title: The Clamp-Like Index: a novel and highly sensitive insulin sensitivity index to calculate hyperinsulinemic clamp glucose infusion rates from oral glucose tolerance tests in nondiabetic subjects.
abstract: OBJECTIVE
  Insulin resistance, the underlying pathophysiological mechanism of the metabolic syndrome, can not only predict type 2 diabetes development but also cardiovascular disease. Thus, precise insulin resistance measurement in individuals at risk for metabolic diseases would support clinical risk stratification. However, the gold standard for measuring insulin resistance, the hyperinsulinemic clamp test, is too labor intensive to be performed in large clinical studies/settings.
  
  
  METHODS
  Using plasma glucose and C-peptide concentrations from oral glucose tolerance tests (OGTTs), we developed the novel "clamp-like index" (CLIX) for insulin sensitivity calculation and compared CLIX to clamp glucose infusion rates (GIR) (100-120 min). We evaluated CLIX in 89 nondiabetic subjects (58 female and 31 male, aged 45 +/- 1 years, BMI 27.5 +/- 0.8 kg/m(2)) who underwent frequently sampled 3-h 75-g OGTTs and 2-h hyperinsulinemic-isoglycemic clamp (40 mU/min per m(2)) tests.
  
  
  RESULTS
  CLIX, calculated as serum creatinine (x0.85 if male)/(mean AUC(glucose) x mean AUC(C-peptide)) x 6,600, was highly correlated (r = 0.670, P < 10(-12)) with and comparable to clamp GIRs(100-120 min). In subgroup analyses, GIRs(100-120 min) were lower (P < 0.005) in type 2 diabetic offspring (6.2 +/- 0.7 mg x min(-1) x kg(-1)) than in sex-, age-, and BMI-matched subjects without a family history of type 2 diabetes (8.6 +/- 0.5 mg x min(-1) x kg(-1)), which was also reflected by CLIX (insulin-resistant offspring 6.4 +/- 0.6 vs. those without a family history of type 2 diabetes 9.0 +/- 0.5; P < 0.002). When compared with normal-weight subjects (GIR 8.8 +/- 0.4 mg x min(-1) x kg(-1); CLIX 9.0 +/- 0.5), both GIRs(100-120 min) and CLIX of obese (5.2 +/- 0.9 mg x min (-1) x kg(-1); 5.7 +/- 0.9) and morbidly obese (2.4 +/- 0.4 mg x min (-1) x kg(-1); 3.3 +/- 0.5) humans were lower (each P < 0.02).
  
  
  CONCLUSIONS
  CLIX, a novel index obtained from plasma OGTT glucose and C-peptide levels and serum creatinine, without inclusion of anthropometrical measures to calculate insulin sensitivity in nondiabetic humans, highly correlates with clamp GIRs and reveals even slight insulin sensitivity alterations over a broad BMI range and is as sensitive as the hyperinsulinemic clamp test.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Austria. christian-heinz.anderwald@meduniwien.ac.at
authors.forename: Christian
authors.initials: C
authors.lastname: Anderwald
authors.forename: Marietta
authors.initials: M
authors.lastname: Anderwald-Stadler
authors.forename: Miriam
authors.initials: M
authors.lastname: Promintzer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Prager
authors.forename: Martina
authors.initials: M
authors.lastname: Mandl
authors.forename: Peter
authors.initials: P
authors.lastname: Nowotny
authors.forename: Martin G
authors.initials: MG
authors.lastname: Bischof
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ludvik
authors.forename: Thomas
authors.initials: T
authors.lastname: Kästenbauer
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
mesh_terms: D000328:Adult; D001786:Blood Glucose; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000175:diagnosis*; D007328:Insulin; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis; D008875:Middle Aged; D019999:Pharmaceutical Solutions / Q000008:administration & dosage
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019999:Pharmaceutical Solutions; D005947:Glucose