Hidehisa Sasaki

The effect of insulin sensitizer, troglitazone, on lipoprotein lipase mass in preheparin serum.

Lipoprotein lipase mass exists in preheparin serum, even though the activity is scarcely found. The implication of this is unclear. We studied the effect of an insulin sensitizer, troglitazone, on this preheparin serum lipoprotein lipase mass (preheparin LPL mass) in non-insulin-dependent diabetes mellitus (NIDDM) patients as well as on serum lipid levels and low density lipoproteins (LDL) particle size. Thirty-one NIDDM patients with poor control were administered troglitazone 400 mg/day. Hemoglobin A1c had significantly decreased (13%, P < 0.001) 2 months later. Preheparin LPL mass had gradually increased and a 69% increase (P<0.01) was observed 4 months later. Triglyceride significantly decreased (23%, P < 0.01) and high density lipoprotein-cholesterol increased (10%, P < 0.01), whereas total cholesterol and LDL levels did not change 4 months later. The size of LDL increased significantly (P < 0.01). These results were consistent with the idea that preheparin LPL mass might be relating to the insulin sensitivity enhanced by troglitazone, as well as LDL particle size.

Low lipoprotein lipase mass in preheparin serum of type 2 diabetes mellitus patients and its recovery with insulin therapy

There exists lipoprotein lipase mass in preheparin serum, even though the activity is scarcely found. We studied the preheparin serum lipoprotein lipase mass levels (prehaparin LPL mass) in type 2 diabetes mellitus patients and the effect of insulin therapy on the levels of preheparin LPL mass. In 40 type 2 diabetes mellitus patients, preheparin LPL mass were measured by the sandwich enzyme-linked immunosorbent assay (ELISA), and were compared with those of non-diabetic healthy control. The correlation between preheparin LPL mass and Hemoglobin A(1c) (HbA(1c)), serum lipids were studied. Preheparin LPL mass were measured before and after insulin therapy. Preheparin LPL mass of type 2 diabetes mellitus patients was significantly lower than that of non-diabetic healthy control. In diabetic patients, preheparin LPL mass were negatively correlated with HbA(1c). Fifteen patients started to take insulin therapy. Preheparin LPL mass increased significantly at 4th week, when fasting blood glucose decreased. These results suggested that preheparin LPL mass was greatly regulated by insulin action.

Importance of Efficient Coordination of Long-Term, Large-Scale Clinical Trials and Problems Arising-Role of Hospital Pharmacists in this Activity-

We felt that pharmacists should participate more actively in the evaluation of efficacy and safety in clinical trials. To improve the capability of pharmacists in this respect, we evaluated the support we gave to the investigators of the Japan EPA Lipid Intervention Study (JELIS), a long-term, large-scale clinical trial conducted at the Department of Pharmacy of our hospital. To identify the problems in our support, we investigated the number of days required to complete the Case Report Form (CRF) and the reliability of the data collected, by considering the adequacy of the items observed and the clinical inspection terms. Our findings indicated that it was feasible for pharmacists to handle the coordination of JELIS in addition to their everyday workload and we also noted an improvement in the clinical inspection rate, from 76.6% to 100% for JELIS I and from 97.5% to 100% for JELIS II. Moreover, we found the number of days required to complete the CRF was reduced from 109.8 days to 20.3 days for JELIS I and from 79.5 days to 21.0 days for JELIS II. These results show that the pharmacists in our hospital helped to maintain the reliability of clinical data.

Effects of Treatment with Probucol, a Hypolipidemic Agent, on Diabetic Nephropathy.

A year-long prospective study was conducted to elucidate the effects of probucol, an anti-oxidative hypolipidemic agent, on the progression of diabetic nephropathy.A total of 152 diabetic outpatients with an urinary albumin level of 200mg/g·Cr or more, and who routinely visited our hospital were divided into two groups of 75 patients treated with probucol (500mg/day) and 77 non-treated patients. All patients were observed for 12 months. The results reveled no significant difference in the blood pressure or HbA1clevel between the two groups. However, the serum lipid levels in the probucol-treated group decreased by 16 to 18% (p< 0.01) for total cholesterol, 19 to 28% for neutral fat, and 17 to 21% (p<0.01) for HDL-cholesterol, while they did not significantly change in the non-treated group. As for the renal function, probucol suppressed the progression of nephropathy in a patients group with a moderate to severe serum creatinine and urinary albumin level and another patient group with a mild to moderate urinary protein level at severity level of from ± to 2 +. Kidney dialysis was required in 2 probucol-treated patients and 9 nontreated patients, where the rate of dialysis shift after the serum creatinine concentration exceeded 2.0mg/dL was 15% in the probucol-treated group and 58% in the non-treated group.From the present results, it was suggested that probucol suppresses the progression of diabetic nephropathy, thereby extending the period until dialysis is required.