Yuko Yamazaki

Fetuin-A and atherosclerotic calcified plaque in patients with type 2 diabetes mellitus.

Fetuin-A is a multifunctional circulating glycoprotein. Among its roles, inhibition of ectopic calcification is a prominent feature. Low fetuin-A levels in dialysis patients are associated with cardiovascular mortality, possibly via accelerating vascular calcification. However, except for dialyzed conditions, a correlation between fetuin-A levels and vascular calcification remains controversial. Furthermore, any inhibitory effect of fetuin-A on atherosclerotic calcified plaques (CPs) remains unclear compared with its effect on medial artery calcification that is often found in dialyzed patients. Therefore, we examined the association between fetuin-A levels and atherosclerotic CPs. For this study, 416 consecutive patients with type 2 diabetes mellitus and without renal dysfunction were examined. We measured serum fetuin-A levels and investigated for the presence of CP in the common carotid and femoral arteries using ultrasonography. Fetuin-A levels were significantly lower in patients with CP than those without CP (262.6 +/- 56.7 and 281.5 +/- 64.6 microg/mL, respectively; P = .001). Multivariate logistic regression analysis showed that fetuin-A levels were inversely associated with the presence of CP (odds ratio = 0.753; 95% confidence interval, 0.608-0.933; P = .010). These results suggest that fetuin-A may inhibit the calcification of atherosclerotic plaques independently of the dialyzed condition.

Plasma polyunsaturated fatty acid profile and delta-5 desaturase activity are altered in patients with type 2 diabetes

OBJECTIVE The association between imbalance of polyunsaturated fatty acids (PUFAs), especially low plasma n-3 to n-6 PUFA ratio, and risk of cardiovascular diseases is well known. A balance of plasma PUFAs is determined not only by dietary fatty acid intake, but also by the endogenous fatty acid metabolism, which could be dysregulated by diabetes. In this study, we investigated the plasma n-3 and n-6 PUFA profile and fatty acid desaturase activity in patients with type 2 diabetes (T2D). MATERIALS/METHODS The subjects were 396 patients with T2D and 122 healthy controls. Plasma eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA) levels were measured by capillary gas chromatography. RESULTS Plasma DHA, AA, and DGLA levels were significantly higher, and EPA levels tended to be lower in patients with T2D than in the controls. Patients with T2D also exhibited significantly lower EPA/AA, DHA/AA, and (EPA+DHA)/AA ratios, and a higher AA/DGLA ratio than the controls. Multiple regression analyses, including age, sex, body mass index, and metabolic parameters in the total population, revealed that the presence of T2D was independently associated with elevated plasma DHA, AA, and DGLA levels and decreased EPA/AA, DHA/AA, and (EPA+DHA)/AA ratios. Furthermore, T2D was independently and positively related to the AA/DGLA ratio, which serves as an estimate of delta (Δ)-5 desaturase activity. CONCLUSIONS Elevated plasma AA levels and decreased n-3 PUFA/AA ratios in T2D are attributable, at least partly, to Δ5 desaturase activation.

Association of serum TRAIL levels with atherosclerosis in patients with type 2 diabetes mellitus

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was originally isolated as an inducer of apoptosis. Recent cross-sectional and prospective studies suggest an inverse association of serum TRAIL levels with the severity of coronary artery disease (CAD) and with an adverse outcome in patients with CAD or heart failure. However, it is unknown whether TRAIL can inversely reflect the progression of atherosclerosis from its early stage. We therefore examined the association between TRAIL measured by ELISA and intima-media thickness (IMT) in carotid and femoral arteries evaluated by ultrasonography as a surrogate marker of atherosclerosis in 416 type 2 diabetic patients without any symptoms of CAD and heart failure. Concurrently, the existence of calcified plaque (CP) was examined. There was no significant association between TRAIL and carotid IMT (ρ=-0.096, p=0.052) or femoral IMT (ρ=-0.025, p=0.610), although TRAIL was associated with carotid IMT in a subset of patients with macrovascular diseases (ρ=-0.174, p=0.034). No difference in TRAIL levels was found between two groups with or without CP. TRAIL may not be a good candidate as a biomarker to evaluate early-stage atherosclerotic lesions.

Immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with diabetes mellitus: With special reference to age, body mass index, and HbA1c

Subjects with diabetes mellitus are considered to be at high risk of influenza infection and influenza-associated complications. To evaluate the immunogenicity of the influenza A(H1N1)pdm09 vaccine among these subjects, we performed a prospective cohort study and measured hemagglutination inhibition antibody titers at baseline and 3 weeks after vaccination in 49 patients. No serious adverse events were reported. We were able to perform analyses for 48 patients, after excluding one patient with suspected infection. The vaccine induced a rise of about 9-fold in the mean antibody level. The sero-response proportion was 79%, and the sero-protection proportion was 73%. Patients with older age and lower body mass index tended to show lower immune response. Multivariate analysis indicated an independent negative effect of hemoglobin A1c level on the sero-protection proportion. A single A(H1N1)pdm09 vaccination achieved a sufficient level of immunity among diabetic patients, but both clinicians and patients should be aware of the potential for reductions in immune response.

Advantage of insulin glulisine over regular insulin in patients with type 2 diabetes and severe renal insufficiency.

OBJECTIVES To compare the efficacy and safety of insulin glulisine over regular insulin in patients with type 2 diabetes and severe renal insufficiency. SUBJECTS Our study included 18 patients with type 2 diabetes and a mean (range) estimated glomerular filtration rate of 13.2 mL/minute/1.73 m(2) (5.8-27.6), which corresponds to stage 4-5 chronic kidney disease. DESIGN After titration of doses, regular insulin was administered thrice daily on Day 1, along with continuous glucose monitoring for 24 h starting at 7 am. Exactly equal doses of insulin glulisine were administered on Day 2. Area under the curve (AUC) for blood glucose level variation after breakfast (AUC-B 0-4), lunch (AUC-L 0-6), and dinner (AUC-D 0-6) were evaluated. RESULTS AUC-B 0-4 and AUC-D 0-6 were significantly lower with insulin glulisine than with regular insulin (AUC-B 0-4: 3.3 ± 4.7 vs. 6.2 ± 5.4 × 10(2) mmol/L·minute, respectively, P = .028; AUC-D 0-6: 1.8 ± 7.3 vs. 6.5 ± 6.2 × 10(2) mmol/L·minute, respectively, P = .023). In contrast, AUC-L 0-6 was higher with insulin glulisine than with regular insulin (AUC-L 0-6: 7.6 ± 6.4 vs. 4.2 ± 8.7 × 10(2) mmol/L·minute, respectively, P = .099), suggesting a prolonged hypoglycemic action of regular insulin after lunch. CONCLUSIONS Insulin glulisine effectively suppressed postprandial hyperglycemia, whereas regular insulin caused a prolonged hypoglycemic action. These findings support the effectiveness and safety of insulin glulisine in patients with type 2 diabetes and severe renal insufficiency.

Visceral Adiposity is Preferentially Associated with Vascular Stiffness Rather than Thickness in Men with Type 2 Diabetes.

Aim: Visceral fat accumulation is known to underlie the clustering of cardiovascular risk factors. However, it is not completely understood how visceral fat accumulation influences the development of cardiovascular disease. In this study, we investigated the clinical impact of visceral adiposity on vascular stiffness and thickness in patients with type 2 diabetes (T2D). Methods: One hundred and sixty-one patients with T2D, including 92 men and 69 women, were included in this cross-sectional study. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by dual bioelectrical impedance analysis. Stiffness parameter β and intima-media thickness (IMT) of the common carotid artery were measured by ultrasonography. Results: The mean age and duration of diabetes in the study population were 61 years and 13.9 years, respectively. In men, VFA and waist circumference (WC) were positively correlated with stiffness parameter β, whereas body mass index (BMI), WC, and SFA were negatively correlated with IMT. In contrast, in women, none of the obesity-related indices were significantly correlated with stiffness parameter β or IMT. In multiple regression analyses, VFA as well as WC, BMI, and SFA were independently associated with stiffness parameter β after adjustment for age and other potential confounders in men but not in women. None of the obesity-related indices were independently associated with IMT for either sex. Conclusion: In men with T2D, visceral adiposity is associated with carotid arterial stiffness but not thickness.

Plasma soluble leptin receptor levels are associated with pancreatic β-cell dysfunction in patients with type 2 diabetes

A soluble form of the leptin receptor (soluble Ob‐R) in the circulation regulates leptins bioactivity, and is inversely associated with body adiposity and circulating leptin levels. However, no study has examined the clinical impact of soluble Ob‐R on glucose metabolism in diabetes. The present study aimed to investigate the association of plasma soluble Ob‐R levels with insulin resistance and pancreatic β‐cell function in patients with type 2 diabetes.

Plasma C1q/TNF-Related Protein-9 Levels Are Associated with Atherosclerosis in Patients with Type 2 Diabetes without Renal Dysfunction

Aim. C1q/tumor necrosis factor-related protein-9 (CTRP9), a paralog of adiponectin, is expressed in adipose tissue. CTRP9 exerts protective effects against obesity and atherosclerosis in rodents. We investigated the association between plasma CTRP9 levels and atherosclerosis in patients with type 2 diabetes. Methods. We included 419 patients with type 2 diabetes, 161 of whom had chronic kidney disease (CKD). Fasting plasma CTRP9 and total adiponectin levels were measured with enzyme-linked immunosorbent assay. The intima-media thickness (IMT) of the common carotid artery was measured with ultrasonography. Results. Plasma CTRP9 levels were higher in the CKD group than in the non-CKD group. Plasma CTRP9 levels were positively correlated with carotid IMT in the non-CKD group. Multivariate analyses revealed that plasma CTRP9 levels were positively associated with carotid IMT in the non-CKD group, independent of age, sex, body mass index, adiponectin, and other cardiovascular risk factors. However, plasma CTRP9 levels were not associated with carotid IMT in the CKD group. Conclusion. Plasma CTRP9 levels are associated with atherosclerosis in diabetic patients without CKD, independently of obesity, adiponectin, and traditional cardiovascular risk factors. This study indicates a potential role of CTRP9 in atherosclerosis progression in human type 2 diabetes.

The Association between Monocyte Surface CD163 and Insulin Resistance in Patients with Type 2 Diabetes

Aim To investigate the association between monocyte CD163 and insulin resistance in patients with type 2 diabetes. Methods One hundred sixty-six patients with type 2 diabetes without inflammatory or chronic kidney disease were recruited. The monocyte CD163 levels were measured by flow cytometry and soluble CD163 (sCD163) by ELISA. Insulin resistance was evaluated by the index of the homeostasis model assessment (HOMA-R). Results The median sCD163 and monocyte CD163 expression levels were 582.9 (472.4–720.0) ng/ml and 6061 (4486–7876) mean fluorescent intensity (MFI), respectively. In a simple regression analysis, monocyte CD163 was inversely correlated with log [HOMA-R] (r = –0.257, p = 0.010), and sCD163 was positively correlated with log [HOMA-R] (r = 0.198, p = 0.042). In multiple regression analyses, monocyte CD163 was an independent contributor to log [HOMA-R] (β = –0.220, p = 0.020) even after adjustment of various clinical factors for HOMA-R (R2 = 0.281, p = 0.001), whereas sCD163 was not. Conclusions Monocyte surface CD163 expression levels were more significantly associated with insulin resistance than sCD163 in patients with type 2 diabetes, suggesting a novel pathophysiological role of CD163.

Positive Association of Plasma Leptin with Sleep Quality in Obese Type 2 Diabetic Patients

Poor sleep quality is associated with obesity and diabetes. The adipocyte‐derived hormone, leptin, was recently shown to underlie the link between abnormal sleep and obesity. We aimed to investigate the association between leptin and sleep quality in type 2 diabetes patients.