Insulin resistance in hyperthyroidism: the role of IL6 and TNFα

Abstract

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 a (TNFa) 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 HRversus EU: (a) arterial glucose was similar (AUC 0-360 2087G57 vs 2010G43 mM!min), but insulin was increased (AUC 0-360 17 267G2447 vs 10 331G666 mU/ml!min, PZ0.01), (b) homeostasis model assessment (HOMA) was increased (2.3G0.4 vs 1G0.1 kg/m 2 , PZ0.007), (c) arterial NEFA were increased (AUC 0-360 136G18 vs 89G7 mmol/l!min, PZ0.03), (d) arterial IL6 (2G0.3 vs 0.9G0.1 pg/ml, PZ0.0009) and TNFa (4.2G0.8 vs 1.5G0.2 pg/ml, PZ0.003) were increased, and (e) IL6 production from the subcutaneous adipose tissue (AT) was increased (18G6 vs 5G1 pg/min per 100 ml tissue, PZ0.04). ii) (a) Subcutaneous venous IL6 was positively associated with HOMA (b-coefficientZ1.7G0.7, PZ0.049) and (b) although TNFa was not produced by the subcutaneous AT, arterial TNFa was positively associated with NEFA (AUC 0-360 ; b-coefficientZ0.045G0.01, PZ0.005). Conclusions: In 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 TNFa by the subcutaneous AT, increased systemic TNFa levels may be related to the development of insulin resistance in lipolysis.

Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism

“…However, we have recently shown that glucose uptake in muscle in HR is indeed resistant to insulin, but this defect is masked by a marked increase in blood flow (4); this could be attributed to the dramatic decrease in intracellular pathways of insulin-stimulated glucose metabolism (such as glycogen synthesis) (25,26). In addition, tumor necrosis factor a and interleukin 6 may contribute to insulin resistance in the metabolism of both lipids and glucose in HR (27). These findings support the results of the present study: in HR patients, glucose uptake in monocytes in the presence of insulin was significantly decreased compared to euthyroid subjects; the SHR group showed an intermediate response suggesting that SHR is an intermediate metabolic condition between EU and HR (which is further supported by the intermediate levels of the thyroid hormones in our SHR group).…”

Insulinooporność a choroby tarczycy

“…Alternatively, peripheral insulin resistance in hyperthyroidism may be explained by the increased secretion of bioactive mediators (adiponectins), such as interleukin-6 and TNF-alpha, by adipocytes. Higher levels of these adiponectins have been observed in women with hyperthyroidism [18].…”

Interleukin-18 induces insulin resistance in the hyperthyroid state

“…**P < 0.01 however, this finding remains controversial [27]. It is widely reported that IL-6 and tumor necrosis factor alfa (TNFα) are related to the development of insulin resistance in hyperthyroidism [28]. The roles of these 2 cytokines are important in the pathogenesis of insulin resistance.…”