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New biomarkers associate with unfavourable metabolic features already in childhood

  • Health and well-being

Higher serum concentrations of biochemical markers IL-1Ra and irisin associate with some cardiometabolic risk factors in 12-year-old children, according to the doctoral dissertation of Satu Seppä, Lic Med.

Cardiometabolic risk consists of several factors including impaired glucose and lipid metabolism, elevated blood pressure, overweight, obesity and low-grade inflammation. Metabolic programming predisposing to cardiometabolic diseases begins prenatally or in early childhood. Intrauterine growth restriction, small birth size and maternal pre-eclampsia have been associated with an increased risk for metabolic and cardiovascular diseases.

Insulin resistance is a common metabolic alteration related to cardiovascular disturbances. In insulin resistant states glucose uptake is reduced in response to physiological insulin levels. Adipose tissue has been proposed to have a role in the pathogenesis of insulin resistance by secreting adipocytokines that affect insulin action. Metabolic stress in the white adipose tissue leads to dysregulated adipocytokine synthesis and secretion, which may contribute to obesity-associated metabolic, inflammatory, and cardiovascular comorbidities. In addition to adipocytokines, also certain cytokines and bioactive peptides derived from muscle, liver and bone have been related to energy homeostasis, glucose metabolism, adipogenesis and low-grade inflammation.

New insulin sensitivity and low-grade inflammation markers have been associated with insulin resistance, type 2 diabetes and cardiovascular diseases in adults. The circulating concentrations of some of these biomarkers have been altered years before the onset of the disease. The aim of Seppä’s doctoral thesis was to evaluate, whether biochemical markers that have recently been linked to insulin sensitivity and low-grade inflammation (IL-1Ra, FGF-21, HMW adiponectin, irisin and osteocalcin) associate with cardiometabolic characteristics in 12-year-old children and whether they could be used in detecting cardiometabolic risk. Furthermore, the influence of low birth weight and exposure to maternal pre-eclampsia on these markers was evaluated.

The cohort of 192 children were studied at Kuopio University Hospital at the age of 12 years. Seventy of them had been born small for gestational age, 78 appropriate for gestational age and 44 from pre-eclamptic pregnancies as appropriate for gestational age.

The results of this thesis demonstrated that higher serum IL-1Ra associated with lower insulin sensitivity, higher concentrations of the inflammation marker high-sensitivity CRP, measures of body weight and a less favourable lipid profile. Serum irisin associated negatively with insulin sensitivity markers independently of body mass index. However, the associations were rather weak. Serum HMW adiponectin was a positive predictor for high-density lipoprotein cholesterol, whereas its associations with insulin sensitivity markers were dependent on body mass index.

The measured biomarkers did not differ with regard to birth weight or exposure to maternal pre-eclampsia.

The doctoral thesis of Satu Seppä, Licentiate of Medicine, entitled Cardiometabolic risk factors in 12-year-old children: the role of insulin sensitivity, low-grade inflammation, birth weight and maternal pre-eclampsia will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Harri Niinikoski of University of Turku, and the Custos will be Professor emeritus Raimo Voutilainen of the University of Eastern Finland. The public examination will be held in Finnish at Kuopio Campus and online on 7 August 2020 starting at 12 noon.

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