Kyoko Saiga

Leptin : adiponectin ratio as an atherosclerotic index in patients with type 2 diabetes : relationship of the index to carotid intima–media thickness

To the Editor: Diabetic metabolic abnormalities induce vascular dysfunction that predisposes diabetic patients to atherosclerosis [1]. Complications of atherosclerosis cause much of the disability and most of the mortality in diabetic patients [1]. Clinical atherosclerotic manifestations in diabetes occur primarily in vascular beds such as extracranial carotid arteries and coronary arteries [1]. On the other hand, two adipocytokines, leptin and adiponectin, play important roles in the metabolic regulation of obesity and obesity-related complications [2]. In obese subjects, plasma leptin concentrations are elevated and adiponectin concentrations decreased. Consequently, it is speculated that leptin could accelerate and adiponectin restrain the development of atherosclerosis [2]. Recently, Satoh et al. [2] reported that the plasma leptin : adiponectin ratio (L : A) is correlated with pulse wave velocity values and may be a useful biomarker for atherogenesis in obese type 2 diabetic patients. However, the significance of the L : A in diabetes has still not been thoroughly investigated. Considerable research has established carotid intima– media thickness (CIMT) as a clinical surrogate marker of atherosclerosis [3]. Although pulse wave velocity values can be roughly correlated with CIMT [3], when assessing pulse wave velocity in clinical practice, confounding factors such as abnormalities of blood pressure (BP), blood flow and sympathetic tones might increase the variability of pulse wave velocity [4] that is often observed in subjects with obesity and type 2 diabetes. Also, atherosclerosis involves two different processes: atherosis and sclerosis of the arterial wall [3]. CIMT seems to reflect atherotic (structural) changes more accurately than pulse wave velocity values, whereas the latter is considered as more of a reflection of sclerotic (functional) changes [3, 5]. Type 2 diabetes accelerates both types of change, whereas hyperlipidaemia causes mostly atherotic changes [3]. In another study using CIMT measurements [6], type 2 diabetes caused atherosclerosis at a more accelerated rate than hypercholesterolaemia, suggesting an important role of CIMT as a surrogate of atherosclerosis in diabetes. It is therefore crucial to determine whether the findings of Satoh et al. [2] are replicable with regard to CIMT measurement. With these results in mind, we examined the relationship between L : A and CIMT in patients with diabetes. A total of 152 Japanese type 2 diabetic patients (73 men, 79 women; mean age=70.1±8.7 years [mean±standard deviation]), with stable conditions, and treated with diet and/or sulfonylureas, were enrolled for this study. Sixtythree subjects were treated with sulfonylureas and 89 were treated with diet only. The study was approved by the institutional ethics committee and each subject gave informed consent. Smokers were defined as current smokers. Of the smokers, 39 were men and 10 were women. Overnight fasting plasma insulin, lipid panels and blood HbA1c values were measured by the standard procedures. Plasma leptin levels were measured using a commercially available enzyme immunoassay kit (Cayman Chemical Company, Ann Arbor, MI, USA), and adiponectin levels were measured with an enzyme-linked immunosorbent assay kit (Otsuka Pharmaceutical, Tokyo, Japan). We measured BP in the right upper arm of seated patients using a standard sphygmomanometer. CIMT was determined using a Bmode ultrasound scanner (SSD-900; Aloka, Tokyo, Japan) K. Kotani (*) . K. Saiga . Y. Kurozawa Division of Health Administration and Promotion, Tottori University, 86 Nishi-cho, Yonago, 683-8503, Japan e-mail: kakotani@grape.med.tottori-u.ac.jp Tel.: +81-859-348026 Fax: +81-859-348085

Serum adiponectin levels and lifestyle factors in Japanese men

Adiponectin plays an important role in the development of various lifestyle-related diseases such as obesity, hypertension, type II diabetes mellitus, hyperlipidemia, and metabolic syndrome, leading to the development of heart and vascular diseases. However, the determinants that affect circulating adiponectin levels, including lifestyle factors, have still not been thoroughly investigated, in a general male population in particular. A total of 109 healthy Japanese male subjects (mean age, 55 ± 14 years) with constant lifestyles were enrolled. All were on no medication. Fasting serum adiponectin levels were measured with an enzyme-linked immunosorbent assay. Each subjects lifestyle was assessed by the self-administered Breslow Questionnaire (a well-established method to estimate various lifestyles) with minor modifications. Partial correlation analysis for serum adiponectin levels, after controlling age and all lifestyle factors, revealed a significant and independent negative correlation between serum adiponectin levels and body mass index (BMI) (r = −0.222, P = 0.025), and a significant and independent positive correlation between serum adiponectin levels and sleep duration (r = 0.252, P = 0.011). No significant correlations were observed between adiponectin and other lifestyle factors. These data suggest that increased BMI and shorter sleep duration may be significant independent risks for low serum adiponectin levels in healthy males. Therefore, these factors may be intervention targets to modulate adiponectin to its proper levels for the prevention of cardiovascular disorders.

Clustered components of the metabolic syndrome and platelet counts in Japanese females

Abstract Background: Blood platelet counts (PCs) play a role in the development of cardiovascular disease (CVD). The metabolic syndrome (MS) is also associated with high CVD risk. However, the connection between PCs and MS has not yet been thoroughly investigated in relation to various biosocial factors that can affect both PCs and the pathophysiology of MS. Methods: A total of 152 asymptomatic female subjects (mean age 50 years) with almost normal levels of hemoglobin and white blood cell counts were recruited. MS was diagnosed according to the NCEP-ATP III criteria with a minor modification. The relationships between PCs and MS were analyzed according to the number of MS components (0, 1–2, ≥3). Biosocial factors including age and some lifestyle factors (smoking, alcohol intake and physical activity) were included in the analyses. Results: PCs in subjects with ≥3 MS components (233±43 [SD]×109 /L) were strikingly and significantly higher than in subjects with 0 (194±34×109/L) or 1–2 MS components (207±38×109/L). General linear model analysis for PCs, adjusted for all biosocial factors and number of MS components, revealed a significant and positive correlation between PCs and number of MS components (p<0.0001). Conclusions: The results suggest that PCs may be a potential marker associated with clustered MS components, independent of some biosocial factors, in Japanese females. Clin Chem Lab Med 2007;45:376–9.

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.

Epstein-Barr virus DNA is detected in peripheral blood mononuclear cells of EBV-seronegative infants with infectious mononucleosis-like symptoms

We demonstrated Epstein–Barr virus (EBV) DNA in peripheral blood mononuclear cells (PBMCs) from infants with infectious mononucleosis- (IM) like symptoms. Thirteen of the 17 patients did not have EBV antibodies; however, EBV DNA was detected in 8 PBMC from the 13 seronegative patients by PCR. The 4 patients were retested in 6–12 months later. Three patients were still seronegative; however EBV DNA was not detected. One patient seroconverted and EBV DNA could still be detected. The transcript of EBNA1 was detected in one patient, but neither EBNA2 nor LMP2A were detected in all PBMC from the 4 tested patients. Type 1 EBV DNA was detected in 5 PBMC of 7 tested patients, and type 2 EBV DNA was detected in type 1 positive PBMC of one patient as well. The IL-1 β polymorphism that is reported to be one of the immunological factors of EBV seronegativity revealed no difference in IM-like patients. These results indicated that EBV infection occurs in EBV-seronegative IM-like infants; however, the modes of infection are clearly different from IM.

Reduction in protein S activity during normal pregnancy

We investigated the serial changes in blood protein S (PS) and related proteins in 11 normal pregnant women. The PS activity decreased significantly in the third trimester and reached minimum levels (23.3%) one hour after delivery. Although the PS activity was reduced markedly below the normal limits, all the women delivered safely. The mechanisms that cause the reduction in PS activity and the clinically dangerous conditions involving PS activity during pregnancy warrant further investigation.

The uncoupling protein-1 gene -3826A/G polymorphism and hypertension in Japanese subjects.

Abstract Background: The possible effects of the uncoupling protein-1 (UCP-1) gene −3826A/G polymorphism on hypertension (HT) have yet to be elucidated. Methods: A total of 578 Japanese subjects (231 males and 347 females, mean age 58.4 years) were enrolled in the study to investigate the association between HT and the −3826A/G polymorphism by genomic PCR and Bcl1-restriction fragment length polymorphism methods. Results: Multivariate logistic regression analysis for HT, adjusted for genotype (recessive model, AA+AG vs. GG) and other covariates such as cardiovascular risk factors [e.g., smoking, body mass index (BMI), dyslipidemia and diabetes] showed age [odds ratio (OR) 1.11 (95% confidence interval 1.08–1.13)] and BMI [OR 1.13 (1.06–1.21)] as independent significant factors. In the subgroup analysis, as well as age and BMI, GG genotype [OR 2.32 (1.08–4.99)] was also an independent significant factor for HT in males. Similarly, as well as age and BMI, GG genotype [OR 1.89 (1.00–3.57)] was also an independent significant factor for HT in the relatively older subgroup (≥60 years). Conclusions: The results suggest that the GG genotype may be associated with the presence of HT in Japanese males and older subjects. Further investigation is needed to confirm our hypothesis. Clin Chem Lab Med 2007;45:1186–9.