Yoshiko Sano

The relationship between usual coffee consumption and serum C-reactive protein level in a Japanese female population.

Abstract Background: Usual coffee consumption may decrease insulin resistance and type 2 diabetes incidence, and reduce cardiovascular disease risk. As a mechanism, coffee-induced lower levels of C-reactive protein (CRP), a marker for the development of these diseases, can be considered. The associations between coffee consumption and CRP should be established by studies on various populations, yet studies in Japanese people, who do not necessarily consume as much coffee daily, are limited. Methods: In total, 459 community-living Japanese women, aged 23–83 years, were investigated. Clinical data including age, body mass index, blood pressure, HbA1c, serum high sensitive CRP (hsCRP) and lifestyle habits, such as coffee consumption, were included in the analyses. All analyses were performed in two groups of the population, i.e., age <60 and ≥60 years. Results: Significantly lower levels of hsCRP were observed in the group of ≥1 cup/day than in that of <1 cup/day in the respective groups of <60 years (p=0.001) and ≥60 years (p<0.0001). In multiple regression analysis, coffee consumption was significantly, independently and inversely correlated to log-hsCRP in the respective groups of <60 years (p=0.017) and ≥60 years (p<0.0001). Conclusions: It was noteworthy that the benefits of coffee consumption, even if ≥1 cup/day, on serum hsCRP levels were confirmed in Japanese women, following similarly to other ethnic data. Clin Chem Lab Med 2008;46:1434–7.

Short-Term Low Calorie Diet Intervention Reduces Serum Advanced Glycation End Products in Healthy Overweight or Obese Adults

Background: Obesity is a metabolic and cardiovascular risk factor. A low calorie diet (LCD) is one of the treatment modalities for weight loss. Serum advanced glycation end products (AGEs) are linked to increased atherogenicity and inflammation in diseases such as diabetes and renal failure. Obesity has an inflammatory component, but interestingly there are no studies on serum AGE levels in obesity or on the effects of LCD as a therapeutic measure on these markers of glycation. Aim: We hypothesized that weight loss by caloric restriction has a beneficial effect on serum AGE levels. We investigated the prospective effects of a sole LCD intervention for weight loss on serum AGEs in a cohort of overweight and non-morbidly obese but otherwise healthy subjects. Methods: A total of 37 Japanese subjects (30 females, 7 males, mean age 48.2 ± 9.3 years) with a mean BMI of 28.3 ± 3.2 participated in this study. During the intervention period of 2 months, they were placed on an LCD (Diet’s™; 5,023 kJ/day) with meal replacement every dinner. The following data were evaluated pre- and post-intervention: AGEs, BMI, waist circumference, blood pressure, serum glucose, cholesterol, triglycerides, HDL- and LDL- cholesterol. Results and Discussion: After the intervention, BMI levels were clearly reduced by 6.3% (p < 0.001), waist circumference by 5.7% (p < 0.002) and triglycerides by 11.9 % (p < 0.002). At baseline, AGEs levels were 63 ± 11 AU for obese subjects and 63 ± 14 for control subjects (not significant). After intervention, AGEs were reduced by 7.21% (range 0–35%, p < 0.001). The percent change in AGEs was significantly and positively correlated with that of triglycerides (r = 0.42, p < 0.009), waist circumference (r = 0.40, p < 0.011), and BMI (r = 0.42, p < 0.007). We show for the first time that serum AGEs can be reduced by an LCD intervention on weight loss, a change that correlates with the reduction in triglycerides. This may plausibly be a reflection of a reduction in glycation/lipoxidation due to the caloric restriction and its metabolic consequences, or it may be due to the decreased intake of food containing glycotoxins, or a combination of both.

The association of the Clock 3111 T/C SNP with lipids and lipoproteins including small dense low-density lipoprotein: results from the Mima study

BackgroundThe clock molecule plays major roles in circadian rhythmicity and regulating lipid and glucose metabolism in peripheral organs. Disruption of the circadian rhythm can lead to cardiometabolic disorders. The existence of small dense low-density lipoprotein (sdLDL) in the circulation, an abnormality of lipid metabolism, in part associated with lifestyle, is also one of risk parameters for cardiometabolic disorders. The 3111 T/C single nucleotide polymorphism (SNP) of the Clock gene has been reported to be associated with lifestyle including morning/evening preference. We investigated whether the Clock 3111 T/C SNP may affect lipids and lipoproteins including sdLDL.MethodsIn 365 community-dwelling subjects (170 men and 195 women, mean age 63 ± 14 years), the 3111 T/C SNP was genotyped using a fluorescent allele-specific DNA primer assay system. The levels of sdLDL were measured with the electrophoretic separation of lipoproteins employing the Lipoprint system.ResultsThe frequency of the Clock 3111 C allele was 0.14. The area of sdLDL did not differ between the subjects with obesity and those without. In carriers of T/T homozygotes, the area of sdLDL was significantly higher compared with carriers of the C allele (T/C or C/C) (1.7 ± 3.4 vs. 0.8 ± 1.9%; p < 0.05). A multiple regression analysis showed that the area of sdLDL was significantly and negatively correlated with the Clock 3111 T/C SNP (β = -0.114, p < 0.05), independently of age, sex, body mass index, and exercise habits.ConclusionOur findings indicated that the Clock 3111 T/C SNP might be associated with the existence of sdLDL.

The common −55 C/T polymorphism in the promoter region of the uncoupling protein 3 gene reduces prevalence of obesity and elevates serum high-density lipoprotein cholesterol levels in the general Japanese population

Uncoupling protein 3 (UCP3) is considered to be associated with obesity, given its function in the regulation of energy and lipid metabolism. An increased body mass index (BMI) and a decreased level of high-density lipoprotein cholesterol (HDL-C) are risk factors for cardiovascular disease. The purpose of this study was to investigate whether the UCP3 promoter -55 C/T single nucleotide polymorphism (UCP3 -55 C/T SNP) was associated with obesity according to the criteria for Japanese (BMI > or = 25 kg/m2), BMI, and serum HDL-C levels in the general Japanese population. The subjects, numbering 282 and aged 65 +/- 13 years (mean +/- SD), were recruited through an annual health checkup of residents of Mima city, Tokushima, in Japan. Body mass index, blood pressure, biochemical indexes including lipid, and lipoprotein profiles were measured. The UCP3 -55 C/T SNP was determined with a fluorescence-based allele-specific DNA primer assay system. The frequency of the -55 T allele was 30.0%. Subjects with the T/T genotype had significantly higher HDL-C levels than those with the C/C genotype or the C/T genotype. Furthermore, subjects with the T/T genotype had a significantly lower BMI than those with the C/C genotype. A multivariate analysis revealed that the -55 T allele was a significant independent variable contributing to the variance in HDL-C levels and BMI. The T/T genotype was associated with a lower prevalence of obesity than the C/C and C/T genotypes, with an odds ratio of 0.358 (95% confidence interval, 0.132-0.972; P = .037). In conclusion, the UCP3 -55 C/T SNP was associated with elevated HDL-C levels and a reduced BMI, independent of modifiable factors such as lifestyle. Furthermore, this polymorphism, when expressed in its homozygous form, reduced the prevalence of obesity in Japanese.

Genetic polymorphisms of the renin-angiotensin system and obesity-related metabolic changes in response to low-energy diets in obese women

OBJECTIVE Genetic polymorphisms of the renin-angiotensin system have been implicated in cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 3123C/A polymorphism of the angiotensin II type 2 receptor (AT(2)R) gene affect blood pressure and other obesity-related metabolic changes in response to low-energy diets using meal replacement shakes for weight loss. METHODS Clinical, metabolic, and biochemical profiles were measured before and after a 2-mo intervention in 32 obese women (age 49.9 ± 8.4 [SD] y; BMI 28.4 ± 3.3 kg/m²) restricted to 1200 kcal/d (5021 kJ/d). The polymorphisms were determined with an intercalater-mediated FRET probe assay system. RESULTS Although weight loss and nutrient intake levels did not differ among the genotypes, the reduction in body fat after weight loss was significantly less in the ACE deletion/deletion (D/D) genotype than insertion/insertion (I/I) plus I/D genotype (-2.25 ± 1.40% versus -0.80 ± 1.57%, P < 0.05). The AT₂R A/A group had significantly less improved levels of systolic blood pressure (-7.23 ± 8.50 versus 2.50 ± 12.6 mmHg, P < 0.05), low-density lipoprotein-cholesterol (-0.36 ± 0.29 versus -0.09 ± 0.25 mmol/L, P < 0.05), carbohydrate (-54.4 ± 27.2 versus -31.8 ± 16.3 mg/min, P < 0.05) and fat oxidation (8.31 ± 11.86 versus 0.05 ± 9.99 mg/min, P < 0.05) than the C/C plus C/A genotypes. CONCLUSION The present findings suggest that the homozygous form of the ACE gene may hinder the improvement of body fat and that the homozygous form of the AT₂R gene may make improving systolic blood pressure and some obesity-related metabolic parameters through a dietary intervention difficult among obese women.

Changes on the physiological lactonase activity of serum paraoxonase 1 by a diet intervention for weight loss in healthy overweight and obese women.

Low caloric diet (LCD) is used for weight loss. Paraoxonase 1 (PON-1) is associated with the antioxidant functions of high-density lipoprotein (HDL). Among limited data on the relationships between obesity and PON-1, there has been no study on the effects of a stand-alone LCD on the physiological lactonase activity of PON-1. We investigated the prospective effects of LCD intervention (2 months) for weight loss on serum PON-1 activities (lactonase, arylesterase [mono-esterase] and tri-esterase) and HDL cholesterol (HDL-C), and their association with low-density lipoprotein cholesterol (LDL-C) in overweight and non-morbidly obese but otherwise healthy women (n = 30; mean age, 50.3 years; mean body mass index [BMI], 28.5 kg/m2). In addition to the data such as BMI, blood pressure, blood glucose and lipids, PON-1 activities were examined between pre- and post-intervention. The intervention reduced all metabolic outcomes, and PON-1 lactonase activity (determined with 5-[thiobutyl]butyrolactone) significantly decreased by 6.1%, paralleled by arylesterase (by 7.3%) and tri-esterase (by 7.8%). In multiple regression analysis, the percent change of PON-1 lactonase was significantly, positively and independently correlated to that of LDL-C (β = 0.51), HDL-C (β = 0.40), and BMI (β = 0.37). Our results showed that the solo diet treatment on weight loss might reduce serum PON-1 lactonase activity with reduced HDL-C and LDL-C. The relationship between the lactonase and LDL-C may be adaptive, plausibly hypothesizing less need for PON-1 activity as an antioxidant property to protect lipoproteins. Further research is needed to confirm this prediction.

The relationship between adiponectin, an adiponectin gene polymorphism, and high-density lipoprotein particle size: from the Mima study

This study examined the association among serum adiponectin levels, a single nucleotide polymorphism (SNP) of the adiponectin gene, and the size of serum high-density lipoprotein (HDL) particles in a general population. A total of 275 subjects were examined as part of the community-based Mima study. Serum adiponectin levels were measured with an enzyme-linked immunosorbent assay. Serum small-sized HDL was measured with the electrophoretic separation of lipoproteins using the Lipoprint system. Single nucleotide polymorphism G276T (rs1501299, SNP276) of the adiponectin gene was determined with a fluorescent allele-specific DNA primer assay system. Age- and sex-adjusted correlation test revealed a significant inverse relationship between small-sized HDL and adiponectin levels (r = -0.236, P < .001). More percentages of small-sized HDL were observed in the subjects with the SNP276 G/G and G/T genotypes than in those with the T/T genotype (5.5% ± 5.0% vs 3.0% ± 2.9%, P = .016). In a multiple regression analysis, small-sized HDL was significantly and independently correlated with triglycerides levels (β = 0.133, P = .030), adiponectin levels (β = -0.242, P < .001), and the SNP276 G allele (β = -0.142, P = .014). Our findings indicated that adiponectin and SNP276 of the adiponectin gene may modify the size of HDL particles.

Lifestyles and oxidative stress in type 2 diabetic patients.

Kazuhiko Kotani, Naoki Sakane, Kokoro Tsuzaki, Yukiyo Matsuoka, Yoshiko Sano, Taku Hamada and Kazunori Yamada Division of Preventive Medicine and Diabetes Education, Clinical Research Institute for Endocrine and Metabolic Disease, National Hospital Organization Kyoto Medical Center, Kyoto, Japan; Division of Health Administration and Promotion, Faculty of Medicine, Tottori University, Tottori, Japan; Center for Diabetes, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

The angiotensin II type 2 receptor gene polymorphism and body mass index in healthy Japanese women

Background: Angiotensin II (AngII), through the AngII type 2 receptor (AT2-R), might exert some effect on adipocyte-and lipogenesis-related biology. The Adenine/Cytosine 3123 (A/C3123) polymorphism in the AT2-R gene is reportedly involved in some diseases, such as hypertension. Methods: A total of 201 healthy Japanese women (mean age 43.2 years) were enrolled in the study to investigate the association among the AT2-R A/C3123 polymorphism detected by polymerase chain reaction methods, body mass index (BMI) and other obesity-linked metabolic parameters (blood pressure, serum lipid/lipoprotein, plasma glucose). Results: Homozygotes of the C-allele in the AT2-R A/C3123 polymorphism were associated with small but significant increases in BMI levels. There were no differences between genotype-based groups in the obesity-linked metabolic parameters. Conclusion: These findings suggest that the AT2-R A/C3123 polymorphism could be a polymorphic marker related to BMI in Japanese women.

Adiponectin gene single-nucleotide polymorphisms and treatment response to obesity

Background: In the adiponectin gene polymorphisms, single-nucleotide polymorphism (SNP)−45 and SNP276 have reportedly been associated with obesity, Type 2 diabetes, and other features of metabolic syndrome. Aim: Whether these adiponectin SNP affect obesity-related parameters during caloric restriction in obese subjects. Subjects and methods: Thirty-two obese Japanese women were treated by meal replacement with a low calorie diet for 8 weeks and asked to maintain their habitual lifestyle. Obesity-related parameters were measured before and after the treatment period. We determined four SNP (T45G, I164T, G276T, and C-11377G) using a fluorescent allele-specific DNA primer assay system and FRET probe assay system. Results: After the treatment, the extent of decrease in waist circumference was greater in the subjects with the G/G or G/T genotype of SNP276 than in those with the T/T genotype (p=0.026). As for SNP45, the extent of decrease in triglyceride levels was greater in the subjects with the T/T genotype than in those with the T/G genotype (p=0.003). For SNP-11377, the extent of decrease in systolic blood pressure and fasting plasma glucose was greater in the subjects with the C/G or G/G genotype than in those with the C/C genotype (p=0.044). Conclusion: Our findings indicate that each SNP in the adiponectin gene might modify the change in obesity-related parameters during meal replacement with a low calorie diet.