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Insulin resistance (IR), an impaired cellular, tissue and whole body response to insulin, is a major pathophysiological defect of type 2 diabetes mellitus. Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. We examined expression and/or activation of a number of components of the insulin-signalling cascade in skeletal muscle of 22 healthy young men (with body mass index (BMI) range, 20-37 kg/m(2)). Whole body insulin sensitivity (M value) and body composition was determined by the hyperinsulinaemic (40 mU. min(-1).m(-2).), euglycaemic clamp and by dual energy X-ray absorptiometry (DEXA) respectively. Skeletal muscle (vastus lateralis) biopsies were taken before and after one hour of hyperinsulinaemia and the muscle insulin signalling proteins examined by western blot and immunoprecipitation assay. There was a strong inverse relationship between M-value and BMI. The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR.

Adiponectin, a hormone produced and secreted by adipocytes, is present in circulation in high circulating concentrations, suggesting an important physiological role. An indirect regulator of glucose metabolism, adiponectin increases insulin sensitivity, improves glucose tolerance and inhibits inflammation. Plasma adiponectin relates inversely to adiposity and, importantly, reflects the sequelae of accumulation of excess adiposity. The role of adiponectin in adults has been explored in detail. Studies in children are now available and, given the increasing rates of childhood obesity, it is important to establish the role of adiponectin in mediating insulin resistance and cardiovascular disease in this age group. This paper reviews the regulation of adiponectin, its effect on body mass, glucose metabolism and cardiovascular risk in infants, children and adolescents. It demonstrates clear links between adiponectin and features of the metabolic syndrome in obese children and adolescents. However, adiponectin's role as a predictor of metabolic dysfunction in healthy, normal-weight youngsters is less clear.

Background: High birth weight predicts subsequent obesity, but paradoxically, a reduced risk of subsequent cardiovascular disease compared with low birth weight. This apparent paradox might be explained if high birth weight programmed a greater proportion of subsequent lean mass, which carries less cardiovascular risk than fat tissue. Aim: The aim of this study was to test the hypothesis that the direct correlation between birth weight and subsequent body mass index (BMI) represents an association between birth weight and lean tissue, and to assess the metabolic impact of this relationship. Methods: A total of 234 healthy prepubertal children (133 boys, 101 girls, mean age 5.9 yr ± 0.3 standard deviation) were studied. Birth weights were obtained from maternity records. Lean mass was measured by bioelectrical impedance. Anthropometric measures included height, weight (BMI), waist circumference, and subcutaneous fat mass (FM). Insulin resistance was assessed by the homeostasis model method. Metabolic correlates of insulin resistance included total and high-density lipoprotein cholesterol, triglycerides, and sex-hormone-binding globulin. Results: Birth weight correlated significantly with lean mass in boys (r = 0.41, p < 0.001) and girls (r = 0.27, p < 0.01). Adjusting for BMI did not improve the correlation further. After adjustment for FM, lean mass correlated inversely with triglycerides in boys only (r = −0.41, p < 0.01). Birth weight correlated inversely with triglycerides in boys (r = −0.18, p < 0.05); after adjustment for lean mass, this correlation was not significant. Interpretation: In boys, the relationships between birth weight, triglycerides, and lean mass are consistent with the hypothesis. Overall, our findings provide limited evidence in support of the argument that higher birth weight predicts lower metabolic risk because it marks programming of more lean mass. [ABSTRACT FROM AUTHOR]

The article focuses on a study on the relationship between adiposity and insulin resistance in a cohort of prepubertal British students. It reveals that insulin resistance was not significantly associated with high density lipoproteins (HDL) cholesterol and it correlated weakly with adiponectin in boys aged 5 and 6 years. The study concludes that the decline in insulin resistance in children between ages 5 and 7 years is consistent with the lowering of their triglycerides level and rising of HDL cholesterol.

OBJECTIVE. The aim of this study was to evaluate whether adaptive responses made to the uterine or very early infant environment are affecting the current metabolic health of young children in the United Kingdom. METHODS. Participants were 300 healthy children and their parents from the Early-Bird Diabetes Study cohort. Children were recruited from randomly selected schools at 5 years of age. Retrospective measures were maternal prepregnancy weight (n = 230), maternal fasting glucose levels at 28 weeks of pregnancy (n = 27), birth weight, and infant weight at ages 3 and 6 weeks. Prospective measures were insulin resistance, height, weight, and percentage of body fat (sum of 5 skinfold measurements) at ages 5, 6, 7, and 8 years. RESULTS. Maternal third-trimester fasting glucose levels were associated positively with birth weight but were not associated with either weight or insulin resistance for the same children at 8 years. Birth weight was unrelated to insulin resistance at 8 years. There were no relationships between weight change in the first weeks of life and weight, percentage of fat, or insulin resistance at 8 years. Longer breastfeeding correlated inversely, although weakly, with percentage of body fat for boys only. Current weight was correlated with insulin resistance at 8 years. CONCLUSIONS. For these contemporary children, neither the gestational environment nor early postnatal growth predicted insulin resistance, which was best predicted by current weight. There was no evidence that predictive adaptive responses made by the fetus or infant affected the child's weight or insulin resistance later in childhood. [ABSTRACT FROM AUTHOR]