The thrifty phenotype hypothesis proposes that the epidemiological associations between poor fetal and infant growth and the subsequent development of type 2 diabetes and the metabolic syndrome result from the effects of poor nutrition in early life, which produces permanent changes in glucose-insulin metabolism. These changes include reduced capacity for insulin secretion and insulin resistance which, combined with effects of obesity, ageing and physical inactivity, are the most important factors in determining type 2 diabetes. Since the hypothesis was proposed, many studies world-wide have confirmed the initial epidemiological evidence, although the strength of the relationships has varied from one study to another. The relationship with insulin resistance is clear at all ages studied. Less clear is the relationship with insulin secretion. The relative contribution of genes and environment to these relationships remains a matter of debate. The contributions of maternal hyperglycaemia and the trajectory of postnatal growth need to be clarified.

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The thrifty phenotype hypothesis.

Objective: To identify predictors of postnatal catch-up growth from birth to two years and its relation to size and obesity at five years. Design: Regional prospective cohort study. Setting: Avon longitudinal study of pregnancy and childhood, United Kingdom. Subjects: 848 full term singletons from a 10% random sample of the Avon longitudinal study of pregnancy and childhood. Main outcome measures: Maternal birth weight, prepregnancy weight, pregnancy weight gain, height, smoking, and parity, and paternal height. Weight and length of infants at birth, two years, and five years expressed as standard deviation (SD) scores from the UK reference scores for 1990. Percentage fat mass and total fat mass (estimated from skinfolds) and waist circumference at five years. Results: Size at birth was representative of the national reference. Overall, 30.7% (260 of 848) of infants showed a gain in SD score for weight greater than 0.67 SD scores between zero and two years, indicating clinically significant catch-up growth. These children had lower weight, length, and ponderal index at birth than other children, and were more often from primiparous pregnancies. They also had taller fathers than other children, and their mothers had lower birth weights and were more likely to smoke during pregnancy. Children who showed catch-up growth between zero and two years were heavier, taller, and fatter (body mass index, percentage body fat, and waist circumference) at five years than other children. Conclusions: In this contemporary well nourished cohort, catch-up growth was predicted by factors relating to intrauterine restraint of fetal growth. Children who showed catch-up growth between zero and two years were fatter and had more central fat distribution at five years than other children. Mechanisms that signal and regulate early catch-up growth in the postnatal period may influence associations between small size at birth and risks for disease in adulthood.

https://www.bmj.com/content/bmj/320/7240/967.full.pdf

Association between postnatal catch-up growth and obesity in childhood: prospective cohort study.

Overweight/obesity continues to increase in children and adolescents, and annual obesity-related hospital costs in 6-17 yr olds have reached 127 million dollars per year. Overweight children and adolescents are now being diagnosed with impaired glucose tolerance and type 2 diabetes, and they show early signs of the insulin resistance syndrome and cardiovascular risk. Several risk factors have been identified as contributors to the development of type 2 diabetes and cardiovascular risk in youth. These factors include increased body fat and abdominal fat, insulin resistance, ethnicity (with greater risk in African-American, Hispanic, and Native American children), and onset of puberty. There is no clear explanation of how these factors increase risk, but they appear to act in an additive fashion. We hypothesize that the constellation of these risk factors may be especially problematic during the critical period of adolescent development, especially in individuals who may have compromised beta-cell function and an inability to compensate for severe insulin resistance. Therefore, the purpose of this paper is to review the pathophysiology of type 2 diabetes and cardiovascular risk in obese children and adolescents.

Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents.

Objective: Low birth weight remains a major cause of morbidity and mortality in early infancy and childhood. It is associated with an increased risk of health problems later in life, particularly coronary heart disease and stroke. A meeting was convened to identify the key health issues facing a child born small for gestational age (SGA) and to propose management strategies.

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Management of the Child Born Small for Gestational Age through to Adulthood: A Consensus Statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society

Objective: To explore the underlying mechanisms between organisational downsizing and deterioration of health of employees. 
Design: Longitudinal cohort study. Data were assembled from before downsizing (time 1); during major downsizing affecting some job categories (time 2); and after downsizing (time 3). Contributions of changes in work, support, and health related behaviours between time 1 and time 2 to the relation between downsizing and sickness absence at time 3 were assessed by multilevel modelling. Mean length of follow up was 4.9 years. 
Setting: Raisio, a town in Finland. 
Subjects: 764 municipal employees who remained in employment after downsizing. 
Main outcome measures: Records of absences from work from all causes with medical certificate. 
Results: Downsizing was associated with negative changes in work, impaired support from spouse, and increased prevalence of smoking. Sickness absence rate from all causes was 2.17 (95% confidence interval 1.54 to 3.07) times higher after major downsizing than after minor downsizing. Adjustment for changes in work (for instance, physical demands, job control, and job insecurity) diminished the relation between downsizing and sickness absence by 49%. Adjustments for impaired social support or increased smoking did not alter the relation between downsizing and sickness absence. The findings were unaffected by sex and income. 
Conclusions: The exploration of potential mediating factors provides new information about the possible causal pathways linking organisational downsizing and health. Downsizing results in changes in work, social relationships, and health related behaviours. The observed increase in certificated sickness absence was partially explained by concomitant increases in physical demands and job insecurity and a reduction in job control. A considerable proportion of the increase, however, remained unexplained by the factors measured.

https://www.bmj.com/content/bmj/320/7240/971.full.pdf

Factors underlying the effect of organisational downsizing on health of employees: longitudinal cohort study

A number of studies have shown that glucose tolerance falls with decreasing birth weight and that people with low birth weight and high body mass index (BMI) as adults are those at greatest risk of developing Type II (non-insulin-dependent) diabetes mellitus. No such studies have been carried out in African populations. Therefore we investigated the relation between glucose tolerance and birth weight in a group of 7-year-old black South Africans for whom longitudinal anthropometric data were available. Oral glucose tolerance tests (OGTTs) were carried out on 152 subjects and inverse correlations were found between birth weight and the total amount of insulin secreted during the first 30 min (r = –0.19, p = 0.04) and last 90 min (r = –0.19, p = 0.04) of the oral glucose tolerance test and also between birth weight and the 30 min glucose concentrations (r = –0.20, p = 0.02). Children born with low birth weights but who had high weights at 7 years had higher insulin concentrations and indices of obesity compared with those with low birth weights and low weights at 7 years. There were also positive correlations between weight velocity and BMI (r = 0.24, p = 0.02) and weight velocity and insulin resistance (r = 0.18, p = 0.04) as measured using homeostasis model assessment (HOMA). Thus, low birth weight in conjunction with rapid childhood gains in weight especially as subcutaneous fat, produces poor glucose tolerance in 7-year-old children and can make them susceptible to the development of Type II diabetes later in life. [Diabetologia (1998) 41: 1163–1167]

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Association between poor glucose tolerance and rapid post natal weight gain in seven-year-old children

Aims/hypothesis. This study aimed to assess the effects of fetal and childhood growth on beta-cell activity and insulin sensitivity in 7-year-old children. Methods. Insulin, des-31,32 proinsulin, proinsulin, non-esterified fatty acids and glucose concentrations were measured in oral glucose tolerance tests in 152 South African children for whom longitudinal weight data was available. Results. Children with low weights at birth and 7 years (low–low) had relatively low beta-cell activity whereas children with low birth weight and high weight at 7 years (low–high) had relatively high beta-cell activity. The low–low group had higher 30-min glucose concentrations than children with high birth weights. When each insulin-related peptide was expressed as a percentage of all these peptides the low–low children had the highest percentage of insulin but the lowest of the prohormones. The low–high children had the lowest percentage of insulin but the highest of the prohormones. Non-esterified fatty acid concentrations were lowest and their suppression post-glucose load highest in the low–high group. Conclusion/interpretation. Poor fetal and neonatal growth give rise to low beta-cell numbers compensated for by increased efficiency of proinsulin processing to insulin. Poor fetal followed by higher postnatal growth results in low beta-cell numbers and reduced whole-body glucose uptake which leads to reduced efficiency in the processing of proinsulin. Growth in utero and postnatally therefore have profound effects on beta-cell activity and insulin sensitivity with poor fetal coupled with high postnatal growth being detrimental to these processes but not detrimental to the suppression of lipolysis. [Diabetologia (2000) 43: 978–985]

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Relation between weight gain and beta-cell secretory activity and non-esterified fatty acid production in 7-year-old African children: results from the Birth to Ten study.

Background Infection with SARS-CoV-2 has shown to cause an increase in D-dimers, which correlate with severity and prognosis for in-hospital mortality. The B.1.617.2 (delta) variant is known to cause a raised D-dimer level, with data on D-dimers in the B.1.1.529 (omicron) variant being scarce. Objectives To determine the effect of age, gender and SARS-CoV-2 variant on the D-dimer in South Africans admitted to tertiary medical centres from May 2021 to December 2021. Method The study was performed retrospectively on 16 010 adult patients with a SARS-CoV-2 infection. Age, gender, SARS-CoV-2 PCR and D-dimer levels on admission were collected from two national laboratories. Admissions from 01 May 2021 to 31 October 2021 were classified as B.1.617.2, whereas admissions from 01 November 2021 to 23 December 2021 were classified as B.1.1.529 infections. Results Omicron infections had a median D-dimer level of 0.54 µg/mL (95% CI: 0.32, 1.08, p < 0.001). Multivariable regression analysis showed that infection with omicron had a 34.30% (95% CI: 28.97, 39.23) reduction in D-dimer values, compared with delta infections. Middle aged, aged and aged over 80 years had D-dimer results greater than the adult baseline (42.6%, 95% CI: 38.0, 47.3, 124.6%, 95% CI: 116.0, 133.7 and 216.1%, 95% CI: 199.5, 233.3). Males on average had a 7.1% (95% CI: 4.6, 9.6) lower D-dimer level than females. Conclusion Infection with the B.1.1.529 variant, compared with B.1.617.2 variant, had significantly lower D-dimer levels, with age being a more significant predictor of D-dimer levels, than gender and SARS-CoV-2 variant of infection. Contribution This study provides novel insight into the hypercoagulable impact of various SARS-CoV-2 variants, which can guide the management of patients.

J. Trusler

Papers

Association between poor glucose tolerance and rapid post natal weight gain in seven-year-old children

Relation between weight gain and beta-cell secretory activity and non-esterified fatty acid production in 7-year-old African children: results from the Birth to Ten study.

D-dimers in omicron versus delta: A retrospective analysis