OBJECTIVE -Brachial-ankle pulse wave velocity (baPWV), as an indicator of atherosclerosis in impaired fasting glucose (IFG), was studied in 232 subjects randomly selected from inhabitants of two rural communities in Japan.RESEARCH DESIGN AND METHODS -BMI, systolic blood pressure (SBP), fasting blood glucose (FBS), lipid parameters, ankle brachial pressure index (ABI), and baPWV were measured in each subject. ABI and baPWV were measured using the recently developed device, form ABI/PWV. The subjects were divided into three groups according FBS level: a normal group consisting of subjects with FBS Ͻ110 mg/dl, an IFG group consisting of subjects with FBS 110 -125 mg/dl, and a diabetic group consisting of subjects with FBS Ն126 mg/dl and subjects taking hypoglycemic agents. The parameters in the three groups were compared.RESULTS -It was found that the baPWV value increased with increasing plasma glucose level. Significant differences were found between the baPWV values in the normal and IFG groups (1,518 vs. 1,673 cm/s, P ϭ 0.01) and in the normal and diabetic groups (1,518 vs. 1,771 cm/s, P Ͻ 0.0001). The results of multiple regression analysis showed that FBS was closely related to baPWV as well as to age and SBP. CONCLUSIONS -The relationship between IFG and atherosclerosis remains controversial. Further studies are needed to evaluate whether strict control of blood glucose level in patients with IFG will result in the prevention of atherosclerosis progression. Diabetes Care 26:437-440, 2003M uch interest has been shown over the past few decades in aortic pulse wave velocity (PWV) as a noninvasive method for assessing atherosclerosis, and there have been many recent reports on PWV and the development of atherosclerotic disease (1-4). In this study, we investigated the usefulness of PWV as an indicator of early-stage atherosclerosis in impaired fasting glucose (IFG) in inhabitants of two rural communities in Japan by using a new device for measuring PWV.RESEARCH DESIGN AND METHODS -The subjects included 232 men (mean age 65.2 Ϯ 9.5 years) selected from 1,479 inhabitants of the towns of Tanno and Sobetsu in Hokkaido who underwent medical examinations in 2000. Systolic blood pressure (SBP), diastolic blood pressure, BMI, and levels of fasting blood glucose (FBS), HbA 1c , total cholesterol, triglyceride, and HDL were measured in all subjects. Bilateral brachial-ankle PWV (baPWV) was measured in all subjects using a new device, form ABI/ PWV (BP-203RPE; Nihon Colin).Form ABI/PWV is a device with four cuffs that can simultaneously measure blood pressure levels in both arms and both legs and automatically calculate the ankle brachial pressure index (ABI). This device can also record pulse waves by sensors in the cuffs, store data on the start point of each pulse wave in the right arm and both legs in memory, record the time difference between transmission time to arm and transmission time to ankle as "transmission time," calculate the transmission distance from the right arm to each ankle according to body height, and...

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Warfarin is the most commonly used oral anticoagulant for treatment of thromboembolism, but adjustment of the dose appropriate to each patient is not so easy because of the large inter-individual variation in dose requirement. We analyzed single nucleotide polymorphism (SNP) genotypes of the VKORC1 and CYP2C9 genes using DNA from 828 Japanese patients treated with warfarin, and investigated association between SNP genotype and warfarin-maintenance dose. Five SNPs in VKORC1, 5¢ flankingÀ1413A>G, intron 1À136T>C, intron 2+124C>G, intron 2+837T>C and exon 3 343G>A, were in absolute linkage disequilibrium, and showed a significant association with daily warfarin dose of these patients. The median warfarin dose of patients with homozygosity for the minor allele was 4.0 mg/day, which is significantly higher than those heterozygous for the minor allele (3.5 mg/day) or those homozygous for the major allele (2.5 mg/day; P=5.1·10 À11 in the case of intron 1À136T>C SNP). We then genotyped the CYP2C9 gene for the Japanese common genetic variant, CYP2C9*3 and, based on the genotype of these two genes, classified patients into three categories, which we call ''warfarin-responsive index.'' The median warfarin daily dose varied significantly in this classification according to the warfarin-responsive index (2.0 mg/day for index 0 group, 2.5 mg/day for index 1 group, and 3.5 mg/day for index 2 group; P=4.4·10 À13 ). Thus, analysis of the combination of VKORC1 and CYP2C9 genotypes should identify warfarin-sensitive patients who require a lower dose of drug, allowing personalized warfarin treatment.

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Abnormalities in plasma composition of essential fatty acids (EFAs) may be associated with the etiology of pruritus and other skin problems in patients undergoing hemodialysis. To study whether an oral supplementation with ω–6 (n–6) EFAs would restore deranged plasma EFAs and ameliorate skin symptoms, 9 and 7 dialysis patients were randomly assigned to receive either γ-linolenic acid (GLA)-rich evening primrose oil (EPO) or linoleic acid (LA) (2 g/day each) for 6 weeks. Plasma concentrations of EFA were analyzed by gas chromatography and uremic skin symptoms were assessed for dryness, pruritus and erythema by questionnaire and visual inspection in a double-blind manner. The patients given EPO exhibited a significant (p < 0.05) increase in plasma dihomo-γ-linolenic acid (a precursor of anti-inflammatory prostaglandin E₁) with no concomitant change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin E₂ and leukotriene B₄). In contrast, those given LA exhibited a significant (p < 0.05) increase in LA but not in any other n–6 EFAs, whereas they exhibited a significant (p < 0.05) decrease in plasma docosahexaenoic acid. The patients given EPO showed a significant (p < 0.05) improvement in the skin scores for the three different uremic skin symptoms over the baseline values and a trend toward a greater improvement (0.05 < p < 0.1) in pruritus scores than those given LA. Results indicate that GLA-rich EPO would be a more favorable supplemental source than LA in terms of shifting eicosanoid metabolism toward a less inflammation status through modifying plasma concentrations of their precursor n–6 EFAs. Further studies are required to confirm the efficacy and safety of EPO therapy for the treatment of uremic pruritus.