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Enhanced Macrophage Cholesterol Efflux Capacity in Middle-Aged Adults with Childhood-Onset Type 1 Diabetes: A Cross-Sectional Analysis

Mead, Charles (2021) Enhanced Macrophage Cholesterol Efflux Capacity in Middle-Aged Adults with Childhood-Onset Type 1 Diabetes: A Cross-Sectional Analysis. Master Essay, University of Pittsburgh.

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Abstract

Background
Individual s with type 1 diabetes (T1D) exhibit higher rates of coronary artery disease (CAD) compared with the general population, despite higher concentrations of the cardioprotective HDL-C, thus we hypothesized that HDL may not be a good indicator of HDL function. This study assessed differences in novel markers of HDL particle concentration (HDL-P) and macrophage cholesterol efflux capacity (CEC) between middle-aged adults with childhood-onset T1D and controls with normal glucose tolerance (NGT).
Methods
HDL-P and CEC were determined among 187 individuals with T1D (mean age 51 years, T1D duration 43 years, 52% women) and 200 controls of similar demographic distribution. As a larger number of those with T1D (n=44) had CAD compared to controls (n=4), analyses were restricted to individuals free of CAD to assure more comparable groups. HDL-P and macrophage CEC were quantified by calibrated ion mobility analysis and a validated cell-based assay, respectively. Descriptive analyses were conducted to assess differences by sex and T1D status, as well as the relationships of the novel HDL markers. Separate multivariable linear regression models were constructed for each novel HDL marker to evaluate whether T1D status was an independent correlate. The presence of effect modification by sex was also assessed.
Results
Individuals with T1D and women (regardless T1D status) exhibited favorable traditional lipid profiles. Significant sex differences (regardless T1D status) were also detected in total HDL-P (higher in women) and the four major HDL subpopulations – extra-small (higher in men), small (higher in men), medium (higher in women), and large (higher in women), although concentrations were similar by T1D status. Total macrophage CEC was higher in those with T1D (all p<0.01). T1D was associated with a 1.06 μmol/L lower M-HDL-P concentrations but 0.39 μmol/L higher L-HDL-P concentrations and 0.26% higher total macrophage CEC compared to NGT (p=<0.01), after sex and HDL-C adjustment.
Conclusion
In this case-control study of middle-aged adults free of CAD, individuals with childhood-onset T1D had lower concentrations of M-HDL-P but higher levels of L-HDL-P and total macrophage CEC. Further research is needed to contextualize these findings and expand upon the public health implications of HDL dysfunction.


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Details

Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Mead, Charleschm202@pitt.educhm2020000-0001-9184-6420
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
Thesis advisorCostacou, Tinacostacou@pitt.educostacouUNSPECIFIED
Committee MemberYouk, Ada Oayouk@pitt.eduayoukUNSPECIFIED
Committee MemberSonger, Thomastjs@pitt.edutjsUNSPECIFIED
Date: 17 December 2021
Date Type: Completion
Submission Date: 10 December 2021
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 47
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Uncontrolled Keywords: Type 1 diabetes, Coronary Artery Disease, HDL, CEC
Date Deposited: 06 Jan 2022 14:10
Last Modified: 06 Jan 2022 14:10
URI: http://d-scholarship.pitt.edu/id/eprint/42066

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