We have previously shown that both kidney-alone and combined kidney- pancreas transplantation lower VLDL and IDL apoB while increasing LDL apoB, apoA-I, and HDL free cholesterol (FC). In this report, we analyze the lipoproteins of 31 patients who have undergone combined kidney-pancreas transplantation. Systemic venous drainage of the pancreas was utilized in 20 of these patients while 11 had portal venous drainage. Six lipoprotein subfractions (VLDL, IDL, LDL, HDL-L, HDL-M, HDL-D) were isolated by rapid gradient ultracentrifugation using a fixed-angle rotor. The apolipoprotein (by reverse-phase HPLC) and lipid (by enzymatic assays) composition of each subfraction was determined. After three months, there were few group differences. However, the portal group had substantial reductions in VLDL apoB at both six (-50% vs. +1%) and twelve months (-57% vs. +149%, P=.042) while the systemic group bad increases in VLDL apoB. Similar differences were seen in IDL apoB (six months: -38% vs. +13%; twelve months: -61% vs. +56%, P=.008). LDL apoB increased in both groups at six months (portal: +7%; systemic: +30%) but fell in the portal group at twelve months (-17% vs. +41%, P=.0007). IDL triglyceride, cholesterol ester, phospholipids, and free cholesterol also fell by 19% to 47% in the portal group while they rose by 8% to 44% in the systemic patients, six and twelve months after surgery (P<.05). In addition, the VLDL and LDL free cholesterol to phospholipid ratios (FC/PL) fell (improved) by 16% to 26% in the portal patients while they rose by 9% to 28% in the systemic subjects during this time (P<.04). Finally, there were substantial improvements in the LDL composition of the portal patients compared to the systemic patients at six (PL/apoB: +23% vs. -16%, P=.005; CE/apoB: +14% vs. -14%, P=.037) and twelve months (PL/apoB: +39% vs. -13%, P=.011; CE/apoB: +41% vs. -15%, P=.011). These data indicate that portal drainage of the transplanted pancreas reduced the number of VLDL, IDL, and LDL particles, reduced the total mass of IDL (by 35%), and normalized the VLDL and LDL particle composition. These improvements were not seen in the patients who received systemic drainage of their pancreas. HDL-M also improved in the portal patients (TG: -29% vs. +12%, P=.025) (PL: +22% vs. - 5%, P=.014) (total mass: +16% vs. +0.2%, P=.044) but not in the systemic patients six months after surgery. These results suggest that portal venous drainage of the pancreas leads to greater improvements in the lipoprotein composition of IDDM patients than does systemic drainage.
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