Age-Dependent Nongenetic Influences of Birth Weight and Adult Body Fat on Insulin Sensitivity in Twins

Monrad, Rikke Nygaard; Grunnet, Louise Groth; Rasmussen, Eva Lind; Malis, Charlotte; Vaag, Allan; Poulsen, Pernille

doi:10.1210/jc.2008-1858

Cited by 26 publications

(20 citation statements)

References 31 publications

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“…The physiological data from this population have been described in detail [6,22,25,27,29,32,33]. In brief, the old twins had significantly higher BMI, total fat percentage and fasting plasma glucose than the young twins ( Association between IRTK, IRS-1-PI3K and Akt activity IRTK activity was not positively correlated to any downstream kinase in proximal insulin signalling, whereas IRS-1-PI3K activity was associated with Akt2 activity (r= 0.31, p<0.001; Fig.…”

Section: Clinical and Metabolic Characteristicsmentioning

confidence: 95%

Differential aetiology and impact of phosphoinositide 3-kinase (PI3K) and Akt signalling in skeletal muscle on in vivo insulin action

et al. 2010

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Aims/hypothesis Insulin resistance in skeletal muscle is a key factor in the development of type 2 diabetes and although some studies indicate that this could be partly attributed to reduced content and activity of various proximal and distal insulin signalling molecules, consensus is lacking. We therefore aimed to investigate the regulation of proximal insulin signalling in skeletal muscle and its effect on glucose metabolism in a large non-diabetic population.Methods We examined 184 non-diabetic twins with goldstandard techniques including the euglycaemic-hyperinsulinaemic clamp. Insulin signalling was evaluated at three key levels, i.e. the insulin receptor, IRS-1 and V-akt murine thymoma viral oncogene (Akt) levels, employing kinase assays and phospho-specific western blotting. Results Proximal insulin signalling was not associated with obesity, age or sex. However, birthweight was positively associated with IRS-1-associated phosphoinositide 3-kinase (PI3K; IRS-1-PI3K) activity (p=0.04); maximal aerobic capacity ðV Á O 2max Þ, paradoxically, was negatively associated with IRS-1-PI3K (p=0.02) and Akt2 activity (p=0.01). Additionally, we found low heritability estimates for most measures of insulin signalling activity. Glucose disposal was positively associated with Akt-308 phosphorylation (p<0.001) and Akt2 activity (p=0.05), but not with insulin receptor tyrosine kinase or IRS-1-PI3K activity. Conclusions/interpretation With the exception of birthweight, 'classical' modifiers of insulin action, including genetics, age, sex, obesity and V Á O 2max , do not seem to mediate their most central effects on whole-body insulin sensitivity through modulation of proximal insulin signalling in skeletal muscle. We also demonstrated an association between Akt activity and in vivo insulin sensitivity, suggesting a role of Akt in control of in vivo insulin resistance and potentially in type 2 diabetes.

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Section: Clinical and Metabolic Characteristicsmentioning

confidence: 95%

Differential aetiology and impact of phosphoinositide 3-kinase (PI3K) and Akt signalling in skeletal muscle on in vivo insulin action

et al. 2010

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“…These studies demonstrated that the diabetic twin had the lower birthweight (6)(7)(8) . Birth-weight has also been shown to be non-genetically linked with insulin sensitivity and glucose intolerance in elderly subjects (9,10) , perhaps suggesting that the ageing process may be exacerbating the effects of low birth-weight. Studies of individuals exposed to famine while in utero, have also demonstrated very powerful direct evidence for the importance of maternal nutrition in early development.…”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

The impact of early nutrition on the ageing trajectory

Tarry-Adkins

Ozanne

2014

Proc. Nutr. Soc.

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Epidemiological studies, including those in identical twins, and in individuals in utero during periods of famine have provided robust evidence of strong correlations between low birthweight and subsequent risk of disease in later life, including type 2 diabetes (T2D), CVD, and metabolic syndrome. These and studies in animal models have suggested that the early environment, especially early nutrition, plays an important role in mediating these associations. The concept of early life programming is therefore widely accepted; however the molecular mechanisms by which early environmental insults can have long-term effects on a cell and consequently the metabolism of an organism in later life, are relatively unclear. So far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification and microRNA) and permanent changes in cellular ageing. Many of the conditions associated with early-life nutrition are also those which have an age-associated aetiology. Recently, a common molecular mechanism in animal models of developmental programming and epidemiological studies has been development of oxidative stress and macromolecule damage, specifically DNA damage and telomere shortening. These are phenotypes common to accelerated cellular ageing. Thus, this review will encompass epidemiological and animal models of developmental programming with specific emphasis on cellular ageing and how these could lead to potential therapeutic interventions and strategies which could combat the burden of common age-associated disease, such as T2D and CVD.

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“…Second, birth weight was not included in the final modeling. Previous studies suggest that MZ twins are exposed to a more adverse intrauterine environment than are DZ twins, and birth weight has a potential influence on adult adiposity and IS levels (27). However, of 500 participants who reported birth weight in the present study, no birth weight differences (mean 6 SD) were observed between MZ and DZ twins in males (2731 6 689 g compared with 2784 6 636 g) or in females (2658 6 562 g compared with 2678 6 663 g).…”

Section: Study Strengths and Limitationsmentioning

confidence: 99%

Adiposity is inversely related to insulin sensitivity in relatively lean Chinese adolescents: a population-based twin study

Ouyang¹,

Christoffel²,

Brickman³

et al. 2010

The American Journal of Clinical Nutrition

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Age-Dependent Nongenetic Influences of Birth Weight and Adult Body Fat on Insulin Sensitivity in Twins

Cited by 26 publications

References 31 publications

Differential aetiology and impact of phosphoinositide 3-kinase (PI3K) and Akt signalling in skeletal muscle on in vivo insulin action

Differential aetiology and impact of phosphoinositide 3-kinase (PI3K) and Akt signalling in skeletal muscle on in vivo insulin action

The impact of early nutrition on the ageing trajectory

Adiposity is inversely related to insulin sensitivity in relatively lean Chinese adolescents: a population-based twin study

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