(VP102) SOUTH ASIAN INDIVIDUALS WITH TYPE 2 DIABETES HAVE LESS VASCULAR REGENERATIVE CELL CONTENT

Background: People of South Asian origin have 1.5-fold higher cardiovascular risk and 3-5-fold increased rates of type 2 diabetes (T2D) compared to white European individuals. We previously established that people living with T2D exhibit vascular regenerative cell exhaustion (VRCE), defined as the depletion of pro-vascular cell subsets that coordinate vessel repair mechanisms. We also found that the frequency of ALDHhiSSClow cells (primitive hematopoietic and endothelial progenitor cells that coordinate new vessel regeneration) in people living with T2D was 2-fold lower than in those without T2D. We postulated that the excess cardiometabolic burden shouldered by South Asian individuals may be attributed, in part, to differences in the VRCE profile.

METHODS AND RESULTS: We assessed the frequencies of circulating vascular regenerative cells in 55 South Asian and 37 white European individuals ≥40 years of age with T2D. We used a flow cytometry assay that detects blood cells with high aldehyde dehydrogenase-activity (ALDHhi), an antioxidant enzyme that is highly expressed in pro-vascular progenitor cells. South Asian participants, compared to the white European individuals, were younger (65.8 vs 70.0 years), had shorter durations of T2D (9.71 vs 14.5 years), and were of lower weight (74.7 vs 91.9 kg) and BMI (27.3 vs 30.3 kg/m2; all P< 0.05). Despite these beneficial metrics, vascular regenerative cell content in South Asian adults was severely compromised. The frequency of circulating ALDHhiSSClow cells co-expressing the primitive cell marker CD133 was lower in South Asian vs white European individuals (51.4 vs 58.9%, P< 0.01). The frequency of ALDHhiSSCmid cells which represent monocytes that promote vessel repair over inflammatory functions was also lower in South Asian vs white European individuals (4.44 vs 6.29%, P< 0.05), as was that for ALDHhiSSCmid cells with vessel regenerative (CD163+) polarization (83.6 vs 89.0%, P< 0.01). No between-group difference was observed for the frequency of ALDHhiSSChi granulocyte precursors, indicating that inflammatory granulocyte cell burden was comparable between South Asian and white European participants.

Conclusion: These data document significant VRCE in South Asian adults with T2D and suggest that impaired blood vessel repair may contribute to the elevated cardiometabolic risk profile of people of South Asian origin.