Insulin resistance in hyperthyroidism: the role of IL6 and TNFα

Objective: Although 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 alpha (TNF alpha) are related to the development of insulin resistance in hyperthyroidism of nonautoimmune origin. Design and methods: A 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 TNFa were measured preprandially from the superficial epigastric vein and from the radial artery. Results: i) In HR versus EU: (a) arterial glucose was similar (AUC(0-360) 2087 +/- 57 vs 2010 +/- 43 mM x min), but insulin was increased (AUC(0-360) 17 267 +/- 2447 vs 10 331 +/- 666 mu U/mlXmin, P=0.01), (b) homeostasis model assessment (HOMA) was increased (2.3 +/- 0.4 vs 1 +/- 0.1 kg/m(2), P=0.007), (c) arterial NEFA were increased (AUC(0-360) 136 +/- 18 vs 89 +/- 7mmol/lXmin, P=0.03), (d) arterial IL6 (2 +/- 0.3 vs 0.9 +/- 0.1 pg/ml, P=0.0009) and TNFa (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(beta-coefficient=1.7 +/- 0.7, P=0.049) and (b) although TNF alpha was not producedby the subcutaneous AT, arterial TNFawas positively associatedwithNEFA(AUC0-360; b-coefficientZ0.045G0.01, PZ0.005). Conclusions: Inhyperthyroidism: i) glucose and lipidmetabolismare resistant to insulin, ii) subcutaneousAT releases IL6, which could then act as an endocrine mediator of insulin resistance, iii) although there is no net secretion of TNFa by the subcutaneous AT, increased systemic TNFa levels may be related to the development of insulin resistance in lipolysis.