Weight loss among metabolically healthy obese men and women: harmful or beneficial?<br />Peter M. Janiszewski & Robert Ros...
Clinical Obesity Treatment Guidelines<br />Measure BMI and WC<br />5-10 %    Weight Loss<br />Yes<br />Yes<br />BMI = 25-3...
Clinical Obesity Treatment Guidelines<br />Measure BMI and WC<br />Yes<br />5-10 %    Weight Loss<br />BMI ≥ 30 kg/m2<br /...
Metabolically Abnormal vs. Metabolically Healthy Obese<br />Metabolically Abnormal Obese (MAO)<br />~70 % of obese individ...
 High Fat Mass
 Low Insulin Sensitivity
 High Triglycerides
 Low HDL
 High Diabetes and CVD risk
 High BMI
 High Fat Mass
 High Insulin Sensitivity
 Low Triglycerides
 High HDL
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Weight loss among metabolically healthy obese men and women: harmful or beneficial?

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Dr. Peter Janiszewski presents his recent research findings at the 2009 Annual Meeting of the Canadian Society of Exercise Physiology.

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  • Clinical obesity treatment guidelines such as this one from the NIH provide straightforward algorithms to aid clinicians in deciding which patient is in need of obesity treatment. First, the body mass index and the waist circumference of the subject is measured (mention debate between bouchard and ross). If the patient’s BMI is between 25-30 (overweight) or WC is elevated (abdominal obesity), these anthropometric criteria alert the clinician to further assess cardiometabolic risk factors (glucose, triglycerides, blood pressure). IF the BMI or WC elevated and patient has elevated risk factors, only then should they be counseled to lose weight – the typically recommended 5-10%. If on the other hand they have elevated BMI or WC but no cardiometabolic risk, only periodic check-up is recommended.
  • However, if the subject’s BMI exceeds 30kg/m2, that is they are clinically obese, this algorithm suggests that weight loss is the only treatment option – regardless of cardiometabolic status. In other words, it is suggested that every obese patient, no matter their cardiometabolic profile, should be counseled to lose 5-10% of their body weight.
  • The notion that all obese individuals should be counseled to lose weight without assessment of cardiometabolic risk is quite well founded given that the large majority of obese individuals are considered to be “Metabolically Abnormal”, that is they are insulin resistant, dyslipidemic, and have a high prospective risk of developing diabetes and cardiovascular disease. However, it must also be noted that there exists an alternate phenotype of obesity – what has come to be know as the metabolically health obese. Despite their obesity and excess fat mass, these individuals are insulin sensitive, have normal blood lipid levels, normal blood pressure, and are at no greater prospective risk of developing diabetes or CVD than their lean counterparts. The important thing to note here is the fact that according to estimates, 30% of obese individuals is actually considered metabolically healthy. That is 1 in 3 obese individuals are void of the metabolic aberrations which are thought to go hand in hand with excess weight. This notion has led some to question whether it is appropriate to counsel all individuals with an elevated BMI to reduce body weight, given that a third of them may actually be metabolically healthy. In other words, it has been suggested that many obese persons are unnecessarily being told to reduce body weight. Instead, some argue that simply striving to maintain current weight or stop further weight gain may be the most appropriate treatment strategy for metabolically healthy obese patients.
  • But the story became even more intriguing when Karelis and colleagues published a brief report in Diabetologia in the previous year. In this study MAO and MHO postmenopausal women were subjected to 6 months of hypocaloric diet (approximately -500-800 kcals/day). Not surprisingly, among those women deemed to be MAO, or with low IS at baseline, 6 months of diet induced weight loss resulted in a 26% increase in insulin sensitivity. In stark contrast, among women who were deemed to be MHO, or had high insulin sensitivity at baseline, the same intervention was associated with
  • In stark contrast, among women who were deemed to be MHO, or had high insulin sensitivity at baseline, the same intervention was associated with a 13% decrease in IS. That is diet induced weight loss among MHO individuals may not only be unnecessary but potentially harmful.
  • These intriguing concepts bring us to the objective of the current investigation, which was to…. That is we wanted to extend the previous observations by Karelis and colleagues to exercise intervention as well as men.
  • Very briefly, for this study we used an opportunistic sample of 109 obese men and women who had previously participated in various weight loss studies in our lab at Queen’s university. In this study we chose to divide our sample into MHO and MAO groups based on their cardiometabolic risk factor clustering as per the NCEP-ATPIII definition of the metabolic syndrome, such that all obese individuals with 2 or less risk factors were deemed to be MHO and all those with 3 or more were deemded to be MAO.
  • Here are the characteristics of our 4 groups at baseline – age ranged from mid 40’s to early 60’s, and was higher in the MHO vs AMO groups, and thus all subsequent comparisons controlled for age. We see they are all obese – with average BMI’s in the class 1 obese category. And finally we see that on most of the cardiometabolic variables assessed the MHO are significantly better off than the MAO subjects. And by design, all the MAO subjects had metsyn whereas none of the MHO subjects met the definition.
  • Here we see the effect of the intervention with control for age and treatment modality in the repeated measures comparisons. First variable of interest in body weight, and we see that body weight was significantly reduced in all groups in the range of 4-6 kgs. Similarly we see a significant reduction in fat mass in all the groups independent of gender or metabolic risk group. Now I will show you the effect of the diet or exercise intervention on cardiometabolic risk factors, and I will use just a few examples of the trends observed. In terms of fasting plasma glucose, we see that the 2 MAO groups showed a reduction, however this was only significant in the MAO men, whereas the values did not budge in the MHO – not surprising given their baseline values were already very low. We also see a similar patern with level of triglycerides, such that the MAO men and women who start with elevated TG levels show a significant reduction, whereas no significant change is seen among the MHO men and women. Again not surprising given their baseline values. So from these results we can concluded that diet and or exercise induced weight loss among MHO individuals is less likely to result in significant metabolic improvements in contrast to that seen among MAO subjects. However, it is also true that we show no evidence of any worsening of metabolic status in response to treatment.
  • And finally when we look at changes in insulin sensitivity as assessed via a euglycemic-hyperinsulinemic clamp prodecure we see the following. In these figures each coloured line represents a single subject from pre to post and the dashed yellow line represents the mean change in that group. Improvements in MAO men – significant. While this figure may not look too impressive due to the scale, the change in the MHO men actually represented a 22% increase in IS from baseline – also statistically significant. And similar findings for MAO women as well as MHO women – here the increase in IS was just below 20%. Thus, you may notice that our findings do not agree with that of Karelis and colleagues who showed that with a similar degree of weight reduction MHO women reduced their IS. However, keep in mind that these results are collapsed across treatment modality (but controlled for).
  • Thus we also looked to see if response in IS differed by modality of weight loss treatment, and thus we collapsed across gender and divided results by modaility. And we see that in the MAO individuals, just as in the MHO individuals IS was improved regardless of the modality. AS you can see the diet intervention appeared to have the same positive effect on IS as the others. Genders combined.
  • This of course is true when you consider the benefits of modest weight-loss on non-metabolic consequences of obesity such as knee osteaoarthritis, sexual function, quality of life, etc.
  • Weight loss among metabolically healthy obese men and women: harmful or beneficial?

    1. 1. Weight loss among metabolically healthy obese men and women: harmful or beneficial?<br />Peter M. Janiszewski & Robert Ross<br />School of Kinesiology and Health Studies<br />
    2. 2. Clinical Obesity Treatment Guidelines<br />Measure BMI and WC<br />5-10 % Weight Loss<br />Yes<br />Yes<br />BMI = 25-30 kg/m2ORWC >102/88 cm<br />High BMI or WC AND Risk Factors<br />Assess Risk Factors<br />No<br />No<br />Periodic Check-up<br />Adapted from: NIH-NHLBI (1998) Obesity Research<br />
    3. 3. Clinical Obesity Treatment Guidelines<br />Measure BMI and WC<br />Yes<br />5-10 % Weight Loss<br />BMI ≥ 30 kg/m2<br />Adapted from: NIH-NHLBI (1998) Obesity Research<br />
    4. 4. Metabolically Abnormal vs. Metabolically Healthy Obese<br />Metabolically Abnormal Obese (MAO)<br />~70 % of obese individuals<br />Metabolically Healthy Obese (MHO)<br />~30 % of obese individuals<br /><ul><li> High BMI
    5. 5. High Fat Mass
    6. 6. Low Insulin Sensitivity
    7. 7. High Triglycerides
    8. 8. Low HDL
    9. 9. High Diabetes and CVD risk
    10. 10. High BMI
    11. 11. High Fat Mass
    12. 12. High Insulin Sensitivity
    13. 13. Low Triglycerides
    14. 14. High HDL
    15. 15. Low Diabetes and CVD risk</li></li></ul><li>Diet-Induced Weight Loss in MAO vs. MHO Women<br />Pre<br />Post<br />Insulin Sensitivity (μmol/min/kg FFM)<br />↑26.1%<br />Karelis et al. (2008) Diabetologia<br />
    16. 16. Diet-Induced Weight Loss in MAO vs. MHO Women<br />Pre<br />Post<br />Insulin Sensitivity (μmol/min/kg FFM)<br />↑26.1%<br />↓12.8%<br />Karelis et al. (2008) Diabetologia<br />
    17. 17. Objective<br /> Investigate the effects of exercise- and diet-induced weight reduction on cardiometabolic risk factors among MHO and MAO men and women<br />
    18. 18. Methods<br /><ul><li>109 obese men and women were divided into MHO or MAO based on NCEP-ATP III criteria for metabolic syndrome:
    19. 19. MHO: ≤ 2 of elevated waist circumference, elevated fasting plasma glucose, elevated triglycerides, low HDL-cholesterol, and elevated blood pressure
    20. 20. MAO: > 2 of above risk factors
    21. 21. Participants underwent 3-6 months of aerobic or aerobic/resistance exercise or diet weight-loss intervention.
    22. 22. Changes in anthropometry, body composition by magnetic resonance imaging, and cardiometabolic risk, including insulin sensitivity by hyperinsulinemic-euglycemic clamp, were assessed.</li></li></ul><li>Results: Subject Characteristics<br />Data presented as the group means ± SD. <br />Age included as a covariate in analyses.<br />a Significantly different from men (P < 0.05). <br />b Significantly different from at-risk group of same gender (P < 0.05).<br />
    23. 23. Results: Effect of Intervention<br />*<br />*<br />*<br />*<br />*<br />*<br />*<br />*<br />Body Weight (kg)<br />Fat Mass (kg)<br />Men<br />Men<br />Women<br />Women<br />*<br />*<br />*<br />Glucose (mmol/L)<br />TG (mmol/L)<br />Men<br />Men<br />Women<br />Women<br />* Significantly different from baseline (P<0.05). Analyses controlled for age and treatment modality. <br />
    24. 24. Results: Changes in Insulin Sensitivity<br />MHO Men<br />MAO Men<br />Insulin Sensitivity (mg/kg∙SM/min)<br />Insulin Sensitivity (mg/kg∙SM/min)<br />Pre<br />Post<br />Post<br />Pre<br />MAO Women<br />MHO women<br />Insulin Sensitivity (mg/kg∙SM/min)<br />Insulin Sensitivity (mg/kg∙SM/min)<br />Pre<br />Pre<br />Post<br />Post<br />
    25. 25. Results: Changes in Insulin Sensitivity<br />MHO<br />MAO<br />Insulin Sensitivity (mg/kg∙SM/min)<br />Insulin Sensitivity (mg/kg∙SM/min)<br />Pre<br />Post<br />Pre<br />Post<br />3 Months Diet <br />3 Months Aerobic Exercise<br />6 Months Resistance/Aerobic Exercise<br />6 Months Aerobic Exercise<br />
    26. 26. Conclusions<br /><ul><li>Exercise- or diet-induced weight loss among MHO subjects is not associated with an increase in cardiometabolic risk, but in fact, may lead to further improvements in certain metabolic outcomes (insulin sensitivity)
    27. 27. While the cardiometabolic benefit may be modest, a 5-10% weight loss among MHO individuals should still be considered an appropriate clinical treatment option</li></li></ul><li>Acknowledgements<br />

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