title: Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study.
abstract: BACKGROUND
  In subjects with normal glucose tolerance (NGT) 1-hour postload plasma glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2 diabetes (T2DM) and is associated with subclinical atherosclerosis.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate β-cell function, insulin resistance, and cardiovascular risk profile in subjects with NGT with a 1-h OGTT glucose of >155 mg/dL.
  
  
  METHODS
  The GENFIEV (Genetics, PHYsiopathology, and Evolution of Type 2 diabetes) study is a multicenter study recruiting individuals at high risk of T2DM. A total of 926 subjects underwent a 75-g OGTT for assessment of plasma glucose and C-peptide for mathematical modeling of β-cell function (derivative and proportional control). Fasting insulin, lipid profile, and clinical parameters were determined as well.
  
  
  RESULTS
  A 1-hour OGTT glucose of >155 mg/dL was found in 39% of subjects with NGT, 76% with impaired fasting glucose (IFG), 90% with impaired glucose tolerance (IGT), and 99% and 98% with IFG + IGT or newly diagnosed T2DM, respectively. Among subjects with NGT (n = 474), those with 1-hour OGTT glucose of >155 mg/dL were more insulin-resistant and had worse β-cell function than those with 1-hour OGTT glucose of ≤155 mg/dL. Moreover, glycosylated hemoglobin, blood pressure, low-density lipoprotein cholesterol, and triglycerides were higher in subjects with NGT with 1-hour OGTT glucose of >155 mg/dL, whereas high-density lipoprotein cholesterol was lower compared with that in subjects with NGT with 1-hour OGTT glucose of ≤155 mg/dL. Compared with subjects with IGT, those with NGT with 1-hour OGTT glucose of >155 mg/dL had comparable cardiovascular risk profile and insulin resistance but slightly better β-cell function.
  
  
  CONCLUSIONS
  Among subjects with NGT, those with 1-hour OGTT glucose of >155 mg/dL showed lower insulin sensitivity, impaired β-cell function, and worse cardiovascular risk profile and therefore are at greater risk of developing T2DM and cardiovascular disease.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, 56124 Pisa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bianchi
authors.forename: Roberto
authors.initials: R
authors.lastname: Miccoli
authors.forename: Maddalena
authors.initials: M
authors.lastname: Trombetta
authors.forename: Francesco
authors.initials: F
authors.lastname: Giorgino
authors.forename: Simona
authors.initials: S
authors.lastname: Frontoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Faloia
authors.forename: Giulio
authors.initials: G
authors.lastname: Marchesini
authors.forename: Maria A
authors.initials: MA
authors.lastname: Dolci
authors.forename: Franco
authors.initials: F
authors.lastname: Cavalot
authors.forename: Gisella
authors.initials: G
authors.lastname: Cavallo
authors.forename: Frida
authors.initials: F
authors.lastname: Leonetti
authors.forename: Riccardo C
authors.initials: RC
authors.lastname: Bonadonna
authors.forename: Stefano
authors.initials: S
authors.lastname: Del Prato
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D050177:Overweight / Q000150:complications; D011236:Prediabetic State / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D012306:Risk
chemical_list: D001786:Blood Glucose; D007328:Insulin