Complement and Cardiovascular Risk in Adolescents

Completed

Conditions: Type 2 Diabetes
Cardiovascular Disease

Registration Number: NCT02821104

Lead Sponsor: Ohio State University

Brief Summary: This study evaluates how genetic variations in complement, a part of the immune system, affect cardiovascular risk in adolescents.

Detailed Description: Cardiometabolic diseases usually do not produce significant mortality and morbidity until adulthood. There is clear evidence, however, that these diseases have their origins in childhood and adolescence. With the rising incidence of obesity associated with poorer eating and less physical activity in children and adolescents it is important that the investigators study these diseases early in their course if the investigators are to prevent future cardiometabolic disease. While obesity clearly increases cardiometabolic risk, not all obese subjects are at increased risk; approximately 25-30% of obese adults and adolescents are metabolically healthy. The complement system is key physiological component in controlling inflammation and recent studies have indicated complement plays an important role in increasing obesity and cardiometabolic risk. Adults with proven cardiometabolic disease or at future risk for cardiometabolic disease have increased levels of the complement components C3, C3a-desArg, and C4 compared to healthy, not at risk, control subjects, independent of obesity. Increased C3 or C3a-desArg levels in adolescents are associated with increased cardiometabolic risk independent of obesity. Two specific single nucleotide polymorphisms (SNPs) in the intron for C3, rs11569562 and rs2250656, both with A\>G polymorphisms, are associated with increased serum C3 levels, and increases in a variety of cardiovascular risk factors. No one has investigated how C3 polymorphisms affect risk factors in adolescents. The C4 gene has significant copy number variation and increased copy number is associated with increased C4 levels. The relationship of C4 gene copy number to cardiometabolic risk has not been studied in adults or adolescents. The short-term objectives of this study are to explore differences in cardiometabolic risk factors in overweight and obese adolescents with C3 polymorphisms and also to explore how C4 gene copy number variation affects risk factors. The investigators overall hypothesis is that variations in C3 polymorphisms, C4 gene copy number or both will have significant impact on cardiometabolic health in overweight and obese adolescents. Both traditional and nontraditional cardiometabolic risk markers, including measures of body habitus, blood pressure, lipids, vascular function, insulin secretion and sensitivity, inflammation, and clotting will be investigated in 100 overweight and obese adolescents. The investigators proposed study will help us understand the role of complement and its genetics in the development of cardiometabolic risk and in potentially developing genetic biomarkers for adolescents at increased risk.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 77

Inclusion Criteria

Healthy adolescents age 12 to 18 years
Medication free for 2 weeks except oral contraceptives in females
Non Hispanic white

Exclusion Criteria

Chronic medications except for contraceptives in females.
History of autoimmune disease either endocrine or connective tissue type
History of hematologic or renal disease, malignancy or other chronic disease
Hispanic ethnicity,
African-American or Asian race

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Complement C3 Genotype	Baseline	Genetic C3F genotype allele presence
C4 Copy Number	Baseline	C4A or C4B gene copy numbers

Secondary Outcome Measures

Name	Time	Method
Endothelin 1	baseline
BMI	Baseline	Body mass index
Waist Circumference	Baseline	Waist circumference at narrowest point
Body Fat	Baseline	Percent body fat BodPod
Endothelial Function	8 min	reactive hyperemia response to upper arm occlusion
Vascular Stiffness	baseline	augmentation index of reflected blood pressure wave
Inflammation	baseline	IL6
Clotting	baseline	PAI1
Insulin Sensitivity	baseline	Oral glucose tolerance test