PLASMA PHOSPHOLIPID TRANSFER PROTEIN-ACTIVITY IS RELATED TO INSULIN-RESISTANCE - IMPAIRED ACUTE LOWERING BY INSULIN IN OBESE TYPE-II DIABETIC-PATIENTS

Cholesteryl ester transfer protein (CETP) and phospholipid transfer pr otein (PLTP) have important functions in high density lipoprotein (HDL ) metabolism. We determined the association of plasma CETP and PLTP ac tivities (measured with exogenous' substrate assays) with insulin resi stance, plasma triglycerides (TG) and non-esterified fatty acids (NEFA ), and assessed the lipid transfer protein response to insulin during a 6-7 h hyperinsulinaemic euglycaemic clamp in non-obese and obese hea lthy subjects and patients with Type II (non-insulin-dependent) diabet es mellitus (n = 8 per group). Plasma PLTP activity was higher in obes e healthy subjects and obese Type II diabetic patients compared with n on-obese healthy subjects (p < 0.05 to 0.01) and was correlated with i nsulin resistance, plasma TG and NEFA (p = 0.02 to < 0.01). In non-obe se healthy subjects, insulin decreased plasma TG and increased the HDL cholesteryl ester (CE)/TG ratio (p < 0.01 compared with saline infusi on). Plasma PLTP activity fell by 14% at the end of the clamp (p < 0.0 1 compared with saline) but CETP activity did not change. The decrease s in plasma NEFA, TG and PLTP activity and the rise in HDL CE/TG were smaller in obese Type II diabetic patients than in non-obese healthy s ubjects (p < 0.01 for all). Baseline HDL CE/TG was negatively correlat ed with plasma TG (p < 0.001, n = 32) and PLTP activity (p < 0.01) but not with CETP activity. Likewise, the rise in HDL CE/TG during the cl amp was related to the fall in plasma TG (p < 0.001) and in PLTP activ ity (p < 0.02). It is concluded that plasma PLTP, but not CETP, is reg ulated by insulin in an acute setting. High plasma PLTP activity is as sociated with insulin resistance in conjunction with altered NEFA and triglyceride metabolism. High plasma TG and PLTP activity have coordin ate effects on HDL metabolism.