Healthy reference population

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Healthy reference population

Description

A 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].

Abbreviation: HRP

Reference: Body mass excess


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Healthy reference population     Body mass excess         BFE         BME cutoffs         BMI         H         M         VO2max         mitObesity drugs



The HRP database

Work in progress by Gnaiger E 2020-02-10 linked to a preprint in preparation on BME and mitObesity.

Committee on Biological Handbooks (CBH 1962): three allometric phases

Anthropometric studies carried out on adults since the 1960ies are prone to reflect the impact of high-caloric nutrition on allometric relationships, referring us to earlier time points for a HRP. The original studies in the CBH 1962 dataset (N=17523; Zucker 1962) were published between 1931 and 1944 and thus apply to a population (USA) before emergence of the fast-food and soft drink epidemic, and with a lifestyle demanding a balanced physical activity without the impact of local war or economic disaster on starvation. The CBH dataset includes men only, but it is emphasized that "evidence indicates that curves for females (not represented) are identical in slope and position with those of males".
The Committee on Biological Handbooks (1962) distinguishes three allometric phases from newborns to adults, with breaks of standing heights at 0.74 and 1.21 m/x (10 and 22 kg/x; Fig. 1; Fig. 2a and 2b). The corresponding allometric power functions are:
 Eq. 1:  ln M° = ln B + A·ln H
 Eq. 2:  ln H = ln β + α·ln M°
HRP CBH1962-WHO2006 H-BM.png
Figure 1: Allometric relation between height, H [m∙x-1], and body mass, M° [kg∙x-1], in the healthy reference population (HRP) from infancy to old age. The double-logarithmic plot is from the Committee on Biological Handbooks data set, summarizing five large groups of measurements (CBH 1962; Zimmer 1962). In the CBH 1962 data set three allometric phases are separated with breaks at standing heights of 0.74 and 1.2 m/x corresponding to 10 and 22 kg/x. The WHO Child Growth Standards (WHO-CGS) agree with the CBH 1962 data set within 2 % at H>1.26 m/x. Below 1.3 m/x the WHO-CGS body mass for girls and boys are lower than the CBH data, separated into allometric phases with breaks indicated by dotted lines at 1.26, 1.02 and 0.62 m/x. A trend towards overweight is indicated as a gain in body-mass at constant height (red arrows). The red circled cross indicates ‘Reference Man’ (Sender et al 2016). The allometric exponents, A, are given in the form of Eq. 1.
The parameters in Eq. 1 and Eq. 2 are related as
 Eq. 3:  A = 1/α

 Eq. 4:  B = β-1/α
Range of H α β A B
- 0.74 m/x 0.34 0.3360 2.941 24.73
0.74 - 1.21 m/x 0.63 0.1726 1.587 16.26
1.21 - 1.8 m/x 0.35 0.4110 2.857 12.68

WHO Child Growth Standards (WHO-CGS): four allometric phases

The WHO Child Growth Standards are based on large samples with similar numbers of girls and boys in longitudinal (N=1737 children) and cross-sectional studies (N=6669). The studies were conducted between 1997 and 2003 (WHO 2006 Acta Paediatr; WHO 2006 Geneva: World Health Organization; De Onis 2007 Bull World Health Organization). The WHO-CGS on height and body mass of children and adolescents is based on a particularly quality-controlled selection of healthy populations (De Onis 2007 Bull World Health Organization). "The WHO Child Growth Standards depict normal growth under optimal environmental conditions and can be used to assess children everywhere, regardless of ethnicity, socio-economic status and type of feeding" (WHO 2006 Acta Paediatr).
The WHO-CGS data set is characterized by three allometric phases in childhood to early adolescence (up to height 1.26 m/x), and a final phase which agrees closely with the CBH 1962 data set (Fig. 2).
BfH CBH-WHOCGS.png
Figure 2: Body mass as a function of height up to 1.4 m/x in the data sets of the Committee on Biological Handbooks (CBH 1962; based on publications between 1931 and 1944) and WHO Child Growth Standards (WHO-CGS; based on surveys between 1997 and 2003). a: Girls and boys of the WHO-CGS data set agree closely with the boys from the CBH data set, but show a trend towards lower body mass for height, despite of the later date of the surveys. b: The data of girls and boys are averaged at any given height and fitted by a power function which reveals four phases with breaks at 0.62 m/x (17.0 kg/x), 1.02 m/x (15.6 kg/x), and 1.26 m/x (24.6 kg/x). c: The relative deviation of the body mass, M, from the fitted line, M°, is the body mass excess, BME = (M-M°)/M°. The full lines show the deviation from the fitted line for girls and boys, and the dashed line shows the deviation of the average for girls and boys.
The WHO-CGS data suggest a lower reference body mass for height in the range of 0.7 to 1.1 m/x of children compared to the CBH 1962 data set (USA 1931-1944), even though the WGH-CGS surveys were carried out later (1997-2003), when the general trend towards overweight was already in full swing in the USA (NCD-RisC 2017 Lancet). This reflects the fact that the general trend of the average population towards overweight differs from a population selected as a healthy standard. The negative deviation of the CBH 1962 data set up to 0.7 m/x (Fig. 2c) illustrates 'how children should grow when not only free of disease but also when reared following healthy practices such as breastfeeding and a nonsmoking environment' (WHO 2006 Acta Paediatr).
HRP M-H.png
Figure 3: Four phases of the allometric relationship between body mass, M°, and height, H, in the healthy reference population (HRP), and shift of M at body mass excess, BME, indicating underweight (BME = -0.2 and -0.1) or overweight (BME = 0.2) and increasing degrees of obesity (BME = 0.4 to 1.0).
The WHO-CGS and CBH 1962 data sets agree within 2 % in the region of overlap at heights of 1.27 to 1.38 m/x, in which phase the parameters of the WHO-CGS data set are A = 2.597 and B = 13.56 (Fig. 2b; green line). Therefore, these data sets were combined, using the allometric parameters calculated from the WHO-CGS data for girls and boys combined at heights <1.26 m/x, and the CBH 1962 parameters at heights >1.26 m/x. Thus a baseline is established of the healthy reference population with four allometric phases (Fig. 3):
Range of H α β A B
0.45 - 0.62 m/x 0.3240 0.3373 3.086 28.60
0.63 - 1.02 m/x 0.5869 0.2034 1.704 15.08
1.03 - 1.26 m/x 0.4591 0.2894 2.178 14.89
1.27 m/x - 0.35 0.4110 2.857 12.68


Body mass excess (BME) and body mass index (BMI)

At any given height, the personal body mass may deviate from the reference body mass, M°, in the HRP for the same height. This difference is the excess body mass, ME = M-M°. When normalized for M°, we obtain the simple definition of the body mass excess, BME = ME/M°. By this definition, the BME equals zero in the HRP at all heights. For comparison, it is instructive to calculate the BMI as a function of height in the HRP, defining this as the BMI° or precision-BMI at BME=0. The normal BMI of 20 kg·m-2 is obtained in the HRP at H=1.7 m/x and M°=57.7 kg/x. If this normal BMI would represent a general index independent of height, it should be constant for the HRP, which is clearly not the case, neither for adults nor children (Fig. 4).
HRP-BMI.png
Figure 4: Precision-BMI of the HRP, BMI°, with the BMI°=20 kg·m-2 at the height of 1.70 m/x in the healthy reference population (dashed lines). The circle marks the harmonization point between the BMI of 20 kg·m-2 (normal) and the precision-BMI°. For persons smaller than 1.7 m/x, the BMI° is below 20 kg·m-2, such that a BMI of 17.9 instead of 20 kg·m-2 is the precision reference at a height of 1.5 m/x. On the other hand, at a height of 1.9 m/x a BMI of 22 instead of 20 kg·m-2 is the precision reference (dotted lines).
The concept of body mass excess, BME, is simple and easy to communicate to the general public. In contrast, neither the BMI nor the concept of a precision-BMI can be explained easily. With the BMI firmly established by convention in the WHO, however, it is important to harmonize the concepts of BME and BMI. Fig. 4 provides the first step for harmonization by assigning to the height of 'reference man' (Sender 2016 PLOS Biol) the BMI of 20 kg·m-2 as BMI°. BME cutoff points for overweight and obese are then obtained for BMI cutoffs of 25 and 30 kg·m-2 at heights of 1.79 and 1.85 m/x, respectively.
» Further details: BME cutoff points).
Figure 5: Growth curves and allometry of body mass and height in girls and boys from 5 to 19 years (WHO 2006). (a) and (b): Height and body mass as a function of age. The curves are very similar up to 13 years. (c) and (d) Body mass and precision-body mass index, BMI°, as a function of height. Three allometric phases are indicated by the shaded areas. The BMI does not yield an index that is independent of height.
Fig. 5 is based on the WHO Child Growth Standards (De Onis 2007 Bull World Health Organization). It illustrates the limitation of the BMI as an index of overweight and obesity. The precision body mass index, BMI°, is claculated for the healthy reference population (HRP), in which neither underweight nor overweight prevails and which, therefore, should be characterized by a constant index. This is achieved by the body mass excess, BME, which relates the actual body mass, M, to the reference body mass, M°, at a given height, BME=(M-M°)/M°. The BME is constant at 0.0 for the HRP for both sexes independent of height. In contrast, the increase of the precision BMI° from 15 to 21 kg·m-2 from 1.0 to 1.8 m/x represents a confounding factor which explains the necessity of adjusting the BMI cutoff points. Instead of a focus on adjusted BMI cutoff points (De Onis 2019 Public Health Nutrition), overweight and obesity should assessed in terms of the BME and BME cutoff points.




References: HRP

 Reference
De Onis 2007 Bull World Health Organizationde Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J (2007) Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organization 85:660-7.
WHO 2006 Acta PaediatrWHO Multicentre Growth Reference Study Group (2006) WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl 450:76-85.
WHO 2006 Geneva: World Health OrganizationWHO Multicentre Growth Reference Study Group (2006) WHO child growth standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: Methods and development. Geneva: World Health Organization 312 pp.
Zucker 1962 Committee on Biological Handbooks, Fed Amer Soc Exp BiolZucker TF (1962) Regression of standing and sitting weights on body weight: man. In: Growth including reproduction and morphological development. Altman PL, Dittmer DS, eds: Committee on Biological Handbooks, Fed Amer Soc Exp Biol:336-7.
References in Zucker (1962)
  1. Bayley N, Davis FC (1935) Growth changes in bodily size and proportions during the first three years. Biometrika 27:26-87.
  2. Gray H, Ayres JG (1931) Growth in private school children. Behavior Res Fund Monog, Univ Chicago Press, Chicago:282 pp. – With averages and variabilities based on 3110 measurings on boys and 1473 on girls from the ages of one to nineteen years.
  3. Meredith HV (1935) Univ Iowa studies in child welfare 11(3).
  4. Peatman JG, Higgons RA (1938) Growth norms from birth to the age of five years: a study of children reared with optimal pediatric and home care. Am J Diseases Children 55:1233-1247.
  5. Simmons KW (1944) Monographs Soc Research in Child Develop 9(1).


Publications: BME and height

» Height of humans
 Reference
Bosy-Westphal 2009 Br J NutrBosy-Westphal A, Plachta-Danielzik S, Dörhöfer RP, Müller MJ (2009) Short stature and obesity: positive association in adults but inverse association in children and adolescents. Br J Nutr 102:453-61.
De Onis 2007 Bull World Health Organizationde Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J (2007) Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organization 85:660-7.
Gnaiger 2019 MiP2019
Erich Gnaiger
OXPHOS capacity in human muscle tissue and body mass excess – the MitoEAGLE mission towards an integrative database (Version 6; 2020-01-12).
Hood 2019 Nutr DiabetesHood K, Ashcraft J, Watts K, Hong S, Choi W, Heymsfield SB, Gautam RK, Thomas D (2019) Allometric scaling of weight to height and resulting body mass index thresholds in two Asian populations. Nutr Diabetes 9:2. doi: 10.1038/s41387-018-0068-3.
Indian Academy of Pediatrics Growth Charts Committee 2015 Indian PediatrIndian Academy of Pediatrics Growth Charts Committee, Khadilkar V, Yadav S, Agrawal KK, Tamboli S, Banerjee M, Cherian A, Goyal JP, Khadilkar A, Kumaravel V, Mohan V, Narayanappa D, Ray I, Yewale V (2015) Revised IAP growth charts for height, weight and body mass index for 5- to 18-year-old Indian children. Indian Pediatr 52:47-55.
Zucker 1962 Committee on Biological Handbooks, Fed Amer Soc Exp BiolZucker TF (1962) Regression of standing and sitting weights on body weight: man. In: Growth including reproduction and morphological development. Altman PL, Dittmer DS, eds: Committee on Biological Handbooks, Fed Amer Soc Exp Biol:336-7.

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.
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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