Yoshiyuki Hamamoto

Tazuke Kofukai Medical Research Institute, Kitano Hospital, Ōsaka, Ōsaka, Japan

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Publications (59)135.37 Total impact

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    ABSTRACT: Aims: Hypersecretion of glucagon and reduced insulin secretion both contribute to hyperglycemia in type 2 diabetes (T2DM). However, the relative contributions of impaired glucagon and insulin secretions in glucose excursions at the various stages of T2DM development remain to be determined. Methods: The responses of glucagon and insulin as well as those of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were examined before and after ingestion of glucose or mixed meal in Japanese subjects with normal or impaired glucose tolerance (NGT and IGT) and in non-obese, untreated T2DM of short duration. Results: In OGTT, T2DM showed a rise in glucagon at 0-30 min, unlike NGT and IGT, along with reduced insulin. In MTT, all three groups showed a rise in glucagon at 0-30 min, with that in T2DM being highest, while T2DM showed a significant reduction in insulin. Linear regression analyses revealed that glucose area under the curve (AUC)0-120 min was associated with glucagon-AUC0-30 min and insulin-AUC0-30 min in both OGTT and MTT. Total and biologically intact GIP and GLP-1 levels were similar among the three groups. Conclusions: Disordered early phase insulin and glucagon secretions but not incretin secretion are involved in hyperglycemia after ingestion of nutrients in T2DM of even a short duration.
    Journal of Diabetes and its Complications 04/2015; 29(3):413-421. DOI:10.1016/j.jdiacomp.2014.12.010 · 3.01 Impact Factor
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    ABSTRACT: To investigate the relationship between plasma betatrophin concentrations and insulin secretion capacity in people with Type 2 diabetes. Glucagon stimulation tests (1 mg) were performed in 70 people with Type 2 diabetes after an overnight fast. Plasma betatrophin concentrations were measured using an enzyme-linked immunosorbent assay. Insulin secretion capacity was evaluated by measuring increments of C-peptide concentration in response to glucagon stimulation, and creatinine clearance was determined by comparing creatinine concentrations in serum and 24-h urine samples. Plasma betatrophin concentrations were positively correlated with duration of Type 2 diabetes (r = 0.34, P = 0.003), and negatively correlated with increments of C-peptide concentration (r = 0.37, P = 0.001) and creatinine clearance (r = 0.37, P = 0.001). The correlation with increments of C-peptide concentration remained significant after adjustment for age and duration of Type 2 diabetes (r = 0.25, P = 0.037). Multivariate analysis identified age and increments of C-peptide concentration as independent factors associated with plasma betatrophin levels. Plasma betatrophin levels inversely correlate with insulin secretion capacity, suggesting that betatrophin levels are regulated by insulin secretion capacity in humans. © 2015 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.
    Diabetic Medicine 01/2015; 32(5). DOI:10.1111/dme.12696 · 3.12 Impact Factor
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    ABSTRACT: We herein report three cases of gonadotroph adenoma in men (36-72 years of age) presenting with visual impairment and suprasellar masses measuring approximately 20 to 30 mm in diameter. Endocrinological examinations were normal, except for slightly increased follicle stimulating hormone (FSH) levels in two cases. Based on the tentative diagnosis of non-functioning pituitary adenoma, transsphenoidal surgery was performed, which revealed that the tumors consisted of FSH- and LH-positive cells. As gonadotroph adenoma is very common among patients with clinically silent pituitary adenoma, it should be diagnosed using pathological examinations.
    Internal Medicine 06/2013; 52(11):1199-1202. DOI:10.2169/internalmedicine.52.7855 · 0.90 Impact Factor
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    ABSTRACT: Since infection with Helicobacter pylori has been suggested to play a pathogenic role in diabetes mellitus, we investigated whether eradication therapy for H. pylori might affect glycemic control in Japanese subjects with type 2 diabetes. A total of 72 subjects (55 males, 17 females; aged 63.7 years) with type 2 diabetes who received eradication therapy for H. pylori were included. The change of their blood glycosylated hemoglobin (A1C) levels 3 months before (-3 m) the H. pylori eradication, as well as 3 months (3 m) and 6 months (6 m) after were evaluated. Their A1C levels did not show any significant change after therapy {6.9 [0.1]% (-3 m) to 7.0 [0.1]% (3 m); P = 0.3, 7.0 [0.1] (6 m); P = 0.3}. Our findings suggest that the eradication therapy for H. pylori does not, at least profoundly, affect glycemic control in Japanese subjects with type 2 diabetes.
    05/2013; 4:41-3. DOI:10.4137/JCM.S10828
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    ABSTRACT: Aim: The aim of this study was to determine the correlation between the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis and glucose intolerance in acromegaly during the early postoperative period. Subjects and methods: The study included 20 patients with acromegaly caused by GH-secreting pituitary adenoma who received transsphenoidal surgery in our hospital. Glucose tolerance was evaluated with oral glucose tolerance tests (OGTTs) performed during pre- and early postoperative periods (9 [7-18] days after surgery). Homeostasis model assessment of insulin resistance (HOMA-IR) and insulinogenic index (IGI) were calculated, and correlation analyses were performed between these values and the GH-IGF-I axis. Patients were divided according to postoperative changes of the axis, and glucose tolerance was compared between the groups. Results: In preoperative OGTTs, nine patients had impaired glucose tolerance and two had diabetes mellitus patterns. Postoperatively, significant reduction was observed both in fasting plasma glucose levels (p<0.01) and in HOMA-IR (p<0.01), whereas IGI showed no significant change. HOMA-IR was significantly correlated with serum IGF-I levels both before (r=0.83, p<0.01) and after (r=0.57, p<0.01) surgery, although it was not correlated with serum GH levels. Patients who achieved more than 50% postoperative reduction in serum IGF-I levels showed significant improvement in OGTTs results (p<0.05). Conclusions: In patients with acromegaly, serum IGF-I levels, but not GH levels, were significantly correlated with insulin resistance. Early postoperative improvement of glucose tolerance is observed in patients who achieved postoperative reduction in serum IGF-I levels.
    Journal of endocrinological investigation 05/2013; 36(10). DOI:10.3275/8964 · 1.45 Impact Factor
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    ABSTRACT: Objective: To evaluate varicella zoster virus-specific cell-mediated immunity and humoral immunogenicity against the herpes zoster vaccine, which is licensed as the Live Varicella Vaccine (Oka Strain) in Japan, in elderly people with or without diabetes mellitus. Methods: A pilot study was conducted between May 2010 and November 2010 at Kitano Hospital, a general hospital in the city of Osaka in Japan. A varicella skin test, interferon-gamma enzyme-linked immunospot assay and immunoadherence hemagglutination tests were performed 0, 3, and 6 months after vaccination. Vaccine safety was also assessed using questionnaires for 42 days and development of zoster during the one-year observational period. We enrolled 10 healthy volunteers and 10 patients with diabetes mellitus aged 60-70 years. Results: The live herpes zoster vaccine boosted virus-specific, cell-mediated and humoral immunity between elderly people, with or without diabetes. Moreover, no systemic adverse reaction was found. None of the study participants developed herpes zoster. Conclusion: The live herpes zoster vaccine was used safely. It effectively enhanced specific immunity to varicella zoster virus in older people with or without diabetes mellitus.
    The Journal of infection 04/2013; 67(3). DOI:10.1016/j.jinf.2013.04.010 · 4.44 Impact Factor
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    ABSTRACT: Background: Recently, it has been reported that the incidence of primary aldosteronism (PA) among patients with hypertension is much more frequent than previously reported. Aim: In the present study, we investigated the frequency and features of PA associated with subclinical Cushing syndrome (SCS). Material and Methods: Subjects included consecutive patients (n=39) who were diagnosed as PA and performed adrenal venous sampling (AVS) between 2003 and 2011 in our institute. Results: In 39 subjects who were diagnosed as PA, 29 patients were operated and five cases (12.8 %) showed no suppression in low-dose dexamethasone suppression test (DST). Four cases of them were demonstrated to be associated with SCS, and one case was associated with overt Cushing syndrome (CS). Postoperatively, three cases received replacement therapy of hydrocortisone, while others did not. Pathological findings indicated the diagnosis of aldosterone-producing adenoma (APA) in four cases associated with SCS, and of idiopathic hyperaldosteronism (IHA) in one case associated with overt CS. In all five cases, immunohistochemical analysis demonstrated the immunoreactivities of both 3βHSD and P450c17 in the adrenocortical tumors, the marked cortical atrophy in the zona fasciculata and reticularis, the decreased dehydroepiandrosterone sulfotransferase (DHEA-ST) expression, and suppression of hypothalamo-pituitary-adrenal (HPA) axis indicating the autonomous secretion of cortisol from the tumor. Conclusions: The present study suggests that PA is frequently associated with SCS with prevalence of more than 10%, justifying the routine examinations for SCS in PA cases.
    Journal of endocrinological investigation 02/2013; 36(8). DOI:10.3275/8818 · 1.45 Impact Factor
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    ABSTRACT: Objective: We prospectively investigated the efficacy of the screening methods for asymptomatic coronary heart disease (CHD) in Japanese patients with type 2 diabetes using the treadmill tolerance test (TTT) as a first-line test or the American Diabetes Association (ADA) guidelines. Methods: The subjects included consecutive inpatients with type 2 diabetes (n=331) assessed with both electrocardiogram (ECG) at rest and TTT. Subjects with abnormal TTT findings were evaluated using stress myocardial perfusion scintigraphy (MPS). Results: A total of 60 out of 69 subjects with positive TTT findings underwent MPS, among whom a total of 22 subjects (6.6% of the total number of subjects) had positive MPS results. Among those with positive MPS results, a total of 14 subjects underwent coronary angiography, eight of whom were determined to have significant coronary artery stenosis. The prevalence rates of hypertension and micro/macroalbuminuria were significantly higher in the MPS-positive group (77.3% and 54.5%, respectively) than in the TTT-negative group (44.7% and 27.1%, respectively). Among the subjects with positive MPS results, 68.2% met the 1998 ADA criteria. Conclusion: Neither the TTT as a first-line test nor the ADA guidelines are sufficiently adequate screening methods to detect asymptomatic CHD in Japanese subjects with type 2 diabetes. Conducting routine screening for asymptomatic CHD in Japanese patients with type 2 diabetes may therefore not be very useful.
    Internal Medicine 12/2012; 51(24):3337-42. DOI:10.2169/internalmedicine.51.7878 · 0.90 Impact Factor
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    ABSTRACT: We retrospectively examined the frequency of bladder cancer in Japanese patients with type 2 diabetes in relation to use of pioglitazone. Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72]).
    Diabetes research and clinical practice 12/2012; 99(2). DOI:10.1016/j.diabres.2012.11.013 · 2.54 Impact Factor
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    ABSTRACT: Obesity is a major risk factor for sleep-disordered breathing (SDB). However, many Japanese subjects with diabetes are less obese despite compared with Caucasian. We evaluated the relationship between SDB and clinical characteristics other than obesity, especially in relation to cardiac autonomic neuropathy (CAN) in Japanese subjects with diabetes. The study included a total of 261 consecutive Japanese subjects with type 2 diabetes, including nonobese subjects defined as BMI <25 kg/m(2) for Japanese. SDB was screened by 4% oxygen desaturation index (ODI) level of 5 or more events per hour, which was measured by nocturnal pulse oximetry. CAN was examined with the variation of R-R intervals (CVRR). The SDB were found in 24.5% of total subjects and 16.3% of nonobese subjects with type 2 diabetes, respectively. The nonobese type 2 diabetes subjects with SDB had significantly lower coefficient of CVRR than those without SDB. Multiple regression analysis revealed that BMI and heart rate were significant independent factors for SDB in total subjects with type 2 diabetes, but CVRR was the only significant independent factor for SDB in nonobese subjects with type 2 diabetes. These findings suggest that the presence of SDB should be kept in mind in type 2 diabetic patients with abnormality in CVRR variation in electrocardiogram even though they are not obese.
    Endocrine Journal 09/2012; 60(2). DOI:10.1507/endocrj.EJ11-0327 · 2.00 Impact Factor
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    ABSTRACT: Telmisartan has been reported to have beneficial effects on insulin resistance and lipid profiles by acting as a peroxisome proliferator-activated receptor-γ (PPARγ) agonist. In this study we investigated the relationship between telmisartan dose and glycaemic control in Japanese subjects with type 2 diabetes mellitus and hypertension. Patients (n = 263) who were prescribed telmisartan 20, 40 or 80 mg/day at our clinic were retrospectively identified from our clinical database. Only patients without changes in their treatments for diabetes and hypertension for 6 months after starting telmisartan were included in this study. Glycosylated haemoglobin A(1c) (HbA(1c)) levels were measured at 0, 3 and 6 months after starting telmisartan. At 3 and 6 months after starting telmisartan, HbA(1c) levels were significantly decreased in patients treated with telmisartan 40 or 80 mg/day but not in patients treated with telmisartan 20 mg/day (mean ± standard error change at 6 months: -0.29 ± 0.10%, p < 0.001; -0.48 ± 0.15%, p < 0.001; and -0.03 ± 0.10%, p = 0.33; respectively). When patients were classified into two groups by telmisartan dose (20 vs ≥40 mg/day), there was no significant correlation between baseline HbA(1c) and change in HbA(1c) levels over time in the 20 mg/day group. However, in patients treated with ≥40 mg/day of telmisartan, baseline HbA(1c) was negatively correlated with the change in HbA(1c) at 6 months. Multiple regression analysis confirmed that baseline HbA(1c) and telmisartan dose were the predictive factors. Our results suggest that telmisartan influences glycaemic control in a dose-dependent manner; doses ≥40 mg/day may be needed to improve glycaemic control. Our data also suggest that patients with higher baseline HbA(1c) may experience greater improvements in glycaemic control with telmisartan.
    Clinical Drug Investigation 07/2012; 32(9):577-82. DOI:10.2165/11633890-000000000-00000 · 1.56 Impact Factor
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    ABSTRACT: Aims/Introduction: We examined whether levels of glutamic acid decarboxylase autoantibodies (GADAb) might show the clinical heterogeneity of adult Japanese diabetes. Materials and Methods: In this cross‐sectional study, the serum levels of GADAb were measured in a total of 1857 consecutive adult diabetic patients aged 20 years or older. The patients with positive GADAb, arbitrarily defined as ≥1.5 U/mL, were divided into quartiles according to the number of patients. The age‐ and sex‐matched diabetic patients without GADAb were selected as a control group. Results: A total of 103 (5.5%) of the diabetic patients had GADAb, and showed higher HbA1c and serum high‐density lipoprotein (HDL) cholesterol levels, lower body mass index (BMI), urinary C‐peptide immunoreactivity (CPR), serum triglycerides (TG) and uric acid (UA) levels, and lower prevalence of metabolic syndrome than the control group (P < 0.05). Quartiles 3 and 4 (i.e. GADAb ≥4.6 U/mL) showed a higher HbA1c level, lower BMI, urinary CPR, serum TG and UA levels, quartile 2 (2.5 ≤ GADAb < 4.6 U/mL) showed a lower BMI level than the control group (P < 0.05). Among the clinical parameters, we observed significant upward trends for both HbA1c and serum HDL cholesterol levels, and significant downward trends for BMI, serum TG and UA, urinary CPR levels, and prevalence of metabolic syndrome across GADAb quartiles (P < 0.05 for trend). Conclusions: These results show that the clinical phenotype of adult Japanese diabetes correlates with GADAb levels, and that patients with GADAb (≥2.5 U/mL) show different characteristics from those without GADAb, although further longitudinal studies are required. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00190.x, 2011)
    06/2012; 3(3):266-70. DOI:10.1111/j.2040-1124.2011.00190.x
  • Y Wada · Y Hamamoto · H Ikeda · S Honjo · Y Kawasaki · K Mori · H Koshiyama
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    ABSTRACT: It has been recognized that blood pressure shows a seasonal variation, but it remains unknown whether diabetic nephropathy shows a seasonal variation. In the present study, we investigated the change in urinary albumin/creatinine ratio in relation to the season in Japanese patients with Type 2 diabetes. A total of 430 subjects (275 male, 155 female) with Type 2 diabetes and early nephropathy (defined by UACR 30-300 mg/g creatinine) were included. One year was divided into four seasons and each season was defined as winter (December-February), spring (March-May), summer (June-August), and fall (September-November), and systolic and diastolic blood pressure, serum creatinine levels, and the urinary albumin/creatinine ratio were examined. The estimated glomerular filtration rate was also calculated and evaluated. The mean age (± SE) was 64.8 ± 0.8 years. The mean systolic blood pressure was significantly higher in winter than in summer (136 ± 0.68 vs. 133 ± 0.68 mmHg, P < 0.001). The urinary albumin/creatinine ratio showed a significantly higher value in winter than in summer (72.8 ± 4.4 vs. 54.6 ± 3.4 mg/g creatinine, P < 0.001). The curve of seasonal variation of this ratio showed a similar change to that of systolic blood pressure. No significant seasonal variation was observed in estimated glomerular filtration rate and diastolic blood pressure. Our results suggest that there is a hitherto unknown seasonal variation in the urinary albumin/creatinine ratio, and that it may be necessary to consider this seasonal change, especially when performing an intervention study of nephropathy.
    Diabetic Medicine 10/2011; 29(4):506-8. DOI:10.1111/j.1464-5491.2011.03472.x · 3.12 Impact Factor
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    Yoshiyuki Hamamoto · Hiroyuki Koshiyama
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    ABSTRACT: It still remains unknown whether angiotensin-receptor blockers (ARBs) are cardioprotective in patients with type 2 diabetes. The recent two clinical trials, the ROADMAP and the ORIENT, have suggested that fatal cardiovascular events or cardiovascular deaths were unexpectedly higher in olmesartan group. These results suggest that aggressive blood pressure lowering may cause a higher risk in some high-risk patients, especially in those with preexisting coronary heart disease, indicating a possibility that the J-curve phenomenon may exist in some group of patients.
    06/2011; 2:25-8. DOI:10.4137/JCM.S7521
  • Atherosclerosis Supplements 06/2011; 12(1):112-113. DOI:10.1016/S1567-5688(11)70531-1 · 2.29 Impact Factor
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    ABSTRACT: Lymphocytic hypophysitis is divided into three forms according to the involved tissues, lymphocytic adenohypophysitis, lymphocytic infundibulo-neurohypophysitis, and lymphocytic panhypophysitis (LPH). The term LPH was first proposed by us in 1995, although its entity and pathogenesis still remain controversial. Here we report five cases of LPH, who visited our clinics during 1994 to 2009. All cases were female of 20 to 77 years of age, and one case was associated with pregnancy. They presented with polyuria (n = 4), headache (n = 3), general malaise, polydipsia (n = 2), blunted vision, diplopia, amenorrhea or appetite loss (n = 1). Magnetic resonance imaging showed the pituitary swelling, the thickened stalk, the loss of the T1 hyperintense neurohypophysis (n = 4), or the atrophic pituitary (n = 1). Endocrinological examinations revealed deficiencies of TSH, ADH in all cases, GH, ACTH in three cases, LH, PRL in two cases, and FSH in one case, respectively. The severity of ADH deficiency varied among the cases. Anti-pituitary antibody was not detected in the cases examined. The biopsy of the pituitary lesions was performed except for one case, all of which revealed the diffuse lymphocytic infiltration. These results suggest that LPH is characterized by the female predominance, the atypical patterns of anterior pituitary hormone deficiencies and the variable degrees of diabetes insipidus in Japanese.
    05/2011; 2:15-20. DOI:10.4137/JCM.S6254
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    ABSTRACT: Aims/Introduction: Endoplasmic reticulum (ER) stress is one of the contributing factors in the development of type 2 diabetes. To investigate the cytoprotective effect of glucagon‐like peptide 1 receptor (GLP‐1R) signaling in vivo, we examined the action of exendin‐4 (Ex‐4), a potent GLP‐1R agonist, on β‐cell apoptosis in Akita mice, an animal model of ER stress‐mediated diabetes. Materials and Methods: Ex‐4, phosphate‐buffered saline (PBS) or phlorizin were injected intraperitoneally twice a day from 3 to 5 weeks‐of‐age. We evaluated the changes in blood glucose levels, bodyweights, and pancreatic insulin‐positive area and number of islets. The effect of Ex‐4 on the numbers of C/EBP‐homologous protein (CHOP)‐, TdT‐mediated dUTP‐biotin nick‐end labeling (TUNEL)‐ or proliferating cell nuclear antigen‐positive β‐cells were also evaluated. Results: Ex‐4 significantly reduced blood glucose levels and increased both the insulin‐positive area and the number of islets compared with PBS‐treated mice. In contrast, there was no significant difference in the insulin‐positive area between PBS‐treated mice and phlorizin‐treated mice, in which blood glucose levels were controlled similarly to those in Ex‐4‐treated mice. Furthermore, treatment of Akita mice with Ex‐4 resulted in a significant decrease in the number of CHOP‐positive β‐cells and TUNEL‐positive β‐cells, and in CHOP mRNA levels in β‐cells, but there was no significant difference between the PBS‐treated group and the phlorizin‐treated group. Proliferating cell nuclear antigen staining showed no significant difference among the three groups in proliferation of β‐cells. Conclusions: These data suggest that Ex‐4 treatment can attenuate ER stress‐mediated β‐cell damage, mainly through a reduction of apoptotic cell death that is independent of lowered blood glucose levels. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00075.x, 2010)
    03/2011; 2(2):104 - 110. DOI:10.1111/j.2040-1124.2010.00075.x

Publication Stats

393 Citations
135.37 Total Impact Points


  • 2006–2015
    • Tazuke Kofukai Medical Research Institute, Kitano Hospital
      Ōsaka, Ōsaka, Japan
  • 2012–2013
    • Centre For Diabetes And Endocrinology
      Johannesburg, Gauteng, South Africa
  • 2010
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1999–2010
    • Kyoto University
      • • Department of Diabetes and Clinical Nutrition
      • • Quantum Science and Engineering Center
      • • Graduate School of Medicine / Faculty of Medicine
      Kioto, Kyōto, Japan
  • 2008
    • Joslin Diabetes Center
      • Section on Islet Cell and Regenerative Biology
      Boston, Massachusetts, United States
  • 2003
    • Harvard Medical School
      Boston, Massachusetts, United States