title: Insulin resistance in obesity can be reliably identified from fasting plasma insulin.
abstract: OBJECTIVE
  Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables.
  
  
  METHODS
  We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified.
  
  
  RESULTS
  Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd <37.3 μmol kg(-1) min(-1) did not differ from insulin-sensitive obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), P<0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) (4.5±2.2 vs 2.7±1.4, P=0.004). Insulin-resistant obese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1).
  
  
  CONCLUSIONS
  Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: K W
authors.initials: KW
authors.lastname: ter Horst
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: P W
authors.initials: PW
authors.lastname: Gilijamse
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: K E
authors.initials: KE
authors.lastname: Koopman
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: B A
authors.initials: BA
authors.lastname: de Weijer
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Brands
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: R S
authors.initials: RS
authors.lastname: Kootte
authors.affiliation: Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
authors.affiliation: Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Ackermans
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Nieuwdorp
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M R
authors.initials: MR
authors.lastname: Soeters
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Serlie
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D005215:Fasting / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood* / Q000627:therapeutic use; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009426:Netherlands / Q000453:epidemiology; D009765:Obesity; D011237:Predictive Value of Tests; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin