Effects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetes
(2001) In Diabetes, Obesity and Metabolism 3(6). p.403-409- Abstract
- Objective: To study the effects and serum levels of glibenclamide (Gb) and its active metabolites in patients on chronic Gb medication on different daily doses. Material and methods: Fifty patients with type 2 diabetes on regular Gb therapy (1.75-14.0 mg daily). Blood samples were taken immediately before and 90 min after regular Gb intake. A standardized breakfast was served 30 min after drug intake. Serum insulin and proinsulin levels were determined by ELISA methods without cross-reactivities. Serum drug levels were determined by HPLC. Fischer's Rto Z-test (correlation coefficients) and paired Student t-tests were used when comparing values within the entire group and unpaired non-parametric Mann-Whitney tests were used when comparing... (More)
- Objective: To study the effects and serum levels of glibenclamide (Gb) and its active metabolites in patients on chronic Gb medication on different daily doses. Material and methods: Fifty patients with type 2 diabetes on regular Gb therapy (1.75-14.0 mg daily). Blood samples were taken immediately before and 90 min after regular Gb intake. A standardized breakfast was served 30 min after drug intake. Serum insulin and proinsulin levels were determined by ELISA methods without cross-reactivities. Serum drug levels were determined by HPLC. Fischer's Rto Z-test (correlation coefficients) and paired Student t-tests were used when comparing values within the entire group and unpaired non-parametric Mann-Whitney tests were used when comparing high and low dose levels. A p-value <0.05 was considered significant. Results: There were significant correlations between daily Gb dose, on the one hand, and, on the other, HbAl(c) (r=0.55), <Delta>-insulin (r=-0.59) and Delta -proinsulin (r=-0.52) levels. Significant correlations between Gb therapy duration and insulin (r=-0.40) and proinsulin (r=-0.34) secretion and between Gb dose and ratio proinsulin/insulin (RPI) at both time points (r=0.32 and 0.30) were also found. The RPI was lower after Gb intake. In patients on greater than or equal to 10.5 mg steady state serum metabolite levels (Ml and Ml + M2) were higher (29(0-120) and 33 (0-120) ng/ml) than those of Gb itself (18(0-64) ng/ml). A great inter-subject variability in Gb levels at both time points was seen. Conclusions: Our results indicate that, in patients on chronic medication, Gb is capable of stimulating both insulin and proinsulin secretion; the effect on insulin release is relatively greater. The effect was more pronounced in patients on a low Gb dose, either because of less impaired beta -cells in those receiving low doses, or due to reduced sulphonylurea sensitivity in those on high dosage (down-regulation). In patients on a daily dose of 10.5 mg or more, serum metabolite levels of clinical relevance were demonstrated; the metabolites may contribute to hypoglycaemic events. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1118542
- author
- Jönsson, A. ; Hallengren, Bengt LU ; Rydberg, T. and Melander, A.
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- sulphonylurea, insulin, proinsulin, glibenclamide, metabolites
- in
- Diabetes, Obesity and Metabolism
- volume
- 3
- issue
- 6
- pages
- 403 - 409
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000173051600003
- scopus:0035666448
- ISSN
- 1462-8902
- DOI
- 10.1046/j.1463-1326.2001.00152.x
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pediatrics/Urology/Gynecology/Endocrinology (013240400)
- id
- 3e39c7be-2963-417b-8fc3-24eabfa6cc99 (old id 1118542)
- date added to LUP
- 2016-04-01 12:31:54
- date last changed
- 2022-03-29 02:08:15
@article{3e39c7be-2963-417b-8fc3-24eabfa6cc99,
abstract = {{Objective: To study the effects and serum levels of glibenclamide (Gb) and its active metabolites in patients on chronic Gb medication on different daily doses. Material and methods: Fifty patients with type 2 diabetes on regular Gb therapy (1.75-14.0 mg daily). Blood samples were taken immediately before and 90 min after regular Gb intake. A standardized breakfast was served 30 min after drug intake. Serum insulin and proinsulin levels were determined by ELISA methods without cross-reactivities. Serum drug levels were determined by HPLC. Fischer's Rto Z-test (correlation coefficients) and paired Student t-tests were used when comparing values within the entire group and unpaired non-parametric Mann-Whitney tests were used when comparing high and low dose levels. A p-value <0.05 was considered significant. Results: There were significant correlations between daily Gb dose, on the one hand, and, on the other, HbAl(c) (r=0.55), <Delta>-insulin (r=-0.59) and Delta -proinsulin (r=-0.52) levels. Significant correlations between Gb therapy duration and insulin (r=-0.40) and proinsulin (r=-0.34) secretion and between Gb dose and ratio proinsulin/insulin (RPI) at both time points (r=0.32 and 0.30) were also found. The RPI was lower after Gb intake. In patients on greater than or equal to 10.5 mg steady state serum metabolite levels (Ml and Ml + M2) were higher (29(0-120) and 33 (0-120) ng/ml) than those of Gb itself (18(0-64) ng/ml). A great inter-subject variability in Gb levels at both time points was seen. Conclusions: Our results indicate that, in patients on chronic medication, Gb is capable of stimulating both insulin and proinsulin secretion; the effect on insulin release is relatively greater. The effect was more pronounced in patients on a low Gb dose, either because of less impaired beta -cells in those receiving low doses, or due to reduced sulphonylurea sensitivity in those on high dosage (down-regulation). In patients on a daily dose of 10.5 mg or more, serum metabolite levels of clinical relevance were demonstrated; the metabolites may contribute to hypoglycaemic events.}},
author = {{Jönsson, A. and Hallengren, Bengt and Rydberg, T. and Melander, A.}},
issn = {{1462-8902}},
keywords = {{sulphonylurea; insulin; proinsulin; glibenclamide; metabolites}},
language = {{eng}},
number = {{6}},
pages = {{403--409}},
publisher = {{Wiley-Blackwell}},
series = {{Diabetes, Obesity and Metabolism}},
title = {{Effects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetes}},
url = {{http://dx.doi.org/10.1046/j.1463-1326.2001.00152.x}},
doi = {{10.1046/j.1463-1326.2001.00152.x}},
volume = {{3}},
year = {{2001}},
}