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Effects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetes
Author(s) -
Jönsson A.,
Hallengren B.,
Rydberg T.,
Melander A.
Publication year - 2001
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1046/j.1463-1326.2001.00152.x
Subject(s) - glibenclamide , proinsulin , insulin , metabolite , medicine , endocrinology , diabetes mellitus , type 2 diabetes , chemistry
SUMMARYObjective 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 R to 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), Δ‐insulin ( r = − 0.59) and Δ‐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 ≥ 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 β‐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.