Hiroshi Nomoto

Hiroshi Nomoto
Hokkaido University | Hokudai · Department of Rheumatology, Endocrinology and Nephrology

PhD

About

110
Publications
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Publications

Publications (110)
Article
Full-text available
Background Dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium–glucose co-transporter 2 (SGLT2) inhibitors improve hyperglycemia, and the usefulness of co-administration of DPP-4 inhibitors and insulin therapy has been well established. However, it has been still uncertain whether combination therapy of SGLT2 inhibitors and insulin is superior to...
Article
Aim: To investigate the achievement of individualized target HbA1c based on the Japanese guideline after geriatric assessment with the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) and to evaluate patient characteristics acting as barriers to achieving the target HbA1c in elderly outpatients with diabetes....
Article
Full-text available
We aimed to determine the mechanism by which the sodium glucose co-transporter 2 inhibitor, luseogliflozin, preserves pancreatic beta-cell mass and function in db/db mice. Six-week-old db/db mice were fed to standard chow or standard chow containing 0.01% luseogliflozin. After 4 weeks, DNA microarray analysis, real-time PCR analysis, and measuremen...
Article
Background: In pancreatic β-cells under diabetic conditions, metabolic stressors cause mitochondrial dysfunction and reduce oxidative phosphorylation, resulting in impaired intracellular metabolism. It has been suggested that aberrant activation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) plays a role in this impairment. Howev...
Article
Background: Improvement of beta-cell function is reportedly involved in the improvement of glucose tolerance and remission of diabetes after bariatric and metabolic surgery. However, the impact of this surgery on beta-cell function in Japanese patients is not clear. The objective of this study was to investigate the effect of this surgery on beta-c...
Article
Background: Bariatric/metabolic surgery is a valid treatment option for patients with obesity, type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD) . Although magnetic resonance imaging (MRI) is more accurate, the evaluation of NAFLD is generally limited to ultrasonography and various scoring systems. Here, we show a therapeutic effe...
Article
Background: Impaired endogenous insulin secretion was related to instability of glucose variability (GV) in patients with type 2 diabetes (T2DM) in our previous studies. However, some patients, including those with fasting serum C-peptide (CPR) ≤2 ng/mL, did not show this relationship. Given these findings, the present study aimed to identify other...
Article
Background and Aims: Our previous study revealed that more than half of patients with impaired glucose tolerance (IGT) before renal transplantation improved to normal glucose tolerance after transplantation. However, the mechanism was not clear. This study aimed to investigate whether changes in glucose tolerance were associated with insulin secret...
Article
Background and Aims: It has been shown that metabolic remodeling from oxidative phosphorylation to glycolysis via activation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) occurs in pancreatic beta cells in non-Asians with diabetes, resulting in impaired beta cell function. We used multiple autopsy pancreatic sections to investig...
Article
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Introduction Incretin-based therapies exert antihyperglycaemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent fashion. The first-in-class oral glucagon-like peptide-1 receptor agonist semaglutide has potent effects on glycaemic and weight control, but little evidence has been published for the superiority...
Article
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Purpose To explore the clinical significance of anti-rabphillin-3A antibody for the differential diagnosis of lymphocytic panhypophysitis. Methods and results A 58-year-old Japanese man developed uveitis of unknown cause in 2017. In 2019, he became aware of polyuria. In August 2020, he noticed transient diplopia and was diagnosed with right abduce...
Article
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Incretins reduce glycemic variability (GV) in patients with type 2 diabetes, but it is unknown whether switching from a combination of basal insulin and a DPP-4 inhibitor to insulin degludec/liraglutide (IDegLira) improves GV. We performed an exploratory prospective observational study to compare the effect of IDegLira and the combination on GV. We...
Article
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Aims/hypothesis Type 2 diabetes is characterised by islet amyloid and toxic oligomers of islet amyloid polypeptide (IAPP). We posed the questions, (1) does IAPP toxicity induce an islet response comparable to that in humans with type 2 diabetes, and if so, (2) what are the key transcriptional drivers of this response? Methods The islet transcripto...
Article
Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are well-established means of improving glycemia and preventing cardio-renal events in patients with type 2 diabetes. However, their efficacy and safety have yet to be fully characterized in patients with type 1 diabetes (T1D). We studied patients with T1D who regularly attended one of five diabet...
Article
Background and Aims Almost all of the energy in noodle dishes is derived from carbohydrates, particularly starch. Recently, we invented a pasta with reduced starch content to about 50% and increased dietary fiber content, designated low-starch high-fiber pasta (LSHFP). In this study, we investigated the ingestion of LSHFP on the postprandial glucos...
Article
Full-text available
Rationale: Tumor-induced osteomalacia (TIO) is curable by tumor resection, but detection of the tumor can be challenging. Overproduction of fibroblast growth factor 23 (FGF23) by the tumor causes hypophosphatemia and consequently induces inappropriate bone turnover. Conventionally oral phosphate supplementation was the only treatment for TIO, but...
Article
Aims: Glucokinase activators (GKAs) show a hypoglycaemic effect through augmentation of insulin secretion in pancreatic beta-cells and glucose utilization in the liver. The results from some clinical studies of GKAs suggested they show an unsustained hypoglycaemic effect. We investigated how sub-chronic administration of a GKA results in attenuati...
Article
Full-text available
Aims: Sodium-glucose cotransporter-2 inhibitor (SGLT2i) reduces clinic blood pressure (BP), but the effects on BP circadian rhythm remain unclear. The present study aimed to determine the nighttime antihypertensive effect of SGLT2i compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) in patients with type 2 diabetes and hypertension. Materials...
Article
Full-text available
Objective Glucose-dependent insulinotropic polypeptide (GIP) is speculated to worsen growth hormone (GH) hypersecretion in acromegaly and to be a cause of paradoxical increases in GH (PI-GH) during 75-g oral glucose tolerance testing (75-g OGTT). Dipeptidyl peptidase-4 inhibitors (DPP4is), which increase the circulating concentration of active GIP,...
Article
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Dipeptidyl peptidase‐4 (DPP‐4), namely CD26, is expressed on the surface of immune cells, suggesting that inhibition of DPP‐4 may affect the immune system. The current multicenter observational case‐control study was conducted to investigate the effects of DPP‐4 inhibitor (DPP‐4i) administration on Graves’ disease (GD) activity. This study comprise...
Article
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Background: Fibroblast growth factor 23 (FGF23) decreases serum phosphate levels by inhibiting proximal tubular phosphate reabsorption and intestinal phosphate absorption by decreasing serum 1,25-dihydroxyvitamin D level, thereby regulating phosphate metabolism. Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by FGF23 over...
Article
Full-text available
Objective: We previously reported that Neuromedin B (NMB) is expressed in murine pituitary corticotrophs under adrenal insufficiency (1). Because NMB is also expressed in several cancer cells and stimulates ACTH secretion, we hypothesized that NMB is related to corticotroph adenoma cell proliferation and hormone secretion. To examine this hypothesi...
Article
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The contribution of endogenous insulin secretion to glycemic variability (GV) may differ between patients with impaired insulin secretion and those with preserved secretion. Our objective was to determine the linearity of the relationship between fasting C-peptide (CPR) as a marker of endogenous insulin secretion and GV in type 2 diabetes (T2DM), r...
Article
Full-text available
Background This study aimed to explore predictive factors of time below target glucose range (TBR) ≥ 1% among patients’ characteristics and glycemic variability (GV) indices using continuous glucose monitoring data in elderly patients with type 2 diabetes. Methods We conducted a prospective observational study on 179 (71 female) Japanese outpatien...
Article
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Aims/introduction: We aimed to determine whether glucokinase is required for beta cell mass expansion induced by high-starch diet (HSTD)-feeding, as has been shown in its high-fat diet-induced expansion. Materials and methods: Eight-week-old male wild-type (Gck+/+ ) or glucokinase haploinsufficient (Gck+/- ) mice were fed either a normal chow (N...
Article
Efficacy of glucokinase activation on glycemic control is limited to a short-term period. One reason might be related with the excess glucose signalling by glucokinase activation towards beta-cells. In this study, we investigated the effect of glucokinase haploinsufficiency on glucose tolerance as well as beta-cell function and mass using a mouse m...
Article
Full-text available
Introduction: Glucagon-like peptide (GLP)-1 receptor agonists exert potent hypoglycemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent manner. Once-weekly subcutaneous administration of the GLP-1 receptor agonist semaglutide has beneficial effects on glycemic and body weight control, but it is currently u...
Article
Full-text available
Aims/Introduction We recently reported the beneficial effect of the combination of SGLT2 inhibitor and DPP‐4 inhibitor on daily glycemic variability in patients with type 2 diabetes mellitus (T2DM). Additional favorable effects of combination therapy were explored in this secondary analysis. Materials and Methods The CALMER study was a multicenter...
Article
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We provide the details of the successful management of a patient with active Cushing’s disease complicated with coronavirus disease 2019 (COVID-19) pneumonia. The patient was a 27-year-old Japanese female healthcare worker who was scheduled to undergo pituitary surgery for Cushing’s disease. She had been in close contact with an undiagnosed patient...
Article
Full-text available
Aims/Introduction To identify the effect of combination therapy with a dipeptidyl peptidase‐4 (DPP‐4) inhibitor and a sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor compared with switching from a DPP‐4 inhibitor to a SGLT2 inhibitor on improving the glucose variability in patients with or without impaired endogenous insulin secretion. Materials...
Preprint
Full-text available
Background This study aimed to explore predictive factors of time below target glucose range (TBR) ≥ 1% among patients’ characteristics and glycemic variability (GV) indices using continuous glucose monitoring data in elderly patients with type 2 diabetes.Methods We conducted a prospective observational study on 179 (71 female) Japanese outpatients...
Article
Full-text available
Aims/Introduction Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors, as well as thiazolidines, suppress nonalcoholic fatty liver disease (NAFLD); however, few comparative studies have been reported. Dapagliflozin has demonstrated non‐inferiority compared with pioglitazone for glycemic control and superiority regarding weight reduction in patients...
Article
A silent pituitary adenoma (SPA) is characterized by the expression of pituitary hormones, detected by immunohistochemical staining, in the absence of clinical signs or symptoms of hormonal excess. Compared with functional pituitary adenomas, little is known regarding the involvement of SPAs in metabolic disorders. This study aimed to examine the c...
Article
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Aims/Introduction To identify the coefficient of variation (CV) threshold for unstable glucose variability (GV) and hypoglycemia, and to characterize a patient population with unstable GV and hypoglycemia. Materials and Methods This was an observational study that enrolled 284 Japanese outpatients with type 2 diabetes who underwent continuous gluc...
Article
Hypophosphatasia (HPP) is caused by mutations in the tissue nonspecific alkaline phosphatase (TNSALP) gene in an autosomal recessive or dominant manner and characterized by defective mineralization of bone and low serum ALP levels. In this report, we present a family with HPP mother (case 1) and HPP child (case 2) who have identical TNSALP gene mut...
Article
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Aims/Introduction Alcohol ingestion has been reported to cause hypoglycemia. However, the mechanism involved has not been unequivocally established. This study comprised healthy volunteer. We conducted a prospective trial to compare the effects of glucose and alcohol ingestion, alone or in combination, on glucose and lipid metabolism. Materials an...
Article
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Introduction SGLT2 inhibitors (SGLT2i) are used worldwide because of their multiple benefits for patients with type 2 diabetes. The purpose of this study was to determine the efficacy and safety of SGLT2i in patients with type 1 diabetes (T1DM). Materials and Methods Patients with T1DM who had been treated with SGLT2i for >12 weeks were included i...
Article
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Background: Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant disease characterized by hyperthyroxinemia without symptoms of thyrotoxicosis, due to a high affinity of mutant albumin for thyroxine. No report has described cortisol-albumin binding in FDH patient, and here we present a case of FDH presenting with false hypercort...
Article
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Background: Resistance against thyroid hormone β (RTHβ) is characterized by reduced tissue sensitivity to thyroid hormone. Patients with RTHβ resistance typically demonstrate increases in FT3 and FT4 accompanied by inappropriately elevated TSH. Mutations in the TRβ gene are the most common genetic disorder in thyroid hormone resistance and result i...
Article
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Background: Patients with diabetes present hypercortisolemia, which may exacerbate not only glycemic control but also diabetic complications and fatty liver (1). Blood steroid hormone levels including corticosterone and aldosterone are high in db/db mice (2), although the mechanism is still unclear. Objective: To reveal the mechanism underlying the...
Article
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BACKGROUND: Cyclic Cushing’s disease is rare and treatments have not been established for post-surgical recurrent cases. Here, we report a patient with recurrent cyclic Cushing’s disease, whose subjective symptoms improved by administration of metyrapone and hydrocortisone. Clinical Case: A 45-year-old woman had exhibited face and peripheral edema,...
Article
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Introduction Nocturnal hypertension is clinically important for patients with type 2 diabetes (T2D), considering its strong correlation with cardiovascular events. We aim to test the hypothesis that the sodium-glucose cotransporter 2 inhibitor, luseogliflozin, ameliorates nocturnal hypertension more effectively than a dipeptidyl peptidase (DPP)-4 i...
Article
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Aims/hypothesis The conserved hypoxia inducible factor 1 α (HIF1α) injury-response pro-survival pathway has recently been implicated in early beta cell dysfunction but slow beta cell loss in type 2 diabetes. We hypothesised that the unexplained prolonged prediabetes phase in type 1 diabetes may also be, in part, due to activation of the HIF1α signa...
Article
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There is unexplained deficit in size and function of the exocrine pancreas in type 1 diabetes (T1D). We obtained pancreas from an individual with pre-T1D obtained at surgery and addressed the question, what is the relative inflammation in the exocrine and endocrine pancreas in pre-T1D in the absence of the potential confounding changes at autopsy o...
Article
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This multicenter, prospective, randomized, open‐label, blinded‐endpoint, parallel‐group, short‐term (4–5 weeks) controlled trial was conducted to investigate the superiority of the lowering effect in mean amplitude of glycemic excursions (MAGE) during meal tolerance tests (MTT) for the combination of DPP‐4 inhibitor (DPP‐4i) and SGLT2 inhibitor (SG...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
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The islet in type 2 diabetes (T2D) is characterized by amyloid deposits derived from islet amyloid polypeptide (IAPP), a protein co-expressed with insulin by β-cells. In common with amyloidogenic proteins implicated in neurodegeneration, human IAPP (hIAPP) forms membrane permeant toxic oligomers implicated in misfolded protein stress. Here, we esta...
Article
Objective: To explore the beneficial effects of dapagliflozin and/or insulin glargine on the pancreatic beta cell mass and hepatic steatosis in db/db mice. Methods: Six-week-old db/db mice were assigned to one of four groups: untreated (Placebo), treated with dapagliflozin (Dapa), treated with insulin glargine (Gla), or treated with dapagliflozi...
Article
Full-text available
Patients with acromegaly are at increased risk of developing certain tumors, including goiter and thyroid nodules, and occasionally autonomous thyroid nodules. A 53-year-old woman presented at our hospital with untreated acromegaly. She had typical physical features of acromegaly with pituitary adenoma, and thyrotoxicosis with thyroid-stimulating h...
Data
Figure S1 Comparison of changes in glycated albumin (GA) before and after treatment in each group. Values indicate the mean, and P‐values were generated using paired or unpaired Student's t‐tests, with P < 0.01 (**) being considered to represent statistical significance. Repaglinide, the group that switched from a sulfonylurea to repaglinide at the...
Data
Figure S1 ¦ Receiver operating characteristic for the cut‐off value of sulfonylurea dose and age to identify non‐exacerbation of glycated hemoglobin in the group that discontinued sulfonylurea. Figure S2 ¦ Incidence of hypoglycemic episodes in the group that discontinued sulfonylurea compared with the group that maintained sulfonylurea, but at the...
Data
Table S1 Laboratory data for the study population at baseline and 12 weeks. Table S2 Association between sulfonylurea dose and rate of improvement after switching from sulfonylurea to repaglinide. Table S3 Analysis of the contributing factors to the change in glycated albumin or the glycated albumin to glycated hemoglobin ratio in the repaglinide...
Data
Casual blood glucose levels before the administration of everolimus.
Data
Casual blood glucose levels after the administration of everolimus.
Data
Casual blood glucose levels before receiving a subtotal stomach-preserving pancreaticoduodenectomy (October, 2008).
Data
Casual blood glucose levels after the administration of everolimus (from Day 31 to Day 189).
Article
Full-text available
Aims/Introduction We investigated the difference in efficacy and safety between discontinuation and maintaining of sulfonylurea when adding a sodium‐glucose cotransporter 2 inhibitor (SGLT2i). Materials and Methods In this multicentre, prospective observational study, 200 patients with type 2 diabetes treated with sulfonylurea and with a need to a...
Article
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Aims/introduction: We compared treatment satisfaction in type 2 diabetes patients taking daily and weekly glucagon-like peptide-1 (GLP-1) receptor agonists. Materials and methods: The study was a 12-week, multicenter, open-label, prospective, randomized, parallel-group comparison trial. The participants were Japanese patients with type 2 diabete...