Proinflammatory cytokines and serum lipids in patients with diabetes mellitus 2
Constantinos Tzioras, Adromaxi Brionidou, Nikos Klonaris & Alexandros Bantila
Introduction: Recently, several cytokines attracted considerable attention as potential effectors of insulin resistance and endothelium dysfunction, both associated with type 2 diabetes mellitus (T2DM) pathophysiology.
Serum lipids disturbances also observed in inflammation and immunologic disorders have been found to largely depend on proinflammatory cytokines release.
Aim: To establish the presence of cytokines levels disturbances in patients with diabetes mellitus 2 and investigate their correlation with serum lipids.
Patients and methods: Forty patients with T2DM (20 women and 20 men, mean age 67.2±1.65 years) and 35 control subjects matched for age, gender and BMI were studied.
Among diabetic patients, 31 were treated with antidiabetics and diet and 9 of them were on diet alone and disease duration was <3 years.
Plasma triglycerides, total and HDL-cholesterol were assayed by an enzymatic, colorimetric method in an autoanalyzer (Roche Laboratory Systems) and LDL-cholesterol was calculated according to the Friedewald formula.
Serum cytokines levels were measured by an immunoenzymatic method with commercial kits obtained from R&D for the assay of TNF-α and from Endogen for the assay of IL-1β, IL-2 and INF-γ.
Statistical analysis was perfomed by using MannWhitney test for comparisons between groups and Pearsons coefficient for correlations.
Results: Diabetic patients had significantly increased levels of proinflammatory cytokines compared to controls (IL-2 124.8±3.9 vs 74±3.6 pg/ml, IL-β 56.1±1.0 vs 34.2±1.8 pg/ml, TNF-α 43.9±1.0 vs 24.8±1.7 pg/ml, INF-γ 84.2±1.0 vs 51.2±2.5 pg/ml, all with P<0.001).
A strong positive correlation was found between IL-2 with total cholesterol and triglycerides levels (r=0.45, P<0.012 and r=0.37, P<0.03 respectively) as well as INF-γ with triglycerides levels (r=0.35, P<0.04). No correlation was found between other cytokines and lipid levels.
Conclusions: Increased levels of proinflammatory cytokines IL-2, IL-β, TNF-α, INF-γ in T2DM patients indicate that the pathophysiological mechanisms leading to insulin resistance and β-cell damage, include an activation of the inflammation cascade. Whether, the observed parallel increase in lipids levels is the cause or the result of this inflammation remains to be elucidated.
The increase of pre-inflammatory cytokines IL-2, INF-γ is followed by an increase of serum cholesterol and triglycerides indicating a possible etiological correlation between the over secretion of cytokines and lipid disorders observed in diabetes mellitus 2.