Genetic and environmental factors in associations between infant growth and adult cardiometabolic risk profile in twins

Background: Accelerated infant growth is associated with an al-tered, mostly adverse adult cardiometabolic risk profile. The impor-tance of genetic and environmental factors to these associations isunclear.Objective: The objective was to examine the importance of geneticand environmental factors in the associations between infant growthand adult cardiometabolic risk factors (anthropometrics, lipids, in-sulin sensitivity, leptin, blood pressure, and fibrinogen) in twins.Design: Cardiometabolic risk factors were assessed in 240 twinpairs (aged 18–34 y) from the East Flanders Prospective Twin Sur-vey. Infant growth was defined as change in weight z score. Weregressed intrapair differences in growth during 4 growth windows(0–1, 1–6, 6–12, and 12–24 mo) against intrapair differences in therisk factors in monozygotic and dizygotic twins separately.Results: Within monozygotic twin pairs only, associations betweeninfant growth and most adult lipids, glucose, leptin, and blood pres-sure (eg, systolic blood pressure: b = 5.95 mm Hg per change inz score, P = 0.01 in monozygotic twins; b = 21.64, P = 0.82 indizygotic twins from 12 to 24 mo) were found. Within dizygotictwin pairs only, associations between growth and triglycerides andfibrinogen (eg, fibrinogen: b = 0.07 ln mg/dL per change in z score,P=0.31 in monozygotic twins; b = 0.79, P = 0.01 in dizygotictwins from 0 to 1 mo) were identified. Most associations showeda detrimental effect of accelerated growth, but beneficial associa-tions were also identified (eg, total–to–high-density-lipoprotein cho-lesterol ratio: b = 20.22 per change in z score from 1 to 6 mo, P =0.008 in monozygotic twins).Conclusion: Our data showed that environmental factors play a rolein the associations between infant growth and most adult lipids,glucose, leptin, and blood pressure, whereas genetic factors are in-volved regarding triglycerides and fibrinogen. Am J Clin Nutrdoi: 10.3945/ajcn.112.039131.INTRODUCTIONCardiovascular disease is a major cause of mortality world-wide (1). The incidence of cardiovascular disease is increased inindividuals with an adverse cardiometabolic risk profile, whichincludes obesity, an unfavorable lipid profile, insulin resistance,and high blood pressure. It has become clear that besides theimportance of lifestyle, factors in early life are also involved inthe development of this risk profile. Low birth weight is relatedto an adverse cardiometabolic risk profile and cardiovasculardisease later in life (2–4). In addition, subsequent acceleratedpostnatal growth has been proposed as a mechanism that linkslow birth weight to an unfavorable cardiometabolic risk profile(5, 6). Growth during infancy (mostly defined as 0–2 y) has beenpositively associated with obesity (7), hypertension (8), an ad-verse cardiometabolic risk profile (9), and metabolic syndrome(10). On the contrary, there is also some evidence that slowinfant growth is associated with certain harmful cardiometabolicoutcomes in adulthood, eg, regarding lipids (11, 12), insulin re-sistance (13, 14), and stroke (15).Importantly, to regard “infancy” as one growth window from0 to 2 y may be too broad a definition. For example, it wasreported that the first 3 mo of life may be most important for thedevelopment of an adverse cardiometabolic risk profile (16). Inaddition, accelerated growth in the first 2 wk of life is relatedto adult endothelial dysfunction, a precursor of atherosclerosis