title: Insulin sensitivity, β-cell function, and incretin effect in individuals with elevated 1-hour postload plasma glucose levels.
abstract: OBJECTIVE
  Individuals with normal glucose tolerance (NGT), whose 1-h postload plasma glucose is ≥155 mg/dL (NGT 1h-high), have an increased risk of type 2 diabetes. The purpose of this study was to characterize their metabolic phenotype.
  
  
  METHODS
  A total of 305 nondiabetic offspring of type 2 diabetic patients was consecutively recruited. Insulin secretion was assessed using both indexes derived from oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp.
  
  
  RESULTS
  Compared with individuals with a 1-h postload plasma glucose <155 mg/dL (NGT 1h-low), NGT 1h-high individuals exhibited lower insulin sensitivity after adjustment for age, sex, and BMI. Insulin secretion estimated from the OGTT did not differ between the two groups of individuals. By contrast, compared with NGT 1h-low individuals, the acute insulin response during an IVGTT and the disposition index were significantly reduced in NGT 1h-high individuals after adjustment for age, sex, and BMI. Incretin effect, estimated as the ratio between total insulin responses during OGTT and IVGTT, was higher in NGT 1h-high individuals compared with NGT 1h-low individuals.
  
  
  CONCLUSIONS
  NGT 1h-high individuals may represent an intermediate state of glucose intolerance between NGT and type 2 diabetes characterized by insulin resistance and reduced β-cell function, the two main pathophysiological defects responsible for the development of type 2 diabetes. Postload hyperglycemia is the result of an intrinsic β-cell defect rather than impaired incretin effect.
authors.affiliation: Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Marini
authors.forename: Elena
authors.initials: E
authors.lastname: Succurro
authors.forename: Simona
authors.initials: S
authors.lastname: Frontoni
authors.forename: Simona
authors.initials: S
authors.lastname: Mastroianni
authors.forename: Franco
authors.initials: F
authors.lastname: Arturi
authors.forename: Angela
authors.initials: A
authors.lastname: Sciacqua
authors.forename: Renato
authors.initials: R
authors.lastname: Lauro
authors.forename: Marta L
authors.initials: ML
authors.lastname: Hribal
authors.forename: Francesco
authors.initials: F
authors.lastname: Perticone
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sesti
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D016241:Child of Impaired Parents; D003924:Diabetes Mellitus, Type 2; D005060:Europe; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D054795:Incretins / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D054795:Incretins