Abstract
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Abstract
Year 2021
October 2021

SHBC1495

Abstract Title
Association of plasma hypoxia-inducible factor-1 alpha with type 2 diabetes in individuals with severe obesity
Authors

B.PANDIAN1, A.MOH1, C.H.TAN1, A.CHENG1, B.C.TAN1, D. NG1, B.K. LIM1, M. ANG1, S.LOW1, C.F.SUM2, T.SUBRAMANIAM1, S.C.LIM1

Institutions

Khoo Teck Puat Hospital1, Admiralty Medical Centre2

Background & Hypothesis

Obesity and type 2 diabetes (T2D) are frequently linked to hypoxia. Cellular response to hypoxia is regulated by hypoxia-inducible factor (HIF)-1α, which is known to induce the expression of target genes involved in diverse physiological and pathological processes. The role of hyperglycemia in the regulation of HIF-1α expression and activity? remains controversial. This cross-sectional study aimed to evaluate the association between plasma HIF-1α and T2D in people with severe obesity.

Methods

The cohort involved adults with severe obesity recruited at the Khoo Teck Puat Hospital (N=252, age:45±8 years, 38% men, body mass index:41.1±6.5kg/m2). Plasma HIF-1α levels were measured by immunoassay. Spearman’s correlation and modified Poisson regression analysis were used to evaluate the relationship of HIF-1α with HbA1c and T2D, respectively.

Results

Fifty-two percent (N=131) of the subjects had T2D. A positive correlation was observed between HIF-1α and HbA1c (rho=0.295, P=<0.001). Individuals with T2D displayed higher median HIF-1α levels compared with their non-T2D counterparts [207.1 (interquartile range:180.4−246.1) vs 155.1 (interquartile range:132.0−189.6) pg/ml; P<0.001)]. The association between natural log-transformed HIF-1a and T2D (outcome) remained significant after adjustment for age, gender, body mass index and HbA1c (risk ratio:2.63, 95% CI:1.85−3.74, P<0.001).

Discussion & Conclusion

To our knowledge, this is the first study to demonstrate an association between circulating HIF-1α and T2D in people with severe obesity. Our data suggest that hyperglycemia may result in the accumulation of HIF-1α protein, which could, in turn, contribute to the development of T2D-associated complications. Hence, inhibition of HIF-1α expression may exert beneficial effects on T2D and its complications.

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