Introduction:Type2 diabetes (T2D) is most prevalent in non-Caucasians, especially South Asians (SA)1 . We have reported that young (19-23yr) SA and South-East/East Asian (SEA) males and females (BMI<24 kg/m2) without T2D, already present with an elevated post-meal insulin2,3 . Our study has shown increased leptin in SA females only, suggesting an early abnormality of adipose tissue in this group as a possible contributor to future insulin resistance4 . To examine mechanism(s) contributing to elevated post-meal insulin, the current study measured C-peptide (a marker of pancreatic beta-cell secretion) and hepatic clearance of insulin (using the molar ratios of incremental integrated areas of C-peptide and insulin) in male (M-) and female (F-) SA, SEA and Caucasians (C) (each n=15, total n=90). Method:Glucose, insulin and C-peptide were measured in blood obtained when fasting and for up to 2 hr following a 75g glucose challenge. Results:There was no difference in fasting glucose and insulin, BMI, waist circumferences or %body fat. Non-fasting insulin and insulin area under curve (AUC) was higher in M-SA, M-SEA and F-SA compared with C counterparts (P≤.012). There was no difference in fasting or post-meal C-peptide and C-peptide AUC in males. Compared with F-C, fasting C-peptide in F-SEA (P=.002), post-meal C-peptide in F-SEA and F-SA (P<.05) and C-peptide AUC in F-SEA and F-SA (P≤.001) were higher. Female C-peptide AUC correlated with insulin AUC (r=.505,n=41,P<.01). Molar ratios were lower in M-SA and M-SEA, compared with M-C (P=.007). There was no difference in molar ratios amongst the female groups. Conclusion:The increase in post-meal insulin in young male SA and SEA may be due to a reduction in hepatic clearance of this peptide. There is no current evidence of this in similarly aged SA and SEA females, suggesting gender differences in early contributing mechanisms to future T2D.