Adiposity gain during childhood, ACE I/D polymorphisms and metabolic outcomes.
We aimed to (i) determine the relative importance of childhood gain in upper body adiposity for insulin resistance (IR) and triglyceridemia (TG); (ii) examine whether the associations between adiposity and metabolic indices were more evident in those with the ACE DD genotype. We examined a birth cohort study of 292 children with measures in the neonatal period (day 4) including subscapular and triceps skinfolds; repeat skinfold measures at age 8, cardiorespiratory (CR) fitness, IR by the homeostasis model assessment (HOMA) equation (HOMA-IR) and serum triglyceride (TG) concentrations and measures of ACE I/D gene variants. A multiple linear regression analysis incorporating a life course approach was undertaken. Childhood gain in upper body adiposity was positively associated with HOMA-IR and TG independently of neonatal skinfolds (P < or = 0.02). The magnitude of these associations was higher among those of the ACE DD genotype. For example, subscapular skinfold gain was not strongly associated with HOMA-IR or TG among those with II or ID genotype (b = 0.03, P = 0.05; b = 0.02, P = 0.18 respectively) but was positively associated among those with the DD genotype (b = 0.11, P = 0.001; b = 0.08, P = 0.003); difference in effect P = 0.05; P = 0.01 respectively. Upper body fat accumulation during childhood was positively associated with HOMA-IR and TG independently of neonatal skinfolds. Further, the stronger associations for those with the ACE DD genotype is consistent with randomised controlled trial findings that ACE inhibition is associated with a reduced risk of developing type 2 diabetes. Further work is required to confirm and extend these findings.
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia. anne-louise.ponsonby@mcri.edu.au
Anne-Louise
AL
Ponsonby
Leigh
L
Blizzard
Angela
A
Pezic
Jenny A
JA
Cochrane
Justine A
JA
Ellis
Ruth
R
Morley
Jo L
JL
Dickinson
Michele M
MM
Sale
Stephen M
SM
Richards
Terence
T
Dwyer
D050154:Adiposity / Q000235:genetics* / Q000502:physiology; D001724:Birth Weight; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012885:Skinfold Thickness; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D004247:DNA; D007703:Peptidyl-Dipeptidase A