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Effects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetes

Jönsson, A.; Hallengren, Bengt LU ; Rydberg, T. and Melander, A. (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)
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author
organization
publishing date
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
id
3e39c7be-2963-417b-8fc3-24eabfa6cc99 (old id 1118542)
date added to LUP
2008-07-01 09:52:47
date last changed
2018-01-07 06:19:16
@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 &lt;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), &lt;Delta&gt;-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},
  keyword      = {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},
  volume       = {3},
  year         = {2001},
}