Selected Summaries 200
Waist–hip ratio: A thrifty phenotype?
Yusuf S, Hawken S, Ôunpuu S, Bautista L, Franzosi
MG, Commerford P, Lang CC, Rumboldt Z, Onen CL, Lisheng
L, Tanomsup S, Wangai P Jr, Razak F, Sharma AM, Anand SS,
on behalf of the INTERHEART Study Investigators. (Population
Health Research Institute, McMaster University and Hamilton
Health Sciences, Hamilton, Canada; University of Wisconsin
Medical School, Wisconsin, USA; Istituto Mario Negri, Milano,
Italy; University of Cape Town, South Africa; Ninewells
Hospital and Medical School, Dundee, UK; University of
Split, Croatia; Gaborone Private Hospital, Botswana; Cardiovascular
Institute and Fu Wai Hospital, Beijing, China; Ramathibodi
Hospital, Bangkok, Thailand; Nairobi Women’s Hospital,
Nairobi, Kenya.) Obesity and the risk of myocardial infarction
in 27 000 participants from 52 countries: A case–control
study. Lancet 2005;366:1640–9.
In the second report of the Interheart study, Salim Yusuf
and colleagues have reported on the associations between
different obesity measures and myocardial infarction.
In a case–control study of over 27 000 men and
women belonging to many different ethnic groups in 52
countries, they found that the waist–hip ratio
(WHR) has a much stronger association with myocardial
infarction than the body mass index (BMI) or the waist
circumference. Of the two measures of central size, waist
circumference was predictive while hip circumference
was protective. The authors and an accompanying leader
in the Lancet suggest that the BMI is an inappropriate
risk factor for myocardial infarction and that it should
be replaced by waist and hip measurements.
The Interheart study is a marvellous achievement in collaborative
epidemiology, and the number of myocardial infarctions
(more than 12 000) must be one of the largest ever studied.
However, a cross-sectional case–control design does
not establish causality, and ‘obesity’ has
a number of metabolic, mechanical and other risks, which
may or may not be captured by one measurement. Further
studies are necessary before we can say that BMI should
be replaced in clinical practice, but doctors should now
start using a measuring tape in addition to a weighing
scale, height stadiometer and the stethoscope. More efforts
are necessary to standardize the measurement of waist and
hip circumferences, which are somewhat difficult because
of anatomical reasons and social inhibitions.
BMI is the most frequently used index
of obesity, and has the advantage that it is easily measured.
WHO has provided ‘normal’ values
and guidelines on the diagnosis of ‘undernutrition’ and ‘overnutrition’,
and these dictate current clinical practice. Over the past
few years there is a growing concern that the WHO criteria
for the diagnosis of ‘overweight’ and ‘obesity’ may
not be universally appropriate, and that body composition
rather than size may be the more relevant risk factor for
non-communicable diseases (NCD). Thus, Asian Indians have
a high risk of type 2 diabetes at a low BMI.1 Such considerations led to new ‘population-specific’ recommendations
for ‘public health action points’ of BMI.1 The differences in the risk of a given BMI in different
are partly due to differences in ‘adiposity’ (body
fat percentage) and its distribution. Thus, Asian Indians
have a higher adiposity for a given level of obesity,1
and it is more central2,3 compared with other populations.
suggested BMI cut-off point for Asian Indians is 23 kg/m2,
which is lower than that for other populations. On the
other hand, Pacific Islanders have a larger body frame
muscular; the cut-off point for them is 27 kg/m2.
Jean Vague, a French physician, first suggested that cardio-vascular
and metabolic risk in women is more closely related to ‘android’ (upper
body or abdominal) than to ‘gynoid’ (lower body)
obesity.4 Thus, ‘apples’ suffer more than ‘pears’.
A real boost for this idea came after the publication of
prospective follow up reports from Sweden, which showed
that higher WHR predicted incident type 2 diabetes, cardiovascular
events and death in Swedish women5 and men.6 The first
of the association between WHR and hyperglycaemia in Indians
was from Pune.7
Per Bjorntorp and Rosmond elaborated the concept of central
obesity and proposed that the risk was related to ‘visceral’ (rather
than subcutaneous) fat which drained in the portal circulation.
This produces morphological (steatosis) and metabolic derangements
in the liver8 causing insulin resistance, abnormal lipid
metabolism and a pro-coagulatory, pro-thrombotic and pro-inflammatory
state. These arguments were supported by newer imaging techniques
(CT and MRI), which allowed separation of abdominal fat into
subcutaneous and ‘visceral’ compartments. However,
it is still debated if subcutaneous abdominal or visceral
fat carries a higher risk for NCD.
The conventional explanation for the
metabolic and vascular risks of adiposity has revolved
around the role of fatty
acids that cause insulin resistance by metabolic competition
acid’ cycle). In addition, fatty acids are vasculotoxic
and are ligands for nuclear factors which have a profound
effect on metabolism (for example, peroxisome proliferator-activated
receptors, PPARs).9 Fat tissue is now recognized as the
largest ‘endocrine’ organ,
secreting a number of protein molecules (‘adipokines’)
which affect intermediary metabolism (leptin, resistin
and adiponectin), inflammation (interleukin-6), thrombosis
activator inhibitor-1), etc.10 It is not clear how adipose
tissue in different parts of the body behaves differently.
Understanding the factors that influence deposition of
lean and fat tissue is thus of paramount importance. Body
of the human foetus is influenced by maternal adiposity,
metabolism and nutrition.11 Maternal glycaemia (even in
the normal range) is a well known risk factor for foetal
and subsequent obesity and type 2 diabetes;12,13 maternal
lipids may be equally important. On the other hand, low
birth weight and thinness (‘thrifty phenotype’)14 have
also been associated with increased risk of NCD. This apparent
paradox was resolved when low birth weight babies were shown
to be ‘thin but fat’,15 and to grow into ‘obese’ children
and adults.11,16 There is as yet little information on
the specific genetic and maternal nutritional factors that
foetal body composition, and it is interesting to notethat
there are few, if any, paternal determinants of foetal
adiposity. Recently, we have shown that an imbalance in
maternal vitamin B12 and folate nutrition could programme
adiposity and insulin resistance in Indian babies.17 Rapid
childhood growth (presumably due to abundant nutrition)
increases the risk of central adiposity.18
What might be the evolutionary advantage of ‘central
adiposity’ for the developing foetus? Post partum,
the fat provides energy and helps thermoregulation. The
driving force for fat deposition may be the need for brain
preservation, a requisite for species survival. The brain
is composed mostly of fat, and the requisite nutrients
are supplied by diversion of blood flow to the preductal
circuit, depriving the ‘caudal’ structures
(heart, liver, kidneys, pancreas and legs). Short legs,
representing ‘caudal diminution’ predict diabetes
and cardiovascular disease.19 Higher WHR thus represents
an exaggerated thrifty phenotype due to rapid nutritional
transition: small hips represent foetal deprivation and
large waist the subsequent abundance. Thus, prevention
of cardiovascular disease may depend on the use of appropriate
measures during foetal life and childhood, whereas measures
targeting adults will probably be much less effective.
- WHO Expert Consultation. Appropriate body-mass index
for Asian populations and its implications for policy
and intervention strategies. Lancet 2004;363:157–63.
- McKeigue PM, Shah B, Marmot MG. Relation of central
obesity and insulin resistance with high diabetes
prevalence and cardiovascular risk in South Asians.
- Banerji MA, Faridi N, Atluri R, Chaiken RL, Lebovitz
HE. Body composition, visceral fat, leptin, and insulin
resistance in Asian Indian men. J Clin
Endocrinol Metab 1999;84:137–44.
- Vague J. Sexual differentiation, a factor affecting
the forms of obesity. Presse Med 1947;30:339–40.
- Lapidus L, Bengtsson C, Larsson B, Pennert K, Rybo
E, Sjostrom L. Distribution of adipose tissue and
risk of cardiovascular disease
death: A 12
year follow up of participants in the population study of women
in Gothenburg, Sweden.
Br Med J (Clin Res Ed) 1984;289:1257–61.
- Ohlson LO, Larsson B, Bjorntorp P, Eriksson H, Svardsudd
K, Welin L, et al. Risk factors for type 2 (non-insulin-dependent)
and one-half years of follow-up of the participants in a study
of Swedish men born
in 1913. Diabetologia 1988;31:798–805.
- Shelgikar KM, Hockaday TD, Yajnik CS. Central rather
than generalized obesity is related to hyperglycaemia
in Asian Indian subjects.
Diabet Med 1991;8:712–17.
- Bjorntorp P, Rosmond R. Visceral obesity and diabetes.
Drugs 1999;58 (Suppl 1):13–18.
- Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin
J, Johnson A, et al. Elevated circulating free fatty
J Clin Invest 1997;100:1230–9.
- Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell
MA. The adipocyte: A model for integration of endocrine
metabolic signaling in
Am J Physiol Endorinol Metab 2001;280:E827–E847.
- Yajnik CS. Obesity epidemic in India: Intrauterine
origins? Proc Nutr Soc 2004;63:387–96.
- Pettitt DJ, Baird HR, Aleck KA, Bennett PH, Knowler
WC. Excessive obesity in offspring of Pima Indian
pregnancy. N Engl
J Med 1983;308:242–5.
- Pettitt DJ, Aleck KA, Baird HR, Carraher MJ, Bennett
PH, Knowler WC. Congenital susceptibility to NIDDM:
Role of intrauterine
environment. Diabetes 1988;37:622–8.
- Hales CN, Barker DJ. The thrifty phenotype
hypothesis. Br Med Bull 2001;60:5–20.
- Yajnik CS, Fall CH, Coyaji KJ, Hirve SS, Rao
S, Barker DJ, et al. Neonatal anthropometry:
The thin–fat Indian baby. The Pune Maternal Nutrition Study.
Int J Obes Relat Metab Disord 2003;27:173–80.
- Kensara OA, Wootton SA, Phillips DI, Patel
M, Jackson AA, Elia M, Hertfordshire Study
Group. Fetal programming
weight and body composition measured with
dual-energy X-ray absorptiometry and anthropometric
methods in older Englishmen. Am J Clin
- Deshpande SS, Yajnik CS, Naik SS, Bhat
DS, Fisher DJ, Refsum H, et al. Low maternal
at 6 years: Pune Maternal Nutrition Study.
Pediatr Res 2005;58:1017.
- Sachdev HS, Fall CH, Osmond C, Lakshmy
R, Dey Biswas SK, Leary SD, et al. Anthropometric
size at birth and serial measurements
mass index in childhood in the New Delhi
birth cohort. Am J Clin Nutr 2005;82:456–66.
- Smith GD, Greenwood R, Gunnell D,
Sweetnam P, Yarnell J, Elwood P. Leg
resistance, and coronary
J Epidemiol Community Health 2001;55:867–72.