Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in blood levels of 3-deoxyglucosone in nonobese patients with type 2 diabetes
(2011) In European Journal of Endocrinology 164(3). p.371-379- Abstract
- Objective: Metformin has been reported to reduce alpha-dicarbonyls, which are known to contribute to diabetic complications. It is unclear whether this is due to direct quenching of alpha-dicarbonyls or to an improvement in glycemic control. We therefore compared the effects of metformin versus repaglinide, an antihyperglycemic agent with an insulin-secreting mechanism, on the levels of the alpha-dicarbonyl 3-deoxyglucosone (3DG). Methods: We conducted a single-center, double-masked, double-dummy, crossover study involving 96 nonobese patients with type 2 diabetes. After a 1-month run-in on diet-only treatment, patients were randomized to either repaglinide (6 mg daily) followed by metformin (2 g daily) or vice versa each during 4 months... (More)
- Objective: Metformin has been reported to reduce alpha-dicarbonyls, which are known to contribute to diabetic complications. It is unclear whether this is due to direct quenching of alpha-dicarbonyls or to an improvement in glycemic control. We therefore compared the effects of metformin versus repaglinide, an antihyperglycemic agent with an insulin-secreting mechanism, on the levels of the alpha-dicarbonyl 3-deoxyglucosone (3DG). Methods: We conducted a single-center, double-masked, double-dummy, crossover study involving 96 nonobese patients with type 2 diabetes. After a 1-month run-in on diet-only treatment, patients were randomized to either repaglinide (6 mg daily) followed by metformin (2 g daily) or vice versa each during 4 months with a 1-month washout between interventions. Results: 3DG levels decreased after both metformin (-19.3% (95% confidence interval (CI): -23.5, -14.8)) and repaglinide (-20.8% (95% CI: -24.9, -16.3)) treatments, but no difference was found between treatments (1.8% (95% CI: -3.8, 7.8)). Regardless of the treatment, changes in glycemic variables were associated with changes in 3DG. Specifically, 3DG decreased by 22.7% (95% CI: 19.0, 26.5) per S. D. decrease in fasting plasma glucose (PG), by 20.0% (95% CI: 16.2, 23.9) per S. D. decrease in seven-point mean plasma glucose, by 22.5% (95% CI: 18.6, 26.6) per S. D. decrease in area under the curve for PG, by 17.2% (95% CI: 13.8, 20.6) per S. D. decrease in HbAlc, and by 10.9% (95% CI: 6.4, 15.5) per S. D. decrease in Amadori albumin. In addition, decreases in 3DG were associated with decreases in advanced glycation endproducts and endothelial markers. Conclusion: Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in 3DG levels in nonobese individuals with type 2 diabetes. This may constitute a shared metabolic pathway through which both treatments have a beneficial impact on the cardiovascular risk. (Less)
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- author
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Endocrinology
- volume
- 164
- issue
- 3
- pages
- 371 - 379
- publisher
- Society of the European Journal of Endocrinology
- external identifiers
-
- wos:000287969100008
- scopus:79951971683
- pmid:21205874
- ISSN
- 1479-683X
- DOI
- 10.1530/EJE-10-0851
- language
- English
- LU publication?
- yes
- id
- e988b1af-3df1-485c-8754-50a7b612a969 (old id 1869787)
- date added to LUP
- 2016-04-01 10:51:29
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- 2024-01-07 02:50:17
@article{e988b1af-3df1-485c-8754-50a7b612a969, abstract = {{Objective: Metformin has been reported to reduce alpha-dicarbonyls, which are known to contribute to diabetic complications. It is unclear whether this is due to direct quenching of alpha-dicarbonyls or to an improvement in glycemic control. We therefore compared the effects of metformin versus repaglinide, an antihyperglycemic agent with an insulin-secreting mechanism, on the levels of the alpha-dicarbonyl 3-deoxyglucosone (3DG). Methods: We conducted a single-center, double-masked, double-dummy, crossover study involving 96 nonobese patients with type 2 diabetes. After a 1-month run-in on diet-only treatment, patients were randomized to either repaglinide (6 mg daily) followed by metformin (2 g daily) or vice versa each during 4 months with a 1-month washout between interventions. Results: 3DG levels decreased after both metformin (-19.3% (95% confidence interval (CI): -23.5, -14.8)) and repaglinide (-20.8% (95% CI: -24.9, -16.3)) treatments, but no difference was found between treatments (1.8% (95% CI: -3.8, 7.8)). Regardless of the treatment, changes in glycemic variables were associated with changes in 3DG. Specifically, 3DG decreased by 22.7% (95% CI: 19.0, 26.5) per S. D. decrease in fasting plasma glucose (PG), by 20.0% (95% CI: 16.2, 23.9) per S. D. decrease in seven-point mean plasma glucose, by 22.5% (95% CI: 18.6, 26.6) per S. D. decrease in area under the curve for PG, by 17.2% (95% CI: 13.8, 20.6) per S. D. decrease in HbAlc, and by 10.9% (95% CI: 6.4, 15.5) per S. D. decrease in Amadori albumin. In addition, decreases in 3DG were associated with decreases in advanced glycation endproducts and endothelial markers. Conclusion: Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in 3DG levels in nonobese individuals with type 2 diabetes. This may constitute a shared metabolic pathway through which both treatments have a beneficial impact on the cardiovascular risk.}}, author = {{Engelen, Lian and Lund, Soren S. and Ferreira, Isabel and Tarnow, Lise and Parving, Hans-Henrik and Gram, Jorgen and Winther, Kaj and Pedersen, Oluf and Teerlink, Tom and Barto, Rob and Stehouwer, Coen D. A. and Vaag, Allan and Schalkwijk, Casper G.}}, issn = {{1479-683X}}, language = {{eng}}, number = {{3}}, pages = {{371--379}}, publisher = {{Society of the European Journal of Endocrinology}}, series = {{European Journal of Endocrinology}}, title = {{Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in blood levels of 3-deoxyglucosone in nonobese patients with type 2 diabetes}}, url = {{http://dx.doi.org/10.1530/EJE-10-0851}}, doi = {{10.1530/EJE-10-0851}}, volume = {{164}}, year = {{2011}}, }