Masahiro Tsutsui

Different change in lipoprotein(a) levels from lipid levels of other lipoproteins with improved glycemic control in patients with NIDDM.

OBJECTIVE To evaluate change both in lipoprotein(a) [Lp(a)] and lipid levels in other lipoproteins in non-insulin-dependent diabetes mellitus (NIDDM) after short-term improvement of glycemie control. RESEARCH DESIGN AND METHODS We compared Lp(a) levels in 210 NIDDM patients with those in 46 control subjects and evaluated the relationship between glycemie control and Lp(a) levels in diabetic patients. In addition, changes in Lp(a) levels and lipid levels were assessed after the improvement of glycemie control in 54 poorly controlled NIDDM patients. RESULTS In NIDDM, Lp(a) levels in all patients, 62 patients with HbA1c <6.0%, and 75 patients with HbA1c between 6.0 and 8.0%, were significantly higher than those in control subjects (19.1 [1.7-106.6], 19.2 [6.0-106.6], and 20.3 [2.7-75.3] vs. 15.4 [2.0-61.7] mg/dl, median [range], P < 0.05). Lp(a) levels in 73 patients with HbA1c of ≥8.0% (18.7 [1.7-58.8] mg/dl) were not significantly different from those in control subjects. After glycemie control, lipid levels in plasma and in other lipoproteins fell significantly, but Lp(a) did not change (from 18.3 [1.7-58.8] to 18.4 [6.6-95.3] mg/dl). Changes in lipid levels, including Lp(a), did not correlate with those in fasting plasma glucose or HbAlc. CONCLUSIONS These results suggest that elevated Lp(a) levels do not reflect poor glycemie control and that Lp(a) levels are independent of lipid levels in other lipoproteins after improved glycemie control in NIDDM.

The effect of a new oral hypoglycemic drug, CS-045, on glucose tolerance and serum lipids in nonobese japanese patients with non-insulin-dependent diabetes mellitus: A pilot study

Abstract This study examined the effects of a new oral hypoglycemic drug, CS-045, on glucose tolerance and serum lipids in 10 nonobese patients with non-insulin-dependent diabetes mellitus (NIDDM). Plasma glucose levels before and at 2, 3, 4, 6, 8, 10, 15, 20, and 30 minutes after administration of the intravenous glucose tolerance test (IVGTT) were significantly ( P P P P P

A case of tangier disease with a novel mutation in the c-terminal region of ATP-binding cassette transporter A1

Tangier disease (TD), a rare disorder characterized by extremely low levels of high density lipoprotein cholesterol (HDL‐C), is caused by mutations in the ATP‐binding cassette transporter A1 (ABCA1) gene. Here, we describe a new patient with TD. The 42‐year‐old proband had obvious juvenile cataracts, mild hepatosplenomegaly, and an extremely low level of HDL‐C (1 mg/dl), consistent with the diagnosis of TD. The proband was homozygous for a novel CTC6914‐6TT → 2203X mutation in the carboxy terminus of the ABCA1 protein. ApoAI‐mediated cholesterol efflux from patient fibroblasts was markedly decreased compared to control, despite normal levels of protein expression. This indicates that this mutant protein is normally transcribed and exists as a stable product, yet is functionally defective. These results point to a critical role for the intracellular C‐terminal region of the ABCA1 gene product in regulating cholesterol efflux and HDL‐cholesterol levels.

Lipid composition of platelets in patients with non-insulin-dependent diabetes mellitus: studies before and after treatment of diabetes.

The study was designed to investigate whether impaired composition of platelet lipids in untreated diabetic patients improved after diabetic treatment. Fourteen untreated patients with non‐insulin‐dependent diabetes mellitus (NIDDM) and 15 healthy control subjects were studied. In the diabetic patients, the ratio of free cholesterol to phospholipid (FC/PL) in platelets of 0.33 ± 0.02 (mean ± SEM) at pre‐treatment, which was statistically (p < 0.05) higher than that of 0.26 ± 0.02 in control subjects, was significantly decreased to the value of 0.29 ± 0.02 (p < 0.01) after insulin therapy. Platelet FC level of 9.77 ± 0.77 μg 10−8 cells pre‐treatment was significantly (p < 0.01) reduced to the value of 7.72 ± 0.38 μg 10−8 cells post‐treatment. Platelet PL level showed no significant changes after the treatment. There was a significantly (p < 0.01) positive correlation between the decrease in FC/PL of platelets and that in haemoglobin A1c (HbA1c) after treatment for diabetes (rs = −0.729). These results indicate that the impaired lipid composition in platelets can be improved after an adequate glycaemic control in patients with NIDDM.

Acid cholesteryl ester hydralase activity of mononuclear leukocytes in patients with non-insulin-dependent diabetes mellitus: studies before and after treatment of diabetes

The change of acid cholesteryl ester hydrolase activity in mononuclear leukocyte following treatment of diabetes mellitus was studied in 21 patients with non-insulin-dependent diabetes mellitus (NIDDM). Enzyme activity before treatment in the patients was significantly lower than that in 14 age-matched healthy subjects (1.20 +/- 0.15; mean +/- S.E. vs. 2.20 +/- 0.17 nmol/mg protein/h, P less than 0.01). Enzyme activity before treatment in the patients was significantly increased (P less than 0.05) after 4-8 weeks of treatment. However, enzyme activity of 1.43 +/- 0.14 nmol/mg protein/h observed after treatment in the patients was significantly lower (P less than 0.01) than that in the healthy subjects. There was a significant negative correlation between enzyme activity before treatment and the increase in enzyme activity following treatment (rs = -0.555, P less than 0.01, n = 21). These results indicate that low level of enzyme activity may be insufficiently improved by the treatment of diabetes, and the risk for the development of atherosclerosis as viewed from the enzyme activity may persist even after the treatment in NIDDM.

High incidence of diabetic nephropathy in non-insulin-dependent diabetic patients with heterozygous familial hypercholesterolemia

Abstract The present study was performed to assess the influence of hyperlipidemia on the appearance and development of diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). This was done by comparing the incidence of nephropathy in 35 diabetic patients with heterozygous familial hypercholesterolemia (FH) with the incidence of nephropathy in 165 patients without FH. There was no significant difference in sex, age, body mass index, or mean duration of diabetes between the two groups. Both groups received similar treatment for diabetes. No significant difference in mean hemoglobin A 1c levels or prevalence of hypertension was noted between the two groups. Total serum cholesterol and triglyceride levels were significantly higher ( P P

Enhanced accumulation of cholesterol ester in macrophages from diabetic rats incubated with oxidized low-density lipoprotein

Abstract The metabolism of cholesterol ester (CE) was studied in peritoneal macrophages taken from rats with streptozocin-induced diabetes. Levels of CE and synthesized [ 14 C]-cholesterol oleate did not differ significantly between the macrophages from diabetic and control rats incubated with low-density lipoprotein (LDL). However, when macrophages were incubated with Cu 2+ -induced oxidized LDL, CE levels were significantly higher in diabetic rats than in control rats (3.03± 0.09 μg/10 6 cells versus 2.66±0.09 μg/10 6 cells; P 14 C]-cholesterol oleate did not differ significantly between the two groups of rats. The findings suggest that CE accumulates in macrophages in the presence of diabetes mellitus and may play a role in the development of atherosclerosis in diabetes mellitus.