EFFECTS OF INSULIN-TREATMENT ON LIPOPROTEIN COMPOSITION AND FUNCTION IN PATIENTS WITH IDDM

Normolipidemic patients of both sexes with insulin-dependent diabetes mellitus have the same pervasive changes in lipoprotein surface and core lipid composition. The disproportionate increase observed in their lipoprotein free (unesterified) cholesterol relative to the predominant surface phospholipid lecithin (phosphatidycholine) is reflected by elevation of the FC-L ratio in their whole plasma, VLDL, HDL2, and HDL3. As a possible consequence of this qualitative disturbance, cholesteryl ester transfer is pathologically increased and the mass of cholesteryl ester transferred from HDL to VLDL+LDL is significantly greater in IDDM patients than in control subjects at 1, 2, and 4 hr (P < 0.001). Consistent with accelerated CET in vivo, the TG-CE core lipid ratio was decreased in VLDL from six subjects (IDDM 9.5 +/- 0.8 vs. control 12.9 +/- 3.4; P < 0.01) and increased in their HDL (diabetic 0.55 +/- 0.11 vs. control 0.42 +/- 0.04: P < 0.025). These abnormalities in lipoprotein composition and CET do not correlate with glycemic control and persist after intensive management with s.c. insulin. They may be related to the peripheral hyperinsulinemia that is an unavoidable consequence of conventional s.c. insulin administration because preliminary studies indicate that these disturbances in lipoprotein composition and function are reversed when systemic insulin levels are lowered and insulin is delivered into the portal circulation from an i.p. catheter connected to an implanted programmable s.c. insulin pump.