Complement C3 is a risk factor for the development of diabetes: a population-based cohort study

Area of Science:

• Biochemistry and Molecular Biology
• Metabolic Diseases and Endocrinology
• Immunology and Inflammation

Background:

• Previous cross-sectional studies indicated a link between plasma levels of complement C3, insulin, and glucose.
• The role of inflammation-sensitive plasma proteins (ISPs) in diabetes development requires further prospective investigation.

Purpose of the Study:

• To prospectively examine the association between baseline levels of complement C3, C4, and other ISPs and the incidence of type 2 diabetes.
• To determine if elevated ISPs predict future diabetes development in a cohort of healthy middle-aged men.

Main Methods:

• A prospective cohort study involving 2,815 nondiabetic men aged 38-50 years.
• Baseline plasma levels of complement C3, C4, fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and ceruloplasmin were measured.
• Diabetes development was assessed over a mean follow-up period of 6.1 years, with statistical adjustments for confounders.

Main Results:

• Higher baseline quartiles of complement C3 were strongly associated with an increased risk of developing diabetes (P < 0.00001).
• Elevated levels of fibrinogen, haptoglobin, C4, and a higher number of ISPs also showed a relationship with future diabetes.
• Complement C3 remained the only significant predictor of diabetes development after adjusting for BMI, insulin, and other inflammatory markers.

Conclusions:

• Plasma levels of complement C3 are a significant independent predictor of future type 2 diabetes development.
• Complement C3 may play a crucial role in the pathophysiology of diabetes, warranting further research into its mechanisms.