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      Maternal Hyperglycemia During Pregnancy Predicts Adiposity of the Offspring

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          Abstract

          OBJECTIVE

          To investigate associations between maternal pregnancy hyperglycemia, gestational diabetes mellitus (GDM), and offspring adiposity.

          RESEARCH DESIGN AND METHODS

          We evaluated these associations in a longitudinal study of 421 mother-daughter pairs at Kaiser Permanente Northern California. Maternal pregnancy glucose values were obtained from maternal medical records. Outcomes included three measures of girls’ adiposity, measured annually: 1) ≥85th age-specific percentile for BMI; 2) percent body fat (%BF); and 3) waist-to-height ratio (WHR).

          RESULTS

          Adjusting for maternal age at delivery, race/ethnicity, pregravid BMI, girl’s age, and girl’s age at onset of puberty, having a mother with GDM increased a girl’s risk of having a BMI ≥85th percentile or having %BF or WHR in the highest quartile (Q4), compared with those in the lowest quintile of blood glucose (odds ratio [OR] 3.56 [95% CI 1.28–9.92]; OR 3.13 [95% CI 1.08–9.09]; and OR 2.80 [95% CI 1.00–7.84], respectively). There was a significant interaction between the presence of GDM and pregravid BMI; girls whose mothers had both risk factors had the highest odds of having a BMI ≥85th percentile (OR 5.56 [95%CI 1.70–18.2]; Q4 %BF, OR 6.04 [95%CI 1.76–20.7]; and Q4 WHR, OR 3.60 [95%CI 1.35–9.58]). Similar, although weaker, associations were found in the association between hyperglycemia and offspring adiposity.

          CONCLUSIONS

          Girls who were exposed to maternal GDM or hyperglycemia in utero are at higher risk of childhood adiposity; risk increases if the mother is overweight or obese. Screening and intervention for this high-risk group is warranted to slow the intergenerational transmission of obesity and its sequelae.

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          Most cited references25

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          Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships.

          Intrauterine exposure to diabetes is associated with an excess of diabetes and obesity in the offspring, but the effects of intrauterine exposure are confounded by genetic factors. To determine the role of the intrauterine diabetic environment per se, the prevalence of diabetes and the mean BMI were compared in siblings born before and after their mother was recognized as having diabetes. Nuclear families in which at least one sibling was born before and one after the mother was diagnosed with type 2 diabetes were selected. Consequently, the siblings born before and after differed in their exposure to diabetes in utero. A total of 58 siblings from 19 families in which at least one sibling had diabetes were examined at similar ages (within 3 years). The risk of diabetes was significantly higher in siblings born after the mother developed diabetes than in those born before the mother's diagnosis of diabetes (odds ratio 3.7, P = 0.02). In 52 families, among 183 siblings without diabetes, the mean BMI was 2.6 kg/m2 higher in offspring of diabetic than in offspring of nondiabetic pregnancies (P = 0.003). In contrast, there were no significant differences in risk of diabetes or BMI between offspring born before and after the father was diagnosed with diabetes. Intrauterine exposure to diabetes per se conveys a high risk for the development of diabetes and obesity in offspring in excess of risk attributable to genetic factors alone.
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            Childhood obesity and adult morbidities.

            The prevalence and severity of obesity have increased in recent years, likely the result of complex interactions between genes, dietary intake, physical activity, and the environment. The expression of genes favoring the storage of excess calories as fat, which have been selected for over many millennia and are relatively static, has become maladaptive in a rapidly changing environment that minimizes opportunities for energy expenditure and maximizes opportunities for energy intake. The consequences of childhood and adolescent obesity include earlier puberty and menarche in girls, type 2 diabetes and increased incidence of the metabolic syndrome in youth and adults, and obesity in adulthood. These changes are associated with cardiovascular disease as well as with several cancers in adults, likely through insulin resistance and production of inflammatory cytokines. Although concerns have arisen regarding environmental exposures, there have been no formal expert recommendations. Currently, the most important factors underlying the obesity epidemic are the current opportunities for energy intake coupled with limited energy expenditure.
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              Fetal origins of obesity.

              The worldwide epidemic of obesity continues unabated. Obesity is notoriously difficult to treat, and, thus, prevention is critical. A new paradigm for prevention, which evolved from the notion that environmental factors in utero may influence lifelong health, has emerged in recent years. A large number of epidemiological studies have demonstrated a direct relationship between birth weight and BMI attained in later life. Although the data are limited by lack of information on potential confounders, these associations seem robust. Possible mechanisms include lasting changes in proportions of fat and lean body mass, central nervous system appetite control, and pancreatic structure and function. Additionally, lower birth weight seems to be associated with later risk for central obesity, which also confers increased cardiovascular risk. This association may be mediated through changes in the hypothalamic pituitary axis, insulin secretion and sensing, and vascular responsiveness. The combination of lower birth weight and higher attained BMI is most strongly associated with later disease risk. We are faced with the seeming paradox of increased adiposity at both ends of the birth weight spectrum-higher BMI with higher birth weight and increased central obesity with lower birth weight. Future research on molecular genetics, intrauterine growth, growth trajectories after birth, and relationships of fat and lean mass will elucidate relationships between early life experiences and later body proportions. Prevention of obesity starting in childhood is critical and can have lifelong, perhaps multigenerational, impact.
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                November 2014
                10 October 2014
                : 37
                : 11
                : 2996-3002
                Affiliations
                [1] 1Kaiser Permanente Division of Research, Oakland, CA
                [2] 2California Department of Public Health, Richmond, CA
                [3] 3Kaiser Permanente San Francisco Medical Center, San Francisco, CA
                [4] 4University of California, Berkeley, Berkeley, CA
                [5] 5University of California, San Francisco, San Francisco, CA
                Author notes
                Corresponding author: Ai Kubo, ai.kubo@ 123456kp.org .
                Article
                1438
                10.2337/dc14-1438
                4207207
                25150158
                67645dee-690e-4299-91bb-f7d868c74bd0
                © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
                History
                : 10 June 2014
                : 31 July 2014
                Page count
                Pages: 7
                Categories
                Epidemiology/Health Services Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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