title: Insulin sensitivity, and β-cell function in relation to hemoglobin A1C.
abstract: OBJECTIVE
  The A1C diagnostic criterion for identifying individuals at increased risk for diabetes, introduced by the American Diabetes Association in 2010, was not defined on the basis of the principal pathophysiological abnormalities responsible for the development and progression of type 2 diabetes; we therefore wished to gain a deeper insight into the metabolic abnormalities characterizing the group of at risk individuals with an A1C value of 5.7-6.4%.
  
  
  RESULTS
  As many as 338 non-diabetic offspring of type 2 diabetic patients were 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. As compared with subjects with A1C <5.7%, individuals with A1C of 5.7-6.4% exhibited lower insulin sensitivity after adjusting for age, gender and body mass index (BMI). Insulin secretion estimated from the OGTT, did not differ between the two groups. By contrast, as compared with subjects with A1C <5.7%, the acute insulin response (AIR) during an IVGTT and both IVGTT-derived and OGTT-derived disposition indexes were reduced in individuals with A1C of 5.7-6.4% after adjusting for age, gender and BMI. As A1C increased to ≥ 5.7%, a sharp decrease in insulin sensitivity and β-cell function, measured as disposition index, was observed.
  
  
  CONCLUSIONS
  Caucasian individuals with A1C ≥ 5.7% exhibit both core pathophysiological defects of type 2 diabetes i.e. insulin resistance and β-cell dysfunction.
authors.affiliation: Department of Systems Medicine, University of Rome-Tor Vergata, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Marini
authors.affiliation: Department of Systems Medicine, University of Rome-Tor Vergata, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Frontoni
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Succurro
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Arturi
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sciacqua
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Hribal
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Perticone
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Italy. Electronic address: sesti@unicz.it.
authors.forename: G
authors.initials: G
authors.lastname: Sesti
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin
keywords: A1C; Insulin secretion; Insulin sensitivity