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

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 5; pp. 2100 - 2105
• Main Authors: Bianchi, Cristina, Miccoli, Roberto, Trombetta, Maddalena, Giorgino, Francesco, Frontoni, Simona, Faloia, Emanuela, Marchesini, Giulio, Dolci, Maria A., Cavalot, Franco, Cavallo, Gisella, Leonetti, Frida, Bonadonna, Riccardo C., Del Prato, Stefano
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.05.2013; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adult; Arteriosclerosis; Beta cells; Biological and medical sciences; Blood Glucose - analysis; Blood pressure; Body Mass Index; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - etiology; Cholesterol; Cross-Sectional Studies; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - etiology; Endocrinopathies; Fasting; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucose; Glucose Intolerance - blood; Glucose Intolerance - complications; Glucose Intolerance - metabolism; Glucose Intolerance - physiopathology; Glucose tolerance; Glucose Tolerance Test; Hemoglobin; High density lipoprotein; Humans; Insulin - blood; Insulin - metabolism; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells - metabolism; Italy - epidemiology; Male; Mathematical models; Medical sciences; Middle Aged; Models, Biological; Overweight - complications; Prediabetic State - blood; Prediabetic State - complications; Prediabetic State - metabolism; Prediabetic State - physiopathology; Risk; Triglycerides; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Italy; Endocrinopathy; Human; Obesity; Pancreatic hormone; Cell function; Nutrition; Nutrition disorder; Tolerance; Metabolic diseases; Cardiovascular disease; Glucose tolerance test; Glucose; Normal; Insulin; Target tissue resistance; Risk factor; Cardiovascular risk; Insulin resistance; β Cell; Endocrinology; Nutritional status; Glycemia
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2012-3971

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.