The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes

Cardiovascular Diabetology

Original Investigation

Trevor J. Orchard¹  Tibor Ivanyi²  Caryl J. Antalis³  Shuyu Zhang³  Byron J. Hoogwerf³  Margery A. Connelly⁴  James D. Otvos⁴  Bertrand Cariou⁵ 

[1] Department of Epidemiology, GSPH, University of Pittsburgh, Pittsburgh, PA, USA;Eli Lilly and Company, 1075, Budapest, Hungary;Eli Lilly and Company, Lilly Corporate Center, 46285, Indianapolis, IN, USA;LipoScience, Laboratory Corporation of America Holdings, 27560, Morrisville, NC, USA;l’Institut du Thorax, CHU Nantes INSERM, CNRS, UNIV Nantes, Nantes, France;

关键词: Diabetes;    Basal insulin peglispro;    Insulin glargine;    Lipoproteins;    NMR;    Apolipoproteins;    Liver fat;    MRI;    Adiponectin;   

DOI  :  10.1186/s12933-017-0555-1

 received in 2017-03-06, accepted in 2017-05-26,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundIn Phase 2/3 studies of basal insulin peglispro (BIL) compared to insulin glargine, patients with type 1 or type 2 diabetes previously treated with insulin and randomized to BIL had an increase in serum triglycerides (TGs). To further understand lipoprotein changes, a lipid substudy which included liver fat content was designed to assess relationships among the measured variables for each diabetes cohort and compare the hepato-preferential insulin BIL to glargine.MethodsIn three cohorts of patients with diabetes (type 1, type 2 insulin naïve, and type 2 previously on insulin; n = 652), liver fat content (LFC) was determined by magnetic resonance imaging (MRI) and blood lipids were analyzed by nuclear magnetic resonance (NMR) spectroscopy at baseline, 26 and 52 weeks of treatment. Apolipoproteins, adiponectin, and other lipid parameters were also measured. Descriptive statistics were done, as well as correlation analyses to look for relationships among LFC and lipoproteins or other lipid measures.ResultsIn patients with type 1 diabetes treated with BIL, but not glargine, small LDL and medium and large VLDL subclass concentrations increased from baseline. In patients with type 2 diabetes previously on insulin and treated with BIL, large VLDL concentration increased from baseline. In insulin naïve patients with type 2 diabetes treated with BIL, there were very few changes, while in those treated with glargine, small LDL and large VLDL decreased from baseline. Baseline LFC correlated significantly in one or more cohorts with baseline large VLDL, small LDL, VLDL size, and Apo C3. Changes in LFC by treatment showed generally weak correlations with lipoprotein changes, except for positive correlations with large VLDL and VLDL size. Adiponectin was higher in patients with type 1 diabetes compared to patients with type 2 diabetes, but decreased with treatment with both BIL and glargine.ConclusionsThe lipoprotein changes were in line with the observed changes in serum TGs; i.e., the cohorts experiencing increased TGs and LFC with BIL treatment had decreased LDL size and increased VLDL size. These data and analyses add to the currently available information on the metabolic effects of insulins in a very carefully characterized cohort of patients with diabetes.Clinicaltrials.gov registration numbers and dates NCT01481779 (2011), NCT01435616 (2011), NCT01454284 (2011), NCT01582451 (2012)

【 授权许可】

CC BY   
© The Author(s) 2017