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To determine whether rigorous insulin therapy, which normalized the routinely measured plasma llplds, also reversed qualitative abnormalities In the composition of llpoprotelns In noninsulin-dependent diabetes mdlltus (NIDDM), we studied 18 NIDDM patients (eight men and 10 women) before and 2 months after Intensive insulin therapy. Glycosylated hemoglobin levels (11.7% vs. 8.7%), plasma trtglyceride (TG) (250±91 vs. 164±56 mg/dl, p< 0.001), and cholesterol (214±43 vs. 198±31 mg/dl, p< 0.025) all fell, and both HDL2cholesterol and HDL3cholesterol Increased (59.1% and 10.9%, respectively, p< 0.001). However, abnormalities In two indices of lipoprotein surface constituents, which were present before insulin therapy, remained so thereafter. The first of these, the new cardiovascular risk factor, the plasma free cholesterol/lecithin ratio, which was Increased before treatment, fell only slightly after therapy (pro-therapy 1.02±0.29 vs. post-therapy 0.90±0.17, p< 0.4; reference group, 0.83±0.14), and remained elevated In very low density lipoprotein (VLDL) and low density lipoprotein (LDL). Secondly, the sphlngomyelln/lectthln ratio, an Index of the surface rigidity of llpoprotelns, was abnormal before treatment In VLDL, HDL2, and HDL3, and this alteration persisted after Insulin therapy In HDL, (p< 0.001). Lipoprotein core Hold abnormalities were also present before treatment the TG/cholesteryl ester ratio was reduced In VLDL and Increased in LDL, HDL2and HDL3. Rigorous Insulin therapy Improved, but failed to fully correct, this disturbance. In HDL2apollpoproteln (apo) A-l Increased significantly (p< 0.005), and apo A-ll and apo E were unchanged; In contrast, In HDL3, apo A-l was unchanged, and apo A-ll and apo E both decreased (p< 0.005) after Insulin therapy. Since llpoprotelns with altered surface and core llpMs have been shown to have an Impaired capacity to transfer their constituents to other llpoproteins and cells and compromised participation In reverse cholesterol transport, persistence of these qualitative changes may sustain the Increased cardiovascular risk In NIDDM even when clinical control Is excellent and the routinely measured plasma llptds appear normal.
Arteriosclerosis – Wolters Kluwer Health
Published: Mar 1, 1990
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