Numerical Study on a Focus-Control Method Using Breast Model With Intentionally Assigned High-Absorbing Layer Near Skin for High-Intensity Focused Ultrasound Treatment.

To prevent undesirable skin burns that occur in high-intensity focused ultrasound (HIFU) treatment, we numerically study focus-control methods, such as phase compensation (PC) and amplitude adaptation (AA). We intentionally assign a high-absorbing layer (HAL) near the part of the skin, where heat generation and tissue ablation are observed, because of high energy loss in the interface between water and breast skin. Results show that PC improves the effectiveness of focusing by enhancing the focal peak and reducing the focal deviation; however, PC does not suppress skin burn. AA and PC eliminate skin burns only if appropriate amplitude weights are applied. A preliminary discussion on three algorithms for obtaining amplitude weights is conducted as follows; First, we switched off transducer channels using distance-to-HAL. This algorithm eliminates skin burns while causing other undesirable burns by preserving 100% input energy. Second, we use cross-correlated amplitude weights. It eliminates skin burn after properly limiting large-amplitude weights while producing focal necrosis in a smaller and slower manner. Third, we introduced root-mean-square (rms) level of back-propagated wave (BPW) into cross-correlated amplitude weights. This new algorithm produces focal ablation in 20 s without causing any skin burn. Although longer irradiation time brings back skin burn, the result is satisfying since short irradiation time is needed in HIFU treatment to avoid exceeding the physical endurance of human patients. Moreover, this work indicates that focus-control associated with an acoustic peak is insufficient. The effects of the high attenuation area are significant and should be captured.

Numerical study on sector-vortex phased irradiation method using annular array transducer in High-Intensity Focused Ultrasound treatment.

Sector-vortex phased irradiation from annular array transducer was numerically studied with breast model constructed from MRI data of real patient. Phase compensation (PC) based on time reversal pre-computation was applied in order to handle phase delay caused by heterogeneity of breast tissues, and results showed great effectiveness on single-focus case, insignificant effectiveness on multi-focus cases with 4 and 8 phase-sectors, but ineffectiveness on multi-focus case with 12 phase-sectors, where enormous undesired outer ablation occurred. For single-focus case, phase compensation not only produced real focus very close to targeted site (0.1 mm deviation), but also decreased thermal peak ratio (outer/focal) largely by 30%. However, phase compensation did not increase total ablated size. For multi-focus cases with 4 and 8 phase-sectors, deformed focal shapes by tissue heterogeneity were restored by phase compensation, but the 4-phase-sector case had higher thermal peak ratio and smaller ablation than 8-phase-sector case for strong cancelling effect between phase-sector borders. Ineffectiveness of phase compensation on multi-focus case with 12 phase-sectors had three considerable reasons. 1st, inequality of piezo-element number between sectors; 2nd, heterogeneous attenuation of breast model; 3rd, insufficient number of piezo-elements per sector; where the 2nd reason originated from breast model, and other two reasons were related to array transducer. This research gave several preliminary indications. 1st, ineffectiveness of phase compensation occurs on case with large phase-sector number when using annular array transducer; 2nd, with same input energy and same irradiation time, sector-vortex phased irradiation creates smaller focal ablation, but withstands longer than single-focus irradiation free of outer ablation; 3rd, phase-difference π between neighboring phase-sectors is disadvantageous because of energy loss; 4th, phase compensation is effective on single-focus for improving pinpoint ablation but not for increasing total ablated size.

Effects of breast structure on high-intensity focused ultrasound focal error.

BACKGROUND: The development of imaging technologies and breast cancer screening allowed early detection of breast cancers. High-intensity focused ultrasound (HIFU) is a non-invasive cancer treatment, but the success of HIFU ablation was depending on the system type, imaging technique, ablation protocol, and patient selection. Therefore, we aimed to determine the relationship between breast tissue structure and focal error during breast cancer HIFU treatment. METHODS: Numerical simulations of the breast cancer HIFU ablation were performed using digital breast phantoms constructed using the magnetic resonance imaging data obtained from 12 patients. RESULTS: The focal shapes were distorted despite breast tissue representing soft tissue. Focal errors are caused by the complex distribution of fibroglandular tissue, and they depend on the target position and the arrangement of the transducer. We demonstrated that the focusing ratio increases with the decrease in the local acoustic inhomogeneity, implying that it may be used as an indicator to reduce the HIFU focal error depending on the breast structure. CONCLUSIONS: The obtained results demonstrated that the focal error observed during the breast cancer HIFU treatment is highly dependent on the structure of fibroglandular tissue. The optimal arrangement of the transducer to the target can be obtained by minimizing the local acoustic inhomogeneity before the breast cancer HIFU treatment.

Acute compartment syndrome as the initial manifestation of chronic-phase chronic myeloid leukemia: a case report and review of the literature.

BACKGROUND: Acute compartment syndrome is an orthopedic emergency requiring urgent fasciotomy to prevent irreversible damage. In hematological malignancies, acute compartment syndrome caused by severe soft tissue bleeding is extremely rare. We present a patient with chronic-phase chronic myeloid leukemia who had acute compartment syndrome caused by severe soft tissue bleeding in her right forearm. CASE PRESENTATION: A 72-year-old Japanese woman was referred to our hospital with swelling and pain of her right forearm without a previous history of trauma. She was diagnosed with chronic-phase chronic myeloid leukemia. Extreme thrombocytosis was present, although no evidence of acquired von Willebrand disorder was found. Compartment syndrome caused by soft tissue bleeding was confirmed. An emergency fasciotomy for decompression was conducted. However, sustained postoperative bleeding occurred and required massive red cell concentrate transfusion. As her platelet count decreased by cytoreductive therapy, complete hemostasis was achieved. CONCLUSIONS: Patients with an extremely high platelet count might be at high risk for severe bleeding complications even without acquired von Willebrand disease. For the control of severe bleeding complications in patients with myeloproliferative disorder, the importance of thrombocyte reduction should be recognized.

Increment of serum C-peptide measured by glucagon test closely correlates with human relative beta-cell area.

Pancreatic beta-cell mass contributes to glucose tolerance. The aim of this study was to evaluate the relationships between human beta-cell mass and various clinical parameters, including insulin secretory capacity. The study included 32 Japanese patients who underwent pancreatectomy and were naive to oral hypoglycemic agents and insulin. They were classified into those with normal glucose tolerance (n=13), impaired glucose tolerance (n=9) and diabetes (n=10), and their insulin secretory capacity and insulin resistance were evaluated. Immunohistochemistry was used to determine relative beta-cell area (%) which represented the proportion of insulin-positive cell area to whole pancreatic section. Increment of C-peptide immunoreactivity level by glucagon test (ΔC-peptide, increment of serum C-peptide [nmol/L] at 6 min after intravenous injection of 1-mg glucagon; r=0.64, p=0.002), homeostasis model assessment of beta-cell function (HOMA-beta, fasting immunoreactive insulin [µIU/mL] x 20 / (fasting plasma glucose [mmol/L] - 3.5); r=0.50, p=0.003), C-peptide index (CPI, fasting C-peptide [nmol/L] / fasting plasma glucose [mmol/L]; r=0.36, p=0.042), and fasting immunoreactive insulin (F-IRI [pmol/L]; r=0.36, p=0.044) correlated significantly and positively with the relative beta-cell area. The area under the curve of plasma glucose level from 0 to 120 min by 75 g-OGTT (AUC0-120) also correlated significantly and inversely with the relative beta-cell area (r=-0.36, p=0.045). Stepwise multiple regression analysis identified ΔC-peptide as the only independent and significant determinant of the relative beta-cell area. We conclude that ΔC-peptide, HOMA-beta, CPI, F-IRI and AUC0-120 correlated closely with the relative beta-cell area, and ΔC-peptide was the most valuable index for the prediction of the area.

Choroidal thickness changes after diabetes type 2 and blood pressure control in a hospitalized situation.

PURPOSE: To investigate the effect of acute diabetic control on choroidal thickness in patients with Type 2 diabetes. METHODS: Seventeen eyes of 17 patients with Type 2 diabetes were included in this prospective observational study. The patients with Type 2 diabetes who were scheduled to undergo a program of intensive diabetic control underwent prototype high-penetration optical coherence tomography before and 2 weeks after the start of treatment. The choroidal thickness changes 2 weeks after the protocol of intensive diabetic control were assessed, and associated ophthalmologic and general parameters were explored. Seventeen eyes of 17 healthy volunteers were included to compare diabetic patients. The choroidal thickness also was measured in this group at baseline and after 2 weeks. And the intraobserver and interobserver reproducibility were verified using this control group. RESULTS: The intraobserver (intraclass coefficient, 0.992) and interobserver reproducibility (0.982) in our subfoveal choroidal thickness measurement were high. The mean subfoveal choroidal thickness after 2 weeks (226 ± 56 µm) was significantly greater than at baseline (215 ± 52 µm, P < 0.05); there was no difference between the baseline and 2-week values in the control group (baseline, 312 ± 113 vs. 2-week value, 307 ± 103 µm; P = 0.17). The changes in refractive error (P < 0.001), axial length (P < 0.01), and diastolic blood pressure (P < 0.01) were associated significantly with changes in choroidal thickness 2 weeks after the intensive control. The pretreatment body mass index (P < 0.05) and hemoglobin A1c (P < 0.005) also were associated significantly with increased choroidal thickness. CONCLUSION: Diabetic patients showed a significant increase of choroidal thickness after the intensive control. Various ophthalmologic and systemic parameters seem to affect the choroidal thickness changes. This may be related to the progression of retinopathy after acute glycemic control.

Usefulness of the insulin tolerance test in patients with type 2 diabetes receiving insulin therapy.

AIMS/INTRODUCTION: To establish the validity of the plasma glucose disappearance rate (KITT), derived from an insulin-tolerance test (ITT), for evaluating the insulin sensitivity of patients with type 2 diabetes after insulin therapy. MATERIALS AND METHODS: In the first arm of the study, 19 patients with poorly controlled diabetes were treated with insulin and underwent an ITT and a euglycemic clamp test (clamp-IR). The relationship between the insulin resistance index, as assessed by both the clamp-IR and KITT tests, was examined. In the second arm of the study, the relationships between KITT values and various clinical parameters were investigated in 135 patients with poorly controlled diabetes, after achieving glycemic control with insulin. RESULTS: In study 1, a close correlation between KITT and the average glucose infusion rate during the last 30 min of the standard clamp-IR test (M-value) was noted (P < 0.001). In study 2, body mass index (P = 0.0011), waist circumference (P = 0.0004), visceral fat area (P = 0.0011) and the log-transformed homeostasis model assessment of insulin resistance value (P = 0.0003) were negatively correlated with the log-transformed KITT. High-density lipoprotein cholesterol (P = 0.0183), low-density lipoprotein cholesterol (P = 0.0121) and adiponectin (P = 0.0384) levels were positively correlated with the log-transformed KITT. CONCLUSIONS: The ITT is a valid and useful test for evaluating the insulin sensitivity of patients with diabetes, even after treatment with insulin.

Low gene expression levels of activating receptors of natural killer cells (NKG2E and CD94) in patients with fulminant type 1 diabetes.

Fulminant type 1 diabetes is an independent subtype of type 1 diabetes characterized by extremely rapid onset and absence of islet-related autoantibodies. However, detailed pathophysiology of this subtype is poorly understood. In this study, a comprehensive approach was applied to understand the pathogenesis of fulminant type 1 diabetes. We determined the genes that were differentially expressed in fulminant type 1 diabetes compared with type 1A diabetes and healthy control, using gene expression microarray in peripheral blood cells. Using volcano plot analysis, we found reduced expression of killer cell lectin-like receptor subfamily C, member 3 (KLRC3) which encodes NKG2E, a natural killer (NK) cell activating receptor, in fulminant type 1 diabetes, compared with healthy controls. This difference was confirmed by real-time RT-PCR among NK-enriched cells. The expression of KLRD1 (CD94), which forms heterodimer with NKG2E (KLRC3), was also reduced in NK-enriched cells in fulminant type 1 diabetes. Furthermore, flow cytometry showed significantly lower proportion of NK cells among peripheral blood mononuclear cells (PBMCs) in fulminant type 1 diabetes than in healthy controls. In patients with fulminant type 1 diabetes, the relative proportion of NK cells correlated significantly with the time period between onset of fever to the appearance of hyperglycemic-related symptoms. We conclude the presence of reduced NK activating receptor gene expression and low proportion of NK cells in fulminant type 1 diabetes.

Temperature distributions measurement of high intensity focused ultrasound using a thin-film thermocouple array and estimation of thermal error caused by viscous heating.

To improve the throughput of high intensity focused ultrasound (HIFU) treatment, we have considered a focus switching method at two points. For this method, it is necessary to evaluate the thermal distribution under exposure to ultrasound. The thermal distribution was measured using a prototype thin-film thermocouple array, which has the advantage of minimizing the influence of the thermocouple on the acoustic and temperature fields. Focus switching was employed to enlarge the area of temperature increase and evaluate the proposed evaluation parameters with respect to safety and uniformity. The results indicate that focus switching can effectively expand the thermal lesion while maintaining a steep thermal boundary. In addition, the influence caused by the thin-film thermocouple array was estimated experimentally. This thermocouple was demonstrated to be an effective tool for the measurement of temperature distributions induced by HIFU.

Microbubble behavior in an ultrasound field for high intensity focused ultrasound therapy enhancement.

The enhancement of heating due to inertial cavitation has been focused to reduce the long treatment time of conventional high-intensity focused ultrasound (HIFU) therapy. The influences of the physical properties of surrounding tissues, initial void fraction, and spatial distribution of bubbles on microbubble-enhanced HIFU are examined. A bubble dynamics equation based on the Keller-Miksis equation is employed in consideration of the elasticity of surrounding tissue. The mixture phase and bubbles are coupled by the Euler-Lagrange method to take into account the interaction between ultrasound and bubbles. As a result, the temperature around the target increases with the initial void fraction. But at the high void fraction of 10(-5), ultrasound is too attenuated to heat the target, and the heating region moves to the transducer side. On the other hand, both the viscosity and shear elasticity of the surrounding media reduce the attenuation of ultrasound propagation through the bubbly mixture. Numerical results show that localized heating is induced with increasing viscosity or shear elasticity, though it depends on the pressure amplitudes. In addition, it was numerically confirmed that the localization of the microbubble distribution is important to obtain efficient localized heating.

Vascular complications and changes in body mass index in Japanese type 2 diabetic patients with abdominal obesity.

BACKGROUND: Although many Asian type 2 diabetic patients have been considered to be not obese and have low capacity of insulin secretion, the proportion of obese patients with visceral fat accumulation has increased in recent years. We found previously considerable number of Japanese non-obese subjects (body mass index (BMI) < 25 kg/m²) with visceral fat accumulation and multiple cardiovascular risk factors. The aim of the study was to investigate the difference in clinical features of type 2 diabetic patients with and without visceral fat accumulation, focusing on vascular complications and changes in BMI. METHODS: We enrolled 88 Japanese hospitalized type 2 diabetic patients. Abdominal obesity represented waist circumference (WC) of ≥85 cm for males and ≥90 cm for females (corresponding to visceral fat area of 100 cm²). Subjects were divided into two groups; with or without abdominal obesity. RESULTS: Hypertension, dyslipidemia and cardiovascular diseases were significantly more in the patients with abdominal obesity. The prevalence of cardiovascular disease in the non-obese patients (BMI < 25 kg/m²) with abdominal obesity were similar in obese patients (BMI ≥25 kg/m²). The mean BMI of the patients with abdominal obesity was < 25 kg/m² at 20 years of age, but reached maximum to more than 30 kg/m² in the course. Furthermore, substantial portion of the type 2 diabetic patients (52% in males and 43% in females) were not obese at 20 year-old (BMI < 25 kg/m²), but developed abdominal obesity by the time of admission. CONCLUSION: These results emphasize the need to control multiple risk factors and prevent atherosclerotic disease in patients with abdominal obesity. The significant weight gain after 20 years of age in patients with abdominal obesity stresses the importance of lifestyle modification in younger generation, to prevent potential development of type 2 diabetes and future atherosclerotic cardiovascular disease.

Mechanical clot damage from cavitation during sonothrombolysis.

Recent studies have shown that high intensity focused ultrasound (HIFU) accelerates thrombolysis for ischemic stroke. Although the mechanisms are not fully understood, cavitation is thought to play an important role. The goal of this paper is to investigate the potential for cavitation to cause mechanical damage to a blood clot. The amount of damage to the fiber network caused by a single bubble expansion and collapse is estimated by two independent approaches: One based on the stretch of individual fibers and the other based on the energy available to break individual fibers. The two methods yield consistent results. The energy method is extended to the more important scenario of a bubble outside a blood clot that collapses asymmetrically creating an impinging jet. This leads to significantly more damage compared to a bubble embedded within the clot structure. Finally, as an example of how one can apply the theory, a simulation of the propagation of HIFU waves through model calvaria of varying density is explored. The maximum amount of energy available to cause damage to a blood clot increases as the density of the calvaria decreases.

Early postprandial glucagon surge affects postprandial glucose levels in obese and non-obese patients with type 2 diabetes.

Postprandial glucagon secretion was shown to be dysregulated in patients with type 2 diabetes. However, the differences in secretory patterns between obese and non-obese patients and their physiological effects on plasma glucose levels are not fully understood. This study population consisted of 21 (10 obese and 11 non-obese) consecutive patients with type 2 diabetes admitted for glycemic control. A 3-hour mixed-meal tolerance test was performed after glycemic control improved. Six non-diabetic subjects were also enrolled in the test. Postprandial glucagon levels increased after 30 min in diabetic patients but not in non-diabetic subjects. The glucagon levels in obese diabetic patients were significantly higher than those in non-obese diabetic patients, while the percent values of postprandial glucagon levels were not different between these groups. In diabetic patients, there were significant positive correlations between the percent value at 30 min and the early postprandial glucose levels at 0, 15 and 30 min and the areas under the curve (AUC0-30 and AUC30-90). Interestingly, the ratio of this percent glucagon value to the C-peptide level at 30 min was significantly associated with the late half of the postprandial glucose levels at 90, 120, 150 and 180 min and the AUC90-180. This is the first report that demonstrates the glucagon secretory patterns and the close correlations in detailed time course between the early postprandial glucagon response and the early and the late half of the postprandial glucose levels in obese and non-obese patients with type 2 diabetes.

Homeostasis model assessment of insulin resistance for evaluating insulin sensitivity in patients with type 2 diabetes on insulin therapy.

Homeostasis model assessment of insulin resistance (HOMA-IR) is a simple and useful method for evaluating insulin sensitivity. But it is difficult to apply to type2 diabetes patients treated with insulin. We have devised a method for measuring HOMA-IR and investigated the validity of HOMA-IR for evaluating insulin sensitivity in patients with type 2 diabetes on insulin therapy. In the first arm of the study, 19 poorly controlled diabetic subjects were treated with insulin and underwent euglycemic clamp study. Then the relationship between insulin resistance index assessed by the clamp test (clamp-IR) and HOMA-IR was investigated in these subjects. Log transformed HOMA-IR correlated with log transformed M/I values derived from the standard euglycemic clamp (r=-0.753, p=0.002). In the second arm of the study, we investigated the relationship between HOMA-IR and various clinical parameters in 156 patients with poorly controlled diabetes after glycemic control. Log transformed HOMA-IR correlated negatively with age (r=-0.292, p=0.0002), HDL-C (r=-0.342, p<0.0001), log transformed serum adiponectin (r=-0.309, p=0.0006) and log transformed KITT (r=-0.264, p=0.0009), and positively with body mass index (r=0.499, p<0.0001), waist circumstance (r=0.461, p<0.0001), visceral fat area (r=0.401, p<0.0001), diastolic blood pressure (r=0.223, p=0.0054), log transformed triglyceride (r=0.497, p<0.0001), urinary CPR (r=0.216, p=0.0099), ΔCPR of glucagon stimulation test (r=0.496, p<0.0001) and log transformed insulinogenic index (r=0.325, p=0.0002). These results suggest that HOMA-IR is a useful test for the evaluation of insulin sensitivity even in patients with type 2 diabetes treated with insulin.

Dipeptidyl peptidase-4 inhibitors are effective in Japanese type 2 diabetic patients with sustained endogenous insulin-secreting capacity, a higher body mass index and insulin resistance.

AIMS/INTRODUCTION: Recently, dipeptidyl peptidase-4 (DPP-4) inhibitors have become available in Japan. It has not yet been clarified what clinical parameters could discriminate DPP-4 inhibitor-effective patients from DPP-4 inhibitor-ineffective patients. MATERIALS AND METHODS: We reviewed 33 consecutive patients with type 2 diabetes admitted to Osaka University Hospital for glycemic control. All of the patients were treated with medical nutrition therapy plus insulin therapy to improve fasting plasma glucose (FPG) and postprandial glucose below 150 and 200 mg/dL, respectively. After insulin secretion and insulin resistance were evaluated, insulin was replaced by DPP-4 inhibitors. The efficacy of DPP-4 inhibitors was determined according to whether glycemic control was maintained at the target levels. RESULTS: Dipeptidyl peptidase-4 inhibitors were effective in 16 of 33 patients. DPP-4 inhibitor-effective patients were younger than DPP-4 inhibitor-ineffective patients. Body mass index (BMI) was significantly higher in DPP-4 inhibitor-effective patients. Endogeneous insulin-secreting capacity, including insulinogenic index (II), fasting plasma C-peptide (F-CPR) and C-peptide index (CPI), was more sustained in DPP-4 inhibitor-effective patients than DPP-4 inhibitor-ineffective patients. Insulin resistance evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) was significantly higher in DPP-4 inhibitor-effective patients than DPP-4 inhibitor-ineffective patients. In receiver operating characteristic analyses, the cut-off values for predicting the efficacy of DPP-4 inhibitors were 0.07 for II, 1.5 ng/mL for F-CPR, 1.0 for CPI, 23.0 kg/m(2) for BMI, 1.3 for HOMA-IR and 67.5 years for age. CONCLUSIONS: Dipeptidyl peptidase-4 inhibitors were effective in Japanese type 2 diabetic patients with sustained endogenous insulin-secreting capacity, a higher BMI and insulin resistance.

Weight reduction is associated with improvement of glycemic control in Japanese men, whose hemoglobin A1C is 5.6-6.4%, with visceral fat accumulation, but not without visceral fat accumulation.

AIMS/INTRODUCTION: The aim of the present study was to determine whether weight reduction is associated with improvement of glycemic control in non-obese and obese subjects with or without visceral fat accumulation, whose hemoglobin A1c (A1C) is 5.6-6.4%. MATERIALS AND METHODS: A total of 798 male subjects whose A1C levels were between 5.6% and 6.4% were divided into subgroups based on body mass index (BMI) and/or estimated visceral fat area (eVFA), and were analyzed with respect to the relationships between 1-year changes in BMI (ΔBMI) and A1C (ΔA1C). RESULTS: In both the BMI ≥25 and BMI <25 groups, ΔA1C correlated positively with ΔBMI (BMI ≥25 (n = 321): r = 0.236, P < 0.0001; BMI <25 (n = 477): r = 0.095, P = 0.0387) although the r-value was very small for the latter group. In addition, for the group with eVFA ≥100 cm(2) (n = 436), ΔA1C correlated positively with ΔeVFA (r = 0.150, P = 0.0017), but this correlation was not found for the eVFA <100 cm(2) group (n = 339, P = 0.3505). Furthermore, ΔA1C positively correlated with ΔBMI for the groups in BMI ≥25 with eVFA >100 cm(2) (n = 293, r = 0.256, P < 0.0001) and BMI <25 with eVFA ≥100 cm(2) (n = 145, r = 0.250, P = 0.0024), but not for the groups in BMI ≥25 with eVFA <100 cm(2) (n = 28, P = 0.6401) nor BMI <25 with eVFA <100 cm(2) (n = 332, P = 0.6605). CONCLUSIONS: These results suggest that the assessment of visceral fat, rather than BMI, might be more important in identifying subjects in whom lifestyle intervention aiming at weight reduction could be effective to prevent diabetes. This trial was registered with University Hospital Medical Information Network Clinical Trials Registry (no. UMIN 000002391).

A pilot investigation of visceral fat adiposity and gene expression profile in peripheral blood cells.

Evidence suggests that visceral fat accumulation plays a central role in the development of metabolic syndrome. Excess visceral fat causes local chronic low-grade inflammation and dysregulation of adipocytokines, which contribute in the pathogenesis of the metabolic syndrome. These changes may affect the gene expression in peripheral blood cells. This study for the first time examined the association between visceral fat adiposity and gene expression profile in peripheral blood cells. The gene expression profile was analyzed in peripheral blood cells from 28 obese subjects by microarray analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed using peripheral blood cells from 57 obese subjects. Obesity was defined as body mass index (BMI) greater than 25 kg/m(2) according to the Japanese criteria, and the estimated visceral fat area (eVFA) was measured by abdominal bioelectrical impedance. Analysis of gene expression profile was carried out with Agilent whole human genome 4 × 44 K oligo-DNA microarray. The expression of several genes related to circadian rhythm, inflammation, and oxidative stress correlated significantly with visceral fat accumulation. Period homolog 1 (PER1) mRNA level in blood cells correlated negatively with visceral fat adiposity. Stepwise multiple regression analysis identified eVFA as a significant determinant of PER1 expression. In conclusion, visceral fat adiposity correlated with the expression of genes related to circadian rhythm and inflammation in peripheral blood cells.

Efficacy of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on body weight, eating behavior, and glycemic control, in Japanese obese type 2 diabetes.

BACKGROUND: We recently reported that short-term treatment with liraglutide (20.0 ± 6.4 days) reduced body weight and improved some scales of eating behavior in Japanese type 2 diabetes inpatients. However, it remained uncertain whether such liraglutide-induced improvement is maintained after discharge from the hospital. The aim of the present study was to determine the long-term effects of liraglutide on body weight, glycemic control, and eating behavior in Japanese obese type 2 diabetics. METHODS: Patients with obesity (body mass index (BMI) >25 kg/m(2)) and type 2 diabetes were hospitalized at Osaka University Hospital between November 2010 and December 2011. BMI and glycated hemoglobin (HbA1c) were examined on admission, at discharge and at 1, 3, and 6 months after discharge. For the liraglutide group (BMI; 31.3 ± 5.3 kg/m(2), n = 29), patients were introduced to liraglutide after correction of hyperglycemic by insulin or oral glucose-lowering drugs and maintained on liraglutide after discharge. Eating behavior was assessed in patients treated with liraglutide using The Guideline For Obesity questionnaire issued by the Japan Society for the Study of Obesity, at admission, discharge, 3 and 6 months after discharge. For the insulin group (BMI; 29.1 ± 3.0 kg/m(2), n = 28), each patient was treated with insulin during hospitalization and glycemic control maintained by insulin after discharge. RESULTS: Liraglutide induced significant and persistent weight loss from admission up to 6 months after discharge, while no change in body weight after discharge was noted in the insulin group. Liraglutide produced significant improvements in all major scores of eating behavior questionnaire items and such effect was maintained at 6 months after discharge. Weight loss correlated significantly with the decrease in scores for recognition of weight and constitution, sense of hunger, and eating style. CONCLUSION: Liraglutide produced meaningful long-term weight loss and significantly improved eating behavior in obese Japanese patients with type 2 diabetes.

Successful treatment of reactive hypoglycemia secondary to late dumping syndrome using miglitol.

We herein describe a 59-year-old woman who had undergone a total gastrectomy for gastric carcinoma and suffered from postprandial hypoglycemia characterized by a loss of consciousness and spasms. She was diagnosed with reactive hypoglycemia and treated with nutrition therapy, but the frequency and severity of the hypoglycemic episodes did not decrease. She was subsequently treated successfully with miglitol, an alpha-glucosidase inhibitor (α-GI) taken twice a day; other α-GIs (acarbose and voglibose) were not effective. In conclusion, the administration of miglitol was effective for preventing reactive hypoglycemia secondary to late dumping syndrome.