Birth size, early growth and adult body composition

Human body composition can be presented at several levels ranging from chemical elements to molecular, cellular and tissue level. A two-compartment model that divides the body into fat and fat-free masses is classically used in studies on physical fitness, nutritional status and obesity. The term lean mass is often used synonymously to fat-free mass.

Estimates of total body fat and lean mass can be assessed by a variety of methods. These include anthropometry, such as measuring the thickness of subcutaneous fat by calipers in multiple regions of the body, underwater weighing which is based on different buoyancy of body fat and lean tissue, scanning of the body by dual energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), computed tomography (CT), and bioelectric impedance analysis which is presented below. All these methods have their strengths and limitations. For example, the most accurate methods, MRI and CT,

are expensive and not easily available, and the latter exposes the subject to a considerable level of X-rays especially in repeated examinations.

The largest constituent of fat-free mass is water. Because only water in the body conducts electrical current, the resistance of an electrical current through the body can be used to estimate total body water and thus fat-free mass. This is called bioimpedance analysis. Early analyzers could not distinguish intracellular water from extracellular water and the measurement was restricted to, for example, the upper body. Technological improvements, such as the use of a spectrum of electrical flows and 4 pairs of electrodes to measure the resistance of each limb and trunk separately, have improved the accuracy of this method (187).

Adult obesity and low birth weight are both risk factors for the metabolic syndrome. Paradoxically, adult obesity is predicted by high birth weight (143;

188-192). However, since obesity has mostly been assessed by BMI which denotes lean mass as well as fat mass, methods that distinguish these components may illuminate this paradox. Another reason to analyze body composition in relation to early growth is the evidence of certain growth patterns as predictors of adult cardiovascular disease and type 2 diabetes or their risk factors (64; 65; 71;

129; 193); effects of early growth on body composition may play a role in the development of these diseases. Insulin resistance, the central component of the metabolic syndrome, is in itself linked to low birth weight or thinness at birth (19; 75; 194-196). This association is amplified in subjects whose small size or thinness at birth were followed by later catch-up growth in BMI, even in the absence of actual overweight or development of obesity (19; 171; 197-201).

Studies on body composition have shown that infants born small for gestational age seem to have reduced lean mass, rather than fat mass, throughout childhood and adulthood (111-117). Since the main component of lean mass, muscle mass, is important for glucose homeostasis regulation, the relative deficiency of lean mass may predispose to insulin resistance.

Fat distribution pattern has been suggested to be programmed during fetal life (202-205). While these results seem to support the fetal origin of the metabolic syndrome, with a large waist circumference as a key feature, many of these studies have assessed abdominal obesity by the waist-hip ratio. The relationship of low birth weight with higher waist-hip ratio has been suggested to represent a reduced hip size rather than abdominal deposition of fat (204). Furthermore, anthropometric measurements do not distinguish subcutaneous and intra-abdominal fat, the latter of which is the metabolically active component.

Studies with an accurate method to measure abdominal fat are rare (206-208). In a twin study utilising magnetic resonance imaging birth weight was inversely

associated with abdominal visceral and subcutaneous fat (207). One study suggests an early interplay between insulin resistance and abdominal fat deposition (208). In that study children born small for gestational age, compared with children born appropriate for gestational age, shifted from insulin sensitivity to insulin resistance between ages 2 and 4 years after largely completed catch-up growth by 2 years of age, and the development of insulin resistance was accompanied by increased gain of fat and deposition of fat more centrally according to a DXA scan despite similar gain in BMI.

Few studies with various methods have assessed the effects of childhood growth on body components in later life. A study in 9 year old boys showed that rapid weight gain in infancy was associated with height or lean mass whereas weight gain between 1 and 4 years of age predicted both lean mass and fatness, and rapid weight gain thereafter only fatness (209). Another study on 4 year old children showed that at age 2 years body composition of children born small for gestational age, despite largely completed catch-up growth, did not differ from that of children born appropriate for gestational age (208). In contrast, between ages 2 and 4 years they gained more fat, specifically abdominal fat, and less lean mass while changes in overall weight, height and BMI were similar. In Guatemalan young adults accelerated increase in height between birth and 2 years of age was related to higher fat percentage (210). Three studies in adults have suggested that high rates of weight or BMI gain in infancy and childhood are associated with an increase in both adult lean mass and adiposity (211-213).

However, in the young Indian adults the gain in BMI up to 8 years of age was more strongly associated with adult lean mass than with adiposity while the strength of the association with adult adiposity increased steeply between 2 and 8 years and was sustained up to 14 years of age (212).

3 AIMS OF THE STUDY

The overall aim was to explore the associations of early growth with components of the adult metabolic syndrome. Another focus was on factors that may underlie or modify these associations: a well-characterized gene polymorphism, physical activity and adult body composition, all of which are known to affect insulin sensitivity.

The specific objectives were:

1. To assess the effects of birth size on blood pressure levels in men and women with and without established hypertension at 65-75 years of age (Study I).

2. To assess whether peroxisome proliferator-activated receptor 2 (PPAR2) gene polymorphism interacts with the relationship between birth size and adult blood pressure level or with the relationship between birth size and the use of any class of antihypertensive medication in hypertensive 65-75 year old men and women (Study II).

3. To examine whether habitual regular exercise has a protective effect against glucose intolerance in 65-75 year old subjects with a recognized risk factor for glucose intolerance, i.e. small body size at birth (Study III).

4. To examine how body size at birth is related to adult body composition at 56-70 years of age, and how this is related to grip strength (Study IV).

5. To examine how change in body mass index throughout childhood is related to adult lean and fat mass at 56-70 years of age (Study V).

4 SUBJECTS AND METHODS