Tomohiko Kimura

Kawasaki Medical University

Aims To evaluate the correlation between C‐peptide index (CPI) at 2 h post‐meal and endogenous insulin secretory capacity and to develop clinical models to predict the possibility of withdrawal from insulin therapy in patients with type 2 diabetes. Method This was a single‐centre retrospective study of patients with type 2 diabetes admitted to our...

Introduction Loss of muscle mass and the accumulation of visceral fat are known risk factors for the deterioration of glycemic control in type 2 diabetes mellitus. This study looked at the effects of such factors on glycemic control in Japanese patients with type 2 diabetes mellitus in the form of handgrip strength (HGS) and waist circumference (WC...

Background Imeglimin is a new anti-diabetic drug which promotes insulin secretion from pancreatic β-cells and reduces insulin resistance in insulin target tissues. However, there have been no reports examining the possible anti-atherosclerotic effects of imeglimin. In this study, we investigated the possible anti-atherosclerotic effects of imeglimi...

Aim Dipeptidyl peptidase‐4 (DPP‐4) inhibitors suppress the inactivation of incretin hormones and lower blood glucose levels by inhibiting DPP‐4 function. Sodium‐glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels in an insulin‐independent manner by inhibiting renal reabsorption of glucose. DPP‐4 and SGLT2 inhibitors each have the...

Aim Grip strength (GS) as a surrogate for muscular strength, waist circumference (WC) as a surrogate marker of visceral fat, and body mass index (BMI) as a surrogate marker of obesity should also be considered markers for the management of risks associated with type 2 diabetes mellitus (T2DM). However, in terms of the management of T2DM in elderly...

Introduction The use of immune checkpoint inhibitors (ICIs) is gradually increasing; ICIs produce a variety of immune-related adverse events (irAEs), especially ICI-induced hypoadrenocorticism, which can be a lethal complication if treatment is delayed. Patient concerns A 63-year-old man received chemotherapy with pembrolizumab for nonsmall cell l...

Acute necrotizing esophagitis (ANE) is a rare and potentially life-threatening complication of diabetic ketoacidosis (DKA). While its association with DKA is established, specific clinical characteristics that predict ANE in DKA patients remain less understood. This study aimed to identify these characteristics by analyzing data from 30 DKA patient...

Recently, the development of once-weekly incretin-based injections dulaglutide and semaglutide has drawn a great deal of attention. This study is aimed at comparing the efficacy of once-weekly GLP-1 receptor activator (GLP-1RA) dulaglutide and semaglutide on glycemic control and several metabolic parameters in patients with type 2 diabetes mellitus...

Most primary hypothyroidism in adults is caused by chronic thyroiditis. Autoantibodies such as anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb) are involved in the pathogenesis of chronic thyroiditis. On the other hand, the clinical features of antibody-negative hypothyroidism are not clear. In this study, we aimed to...

It has been shown that chronic hyperglycemia gradually decreases insulin biosynthesis and secretion which is accompanied by reduced expression of very important insulin gene transcription factors MafA and PDX-1. Such phenomena are well known as β-cell glucose toxicity. It has been shown that the downregulation of MafA and/or PDX-1 expression consid...

Aim: To compare the clinical usefulness of once-weekly glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide at the doses approved for use in Japanese patients with type 2 diabetes. Methods: In total, 120 patients with glycated haemoglobin (HbA1c) ≥7% were randomly assigned to dulaglutide (n = 59) or semaglutide group (n = 61), a...

Primary aldosteronism (PA) is a well-known cause of secondary hypertension. We have long performed the simple standing test in patients with PA. On the other hand, there are few reports on the usefulness of the simple standing test in PA. This study is a single-center, retrospective, observational study. A total of 173 patients with hypertension or...

Background Immune checkpoint inhibitors (ICIs) cause a variety of immune-related adverse events (irAEs). Among them, thyroid dysfunction is most frequently observed. Patients with irAEs have higher survival rates than those without irAEs, but there is no certainty as to whether the degree of thyroid dysfunction is associated with treatment response...

Although diabetic neuropathy is a well-known cause of gastrointestinal motility disorders, it is rare that diabetic neuropathy brings about esophageal obstruction. Here, we report a case with Type 3C diabetes mellitus (DM) lasting over 15 years and repeated esophageal obstruction resulting in chicken-meat-induced esophageal obstruction and candidia...

Introduction: Enteral tube feeding is an effective method of providing nutrients for patients who are unable to meet their nutritional requirements, and patients with parenteral nutrition are at an increased risk of infection. The submandibular gland is one of the major salivary glands and sialadenitis are often caused by obstruction of the saliva...

Nonalcoholic fatty liver disease (NAFLD) is closely associated with the development and pathogenesis of type 2 diabetes mellitus (T2DM). Luseogliflozin (Luseo) has been reported to improve NAFLD in T2DM model mice by affecting factors related to fatty acid synthesis and beta oxidation. Anagliptin (Ana) improves NAFLD in mice by altering the M1/M2 m...

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. We recently discovered that neuronal regeneration-related protein (NREP/P311), an epigenetically regulated gene reprogrammed by parental metabolic syndrome, is downregulated in human NAFLD. To investigate the impact of NREP insufficiency, we used RNA-sequen...

Background and aims: Recently, pemafibrate, a selective PPARα modulator, has been developed as a treatment for hypertriglyceridemia and has attracted much attention. The aims of this study were to evaluate the efficacy and safety of pemafibrate in hypertriglyceridemia patients under clinical settings. Methods and results: We evaluated changes in...

Introduction: Congenital adrenal hyperplasia is caused by deficiencies in a number of enzymes involved in hormone biosynthesis in the adrenal glands or sexual glands. Adrenocorticotropic hormone (ACTH) secretion is enhanced by decreased cortisol production, leading to adrenal hyperplasia. The frequency of 21-hydroxylase deficiency (21-OHD) was the...

Background Immune checkpoint inhibitors (ICIs), such as cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors, programmed cell death protein 1 (PD-1) inhibitors, and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors, are often used to treat a variety of malignancies. ICIs are known to cause endocrine-related immune-related adverse events (...

Objective The coronavirus disease 2019 (COVID-19) pandemic has led to a global restriction of public behavior due to lockdowns in various major cities. Lifestyle changes and reduced rates of outpatient lifestyle guidance/consulting may have had some impact on glycemic control in patients with type 2 diabetes. This study analyzed the impact of chang...

Backgrounds: Hypoglycemic alcoholic ketoacidosis is known to be one of the emergent diseases but its frequency is very low compared to hyperglycemic ketoacidosis or hyperosmolar hyperglycemic syndrome observed in subjects with diabetes mellitus. Case presentation: We experienced a case who had alcoholic ketoacidosis and severe hypoglycemia after...

Background Most primary hypothyroidism in adults is caused by chronic thyroiditis. Autoantibodies such as anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb) are involved in the pathogenesis of chronic thyroiditis. On the other hand, there have been reports of seronegative chronic thyroiditis, which can make the clinical...

Abstract Cushing's syndrome and subclinical Cushing's syndrome (SCS) are conditions of increased cortisol secretion from the adrenal glands. Cushing's syndrome includes adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (Cushing's disease) and ACTH-independent Cushing's syndrome (AICS). The purpose of this study was to investigate the...

Decreased pancreatic volume, increased pancreatic fat mass, and serrated pancreatic margins are characteristic morphological changes of the pancreas in subjects with type 2 diabetes mellitus. This retrospective study aimed to clarify the clinical significance of pancreatic morphological changes in subjects with type 2 diabetes mellitus who underwen...

It is known that Baba’s diabetic neuropathy classification (BDC) is useful in quantitative evaluation of Diabetic polyneuropathy (DPN). In this study, we aimed to investigate the possible association between BDC and various diabetic microvascular and macrovascular complications in patients whose neuropathy was evaluated with BDC. As the results, BD...

Background: In subjects with hypothyroidism, edema is often observed, and pleural effusion and pericardial fluid could be also observed. The color of such fluid retention is usually yellow. Here we show a very rare case with hypothyroidism who had bloody pleural effusion and bloody pericardial fluid. Case presentation: A 42-year-old male noticed...

Imeglimin is a new anti-diabetic drug commercialized in Japan (Twymeeg®) and has been drawing much attention in diabetes research area as well as in clinical practice. In this study, we evaluated the effect of imeglimin on pancreatic β-cells. First, single-dose administration of imeglimin enhanced insulin secretion from β-cells and decreased blood...

The role of glucagon and GLP-1 receptors in first and second phase insulin secretion.

Background Pituitary inflammation due to IgG4-related disease is a rare condition and is sometimes accompanied by central diabetes insipidus. Central diabetes insipidus produces a strong thirst sensation, which may be difficult to distinguish when complicated by salivary insufficiency. Case presentation A 45-year-old man was admitted to our departm...

Non-thyroidal illness (NTI) is a condition in which the hypothalamic-pituitary-thyroid system and thyroid hormone metabolism are abnormal due to non-thyroidal diseases. Although NTI has been reported to occur in hyperglycemic emergencies in children, there have been few studies in adult cases. In this study, we examined adult patients with hypergly...

There are many tests for evaluating endogenous insulin secretory capacity. However, there are only a limited number of studies that have examined in detail in clinical practice which method most accurately reflects the ability to secrete endogenous insulin especially in hyperglycemic state. The purpose of this study was to find the endogenous insul...

Various important transcription factors in the pancreas are involved in the process of pancreas development, the differentiation of endocrine progenitor cells into mature insulin-producing pancreatic β-cells and the preservation of mature β-cell function. However, when β-cells are continuously exposed to a high glucose concentration for a long peri...

Introduction: Osteomalacia is caused by an increase in the number of osteoids owing to mineralization failure. There are various causes of osteomalacia, such as hypophosphatemia due to excess production of fibroblast growth factor 23, vitamin D deficiency, insufficient vitamin D action, and renal tubular disorders. Patient concerns: A 53-year-ol...

Rationale: Syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) is a rare cause of hyperthyroidism. Thyroid-stimulating hormone (TSH) levels are usually normal or high, and triiodothyronine (FT3) and free thyroxine (FT4) levels are usually high in subjects with SITSH. Patient concern: A 37-year-old woman had experienced gal...

The evidence of metformin is still accumulating after its launch in the 1950s. Recently, it has been revealed that metformin, at least partially, exerts hypoglycemic effects through the changing of gut microbiota. Ogawa et al. 1 reported that metformin altered glucose absorption from the intestine in human subjects with type 2 diabetes. It has been...

Background Enteral tube feeding is an effective method of providing nutrients for patients who are unable to meet their nutritional requirements and patients with parenteral nutrition are possible the increased risk of infection. The submandibular gland is one of the salivary glands and some of sialadenitis are caused by obstruction of the salivary...

Recently, immune checkpoint inhibitors have been drawing much attention as cancer immunotherapy, but it has been shown that various immune-related adverse events (irAEs) are induced by immune checkpoint inhibitors in various organs, which has become one of the serious issues at present. A 58-year-old Japanese male with malignant melanoma was treate...

Rationale: Hypocalciuric hypercalcemia is classified as acquired hypocalciuric hypercalcemia (AHH) and familial hypocalciuric hypercalcemia (FHH). While FHH is inherited as an autosomal dominant trait, AHH is one of the rare acquired diseases and is usually treated with prednisolone. Here, we report a case with relapsing AHH which was well control...

Background: Extraocular myositis is characterized by acute onset of orbital pain, extraocular muscle swelling, absence of thyroid disease, and effectiveness of steroid therapy. While oculomotor nerve paralysis is often observed in subjects with diabetes mellitus, extraocular muscle paralysis is very rare among various diabetic mononeuropathies. In...

A 58-year-old Japanese man was brought to the emergency room due to disturbance of consciousness. He regained consciousness on the day of admission and started taking hospital meals, but he needed intravenous glucose administration for eight days. The total amount of glucose administration was 4,464 g. It took over three weeks for exogenous insulin...

Background Multiple endocrine neoplasia type 1 (MEN1) is a syndrome characterized by pituitary neoplasia, primary hyperparathyroidism and pancreatic endocrine tumor. Here we show a case of MEN1 with a germline frameshift mutation in its gene accompanied by a giant cervical lipoma and multiple fatty deposits in the pancreas. Case presentation A 28-...

Aim At present, daily DPP-4 inhibitors are quite frequently prescribed in subjects with type 2 diabetes mellitus (T2DM). Recently, it has been drawing much attention that once-weekly incretin-based injection dulaglutide was developed. In this study, we aimed to examine the possible effects of once-weekly GLP-1 receptor activator (GLP-1RA) dulagluti...

Advances in insulin preparations and administration methods have produced a gradual improvement in glycemic control in patients with type 1 diabetes mellitus (DM). Nevertheless, glycated hemoglobin (HbA1c) levels in patients with type 1 DM are still poor compared to those in patients with type 2 DM. Here, we sought to assess the efficacy and safety...

Fundamental pancreatic β-cell function is to produce and secrete insulin in response to blood glucose levels. However, when β-cells are chronically exposed to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and secretion are decreased together with reduced expression of insulin transcription factors. Glucagon-like peptide-1 (...

Background Tamoxifen, which is one of the selective estrogen receptor modulators (SERMs), can bring out life-threatening complication, e.g. hypertriglyceridemia-induced acute pancreatitis, although it is rare. We precisely report changes in lipoprotein metabolism before and after tamoxifen discontinuation because there have been few reports of it....

Introduction Pheochromocytoma is a catecholamine-producing tumor in the adrenal medulla and is often accompanied by hypertension, hyperglycemia, hypermetabolism, headache, and hyperhidrosis, and it is classified as benign and malignant pheochromocytoma. In addition, persistent hypertension is often observed in subjects with malignant pheochromocyto...

Sodium-glucose co-transporter 2 (SGLT2) inhibitors facilitate urine glucose excretion by reducing glucose reabsorption, leading to ameliorate glycemic control. While the main characteristics of type 2 diabetes mellitus are insufficient insulin secretion and insulin resistance, SGLT2 inhibitors have some favorable effects on pancreatic β-cell functi...

While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synt...

Under healthy conditions, pancreatic β-cells produce and secrete the insulin hormone in response to blood glucose levels. Under diabetic conditions, however, β-cells are compelled to continuously secrete larger amounts of insulin to reduce blood glucose levels, and thereby, the β-cell function is debilitated in the long run. In the diabetic state,...

Currently, incretin-based therapies focusing on glucagon-like peptide-1 (GLP-1) mimics and dipeptidyl peptidase-4 (DPP-4) inhibitors are the major tool for the treatment of type 2 diabetes in the world. In the background, unique action of incretin-related drugs can be mentioned in comparison with pre-existing glucose lowering agents. Incretin prepa...

While it is known that patients with nonalcoholic fatty liver disease exhibit enhanced insulin secretion, the factor(s) that contribute to this effect are not fully understood especially in nondiabetic subjects. Our aim was to examine crosstalk between a steatotic liver induced by a diet that is deficient in methionine choline (MCD) and pancreatic...

Introduction Nonalcoholic fatty liver disease (NAFLD) is often observed in subjects with type 2 diabetes mellitus (T2DM), and it is known that the presence of T2DM leads to the aggravation of NAFLD. The aim of this study is to compare the possible effects of three kinds of oral hypoglycemic agents on NAFLD in subjects with T2DM. Materials and Meth...

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Although gene-environment interactions have been implicated in the etiology of several disorders, the impact of paternal and/or maternal metabolic syndrome on the clinical phenotypes of offspring and the underlying genetic and epigenetic contributors of NAFLD have n...

It has been brought to our attention that Fig. 5a showing the vasculature in islets of control flox mice is not in fact an endocrine cell but rather exocrine tissue.

Aims/hypothesis The aim of this study was to elucidate the impact of 3′-phosphoinositide-dependent protein kinase-1 (PDPK1) in vascular endothelial cells on the maintenance of pancreatic beta cell mass and function. Methods Male vascular endothelial cell-specific Pdpk1-knockout mice (Tie2+/−/Pdpk1flox/flox mice) and their wild-type littermates (Ti...

Objective It is important to preserve the pancreatic β-cell function in order to maintain good glycemic control for a long period. The aim of this study was to examine which factors are associated with the β-cell function in subjects with type 2 diabetes mellitus. Methods A total of 372 subjects with type 2 diabetes who had been hospitalized for th...

It is very important to explore how we can reduce urinary albumin excretion which is an independent risk factor for ischemic heart disease. In this study, we retrospectively evaluated the effects of RAS inhibitor therapy on diabetic nephropathy in Japanese subjects whose urinary albumin levels were within normal range. We enrolled 100 subjects with...

It is known that long-chain fatty acids bind to free fatty acid receptor 1 (Ffar1), also known as G protein-coupled receptor 40 (GPR40), and amplify glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells and that Ffar1 agonists facilitates insulin secretion and ameliorates glycemic control. On the other hands, pancreatic and duodenal h...

Aims/Introduction This study examined the association between the onset of micro‐ and macroangiopathy in type 2 diabetes subjects (T2DM) and levels of HbA1c described in “Evidence‐based Practice Guideline for the Treatment for Diabetes in Japan 2013” (KD) or those indicated in “the Japan Diabetes Society and the Japan Geriatrics Society Joint Commi...

It has been thought that incretin signaling prevents arteriosclerosis, and very recently anti-arteriosclerotic effects through GLP-1 receptor were finally demonstrated in clinical human study. The purpose of this study was to investigate how vascular GLP-1 receptor expression is influenced in human subjects. First, we evaluated GLP-1 receptor expre...

Introduction: Sodium-glucose co-transporter 2 (SGLT2) inhibitors function not only to reduce hyperglycemia but also to ameliorate liver injury and reduce body weight. The aim of this study was to examine in which subjects SGLT2 inhibitors are more effective for glycemic control, liver injury, and obesity in Japanese subjects with type 2 diabetes m...

Aims We compared the protective effects of sodium glucose co‐transporter (SGLT) 2 inhibitor luseogliflozin on pancreatic β‐cells between in an early and advanced stage of diabetes and between after short‐ and long‐term use. Materials and Methods Diabetic db/db mice were treated with luseogliflozin for 2 weeks in an early stage (7‐9 weeks of age) a...

Objective Insulin glargine [300 U/mL (Gla-300)] achieved better glycemic control and reduced the risk of hypoglycemia in comparison to glargine [100 U/mL; (Gla-100)] in phase 3 trials. This is the first study to retrospectively evaluate the efficacy and safety of Gla-300 in Japanese type 1 and 2 diabetes patients in a routine clinical setting. Met...

We previously reported that SGLT2 inhibitor luseogliflozin (Luseo) preserved beta-cell mass and function in obese diabetic db/db mice. The aim of this study is to compare the protective effects of Luseo on beta-cells between in an early and advanced stage of diabetes. We used 7-week-old and 16-week-old male db/db mice as an early and advanced stage...

Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic beta cells and suppresses glucagon secretion from alpha cells. It remains controversial, however, whether GLP-1 receptor (GLP-1R) is expressed in mature alpha cells. In this study, unlike previous studies using non-diabetic animals, we demonstrated using diabetic model rat...

Aims It is well-known that chronic exposure to large amounts of ligand leads to downregulation of its receptor. It is not known, however, whether a GLP-1R agonist downregulates its receptor. For this reason, our study examined whether GLP-1R expression is reduced after long-term exposure to dulaglutide (Dula) in non-diabetic and diabetic mice. Met...

Sodium-glucose cotransporter 2 inhibitor tofogliflozin is a new type of antidiabetic drug for individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to examine in which type of individuals and/or under which conditions tofogliflozin could exert more beneficial effects on body composition and/or glycemic control in Japanese indi...

Aim/introduction: Sodium-glucose co-transporter 2 (SGLT2) inhibitors function to increase urinary glucose excretion and improve glycemic control in subjects with type 2 diabetes mellitus. SGLT2 inhibitors as well as diuretics increase urinary volume which leads to the reduction of blood pressure. The aim of this study was to compare the effects of...

Aims: Incretin signalling is known to prevent the development of arteriosclerosis by relaxation response in endothelial cells via the glucagon-like peptide 1 receptor. It remains unclear, however, whether vascular glucagon-like peptide 1 receptor expression is altered under some conditions. The aim of this study is to examine whether vascular gluc...

Werner syndrome is a rare genetic disease characterized by progeria, diabetes mellitus, cataracts and various types of malignancy. However, there are few reports showing adrenal cortex cancer in subjects with Werner syndrome. We herein report an extremely rare case of Werner syndrome accompanied by adrenal cortex cancer. Based on the data obtained...

Dipeptidyl peptidase-4 (DPP-4) inhibitors are often used all over the world and exert various beneficial effects including glucose-lowering effect in many subjects with type 2 diabetes. It is poorly understood, however, which factors are closely related with the durability of glucose-lowering effect by DPP-4 inhibitor. In this study, we examined re...

It is known that male breast cancer is extremely rare and obesity is a strong risk factor of breast cancer in both male and female. In general, the prognosis in breast cancer in males is known to be very poor compared to that in females as it tends to be more advanced stage due to delayed initial diagnosis. Therefore, we should be aware of the poss...

Introduction It is known that chylomicronemia is caused by several pathologies and is classified as primary and secondary chylomicronemia. Since hypertriglycemia is associated with an increased risk of cardiovascular disease and severe pancreatitis, it is very important to make a proper diagnosis of the cause of hypertriglycemia. Case description W...

Type 2 diabetes mellitus is characterized by insulin resistance in various insulin target tissues, such as the liver, adipose tissue, and skeletal muscle, and insufficient insulin secretion from pancreatic β-cells. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which are newly developed antidiabetic agents, decrease blood glucose levels by enha...

Aims: The aim of this study was to search for factors influencing cognitive impairment and to clarify the association between the fluctuation of blood glucose levels and cognitive impairment in elderly Japanese subjects with type 2 diabetes. Methods: We recruited 88 relatively elderly subjects (≥65years old) with type 2 diabetes who were hospita...

Pancreatic β-cell dysfunction and insulin resistance are the main characteristics of type 2 diabetes. Chronic exposure of β-cells to hyperglycemia leads to the deterioration of b-cell function. Such phenomena are well known as pancreatic β-cell glucose toxicity. MafA, a strong transactivator of insulin gene, is particularly important for the mainte...

Objective To examine the association between glycemic control and the new onset of macroangiopathy in Japanese subjects with type 2 diabetes. Methods We examined seven-year follow-up data for 572 patients. We divided the subjects by the average of seven-year glycemic control based on the guidelines. First, we excluded the subjects with a past histo...

We experienced a case of iliopsoas abscess which was markedly recovered after percutaneous and surgical drainage in a subject with poorly controlled type 2 diabetes. When iliopsoas abscess is suspected, physicians should survey patients by CT scan or MRI and should consider invasive treatment including surgical drainage.

We searched for factors influencing the clinical effects of GLP-1 analogue liraglutide in subjects with type 2 diabetes. Multivariate analyses showed that hypertriglyceridemia and baseline HbA1c levels were independent predictors for the efficacy of liraglutide and that CPR index was an independent predictor for the durability of liraglutide.