Comorbidity

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Comorbidity

Description

Comorbidities are common in obesogenic lifestyle-induced early aging. These are preventable, non-communicable diseases with strong associations to obesity. In many studies, cause and effect in the sequence of onset of comorbidities remain elusive. Chronic degenerative diseases are commonly obesity-induced. The search for the link between obesity and the etiology of diverse preventable diseases lead to the hypothesis, that mitochondrial dysfunction is the common mechanism, summarized in the term 'mitObesity'.


Reference: Body mass excess and mitObesity


MitoFit-to-aging.jpg
Healthy reference population     Body mass excess         BFE         BME cutoffs         BMI         H         M         VO2max         mitObesity drugs



MitObesity-and-comorbidities.jpg

Comorbidities in obesity: is mitochondrial dysfunction the link?

Work in progress by Gnaiger E 2020-02-15 linked to a preprint in preparation on BME and mitObesity.  







References: BME and Comorbidity

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 YearReferenceOrganismTissue;cell
Wang 2020 J Mol Med (Berl)2020Wang SY, Zhu Siyu, Wu Jian, Zhang Maomao, Xu Yousheng, Xu Wei, Cui Jinjin, Yu Bo, Cao Wei, Liu Jingjin (2020) Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy. J Mol Med (Berl) 98:245-61.MouseHeart
Cox 2020 JAMA Netw Open2020Cox Bianca, Luyten Leen J, Dockx Yinthe, Provost Eline, Madhloum Narjes, De Boever Patrick, Neven Kristof Y, Sassi Franco, Sleurs Hanne, Vrijens Karen, Vineis Paolo, Plusquin Michelle, Nawrot Tim S (2020) Association between maternal prepregnancy body mass index and anthropometric parameters, blood pressure, and retinal microvasculature in children age 4 to 6 years. JAMA Netw Open 3:e204662Human
Pena 2020 Int J Chronic Dis2020Pena GS, Paez HG, Johnson TK, Halle JL, Carzoli JP, Visavadiya NP, Zourdos MC, Whitehurst MA, Khamoui AV (2020) Hippocampal growth factor and myokine cathepsin B expression following aerobic and resistance training in 3xTg-AD mice. Int J Chronic Dis 2020:Article ID 5919501.MouseNervous system
Corlin 2020 JAMA Cardiol2020Corlin Laura, Short Meghan I, Vasan Ramachandran S, Xanthakis Vanessa (2020) Association of the duration of ideal cardiovascular health through adulthood with cardiometabolic outcomes and mortality in the Framingham offspring study. JAMA Cardiol Published online March 11, 2020.Human
Stefan 2020 Nat Rev Endocrinol2020Stefan N, Birkenfeld AL, Schulze MB, Ludwig DS (2020) Obesity and impaired metabolic health in patients with COVID-19. Nat Rev Endocrinol 2020:1‐2 [published online ahead of print, 2020 Apr 23].Human
Bahrami 2020 JAMA Psychiatry2020Bahrami S, Steen NE, Shadrin A, O'Connell K, Frei O, Bettella F, Wirgenes KV, Krull F, Fan CC, Dale AM, Smeland OB, Djurovic S, Andreassen OA (2020) Shared genetic loci between body mass index and major psychiatric disorders: a genome-wide association study. JAMA Psychiatry 2020 Jan 8. doi: 10.1001/jamapsychiatry.2019.4188.Human
Qingxian 2020 Lancet2020Qingxian Cai, Chen Fengjuan, Fang Luo, Xiaohui Liu, Tao Wang, Qikai Wu, Qing He, Zhaoqin Wang, Yingxia Liu, Jun Chen, Lei Liu, Lin Xu (2020) Obesity and COVID-19 severity in a designated hospital in Shenzhen, China. Lancet Preprint at SSRN https://doi.org/10.2139/ssrn.3556658.Human
Bhatraju 2020 N Engl J Med2020Bhatraju Pavan K, Ghassemieh Bijan J, Nichols Michelle, Kim Richard, Jerome Keith R, Nalla Arun K, Greninger Alexander L, Pipavath Sudhakar, Wurfel Mark M, Evans Laura, Kritek Patricia A, West T Eoin, Luks Andrew, Gerbino Anthony, Dale Chris R, Goldman Jason D, O’Mahony Shane, Mikacenic Carmen (2020) Covid-19 in critically ill patients in the Seattle region - case series. N Engl J Med 2020;NEJMoa2004500 [published online ahead of print, 2020 Mar 30].Human
Meng 2020 JAMA Netw Open2020Meng R, Yu C, Liu N, He M, Lv J, Guo Y, Bian Z, Yang L, Chen Y, Zhang X, Chen Z, Wu T, Pan A, Li L, China Kadoorie Biobank Collaborative Group (2020) Association of depression with all-cause and cardiovascular disease mortality among adults in China. JAMA Netw Open 3:e1921043.Human
Petrilli 2020 medRxiv2020Petrilli Christopher M, Jones Simon A, Yang Jie, Rajagopalan Harish, O'Donnell Luke F, Chernyak Yelena, Tobin Katie, Cerfolio Robert J, Francois Fritz, Horwitz Leora I (2020) Factors associated with hospitalization and critical illness among 4,103 patients with COVID-19 disease in New York City. medRxiv doi: https://doi.org/10.1101/2020.04.08.20057794 .Human
Fumagalli 2019 JAMA Cardiol2019Fumagalli C, Maurizi N, Day SM, Ashley EA, Michels M, Colan SD, Jacoby D, Marchionni N, Vincent-Tompkins J, Ho CY, Olivotto I, SHARE Investigators (2019) Association of obesity with adverse long-term outcomes in hypertrophic cardiomyopathy. JAMA Cardiol 2019 Nov 6:1-8. doi: 10.1001/jamacardio.2019.4268.Human
Kenny 2019 Circ Res2019Kenny HC, Abel ED (2019) Heart failure in Type 2 Diabetes Mellitus. Circ Res 124:121–41.HumanHeart
Gabandé-Rodríguez 2019 Cells2019Gabandé-Rodríguez E, M Gómez de Las Heras M, Mittelbrunn M (2019) Control of inflammation by calorie restriction mimetics: on the crossroad of autophagy and mitochondria. Cells 2019;9:E82.
Bialas 2018 Int J Chron Obstruct Pulmon Dis2018Białas AJ, Siewiera K, Watała C, Rybicka A, Grobelski B, Kośmider L, Kurek J, Miłkowska-Dymanowska J, Piotrowski WJ, Górski P (2018) Mitochondrial functioning abnormalities observed in blood platelets of chronic smoke-exposed guinea pigs – a pilot study. Int J Chron Obstruct Pulmon Dis 13:3707—17 .Guinea pigPlatelet
Collins 2018 Front Physiol2018Collins Kelsey H, Herzog Walter, MacDonald Graham Z, Reimer Raylene A, Rios Jaqueline L, Smith Ian C, Zernicke Ronald F, Hart David A (2018) Obesity, metabolic syndrome, and musculoskeletal disease: common inflammatory pathways suggest a central role for loss of muscle integrity. Front Physiol 9:112.HumanSkeletal muscle
Gutierrez-Sacristan 2018 Bioinformatics2018Gutiérrez-Sacristán A, Bravo À, Giannoula A, Mayer MA, Sanz F, Furlong LI (2018) comoRbidity: an R package for the systematic analysis of disease comorbidities. Bioinformatics 34:3228–3230.Human
Jia 2018 Circ Res2018Jia G, Hill MA, Sowers JR (2018) Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ Res 122:624–38.HumanHeart
Madeo 2018 Science2018Madeo F, Eisenberg T, Pietrocola F, Kroemer G (2018) Spermidine in health and disease. Science 359:eaan2788.Human
Abdurrachim 2017 Cardiovasc Res2017Abdurrachim D, Nabben M, Hoerr V, Kuhlmann MT, Bovenkamp P, Ciapaite J, Geraets IME, Coumans W, Luiken JJFP, Glatz JFC, Schäfers M, Nicolay K, Faber C, Hermann S, Prompers JJ (2017) Diabetic db/db mice do not develop heart failure upon pressure overload: a longitudinal in vivo PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations. Cardiovasc Res 113:1148-60.MouseHeart
Bowen 2017 J Am Heart Assoc2017Bowen TS, Brauer D, Rolim NPL, Bækkerud FH, Kricke A, Ormbostad Berre AM, Fischer T, Linke A, da Silva GJ, Wisloff U, Adams V (2017) Exercise training reveals inflexibility of the diaphragm in an animal model of patients with obesity-driven heart failure with a preserved ejection fraction. J Am Heart Assoc 6. pii: e006416.RatSkeletal muscle
Apovian 2016 Am J Manag Care2016Apovian CM (2016) Obesity: definition, comorbidities, causes, and burden. Am J Manag Care 22(7 Suppl):s176–85.Human
Pedersen 2015 Scand J Med Sci Sports2015Pedersen BK, Saltin B (2015) Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports 25:1-72.Human
Karabatsiakis 2014 Transl Psychiatry2014Karabatsiakis A, Boeck C, Salinas-Manrique J, Kolassa S, Calzia E, Dietrich DE, Kolassa IT (2014) Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression. Transl Psychiatry 4:e397.HumanBlood cells
Croston 2014 Am J Physiol Heart Circ Physiol2014Croston TL, Thapa D, Holden AA, Tveter KJ, Lewis SE, Shepherd DL, Nichols CE, Long DM, Olfert IM, Jagannathan R, Hollander JM (2014) Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart. Am J Physiol Heart Circ Physiol 307:H54-65.HumanHeart
Broskey 2014 J Clin Endocrinol Metab2014Broskey NT, Greggio C, Boss A, Boutant M, Dwyer A, Schlueter L, Hans D, Gremion G, Kreis R, Boesch C, Canto AC, Amati F (2014) Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training. J Clin Endocrinol Metab 99:1852-61.HumanSkeletal muscle
Hernandez-Aguilera 2013 Mediators Inflamm2013Hernández-Aguilera A, Rull A, Rodríguez-Gallego E, Riera-Borrull M, Luciano-Mateo F, Camps J, Menéndez JA, Joven J (2013) Mitochondrial dysfunction: a basic mechanism in inflammation-related non-communicable diseases and therapeutic opportunities. Mediators Inflamm 2013:135698.HumanFat
Sivertsson 2013 Adv Exp Med Biol2013Sivertsson E, Friederich-Persson M (2013) Inhibition of mammalian target of rapamycin induces renal mitochondrial uncoupling in rats. Adv Exp Med Biol 789:309-14.RatKidney
Thomas 2012 Nutr Res Rev2012Thomas EL, Frost G, Taylor-Robinson SD, Bell JD (2012) Excess body fat in obese and normal-weight subjects. Nutr Res Rev 25:150–61.HumanFat
Misra 2011 Int J Obes (Lond)2011Misra A, Khurana L (2011) Obesity-related non-communicable diseases: South Asians vs White Caucasians. Int J Obes (Lond) 35:167–87.HumanFat
Misra 2009 J Assoc Physicians India2009Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D, Joshi Shashank R, Sadikot S, Gupta R, Gulati Seema, Munjal YP, Concensus Group (2009) Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India 57:163–70.HumanFat
Guralnik 1995 N Engl J Med1995Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB (1995) Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med 332:556–561.HumanSkeletal muscle
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MitoPedia: BME and mitObesity

» Body mass excess and mitObesity | BME and mitObesity news | Summary |

TermAbbreviationDescription
BME cutoff pointsBME cutoffObesity is defined as a disease associated with an excess of body fat with respect to a healthy reference condition. Cutoff points for body mass excess, BME cutoff points, define the critical values for underweight (-0.1 and -0.2), overweight (0.2), and various degrees of obesity (0.4, 0.6, 0.8, and above). BME cutoffs are calibrated by crossover-points of BME with established BMI cutoffs.
Body fat excessBFEIn the healthy reference population (HRP), there is zero body fat excess, BFE, and the fraction of excess body fat in the HRP is expressed - by definition - relative to the reference body mass, M°, at any given height. Importantly, body fat excess, BFE, and body mass excess, BME, are linearly related, which is not the case for the body mass index, BMI.
Body massm [kg]; M [kg·x-1]The body mass, M, is the mass (kilogram [kg]) of an individual (object) [x] and is expressed in units [kg/x]. Whereas the body weight changes as a function of gravitational force (you are weightless at zero gravity; your floating weight in water is different from your weight in air), your mass is independent of gravitational force, and it is the same in air and water.
Body mass excessBMEThe body mass excess, BME, is an index of obesity and as such BME is a lifestyle metric. The BME is a measure of the extent to which your actual body mass, M [kg/x], deviates from M° [kg/x], which is the reference body mass [kg] per individual [x] without excess body fat in the healthy reference population, HRP. A balanced BME is BME° = 0.0 with a band width of -0.1 towards underweight and +0.2 towards overweight. The BME is linearly related to the body fat excess.
Body mass indexBMIThe body mass index, BMI, is the ratio of body mass to height squared (BMI=M·H-2), recommended by the WHO as a general indicator of underweight (BMI<18.5 kg·m-2), overweight (BMI>25 kg·m-2) and obesity (BMI>30 kg·m-2). Keys et al (1972; see 2014) emphasized that 'the prime criterion must be the relative independence of the index from height'. It is exactly the dependence of the BMI on height - from children to adults, women to men, Caucasians to Asians -, which requires adjustments of BMI-cutoff points. This deficiency is resolved by the body mass excess relative to the healthy reference population.
ComorbidityComorbidities are common in obesogenic lifestyle-induced early aging. These are preventable, non-communicable diseases with strong associations to obesity. In many studies, cause and effect in the sequence of onset of comorbidities remain elusive. Chronic degenerative diseases are commonly obesity-induced. The search for the link between obesity and the etiology of diverse preventable diseases lead to the hypothesis, that mitochondrial dysfunction is the common mechanism, summarized in the term 'mitObesity'.
Healthy reference populationHRPA healthy reference population, HRP, establishes the baseline for the relation between body mass and height in healthy people of zero underweight or overweight, providing a reference for evaluation of deviations towards underweight or overweight and obesity. The WHO Child Growth Standards (WHO-CGS) on height and body mass refer to healthy girls and boys from Brazil, Ghana, India, Norway, Oman and the USA. The Committee on Biological Handbooks compiled data on height and body mass of healthy males from infancy to old age (USA), published before emergence of the fast-food and soft-drink epidemic. Four allometric phases are distinguished with distinct allometric exponents. At heights above 1.26 m/x the allometric exponent is 2.9, equal in women and men, and significantly different from the exponent of 2.0 implicated in the body mass index, BMI [kg/m2].
Height of humansh [m]; H [m·x-1]The height of humans, h, is given in SI units in meters [m]. Humans are countable objects, and the symbol and unit of the number of objects is N [x]. The average height of N objects is, H = h/N [m/x], where h is the heights of all N objects measured on top of each other. Therefore, the height per human has the unit [m·x-1] (compare body mass [kg·x-1]). Without further identifyer, H is considered as the standing height of a human, measured without shoes, hair ornaments and heavy outer garments.
Lengthl [m]Length l is an SI base quantity with SI base unit meter m. Quantities derived from length are area A [m2] and volume V [m3]. Length is an extensive quantity, increasing additively with the number of objects. The term 'height' h is used for length in cases of vertical position (see height of humans). Length of height per object, LUX [m·x-1] is length per unit-entity UX, in contrast to lentgth of a system, which may contain one or many entities, such as the length of a pipeline assembled from a number NX of individual pipes. Length is a quantity linked to direct sensory, practical experience, as reflected in terms related to length: long/short (height: tall/small). Terms such as 'long/short distance' are then used by analogy in the context of the more abstract quantity time (long/short duration).
MitObesity drugsBioactive mitObesity compounds are drugs and nutraceuticals with more or less reproducible beneficial effects in the treatment of diverse preventable degenerative diseases implicated in comorbidities linked to obesity, characterized by common mechanisms of action targeting mitochondria.
ObesityObesity is a disease resulting from excessive accumulation of body fat. In common obesity (non-syndromic obesity) excessive body fat is due to an obesogenic lifestyle with lack of physical exercise ('couch') and caloric surplus of food consumption ('potato'), causing several comorbidities which are characterized as preventable non-communicable diseases. Persistent body fat excess associated with deficits of physical activity induces a weight-lifting effect on increasing muscle mass with decreasing mitochondrial capacity. Body fat excess, therefore, correlates with body mass excess up to a critical stage of obesogenic lifestyle-induced sarcopenia, when loss of muscle mass results in further deterioration of physical performance particularly at older age.
VO2maxVO2max; VO2max/MMaximum oxygen consumption, VO2max, is and index of cardiorespiratory fitness, measured by spiroergometry on human and animal organisms capable of controlled physical exercise performance on a treadmill or cycle ergometer. VO2max is the maximum respiration of an organism, expressed as the volume of O2 at STPD consumed per unit of time per individual object [mL.min-1.x-1]. If normalized per body mass of the individual object, M [kg.x-1], mass specific maximum oxygen consumption, VO2max/M, is expressed in units [mL.min-1.kg-1].


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