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Two paradigms offer useful conceptual frameworks for understanding the developmental origins of obesity. One is termed the “life course approach to chronic disease” [12]. Factors may act in the preconceptional phase through the prenatal period, into infancy, childhood, and beyond, to determine the risk of chronic disease. Orthogonal to the time axis, influencing factors can range from the social/built/natural environment (macro) through behavior, physiology, and genetics (micro). Factors interact with each other over the life course, with different determinants being more or less important at different life stages. Under this paradigm, some factors may be more deterministic than others.

“Programming” refers to insults at critical or sensitive periods of development that have lifelong, sometimes irreversible consequences. A commonly known example is that of the synthetic estrogen diethylstilbestrol (DES), for which intrauterine exposure is associated with risk for clear cell adenocarcinoma of the vagina and cervix in late life, but postnatal exposure is not [13]. Furthermore, exposure to hyperglycemia during fetal life predisposes subsequent increased risks for obesity and type 2 diabetes [14–16]. Other factors may contribute to chronic disease through accumulation of risk. For example, chronic exposure to elevated lipid levels across childhood is associated with pre‐atherosclerotic coronary lesions among adolescents [17]. Similarly, excess consumption of energy relative to energy expenditure is expected to result in greater adiposity at any point in the life course, with greater adiposity following longer‐lasting excesses.

A second, related paradigm is called the developmental origins of health and disease (DOHaD). Based on similar principles, DOHaD focuses primarily on the prenatal period and infancy as determinants of long‐term health [18]. Both of these frameworks call attention to the period of developmental plasticity in determining lifelong trajectories of health. This plastic period is different for different organs and systems but is generally felt to be most important before birth or the first years of life (Fig. 3.1) [18,19]. Factors that occur later in life, e.g. childhood or adult risk factors, then modify trajectories started during early life. For example, among rats prenatally programmed to develop obesity, hyperinsulinemia, and hyperleptinemia, leptin treatment soon after birth normalized caloric intake, locomotor activity, body weight, fat mass, and fasting plasma glucose, insulin, and leptin concentrations in adult life [20].

Figure 3.1 Lifecourse view of noncommunicable disease risk.

Source: From Hanson and Gluckman [19]. Copyright © 2014 the American Physiological Society.