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Background & Aim
Metabolic abnormalities in type 2 diabetes affect the production and the clearance of plasma lipoproteins. Although the improvement of low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol levels are important targets in diabetes, it is not established how changes occur in the production and clearance of plasma lipoproteins in the treatment of diabetes. Serum non-cholesterol sterols are introduced as practical markers to assess endogenous cholesterol synthesis and intestinal cholesterol absorption. This study aimed to investigate the effects of insulin therapy on cholesterol synthesis and absorption markers in patients with type 2 diabetes.
This was a single-center, prospective, 2-week, longitudinal pilot study. Patients with type 2 diabetes who were admitted to start insulin therapy without using lipid-lowering agents were recruited. On the day of hospitalization, the patients discontinued all oral hypoglycemic agents and started with basal-bolus insulin therapy. Cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) markers were assessed at baseline and after 2 weeks of insulin treatment.
In eighteen subjects, the mean age of the patients was 56 ± 10 years (mean ± SD). At baseline, body mass index was 24.3 ± 5.0 kg/m2, and HbA1c was 11.6 ± 1.7%. After 2 weeks of insulin therapy, total cholesterol (from 205 ± 48 to 184 ± 43 mg/dL, p = 0.004), lathosterol (from 2.6 ± 1.3 to 2.0 ± 0.7 μg/mL, p = 0.001), campesterol (from 4.3 ± 2.7 to 3.0 ± 2.1 μg/mL, p < 0.0001), and sitosterol (from 2.4 ± 1.6 to 1.7 ± 1.4 μg/mL, p < 0.0001) were significantly decreased, and cholestanol (from 2.5 ± 1.0 to 2.3 ± 0.8 μg/mL, p = 0.05) tended to decrease.
This study showed that insulin therapy reduces cholesterol synthesis and absorption markers in patients with type 2 diabetes hospitalized within 2 weeks. The decrease in cholesterol synthesis and absorption seems to be useful for improving lipid metabolism and reducing the risk of atherosclerosis. Further randomized controlled studies are required to confirm the efficacy of insulin therapy for cholesterol synthesis and absorption markers.
Abbreviation:Niemann-Pick C1-Like 1 ((NPC1L1)), estimated glomerular filtration rate ((eGFR)), standard deviation ((SD)), interquartile range ((IQR)), waist circumference ((WC)), blood pressure ((BP)), Fasting plasma glucose ((FPG)), Glycated hemoglobin ((HbA1c)), Glycated albumin ((GA)), Serum C-peptide immunoreactivity ((S-CPR)), urinary C-peptide immunoreactivity ((U-CPR)), Immunoreactive insulin ((IRI)), Urinary albumin ((U-Alb)), Lipoprotein lipase ((LPL)), Apolipoprotein ((Apo)), body mass index ((BMI)), sterol regulatory element binding protein-2 ((SREBP-2)), hydroxymethylglutaryl-CoA ((HMG-CoA)), liver X receptor ((LXR)), ATP-binding cassette sub-family G member 5/8 ((ABCG5/G8))
Accepted: March 3, 2023
Received in revised form: February 22, 2023
Received: September 11, 2022
Publication stageIn Press Accepted Manuscript
© 2023 The Authors. Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.
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