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Low birth weight, a risk factor for diseases in later life, is a surrogate of insulin resistance at birth

Tian, Meia; Reichetzeder, Christophb; Li, Jiana; Hocher, Bertholda,c,d

doi: 10.1097/HJH.0000000000002156
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Low birth weight (LBW) is associated with diseases in adulthood. The birthweight attributed risk is independent of confounding such as gestational age, sex of the newborn but also social factors. The birthweight attributed risk for diseases in later life holds for the whole spectrum of birthweight. This raises the question what pathophysiological principle is actually behind the association. In this review, we provide evidence that LBW is a surrogate of insulin resistance. Insulin resistance has been identified as a key factor leading to type 2 diabetes, cardiovascular disease as well as kidney diseases. We first provide evidence linking LBW to insulin resistance during intrauterine life. This might be caused by both genetic (genetic variations of genes controlling glucose homeostasis) and/or environmental factors (due to alterations of macronutrition and micronutrition of the mother during pregnancy, but also effects of paternal nutrition prior to conception) leading via epigenetic modifications to early life insulin resistance and alterations of intrauterine growth, as insulin is a growth factor in early life. LBW is rather a surrogate of insulin resistance in early life – either due to inborn genetic or environmental reasons – rather than a player on its own.

aKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China

bInstitute of Nutritional Science, University of Potsdam, Nuthetal

cFifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany

dReproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China

Correspondence to Berthold Hocher, Prof Dr, Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China. E-mail: berthold.hocher@medma.uni-heidelberg.de

Abbreviations: CKD, chronic kidney disease; CVD, cardiovascular disease; FGR, fetal growth restriction; GDM, gestational diabetes mellitus; GFR, glomerular filtration rate; GH-IGF, growth hormone-insulin-like growth factor; HPA, hypothalamo–pituitary–adrenal; LBW, low birth weight; mTOR, mammalian target of rapamycin; PCOS, polycystic ovary syndrome; PM2.5, fine particulate matter; POMC, pro-opiomelanocortin; PPAR, peroxisome proliferator-activated receptor; T2DM, type 2 diabetes mellitus; TGH, total glycated hemoglobin

Received 26 February, 2019

Revised 6 April, 2019

Accepted 22 April, 2019

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