SAT-842 - IGFBP-2 Reveals Ancestry-Related Differences in Metabolic Regulation in South Asians

IGFBP-2 Reveals Ancestry-Related Differences in Metabolic Regulation in South Asians

Background: South Asians (SA) have a higher burden of cardiometabolic disease at lower adiposity compared with Non-Hispanic White (NHW) adults. Insulin-like growth factor binding proteins (IGFBPs) are linked to metabolic regulation, but whether they reflect ancestry-specific differences independent of insulin resistance and adiposity is unclear.

Objective: To examine ancestry-specific associations of circulating IGFBP-1, IGFBP-2, and IGFBP-4 with metabolic and adiposity measures in SA and NHW adults.

Methods: We conducted a cross-sectional study of 113 healthy adults (55 SA, 58 NHW). Plasma IGFBP-1, IGFBP-2, and IGFBP-4 were measured by ELISA. Insulin resistance and sensitivity were assessed using HOMA-IR, QUICKI, and the NMR-derived lipoprotein insulin resistance (LPIR) index. Body composition was measured by dual-energy X-ray absorptiometry. Multivariable linear regression models were fit for log-transformed IGFBPs, adjusting for age, sex, C-peptide, LPIR, and percent body fat. Adjusted analyses were restricted to 85 participants with complete covariate data.

Results: IGFBP-1 and IGFBP-2 were inversely associated with fasting insulin (r = −0.58 to −0.63), C-peptide (r = −0.61 to −0.62), LPIR (r = −0.49 to −0.50), and adiposity (r = −0.25 to −0.29), and positively associated with insulin sensitivity (r = 0.54–0.69) (all p < 0.05). In contrast, IGFBP-4 was weakly inversely associated with fasting insulin (r = −0.19) and positively associated with adiposity (r = 0.35) and LPIR (r = 0.28). SA participants exhibited lower insulin sensitivity compared with NHW participants. Adjusted geometric mean IGFBP-2 levels were lower in SA compared with NHW participants (139.6 [95% CI, 122.4–159.3] vs. 172.2 [151.8–194.8] ng/mL; p = 0.027). Adjusted IGFBP-1 and IGFBP-4 levels did not differ between groups. No sex-by-ancestry interactions were observed.

Conclusion: IGFBP-2 is lower in South Asians compared with Non-Hispanic Whites independent of adiposity and metabolic factors, whereas IGFBP-1 and IGFBP-4 do not differ after adjustment. These findings suggest that IGFBP-2 may reflect ancestry-related variation in metabolic or IGF-axis regulation not captured by conventional measures.

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