Insulin resistance in hyperthyroidism: the role of IL6 and TNFα

Abstract

ObjectiveAlthough insulin resistance is a common finding in hyperthyroidism, the implicated mechanisms are obscure. The aim of this study was to investigate whether interleukin 6 (IL6) and tumour necrosis factor α (TNFα) are related to the development of insulin resistance in hyperthyroidism of nonautoimmune origin.Design and methodsA meal was given to ten hyperthyroid (HR) and ten euthyroid (EU) women. Plasma samples were taken for 360 min from the radial artery for measurements of glucose, insulin, and nonesterified fatty acids (NEFA). IL6 and TNFα were measured preprandially from the superficial epigastric vein and from the radial artery.Resultsi) In HR versus EU: (a) arterial glucose was similar (AUC0–3602087±57 vs 2010±43 mM×min), but insulin was increased (AUC0–36017 267±2447 vs 10 331±666 μU/ml×min,P=0.01), (b) homeostasis model assessment (HOMA) was increased (2.3±0.4 vs 1±0.1 kg/m2,P=0.007), (c) arterial NEFA were increased (AUC0–360136±18 vs 89±7 mmol/l×min,P=0.03), (d) arterial IL6 (2±0.3 vs 0.9±0.1 pg/ml,P=0.0009) and TNFα (4.2±0.8 vs 1.5±0.2 pg/ml,P=0.003) were increased, and (e) IL6 production from the subcutaneous adipose tissue (AT) was increased (18±6 vs 5±1 pg/min per 100 ml tissue,P=0.04). ii) (a) Subcutaneous venous IL6 was positively associated with HOMA (β-coefficient=1.7±0.7,P=0.049) and (b) although TNFα was not produced by the subcutaneous AT, arterial TNFα was positively associated with NEFA (AUC0–360;β-coefficient=0.045±0.01,P=0.005).ConclusionsIn hyperthyroidism: i) glucose and lipid metabolism are resistant to insulin, ii) subcutaneous AT releases IL6, which could then act as an endocrine mediator of insulin resistance, iii) although there is no net secretion of TNFα by the subcutaneous AT, increased systemic TNFα levels may be related to the development of insulin resistance in lipolysis.