Intraperitoneal insulin therapy corrects abnormalities in cholesteryl ester transfer and lipoprotein lipase activities in insulin-dependent diabetes mellitus

John D. Bagdade, Frederick L. Dunn, Robert H. Eckel, Mary C. Ritter

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Patients with insulin-dependent diabetes mellitus (IDDM) have proatherogenic disturbances in cholesteryl ester transfer (CET) despite intensive subcutaneous insulin therapy (ISC). Since CET is activated by insulin-sensitive lipoprotein lipase (LPL), which normally increases postprandially, we queried whether iatrogenic hyperinsulinism from ISC stimulated LPL and CET by studying well-controlled IDDM patients after ISC and then 6 months after lowering systemic insulin levels by intraperitoneal (IP) insulin delivery. Although glycemic control (HbA1C IDDM, 6.9±1.7%; control, 4.5% to 8%) was excellent during ISC, CET was accelerated (P<.001) and both systemic insulin levels and LPL specific activity were increased (P<.05). Following IP, basal systemic insulin levels declined by more than one half (ISC, 8.22±6.5 versus IP, 2.77±2.4 μU/mL; mean±SD; P<.025), and both LPL and CET activities returned to normal. Plasma triglyceride, cholesterol, high-density lipoprotein-2 (HDL2) cholesterol, HDL3 cholesterol, cholesteryl ester transfer protein mass, and glyce-mic control (HbA1c, 6.3±0.8%) were unchanged and remained normal. These findings indicate that ISC is associated with high levels of basal CET and LPL. These alterations both appear to be closely linked to iatrogenic hyperinsulinemia resulting from ISC. The fact that they are both reversed when systemic insulin levels are reduced by IP suggests that insulin, acting through LPL, influences the nature of the interaction of the lipoproteins engaged in CET. Since accelerated CET is believed to result in the enrichment of certain subpopulations of apolipoprotein B-containing lipoproteins with cholesteryl ester, an alteration presumed to enhance their atherogenicity, its correction by IP therapy suggests that this more physiological mode of insulin delivery may reduce cardiovascular risk in IDDM.

Original languageEnglish (US)
Pages (from-to)1933-1939
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume14
Issue number12
DOIs
StatePublished - Jan 1 1994

Keywords

  • Cholesteryl ester transfer
  • Hyperinsulinism
  • Insulin-dependent diabetes mellitus
  • Intraperitoneal insulin delivery
  • Lipoprotein lipase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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