title: Adipose tissue insulin resistance in adolescents with and without type 2 diabetes.
abstract: BACKGROUND
  The incidence of type 2 diabetes mellitus (T2D) is increasing in youth, yet little is known about the underlying pathophysiology. Decreased insulin suppression of lipolysis and elevated non-esterified free fatty acid (NEFA) concentrations are known to be associated with insulin resistance and T2D in adults, but less is known about the relationship in adolescents.
  
  
  OBJECTIVE
  This study aimed to assess adipose tissue insulin resistance (IR; insulin suppression of lipolysis) and its metabolic correlates in lean, obese and T2D adolescents.
  
  
  METHODS
  Forty-seven lean, obese and T2D youth underwent hyperinsulinaemic (80 mU*m(-2) *min(-1)) euglycaemic clamps. NEFAs were measured at baseline and during steady state. Insulin-mediated suppression of lipolysis (%NEFA suppression from baseline) was calculated, and metabolic risk factors were assessed by %NEFA suppression tertile.
  
  
  RESULTS
  There was expected variability in %NEFA suppression within obese and T2D youth, but a subset had significantly reduced suppression of lipolysis. NEFA suppression tertile was significantly inversely associated with fasting triglycerides (P = 0.0001), log alanine aminotransferase (ALT; P = 0.02) and low-density lipoprotein cholesterol (P = 0.0002).
  
  
  CONCLUSIONS
  Marked adipose tissue IR occurs in some obese and T2D adolescents, which may result in release of triglycerides into the circulation and liver deposition of fatty acids, as evidenced by higher ALT in poor NEFA suppressors.
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Denver, CO, USA; Children's Hospital Colorado, Denver, CO, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Kelsey
authors.forename: J E
authors.initials: JE
authors.lastname: Forster
authors.forename: R E
authors.initials: RE
authors.lastname: Van Pelt
authors.forename: J E B
authors.initials: JE
authors.lastname: Reusch
authors.forename: K J
authors.initials: KJ
authors.lastname: Nadeau
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D016497:Adolescent Health Services; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D008066:Lipolysis; D008297:Male; D009765:Obesity / Q000378:metabolism*; D013851:Thinness / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides
keywords: Adipose tissue insulin resistance; adolescents; free fatty acids; type 2 diabetes