Metformin increases circulating tumour necrosis factor-alpha levels in non-obese non-diabetic patients with coronary heart disease.
Metformin reduces insulin resistance and hyperinsulinaemia, as well as lipid levels and body weight. The mechanisms behind these effects are likely to involve intracellular insulin signalling. Recent evidence implicates tumour necrosis factor-alpha (TNF-alpha) as a modulatory factor on insulin resistance. The present investigation was undertaken to clarify whether metformin affects TNF-alpha and soluble TNF receptor levels. Sixty non-diabetic men with coronary heart disease were treated with diet and lifestyle advice and lovastatin 40 mg/day during a 4-week run-in period. During this period TNF-alpha and soluble TNF receptor p75 remained unchanged, whereas soluble TNF receptor p55 increased by 8% (P < 0.05). Twelve weeks of metformin treatment increased TNF-alpha by 33% (P < 0.05). This effect was restricted to non-obese patients in whom TNF-alpha increased by 68% (P < 0.01). Soluble TNF receptors p55 and p75 remained unchanged in the whole group, whereas soluble TNF receptor p55 increased by 11% (P < 0.05) in non-obese patients. Since metformin reduces insulin resistance both in obese and non-obese subjects but increases TNF-alpha levels only in the latter, it is concluded that the drug does not exert its effect on insulin resistance through regulation of circulating TNF-alpha levels.
Carlsen
S M
SM
Section of Endocrinology, University Hospital of Trondheim, Norway.
Waage
A
A
Grill
V
V
Følling
I
I
D000328:Adult; D003327:Coronary Disease / Q000378:metabolism*; D003920:Diabetes Mellitus; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D009765:Obesity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007004:Hypoglycemic Agents; D014409:Tumor Necrosis Factor-alpha; D008687:Metformin