Complement activation in polycystic ovary syndrome occurs in the
post-prandial and fasted state, and is influenced by obesity and insulin
sensitivity
Abstract
Objective: Polycystic Ovary Syndrome (PCOS) is associated with metabolic
risk. Complement proteins regulate inflammation and lipid clearance but
their role in PCOS-associated metabolic risk is unclear. We sought to
establish whether the complement system is activated in PCOS in the
fasting and postprandial state. Design: Case-control study Setting:
University hospital Population: Fasting complement levels were measured
in 84 women with PCOS and 95 healthy controls. Complement activation
post-oral fat tolerance test (OFTT) was compared in 40 additional
subjects (20 PCOS, 20 controls). Methods: Activation pathway (C3, C4,
C3a(desArg), factor B, factor H, properdin, Factor D) and terminal
pathway (C5, C5a, terminal complement complex [TCC]) proteins were
measured by commercial or in-house assays. Main outcome measures:
Fasting and postprandial complement proteins and their activation
products. Results: Fasting C3, C3a(desArg) and TCC concentrations were
increased in insulin-resistant (Adjusted differences: C3 0.13g/l
[95%CI 0-0.25]; C3a(desArg) 319.2 ng/ml [19.5-619]; TCC 0.66
μg/ml [0.04-1.28]) but not in insulin-sensitive women with PCOS. C3
and factor H levels increased with obesity. Post-OFTT, C3 and C4 levels
increased to a similar extent in PCOS subjects and controls, while
factor H levels increased more in women with PCOS compared to controls
(Adjusted differences (area under the curve): 12,167 μg min/ml
[4,942-19,392]), particularly in the presence of concomitant
obesity. Conclusions: Activation and terminal complement pathway
components are elevated in patients with PCOS, especially in the
presence of insulin resistance and obesity. Interventions which regulate
complement activation may be helpful in reducing cardiometabolic risk.