Effect of doxazosin on the size of LDL particle in the type 2 diabetic patients with hypertension.

Hypertension is common in patients with type 2 diabetes mellitus (DM), and contributes to the progression of its complications in patients with diabetes. Doxazosin is a selective alpha1-adrenoceptor-blocking anti-hypertensive agent and has a favorable impact upon lipid metabolism. We investigated the effect of doxazosin on the lipid metabolism in hypertensive patients with type 2 diabetes, especially low-density lipoprotein (LDL) particle size that is associated with many elements of the insulin resistance syndrome. Cross-sectional study (n=19) was designed to determine whether doxazosin, administered with an angiotensin II-converting enzyme inhibitor (ACEI) and a Ca antagonist, affects LDL particle size. As a follow-up study (n=6), lipid and glucose metabolism and LDL particle size were followed for 12 weeks before and after the initiation of doxazosin administration (1-4 mg/day). The average size of LDL particle was significantly larger in the patients treated with doxazosin (LDL-migration index (LDL-MI): 0.348+/-0.027) than those in the patient treated without doxazosin (0.378+/-0.035), although LDL cholesterol levels did not differ between the two groups. The plasma glucose and HbA1c levels remained unchanged. Lipid profile showed normolipemia throughout the period of the study. However, LDL particle size was demonstrated to become larger during the following period. Small LDL fraction (LDL3-7) diminished remarkably and large LDL (LDL1-2) increased on the polyacrylamide gel electrophoresis (PAGE) LDL system (LipoPrint). From this pilot study, it was concluded that doxazosin is a useful anti-hypertensive agent for hypertensive type 2 diabetic patients in improving the size of LDL particle.

[Relationship between insulin secretion and insulin resistance in nondiabetic subjects with myotonic dystrophy--a case control study].

Hyperinsulinemia in myotonic dystrophy (MyD) is generally considered as a result of insulin resistance. However, as a consequence of abnormality in systemic membrane fluidity in this disease, abnormal insulin clearance or intrinsic pancreatic beta-cell dysfunction could also contribute to the hyperinsulinemia. To clarify the cause of hyperinsulinemia in MyD, we examined the insulin resistance, insulin clearance and the capacity of insulin secretion in 6 patients with MyD. They received a euglycemic hyperinsulinemic (insulin 40 mU/m2/min) clamp study for the quantification of insulin resistance by the glucose infusion rate (GIR). We evaluated their capacity of insulin secretion by the ratio of increment of serum insulin level to that of plasma glucose level 30 minutes after a 75 g oral glucose load (insulinogenic index; I.I.) and the ratio of area under the curve of serum insulin levels to that of plasma glucose levels during a 75 g oral glucose load (AUCIRI/AUCPG). The I.I. (1.1 +/- 0.6 vs 0.4 +/- 0.3, p < 0.05) and the AUCIRI/AUCPG (0.5 +/- 0.2 vs 0.2 +/- 0.1, p < 0.01) in MyD were significantly greater than those of GIR, body mass index and sex matched 6 non-diabetic controls respectively. Insulin clearance, estimated by the level of insulin and C-peptide before and during a euglycemic clamp study did not differ between the two groups. These results indicate that the postload hyperinsulinemia observed in MyD is not solely resulted from insulin resistance. Other factors, such as intrinsic beta-cell disorder may be involved.