Proteomic Alterations of HDL in Youth with Type 1 Diabetes: Outstanding Research at the Symposium

At the 2019 MedStar Health-Georgetown University Research Symposium, three abstracts were recognized as outstanding abstracts from among all of our submissions. These research studies were the three highest scored out of the over 450 submissions to the Research Symposium by the Scientific Review committee and exemplifies the caliber of work presented by the MedStar-Georgetown research community.

“Proteomic Alterations of HDL in Youth with Type 1 Diabetes and their Associations with Glycemic Control: A Case-Control Study” presented a cross-sectional case-control study, comparing the high-density lipoprotein (HDL) cholesterol proteomes of youth with type 1 diabetes and healthy controls. It sought to evaluate the influence of glycemic control on HDL protein composition.

Led by Jenny (Evgenia) Gourgari, MD, the research team included Junfeng Ma, PhD; Martin Playford, PhD; Nehal Mehta, MD; Radoslav Goldman, PhD; Alan Remaley, MD, PhD; and Scott Gordon. This research was presented in the basic/translational science category.

Patients with type 1 diabetes typically have normal or even elevated plasma HDL cholesterol concentrations. However, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles which reduced the ability of the body to protect against cardiovascular disease.

Blood samples were obtained from 26 patients with type 1 diabetes and 13 healthy controls. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification.

The samples were analyzed and 78 HDL-bound proteins were measured. The results showed that youth with type 1 diabetes had significantly increased amounts of complement factor H related protein compared to the healthy controls. When patients were analyzed based on glucose control, several trends emerged. Some proteins were altered in type 1 diabetes and not influenced by glycemic control, while others were partially or completely corrected with optimal glucose control. Some proteins including complement component C3  and albumin were significantly different only in type 1 diabetes patients with optimal glucose control, suggesting a possible effect of exogenous insulin.

The research concluded that youth with type 1 diabetes have proteomic alterations of their HDL compared to healthy controls, despite a similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known.

The authors suggested that future efforts should focus on investigating further the role of these HDL associated proteins in regards to HDL function and their role in cardiovascular disease risk in patients with type 1 diabetes. 

Congratulations to the research team for their outstanding research! You can read about the other winners here and here.