Jun Minamikawa

Effect of calcium channel blocker amlodipine on the intimal-medial thickness of carotid arterial wall in type 2 diabetes.

Although several reports have suggested that calcium channel blockers may inhibit progression of atherosclerosis in animals, it is still controversial whether they have any clinically significant antiatherogenic action in humans. The measurement of intimal-medial thickness (IMT) of the common carotid artery by B-mode ultrasound technique has been recognized as a powerful and noninvasive method to evaluate early atherosclerotic lesions. We investigated the effect of treatment with amlodipine, a powerful calcium channel blocker, on IMT. Twenty-two hypertensive patients with type 2 diabetes were enrolled in a prospective open study. An amlodipine group (amlodipine, 5 mg; n = 11) and a control group receiving angiotensin-converting enzyme inhibitors (n = 11) were studied before and 6 months after treatment. Amlodipine treatment caused a significant decrease in IMT compared with control (-0.052 +/- 0.017 vs. 0.011 +/- 0.021 mm; p < 0.05). Although the exact mechanisms remain to be elucidated, our preliminary result suggests that amlodipine has an antiatherogenic action in type 2 diabetes.

Comparison of effects of amlodipine and angiotensin receptor blockers on the intima–media thickness of carotid arterial wall (AAA study: Amlodipine vs. ARB in atherosclerosis study)

Although there have been increasing reports, which suggest that angiotensin receptor blockers (ARBs) may have anti-atherogenic actions, most of them are performed in vitro and there are a few reports about anti-atherogenic action in vivo. Especially, in humans, there have been no reports about effect of ARBs on atheroslocerosis. On the other hand, there have been several reports, including ours, which indicate that amlodipine, a calcium channel blocker, has a unique property to cause a reduction in the intima-media thickness (IMT) of common carotid artery, which is established to be an indicator of early atherosclerotic lesion, in humans. The present study investigated which of amlodipine and/or ARBs might have more profound effect on IMT progression. The study included 104 hypertensive patients with type 2 diabetes. They were divided into the two groups: the amlodipine group (n=58), who received amlodipine (2.5-5mg/day) and the ARB group (n=46), who received losartan (25-50mg/day), candesartan (4-8 mg/day), valsaratan (40-80 mg/day) or telmisartan (20-40 mg/day). IMT changes were examined during an average of 56.9 weeks. The amlodipine group showed a significant decrease in IMT compared to the ARB group (-0.046 [S.E. 0.161] mm vs. 0.080 [S.E. 0.255] mm, P<0.05). These results suggest that amlodipine has an inhibitory effect on early atherosclerotic process, and that ARBs do not have any effect on it in hypertensive patients with type 2 diabetes.

Carotid Arterial Intimal-Medial Thickening and Plaque Formation in NIDDM

the community of the Sandy Lake reserve in Northern Ontario (1). Subjects ranged in age from 10 to 79 years. The prevalence of inadequate dietary folate intake in these subjects was 37%, which was more than twice the average for the rest of Canada (8). We found that the MTHFR C677T allele frequency was 0.124, which was significantly less than the frequency of 0.351 observed in 1,497 reference Caucasian subjects (P < 0.0001). Furthermore, 1.6% of Oji-Cree were C677T/C677T homozygous, which was significantly less than the 12% of 1,497 reference Caucasians who were homozygous (P < 0.0001). The remarkably low MTHFR C677T allele frequency among the Oji-Cree might have resulted from a founder effect involving the ancestors of the clans forming the current reserve population or from selection pressure related to the mutants thermolability and to the cold climate of northern Ontario. In any event, the distinctive genetic features of the Ontario Oji-Cree, including the low frequency of MTHFR C677T, could explain their low prevalence of cardiovascular disease. Such a present low prevalence of disease is even more remarkable given the high community prevalence of dietary folate deficiency (8). Given the very high prevalence of NIDDM in this community, which has developed relatively recently (1), it will be important to follow this community prospectively to observe the future expression of cardiovascular disease.

Relationship Between Postprandial Triglyceride Level and Intima-Media Thickness of Carotid Artery after Troglitazone Treatment in Type 2 Diabetes

Recently it has been indicated that PPAR γ interacts with oxidized LDL, suggesting an important role of PPAR γ in pathogenesis of atherosclerosis. We have recently demonstrated that troglitazone, a PPAR γ agonist, has a potent inhibitory effect on intima-media thickness (IMT) in type 2 diabetes. There have been increasing evidences that postprandial triglyceridemia is related to atherosclerotic diseases. In order to investigate the relation between effects of PPAR γ activation, postprandial triglyceride and atherosclerosis, we examined the effect of troglitazone on postprandial triglyceride and IMT in type 2 diabetes. Troglitazone treatment for 9 months caused a decrease in IMT, postprandial triglycerides and HbAlc, whereas total cholesterol level was unchanged. However, there was no statistically significant association between a decrease in IMT and those in postprandial triglycerides or in HbAlc. The reduction in IMT was larger in the subjects with higher initial IMT than in those with lower initial IMT. These results indicate that 1) troglitazone has both an antiatherogenic action and a lowering effect on postprandial triglycerides in type 2 diabetes, and that 2) the mechanisms through which troglitazone shows antiatherogenic action are different from those through which it improves glycemic control or postprandial lipoprotein metabolism.