The association between metabolically healthy obesity and risk of cancer: A systematic review and meta‐analysis of prospective cohort studies

Lin, Chien-Ju; Chang, Yu‐Chen; Cheng, Ting-Yao; Lo, Kai; Liu, Shu-Jung; Yeh, Tzu-Lin

doi:10.1111/obr.13049

Cited by 38 publications

(36 citation statements)

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“…Obesity is a major and multidimensional health problem worldwide and a major risk factor for additional health concerns such as cardiovascular diseases, diabetes mellitus, musculoskeletal disorders, and some cancers. 1 , 2 , 3 In Europe, the currently approved drugs for obesity are perorally administered orlistat (Alli and Xenical), perorally administered bupropion/naltrexone (Mysimba), and subcutaneously injected liraglutide (Saxenda). With the exception of the oral dosage forms of orlistat, all currently approved anti‐obesity pharmaceutical products have some systemic side effects.…”

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confidence: 99%

Safety of a Novel Weight Loss Combination Product Containing Orlistat and Acarbose

Grudén

Forslund

Alderborn

et al. 2021

Clinical Pharm in Drug Dev

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The safety of a novel modified-release oral capsule with orlistat and acarbose (MR-OA) was investigated in 67 obese middle-aged White men with a body mass index of 32 to 40 kg/m 2 or 30 to 32 kg/m 2 plus waist circumference >102 cm. The purpose of this investigation was to compare MR-OA with the existing conventional orlistat regarding systemic safety defined as plasma orlistat concentration at the end of the treatment period of 14 days. Participants took the MR-OA fixed-dose combination formulation 3 times a day together with a major meal. Three different doses of MR-OA were evaluated-60/20, 90/30, and 120/40 (mg orlistat/mg acarbose)-as well as 1 reference group who received the conventional orlistat, Xenical, with 120 mg of orlistat. Blood plasma was sampled on days 1 and 14. The orlistat plasma concentrations of the MR-OA dose showed a delayed absorption and were lower compared with conventional orlistat at the end of the study. All doses were safe and well tolerated without any unexpected adverse events and no serious adverse events. The delay in the rise of orlistat plasma concentration indicates that the modified-release properties of the MR-OA formulation are effective. The systemic exposure of orlistat resulting from MR-OA was similar, albeit a bit lower than the conventional orlistat with 120 mg of orlistat. We can therefore assume that the safety profile regarding the orlistat moiety of MR-OA is comparable to the conventional orlistat and a promising approach for weight control in obese patients. Further clinical evaluation is underway.

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mentioning

confidence: 99%

Safety of a Novel Weight Loss Combination Product Containing Orlistat and Acarbose

Grudén

Forslund

Alderborn

et al. 2021

Clinical Pharm in Drug Dev

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“…Since then, the number of publications on the metabolically healthy (or unhealthy) phenotype has increased dramatically (Ortega et al, 2018). There has been considerable discussion and debate over Please cite this article in press as: Gaesser and Angadi, Obesity treatment: Weight loss versus increasing fitness and physical activity for reducing health risks, iScience (2021), https://doi.org/10.1016/j.isci.2021.102995 iScience Review the MHO phenotype and whether there is such a thing as ''healthy obesity'' (Brown and Kuk, 2015;Eckel et al, 2016;Kramer et al, 2013Kramer et al, , 2014Ortega et al, 2013Ortega et al, , 2015Ortega et al, , 2018Roberson et al, 2014;Hsueh et al, 2020;Huang et al, 2020;Lin et al, 2020;Yeh et al, 2019).…”

Section: Healthy Obesity Phenotype: Importance Of Cardiorespiratory Fitness and Physical Activitymentioning

confidence: 99%

“…Since then, the number of publications on the metabolically healthy (or unhealthy) phenotype has increased dramatically ( Ortega et al., 2018 ). There has been considerable discussion and debate over the MHO phenotype and whether there is such a thing as “healthy obesity” ( Brown and Kuk, 2015 ; Eckel et al., 2016 ; Kramer et al., 2013 , 2014 ; Ortega et al., 2013 , 2015 , 2018 ; Roberson et al., 2014 ; Hsueh et al., 2020 ; Huang et al., 2020 ; Lin et al., 2020 ; Yeh et al., 2019 ).…”

Section: Healthy Obesity Phenotype: Importance Of Cardiorespiratory Fitness and Physical Activitymentioning

confidence: 99%

“…One major limitation of the EOSS and CMDS is that they do not consider PA or CRF in the risk assessment. In fact, virtually all studies to date, including most reviews and meta-analyses, have not included assessments of PA and CRF to characterize MHO ( Brown and Kuk, 2015 ; Eckel et al., 2016 ; Hsueh et al., 2020 ; Huang et al., 2020 ; Kramer et al., 2013 , 2014 ; Lin et al., 2020 ; Yeh et al., 2019 ). This is important because individuals with MHO engage in more moderate-to-vigorous PA and have a higher level of CRF than individuals with a metabolically unhealthy obesity (MUO) phenotype, and also spend less time in sedentary behaviors ( Ortega et al., 2018 ).…”

Section: Healthy Obesity Phenotype: Importance Of Cardiorespiratory Fitness and Physical Activitymentioning

confidence: 99%

“…and (2) What is the magnitude of cardiovascular disease (CVD) risk marker reduction associated with weight loss interventions compared with that of PA interventions? Answers to these questions can help clarify the controversies surrounding the healthy obesity phenotype and the “fat but fit” concept ( Brown and Kuk, 2015 ; Eckel et al., 2016 ; Hsueh et al., 2020 ; Huang et al., 2020 ; Kramer et al., 2013 , 2014 ; Lin et al., 2020 ; Ortega et al., 2013 , 2015 , 2018 ; Roberson et al., 2014 ; Yeh et al., 2019 ). Answers to these questions are also relevant to the recommendations of the American Heart Association that CRF be considered as an important vital sign ( Ross et al., 2016 ), which may be especially useful in risk classification of individuals with obesity-related comorbidities.…”

Section: Introductionmentioning

confidence: 99%

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Obesity treatment: Weight loss versus increasing fitness and physical activity for reducing health risks

Gaesser

Angadi

2021

iScience

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We propose a weight-neutral strategy for obesity treatment on the following grounds: (1) the mortality risk associated with obesity is largely attenuated or eliminated by moderate-to-high levels of cardiorespiratory fitness (CRF) or physical activity (PA), (2) most cardiometabolic risk markers associated with obesity can be improved with exercise training independent of weight loss and by a magnitude similar to that observed with weight-loss programs, (3) weight loss, even if intentional, is not consistently associated with lower mortality risk, (4) increases in CRF or PA are consistently associated with greater reductions in mortality risk than is intentional weight loss, and (5) weight cycling is associated with numerous adverse health outcomes including increased mortality. Adherence to PA may improve if health care professionals consider PA and CRF as essential vital signs and consistently emphasize to their patients the myriad benefits of PA and CRF in the absence of weight loss.

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Associations of metabolic heterogeneity of obesity with frailty progression: Results from two prospective cohorts

Qiu

Yan

et al. 2022

J cachexia sarcopenia muscle

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Background Previous studies indicated that obesity would accelerate frailty progression. However, obesity is heterogeneous by different metabolic status. The associations of metabolic heterogeneity of obesity with frailty progression remain unclear. Methods A total of 6730 participants from the China Health and Retirement Longitudinal Study (CHARLS) and 4713 from the English Longitudinal Study of Ageing (ELSA) were included at baseline. Metabolic heterogeneity of obesity was evaluated based on four obesity and metabolic phenotypes as metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obesity (MHOO), and metabolically unhealthy overweight/obesity (MUOO). Frailty status was assessed by the frailty index (FI) ranging from 0 to 100 and frailty was defined as FI ≥ 25. Linear mixed-effect models were used to analyse the associations of metabolic heterogeneity of obesity with frailty progression. Results In the CHARLS, MUOO and MUNW presented the accelerated FI progression with additional annual increases of 0.284 (95% CI: 0.155 to 0.413, P < 0.001) and 0.169 (95% CI: 0.035 to 0.303, P = 0.013) as compared with MHNW. MHOO presented no accelerated FI progression (β: -0.011, 95% CI: À0.196 to 0.173, P = 0.904) as compared with MHNW. In the ELSA, the accelerated FI progression was marginally significant for MUOO (β: 0.103, 95% CI: À0.005 to 0.210, P = 0.061) and MUNW (β: 0.157, 95% CI: À0.011 to 0.324, P = 0.066), but not for MHOO (β: -0.047, 95% CI: À0.157 to 0.062, P = 0.396) in comparison with MHNW. The associations of MUOO and MUNW with the accelerated FI progression were stronger after excluding the baseline frail participants in both cohorts. The metabolic status changed over time. When compared with stable MHNW, participants who changed from MHNW to MUNW presented the accelerated FI progression with additional annual increases of 0.356 (95% CI: 0.113 to 0.599, P = 0.004) and 0.255 (95% CI: 0.033 to 0.477, P = 0.024) in the CHARLS and ELSA, respectively. The accelerated FI progression was also found in MHOO participants who transitioned to MUOO (CHARLS, β: 0.358, 95% CI: 0.053 to 0.663, P = 0.022; ELSA, β: 0.210, 95% CI: 0.049 to 0.370, P = 0.011). Conclusions Metabolically unhealthy overweight/obesity and normal weight, but not metabolically healthy overweight/obesity, accelerated frailty progression as compared with metabolically healthy normal weight. Regardless of obesity status, transitions from healthy metabolic status to unhealthy metabolic status accelerated frailty progression as compared with stable metabolically healthy normal weight. Our findings highlight the important role of metabolic status in frailty progression and recommend the stratified management of obesity based on metabolic status.

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The association between metabolically healthy obesity and risk of cancer: A systematic review and meta‐analysis of prospective cohort studies

Cited by 38 publications

References 50 publications

Safety of a Novel Weight Loss Combination Product Containing Orlistat and Acarbose

Safety of a Novel Weight Loss Combination Product Containing Orlistat and Acarbose

Obesity treatment: Weight loss versus increasing fitness and physical activity for reducing health risks

Associations of metabolic heterogeneity of obesity with frailty progression: Results from two prospective cohorts

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