HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control

Cardiovasc Diabetol. 2022 Aug 12;21(1):154. doi: 10.1186/s12933-022-01591-9.

Abstract

Background: Reduced cholesterol efflux capacity (CEC) of HDLs is likely to increase cardiovascular risk in type 1 diabetes (T1D). We aimed to assess whether improvement of glycemic control in T1D patients is associated with changes in CEC in relation with changes in carbamylation of HDLs.

Methods: In this open-label trial, 27 uncontrolled T1D patients were given a three-month standard medical intervention to improve glycemic control. HDL fraction was isolated from plasma, and CEC was measured on THP-1 macrophages. Carbamylation of HDLs was evaluated by an immunoassay. Control HDLs from healthy subjects were carbamylated in vitro with potassium cyanate.

Results: HbA1c decreased from 11.4% [10.2-12.9] (median [1st-3rd quartiles]) at baseline to 8.1% [6.6-9.0] after the three-month intervention (P < 0.00001). The CEC of HDLs increased after intervention in 19 (70%) patients (P = 0.038). At the same time, the carbamylation of HDLs decreased in 22 (82%) patients after intervention (P = 0.014). The increase in CEC significantly correlated with the decrease in carbamylated HDLs (r = -0.411, P = 0.034), even after adjustment for the change in HbA1c (β = -0.527, P = 0.003). In vitro carbamylation of control HDLs decreased CEC by 13% (P = 0.041) and 23% (P = 0.021) using 1 and 10 mmol/L of potassium cyanate, respectively.

Conclusions: The improvement of CEC in relation to a decrease in the carbamylation of HDLs may likely contribute to the beneficial cardiovascular effect of glycemic control in T1D patients.

Trial registration: NCT02816099 ClinicalTrials.gov.

Keywords: Carbamylation; Cholesterol efflux; HDL; Type 1 diabetes.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholesterol, HDL
  • Diabetes Mellitus, Type 1* / diagnosis
  • Diabetes Mellitus, Type 1* / drug therapy
  • Glycemic Control
  • Humans
  • Lipoproteins, HDL
  • Protein Carbamylation

Substances

  • Cholesterol, HDL
  • Lipoproteins, HDL

Associated data

  • ClinicalTrials.gov/NCT02816099