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Levels of the soluble LDL receptor-relative LR11 decrease in overweight individuals with type 2 diabetes upon diet-induced weight loss

  • Author Footnotes
    1 These authors contributed equally to this work.
    Kirsten A. Berk
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Internal Medicine, Section Pharmacology Vascular and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands

    Department of Psychiatry, Unit of Medical Psychology and Psychotherapy, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Ranitha Vongpromek
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Internal Medicine, Section Pharmacology Vascular and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Meizi Jiang
    Affiliations
    Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University, Sakura Medical Center, Sakura, Japan
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  • Wolfgang J. Schneider
    Affiliations
    Department of Medical Biochemistry, Medical University of Vienna, Max. F. Perutz Laboratories, Vienna, Austria
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  • Reinier Timman
    Affiliations
    Department of Psychiatry, Unit of Medical Psychology and Psychotherapy, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Adrie J.M. Verhoeven
    Affiliations
    Department of Internal Medicine, Section Pharmacology Vascular and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Hideaki Bujo
    Affiliations
    Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University, Sakura Medical Center, Sakura, Japan
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  • Eric J.G. Sijbrands
    Affiliations
    Department of Internal Medicine, Section Pharmacology Vascular and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Monique T. Mulder
    Correspondence
    Corresponding author. Laboratory of Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Office Ee800, PO-Box 2040, 3000 CA Rotterdam, The Netherlands.
    Affiliations
    Department of Internal Medicine, Section Pharmacology Vascular and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • sLR11 is associated with increased cardiovascular disease (CVD) risk and vascular complications in type 2 diabetes (T2D).
      • Diet-induced weight loss reduced sLR11 levels in overweight and obese T2D patients.
      • The drop in sLR11 was linked to beneficial effects on non-HDL cholesterol and HbA1c.
      • This may contribute to the mechanism by which diet modulates CVD risk.

      Abstract

      Background and aims

      Cardiovascular disease (CVD) is a major complication in patients with type 2 diabetes (T2D), especially in those with obesity. Plasma soluble low density lipoprotein receptor-relative with 11 ligand-binding repeats (sLR11) plays a role in the development of atherosclerosis and has been linked to the metabolism of triglyceride-rich lipoproteins, adiposity, and vascular complications in T2D. We aimed to determine the effect of diet-induced weight loss on plasma sLR11 levels in overweight and obese individuals with T2D.

      Methods

      Plasma sLR11 levels were determined in 64 individuals with T2D and BMI >27 kg/m2 before and after a 20-week weight loss diet. As a reference, sLR11 levels were also determined in 64 healthy, non-obese controls, matched as a group for age and sex.

      Results

      Median plasma sLR11 levels of the T2D study-group at baseline (15.4 ng/mL (IQR 12.9–19.5)) were higher than in controls (10.2 (IQR: 8.7–12.2) ng/mL; p = 0.001). The diet resulted in a weight loss of 9.7 ± 5.2% (p = 0.001) and improved CVD risk factors. sLR11 levels were reduced to 13.3 ng/mL (IQR 11.0–17.1; p = 0.001). Changes in sLR11 levels positively associated with changes in non-HDL cholesterol (B = 1.54, R2 = 0.17, p = 0.001) and HbA1c (B = 0.07, R2 = 0.11, p = 0.007), but not with weight loss (B = 0.04, R2 = 0.05, p = 0.076). The changes in non-HDL cholesterol and HbA1c together explained 24% of the variance of sLR11 reduction (p = 0.001).

      Conclusions

      Weight loss dieting in overweight and obese individuals with T2D resulted in a reduction in plasma sLR11 levels that was associated with improvements in lipid-profile and glycemic state.

      Keywords

      Abbreviations:

      ApoB (apolipoprotein B), BAT (brown adipose tissue), BMI (Body Mass Index), CVD (cardiovascular disease), HbA1c (glycated hemoglobin), HDL (high density lipoprotein), GLP-1 (glucagon-like peptide-1), GLUT4 (glucose transporter 4), LDL (low density lipoprotein), sLR11 (soluble low density lipoprotein receptor-relative with 11 ligand-binding repeats), T2D (diabetes mellitus type 2), TGRL (triglyceride-rich lipoproteins), WAT (white adipose tissue)
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