title: Relationship between glycaemic variability and hyperglycaemic clamp-derived functional variables in (impending) type 1 diabetes.
abstract: OBJECTIVE
  We examined whether measures of glycaemic variability (GV), assessed by continuous glucose monitoring (CGM) and self-monitoring of blood glucose (SMBG), can complement or replace measures of beta cell function and insulin action in detecting the progression of preclinical disease to type 1 diabetes.
  
  
  METHODS
  Twenty-two autoantibody-positive (autoAb(+)) first-degree relatives (FDRs) of patients with type 1 diabetes who were themselves at high 5-year risk (50%) for type 1 diabetes underwent CGM, a hyperglycaemic clamp test and OGTT, and were followed for up to 31 months. Clamp variables were used to estimate beta cell function (first-phase [AUC5-10 min] and second-phase [AUC120-150 min] C-peptide release) combined with insulin resistance (glucose disposal rate; M 120-150 min). Age-matched healthy volunteers (n = 20) and individuals with recent-onset type 1 diabetes (n = 9) served as control groups.
  
  
  RESULTS
  In autoAb(+) FDRs, M 120-150 min below the 10th percentile (P10) of controls achieved 86% diagnostic efficiency in discriminating between normoglycaemic FDRs and individuals with (impending) dysglycaemia. M 120-150 min outperformed AUC5-10 min and AUC120-150 min C-peptide below P10 of controls, which were only 59-68% effective. Among GV variables, CGM above the reference range was better at detecting (impending) dysglycaemia than elevated SMBG (77-82% vs 73% efficiency). Combined CGM measures were equally efficient as M 120-150 min (86%). Daytime GV variables were inversely correlated with clamp variables, and more strongly with M 120-150 min than with AUC5-10 min or AUC120-150 min C-peptide.
  
  
  CONCLUSIONS
  CGM-derived GV and the glucose disposal rate, reflecting both insulin secretion and action, outperformed SMBG and first- or second-phase AUC C-peptide in identifying FDRs with (impending) dysglycaemia or diabetes. Our results indicate the feasibility of developing minimally invasive CGM-based criteria for close metabolic monitoring and as outcome measures in trials.
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.
authors.forename: Annelien
authors.initials: A
authors.lastname: Van Dalem
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.
authors.forename: Simke
authors.initials: S
authors.lastname: Demeester
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.
authors.forename: Eric V
authors.initials: EV
authors.lastname: Balti
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.
authors.forename: Katelijn
authors.initials: K
authors.lastname: Decochez
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium. ilse.weets@uzbrussel.be.|Department of Clinical Chemistry and Radio-immunology, University Hospital Brussels, Brussels, Belgium. ilse.weets@uzbrussel.be.
authors.forename: Ilse
authors.initials: I
authors.lastname: Weets
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.
authors.forename: Evy
authors.initials: E
authors.lastname: Vandemeulebroucke
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.|Department of Diabetology, University Hospital Brussels, Brussels, Belgium.
authors.forename: Ursule
authors.initials: U
authors.lastname: Van de Velde
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Walgraeve
authors.affiliation: CHC Clinique de L'Espérance, Montegnée, Belgium.
authors.forename: Nicole
authors.initials: N
authors.lastname: Seret
authors.affiliation: Department of Endocrinology, Diabetology and Metabolism, University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: De Block
authors.affiliation: Department of Endocrinology, University Hospital Ghent, Ghent, Belgium.
authors.forename: Johannes
authors.initials: J
authors.lastname: Ruige
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.|Department of Endocrinology, University Hospital Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Gillard
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.|Department of Diabetology, University Hospital Brussels, Brussels, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Keymeulen
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pipeleers
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 100, 1090, Brussels, Belgium.|Department of Clinical Chemistry and Radio-immunology, University Hospital Brussels, Brussels, Belgium.
authors.forename: Frans K
authors.initials: FK
authors.lastname: Gorus
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis*; D015190:Blood Glucose Self-Monitoring; D002096:C-Peptide / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D064368:Healthy Volunteers; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin
keywords: Beta cell function; Continuous glucose monitoring; Hyperglycaemic clamp; Insulin resistance; Prediabetes; Prediction; Prevention; Self-monitoring of blood glucose; Type 1 diabetes