Complement-mediated chronic inflammation is associated with diabetic microvascular complication.

Area of Science:

• Immunology
• Endocrinology
• Metabolic Diseases

Background:

• Chronic inflammation is a hallmark of type 2 diabetes mellitus (T2DM).
• Obesity-associated adipokines promote pro-inflammatory cytokines, leading to vascular dysfunction and organ damage.
• Complement component C3a is implicated in inducing tissue inflammation.

Purpose of the Study:

• To investigate the link between diabetic microangiopathy and complement-mediated inflammation in obese T2DM patients.
• To assess plasma levels of complement components and activation intermediates in relation to complication severity.
• To examine in vitro production of acylation stimulating protein (ASP/C3a desArg) by chylomicrons in post-prandial serum.

Main Methods:

• Studied 32 obese T2DM patients and 32 normal donors.
• Measured plasma levels of complement factors (C3, C4, factor B, iC3b, Bb, C4d, C5b-9) and ASP.
• Conducted in vitro incubation of post-prandial serum with chylomicrons to assess ASP production.

Main Results:

• T2DM patients had significantly higher plasma levels of C3, C4, factor B, iC3b, Bb, and ASP.
• Early phase of the alternative complement pathway was excessively activated.
• Plasma ASP correlated with body mass index and high-sensitivity C-reactive protein, and was elevated in patients with macroalbuminuria and proliferative retinopathy.

Conclusions:

• Alternative complement pathway activation is elevated in obese T2DM patients, particularly in post-prandial hyperchylomicronemic states.
• This activation leads to excessive ASP production and C3a-mediated inflammation.
• Complement-mediated inflammation may accelerate both diabetic microangiopathy and macroangiopathy.