Combined Effects of Genetic and Environmental Factors on Insulin Resistance Associated With Reduced Fetal Growth

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. 12; pp. 3473 - 3478
• Main Authors: JAQUET, Delphine, TREGOUËT, David A, GODEFROY, Thierry, NICAUD, Viviane, CHEVENNE, Didi, TIRET, Laurence, CZERNICHOW, Paul, LEVY-MARCHAL, Claire
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.12.2002
• Subjects: Adult; Alleles; Biological and medical sciences; Birth weight; Blood Glucose - analysis; Body fat; Body Mass Index; Diabetes; Embryonic and Fetal Development - genetics; Embryonic and Fetal Development - physiology; Fasting - blood; Female; Fetal growth retardation; Fetus; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic aspects; Genetic polymorphisms; Gestational age; Glucose; Glucose Tolerance Test; Growth retardation; Health aspects; Heterozygote; Humans; Infant, Newborn; Infant, Small for Gestational Age - physiology; Insulin - blood; Insulin resistance; Insulin Resistance - genetics; Insulin Resistance - physiology; Male; Metabolism; Metabolites; Polymorphism, Genetic - physiology; Pregnancy - physiology; Receptors, Adrenergic, beta-3 - genetics; Receptors, Cytoplasmic and Nuclear - genetics; Reference Values; Transcription Factors - genetics; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-TNF
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.12.3473

Combined Effects of Genetic and Environmental Factors on Insulin Resistance Associated With Reduced Fetal Growth Delphine Jaquet 1 , David A. Trégouët 2 , Thierry Godefroy 2 , Viviane Nicaud 2 , Didi Chevenne 3 , Laurence Tiret 2 , Paul Czernichow 1 and Claire Lévy-Marchal 1 1 INSERM Unit 457; Hôpital R. Debré, Paris, France 2 INSERM Unit 525, Faculté de Médecine de la Pitié, Paris, France 3 Department of Biochemistry, Hôpital R. Debré, Paris, France Abstract It has been suggested that the insulin resistance (IR) associated with reduced fetal growth results from interactions between genetic factors and an unfavorable fetal environment. In addition, the adipose tissue seems to play a key role in this association. We investigated whether polymorphisms in tumor necrosis factor (TNF)-α(G−308A), β3 adrenoreceptor (ADRB3)(G+250C), and peroxisome proliferator-activated receptor (PPAR)-γ2(Pro12Ala), key molecules of the adipose tissue, might affect the IR associated with reduced fetal growth. They were genotyped in 171 subjects who were born small for gestational age (SGA) and in 233 subjects who were born appropriate for gestational age (AGA) and underwent an oral glucose tolerance test (OGTT). The SGA group showed higher serum insulin concentrations than the AGA group at fasting ( P = 0.03) and after stimulation ( P = 0.0007), whereas no difference in serum glucose concentrations was observed. The frequencies of the alleles of these three polymorphisms were similar in both groups. In neither group did the polymorphisms affect glucose tolerance. In the SGA group, fasting insulin-to-glucose ratios were significantly higher in the TNF/−308A ( P = 0.03), the PPAR/Ala12 ( P = 0.01), and the ADRB3/+250G ( P = 0.02) carriers than in the noncarriers. Results were comparable for fasting insulin concentration and insulin excursion under OGTT. No such amplification was observed in the AGA group. The effects of the PPAR/ProAla12 ( P = 0.005) and the ADRB3/G+250G ( P = 0.009) gene polymorphisms on IR indexes were significantly potentiated by BMI in the SGA group. In conclusion, our data exemplify the interaction between intrauterine environmental and genetic factors in the development of the IR associated with reduced fetal growth. They also point to the key role of adipose tissue in this association. Footnotes Address correspondence and reprint requests to Delphine Jaquet, MD, INSERM Unit 457, Hôpital R. Debré, 48 Bd. Sérurier, 75019 Paris, France. E-mail: djacquet{at}infobiogen.fr . Received for publication 11 June 2002 and accepted in revised form 2 August 2002. ADRB3, β3 adrenoreceptor; AGA, appropriate for gestational age; AUC, area under the curve; GLM, general linear model; IR, insulin resistance; OGTT, oral glucose tolerance test; PPAR, peroxisome proliferator-activated receptor; SGA, small for gestational age; TNF, tumor necrosis factor. DIABETES