Jump to: Page Content, Site Navigation, Site Search,
You are seeing this message because your web browser does not support basic web standards. Find out more about why this message is appearing and what you can do to make your experience on this site better.
Jean-Pierre Després a Quebec Heart Institute, Laval Hospital Research Centre,
Sainte-Foy, Quebec, Canada G1V 4G5, b Lipid Research Centre, CHUQ Research
Centre, Sainte-Foy, Quebec, Canada G1V 4G2, c Physical Activity Sciences Laboratory,
Laval University, Sainte-Foy, Quebec, Canada G1K 7P4
Correspondence to: J-P
Després jean-pierre.despres{at}crchul.ulaval.ca
It is generally accepted that obesity is a health
hazard because of its association with numerous metabolic complications such as dyslipidaemia, type 2 diabetes, and cardiovascular
diseases.1 On that basis, health agencies
2 3
have proposed that obesity should be defined on the basis of weight in
kg expressed over height in m2, the so called body mass
index,4 initially described by Quetelet in 1869 (table).
Epidemiological studies have reported a progressive increase in the
incidence of chronic diseases such as hypertension, diabetes, and
coronary heart disease with increasing body mass index.1-3 However, despite this well documented evidence,
physicians are, in their daily practice, perplexed by the remarkable
heterogeneity found in their obese patients. For instance, some
patients show a relatively "normal" profile of metabolic risk
factors despite the presence of substantial excess body fat, whereas
others who are only moderately overweight can nevertheless be
characterised by a whole cluster of metabolic complications, increasing
the risk of type 2 diabetes, coronary atherosclerosis, and
cardiovascular disease.
Summary points
A simple measurement such as waist circumference can indicate
accumulation of abdominal fat
Viscerally obese men are characterised by an atherogenic plasma
lipoprotein profile
A triad of non-traditional markers for coronary heart disease
found in viscerally obese middle aged men (hyperinsulinaemia, raised
apolipoprotein B concentration, and small LDL particles) increases the
risk of coronary heart disease 20-fold
Four out of five middle aged men with a waist measurement
90 cm and
triglyceride concentrations
2 mmol/l are characterised by this triad
Even in the absence of hypercholesterolaemia, hyperglycaemia, or
hypertension, obese patients could be at high risk of coronary heart
disease if they have this "hypertriglyceridaemic waist" phenotype
In this regard, epidemiological and metabolic studies conducted over the past 15 years have re-emphasised a notion introduced in the mid-forties by a French physician, Dr Jean Vague, who reported that the complications commonly found in obese patients were more closely related to where the excess fat was rather than to excess weight per se.5 Since this early pioneering work, in which Vague described the high risk form of obesity by the term "android obesity" or male type (upper body) obesity, several studies have confirmed the notion that a high proportion of abdominal fat is a major risk factor for coronary heart disease, type 2 diabetes, and related mortality.6 Furthermore, recent studies have also shown that a preferential accumulation of body fat in the gluteofemoral region, commonly found in premenopausal women and initially described by Vague under the term "gynoid obesity," is not a major threat to cardiovascular health. 7 8
Therefore, there is currently overwhelming evidence that abdominal
obesity is a major clinical and public health issue. In this review we
discuss the clinical implications of this concept regarding the
assessment and the management of risk in abdominally obese patients.
Visceral adipose tissue: the culprit
Epidemiological studies have mainly used anthropometric variables such as the ratio of waist to hip circumferences (waist:hip ratio) to estimate the proportion of abdominal adipose tissue (fig 1).
Sophisticated imaging techniques such as magnetic resonance imaging and
computed tomography, however, can distinguish, with a high level of
precision, intra-abdominal or visceral fat depot from subcutaneous
abdominal fat (fig 1).
6 9
These techniques showed that a simple measurement such as waist circumference was the
best anthropometric correlate of the amount of visceral adipose tissue
(fig 1).9 Furthermore, a seven year
longitudinal study conducted in women revealed that the change in waist
measurement was a better correlate of the change in visceral adipose
tissue observed over this period than the change in the waist:hip
ratio10 for reasons that are illustrated in figure
2.
|
|
| |
Metabolic complications associated with visceral obesity |
|---|
|
|
|---|
Plasma glucose and insulin concentrations and risk of type 2 diabetes
Type 2 diabetes not only increases the risk of retinopathy,
nephropathy, and neuropathy but is also a major risk factor for
atherosclerotic macrovascular disease, as 75% of patients with type 2 diabetes will eventually die from this complication.11
Prospective studies have shown that abdominal obesity is a major risk
factor for the development of type 2 diabetes.6 This
increased risk can be largely attributed to the fact that a high
accumulation of abdominal adipose tissue, especially of visceral
adipose tissue (see fig 1),12 has been associated with glucose intolerance and with hyperinsulinaemia resulting from insulin
resistance.
6 13
Atherogenic dyslipidaemia of visceral obesity: beyond low density
lipoprotein cholesterol
Obese individuals with a high accumulation of visceral adipose
tissue tend to have hypertriglyceridaemia and low concentrations of
high density lipoprotein cholesterol.14 Furthermore, the
reduction in plasma concentration of high density lipoprotein
cholesterol in these viscerally obese people is the major factor
responsible for the increase in their ratio of cholesterol:high density
lipoprotein cholesterol,15 this ratio being a powerful predictor of risk of coronary heart disease.16
|
| |
Atherogenic metabolic profile of visceral obesity: beyond "classic" risk factors |
|---|
|
|
|---|
Prospective studies have shown that the atherogenic metabolic
profile of patients with visceral obesity contributes substantially to
their increased risk of premature coronary heart
disease.18 Results from a prospective study of middle aged
men indicated that the cluster of metabolic abnormalities found in
viscerally obese men was associated with a substantial increase in the
risk of coronary heart disease, even in the absence of classic risk factors such as type 2 diabetes, hypercholesterolaemia, and
hypertension.18 A triad of "new" atherogenic metabolic
risk markers
fasting hyperinsulinaemia, increased apolipoprotein B
concentration, and an increased proportion of small, dense, low density
lipoprotein particles (abnormalities found together in viscerally obese
men, even in the absence of type 2 diabetes)
was found to be
associated with a 20-fold increase in the risk of developing coronary
heart disease in initially asymptomatic middle aged men followed over a
period of five years.18 Therefore, this atherogenic
metabolic triad of risk markers observed in viscerally obese patients
with insulin resistance is associated with a marked increase in the
risk of coronary heart disease.
|
Atherothrombotic, pro-inflammatory abnormalities in viscerally
obese patients
This cluster of complications substantially increases the risk of coronary heart disease in affected patients.
|
| |
Screening tools to identify high risk abdominally obese individuals |
|---|
|
|
|---|
The existence of this atherogenic metabolic triad indicates a need for a simple algorithm which could be used by general physicians and health professionals to screen rapidly for the risks associated with this cluster. A close relation between accumulation of visceral adipose tissue and plasma insulin and apolipoprotein B concentrations has been reported,10 but the direct measurement of accumulation of visceral adipose tissue by computed tomography is costly and involves irradiation of participants. Accumulation, however, can be estimated from anthropometric indices,19 and studies have shown that the waist circumference is a useful measurement not only to predict accumulation (see fig 1) but also to monitor its change over time. 10 20 On the other hand, the variable which has been reported to display the closest association with the presence of atherogenic small, dense, low density lipoprotein particles is the plasma triglyceride concentration measured in the morning after a 12 hour fast. 17 21
Simple screening variables, such as waist circumference and fasting
triglyceride concentrations, have been tested for their ability to
identify high risk, viscerally obese men who would be carriers of the
atherogenic triad.15 Sensitivity and specificity analyses
conducted in a sample of men aged between 30 and 65 years showed that a
cut off point of a 90 cm waist measurement would provide the best
discriminative ability to distinguish men with hyperinsulinaemia and
increased apolipoprotein B concentration from those with normal
concentrations for both variables.15 Furthermore, a
fasting triglyceride concentration of 2 mmol/l provided the best
cut off point to identify men with the small, dense, low density
lipoprotein phenotype.15 By using these simple cut off
values, more than 80% of men with a waist circumference
90 cm and
fasting triglyceride concentrations
2 mmol/l were carriers of the
atherogenic metabolic triad, whereas only 10% of men with a waist
circumference <90 cm and fasting triglyceride <2 mmol/l were
carriers.15 These results emphasise the importance of the
measurement and interpretation of waist circumference and of fasting
triglyceride concentration in the assessment of risk of coronary heart
disease. Although this approach is promising, it is important to point
out that there are sex and ethnic group differences in the relation of
waist measurement to accumulation of visceral adipose tissue as well as
to metabolic complications. Thus, it is likely that different cut off
values defining the hypertriglyceridaemic waist phenotype may be found
in women (before and after the menopause) as well as in other age and
ethnic groups.
Hypertriglyceridaemic waist: a new clinical phenotype defining a
high risk form of overweight/obesity
From the ability of the combined interpretation of waist
measurement and fasting plasma triglyceride concentration to
discriminate a large proportion of carriers from non-carriers of
the features of the atherogenic metabolic triad, we believe that the
hypertriglyceridaemic waist may help to refine our identification of high risk patients beyond the use of waist measurement alone.
Management of obesity: focusing on high risk patients
As obesity is often characterised by metabolic complications that
harm health, it has been suggested that it should be considered as a
disease.3 Unfortunately, if obesity is defined only on the
basis of body mass index, some healthy men and women (at least from a
metabolic point) with values of 30 and more will automatically be
classified at high risk even if they have a fairly normal profile of
metabolic risk factors. This may explain the rather disappointing
results of weight loss trials that use pharmacotherapy, in which a
large proportion of the participants were "metabolically healthy"
women.
25 26
However, on the basis of major metabolic
improvements induced by moderate (5-10%) weight loss (fig 4), the
relevance of an aggressive management of high risk abdominally obese
people identified not on the basis of body weight but also by waist
and fasting triglyceride measurements is emphasised. In
this context, the benefits of pharmacotherapy are likely to outweigh
the potential risks of drug treatment. Obesity as a health problem has
to be defined beyond of weight and cosmetic considerations.
|
|
| |
Footnotes |
|---|
Competing interests: J-PD has received honoraria for consultancy and lectures and funding for his laboratory from Servier Canada, Parke-Davis/Warner-Lambert Canada, Merck-Frosst Canada, Fournier Pharma, Gatorade, DuPont-Merck, Knoll Pharma, Weight Watchers International, Roche Pharma, and Eli Lilly.
Funding: This work was supported by the Canadian Institutes of Health Research (MT-14014 and MGC-15187). J-PD is chair professor of human nutrition and lipidology, which is supported by Parke-Davis/Warner-Lambert, Provigo, and the Foundation of the Quebec Heart Institute. IL is recipient of a fellowship from the Heart and Stroke Foundation of Canada.
| |
References |
|---|
|
|
|---|
| 1. | Bray GA, Bouchard C, James WPT, eds. Handbook of obesity. New York: Marcel Dekker, 1998. |
| 2. | National Heart, Lung, and Blood Institute/National Institutes of Diabetes and Digestive and Kidney Diseases. Clinical guidelines on the identification, evaluation and treatment of overweight and obesity in adults. The evidence report. Bethesda: National Institutes of Health, 1998:1-228. |
| 3. | WHO Consultation on Obesity. Preventing and managing the global epidemic. Geneva: World Health Organization, 1997:1-276. |
| 4. | Keys A, Fidanza F, Karvonen MJ, Kimura N, Taylor HL. Indices of relative weight and obesity. J Chronic Dis 1972; 25: 329-343[CrossRef][Medline]. |
| 5. | Vague J. La différenciation sexuelle, facteur déterminant des formes de l'obésité. Presse Med 1947; 30: 339-340. |
| 6. | Kissebah AH, Freedman DS, Peiris AN. Health risks of obesity. Med Clin North Am 1989; 73: 111-138[Medline]. |
| 7. | Terry RB, Stefanick ML, Haskell WL, Wood PD. Contributions of regional adipose tissue depots to plasma lipoprotein concentrations in overweight men and women: possible protective effects of thigh fat. Metabolism 1991; 40: 733-740[CrossRef][Medline]. |
| 8. | Pouliot MC, Després JP, Nadeau A, Tremblay A, Moorjani S, Lupien PJ, et al. Associations between regional body fat distribution, fasting plasma free fatty acid levels and glucose tolerance in premenopausal women. Int J Obes 1990; 14: 293-302[Medline]. |
| 9. | Pouliot MC, Després JP, Lemieux S, Moorjani S, Bouchard C, Tremblay A, et al. Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol 1994; 73: 460-468[CrossRef][Medline]. |
| 10. | Lemieux S, Prud'homme D, Tremblay A, Bouchard C, Després JP. Anthropometric correlates to changes in visceral adipose tissue over 7 years in women. Int J Obes Relat Metab Disord 1996; 20: 618-624[Medline]. |
| 11. | Pyorala K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev 1987; 3: 463-524[Medline]. |
| 12. | Bergstrom RW, Newell-Morris LL, Leonetti DL, Shuman WP, Wahl PW, Fujimoto WY. Association of elevated fasting C-peptide level and increased intra-abdominal fat distribution with development of NIDDM in Japanese-American men. Diabetes 1990; 39: 104-111[Abstract]. |
| 13. | Pouliot MC, Després JP, Nadeau A, Moorjani S, Prud'homme D, Lupien PJ, et al. Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels. Diabetes 1992; 41: 826-834[Abstract]. |
| 14. |
Després JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C.
Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease.
Arteriosclerosis
1990;
10:
497-511 |
| 15. |
Lemieux I, Pascot A, Couillard C, Lamarche B, Tchernof A, Alméras N, et al.
Hypertriglyceridemic waist. A marker of the atherogenic metabolic triad (hyperinsulinemia, hyperapolipoprotein B, small, dense LDL) in men?
Circulation
2000;
102:
179-184 |
| 16. | Castelli WP. Epidemiology of coronary heart disease: the Framingham study. Am J Med 1984; 76: 4-12[CrossRef][Medline]. |
| 17. | Tchernof A, Lamarche B, Prud'homme D, Nadeau A, Moorjani S, Labrie F, et al. The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care 1996; 19: 629-637[Abstract]. |
| 18. |
Lamarche B, Tchernof A, Mauriège P, Cantin B, Dagenais GR, Lupien PJ, et al.
Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease.
JAMA
1998;
279:
1955-1961 |
| 19. |
Lemieux S, Prud'homme D, Bouchard C, Tremblay A, Després JP.
A single threshold value of waist girth identifies normal-weight and overweight subjects with excess visceral adipose tissue.
Am J Clin Nutr
1996;
64:
685-693 |
| 20. | Lemieux S, Prud'homme D, Nadeau A, Tremblay A, Bouchard C, Després JP. Seven-year changes in body fat and visceral adipose tissue in women. Association with indexes of plasma glucose-insulin homeostasis. Diabetes Care 1996; 19: 983-991[Abstract]. |
| 21. |
McNamara JR, Jenner JL, Li Z, Wilson PW, Schaefer EJ.
Change in LDL particle size is associated with change in plasma triglyceride concentration.
Arterioscler Thromb
1992;
12:
1284-1290 |
| 22. |
Lean ME, Han TS, Morrison CE.
Waist circumference as a measure for indicating need for weight management.
BMJ
1995;
311:
158-161 |
| 23. | Lean ME, Han TS, Seidell JC. Impairment of health and quality of life in people with large waist circumference. Lancet 1998; 351: 853-856[CrossRef][Medline]. |
| 24. |
Han TS, van Leer EM, Seidell JC, Lean ME.
Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample.
BMJ
1995;
311:
1401-1405 |
| 25. |
Williamson DF.
Pharmacotherapy for obesity.
JAMA
1999;
281:
278-280 |
| 26. | Sjostrom L, Rissanen A, Andersen T, Boldrin M, Golay A, Koppeschaar HP, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European multicentre orlistat study group. Lancet 1998; 352: 167-172[CrossRef][Medline]. |
(Accepted 21 December 2000)
Read all Rapid Responses