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Effect of sitagliptin therapy on triglyceride‐rich lipoprotein kinetics in patients with type 2 diabetes
Author(s) -
Tremblay A. J.,
Lamarche B.,
Kelly I.,
Charest A.,
Lépine M.C.,
Droit A.,
Couture P.
Publication year - 2014
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 - 10.1111/dom.12359
Subject(s) - sitagliptin , medicine , endocrinology , apolipoprotein b , very low density lipoprotein , triglyceride , placebo , crossover study , type 2 diabetes , chemistry , cholesterol , lipoprotein , insulin , diabetes mellitus , alternative medicine , pathology
Aim To investigate the effects of sitagliptin therapy on the kinetics of triglyceride‐rich lipoprotein ( TRL ) apolipoprotein (apo)B‐48, VLDL apoB ‐100, apoE and apoC‐III in patients with type 2 diabetes. Methods Twenty‐two subjects with type 2 diabetes were recruited in this double‐blind crossover study, during which the subjects received sitagliptin (100 mg/day) or placebo for a 6‐week period each. At the end of each phase of treatment, the in vivo kinetics of the different apolipoproteins were assessed using a primed‐constant infusion of l ‐[5,5,5‐ D3 ]leucine for 12 h, with the participants in a constantly fed state. Results Sitagliptin therapy significantly reduced fasting plasma triglyceride (−15.4%, p = 0.03), apoB ‐48 (−16.3%, p = 0.03) and free fatty acid concentrations (−9.5%, p = 0.04), as well as plasma HbA1c (placebo: 7.0% ± 0.8 vs. sitagliptin: 6.6% ± 0.7, p < 0.0001) and plasma glucose levels (−13.5%, p = 0.001), without any significant effect on insulin levels. Kinetic results showed that treatment with sitagliptin significantly reduced the pool size of TRL apoB ‐48 by −20.8% (p = 0.03), paralleled by a reduction in the production rate of these particles (−16.0%, p = 0.03). The VLDL apoB ‐100 pool size was also significantly decreased by sitagliptin therapy (−9.3%, p = 0.03), mainly because of a reduction in the hepatic secretion of these lipoproteins, although this difference did not reach statistical significance (−9.2%, p = 0.06). Conclusions Treatment with sitagliptin for 6 weeks reduced triglyceride‐rich apoB ‐containing lipoprotein levels by reducing the synthesis of these particles.