THU269 Ethnic Differences In Hepatic Insulin Clearance: A Cross-Sectional Study Comparing South Asians And Non-Hispanic Whites

Disclosure: A.L. Ramanathan: None. H. Fan: None. R. Muniyappa: None. Background: Hepatic insulin clearance homeostaticallyregulates peripheral plasma insulin concentration. Reduced or impaired insulinclearance promotes insulin resistance and hyperinsulinemia, which increase therisk of type 2 diabetes mellitus (T2DM). South Asians (SA) have an elevatedrisk and prevalence of T2DM compared to other ethnic groups, but insulinclearance by ethnicity has not yet been investigated. Our cross-sectional studyexamines insulin clearance in SA compared to non-Hispanic whites (NHW) todetermine ethnic differences in hepatic extraction in both the fasting andpostprandial states. Methods: Thirty healthy SA (age: 39.1 ± 9.4; female: n=12;BMI: 27.7 ± 4.8 kg/m(2)) and thirty healthy NHW (age: 39.2 ± 11.4;female: n=12; BMI: 26.7 ± 5.3 kg/m(2)) underwent mixed meal tolerancetests (MMTT) to determine plasma glucose, insulin, and C-peptide levels. Wederived parameters of hepatic clearance using a C-peptide kinetics model, aninsulin secretion model, and an insulin kinetics three-compartmental model. Model parameters included distribution volume of insulin (Vp), control ofplasma glucose on hepatic extraction (aG), basal hepatic extraction levels(HEb), and total hepatic extraction levels (HEtot). Differences by ethnicity werecalculated using an unpaired t-test for parametric variables and a Mann-Whitneytest for nonparametric data. Results: Fasting glucose (93.7 ± 9.77 vs. 89.0 ± 6.96 mg/dL,p=0.06) and fasting insulin (13.30 ± 8.04 vs. 6.58 ± 6.61 mu/mL, p<0.001)were higher in SA. Insulin area under the curve during MMTT was also elevatedin SA (12608 ± 6031 vs. 5892 ± 3533 min*mU/mL, p<0.001). Calculated mean Vp(0.0365 ± 0.0133 vs. 0.0564 ± 0.0130 kg(-1), p<0.0001), mean aG(0.2001 ± 0.0409 vs. 0.2285 ± 0.0556 mmol(-1), p=0.03), and basalhepatic extraction (54.9 ± 22.6 vs. 65.6 ± 18.8%, p=0.04) were lower in SA.Total hepatic extraction during MMTT was not different between SA and NHW(p=0.33). Conclusions: SA have reduced basal hepatic clearancecompared to NHW, although total extraction remained similar between the twogroups during MMTT. Further investigations are needed to derive accurateinsulin clearance parameters for ethnic groups with elevated T2DM risk. Presentation: Thursday, June 15, 2023