July 24, 2019

expert reaction to central obesity and mortality risk in postmenopausal women of normal weight

Research into central obesity and mortality risk, published in JAMA, reports that women with normal weight but central obesity have excess risk of mortality, similar to that of women with BMI defined obesity and central obesity. 

Dr Katarina Kos, Senior Lecturer in Diabetes and Obesity Research, University of Exeter, College for Medicine and Health, said:

“What this paper adds is evidence from a large cohort of older women observed over up to 25 years, a time during which many develop heart problems, develop cancer or die. They found a higher health risk in those with central obesity regardless of weight. The authors factored in smoking, oestrogen use, alcohol use and physical activity, all which can affect where in the body fat is put down.

“These findings are not entirely new to those working in the health sector. Diabetes research is aware of the metabolic syndrome, which does not define increased risk of heart disease with BMI but with waist circumference. Similarly Type 2 diabetes is a disease of central obesity rather than just affecting people with high BMI.

“From my work on fat tissue biology, I perceive the fat underneath the skin as good fat and not contributing to actual health risk. The authors mention the obesity paradox, a controversial finding, based on limited evidence in that especially older people with a higher BMI could be somewhat protected from ill health and early death in comparison to leaner people. However, once correcting for factors which make us lose weight, such as pre-existing health conditions, this paradox does not appear to exist. However, this does not mean that central obesity is not an independent and potentially better predictor of health and deserves more focus. The authors explain that central obesity in which unhealthy fat wraps itself around organs and infiltrates organs may be a contributor to why relatively leaner people, especially those who have central fat, may still have increased health and mortality risk despite a ‘healthy’ BMI. 

“Fat contributing to central obesity is known as ectopic fat. It is called ‘ectopic’ for the reason that it is not at the correct place. Fat stored below the skin in what is known as subcutaneous fat tissue is the preferred place to store surplus energy. Unlike central fat, it makes us more likely look physically bigger and it can add considerably to BMI. If we have to imagine examples of ectopic fat, we find it in the liver known as fatty liver disease or find it in the muscle which is similar to when you look at the fat in bacon where it can be found visible as white mottling.

“The authors have an important message, which is for everybody keeping up a healthy lifestyle regardless of our overall build and, not surprisingly, the cohort of lean women with little central fat were found more active.”

Prof Fredrik Karpe, Head of Oxford Centre of Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, said:

“This report comes from a very credible cohort and with large numbers and long follow up giving credible and robust data.

“The investigators look at measures of obesity and their relationship to specific causes of mortality. Although conventionally measured obesity (by body mass index) relates to mortality, the stronger association is seen for upper body fatness. These relationships are particularly obvious in people who are not formally obese, suggesting that body fat distribution is the main driver for complications of fatness, not overall fatness per se. Although this message isn’t entirely new, the fact that it is so clearly shown is important. It is interesting to note that this relationship is seen with rather similar strength for a number of different types of mortality (cancer, cardiovascular etc), which underscores the globally detrimental effect of obesity and in particular some types of fat distribution. 

“From other data it will have to be assumed that the risk encountered by a certain type of fat distribution, which is an intrinsic property of the individual, is reduced by weight loss. It is known from other studies that weight loss affects a person’s most dominant fat depot most, i.e. abdominal fat, which is shown to be detrimental in this study, will be predominantly lost in someone with that fat distribution loses weight.

“I am particularly interested in the potentially protective effect of lower body fat, but unfortunately this study has not reported on that (fat distribution was measured by waist circumference only. Had hip circumference been measured/reported as well, this would have been of interest).

“The only criticism I would have of the study is that the investigators have used a fixed waist circumference for all levels of obesity (88cm), which makes the fat distribution much more extreme in the ‘normal weight’ individuals compared with ‘overweight’ or ‘obese’ individuals. This is easily seen in Table 3 where only 1,390/52,735 had ‘high WC’ in the normal weight group, whereas the corresponding ratio in the obese group was 42,633/4,957, i.e. the overwhelming majority of people in the obese group have a waist line greater than 88cm. A better way of doing it would have been to use a fixed proportion (top 5% in either group). If the investigators had done that, I am quite sure the mortality risk would have been massively higher in the ‘obese group’ and overshone the results that provide the main conclusion of the paper: that the fat distribution in the ‘normal weight’ group is having a strong effect.”

Dr Joy Leahy, Statistical Ambassador, Royal Statistical Society, said:

“This is a large, well conducted observational study examining the risk of a high waist circumference on mortality for women who are normal weight, overweight and obese, according to BMI. The study included 156,624 women and 43,838 deaths. The study provides compelling evidence that excess weight on the waist (>88 cm) is associated with an increased risk of death, even for women of normal weight. An advantage of this study is that many other factors which may influence death were recorded, for example, age, smoking status, level of physical activity, etc. The findings of this study hold true, even when accounting for these additional risk factors.

“It should be noted that women of normal weight with a high waist circumference are a relatively small subgroup, (0.9% of all women in this study and 2.6% of women with normal weight in this study). However, it is relatively easy to measure waist circumference in addition to BMI. Therefore, the results of this study provide a compelling argument for including a measurement of waist circumference in the guidelines for clinical practice for women of normal weight.

“This study focused solely on postmenopausal women, who were normal weight, overweight, or obese. It would be interesting to see if these results extend to underweight women according to BMI, men, and premenopausal or perimenopausal women.”

* ‘Association of Normal-Weight Central Obesity With All-Cause and Cause-Specific Mortality Among Postmenopausal US Women’ by Yangbo Sun et al. will be published in JAMA Network Open at 16:00 UK time on Wednesday 24th July, which is also when the embargo will lift. 

DOI: 10.1001/jamanetworkopen.2019.7337

Declared interests

Dr Katarina Kos:  I have no conflict of interest to declare.

Prof Fredrik Karpe: No conflicts of interest to declare.

Dr Joy Leahy: No conflicts of interest to declare.