Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.
Level 3 - non-randomized controlled study
Non-randomized crossover interventional trial in healthy volunteers
PubMed 23904405 · doi:10.1002/dmrr.2441
What was done
Ten healthy young male volunteers (mean age 24 years, mean body mass index 23.7 kg/m²) participated in a four-day crossover interventional protocol. Days 1 and 2 consisted of 6-hour saline infusions, and days 3 and 4 consisted of 6-hour TNF-α infusions. A 4-hour oral glucose tolerance test was performed on days 1 and 3, and a 4-hour intravenous isoglycaemic glucose tolerance test was performed on days 2 and 4, starting 2 hours into the infusions. Plasma concentrations of TNF-α, IL-6, glucose, incretin hormones, cortisol, and serum C-peptide and insulin were measured. Insulin sensitivity was assessed by HOMA-IR and Matsuda index, and prehepatic insulin secretion rates were calculated.
What was found
The abstract reports directional outcomes without quantitative values or effect sizes. TNF-α infusion provoked symptoms of systemic inflammation and increased plasma concentrations of TNF-α, IL-6, cortisol, and HOMA-IR. Incretin hormone secretion and the calculated incretin effect remained unchanged compared to saline control.
Why it matters
The study shows that acute TNF-α-induced inflammation causes insulin resistance without acutely impairing incretin hormone secretion or the incretin effect in healthy humans.
Limits
Sample size is small (n = 10) and restricted entirely to healthy young lean men, limiting generalizability to females, older individuals, or populations with metabolic disease. The crossover design was fixed-sequence (saline first, TNF-α second) rather than randomized. Acute 6-hour cytokine infusion does not reflect the chronic, low-grade inflammatory state typical of type 2 diabetes, and the abstract reports no numerical data or precision estimates.
Cited by
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