Bedtime NPH Insulin and DPP-4 Enzyme Inhibitor (sitagliptin) Increase Cholesterol Removal from Macrophages

Introduction and Objective: Cardiovascular disease is largely linked to hyperglycemia and alterations in lipoprotein functions. We evaluated the effect of treatment with bedtime NPH insulin or sitagliptin on cholesterol efflux from patients with T2DM. Methods: Thirty-two patients with T2DM, inadequately controlled with metformin and glibenclamide were randomly assigned to 6-month complementary treatment with bedtime NPH insulin or sitagliptin. At baseline and after treatments, glucose, C-peptide, free fatty acids (FFA), and triglycerides were determined at fasting and 2 hours after a meal, besides fasting lipid and HbA1c levels. Serum ApoB-rich lipoproteins (VLDL and LDL) were precipitated by dextran sulfate/magnesium chloride. Macrophages enriched with acetylated LDL and 14C-cholesterol were incubated with serum containing only HDL (2%) for 4 h to determine cholesterol efflux (n=4). Control incubations were performed with culture medium only, without serum. Analyses used Student's t-test and Pearson's correlation. Results: The sitagliptin (n=16) and bedtime NPH insulin (n=16) groups did not differ in age, body mass index, diabetes duration, plasma glucose, Triglycerides, FFA and C-peptide concentrations (before and 2 h after a meal). There was a similar reduction in HbA1c in both groups. Cholesterol levels did not change. The 14C-cholesterol efflux increased in both groups, after 6-month treatment (14.08 ± 1.93 vs. 15.74 ± 2.67% in the NPH group and 14.80 ± 1.37 vs. 15.79 ± 1.40% in the sitagliptin group, P<0.05). There was no difference in the % of cholesterol efflux between groups. A negative correlation was observed between the % of cholesterol efflux and the plasma concentration of FFA in both groups (r= -0.345; p=0.0053). Conclusion: six-month treatment with NPH insulin or sitagliptin increased the capacity of apoB-depleted serum to mediate the removal of cholesterol from macrophages, which may contribute to the prevention of cardiovascular disease in DM. Supported by FAPESP, FMUSP, CNPq Disclosure: A.S. Santos: None. M.S. Santana: None. P.S. Takakura: None. D. Ribeiro: None. M. Correa-Giannella: None. M. Passarelli: None. M. Rossi: None. Funding: Sao Paulo Research Foundation FAPESP(2022/16441-5); Faculty of Medicine of the University of S?o Paulo3-CNPQ- National Council for Scientific and Technological Development