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Effects and serum l...
Effects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetes
- Artikel/kapitelEngelska2001
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LIBRIS-ID:oai:lup.lub.lu.se:3e39c7be-2963-417b-8fc3-24eabfa6cc99
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https://lup.lub.lu.se/record/1118542URI
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https://doi.org/10.1046/j.1463-1326.2001.00152.xDOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
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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), -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.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Hallengren, BengtLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine(Swepub:lu)endo-bha
(författare)
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Rydberg, T.
(författare)
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Melander, A.
(författare)
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Institutionen för kliniska vetenskaper, MalmöMedicinska fakulteten
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Diabetes, Obesity and Metabolism: Wiley3:6, s. 403-4091462-8902
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