Mechanisms
Intraperitoneal insulin normalizes elevated cholesteryl ester transfer in NIDDM, but injections alone do not (Diabetes 1997)
Original title: Effects of multiple daily insulin injections and intraperitoneal insulin therapy on cholesteryl ester transfer and lipoprotein lipase activities in NIDDM
Insulin-requiring men with NIDDM were randomized to intraperitoneal insulin delivery (n=9) or multiple daily insulin injections (n=13) for 7 months. HbA1c improved similarly in both groups (MDI: 9.4 plus or minus 1.1% to 7.2 plus or minus 0.7%; IP: 9.2 plus or minus 1.3% to 7.1 plus or minus 0.5%, both P less than 0.001). Before treatment, cholesteryl ester transfer, estimated by mass and isotopic assays, was greater in NIDDM subjects than nondiabetic controls (P less than 0.001). With treatment, mass transfer declined in both groups but normalized only with intraperitoneal insulin (40.8 plus or minus 23.3 to 10.9 plus or minus 6.5 microg, a 73.2% fall, P less than 0.05, versus 49.0 plus or minus 13.7 to 29.5 plus or minus 15.3 microg, a 39.7% fall, P less than 0.01, with injections), which remained abnormally elevated (P less than 0.005), showing that route of insulin delivery, not glycemic control alone, determines whether cholesteryl ester transfer normalizes.
Original abstract
Although the relationship between the actions of cholesteryl ester transfer protein (CETP) and atherosclerosis is complex, a strong body of evidence suggests that its activity (cholesteryl ester transfer [CET]) is proatherogenic. We have previously shown that CET is increased in IDDM patients receiving conventional subcutaneous insulin treatment and normalized when systemic insulin levels are lowered with intraperitoneal insulin delivery (IP). Since CET has been found by many observers to also be accelerated in NIDDM, we sought to determine whether the same salutary effect could be achieved in insulin-requiring NIDDM men before and 7 months after randomization to an intensive treatment regimen (Rx) of either IP (n = 9) or multiple daily insulin injections (MDI; n = 13). HbA1c improved to the same degree in both groups (MDI group: 9.4 +/- 1.1% pre-Rx vs. 7.2 +/- 0.7% post-Rx [P < 0.001]; IP group: 9.2 +/- 1.3% pre-Rx vs. 7.1 +/- 0.5% post-Rx [P < 0.001]). Compared with pre-Rx levels, plasma triglycerides were not significantly changed by either treatment (MDI group: 136 +/- 80 mg/dl pre-Rx vs. 139 +/- 87 mg/dl post-Rx; IP group: 157 +/- 63 mg/dl pre-Rx vs. 188 +/- 89 mg/dl post-Rx), though an upward trend followed IP. Before randomization, CET estimated with both mass and isotopic assays was greater in the NIDDM subjects than in nondiabetic control subjects (P < 0.001). With improved glycemic control, CE mass transfer declined in both groups, but only reached normal levels in the IP group (MDI group at 2 h: 49.0 +/- 13.7 [mean +/- SD] pg pre-Rx vs. 29.5 +/- 15.3 microg post-Rx [-39.7%, P < 0.01]; IP group at 2 h: 40.8 +/- 23.3 microg pre-Rx vs. 10.9 +/- 6.5 microg post-Rx [-73.2%, P < 0.05]) and remained abnormally increased (P < 0.005) in the subjects receiving MDI. Total lipolytic activity after intensive treatment was unchanged from pretreatment levels, which were similar to those of the reference group. Although directional changes in lipoprotein lipase (LpL) and hepatic triglyceride lipase (HTGL) similar to those found in IDDM after MDI and IP were observed, they were not statistically significant. Thus, while improved glycemic control alone achieved by either MDI or IP reduced the pathological increase in CET in these insulin-treated NIDDM men, normalization was only achieved in those treated with IP. Despite near-normal HbA1c levels, CET remained abnormally increased in NIDDM patients treated rigorously with conventional subcutaneous insulin delivery.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.