Are obesity-related metabolic risk factors modulated by the degree of insulin resistance in adolescents?
OBJECTIVE
Obesity is often associated with insulin resistance and the components of the metabolic syndrome. However, wide variations in insulin sensitivity are noted in obese youth. It is not clear if greater insulin resistance confers a higher risk of cardiovascular comorbidities and risk for type 2 diabetes.


METHODS
We investigated physical and metabolic features of 54 obese adolescents. Subsequently, we pair matched 17 moderately insulin-resistant (MIR group) to 17 severely insulin-resistant (SIR group) youth based on cut points for insulin sensitivity (MIR group insulin sensitivity within 2 SDs and SIR group <2 SDs of normal-weight adolescent values). We evaluated differences in body composition (dual-energy X-ray absorptiometry), abdominal fat (computed tomography scan), cardiorespiratory fitness (CRF) (Vo(2max) on a treadmill), insulin sensitivity and secretion (hyperinsulinemic-euglycemic and hyperglycemic clamps), substrate utilization (indirect calorimetry), and fasting adiponectin and lipid profile.


RESULTS
SIR youth had higher visceral adiposity (78.3 +/- 6.9 vs. 60.3 +/- 6.9 cm(2), P = 0.017) and waist-to-hip ratio (0.91 +/- 0.01 vs. 0.86 +/- 0.02, P = 0.026) and lower HDL (1.0 +/- 0.03 vs. 1.16 +/- 0.06 mmol/l, P = 0.015) than pair-matched MIR subjects. There was a tendency for adiponectin (6.1 +/- 0.5 vs. 8.6 +/- 1.1 microg/ml, P = 0.079) and CRF (49.9 +/- 3.2 vs. 55.2 +/- 3.5 ml x min(-1) x kg(-1) fat-free mass, P = 0.09) to be lower in SIR subjects. SIR youth also had an impaired balance between insulin sensitivity and beta-cell compensation with a lower glucose disposition index.


CONCLUSIONS
Despite similar BMI, the degree of insulin resistance impacts the risk for obesity-related metabolic comorbidities. The SIR youth are at greater risk for type 2 diabetes and cardiovascular disease.
Bacha
Fida
F
Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus and the Weight Management and Wellness Center, Children's Hospital of Pittsburgh, Pennsylvania 15213, USA.
Saad
Rola
R
Gungor
Neslihan
N
Arslanian
Silva A
SA
D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology; D002320:Cardiovascular Physiological Phenomena; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005260:Female; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000033:anatomy & histology; D008297:Male; D009765:Obesity / Q000150:complications*; D012044:Regression Analysis; D012143:Respiratory Physiological Phenomena; D012307:Risk Factors
D001786:Blood Glucose; D007328:Insulin