Association of intrauterine exposure to maternal diabetes and obesity with type 2 diabetes in youth: the SEARCH Case-Control Study

Dana Dabelea, Elizabeth J Mayer-Davis, Archana P Lamichhane, Ralph B D'Agostino Jr, Angela D Liese, Kendra S Vehik, K M Venkat Narayan, Phillip Zeitler, Richard F Hamman, Dana Dabelea, Elizabeth J Mayer-Davis, Archana P Lamichhane, Ralph B D'Agostino Jr, Angela D Liese, Kendra S Vehik, K M Venkat Narayan, Phillip Zeitler, Richard F Hamman

Abstract

Objective: Limited data exist on the association between in utero exposure to maternal diabetes and obesity and type 2 diabetes in diverse youth. These associations were explored in African-American, Hispanic, and non-Hispanic white youth participating in the SEARCH Case-Control Study.

Research design and methods: A total of 79 youth with type 2 diabetes and 190 nondiabetic control youth aged 10-22 years attended a research visit. In utero exposures to maternal diabetes and obesity were recalled by biological mothers.

Results: Youth with type 2 diabetes were more likely to have been exposed to maternal diabetes or obesity in utero than were nondiabetic control youth (P < 0.0001 for each). After adjusting for offspring age, sex, and race/ethnicity, exposure to maternal diabetes (odds ratio [OR] 5.7 [95% CI 2.4-13.4]) and exposure to maternal obesity (2.8 [1.5-5.2]) were independently associated with type 2 diabetes. Adjustment for other perinatal and socioeconomic factors did not alter these associations. When offspring BMI was added, the OR for the association between in utero exposure to obesity and type 2 diabetes was attenuated toward the null (OR 1.1 [0.5-2.4]). Overall, 47.2% (95% CI 30.9-63.5) of type 2 diabetes in youth could be attributed to intrauterine exposure to maternal diabetes and obesity.

Conclusions: Intrauterine exposures to maternal diabetes and obesity are strongly associated with type 2 diabetes in youth. Prevention efforts may need to target, in addition to childhood obesity, the increasing number of pregnancies complicated by obesity and diabetes.

Figures

Figure 1—
Figure 1—
Percentage of youth exposed in utero to maternal diabetes (A) and maternal overweight/obesity (B) by case-control status and race/ethnicity. □, case patients; ▪, control youth. A: Non-Hispanic white (NHW) P = 0.01; Hispanic (H) P = 0.02; African-American (AA) P = 0.02. B: NHW P = 0.1; H P = 0.04; AA P = 0.001.
Figure 2—
Figure 2—
The association between offspring type 2 diabetes status with exposure to maternal diabetes in utero (A) and exposure to maternal overweight/obesity in utero (B) in sequentially adjusted multiple logistic regression models. Model 1: adjusted for offspring age, sex, race/ethnicity; model 2: model 1 + maternal obesity in utero (A) or maternal diabetes in utero (B); model 3: model 2 + maternal alcohol and smoking in pregnancy, maternal current age, parity, offspring's birth weight, breast-feeding, maternal education, household income; and model 4: model 2 + current offspring BMI Z score.

References

    1. Dabelea D, Bell RA, D'Agostino RB Jr, et al.: Incidence of diabetes in youth in the United States. JAMA 297:2716–2724, 2007
    1. Pettitt DJ, Bennett PH, Saad MF, et al.: Abnormal glucose tolerance during pregnancy in Pima Indian women: long-term effects on offspring. Diabetes 40(Suppl. 2):126–130, 1991
    1. Dabelea D, Hanson RL, Bennett PH, et al.: Increasing prevalence of type II diabetes in American Indian children. Diabetologia 41:904–910, 1998
    1. Sebire NJ, Jolly M, Harris JP, et al.: Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London. Int J Obes Relat Metab Disord25:1175–1182, 2001
    1. Salsberry PJ, Reagan PB: Dynamics of early childhood overweight. Pediatrics 116:1329–1338, 2005
    1. Boney CM, Verma A, Tucker R, et al.: Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 115:290–296, 2005
    1. Yeh J, Shelton JA: Increasing prepregnancy body mass index: analysis of trends and contributing variables. AmJ Obstet Gynecol 193:1994–1998, 2005
    1. Mokdad AH, Ford ES, Bowman BA, et al.: Diabetes trends in the U.S.: 1990–1998. Diabetes Care 23:1278–1283, 2000
    1. Dabelea D, Snell-Bergeon JK, Hartsfield CL, et al.: Increasing prevalence of gestational diabetes mellitus over time and by birth cohort: Kaiser Permanente of Colorado GDM Screening Program. Diabetes Care 28:579–584, 2005
    1. Dabelea D: The predisposition to obesity and diabetes in offspring of diabetic mothers. Diabetes Care 30(Suppl. 2):169–175, 2007
    1. Solomon CG, Willett WC, Carey VJ, et al.: A prospective study of pregravid determinants of gestational diabetes mellitus. JAMA 278:1078–1083, 1997
    1. Kuczmarski MF, Kuczmarski RJ, Najjar M: Effects of age on validity of self-reported height, weight, and body mass index: findings from the Third National Health and Nutrition Examination Survey, 1988–1994. J Am Diet Assoc 101:28–34, 2001
    1. Oken E, Taveras EM, Kleinman KP, et al.: Gestational weight gain and child adiposity at age 3 years. Am J Obstet Gynecol 196:322–328, 2007
    1. National Center for Health Statistics. CDC Growth Charts: United States. Atlanta, Centers for Disease Control and Prevention, 2006
    1. Miettinen OS: Proportion of disease caused or prevented by a given exposure, trait or intervention. Am J Epidemiol 99:325–332, 1974
    1. Rockhill B, Newman B, Weinberg C: Use and misuse of population attributable fractions. Am J Public Health 88:15–19, 1998
    1. Dabelea D, Hanson RL, Lindsay RS, et al.: Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 49:2208–2211, 2000
    1. Clausen TD, Mathiesen ER, Hansen T, et al.: High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia. Diabetes Care 31:340–346, 2008
    1. Sobngwi E, Boudou P, Mauvais-Jarvis F, et al.: Effect of a diabetic environment in utero on predisposition to type 2 diabetes. Lancet 361:1861–1865, 2003
    1. Aerts L, Sodoyez-Goffaux F, Sodoyez JC, et al.: The diabetic intrauterine milieu has a long-lasting effect on insulin secretion by B cells and on insulin uptake by target tissues. Am J Obstet Gynecol 159:1287–1292, 1988
    1. Hunter WA, Cundy T, Rabone D, et al.: Insulin sensitivity in the offspring of women with type 1 and type 2 diabetes. Diabetes Care 27:1148–1152, 2004
    1. Gautier JF, Wilson C, Weyer C, et al.: Low acute insulin secretory responses in adult offspring of people with early onset type 2 diabetes. Diabetes 50:1828–1833, 2001
    1. Kitajima M, Oka S, Yasuhi I, Fukuda M, et al.: Maternal serum triglyceride at 24–32 weeks' gestation and newborn weight in nondiabetic women with positive diabetic screens. Obstet Gynecol 97:776–780, 2001
    1. Kartik S, Harrell A, Liu X, et al.: Maternal obesity at conception programs obesity in the offspring. Am J Physiol 291:528–538, 2008
    1. Zhang J, Yu KF: What's the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 280:1690–1691, 1998

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