Special Critical periods of obesity1

Article

in childhood

for

the

development

William
ABSTRACT

H Dietz
Critical periods of development have been well not

been

carefully

explored for efforts entrain period prevalence the process

(12). development and body for stage of that the

Nonetheless, of obesity promote

the

identification may serve of In this will alterations use the the word critical onefor and for the adto the disbe

recognized However,

for many behavioral as others have pointed

and developmental out, such periods Many periods of

processes. of critical periods have not been focus preventive the sug- mechanisms decussion, gesdefined that increase that entrain that a critical the later

the

characterization its distribution. of obesity physiologic We with that will during

widely reported for nutritional diseases. gest that two and possibly three critical velopment tation occurs begins obesity and of between at these and its obesity infancy, 5 and 7 y of and its the age, complications. period and early

observations exist for These include rebound Obesity

fat

and

development in which obesity.

Downloaded from www.ajcn.org by guest on February 16, 2011

as a developmental to describe because (14) does

adiposity

adolescence.

is initiated

periods appears complications. associated the preventive

J Clin Nutr

to increase the The mechanisms obesity of on

risk of persistent period, that account for self remain process should The olescence velopment

its definition not imply the represent Each

to draw along a mechanism period of three these of adiposity critical will be

or after accounts rebound,

the increased risk unclear. Nonetheless, serve stages. KEY ment, to focus
Am

with existence efforts

1994;59:955-9.

at these ages critical periods these

that follows. prenatal period, appear to of obesity.

developmental

periods considered

the dein turn.

WORDS children

Obesity,

diabetes,

fat

distribution,

develop-

Prenatal
Obesity

period

Introduction Obesity ulation of graphic sity, icant the the onset

more

Follow-up is now one the United behavioral of the most prevalent States (1, 2). Although factors (3, 4) appear early in life diseases in the popthat prenatal a variety of demodevelopment associated with obeIn October

studies and and of

1944

of

infants

exposed

to

famine

prenatally

or

of infants perinatal fatness

the

of diabetic mothers overor undernutrition life.

occupation

strongly suggest influences the

and

in later
German

the familial resemblances in fatness5, 6) indicate ( genetic effect on susceptibility to the disease. severity persistence obesity
severe

of

obesity of that obesity persists

disease

and

age into into

(7),

at onset adulthood. adulthood

childhood-onset

restricted food supthe a signifplies to the western Netherlands. At the beginning ofthe occupation In general, the average per capita daily ration approximated 7533 kJ (1800 affect the likelihood of kcalld) (15) and declined to 25 1 1 Id (600 kcal/d) in the 6 mo that Although childhoodfollowed. In May, 1945, after liberation, food supplies again promay be associated with vided 71 14 U (1700 kcal/d). The clear delineation of the onset and obesity accounts

adult

for well

a minority Critical or For described

of the sensitive for

cases (10) many

of obesity periods physiologic of in

present and

in adults

(8, have

9).

end
of

of the
the effects

famine
of

in the
maternal

Netherlands permitted
nutrition on

a careful
subsequent

assessment
growth. At the

development

cesses. trimester malities,

One of

example, of pregnancy later

examples best

exposure produces intrauterine

of

the fetus a variety exposure

phenomenon

been time behavioral (1 1) prowho to rubella in the first was of congenital abnorto the virus
(12) is

of their military had been exposed compared

Holland that

induction, the growth of 19-y-old to famine in utero or in the age-matched

not been

Dutch men perinatal period from Obesity areas

with
had

control
exposed

subjects
to the

drawn
famine (15).

whereas
the

does
the

not.

of

this

effect

of and

fetal 12th

dihydrotestosterone exposure wk of fetal Likewise, the same of

exposure females the period development absence produces

on

the

external female

genitalia. between the pseudoher8th

icine,
2

From
England

the Division
Medical

of Pediatric
Boston, HD25579 to WH

Gastroenterology
and from Tufts NICHD New University and

and Nutrition,
School grant of

New
Mcd-

Intrauterine maphrodites. males during external The

development J Clin

to testosterone produces of

Center, by grant

Boston. Supported P30-DK46200 Medical Center,

dihydrotestosterone in ambiguous or feminized at critical periods

obesity,

from
3

NIDDK.
Address 213, 750 reprint requests Dietz, England

genitalia possibility
entrain

(13). that nutritional

nutritional

Box

alterations
states, such

of Received
has Accepted

as

adult

Washington Street, Boston, MA 02111. May 26, 1993. for publication November 10, 1993.
Nutrition

Am

Nutr

1994;59:955-9.

Printed

in

USA.

1994

American

Society

for

Clinical

955

956
was

DIETZ defined as a weight-for-height appeared lowest

>

120% among

of standard. men exposed

The

preyin
.

alence utero
period.

of obesity

to famine postnatal among

in the last trimester of pregnancy or in the immediate In contrast, the prevalence of obesitywas increased men who of infants that for period the were exposed (Fig of diabetic the third entrainment 1). mothers trimester offer additional may In a large to famine in utero of pregnancy

EJ
I

Non-Diabetics

Diabetics 95% Confidence Interval

young tnmesters Studies the

in the twofirst support represent population 40 for 6O a

F...
..

1#{149}

suggestion

of pregnancy of fatness. mothers or an

critical of Pima diabetic

mothers and based on the

their infants (16), presence of diabetes

were defined as abnormal glucose

U

tolerance test. Prediabetic mothers were mal glucose tolerance who subsequently sity
50th 50th

defined as those with nordeveloped diabetes. Obeas a weight 140% of the

20

in the

infants

and

children

was

defined

percentile desirable weight-for-gestational age or 140% of the percentile ofweight-for-height. Infantsborn to diabetic mothers were fatter at birth than were infants of prediabetic or nondiabetic mothers dren of
significantly

tJ
who Adapted were

AGE FIG 2. Prevalence

:1
Pettit

AT EXAMINATION at subsequent
prediabetic, et al (16).

(years) ages
or

(16). Furthermore, diabetic mothers

higher than

the prevalence at ages -9, 5 10the prevalence

of obesity among chil14, and 15-19 y was

of obesity among

of obesity
diabetic, from

among
nondiabetic

children
during

born
their

of

the

same

age born

to pre-

or

nondiabetic children mothers confirmed

mothers

(Fig

2).

children to mothers pregnancy.

Downloaded from www.ajcn.org by guest on February 16, 2011

The

prevalence appeared of the Several

of obesity among the to be independent of the childs other birth (16). studies have large

of diabetic mothers also obesity status at the time the the the persistent at ages In these observed

follow-up possibility

studies that the

of infants intrauterine

of diabetic environment none of the

mothers, may latter that operate

and entrain

support subcxin utero.

of birth weight for the subsequent 1 1, 15 (18), and 17 y (19), and the tracking of birth weight was infants of diabetic mothers. or maternal obesity, both sequent likely fatness. to parallel However, birth weight,

risk of obesity in adulthood (9). lower than that

effect sequent fatness. Nonetheless, 6 (17),dude the possibility of genetic studies among Pathophysiology diabetes The and subtional are is withundersimplest exposure conceptualization is that appetite during this period. may

observations

determinants

None determined of which affect because these the findings

gestational birth weight are consistent

of the regulation Early the control may affect

effects of in utero nutriand adipocyte numbers in utero exposure to either of hypothaadi-

prevalence

of diabetes

entrained

or overnutrition

differentiation

lamic centers responsible for the in utero exposure to undernutrition pocyte whereas pocyte pair the Likewise, nutrition
U. #{163}0 against or

of food intake (15). Late reduce the extensive of may

replication that late in utero hyperplasia regulation third may

promote

occurs exposure Therefore, intake,

in the last trimester to overnutrition early and undernutrition predispose undernutrition cellularity logical factors or of

pregnancy, cause adimay imobesity. or and overprotect no affect adi-

(15). trimester influence

of food

to later

and postnatal adipose tissue

obesity.

later

Although firm adipose pocyte ticoids pogenic mone The fects effects evidence tissue

these exists mass

mechanisms for either. include

represent Additional differential

hypotheses, that may

0
LU

C:,

site-dependent

sensitivity to or metabolism (21), alterations in lipoprotein enzymes receptor effects usually of (22, numbers of prenatal associated prenatal exposure 23), (24). nutritional with obesity on fatness, or changes

insulin (20) or glucocorlipase or mitochondrial liin insulin or lipolytic on suggest the morbid from that the horefthe en-

exposure appear and diseases English blood

dissociated

trainment of obesity dent processes. For weight increased

and its associated example, in several the risk of elevated

may be indepencohorts, low birth pressure in children in or diabetes mortality (25, 28).

COHORT

FIG 1. Prevalence ofobesity in 19-y-old men exposed to famine either The effects of low birth weight on morbidity persisted after conin utero or during early postnatal life. Exposure to famine in the last trol for geographic region, socioeconomic status, mode of infant trimester of pregnancy or early infancy is associated with a reduced prevfeeding, and smoking. The same studies failed to demonstrate alence of obesity at age 19 y, whereas exposure early in pregnancy is any increase in morbidity or mortality for those individuals associated with an increased prevalence of obesity at age Adapted 19 y. from Ravelli et al(15). whose birth weight was greater than average.

and adults adulthood

(25, 26), abnormal (27), and increased

glucose tolerance cardiovascular

CRITICAL These ses. risk dren nal For first-trimester apparent example, contradictions infants exposure whose offer birth several weight may

PERIODS testable is low incur an

FOR hypothebecause increased

OBESITY whereas as teenagers of 20% of obese (36, risk persists Adolescence only

DEVELOPMENT 10% (9). of obese Approximately females returned adult males 70% to had of normal onset obese weight

957 of their males, over obesity but a only 10-y

to undernutrition

of subsequent whose birth undernutrition and represent

adiposity and hypertension or diabetes. weight is low because of third-trimester may diabetes, the Infants have that

Chil- period mater- ticular hyduring mdi-that

37). These findings indicate that girls may be at parfor adult obesity if their disease is present or develops and adulthood also appears that adolescent-onset may herald to represent obesity a lifelong a critical in females problem. period for the into

incur but who an the

an not are

increased obesity. exposed risk

risk Perhaps obese,

of subsequent the to but latter latter maternal normal-weight

adolescence,

pertension viduals individual overnutrition risk esis related cesses of would

metabolically increased development

(29). may

in utero of obesity, of the of subsequent

entrainment a lower study of

of obesity-associated individuals studied 1935), when 50th was mortality (BMI > 75th compared

morbidity. SS-y a follow-up In during the Third Harvard

Growth

subsequent suggest

morbidity.

Confirmation of diabetic mothers later in development.

hypoth- Study obesity- were on school protween several classified high

(1922overweight years 25th and diseases as school weight

was increased among men who percentile) during their high with men who were (38). both The mortality suggesting lean Morbidity men and persisted that the (BMI befrom women effect mordiadult of even

disease in infants that differ or occur

depends

percentile) adolescents also increased among during on high morbidity resulted effects more did school. and

Period Several bound of divided subsequently again occurs Changes

of adiposity
sources may by begins represent adiposity. height2 decreases to increase. of

rebound
data another The increases (30, The 31). time (m)] suggest critical body in Beginning at which that the period mass the time for index first the of the year second rebound thickness cohort adiposity development [BMI; of wt life, BMI

obese weight at age

significant

subsequent

when rebidity rectly, (kg)

53 y was effects from the to suffer than Danish personal

controlled,

and mortality rather than

from adolescent obesity of adolescent obesity on consequences women. Data of obesity from (41), young and 1991)

Downloaded from www.ajcn.org by guest on February 16, 2011

5 at y of age,

weight. Men tended and ent during adolescence

presadult Norwesupport

has been called the in fatness measured

period of adiposity by triceps-skinfold from a small

increase overweight gian men (30, 31). appear these

Dutch (39), (HT Waaler,

(40), Swedish communication,

observations.

to follow a similar pattern (5). Longitudinal observations 31) gest hood skinfold whose pared 6.5 and a somewhat that the time effect In both thicknesses adiposity with children late (31).

significant

Pathophysiology (30, by which adolescent-onset obesity lead to an larger cohort in southwestern Ohio (32) sug- The mechanisms increased likelihood of adverse sequelae or the persistence of at which adiposity rebound begins may have a obesity is not clear. One potential explanation for the apparent on fatness in adolescence (30, 32) and adultentrainment of morbidity during adolescence may be the pattern adolescents and adults, BMI and subscapularof fat deposition that occurs at this time. Boys, and to a lesser were significantly greater among children extent girls, appear to deposit fat centrally and lose fat periphrebound began early (before.5 y of age), 5 cornin France whose adiposity 31). clearly rebound a relationship was average between as they (6.0-. erally are apparently mature absent (43). and (42). from some Estrogen female gluteal and progesterone abdominal, femoral, androgen depots receptors (44). These receptors or omenexist in abfindings

y) or Although

(after 7 y) (30, these data show

posity rebound has not been of adiposity

and subsequent fatness, the prevalence examined. Therefore, the evidence that rebound represents obesity effect of children a critical is not adiposity who yet period for established. rebound on earlier

tissue adi-tal adipose dominal, omental, of obesity that the the period suggest adolescence the devel- during

However,

sexual dimorphism may be determined be deposited fat may be in adipocyte

of adipose tissue deposition by default. If androgens In gluteal metabolism, the abregion. as

opment of subsequent explanation for the posity a longer parallel. only may be that of period Therefore, gains period

rebound

fat may An alternate are present, sence of androgens, eventual adiRegional differences grow fatter for

intraabdominally. deposited in the receptors or

time. Rates of BMI increases differences in fatness at subsequent onset of the age-related increase No published to subsequent

reflect

an earlier

as differential effects of insulin on glucose uptake and limay remain well polysis may contribute to this process. ages may Intraabdominal fat in obese adults predicts diabetes (45), heart in fatness, (46), hypertension studies have disease fat distribution morbidity thermore, the sex-related differences tion inal (50). Increased fat may act on to reduce release the liver (47, 48), and hyperlipidemia (49). Furmay account for in the incidence a large proportion of of myocardial infarcfrom insulin of intraabdomresistance, glucose to glucose (52). may

and parallel linked the or mortality.

in fatness thereafter. of adiposity rebound

of free fatty acids to produce hepatic suppression

Adolescence
Obesity
Adolescence velopment obesity of appear represents obesity. greater of Both for the the females final risk proposed of than onset for period and males. appears several for persistence the

and

insulin-mediated and release (51). These and non-insulin-dependent

hepatic

production intolerance deLikewise, of decrease

effects contribute diabetes mellitus in the portal to contribute

increased insulin

free clearance

fatty

acids and

circulation hyperinsulinemia

The canalization throughout childhood

(53). Hyperinsulinemia and insulin resistance have been associto increase ated with hypertension (54,55). The high-risk plasma lipid prostudies obfile associated with increased intraabdominal fat appears indeserved an increased incidence of obesity in adolescent girls (34, pendent of hyperinsulinemia and abnormal carbohydrate metab35). Long-term follow-up studies of adolescents suggest that olism (56). An alternative perspective is that insulin resistance 30% of all obese adult women were obese early in adolescence, may represent a primary rather than a secondary event (57, 58). fatness (18, 33). with age Furthermore,

958
Whether to the tissue stimuli acting tributes remission to have have genie relapse and its yet appears any of the same of obesity more Fatty may sensitive potential remains than mechanisms unclear. does gluteal also Abdominal fat to

DIETZ predispose adipose lipolytic fat fat conobesity who no or studies lipoor fat the
Age (years)
7 8 9 10 11 12 13 14 15 16 17 18

9
8
1 I C

persistence (59, 60). on the liver to rates increased indicated stimuli play of obesity. distribution

7
6

acids released from intraabdominal help explain why intraabdominal and are higher may than also those fat. explain in women, However, to lipolytic why

hyperinsulinemia, in men that deposition adipocyte a central Careful and are of

tend C)
V

a a a

5
4

females males 3 2

\,\IIIIhhIItCC%C,,I

of gluteal role in the studies of the synergistic essential.

C) C

responses

likelihood of remission the ontogeny of body factors that affect

persistence

of obesity

Summary These critical obesity observations periods and exist its attendant and effects suggest that at least for the two and possibly

in childhood complications

development

FIG 3. Incidence of obesity among 859 females and 1019 males measured annually between the ages of 7 and y in the Third 18 Harvard Growth Study, 1922-1935. The figure supports the assertion that the periods of adiposity rebound (ages 5-7 y) and adolescence represent times of increased risk for the development of obesity. Children were three not studied before age 7 y. of later

of diabetes,

hypertension.

Downloaded from www.ajcn.org by guest on February 16, 2011

at each of the critical periods outlined obesity that originate unclear. Likewise, age-specific therapeutic success have been confirmed in several studies, at least one of which has been established, and only limited data have followed subjects into adulthood, few longitudinal observations the potential hazards of weight-reduction have followed children with sufficient frequency through child- regarding Such data are essential to identify hood and adolescence to confirm that incident or persistent obe-children. effective time and target for efforts to prevent and sity increases at the periods outlined above. One exception is the Third ments several elude males with lescence Harvard Growth cohort Boston children appear adiposity marked
<

hypercholesterolemia. Although the

cardiovascular of birth weight

disease. on subsequent

The

relative

risks

of the

complications

or persistence rates been the treat

of obesity above remain have published therapy most childhood not in

cost-

Study,

which

included

annual

measure- obesity. in I gratefully acknowledge the inGrand, and Aviva Must for their and Aviva Must for her assistance

U
assistance of Jeffrey A Flier, Richard reviews of early drafts of the manuscript, with the data included in Figure 3. J

on a sizable towns near data from and females the peak of that

of children from (38). Although 7 y of to show rebound, age, an

1st to 12th grades this study did not data in both

incidence early peak and a second than in

that coincides peak in adoReferences males (Fig periods these persistent 3). I. Gortmaker
obesity

is more

in females

These observations represent critical periods obesity The also is the focus mechanisms

support the likelihood that these two periods for the onset of obesity. Whether critical periods for the onset deposition of of our current research. that trigger adipose tissue

SL, Dietz
in the United Freedman GS. Secular

WH,
States. DS,

Sobol
Am

AM,
J Dis of

Wehler
Child GL,

CA.
Harsha in early

Increasing
DW, life:

pediatric
Webber the Bogalusa LS,

l987;141:535-40.

represent

2. Shear
Berenson

CL,

Burke

trends

obesity

Heart Study. Am J Public Health 1988:78:75-7. in spe- 3. Dietz WH, Gortmaker SL. Factors within the physical environment ascific locations at some periods of fetal development and childsociated with childhood obesity. Am J Clin Nutr 1984;39:6l9-24. hood remain unclear. Nonetheless, these periods represent ma- 4. Dietz WH, Gortmaker SL. Do we fatten our children at the TV set? viewing and obesity in children and adolescents. Pediturational stages ideally suited for the study of the interaction of Television atrics 1985:75:807-12. environmental factors with the genes that control development. and changes in fatness from infancy through The mechanisms that entrain the long-term development of the 5. Garn SM. Continuities adulthood. Curr Prob Pediatr 1985:15:1-47. body fat mass, the possibility that the morbidity of obesity may 6. Bouchard C, Savard R, Dupres i-P. Tremblay A, Leblanc C. Body depend on the critical period in which obesity develops, and idencomposition in adopted and biological siblings. Hum Biol tification of the hormones and the means by which they induce 1985:57:61-75. sex-specific regional adipocyte replication are logically the sub- 7. Rimm Ii, Rimm AA. Association between juvenile onset obesity and jects of further investigations. severe adult obesity in 73,532 women. Am J Public Health The existence of critical periods for the development of adi1976:66:479-81. posity and its sequelae may also serve to focus preventive and 8. Abraham 5, Nordsieck M. Relationship excess of weight in children and adults. Public Health Rep 1960:75:263-73. therapeutic efforts on developmental stages when these efforts FEM, Rodgers B, Wadsworth MEJ, Davies JMC. Onset of are likely to be most cost effective. For example, improved dia- 9. Braddon in a 36 year birth cohort. Br Med J 1986;293:299-303. betic control may reduce the effects of gestational diabetes on obesity 10. Tanner JM. Foetus into man. Cambridge, MA: Harvard University birth weight and subsequent fatness. However, efforts to control Press, 1990. weight during the third trimester because of the putative effects 1 1. Illingworth RS, Lister J. The critical or sensitive period with special of weight gain on subsequent fatness cannot be supported based reference to certain feeding problems in infants and children. J Pcon the data reviewed. Until further data are forthcoming, the podiatr l964;65:839-48. tential growth retardation induced by third-trimester weight con- 12. Lucas A. Programming by early nutrition in man. In: Bock OR, trol may be more hazardous than whatever effects third-trimester Whelan J, eds. The childhood environment and adult disease. New weight gain may have on neonatal adiposity. York: John Wiley and Sons, 1991:38-55.

CRITICAL
13. Grumbaeh Wilson 8th 14. 15. ed. Websters Merriam Ravelli famine 16. Pettit sive 17. 18. 19. Binkin childhood Crisp aspects Seidman tudinal eence. 20. Swinburn sociated Invest 21. 22. 23. 24. Bray GA. Am AH, pregnancy. NJ, Di, obesity Co. G-P, exposure Baird N Engl Yip growth. Douglas DS, study BA, with 1991;88: Obesity, Laor of J Dis birth Child Nyomba lower 168-73. a disorder of nutrient of disorders R, HR. JD, MM, Foster New 1980. Stein in ZA, Susser utero Aleek of Fleshood Pediatrics JWB, or weight. A, Gale weight Ross R, J Med and KA, Pima L, JM, MW. early Bennett Indian Obesity infancy. PA, women Philadelphia: Conte DW, FA. cds. Disorders Williams of textbook sex

PERIODS
differentiation. of

FOR

OBESITY
38. In: Must morbidity the Harvard GC 39. after 1992:327:1350-5. Hoofmans dcx onary Sorensen young Mossberg men. at the heart A,

DEVELOPMENT
Jacques and PF, mortality Growth MDAF, age TIA, H-O. WH. The M, Endocrinol Kral sulfate 1990:55:410-5. JO, of 18 disease J Chron Dallal of Study Kromhout and and Sonne-holm Dis 40-Year-follow-up changes Bronnegard with its cancer. S. GE, of Bajema 1922 CJ, to Dictz 1935. C dc 32-year-mortality Epidemiol in extremely children. anatomical A, Elda L. WH. N

959
Long-term of J mass coroverweight Lancet distribution J, Gustafsson Med inEngI Body from

endocrinology.

overweight

adolescents:

a follow-up

WB

Saunders

Co,
Dictionary.

1992:853-95

1.
MA: young N Knowler with Engl WC. diabetes men J

Collegiate

Springfield, in

D, Coulander effects J Clin Mortality of overweight age M, of the on

Med 40.

1989:42:513-20.

1976:295:349-53. Excesin offspring

1977:30:359-67.

during 41.

1983:308:242-5. Trowbridge FL. Stonehill Res DK, overweight

1989:2:491-3.

Birth
E. Some Danon

weight

and

42. 43.

Mueller

1988:82:828-34. developmental YL. in late J Psychosom Stevenson and being 1970:14:313-20. A longiadoles- 44.

of fat. J-A,
sues. Miller ammonium Steroids

Soc Bjorntorp
J Clin LK,

Sci Med

1982;16:19l-6.
Nilsson

Rebuffe-Scrive

P. Steroid
Strain

hormone
Metab OW, of

receptors
1990:71:1215-9. Zumoff human

in human
B. Androgen

adipose tisbinding cytosols. to

1991:145:782-5.

precipitates

adipose

tissue

BL,
rates

Saad
of

MF,
weight

et al. Insulin
gain in Pima

resistance
Indians. The

asJ Clin 45. MONA

Lundgren
iposity and diabetes Gothenburg, Larsson vascular Weinsier of body 1985:7:578-85. Kaplan ance, N.

H, Bengtsson
adipose Sweden. B, Svardsudd adipose and born and The Norris fat deadly disease RL, fat tissue results Int in women:

C, Blohme
distribution from J Obes

0,

Lapidus
in relation

L, Sjostrom
to population L, Bjorntorp

L. Adof in study P. Tibblin of cardioin the

incidence

partitioning:

a prospective 1989:13:413-23. L, Wilhclmsen obesity follow-up The

Downloaded from www.ajcn.org by guest on February 16, 2011

LISA
Leibel body Eckel common Martin lipolysis

hypothesis. RL, Eden

fat distribution RH.

J Nutr 1991:121:1146-62. NK, Fried SK. Physiologic

in humans. lipase: diseases. Annu N Engl Rev J Med a multifunetional

basis
Nutr

for the control

1989:9:417-43. enzyme relevant

of 46.
to

K, Welin tissue death: DJ, pattern quartet: and SJ,

G. Abdominal
study of men

distribution, a 13-year Birch to RS, al. Ct blood upper

and

risk

Lipoprotein metabolic

of participants relative level. obesity, Arch contribution

1989:320:1060-8.

in 1913. Br Med

J 1984:288:1401-4. pressure body Hypertension glucose Intern intolerMed

ML,

Jensen

in obesity.

25.

Barker
Growth mortality

DJP,
in DJP, from risk CN, DJP, in

MD. Effects of body fat distribution on regional 47. J Clin Invest 1991:88:609-13. Osmond C, Golding J, Kuh D, Wadsworth MEJ.
blood cardiovascular AR, DJP, tolerance pressure disease. C, in adult Clark C, and death SH, Am Deheeger Adiposity obesity. M-F, M. Deheeger the Ann AF, for Guo children Leaverton 5, Tracking Am E. PMS, at age Winter from Berchtold J Clin M, Nutr Bellisle J Clin M, Hum from in the PE, development Biol 2 to Fels Mukherje Nutr rebound 64. life. et al. Br PD, Osmond in childhood Br Simmonds Br Med Med Fetal Marjetts heart SJ. and and Fetal infant B, adult and life, and 48. Med1987:298:564-7. J placental 49. and SJ. 50. J 1990;301:259-62. growth

utero, Bull Barker

hypertriglyceridemia, DS, Jacobsen differences Bengtsson a major of myocardial P. Abdominal diabetes P. Portal disease MMI, of free Shrago fatty mellitus. adipose and E, acids and effect C,

hypertension. Barboriak in lipids P. for Am and Diabetes the the JJ, and et et al.

26. 27. 28.

Barker size Hales impaired Barker Weight and

1989:149:1514-20. Freedman and Body fat distribution Circulation body in of risk I99(): Receptor insulin lessons on renal and dynamics. learned sodium 1981:21: from factors 10:493-6. postreceptor Int J Obes obesity. a 1. body J Obes the mcifat male/female B, lipoproteins. al. sex Is abdominal difference 1992:135:266-73. noninsulin for carRev of 1988:4:615-22.

of hypertension

glucose infancy NB, weight M, for

J 1991:303:1019-22. Simmonds disease. Lancet

1990:81:1498-506. Larsson distribution dence 51. Guilloud52. inBjorntorp dependent Bjorntorp diovascular P, from WC. Hennes effects Landsberg N Engl DeFronzo review with and Bjorntorp explanation infarction? obesity tissue Kissebah on hepatic

Osmond

ischaemic P. The

1989;2:577-80. 29. 30. Ruderman normal Batouille dicator 31. Patois month 32. Siervogel terns long-term Study. 33. Zack tudinal 1979;95: 34. Dietz States of Rolland-Cachera E, Sempe of age RM, change serial J Obes Harlan of body Obesity 126-30. WH. in infants, natural BS, Mayer of children, history, J. The and and adolescents after effects. and in the Nutr incidence school chilUnited I. Identification, ML, Am Burke Nutr to Rolland-Cachera Patois predicting Schneider individual. M-F, metabolically-obese, F, Sempe in children: M, M, 1981:34:1617-21. a simple Avons

J Epidemiol development Metab

as generator Arteriosclerosis AH.

1984:39:129-35. of adiposity

diabetes.

Guilloud-Bataille

53.
one Pat-

adulthood. Roche data WR, in weight/stature2 1991;15:479-85.

1987:14:219-29. ED, Chumlea findings 18 years: Longitudinal J.

199 1; 14:83 1-41.

L. Insulin hypertension: of insulin

54.

from Growth 55. A longi-56.

J Med
RA.

1987:317:378-9.
The metabolism: 165-7 between Int clinical plasma and implications. Diabetologia levels lipoprotein to the relationships levels in women.

mt
PM,

Cornoni-Huntley and adolescence.

Ferland
tolerance fat

M, Despres

J-P,
insulin plasma

Nadeau

A, et al. Contributions

of glucose

study

fatness

in childhood

J Pediatr

distribution

1991:15:677-88.

57. Rev

Reaven
man

GM.

Banting
Diabetes

lecture,

1988:

role

of insulin

resistance

in hu-

1981:1:117-37.

disease. for

1988:37:1595-607.

35. Johnson
obesity dren.

prevalence and secondary

58. DeFronzo of
responsible eroselerotic Rebuffe-Scrive different Wahrenberg gional

RA, Ferrannini
NIDDM, M, H, Enk cardiovascular regions differences

E. Insulin
obesity, disease. L, Crona J Clin F,

resistance:
hypertension, Diabetes N, Invest P. et

a multifaceted
dyslipidemia Care al. Fat

syndrome
and metabolism underlying athin reInvest

in a cross-section J Clin

elementary

1956;4:231-8.

1991:14:173-94. cell

36. 37.

Garn SM, Cole PE. Do the obese remain obese and the lean remain 59. lean? Am J Public Health 1980;70:351-3. Garn SM, Bailey SM, Cole PE. Continuities and changes in fatness 60. and obesity. In: Schemmel R, ed. Nutrition physiology and obesity. West Palm Beach, FL: CRC Press, Inc. 1979.

in women. Lonnqvist in lipolysis

1985;75:1973-6. Mechanisms adipose tissue. J Clin

Amer in human

1989;84:458-67.