Undercarboxylated osteocalcin correlates with insulin secretion in Japanese individuals with diabetes.

BACKGROUND: Undercarboxylated osteocalcin (ucOC) is a secreted protein produced by osteoblasts that regulates insulin secretion and insulin sensitivity in rodents. However, the significance of these effects on glucose metabolism in human remains unknown. Moreover, the pathophysiological roles of ucOC on varying degrees of glucose intolerance, including diabetes need to be elucidated. In the present study, correlations between ucOC and indices of insulin secretion and sensitivity were analyzed in normal glucose tolerance (NGT), impaired glucose metabolism (IGM), and diabetes mellitus (DM) groups. METHODS: Based on 75 g OGTT data in Japanese individuals without diabetic medication, or medications which may affect ucOC levels, individuals were classified as having normal glucose tolerance (NGT), impaired glucose metabolism (IGM), or diabetes (DM). In each group, 25 individuals were consecutively recruited [total 75 individuals, age: 65 ± 11 (mean ± SD); BMI: 24.9 ± 3.8 kg/m2]. QUICKI and Matsuda index (MI) were calculated as insulin sensitivity indices. Homeostasis model assessment (HOMA)-ß and insulinogenic index (IGI) were calculated as insulin secretion indices. UcOC was measured using ECLIA. Normally-distributed loge-transformed (ln-) values were used for ucOC, HOMA-ß, IGI, and MI. RESULTS: The ucOC was not significantly different among the three groups. The results of multiple regression analysis showed that ln-ucOC did not significantly correlate with age, sex, BMI, waist circumference, fasting plasma glucose, plasma glucose 120 min after glucose loading, fasting plasma immunoreactive insulin, ln-HOMA-ß, QUICKI, or ln-MI in any of the three groups. Interestingly, ln-ucOC correlated with ln-IGI (r = 0.422, P = 0.0354) and HbA1c (r = - 0.574, P = 0.0027) only in the DM group. There was no significant correlation between ln-IGI and age, sex, BMI, or HbA1c in the DM group. Further, the results of multiple regression analysis showed that ln-IGI could be independently predicted by BMI (ß = 0.598, P = 0.0014) and ln-ucOC (ß = 0.641, P = 0.0007) in the DM group (R2 = 0.488, P = 0.0006). CONCLUSION: In our study, ucOC positively correlated with insulin secretion independently of BMI in Japanese individuals with diabetes. These results suggest that ucOC plays more important roles in insulin secretion than in insulin sensitivity in individuals with diabetes.

Fasting plasma mannose levels are associated with insulin sensitivity independent of BMI in Japanese individuals with diabetes.

BACKGROUND: Recently, an integrated network analysis has revealed dysregulation in the metabolism of mannose, a glucose epimer, in severely obese individuals without diabetes. In addition, fasting plasma mannose levels (M0) are associated with insulin resistance independent of BMI. Since the association between mannose and insulin sensitivity (IS) in those with impaired glucose tolerance remains unknown, we aimed to investigate this association in individuals without severe obesity but with varying degrees of glucose tolerance. METHODS: Based on 75 g OGTT data in Japanese individuals without diabetic medication, individuals were classified as having normal glucose tolerance (NGT), impaired glucose metabolism (IGM), or diabetes (DM). In each group, 25 individuals were consecutively recruited [total 75 individuals, age: 65 ± 11 (mean ± SD); BMI: 24.9 ± 3.8 kg/m2]. QUICKI and Matsuda index (MI) were calculated as IS indices. M0 was assayed using HPLC. Normally-distributed loge-transformed (ln-) values were used for MI and leptin. RESULTS: In the simple regression analysis, ln-MI was negatively correlated with BMI (NGT: r = - 0.639, IGM: r = - 0.466, DM: r = - 0.613) and ln-leptin (NGT: r = - 0.480, IGT: r = - 0.447, DM: r = - 0.593) in all 3 groups. Ln-MI was not significantly correlated with M0 in NGT (r = 0.241, P = 0.245) and IGT (r = - 0.296, P = 0.152) groups, it was moderately and negatively correlated in the DM group (r = - 0.626, P < 0.001). Similar results were obtained, when QUICKI was used instead of MI as an index of IS. In multiple regression analysis in the DM group, QUICKI (Q) and ln-MI (M) were independently predicted by BMI (Q: ß = - 0.413; M: ß = - 0.400) and M0 (Q: ß = - 0.413, M: ß = - 0.426), accounting for 51.2% (P = 0.0004) and 51.2% (P = 0.0004) of the variability, respectively, which was larger than the prediction for BMI alone (Q: 38.4%, M: 37.6%). CONCLUSION: Fasting plasma mannose was associated with IS independent of BMI in Japanese individuals with DM.

Analysis of factors influencing glucose tolerance in Japanese patients with non-alcoholic fatty liver disease.

BACKGROUND: While the association of the prevalence of non-alcoholic fatty liver disease (NAFLD) with impaired glucose metabolism has been reported, the factors influencing glucose tolerance in NAFLD remain to be clarified. METHODS: Glucose tolerance of 131 Japanese patients diagnosed as NAFLD by histological findings of liver biopsy specimen was examined using 75 g-OGTT. According to Matteoni's classification, patients were divided to 4 groups [M1 ~ 4, M1, 2: non-alcoholic fatty liver (NAFL); and M3, 4: non-alcoholic steatohepatitis (NASH)]. Based on the OGTT data, insulinogenic index (IGI) and QUICKI were calculated as indices of insulin secretion and insulin sensitivity, respectively. Plasma glucose 120 min after glucose loading (G120) was used as the index for glucose intolerance. RESULTS: Stepwise multiple regression analysis using G120 as a dependent variable and loge-IGI, QUICKI, sex, BMI, age, NAFL/NASH as independent variables revealed that loge-IGI (ß = -0.595) and QUICKI (ß = -0.323) are significant factors predicting glucose intolerance (R2 = 0.403), indicating an important role of insulin secretion in glucose tolerance. These findings accord with glucose intolerance as high as 89.7% in patients with impaired insulin secretion defined by ≤43.2 pmol/mmol (40 µU/mg) IGI. Stepwise multiple regression analysis using QUICKI as a dependent variable and NAFL/NAFLD, sex, BMI, and age as independent variables revealed that BMI (ß = -0.469) and NAFL/NAFLD (ß = -0.204) are significant factors predicting insulin sensitivity (R2 = 0.248). CONCLUSION: Impairment of insulin secretion is the most important factor to predict glucose intolerance in NAFLD; severity of histological findings is associated with insulin sensitivity independent of adiposity in NAFLD.

Plasma mannose level, a putative indicator of glycogenolysis, and glucose tolerance in Japanese individuals.

AIMS/INTRODUCTION: Mannose is a monosaccharide constituent of glycoproteins and glycolipids. Experiments in rats have shown previously that the plasma mannose level decreases after glucose load, but does not decrease in diabetic rats, and that hepatic glycogenolysis is a source of this plasma mannose; however, these results are not fully elucidated in humans. Plasma mannose levels before/after glucose loading in humans with various degrees of glucose intolerance were examined to analyze their association with clinical factors. MATERIALS AND METHODS: The 75-g oral glucose tolerance test was carried out in Japanese individuals not taking diabetes medications. Participants were classified into normal glucose tolerance, impaired glucose metabolism and diabetes mellitus groups. Insulinogenic index as an index of insulin secretion, and Matsuda Index as an index of insulin sensitivity were calculated. Mannose was assayed by the established method using high-performance liquid chromatography after labeling. RESULTS: After glucose load, the plasma mannose level decreased gradually in the normal glucose tolerance group, but did not decrease in the diabetes mellitus group. Plasma mannose changes during 120 min from baseline (M120 -M0 ) were significantly different among the three groups (normal glucose tolerance: -16.7 ± 1.7; impaired glucose metabolism: -9.0 ± 1.9; diabetes mellitus: -1.4 ± 1.8 µmol/L [n = 25 in each group], P < 0.0001). Plasma glucose 120 min after glucose loading (R2  = 0.412) or loge -insulinogenic index, loge -Matsuda Index and age (R2  = 0.230) were determinants of M120 -M0 in multiple regression analyses. CONCLUSIONS: We clarified the relationship between plasma mannose level and glucose tolerance in humans. The present results are compatible with those using rats, in which mannose derived from glycogenolysis plays an important role in the alteration of mannose levels after glucose loading.

Comparison of liquid crystal display monitors calibrated with gray-scale standard display function and with γ 2.2 and iPad: observer performance in detection of cerebral infarction on brain CT.

OBJECTIVE: The purpose of the study was to compare observer performance in the detection of cerebral infarction on a brain CT using medical-grade liquid crystal display (LCD) monitors calibrated with the gray-scale standard display function and with γ 2.2 and using an iPad with a simulated screen setting. MATERIALS AND METHODS: We amassed 97 sample sets, from 47 patients with proven cerebral infarction and 50 healthy control subjects. Nine radiologists independently assessed brain CT on a gray-scale standard display function LCD, a γ 2.2 LCD, and an iPad in random order over 4-week intervals. Receiver operating characteristic (ROC) analysis was performed by using the continuous scale, and the area under the ROC curve (A(z)) was calculated for each monitor. RESULTS: The A(z) values for gray-scale standard display function LCD, γ 2.2 LCD, and iPad were 0.875, 0.884, and 0.839, respectively. The difference among the three monitors was very small. There was no significant difference between gray-scale standard display function LCD and γ 2.2 LCD. However, the A(z) value was statistically significantly smaller for the iPad than the γ 2.2 LCD (p < 0.05). CONCLUSION: Observer performance for detecting cerebral infarction on the LCD with γ 2.2 calibration was found to be similar to the LCD with gray-scale standard display function calibration. Although observer performance using the iPad was poorer than that using the other LCDs, the difference was small. Therefore, the iPad could not substitute for other LCD monitors. However, owing to the promising potential advantages of tablet PCs, such as portability, further examination is needed into the clinical use of tablet PCs.

High E/e' disrupts the rapid lowering of blood glucose in response to exercise training.

BACKGROUND: No relationship between the ratio of peak early velocity of left ventricular inflow to peak systolic longitudinal velocity of the mitral annulus velocity (E/e') and insulin resistance has yet been shown in patients with cardiac disease. We hypothesized that patients with high E/e' values would tend not to show the rapid blood glucose-lowering in response to exercise training characteristic of impaired glucose tolerance (IGT) or diabetes mellitus (DM) patients. METHODS: The subjects were continuous IGT/DM patients (n = 27) participating in cardiac rehabilitation. All patients' E/e' values were measured by echocardiography. The patients' blood glucose levels (mg/dl) were measured just before (pre-BS) and after (post-BS) exercise training. Post-BS was subtracted from pre-BS to obtain ΔBS, and the relationship between E/e' and ΔBS was investigated. RESULTS: E/e' correlated negatively with ΔBS. Moreover, E/e' was a significant predictor of ΔBS and as such was independent of hemoglobin A1c (HbA1c), pre-BS, and presence of atrial fibrillation on multivariate analysis. CONCLUSIONS: Patients with high E/e', indicating high left ventricular filling pressure, were unlikely to exhibit the rapid glucose-lowering response.

A comparative contrast perception phantom image of brain CT study between high-grade and low-grade liquid crystal displays (LCDs) in electronic medical charts.

The purpose of this study was to clarify whether non-medical-grade liquid crystal displays (LCDs) are acceptable for the soft-copy reading of brain CTs. Four kinds of color LCDs with different image quality levels were used: medical-grade LCD, low-grade general LCD calibrated with the grayscale display function (GSDF), low-grade general LCD calibrated with gamma 2.2 and a notebook personal computer display panel. In Osirix's standard window setting for brain CTs, the average CT values of brain parenchyma in 100 cases were correlated with a grayscale level ranging from 71 to 91 in a 256-step grayscale. At these gray levels, the image contrast on the two low-grade LCDs calibrated with gamma 2.2 was higher than that on the medical-grade LCD. Eleven healthy volunteers participated in the contrast perception study, which used electronically generated target phantom images that simulated subtle abnormalities with a low or high attenuation difference in brain parenchyma. The three low-grade LCDs showed correct response rates and reaction times that were superior to those of the medical-grade display. The grayscale calibrations, GSDF or gamma 2.2, are likely to be more critical than the display grade, suggesting that the use of a low-grade LCD may be acceptable in the image contrast of brain CT.

Direct comparison study between FDG-PET and IMP-SPECT for diagnosing Alzheimer's disease using 3D-SSP analysis in the same patients.

PURPOSE: The purpose of this study was to evaluate and compare the diagnostic ability of 2-[(18)F]-fluoro-2-deoxy-D: -glucose (FDG) positron emission tomography (PET) and N-isopropyl-p-(123)I iodoamphetamine single photon emission computed tomography (IMP-SPECT) using three-dimensional stereotactic surface projections (3D-SSP) in patients with moderate Alzheimer's disease (AD). MATERIALS AND METHODS: FDG-PET and IMP-SPECT were performed within 3 months in 14 patients with probable moderate AD. Z-score maps of FDG-PET and IMP-SPECT images of a patient were obtained by comparison with data obtained from control subjects. Four expert physicians evaluated and graded the glucose hypometabolism and regional cerebral blood flow (rCBF), focusing in particular on the posterior cingulate gyri/precunei and parietotemporal regions, and determined the reliability for AD. Receiver operating characteristic (ROC) curves were applied to the results for clarification. To evaluate the correlation between two modalities, the regions of interest (ROIs) were set in the posterior cingulate gyri/precunei and parietotemporal region on 3D-SSP images, and mean Z-values were calculated. CONCLUSION: No significant difference was observed in the area under the ROC curve (AUC) between FDG-PET and IMP-SPECT images (FDG-PET 0.95, IMP-SPECT 0.94). However, a significant difference (P < 0.05) was observed in the AUC for the posterior cingulate gyri/precuneus (FDG-PET 0.94, IMP-SPECT 0.81). The sensitivity and specificity of each modality were 86%, and 97% for FDG-PET and 70% and 100% for IMP-SPECT. We could find no significant difference between FDG-PET and IMP-SPECT in terms of diagnosing moderate AD using 3D-SSP. There was a high correlation between the two modalities in the parietotemporal region (Spearman's r = 0.82, P < 0.001). The correlation in the posterior cingulate gyri/precunei region was lower than that in the parietotemporal region (Spearman's r = 0.63, P < 0.016).

Development of a practical image-based scatter correction method for brain perfusion SPECT: comparison with the TEW method.

PURPOSE: An image-based scatter correction (IBSC) method was developed to convert scatter-uncorrected into scatter-corrected SPECT images. The purpose of this study was to validate this method by means of phantom simulations and human studies with 99mTc-labeled tracers, based on comparison with the conventional triple energy window (TEW) method. METHODS: The IBSC method corrects scatter on the reconstructed image I(mub)AC with Chang's attenuation correction factor. The scatter component image is estimated by convolving I(mub)AC with a scatter function followed by multiplication with an image-based scatter fraction function. The IBSC method was evaluated with Monte Carlo simulations and 99mTc-ethyl cysteinate dimer SPECT human brain perfusion studies obtained from five volunteers. The image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were compared. RESULTS: Using data obtained from the simulations, the image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were found to be nearly identical for both gray and white matter. In human brain images, no significant differences in image contrast were observed between the IBSC and TEW methods. CONCLUSION: The IBSC method is a simple scatter correction technique feasible for use in clinical routine.

Cross-modal binding and activated attentional networks during audio-visual speech integration: a functional MRI study.

We evaluated the neural substrates of cross-modal binding and divided attention during audio-visual speech integration using functional magnetic resonance imaging. The subjects (n = 17) were exposed to phonemically concordant or discordant auditory and visual speech stimuli. Three different matching tasks were performed: auditory-auditory (AA), visual-visual (VV) and auditory-visual (AV). Subjects were asked whether the prompted pair were congruent or not. We defined the neural substrates for the within-modal matching tasks by VV-AA and AA-VV. We defined the cross-modal area as the intersection of the loci defined by AV-AA and AV-VV. The auditory task activated the bilateral anterior superior temporal gyrus and superior temporal sulcus, the left planum temporale and left lingual gyrus. The visual task activated the bilateral middle and inferior frontal gyrus, right occipito-temporal junction, intraparietal sulcus and left cerebellum. The bilateral dorsal premotor cortex, posterior parietal cortex (including the bilateral superior parietal lobule and the left intraparietal sulcus) and right cerebellum showed more prominent activation during AV compared with AA and VV. Within these areas, the posterior parietal cortex showed more activation during concordant than discordant stimuli, and hence was related to cross-modal binding. Our results indicate a close relationship between cross-modal attentional control and cross-modal binding during speech reading.