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Relationship between glycaemic variability and hyperglycaemic clamp-derived functional variables in (impending) type 1 diabetes

(2015) DIABETOLOGIA. 58(12). p.2753-2764
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Abstract
Aims/hypothesis: 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 [AUC(5-10 min)] and second-phase [AUC(120-150 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 AUC(5-10 min) and AUC(120-150 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 AUC(5-10 min) or AUC(120-150 min) C-peptide. Conclusions/interpretation: 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.
Keywords
Continuous glucose monitoring, Beta cell function, Hyperglycaemic clamp, Insulin resistance, Prediabetes, Prediction, Prevention, Self-monitoring of blood glucose, Type 1 diabetes, BETA-CELL FUNCTION, QUANTIFYING INSULIN-SECRETION, TRIAL-TYPE 1, GLUCOSE-TOLERANCE, CLINICAL ONSET, CHILDREN, PROGRESSION, SENSITIVITY, RESISTANCE, PREDICTION

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Chicago
Van Dalem, Annelien, Simke Demeester, Eric V Balti, Katelijn Decochez, Ilse Weets, Evy Vandemeulebroucke, Ursule Van de Velde, et al. 2015. “Relationship Between Glycaemic Variability and Hyperglycaemic Clamp-derived Functional Variables in (impending) Type 1 Diabetes.” Diabetologia 58 (12): 2753–2764.
APA
Van Dalem, A., Demeester, S., Balti, E. V., Decochez, K., Weets, I., Vandemeulebroucke, E., Van de Velde, U., et al. (2015). Relationship between glycaemic variability and hyperglycaemic clamp-derived functional variables in (impending) type 1 diabetes. DIABETOLOGIA, 58(12), 2753–2764.
Vancouver
1.
Van Dalem A, Demeester S, Balti EV, Decochez K, Weets I, Vandemeulebroucke E, et al. Relationship between glycaemic variability and hyperglycaemic clamp-derived functional variables in (impending) type 1 diabetes. DIABETOLOGIA. 2015;58(12):2753–64.
MLA
Van Dalem, Annelien, Simke Demeester, Eric V Balti, et al. “Relationship Between Glycaemic Variability and Hyperglycaemic Clamp-derived Functional Variables in (impending) Type 1 Diabetes.” DIABETOLOGIA 58.12 (2015): 2753–2764. Print.
@article{7409092,
  abstract     = {Aims/hypothesis: 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 [AUC(5-10 min)] and second-phase [AUC(120-150 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 AUC(5-10 min) and AUC(120-150 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 AUC(5-10 min) or AUC(120-150 min) C-peptide. 
Conclusions/interpretation: 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.},
  author       = {Van Dalem, Annelien and Demeester, Simke and Balti, Eric V and Decochez, Katelijn and Weets, Ilse and Vandemeulebroucke, Evy and Van de Velde, Ursule and Walgraeve, An and Seret, Nicole and De Block, Christophe and Ruige, Johannes and Gillard, Pieter and Keymeulen, Bart and Pipeleers, Daniel G and Gorus, Frans K},
  issn         = {0012-186X},
  journal      = {DIABETOLOGIA},
  language     = {eng},
  number       = {12},
  pages        = {2753--2764},
  title        = {Relationship between glycaemic variability and hyperglycaemic clamp-derived functional variables in (impending) type 1 diabetes},
  url          = {http://dx.doi.org/10.1007/s00125-015-3761-y},
  volume       = {58},
  year         = {2015},
}

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