Characterization of the Influence of Vildagliptin on Model-Assessed {beta}-Cell Function in Patients with Type 2 Diabetes and Mild Hyperglycemia.
(2009) In Journal of Clinical Endocrinology and Metabolism 93(1). p.103-109- Abstract
- Objective: This study was conducted to characterize the effects of vildagliptin on beta-cell function in patients with type 2 diabetes and mild hyperglycemia. Design: A 52-wk double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 306 patients with mild hyperglycemia (A1C = 6.2-7.5%). Plasma glucose and C-peptide levels were measured during standard meal tests performed at baseline, wk 24 and 52, and after 4-wk washout. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution and beta-cell function was quantified with a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change... (More)
- Objective: This study was conducted to characterize the effects of vildagliptin on beta-cell function in patients with type 2 diabetes and mild hyperglycemia. Design: A 52-wk double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 306 patients with mild hyperglycemia (A1C = 6.2-7.5%). Plasma glucose and C-peptide levels were measured during standard meal tests performed at baseline, wk 24 and 52, and after 4-wk washout. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution and beta-cell function was quantified with a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change (rate sensitivity), and a potentiation factor. Results: Vildagliptin significantly increased fasting insulin secretory tone (between-group difference in adjusted mean change from baseline to wk 52 [Delta]= +34.1 +/- 9.5 pmol*min(-1) *m(-2), P<0.001) glucose sensitivity (Delta= +20.7 +/- 5.2 pmol*min(-1) *m(-2) *mM(-1), P < 0.001) and rate sensitivity (Delta= +163.6 +/- 67.0 pmol*m(-2) *mM(-1), P = 0.015) but total insulin secretion (ISR AUC0-2h) and the potentiation factor excursion during meals were unchanged. These improvements in beta-cell function were accompanied by a decrease in the glucose AUC0-2h (Delta = -1.7 +/- 0.5 mM*h, P = 0.002) and in A1C (Delta = -0.3 +/- 0.1%, P < 0.001). None of the effects of vildagliptin remained following 4-wk washout from study medication. Conclusions: Consistent with previous findings from shorter-term studies in patients with more severe hyperglycemia, in patients with mild hyperglycemia, improved beta-cell function is maintained throughout 52-wk treatment with vildagliptin and underlies a sustained improvement in glycemic control. However, no effects remain after washout. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/608691
- author
- Mari, Andrea ; Scherbaum, Werner A ; Nilsson, Peter LU ; Lalanne, Gerard ; Schweizer, Anja ; Dunning, Beth E ; Jauffret, Sophie and Foley, James E
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- GIP, GLP-1, incretin, insulin secretion, dipeptidyl peptidase-IV
- in
- Journal of Clinical Endocrinology and Metabolism
- volume
- 93
- issue
- 1
- pages
- 103 - 109
- publisher
- Oxford University Press
- external identifiers
-
- scopus:38149137991
- pmid:17925336
- wos:000252359400020
- pmid:17925336
- ISSN
- 1945-7197
- DOI
- 10.1210/jc.2007-1639
- language
- English
- LU publication?
- yes
- id
- 47e91364-8dbb-4559-a6ba-0b4e40cd2fca (old id 608691)
- date added to LUP
- 2016-04-01 13:36:35
- date last changed
- 2022-03-21 19:30:30
@article{47e91364-8dbb-4559-a6ba-0b4e40cd2fca, abstract = {{Objective: This study was conducted to characterize the effects of vildagliptin on beta-cell function in patients with type 2 diabetes and mild hyperglycemia. Design: A 52-wk double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 306 patients with mild hyperglycemia (A1C = 6.2-7.5%). Plasma glucose and C-peptide levels were measured during standard meal tests performed at baseline, wk 24 and 52, and after 4-wk washout. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution and beta-cell function was quantified with a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change (rate sensitivity), and a potentiation factor. Results: Vildagliptin significantly increased fasting insulin secretory tone (between-group difference in adjusted mean change from baseline to wk 52 [Delta]= +34.1 +/- 9.5 pmol*min(-1) *m(-2), P<0.001) glucose sensitivity (Delta= +20.7 +/- 5.2 pmol*min(-1) *m(-2) *mM(-1), P < 0.001) and rate sensitivity (Delta= +163.6 +/- 67.0 pmol*m(-2) *mM(-1), P = 0.015) but total insulin secretion (ISR AUC0-2h) and the potentiation factor excursion during meals were unchanged. These improvements in beta-cell function were accompanied by a decrease in the glucose AUC0-2h (Delta = -1.7 +/- 0.5 mM*h, P = 0.002) and in A1C (Delta = -0.3 +/- 0.1%, P < 0.001). None of the effects of vildagliptin remained following 4-wk washout from study medication. Conclusions: Consistent with previous findings from shorter-term studies in patients with more severe hyperglycemia, in patients with mild hyperglycemia, improved beta-cell function is maintained throughout 52-wk treatment with vildagliptin and underlies a sustained improvement in glycemic control. However, no effects remain after washout.}}, author = {{Mari, Andrea and Scherbaum, Werner A and Nilsson, Peter and Lalanne, Gerard and Schweizer, Anja and Dunning, Beth E and Jauffret, Sophie and Foley, James E}}, issn = {{1945-7197}}, keywords = {{GIP; GLP-1; incretin; insulin secretion; dipeptidyl peptidase-IV}}, language = {{eng}}, number = {{1}}, pages = {{103--109}}, publisher = {{Oxford University Press}}, series = {{Journal of Clinical Endocrinology and Metabolism}}, title = {{Characterization of the Influence of Vildagliptin on Model-Assessed {beta}-Cell Function in Patients with Type 2 Diabetes and Mild Hyperglycemia.}}, url = {{http://dx.doi.org/10.1210/jc.2007-1639}}, doi = {{10.1210/jc.2007-1639}}, volume = {{93}}, year = {{2009}}, }