Fetuses of obese mothers develop insulin resistance in utero

Patrick M Catalano, Larraine Presley, Judi Minium, Sylvie Hauguel-de Mouzon, Patrick M Catalano, Larraine Presley, Judi Minium, Sylvie Hauguel-de Mouzon

Abstract

Objective: Offspring of obese mothers have an increased risk for obesity and diabetes. The purpose of this study was to determine whether fetuses of obese women have increased obesity, insulin resistance, and markers of inflammation, supporting the concept of fetal programming.

Research design and methods: Fifty-three lean and 68 obese women with singleton term pregnancies were evaluated at elective cesarean delivery. Maternal and umbilical cord blood was obtained for measures of insulin resistance and cytokines. Neonatal body composition was estimated using anthropometric measurements within 24 h of delivery.

Results: The fetuses of obese mothers had greater percent body fat (13.1 +/- 3.4 vs. 11.6 +/- 2.9%, P = 0.02), homeostasis model assessment of insulin resistance (1.51 +/- 0.86 vs. 1.06 +/- 0.70, P = 0.003), cord leptin (14.5 +/- 13.5 vs. 8.2 +/- 4.7 ng/ml, P = 0.001), and interleukin-6 (3.5 +/- 2.3 vs. 2.4 +/- 1.4 pg/ml, P = 0.02) than fetuses of lean women. There was a strong positive correlation between fetal adiposity and insulin resistance (r = 0.32, P = 0.0008) as well as maternal pregravid BMI and fetal insulin resistance (r = 0.31, P = 0.007) even with adjustment for potential confounders. Cord leptin had a significant correlation with fetal insulin resistance (r = 0.30, P = 0.001), but there was no significant correlation between any other umbilical cord cytokines and fetal insulin resistance.

Conclusions: These data suggest that maternal obesity creates a significant risk for the next generations with metabolic compromise already apparent at birth. Therefore, if prevention of obesity is the goal rather than treatment, the perinatal period may be an important focus of future research.

Figures

Figure 1
Figure 1
HOMA-IR indexes in fetuses of lean and obese mothers. A: The fetuses of obese mothers have higher HOMA-IR indexes, i.e., they are more insulin resistant than those of lean mothers. The lower HOMA-IR values in offspring compared with mothers are indicative of higher insulin sensitivity in utero. B: Regression analysis shows a positive correlation between maternal (Mat) and fetal insulin resistance. ○, lean (BMI <25 kg/m2); ●, obese (BMI >30 kg/m2). Data are means ± SEM. *P < 0.003 and **P < 0.0001 versus lean. □, lean women and fetuses of lean women; , obese women and fetuses of obese women.
Figure 2
Figure 2
Relationship of fetal insulin with fetal adiposity. Regression analyses show a positive correlation between fetal insulin resistance estimated by HOMA-IR at birth and percent neonatal body fat of the fetus.

References

    1. Grundy SM, Brewer B, Cleeman JI, Smith SC, Lenfant C: Definition of the metabolic syndrome: report of the National Heart, Lung and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition. Circulation 2004; 109: 433– 438
    1. The Action to Control Cardiovascular Risk in Diabetes Study Group Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358: 2545– 2559
    1. Ogden CL, Carroll MD, Flegal KM: High body mass index for age among US children and adolescents, 2003–2006. JAMA 2008; 299: 2442– 2443
    1. Barker DJP, Osmond C, Simmonds SJ, Wield GA: The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. Br Med J 1993; 306: 422– 426
    1. Dabelea D, Hanson RL, Lindsay RS, Pettitt DJ, Impesatore G, Gabir MM, Roumain J, Bennett PH, Knowler WC: Intrauterine exposure to obesity conveys risks for type 2 diabetes and obesity: a study of discordant sib ships. Diabetes 2000; 49: 2208– 2211
    1. Flegal KM, Carroll MD, Ogden CL, Johnson CL: Prevalence and trends in obesity among U.S. adults, 1999–2000. JAMA 2002; 288: 1723– 1727
    1. Lawrence JM, Contreras R, Chen W, Sacks DA: Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethically diverse population of pregnant women, 1999–2005. Diabetes Care 2008; 31: 899– 904
    1. Sewell MF, Huston-Presley L, Super DM, Catalano PM: Increased neonatal fat mass, and not lean body mass is associated with maternal obesity. Am J Obstet Gynecol 2006; 195: 1100– 1103
    1. Boney CM, Verner A, Tucker R, Vohr BR: Metabolic syndrome in childhood: association with birth weight, maternal obesity and gestational diabetes mellitus. Pediatrics 2005; 115: E290– E296
    1. Carpenter MW, Coustan DR: Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982; 144: 768– 773
    1. Matthews DR, Hosker JP, Rudinski AS, Naylor BA, Tracher DF, Turner RC: Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412– 419
    1. Catalano PM, Thomas AJ, Avallone DA, Amini SB: Anthropometric estimation of neonatal body composition. Am J Obstet Gynecol 1995; 173: 1176– 1181
    1. Farrag HM, Nawrath LM, Healey JE, Dorcus EJ, Rapoza RE, Oh W, Cowett RM: Persistent glucose production and greater peripheral sensitivity to insulin in the neonate vs. the adult. Am J Physiol 1997; 272: E86– E93
    1. Dyer JS, Rosenfeld CR, Rice J, Rice M, Hardin DS: Insulin resistance in Hispanic large-for-gestational-age neonates at birth. J Clin Endocrinol Metab 2007; 92: 3836– 3843
    1. Catalano PM, Tyzbir ED, Wolfe RR, Roman NM, Amini SB, Sims EAH: Longitudinal change sin basal hepatic glucose production and suppression during insulin infusion in normal pregnant women. Am J Obstet Gynecol 1992; 167: 913– 919
    1. Pedersen J: The Pregnant Diabetic and Her Newborn: Problems and Management Baltimore, Williams & Wilkins, 1967, p. 60– 107
    1. The HAPO Study Cooperative Research Group Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991– 2002
    1. Girard J, Ferre P: Metabolic and hormonal changes around birth. In Biochemical Development of the Fetus and Neonate, Jones CT: Ed. New York, Elsevier Biomedical Press, 1982
    1. Susa JB, Neave C, Sehgal P, Singer DB, Zeller WP, Schwartz R: Chronic hyperinsulinemia in the fetal rhesus monkey: effects of physiological hyperinsulinemia on fetal growth and composition Diabetes 1984; 33: 656– 660
    1. Sbarbati A, Osculati F, Silvagni D, Benati D, Galie M, Camoglio FS, Rigotti G, Maffeis C: Obesity and inflammation: evidence for an elementary lesion. Pediatrics 2006; 117: 220– 223
    1. Nelson SM, Sattar N, Freeman DJ, Walker JD, Lindsay RS: Inflammation and endothelial activation is evident at birth in offspring of mothers with type 1 diabetes. Diabetes 2007; 56: 2697– 2704
    1. Stewart FM, Freeman DJ, Ramsay JE, Greer IA, Caslake M, Ferrell WR: Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers. J Clin Endocrinol Metab 2007; 92: 969– 975
    1. Aaltonen R, Heikkin T, Hakala K, Laine K, Alanen A: Transfer of proinflammatory cytokines across the placenta. Obstet Gynecol 2005; 106: 802– 807
    1. Mingrone G, Manco M, Mora MEU, Guidone C, Iaconelli A: Influence of maternal obesity on insulin sensitivity and secretion of the offspring. Diabetes Care 2008; 31: 1872– 1876
    1. Whitaker RC: Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy. Pediatrics 2004; 114: e29– e36

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