1187-P: Increased C4B Gene Copy Number Is Associated with Increased Inflammation in Adolescent Type 1 Diabetes

Introduction: Cardiovascular disease will be the primary cause of future death for adolescents with type 1 diabetes (T1D). Increased systemic inflammation is likely to play a role in this. The complement system is part of the innate immune system regulating inflammation. C4 total gene copy number (GCN) and C4 subtype (C4A, C4B, C4Long, and C4Short) CGN have been associated with various aspects of the metabolic syndrome.

Objective: To determine if C4 GCN is associated with fasting and/or post-prandial inflammation in adolescents with T1D.

Methodology: 12 non-obese children and adolescents, 10-18 years old, with T1D were recruited from the Diabetes Clinic of Nationwide Children's Hospital. A randomized cross-over design for two subsequent visits was used. Fasting baseline blood samples were taken to measure glucose, TNFα, IL6, C3 and C4 protein levels and total C4, C4A, and C4B GCN. Rapid acting insulin was given to cover meal carbohydrate without glucose correction. Blood samples were repeated at 30, 60, 90, and 120 minutes. Visits 1 and 2 were identical except for GI of the meal. Visits were rescheduled if fasting glucose was > 200 mg/dl. Spearman’s correlation was used.

Results: Total C4 GCN C4A and C4 Long GCN did not correlate with TNFα, IL6, C3, or C4 levels pre or post prandially for either meal. C4 short CGN positively correlated with baseline TNFα for the high glycemic index meal (r_s=0.80, p<0.001) but not the low glycemic index meal. C4B GCN positively correlated with baseline TNFα (r_s=0.64; r_s=0.68 p<0.02) and IL6 (r_s=0.79, p<0.01; r_s=0.67 p<0.02) levels and 30 min TNFα (r_s=0.80; r_s=0.70, p<0.01) for both the high and low glycemic index meals, respectively. C4B GCN also correlated with 60 min C4 levels for both meals (r_s=0.80; r_s=0.70 p<0.01).

Conclusions: High C4B GCN is associated with increased inflammatory markers (TNFα and IL6) in adolescent T1D. This association may indicate that individuals with high C4B GCN are at increased future risk for diabetes related cardiovascular disease.