There is increasing agreement about the atherogenicity of intermediate density lipoprotein (IDL). Our previous work demonstrated abnormal accumulation of IDL (Sf 12-60) in normocholesterolemic NIDDM. Diabetics under insulin treatment had no abnormal lipoprotein profile if they were normocholesterolemic. On the other hand, it is well recognized that hyperinsulinemia has a role in atherogenesis. In order to explore the possibility that there is any relationship between residual endogenous insulin response and IDL metabolism in NIDDM, an oral glucose tolerance test was performed in 61 patients. Forty-one of them were treated on diet and the other by sulphonylureas (SU). Patients who were hyperinsulinemic, with thyroid, renal or hepatic disease and those taking steroids or hypolipidemic drugs were excluded. Cholesterol (Ch) and triglyceride (Tg) levels were measured in three subclasses of Tg-rich lipoprotein fraction—very low density lipoprotein (VLDL): Sf 60-400, intermediate density lipoprotein1 (IDL1): Sf 20-60, IDL2: Sf 12-20. HDL fraction was separated from the plasma by precipitation.Oral glucose tolerance test performed in NIDDM on diet showed significant correlation between ΣIRI/ΣPG and IDL1-Ch/Tg or IDL1+2-Ch/Tg. Since hyperinsulinemic subjects were excluded from the study ΣIRI/ΣPG ratio may represent the insulin sensitivity rather than insulin resistance. The significant correlations shown here suggest the importance of insulin sensitivity for the metabolism of IDL. In SU treated group, there was an inverse relationship between insulinogenic index and HDL-Ch, suggesting the atherogenicity of endogenous insulin. Negative correlation between ΣIRI and HDL-Ch in all the diabetics in this study supports this suggestion. Thus, we demonstrate here the new evidence linking insulin with atherosclerosis.
CS-514, a new inhibitor of endogenous cholesterol biosynthesis, has been shown to reduce plasma cholesterol concentration in both healthy and hypercholesterolemic subjects. In this study we compared the effect of CS-514 and probucol on plasma lipids in hypercholesterolemic subjects. After treatment with probucol, HDL-cholesterol as well as total cholesterol tended to decrease. After a washout period probucol was replaced with comparable doses of CS-514. All the patients showed decreased plasma cholesterol levels after CS-514 treatment. HDL-cholesterol levels increased significantly after CS-514. Plasma triglyceride levels showed no significant change throughout the study period. Thus, the two drugs differed in their effects on HDL-cholesterol.
A 33-year-old man was admitted to our hospital due to DIC and multiple bone metastasis after distal gastrectomy for gastric cancer (Stage IIIB). We diagnosed disseminated carcinomatosis of bone marrow by gastric cancer. The patient was treated with combination chemotherapy of S-1 and CDDP (S-1 80 mg/m (2), po, day 1-21 and CDDP 60 mg/m(2), iv, day 8). After one course of the treatment, DIC was resolved and severe pain in his back and legs which had been poorly controlled was dramatically improved. He could thus be discharged from our hospital and survived for about six months. S-1 and CDDP therapy are considered to be effective for disseminated carcinomatosis of bone marrow due to gastric cancer, even if complicated by DIC.
