mellitus. Reprod Biol Endocrinol. 2015;13:68.PubMedPubMedCentral Teague AM, Fields DA, Aston CE, Short KR, Lyons TJ, Chernausek SD. Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and native American women with diabetes mellitus. Reprod Biol Endocrinol. 2015;13:68.PubMedPubMedCentral
59•.
Zurück zum Zitat Kampmann FB, Thuesen ACB, Hjort L, Bjerregaard AA, Chavarro J, Frystyk J, et al. Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes. Eur J Endocrinol. 2019. A cross-sectional Danish study of offspring aged 9—16 years measured body composition, pubertal status, and metabolic characteristics of offspring exposed to GDM in utero and found that GDM exposure was correlated with higher leptin, lower adiponectin, and lower FGF21 though leptin and adiponectin were likely associated with offspring obesity. Kampmann FB, Thuesen ACB, Hjort L, Bjerregaard AA, Chavarro J, Frystyk J, et al. Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes. Eur J Endocrinol. 2019. A cross-sectional Danish study of offspring aged 9—16 years measured body composition, pubertal status, and metabolic characteristics of offspring exposed to GDM in utero and found that GDM exposure was correlated with higher leptin, lower adiponectin, and lower FGF21 though leptin and adiponectin were likely associated with offspring obesity.
60.
Zurück zum Zitat Esteve E, Ricart W, Fernandez-Real JM. Adipocytokines and insulin resistance: the possible role of lipocalin-2, retinol binding protein-4, and adiponectin. Diabetes Care. 2009;32(Suppl 2):S362–7.PubMedPubMedCentral Esteve E, Ricart W, Fernandez-Real JM. Adipocytokines and insulin resistance: the possible role of lipocalin-2, retinol binding protein-4, and adiponectin. Diabetes Care. 2009;32(Suppl 2):S362–7.PubMedPubMedCentral
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Zurück zum Zitat Amitani M, Asakawa A, Amitani H, Inui A. The role of leptin in the control of insulin glucose axis. Front Neurosci. 2013;7:51.PubMedPubMedCentral Amitani M, Asakawa A, Amitani H, Inui A. The role of leptin in the control of insulin glucose axis. Front Neurosci. 2013;7:51.PubMedPubMedCentral
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Zurück zum Zitat Cottrell EC, Cripps RL, Duncan JS, Barrett P, Mercer JG, Herwig A, et al. Developmental changes in hypothalamic leptin receptor: relationship with the postnatal leptin surge and energy balance neuropeptides in the postnatal rat. Am J Physiol Regul Integr Comp Physiol. 2009;296(3):R631–9.PubMedPubMedCentral Cottrell EC, Cripps RL, Duncan JS, Barrett P, Mercer JG, Herwig A, et al. Developmental changes in hypothalamic leptin receptor: relationship with the postnatal leptin surge and energy balance neuropeptides in the postnatal rat. Am J Physiol Regul Integr Comp Physiol. 2009;296(3):R631–9.PubMedPubMedCentral
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Zurück zum Zitat Herzberg-Schafer S, Heni M, Stefan N, Haring HU, Fritsche A. Impairment of GLP1-induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemia. Diabetes Obes Metab. 2012;14(Suppl 3):85–90.PubMed Herzberg-Schafer S, Heni M, Stefan N, Haring HU, Fritsche A. Impairment of GLP1-induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemia. Diabetes Obes Metab. 2012;14(Suppl 3):85–90.PubMed
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Zurück zum Zitat Chandler-Laney PC, Bush NC, Rouse DJ, Mancuso MS, Gower BA. Gut hormone activity of children born to women with and without gestational diabetes. Pediatr Obes. 2014;9(1):53–62.PubMed Chandler-Laney PC, Bush NC, Rouse DJ, Mancuso MS, Gower BA. Gut hormone activity of children born to women with and without gestational diabetes. Pediatr Obes. 2014;9(1):53–62.PubMed
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Zurück zum Zitat Kelstrup L, Clausen TD, Mathiesen ER, Hansen T, Holst JJ, Damm P. Incretin and glucagon levels in adult offspring exposed to maternal diabetes in pregnancy. J Clin Endocrinol Metab. 2015;100(5):1967–75.PubMed Kelstrup L, Clausen TD, Mathiesen ER, Hansen T, Holst JJ, Damm P. Incretin and glucagon levels in adult offspring exposed to maternal diabetes in pregnancy. J Clin Endocrinol Metab. 2015;100(5):1967–75.PubMed
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Zurück zum Zitat del Rosario MC, Ossowski V, Knowler WC, Bogardus C, Baier LJ, Hanson RL. Potential epigenetic dysregulation of genes associated with MODY and type 2 diabetes in humans exposed to a diabetic intrauterine environment: an analysis of genome-wide DNA methylation. Metabolism. 2014;63(5):654–60.PubMedPubMedCentral del Rosario MC, Ossowski V, Knowler WC, Bogardus C, Baier LJ, Hanson RL. Potential epigenetic dysregulation of genes associated with MODY and type 2 diabetes in humans exposed to a diabetic intrauterine environment: an analysis of genome-wide DNA methylation. Metabolism. 2014;63(5):654–60.PubMedPubMedCentral
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Zurück zum Zitat Chen P, Piaggi P, Traurig M, Bogardus C, Knowler WC, Baier LJ, et al. Differential methylation of genes in individuals exposed to maternal diabetes in utero. Diabetologia. 2017;60(4):645–55. A genomewide DNA methylation study of peripheral blood from Pima Indian offspring revealed differentially methylated CpGs in 39 genomic regions associated with intrauterine DM exposure. Chen P, Piaggi P, Traurig M, Bogardus C, Knowler WC, Baier LJ, et al. Differential methylation of genes in individuals exposed to maternal diabetes in utero. Diabetologia. 2017;60(4):645–55. A genomewide DNA methylation study of peripheral blood from Pima Indian offspring revealed differentially methylated CpGs in 39 genomic regions associated with intrauterine DM exposure.
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Zurück zum Zitat Lin X, Lim IY, Wu Y, Teh AL, Chen L, Aris IM, et al. Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome. BMC Med. 2017;15(1):50.PubMedPubMedCentral Lin X, Lim IY, Wu Y, Teh AL, Chen L, Aris IM, et al. Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome. BMC Med. 2017;15(1):50.PubMedPubMedCentral
69•.
Zurück zum Zitat Hjort L, Martino D, Grunnet LG, Naeem H, Maksimovic J, Olsson AH, et al. Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children. JCI Insight. 2018;3(17). A Danish study genome-wide DNA methylation study comparing the DNA methylation profiles of GDM exposed and control offspring found differentially methylated CpGs in GDM exposed offspring at 9-16 years of age, however, a significant number of methylated CpGs were associated with prepregnancy maternal BMI rather than GDM. Hjort L, Martino D, Grunnet LG, Naeem H, Maksimovic J, Olsson AH, et al. Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children. JCI Insight. 2018;3(17). A Danish study genome-wide DNA methylation study comparing the DNA methylation profiles of GDM exposed and control offspring found differentially methylated CpGs in GDM exposed offspring at 9-16 years of age, however, a significant number of methylated CpGs were associated with prepregnancy maternal BMI rather than GDM.
70.
Zurück zum Zitat Sharp GC, Salas LA, Monnereau C, Allard C, Yousefi P, Everson TM, et al. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium. Hum Mol Genet. 2017;26(20):4067–85.PubMedPubMedCentral Sharp GC, Salas LA, Monnereau C, Allard C, Yousefi P, Everson TM, et al. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium. Hum Mol Genet. 2017;26(20):4067–85.PubMedPubMedCentral
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Zurück zum Zitat Thakali KM, Faske JB, Ishwar A, Alfaro MP, Cleves MA, Badger TM, et al. Maternal obesity and gestational weight gain are modestly associated with umbilical cord DNA methylation. Placenta. 2017;57:194–203.PubMed Thakali KM, Faske JB, Ishwar A, Alfaro MP, Cleves MA, Badger TM, et al. Maternal obesity and gestational weight gain are modestly associated with umbilical cord DNA methylation. Placenta. 2017;57:194–203.PubMed
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Zurück zum Zitat Sharp GC, Lawlor DA, Richmond RC, Fraser A, Simpkin A, Suderman M, et al. Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon longitudinal study of parents and children. Int J Epidemiol. 2015;44(4):1288–304.PubMedPubMedCentral Sharp GC, Lawlor DA, Richmond RC, Fraser A, Simpkin A, Suderman M, et al. Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon longitudinal study of parents and children. Int J Epidemiol. 2015;44(4):1288–304.PubMedPubMedCentral
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Zurück zum Zitat Juvinao-Quintero DL, Hivert M-F, Sharp GC, Relton CL, Elliott HR. DNA methylation and type 2 diabetes: the use of Mendelian randomization to assess causality. Curr Genet Med Rep. 2019;7(4):191–207.PubMedPubMedCentral Juvinao-Quintero DL, Hivert M-F, Sharp GC, Relton CL, Elliott HR. DNA methylation and type 2 diabetes: the use of Mendelian randomization to assess causality. Curr Genet Med Rep. 2019;7(4):191–207.PubMedPubMedCentral
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Zurück zum Zitat Tryggestad JB, Vishwanath A, Jiang S, Mallappa A, Teague AM, Takahashi Y, et al. Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA. Clin Sci (Lond). 2016;130(21):1955–67. Tryggestad JB, Vishwanath A, Jiang S, Mallappa A, Teague AM, Takahashi Y, et al. Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA. Clin Sci (Lond). 2016;130(21):1955–67.
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Zurück zum Zitat Floris I, Descamps B, Vardeu A, Mitic T, Posadino AM, Shantikumar S, et al. Gestational diabetes mellitus impairs fetal endothelial cell functions through a mechanism involving microRNA-101 and histone methyltransferase enhancer of zester homolog-2. Arterioscler Thromb Vasc Biol. 2015;35(3):664–74.PubMed Floris I, Descamps B, Vardeu A, Mitic T, Posadino AM, Shantikumar S, et al. Gestational diabetes mellitus impairs fetal endothelial cell functions through a mechanism involving microRNA-101 and histone methyltransferase enhancer of zester homolog-2. Arterioscler Thromb Vasc Biol. 2015;35(3):664–74.PubMed
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Zurück zum Zitat Houshmand-Oeregaard A, Schrolkamp M, Kelstrup L, Hansen NS, Hjort L, Thuesen ACB, et al. Increased expression of microRNA-15a and microRNA-15b in skeletal muscle from adult offspring of women with diabetes in pregnancy. Hum Mol Genet. 2018;27(10):1763–71.PubMed Houshmand-Oeregaard A, Schrolkamp M, Kelstrup L, Hansen NS, Hjort L, Thuesen ACB, et al. Increased expression of microRNA-15a and microRNA-15b in skeletal muscle from adult offspring of women with diabetes in pregnancy. Hum Mol Genet. 2018;27(10):1763–71.PubMed
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Zurück zum Zitat Jones A, Danielson KM, Benton MC, Ziegler O, Shah R, Stubbs RS, et al. miRNA signatures of insulin resistance in obesity. Obesity (Silver Spring). 2017;25(10):1734–44. Jones A, Danielson KM, Benton MC, Ziegler O, Shah R, Stubbs RS, et al. miRNA signatures of insulin resistance in obesity. Obesity (Silver Spring). 2017;25(10):1734–44.
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Zurück zum Zitat Ma E, Fu Y, Garvey WT. Relationship of circulating miRNAs with insulin sensitivity and associated metabolic risk factors in humans. Metab Syndr Relat Disord. 2018;16(2):82–9.PubMedPubMedCentral Ma E, Fu Y, Garvey WT. Relationship of circulating miRNAs with insulin sensitivity and associated metabolic risk factors in humans. Metab Syndr Relat Disord. 2018;16(2):82–9.PubMedPubMedCentral
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Zurück zum Zitat Shah R, Murthy V, Pacold M, Danielson K, Tanriverdi K, Larson MG, et al. Extracellular RNAs are associated with insulin resistance and metabolic phenotypes. Diabetes Care. 2017;40(4):546–53.PubMedPubMedCentral Shah R, Murthy V, Pacold M, Danielson K, Tanriverdi K, Larson MG, et al. Extracellular RNAs are associated with insulin resistance and metabolic phenotypes. Diabetes Care. 2017;40(4):546–53.PubMedPubMedCentral
80•.
Zurück zum Zitat Noor N, Cardenas A, Rifas-Shiman SL, Pan H, Dreyfuss JM, Oken E, et al. Association of Periconception Paternal Body Mass Index with Persistent Changes in DNA methylation of offspring in childhood. JAMA Netw Open. 2019;2(12):e1916777. This prospective longitudinal study in the US (Project Viva) evaluated genome-wide DNA methylation patterns in offspring from 429 fathermother-child triads at ages 3 and 7 years finding that paternal BMI was associated with the offspring’s DNA methylation, birth weight, and childhood BMI. Noor N, Cardenas A, Rifas-Shiman SL, Pan H, Dreyfuss JM, Oken E, et al. Association of Periconception Paternal Body Mass Index with Persistent Changes in DNA methylation of offspring in childhood. JAMA Netw Open. 2019;2(12):e1916777. This prospective longitudinal study in the US (Project Viva) evaluated genome-wide DNA methylation patterns in offspring from 429 fathermother-child triads at ages 3 and 7 years finding that paternal BMI was associated with the offspring’s DNA methylation, birth weight, and childhood BMI.
81.
Zurück zum Zitat van Otterdijk SD, Michels KB. Transgenerational epigenetic inheritance in mammals: how good is the evidence? FASEB J. 2016;30(7):2457–65.PubMed van Otterdijk SD, Michels KB. Transgenerational epigenetic inheritance in mammals: how good is the evidence? FASEB J. 2016;30(7):2457–65.PubMed
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Zurück zum Zitat Boyle KE, Patinkin ZW, Shapiro AL, Baker PR 2nd, Dabelea D, Friedman JE. Mesenchymal stem cells from infants born to obese mothers exhibit greater potential for Adipogenesis: the healthy start BabyBUMP project. Diabetes. 2016;65(3):647–59.PubMed Boyle KE, Patinkin ZW, Shapiro AL, Baker PR 2nd, Dabelea D, Friedman JE. Mesenchymal stem cells from infants born to obese mothers exhibit greater potential for Adipogenesis: the healthy start BabyBUMP project. Diabetes. 2016;65(3):647–59.PubMed
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Zurück zum Zitat Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep. 2015;35(2). Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep. 2015;35(2).
84•.
Zurück zum Zitat Boyle KE, Patinkin ZW, Shapiro ALB, Bader C, Vanderlinden L, Kechris K, et al. Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants. Mol Metab. 2017;6(11):1503–16. Using data from the Healthy Start longitudinal cohort, umbilical derived mesenchymal stem cells exhibit greater lipid accumulation, lower fatty acid oxidation, and dysregulation of AMPK activity when undergoing myogenesis in vitro. Boyle KE, Patinkin ZW, Shapiro ALB, Bader C, Vanderlinden L, Kechris K, et al. Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants. Mol Metab. 2017;6(11):1503–16. Using data from the Healthy Start longitudinal cohort, umbilical derived mesenchymal stem cells exhibit greater lipid accumulation, lower fatty acid oxidation, and dysregulation of AMPK activity when undergoing myogenesis in vitro.
85•.
Zurück zum Zitat Baker PR 2nd, Patinkin Z, Shapiro AL, De La Houssaye BA, Woontner M, Boyle KE, et al. Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism. JCI Insight. 2017;2(21). This study explores the variation in energy metabolism and gene expression that occur in differentiating umbilical MSC myocytes and adipocytes in offspring of normal weight and obese mothers. Baker PR 2nd, Patinkin Z, Shapiro AL, De La Houssaye BA, Woontner M, Boyle KE, et al. Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism. JCI Insight. 2017;2(21). This study explores the variation in energy metabolism and gene expression that occur in differentiating umbilical MSC myocytes and adipocytes in offspring of normal weight and obese mothers.
86•.
Zurück zum Zitat Baker PR 2nd, Patinkin ZW, Shapiro ALB, de la Houssaye BA, Janssen RC, Vanderlinden LA, et al. Altered gene expression and metabolism in fetal umbilical cord mesenchymal stem cells correspond with differences in 5-month-old infant adiposity gain. Sci Rep. 2017;7(1):18095. This study provides the first evidence of alterations in metabolic pathways in the adipocytes and myocytes in infants with rapid vs. lower postnatal gain in adiposity. Baker PR 2nd, Patinkin ZW, Shapiro ALB, de la Houssaye BA, Janssen RC, Vanderlinden LA, et al. Altered gene expression and metabolism in fetal umbilical cord mesenchymal stem cells correspond with differences in 5-month-old infant adiposity gain. Sci Rep. 2017;7(1):18095. This study provides the first evidence of alterations in metabolic pathways in the adipocytes and myocytes in infants with rapid vs. lower postnatal gain in adiposity.
87•.
Zurück zum Zitat Iaffaldano L, Nardelli C, D'Alessio F, D'Argenio V, Nunziato M, Mauriello L, et al. Altered bioenergetic profile in umbilical cord and amniotic mesenchymal stem cells from newborns of obese women. Stem Cells Dev. 2018;27(3):199–206. This study showed that maternal obesity decreases the efficiency of glycolysis and mitochondrial respiration on placental and umbilical cord mesenchymal stem cells. Iaffaldano L, Nardelli C, D'Alessio F, D'Argenio V, Nunziato M, Mauriello L, et al. Altered bioenergetic profile in umbilical cord and amniotic mesenchymal stem cells from newborns of obese women. Stem Cells Dev. 2018;27(3):199–206. This study showed that maternal obesity decreases the efficiency of glycolysis and mitochondrial respiration on placental and umbilical cord mesenchymal stem cells.
88.
89•.
Zurück zum Zitat Kumbhare SV, Patangia DVV, Patil RH, Shouche YS, Patil NP. Factors influencing the gut microbiome in children: from infancy to childhood. J Biosci. 2019;44(2). A review of factors that influence microbiome composition in children starting in the fetus through childhood. Kumbhare SV, Patangia DVV, Patil RH, Shouche YS, Patil NP. Factors influencing the gut microbiome in children: from infancy to childhood. J Biosci. 2019;44(2). A review of factors that influence microbiome composition in children starting in the fetus through childhood.
90•.
Zurück zum Zitat Robertson RC, Manges AR, Finlay BB, Prendergast AJ. The human microbiome and child growth - first 1000 days and beyond. Trends Microbiol. 2019;27(2):131–47. A review highlighting the emerging evidence on the importance of the microbiome to child health and growth, especially during the first 3 years of life. Robertson RC, Manges AR, Finlay BB, Prendergast AJ. The human microbiome and child growth - first 1000 days and beyond. Trends Microbiol. 2019;27(2):131–47. A review highlighting the emerging evidence on the importance of the microbiome to child health and growth, especially during the first 3 years of life.
91•.
Zurück zum Zitat Soderborg TK, Clark SE, Mulligan CE, Janssen RC, Babcock L, Ir D, et al. The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD. Nat Commun. 2018;9(1):4462. A germ-free mouse model with fecal transplant from infants born to mothers with obesity compared to those born to normal weight mothers demonstrated that early changes to the gut microbiome in infants alters gut permeability, macrophage activity, and hepatic inflammation. Soderborg TK, Clark SE, Mulligan CE, Janssen RC, Babcock L, Ir D, et al. The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD. Nat Commun. 2018;9(1):4462. A germ-free mouse model with fecal transplant from infants born to mothers with obesity compared to those born to normal weight mothers demonstrated that early changes to the gut microbiome in infants alters gut permeability, macrophage activity, and hepatic inflammation.
92•.
Zurück zum Zitat Paun A, Danska JS. Modulation of type 1 and type 2 diabetes risk by the intestinal microbiome. Pediatr Diabetes. 2016;17(7):469–77. This review highlights the association of microbiome composition to pancreatic immunity, insulin resistance, and obesity. Paun A, Danska JS. Modulation of type 1 and type 2 diabetes risk by the intestinal microbiome. Pediatr Diabetes. 2016;17(7):469–77. This review highlights the association of microbiome composition to pancreatic immunity, insulin resistance, and obesity.
93•.
Zurück zum Zitat Kimura I, Miyamoto J, Ohue-Kitano R, Watanabe K, Yamada T, Onuki M, et al. Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice. Science. 2020;367(6481). This murine study demonstrated the importance of short-chain fatty acids from maternal gut microbiota during pregnancy on the development of metabolic syndrome in the offspring. Kimura I, Miyamoto J, Ohue-Kitano R, Watanabe K, Yamada T, Onuki M, et al. Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice. Science. 2020;367(6481). This murine study demonstrated the importance of short-chain fatty acids from maternal gut microbiota during pregnancy on the development of metabolic syndrome in the offspring.
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Zurück zum Zitat Lemas DJ, Young BE, Baker PR 2nd, Tomczik AC, Soderborg TK, Hernandez TL, et al. Alterations in human milk leptin and insulin are associated with early changes in the infant intestinal microbiome. Am J Clin Nutr. 2016;103(5):1291–300.PubMedPubMedCentral Lemas DJ, Young BE, Baker PR 2nd, Tomczik AC, Soderborg TK, Hernandez TL, et al. Alterations in human milk leptin and insulin are associated with early changes in the infant intestinal microbiome. Am J Clin Nutr. 2016;103(5):1291–300.PubMedPubMedCentral
95•.
Zurück zum Zitat Young BE, Levek C, Reynolds RM, Rudolph MC, MacLean P, Hernandez TL, et al. Bioactive components in human milk are differentially associated with rates of lean and fat mass deposition in infants of mothers with normal vs. elevated BMI. Pediatr Obes. 2018;13(10):598–606. This longitudinal observational study examines the impact of human milk components on infant body composition. Young BE, Levek C, Reynolds RM, Rudolph MC, MacLean P, Hernandez TL, et al. Bioactive components in human milk are differentially associated with rates of lean and fat mass deposition in infants of mothers with normal vs. elevated BMI. Pediatr Obes. 2018;13(10):598–606. This longitudinal observational study examines the impact of human milk components on infant body composition.
96•.
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Metadaten
Titel
Type 2 Diabetes in Youth: the Role of Early Life Exposures
verfasst von
Ankur Rughani
Jacob E. Friedman
Jeanie B. Tryggestad
Publikationsdatum
01.09.2020
Verlag
Springer US
Erschienen in
Current Diabetes Reports / Ausgabe 9/2020
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-020-01328-6

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