title: Discriminatory ability of simple OGTT-based beta cell function indices for prediction of prediabetes and type 2 diabetes: the CODAM study.
abstract: The hyperglycaemic clamp technique and the frequently sampled IVGTT are unsuitable techniques to assess beta cell function (BCF) in large cohorts. Therefore, the aim of this study was to evaluate the discriminatory ability of simple OGTT-based BCF indices for prediction of prediabetes (meaning impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes.
  
  
  
  Glucose metabolism status was assessed by 2 h 75 g OGTT at baseline (n = 476, mean age 59.2 years, 38.7% women) and after 7 years of follow-up (n = 416) in the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study (1999-2009). Baseline plasma glucose, insulin and C-peptide values during OGTTs were used to calculate 21 simple indices of BCF. Disposition indices (BCF index × Matsuda index), to compensate for the prevailing level of insulin resistance, were calculated for the BCF indices with the best discriminatory abilities. The discriminatory ability of the BCF indices was estimated by the area under the receiver operating characteristics curve (ROC AUC) with an outcome of incident prediabetes (n = 73) or type 2 diabetes (n = 60 and n = 18 cases, respectively, in individuals who were non-diabetic or had normal glucose metabolism at baseline).
  
  
  
  For incident prediabetes (n = 73), all ROC AUCs were less than 70%, whereas for incident type 2 diabetes, I30/I0, CP30/CP0, ΔI30/ΔG30, ΔCP30/ΔG30(where I, CP and G are the plasma concentrations of insulin, C-peptide and glucose, respectively, at the times indicated), and corrected insulin response at 30 min had ROC AUCs over 70%. In at-baseline non-diabetic individuals, disposition indices ΔI30/ΔG30, ΔCP30/ΔG30and corrected insulin response at 30 min had ROC AUCs of over 80% for incident type 2 diabetes. Moreover, these BCF disposition indices had significantly better discriminatory abilities for incident type 2 diabetes than the Matsuda index alone.
  
  
  
  BCF indices reflecting early-phase insulin secretion have the best ability to discriminate individuals who will develop prediabetes and type 2 diabetes. Of these, ΔCP30/ΔG30, often referred to as the C-peptidogenic index, performed consistently well.
authors.affiliation: Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands. louise.denbiggelaar@maastrichtuniversity.nl.|School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands. louise.denbiggelaar@maastrichtuniversity.nl.
authors.forename: Louise J C J
authors.initials: LJ
authors.lastname: den Biggelaar
authors.affiliation: School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands.|Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Simone J S
authors.initials: SJ
authors.lastname: Sep
authors.affiliation: Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands.|School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands.|School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, the Netherlands.
authors.forename: Simone J P M
authors.initials: SJ
authors.lastname: Eussen
authors.affiliation: CNR Institute of Neurosciences, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.affiliation: School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands.|Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.affiliation: School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands.|Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.affiliation: School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands.|Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands.|Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands.|School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands.|School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, the Netherlands.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dagnelie
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis*; D005260:Female; D005951:Glucose Tolerance Test / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000175:diagnosis*; D012372:ROC Curve
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: Beta cell function; Discrimination; Indices; Insulin secretion; OGTT; Prediabetes; Receiver operating characteristics; Type 2 diabetes mellitus