VOLUME 19, NUMBER 4                                                                         JULY/AUGUST2006

Selected Summaries

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 populations 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. The 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 and are 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 report 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 (Randle ‘glucose–fatty 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 (plasminogen 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 fat 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 adiposity 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 influence 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.


  1. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157–63.
  2. McKeigue PM, Shah B, Marmot MG. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet 1991;337:382–6.
  3. 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.
  4. Vague J. Sexual differentiation, a factor affecting the forms of obesity. Presse Med 1947;30:339–40.
  5. Lapidus L, Bengtsson C, Larsson B, Pennert K, Rybo E, Sjostrom L. Distribution of adipose tissue and risk of cardiovascular disease and 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.
  6. Ohlson LO, Larsson B, Bjorntorp P, Eriksson H, Svardsudd K, Welin L, et al. Risk factors for type 2 (non-insulin-dependent) diabetes mellitus. Thirteen and one-half years of follow-up of the participants in a study of Swedish men born in 1913. Diabetologia 1988;31:798–805.
  7. 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.
  8. Bjorntorp P, Rosmond R. Visceral obesity and diabetes. Drugs 1999;58 (Suppl 1):13–18.
  9. Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, et al. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest 1997;100:1230–9.
  10. Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA. The adipocyte: A model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endorinol Metab 2001;280:E827–E847.
  11. Yajnik CS. Obesity epidemic in India: Intrauterine origins? Proc Nutr Soc 2004;63:387–96.
  12. Pettitt DJ, Baird HR, Aleck KA, Bennett PH, Knowler WC. Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy. N Engl J Med 1983;308:242–5.
  13. 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.
  14. Hales CN, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull 2001;60:5–20.
  15. 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.
  16. Kensara OA, Wootton SA, Phillips DI, Patel M, Jackson AA, Elia M, Hertfordshire Study Group. Fetal programming of body composition: Relation between birth weight and body composition measured with dual-energy X-ray absorptiometry and anthropometric methods in older Englishmen. Am J Clin Nutr 2005;82:980–7.
  17. Deshpande SS, Yajnik CS, Naik SS, Bhat DS, Fisher DJ, Refsum H, et al. Low maternal B12 and high folate predict offspring adiposity and insulin resistance at 6 years: Pune Maternal Nutrition Study. Pediatr Res 2005;58:1017.
  18. Sachdev HS, Fall CH, Osmond C, Lakshmy R, Dey Biswas SK, Leary SD, et al. Anthropometric indicators of body composition in young adults: Relation to size at birth and serial measurements of body mass index in childhood in the New Delhi birth cohort. Am J Clin Nutr 2005;82:456–66.
  19. Smith GD, Greenwood R, Gunnell D, Sweetnam P, Yarnell J, Elwood P. Leg length, insulin resistance, and coronary heart disease risk: The Caerphilly Study. J Epidemiol Community Health 2001;55:867–72.
Diabetes Unit
K.E.M. Hospital Research Centre
Rasta Peth


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