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
Khoo Teck Puat Hospital1, Admiralty Medical Centre2
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.
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.
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).
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.