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

J Clin Endocrinol Metab. 2013 May;98(5):2100-5. doi: 10.1210/jc.2012-3971. Epub 2013 Mar 28.


Context: 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.

Patients and 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.

Trial registration: ClinicalTrials.gov NCT00879801.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / analysis*
  • Body Mass Index
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / etiology
  • Female
  • Glucose Intolerance / blood
  • Glucose Intolerance / complications
  • Glucose Intolerance / metabolism*
  • Glucose Intolerance / physiopathology
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Resistance*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Models, Biological
  • Overweight / complications
  • Prediabetic State / blood
  • Prediabetic State / complications
  • Prediabetic State / metabolism*
  • Prediabetic State / physiopathology
  • Risk


  • Blood Glucose
  • Insulin

Associated data

  • ClinicalTrials.gov/NCT00879801