Insulin resistance in hyperthyroidism: the role of IL6 and TNF alpha.
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 (TNFalpha) are related to the development of insulin resistance in hyperthyroidism of nonautoimmune origin.


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 TNFalpha 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 microU/ml x min, 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+/-7 mmol/lxmin, P=0.03), (d) arterial IL6 (2+/-0.3 vs 0.9+/-0.1 pg/ml, P=0.0009) and TNFalpha (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 TNFalpha was not produced by the subcutaneous AT, arterial TNFalpha was positively associated with NEFA (AUC(0-360); beta-coefficient=0.045+/-0.01, P=0.005).


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 TNFalpha by the subcutaneous AT, increased systemic TNFalpha levels may be related to the development of insulin resistance in lipolysis.
Mitrou
Panayota
P
Hellenic National Center for Research, Prevention and Treatment of Diabetes Mellitus and its Complications (HNDC), Athens, Greece.
Boutati
Eleni
E
Lambadiari
Vaia
V
Tsegka
Aikaterini
A
Raptis
Athanasios E
AE
Tountas
Nikolaos
N
Economopoulos
Theofanis
T
Raptis
Sotirios A
SA
Dimitriadis
George
G
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood* / Q000175:diagnosis; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
D015415:Biomarkers; D001786:Blood Glucose; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha