The IL-6-neutralizing sIL-6R-sgp130 buffer system is disturbed in patients with type 2 diabetes

Area of Science:

• Immunology
• Metabolic Disorders
• Genetics

Background:

• Elevated serum interleukin-6 (IL-6) is linked to type 2 diabetes (T2D).
• IL-6 signaling involves the IL-6 receptor (IL-6R) and glycoprotein 130 (gp130).
• A specific IL-6R gene polymorphism (rs2228145) is associated with T2D risk.

Purpose of the Study:

• To investigate if soluble IL-6R (sIL-6R) and soluble gp130 (sgp130) form an IL-6-neutralizing buffer in healthy humans.
• To determine if this buffer system is impaired in individuals with T2D.

Main Methods:

• Quantification of sIL-6R, sgp130, and IL-6 in serum samples.
• Analysis of the association between sIL-6R-sgp130 levels and T2D status.
• Comparison of buffer capacity in healthy subjects, T2D patients, and atherosclerosis patients.

Main Results:

• sIL-6R and sgp130 form an IL-6-neutralizing buffer in healthy individuals, influenced by an IL-6R SNP.
• T2D patients exhibited significantly lower circulating sIL-6R-sgp130 levels compared to healthy controls (P < 0.001).
• High IL-6 levels in T2D were inversely correlated with sIL-6R (r = -0.57, P < 0.001), indicating buffer dysfunction.

Conclusions:

• The IL-6-neutralizing buffer (sIL-6R-sgp130) is significantly reduced in T2D patients.
• This disturbance in the protective buffer system is strongly associated with the pathophysiology of type 2 diabetes.
• Impaired buffer function was also noted in T2D patients with atherosclerosis, but not in atherosclerosis alone.