Validity of Atherosclerotic Calcified Lesions Observed on Low-Dose Computed Tomography and Cardio-Ankle Vascular Index as Surrogate Markers of Atherosclerosis Progression.

The significance of atherosclerotic calcified lesions observed on low-dose computed tomography (LDCT) performed during general checkups was investigated. The coronary arteries (CA), ascending aorta and aortic arch (AAAA), descending thoracic aorta (DTA), and abdominal aorta (AA) were examined. Semiquantitative calcified index analysis of the DTA and AA in terms of atherosclerosis risk factors and cardio-ankle vascular index (CAVI) measurements was also performed. We included 1594 participants (mean age: 59.2 years; range: 31-91 years). The prevalence of calcified lesions was 71.0%, 66.6%, 57.2%, and 37.9% in the AA, CA, AAAA, and DTA, respectively. Age-related advances in calcification among participants with no major risk factors, revealed that calcification appeared earliest in the AA, followed by the CA, AAAA, and DTA. Participants with calcified lesions in all arteries had a significantly greater CAVI than those without calcification. The CAVI was negatively correlated with low-density lipoprotein cholesterol levels, particularly in participants without calcified lesions in the DTA. Calcified lesions on LDCT could indicate the end stage of atherosclerotic lesions. The CAVI can be used to assess atherosclerotic changes at all stages of disease progression. A combination of LDCT and CAVI could be used as a routine non-invasive assessment of atherosclerosis.

Low Bilirubin Levels Indicate a High Risk of Cerebral Deep White Matter Lesions in Apparently Healthy Subjects.

Recent studies have reported that deep white matter lesions (DWMLs) on magnetic resonance imaging scans are related to the risk of developing impaired cognitive function in future. Bilirubin exhibits a potent antioxidant effect and an inverse relationship has been reported between bilirubin levels and the risk of several atherosclerotic diseases; however, there is limited evidence with regard to the effect of bilirubin levels on cerebrovascular diseases including DWMLs. This cross-sectional study included 1121 apparently healthy Japanese adults. The subjects were divided into three groups according to their bilirubin levels (low, <0.5 mg/dl; intermediate, ≥0.5 mg/dl and <1.0 mg/dl; and high, ≥1.0 mg/dl). The severity of DWMLs was evaluated according to Fazekas scale and their relation to bilirubin levels was examined. The association between bilirubin levels and the presence of severe DWMLs was assessed using multivariate logistic regression analysis. The analysis revealed that the low- and intermediate bilirubin groups indicated 2.36- and 1.33-fold increase in the prevalence of severe DWMLs compared with the high-bilirubin group, respectively (95% confidence interval (CI): 1.12-4.97 (the low-bilirubin group), 95% CI: 0.85-2.07 (the intermediate-bilirubin group). In conclusion, low total bilirubin levels could be associated with a high prevalence of severe DWMLs in apparent healthy subjects.

Visceral-to-subcutaneous fat ratio is independently related to small and large cerebrovascular lesions even in healthy subjects.

BACKGROUND AND AIMS: The severity of obesity is evaluated by visceral-to-subcutaneous fat ratio (VS ratio), which may be useful for predicting atherosclerosis. However, it is unclear how VS ratio affects different types of cerebrovascular lesions. This study was conducted to evaluate the clinical impact of visceral fat accumulation on the cerebrovascular lesions. METHODS: This cross-sectional study included 980 apparently healthy Japanese adults who underwent a health check-up program focused toward atherosclerosis, between 2011 and 2014. Visceral and subcutaneous fat accumulation was measured using abdominal computed tomography, and its relation to cerebrovascular disease was surveyed. RESULTS: Visceral and subcutaneous fat accumulation was 88 ± 50 cm2 and 141 ± 77 cm2, respectively. VS ratio was 0.69 ± 0.38. Intimal thickening in the carotid arteries was detected in 849 cases (86.6%) and stenosis was observed in seven (0.7%). Brain magnetic resonance imaging showed white matter hyperintensities regarded as ischemic changes in 196 subjects (20.0%). Multiple logistic regression analysis adjusted for age, gender, diabetes mellitus, dyslipidemia, hypertension, and hyperuricemia showed that a 0.1 increase in VS ratio was related to the presence of ischemic changes [odds ratio (OR): 1.05, 95% CI: 1.01-1.10, p = 0.009], cerebral artery stenosis or occlusion (OR: 1.14, 95% CI: 1.03-1.25, p = 0.007), and cervical plaque (OR: 1.09, 95% CI: 1.05-1.13, p < 0.001). CONCLUSIONS: VS ratio was independently associated with both large and small vessel lesions in apparently healthy subjects.

Factors affecting consultation length in a Japanese diabetes practice.

AIMS: Sufficient consultation time is important for establishing good doctor-patient relationship. We examined the factors that affect consultation length in Japanese diabetes practice. METHODS: This was a cross-sectional study performed at a diabetes clinic in central Tokyo, Japan. Regular diabetes consultations of 1197 patients with 22 physicians were analyzed. Consultation time and clinical characteristics were obtained from the electronic records. A negative binomial model, which included patient and physician characteristics, was constructed to examine the association of the variables with consultation length. RESULTS: Of the 1197 patients (mean age, 66; women, 25%; type 1 diabetes, 10%), the mean consultation time was 10.1min. In the multivariate model, longer consultation time was recorded in patients with type 1 diabetes, higher glycated hemoglobin (HbA1c), use of insulin injections, and use of hypnotics/anxiolytics. The consultation time was longer in patients with HbA1c of ⩾7.0 to <8.0% (⩾53 to <64mmol/mol), ⩾8.0 to <9.0% (⩾64 to <75mmol/mol) and ⩾9.0% (⩾75mmol/mol), compared to those with HbA1c of <7.0% (<53mmol/mol) with the ratios of 1.03 (95% confidence interval (CI)=0.96-1.10), 1.16 (95% CI=1.07-1.26) and 1.17 (95% CI=1.06-1.29), respectively. Body mass index was also associated with long consultation. Older and female physicians provided longer consultation. CONCLUSIONS: Clinical consultation length in diabetes practice was associated with certain patient and physician characteristics. The findings can be used for making diabetes consultation more efficacious, which could eventually lead to the provision of the most appropriate consultation time for individual patients.

Concentrations of various tryptophan metabolites are higher in patients with diabetes mellitus than in healthy aged male adults.

Tryptophan metabolites in plasma samples from 20 male subjects with type 2 diabetes mellitus (T2DM) and 20 nondiabetic reference males were analyzed by ultra high performance liquid chromatography. Tryptophan levels in the diabetic subjects were significantly lower than those in nondiabetic subjects. The concentrations of 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and xanthurenic acid were found to be higher in the diabetic patients. When the diabetic patients were divided into higher- and lower-tryptophan groups, the concentrations of 5-hydroxytryptophan, indole-3-acetic acid, kynurenine, 5-hydroxykynurenine, and kynurenic acid were found to be higher in the diabetic patients with higher tryptophan levels. However, diabetic patients with lower plasma tryptophan levels had higher levels of 5-hydroxyindoleacetic acid than the patients with higher tryptophan levels. These results suggest that tryptophan was metabolized more in T2DM patients than in nondiabetic subjects. In the kynurenine pathway, the degradation of tryptophan seems to be accelerated in patients with higher plasma levels of tryptophan than in patients with lower levels of tryptophan. In the serotonin pathway, when the level of tryptophan is low, the conversion of serotonin to 5-hydroxyindoleacetic acid appears to be accelerated. In conclusion, our results suggest that T2DM patients may be exposed to stress constantly.

Higher Body Mass Index and Increased Prevalence of Paranasal Sinus Disease.

BACKGROUND: We hypothesized that higher body mass index (BMI) was associated with increased prevalence of paranasal sinus disease and examined the hypothesis in Japanese adults. METHODS: This was a cross-sectional study including 1350 Japanese adults aged 40 years or more who participated in a health check-up program focusing on brain diseases and metabolic syndrome. Participants were divided into quartiles of BMI levels. Paranasal sinus disease was confirmed by a head MRI scan. The association between BMI and paranasal sinus disease was examined using logistic regression analysis, which was adjusted for age, sex, waist:hip ratio, hemoglobin A1c, systolic blood pressure, smoking status, alcohol intake, and white blood cell count. RESULTS: Of the 1350 participants, 151 (11.2%) had paranasal sinus disease. In relation to those in the lowest quartile of BMI, the odds ratios of having the disease among those in the 2nd, 3rd, and 4th quartiles of BMI were 1.89 (95% confidence interval [CI], 1.03-3.48), 2.26 (95% CI, 1.20-4.23) and 2.26 (95% CI, 1.14-4.51), respectively. When BMI was analysed as a continuous variable, an increase of one unit in BMI was significantly associated with increased odds of having the disease, with an OR of 1.08 (95% CI, 1.01-1.16). CONCLUSIONS: The present study suggests that patients with higher BMI are more likely to have paranasal sinus disease.

Clinical Background of Patients with Sperm in Their Urinary Sediment.

INTRODUCTION: The detection rate and associated factors of at least one sperm in urinary sediment is not well-known in real clinical practice. AIMS: The aim of the present study was to evaluate the clinical features associated with the presence of sperm in urinary sediment in a large number of samples. METHODS: We conducted a cross-sectional study at Tokyo Saiseikai Central Hospital. We identified 5,005 males who were aged ≥20 years in whom urinary sedimentation had been performed at least twice between May 2011 and June 2012. The sperm group included patients in whom at least one urinary sediment test performed under a microscope had detected at least one sperm. We evaluated the associations between the presence of at least one sperm in urinary sediment and clinical parameters such as various diseases and the use of particular oral medicines. MAIN OUTCOMES: In total, 1.6% (339/20,937) of urinary sediment samples contained at least one sperm. The sperm group consisted of 282 subjects (5.6%), and the no-sperm group included 4,723 subjects (94.3%). RESULTS: Multivariate analysis demonstrated that younger age (<65) (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.32-2.21), the total number of examinations (≥4) (OR: 1.46, 95%CI: 1.11-1.92), diabetes (OR: 1.72, 95%CI: 1.31-2.25), a history of pelvic surgery for colon cancer (OR: 4.89, 95%CI: 2.38-10.02), alpha-1 blocker use (OR: 1.55, 95%CI: 1.16-2.08), a history of trans-urethral resection of the prostate (OR: 2.77, 95%CI: 1.46-5.13), and selective serotonin reuptake inhibitor use (OR: 2.12, 95%CI: 1.07-4.19) were independent predictors of the presence of at least one sperm in urinary sediment. CONCLUSION: There is considerable overlap between the factors associated with the presence of at least one sperm in urinary sediment and those that are strongly associated with ejaculatory disorders.

Association between diabetes and increased prevalence of paranasal sinus disease: a cross-sectional study in Japanese adults.

BACKGROUND: The association between diabetes and paranasal sinus disease has not been thoroughly investigated. METHODS: We cross-sectionally investigated the association between diabetes and the presence of paranasal sinus disease, which was confirmed by a head MRI scan in 1350 adults who underwent a health screening program focusing on brain diseases and metabolic syndrome. Logistic regression, which was adjusted for age, sex, body mass index, waist-to-hip ratio, hypertension, smoking status, alcohol intake, and white blood cell count, was performed to calculate the odds ratio (OR) of having paranasal sinus disease among adults with diabetes in relation to those without. The dose-response relationship between hemoglobin A1c (HbA1c) levels and the presence of paranasal sinus disease was also investigated. RESULTS: Of the 1350 participants (mean age, 61.6 ± 10.0 years; 71.6% men), 220 diabetes cases were identified. Paranasal sinus disease was diagnosed in 151 adults. The adjusted OR of having paranasal sinus disease was 1.74 (95% confidence interval [CI], 1.12-2.71) in those with diabetes. The odds of having paranasal sinus disease increased with HbA1c levels. Compared to those with HbA1c of ≤5.4%, those with HbA1c of 5.5%-6.4%, 6.5%-7.9%, and ≥8.0% were more likely to have paranasal sinus disease, with adjusted ORs of 1.32 (95% CI, 0.88-1.98), 1.63 (95% CI, 0.86-3.09) and 2.71 (95% CI, 1.12-6.61), respectively (P for trend = 0.019). CONCLUSIONS: Diabetes may be significantly associated with higher prevalence of paranasal sinus disease in Japanese adults. We should keep this increased risk in mind when a diabetic patient is suspected of having paranasal sinus disease.

Negative associations between arterial stiffness parameter evaluated by cardio-ankle vascular index and serum low-density lipoprotein cholesterol concentration in early-stage atherosclerosis.

The cardio-ankle vascular index (CAVI), calculated values from cardio-ankle pulse wave velocity and blood pressure, corresponds predominantly to the stiffness of the aorta and peripheral arteries of the lower limbs. However, the reported associations between CAVI and serum low-density lipoprotein cholesterol (LDL-C) levels remain inconsistent. A cross-sectional study of 1878 consecutive patients (mean age: 59.2 years) who underwent general health checkup showed a negative association between CAVI and serum LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) concentrations with age-adjusted correlation and multiple regression analysis. Using the similar analyses divided by the status of risk factors and degree of maximum carotid intima-media thickness (maxIMT), negative correlations between CAVI and LDL-C or non-HDL-C levels were observed only in nonrisk groups including nondiabetics patients or patients with maxIMT <1.0 mm, in those with expected low extent of advanced atherosclerotic lesions. In contrast, such a correlation was not found in each comparable risk-loaded group.

Association of glycemic status with impaired lung function among recipients of a health screening program: a cross-sectional study in Japanese adults.

BACKGROUND: The dose-response relationship between glycemic status and lung function has not been thoroughly investigated. We hypothesized that there are continuous and inverse associations between glycemic measures and lung function tests and examined the hypothesis in Japanese adults. METHODS: We cross-sectionally investigated associations of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) with forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in 3161 adults who participated in a health screening from 2008 to 2011. The study participants included both diabetic and non-diabetic adults. Multiple linear regression analyses were performed to examine the associations. RESULTS: Inverse associations were observed in both sexes, which were attenuated in women after adjustment for multiple variables. A 1% absolute increase in HbA1c was associated with a -52-mL (95% confidence interval [CI] -111 to 8 mL) difference in FVC and a -25-mL (95% CI -75 to 25 mL) difference in FEV1 in women, and a -128-mL (95% CI -163 to -94 mL) difference in FVC and a -73-mL (95% CI -101 to -44 mL) difference in FEV1 in men. A 10-mg/dL increase in FPG was associated with a -11-mL (95% CI -29 to 8 mL) difference in FVC and a -8-mL (95% CI -24 to 7 mL) difference in FEV1 in women, and a -32-mL (95% CI -44 to -21 mL) difference in FVC and a -19-mL (95% CI -28 to -9 mL) difference in FEV1 in men. CONCLUSIONS: Inverse associations between glycemic measures and lung function were observed. Men seem more susceptible to the alteration in FVC and FEV1 than women.

Plasma Antimicrobial Peptide LL-37 Level Is Inversely Associated with HDL Cholesterol Level in Patients with Type 2 Diabetes Mellitus.

Introduction. Relation between atherosclerosis and innate immunity has attracted attention. As the antimicrobial peptide, LL-37, could have an important role in atherosclerosis, we supposed that there could be a meaningful association of plasma LL-37 level with risk factors for cardiovascular disease in subjects with type 2 diabetes mellitus. Materials and Methods. We evaluated plasma LL-37 level and other clinical markers in Japanese subjects with type 2 diabetes mellitus (n = 133, 115 men and 18 women; age 64.7 ± 11.5 years; HbA1c 8.1 ± 1.6%). Plasma level of LL-37 was measured by ELISA. Results. Mean plasma LL-37 level was 71.2 ± 22.3 ng/mL. Plasma LL-37 level showed significant correlations with HDL cholesterol (r = -0.450, P < 0.01), triglyceride (r = 0.445, P < 0.01), and high sensitive C-reactive protein (r = 0.316, P < 0.01) but no significant correlation with age, body mass index, HbA1c, estimated glomerular filtration rate, 25-hydroxyvitamin D, or vitamin D binding protein. Multiple linear regression analysis showed significant correlations of plasma LL-37 level with HDL cholesterol (ß = -0.411, P < 0.01) and high sensitive C-reactive protein (ß = 0.193, P < 0.05). Conclusion. Plasma LL-37 level was positively correlated with inflammatory markers and negatively correlated with HDL cholesterol in patients with type 2 diabetes mellitus.

Associations of insulin resistance and glycemic control with the risk of kidney stones.

OBJECTIVE: The associations of insulin resistance and glycemic control with the risk of kidney stones were explored. METHODS: Generally healthy Japanese (n=2,171) who visited Saiseikai Central Hospital (Tokyo, Japan) for a health check were included in a cross-sectional study. We calculated odds ratios (OR) of having kidney stones in terms of four measures: fasting serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c), adjusting for possible risk factors for kidney stones. RESULTS: Fasting serum insulin and HOMA-IR were non-significantly associated with the risk of kidney stones, whereas FPG and HbA1c were significantly associated. Compared with those with an FPG of <100 mg/dL, the ORs in those with an FPG of 100 to <126 mg/dL and ≥126 mg/dL were 1.38 (95% confidence interval [CI] =0.95-2.00) and 1.83 (95% CI =1.09-3.06) (p for trend =0.016). In relation to those with an HbA1c of <5.5%, the ORs in those with an HbA1c of 5.5 to <6.0%, 6.0% to <6.5% and ≥6.5% were 1.16 (95% CI =0.76-1.79), 1.25 (95% CI =0.70-2.23) and 1.98 (95% CI =1.11-3.52), respectively (p for trend =0.027). The significant associations between glycemic control measures and the risk of kidney stones were preserved even after the adjustment for factors related to insulin resistance. CONCLUSION: Glycemic control could be an independent risk factor for kidney stones.

Plasma 25-hydroxyvitamin d is independently associated with hemoglobin concentration in male subjects with type 2 diabetes mellitus.

Introduction. It was reported that 25-hydroxyvitamin D level was independently associated with anemia in chronic kidney diseases, but the relation between vitamin D and anemia in diabetes mellitus is not still certain. We analyzed the relation between plasma 25-hydroxyvitamin D level and hemoglobin concentration. Materials and Methods. A cross-sectional study in male patients with type 2 diabetes was performed. Correlation coefficients and standardized partial regression coefficient for the hemoglobin concentration were evaluated. Results. Hemoglobin concentration was positively correlated with body mass index, HbA1c, estimated glomerular filtration rate, cholinesterase, and 25-hydroxyvitamin D level and negatively correlated with age, duration of diabetes mellitus, serum creatinine, and urinary albumin creatinine ratio. Multiple regression analysis revealed the independent relation of 25-hydroxyvitamin D to hemoglobin concentration. Conclusions. Plasma circulating form of vitamin D is significantly associated with hemoglobin concentration in diabetes mellitus independent of the clinical markers for kidney function or nutrition.

A mitochondrial DNA variant associated with left ventricular hypertrophy in diabetes.

Diabetes was reported to be associated with a mitochondrial (mt) DNA mutation at 3243 and variants at 1310, 1438, 3290, 3316, 3394, 12,026, 15,927, and 16,189. Among these mtDNA abnormalities, those at 3243, 3316, 15,927, and 16,189 were also suggested to cause cardiomyopathies. We investigated the prevalence of such mtDNA abnormalities in 68 diabetic patients with LV hypertrophy (LVH), 100 without LVH, and 100 controls. Among the 9 mtDNA abnormalities, those at 3243, 3316, and 15,927 tended to be more prevalent in diabetic patients with LVH than in those without LVH (1%, 1%, and 4% vs. 0%, 0%, and 0%). Notably, the variant at 16,189 was more prevalent in diabetic patients with LVH than without LVH (46% vs. 24%, [Formula: see text] ). The odds ratio for LVH was 3.0 (95% CI, 1.5-6.1) for the 16,189 variant. A common mtDNA variant at 16,189 was found to be associated with LVH in diabetic patients.