Relationship between Diabetes Mellitus and Serum Lathosterol and Campesterol Levels: The CACHE Study DM Analysis

J Atheroscler Thromb. 2023 Jul 1;30(7):735-753. doi: 10.5551/jat.63725. Epub 2022 Sep 29.

Abstract

Aim: Risk of cardiovascular disease is increased in patients with diabetes mellitus (DM). Cholesterol metabolism (hepatic synthesis and intestinal absorption) is known to be associated with cardiovascular risk. Next, we examined the association of DM with cholesterol absorption/synthesis.

Methods: The CACHE Consortium, which is comprised of 13 research groups in Japan possessing data of lathosterol (Latho, synthesis marker) and campesterol (Campe, absorption marker) measured by gas chromatography, compiled the clinical data using the REDCap system. Among the 3597 records, data from 2944 individuals were used for several analyses including this study.

Results: This study analyzed data from eligible 2182 individuals including 830 patients with DM; 42.2% were female, median age was 59 years, and median HbA1c of patients with DM was 7.0%. There was no difference in Latho between DM and non-DM individuals. Campe and Campe/Latho ratio were significantly lower in DM individuals than in non-DM individuals. When the associations of glycemic control markers with these markers were analyzed with multivariable-adjusted regression model using restricted cubic splines, Campe and Campe/Latho ratio showed inverse associations with glucose levels and HbA1c. However, Latho showed an inverted U-shaped association with plasma glucose, whereas Latho showed a U-shaped association with HbA1c. These associations remained even after excluding statin and/or ezetimibe users.

Conclusion: We demonstrated that DM and hyperglycemia were independent factors for lower cholesterol absorption marker levels regardless of statin/ezetimibe use.

Keywords: Campesterol; Cholesterol metabolism; Diabetes; Glycemic control; Lathosterol.

MeSH terms

  • Biomarkers
  • Cholesterol
  • Diabetes Mellitus*
  • Ezetimibe
  • Female
  • Glycated Hemoglobin
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Male
  • Middle Aged
  • Phytosterols*

Substances

  • lathosterol
  • campesterol
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Glycated Hemoglobin
  • Cholesterol
  • Phytosterols
  • Ezetimibe
  • Biomarkers