Improved lipoprotein surface and core lipid composition following intraperitoneal insulin delivery in insulin-dependent diabetes mellitus.

To determine whether insulin delivered into portal circulation by an implanted pump reversed abnormalities in lipoprotein composition in insulin-dependent diabetes mellitus, 10 well-controlled normolipidaemic patients were studied after conventional intensive sub-cutaneous (ISC) insulin management and then 3 and 6 months after intraperitoneal pump implantation (IP). Glycated haemoglobin (ISC: 6.9 +/- 1.7% vs. IP-3 months 6.3 +/- 0.7; IP-6 months 6.3 +/- 0.8; mean +/- S.D.), plasma triglyceride and cholesterol levels, and the cholesterol content of HDL2 and HDL3 were normal and not significantly changed during these treatments. Fasting free insulin concentrations measured before and after 6 months of IP fell by more than half (ISC 8.22 +/- 6.5 vs IP 2.77 +/- 2.4 mU/ml; p < 0.025). The plasma-free cholesterol/lecithin ratio, a potential new cardiovascular risk factor, was increased during ISC, declined progressively after 3 months of IP, and approached normal by 6 months (ISC 0.96 +/- 0.37 mol/mol vs. IP-3 months 0.91 +/- 0.34; IP 6 months 0.86 +/- 0.10; reference group 0.83 +/- 0.33). In all lipoprotein fractions, sphingomyelin concentrations tended to fall, and lecithin concentrations to rise progressively during IP. As a result, the sphingomyelin/lecithin ratio, an index of the surface rigidity of lipoproteins, declined. The fact that some of the compositional modifications associated with ISC were reversed when insulin was administered intraperitoneally suggests that they may have been iatrogenic and resulted from high systemic insulin levels.