Comparison of canagliflozin and teneligliptin on energy intake and body weight in Japanese patients with Type 2 diabetes: a subanalysis of the CANTABILE study.

Background: While the Sodium-glucose co-transporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) are widely used for the glycemic control in type 2 diabetes mellitus, the differences in the effects of SGLT2 inhibitors and DPP4 inhibitors on energy intake and diabetes-related indicators are unclear.

Methods: This was a subanalysis of the CANTABILE study which compared the effects of canagliflozin and teneligliptin on metabolic factors in Japanese patients with Type 2 diabetes. The changes at 24 weeks from the baseline of the diabetes-related indicators including Hemoglobin A1c (HbA1c), energy intake and body weight were compared between the canagliflozin and teneligliptin groups.

Glucagon-like Peptide-1 analogues and delipidation of coronary atheroma in statin-treated type 2 diabetic patients with coronary artery disease: The prespecified sub-analysis of the OPTIMAL randomized clinical trial.

Background And Aims: Randomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet.

Methods: The OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721).

Effect of Luseogliflozin on Myocardial Flow Reserve in Patients with Type 2 Diabetes Mellitus (LUCENT-J Study).

Introduction: In patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors has been shown to reduce hospital admission rates for heart failure (HF). However, the multiple mechanisms hypothesized and investigated to explain the cardioprotection of SGLT2 inhibitors are not fully understood.

Objectives: The effect of luseogliflozin on myocardial flow reserve (MFR) in patients with T2D (LUCENT-J) study aims to examine the effects of SGLT2 inhibitors on myocardial perfusion.

Exploring the genetic diversity of the Japanese population: Insights from a large-scale whole genome sequencing analysis.

The Japanese archipelago is a terminal location for human migration, and the contemporary Japanese people represent a unique population whose genomic diversity has been shaped by multiple migrations from Eurasia. We analyzed the genomic characteristics that define the genetic makeup of the modern Japanese population from a population genetics perspective from the genomic data of 9,287 samples obtained by high-coverage whole-genome sequencing (WGS) by the National Center Biobank Network. The dataset comprised populations from the Ryukyu Islands and other parts of the Japanese archipelago (Hondo).

Diabetic microvascular complications predicts non-heart failure with reduced ejection fraction in type 2 diabetes.

Aims: The relationship between diabetic microvascular complications and the incidence of two types of heart failure-heart failure with reduced ejection fraction (HFrEF) (left ventricular ejection fraction [LVEF] < 40%) and non-HFrEF (LVEF ≥ 40%)-in patients without prior heart failure has not been clarified. We herein examined the association between diabetic microvascular complications and HFrEF or non-HFrEF in patients with type 2 diabetes mellitus (T2DM) without prior heart failure.

Methods And Results: In this retrospective cohort study, we assessed the relationship between the presence of diabetic microvascular complications or severity of diabetic retinopathy (no apparent, non-proliferative and proliferative retinopathy) and nephropathy (normoalbuminuria, microalbuminuria, and macroalbuminuria) at baseline, with the primary outcome of first heart failure hospitalization classified as HFrEF or non-HFrEF in patients with type 2 diabetes mellitus without prior heart failure.

Complement 3 Is a Potential Biomarker for Cerebral Amyloid Angiopathy.

Background: Cerebral amyloid angiopathy is a cerebrovascular disease directly implicated in Alzheimer's disease pathogenesis through amyloid-β deposition. Growing evidence has shown a pivotal role of chronic neuroinflammation both in cerebral amyloid angiopathy and Alzheimer's disease.

Objective: The aim of this study was to investigate whether circulating levels of the complement 3, a crucial component of the innate immune system, are increased in patients with cerebral amyloid angiopathy.

Impaired leptin responsiveness in the nucleus accumbens of leptin-overexpressing transgenic mice with dysregulated sucrose and lipid preference independent of obesity.

While hypothalamic leptin resistance can occur prior to establishment of obesity, clarification is needed as to whether the impaired response to leptin in the reward-related nuclei occurs independently of obesity. To answer this question, we attempted to dissociate the normally coexisting leptin resistance from obesity. We investigated phenotypes of leptin-overexpressing transgenic mice fed for 1 week with 60 % high-fat diet (HFD) (LepTg-HFD1W mice).

Protocol for a Randomized, Crossover Trial to Decrease Time in Hypoglycemia by Combined Intervention of the Usage of Intermittent-Scanning Continuous Glucose Monitoring Device and the Structured Education Regarding its Usage: Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study).

Objective: Intermittent-scanning continuous glucose monitoring (isCGM) is widely used in type 1 diabetes (T1D) patients; however, the education required to prevent hypoglycemia by using isCGM is not established. This study examines the combined effect of isCGM device usage and the education to reduce the time in hypoglycemia in comparison to conventional self-monitoring of blood glucose (SMBG).

Methods: The Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study), a randomized, crossover trial, enrolls 104 T1D patients (age, 20-74 years) with T1D.

An Efficient Culture Method of CD3-Positive T Cells from Human Cryopreserved Buffy Coat Specimens.

In the National Cerebral and Cardiovascular Center (NCVC) Biobank, buffy coats have been collected from patients and stored with cryoprotective agents as a possible source for viable blood cells, using cost-efficient methods for storage. However, whether viable cells for studies can be recovered from these biospecimens has not been verified. To investigate whether T cells can be collected and expanded as viable cells from cryopreserved human buffy coats.

A Prospective Longitudinal Study on the Relationship Between Glucose Fluctuation and Cognitive Function in Type 2 Diabetes: PROPOSAL Study Protocol.

Introduction: Although the risk of dementia among patients with type 2 diabetes mellitus (T2DM) is double that of those without T2DM, the mechanism remains to be elucidated and the glycemic goal to prevent progression of cognitive impairment is unclear. Results from cross-sectional studies suggest that glucose fluctuations are associated with impairment of cognitive function among T2DM patients. Therefore, the aim of the longitudinal study described here is to evaluate the relationships between glucose fluctuation indexes assessed by continuous glucose monitoring (CGM) and cognitive function among elderly patients with T2DM.

Prevalence and Atypical Clinical Characteristics of Mutations Among Patients Admitted for Acute Lacunar Infarctions.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary small vessel disease, with reported frequencies of 2-5/100,000 individuals. Recently, it has been reported that some patients with gene mutations show atypical clinical symptoms of CADASIL. Assuming that CADASIL is underdiagnosed in some cases of lacunar infarction, this study was designed to examine the prevalence of gene mutations in the patients at highest risk who were admitted for lacunar infarctions.

The efficacy of glycemic control with continuous glucose monitoring on atheroma progression: rationale and design of the Observation of Coronary Atheroma Progression under Continuous Glucose Monitoring Guidance in Patients with Type 2 Diabetes Mellitus (OPTIMAL).

Background: Patients with type 2 diabetes mellitus (T2DM) are high-risk subjects who more frequently have micro- and macrovascular diseases including coronary artery disease (CAD). Since impaired glycemic homeostasis directly influences the formation and propagation of atherosclerotic plaques, optimal management of glycemic status is required for the prevention of diabetic atherosclerosis. Continuous glucose monitoring (CGM) provides not only average glucose level but also the degree of glucose fluctuation and hypoglycemia.

CRISPR/Cas9-mediated knockout suppresses plasma triglyceride concentrations and adiposity in rats.

Angiopoietin-like protein (ANGPTL)8 is a liver- and adipocyte-derived protein that controls plasma triglyceride (TG) levels. Most animal studies have used mouse models. Here, we generated an KO rat model using a clustered regulatory interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) system to clarify the roles of ANGPTL8 in glucose and lipid metabolism.

Analysis of mitochondrial function in human induced pluripotent stem cells from patients with mitochondrial diabetes due to the A3243G mutation.

We previously established human induced pluripotent stem (iPS) cells in two diabetic patients from different families with the mitochondrial A3243G mutation and isolated isogenic iPS cell clones with either undetectable or high levels of the mutation in both patients. In the present study, we analyzed the mitochondrial functions of two mutation-undetectable and two mutation-high clones in each patient through four methods to assess complex I activity, mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production. In the first patient, complex I activity, mitochondrial respiration, and mitochondrial ATP production were decreased in the mutation-high clones compared with the mutation-undetectable clones, and mitochondrial membrane potential was decreased in a mutation-high clone compared with a mutation-undetectable clone.

Development of ghrelin transgenic mice for elucidation of clinical implication of ghrelin.

To elucidate the clinical implication of ghrelin, we have been trying to generate variable models of transgenic (Tg) mice overexpressing ghrelin. We generated Tg mice overexpressing des-acyl ghrelin in a wide variety of tissues under the control of β-actin promoter. While plasma des-acyl ghrelin level in the Tg mice was 44-fold greater than that of control mice, there was no differences in the plasma ghrelin level between des-acyl ghrelin Tg and the control mice.

Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system.

Background: The preparation of human neurons derived from human induced pluripotent stem (iPS) cells can serve as a potential tool for evaluating the physiological and pathophysiological properties of human neurons and for drug development.

Methods: In the present study, the functional activity in neuronal cells differentiated from human iPS cells was observed.

Results: The differentiated cells expressed mRNAs for classical neuronal markers (microtubule-associated protein 2, β-tubulin III, calbindin 1, synaptophysin and postsynaptic density protein 95) and for subunits of various excitatory and inhibitory transmitters (NR1, NR2A, NR2B, GABA α1).

Impaired adipogenic capacity in induced pluripotent stem cells from lipodystrophic patients with BSCL2 mutations.

Objective: Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder characterized by marked scarcity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early-onset diabetes. Mutation of the BSCL2/SEIPIN gene causes the most severe form of CGL. The aim of this study was to generate induced pluripotent stem (iPS) cells from patients with CGL harboring BSCL2/SEIPIN mutations.

Leptin restores the insulinotropic effect of exenatide in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet.

Leptin may reduce pancreatic lipid deposition, which increases with progression of obesity and can impair β-cell function. The insulinotropic effect of glucagon-like peptide-1 (GLP-1) and the efficacy of GLP-1 receptor agonist are reduced associated with impaired β-cell function. In this study, we examined whether leptin could restore the efficacy of exenatide, a GLP-1 receptor agonist, in type 2 diabetes with increased adiposity.

Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production.

Like many other human cancers, the development of malignant mesothelioma is closely associated with a chronic inflammatory condition. Both macrophages and mesothelial cells play crucial roles in the inflammatory response caused by asbestos exposure. Here, we show that adipocytes can also contribute to asbestos-induced inflammation through dysregulated adipocytokine production.

In vitro characterization and engraftment of adipocytes derived from human induced pluripotent stem cells and embryonic stem cells.

Human induced pluripotent stem (iPS) and embryonic stem (ES) cells can differentiate into a variety of cell types. We reported on adipogenic potential of human iPS and ES cells in vitro. In the present study, we investigate the survival and maintenance of adipocytes differentiated in vitro from human iPS and ES cells after transplantation.

Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity.

Adipose tissue expresses all components of the renin-angiotensin system including angiotensinogen (AGT). Recent studies have highlighted a potential role of AGT in adipose tissue function and homeostasis. However, some controversies surround the regulatory mechanisms of AGT in obese adipose tissue.

Glucocorticoid reamplification within cells intensifies NF-kappaB and MAPK signaling and reinforces inflammation in activated preadipocytes.

Increased expression and activity of the intracellular glucocorticoid-reactivating enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) contribute to dysfunction of adipose tissue. Although the pathophysiological role of 11 beta-HSD1 in mature adipocytes has long been investigated, its potential role in preadipocytes still remains obscure. The present study demonstrates that the expression of 11 beta-HSD1 in preadipocyte-rich stromal vascular fraction (SVF) cells in fat depots from ob/ob and diet-induced obese mice was markedly elevated compared with lean control.

Index of the systemic balance of end products of glucocorticoid metabolism in fresh urine from humans.

Objective: Dysregulation of tissue-specific intracellular glucocorticoid reactivation is implicated in obesity and related metabolic diseases in humans. The ratio of end products of glucocorticoid metabolism in fresh urine sample, tetrahydrocortisol (THF) + allo-tetrahydrocortisol (allo-THF) vs. tetrahydrocortisone (THE), i.

Adipogenic differentiation of human induced pluripotent stem cells: comparison with that of human embryonic stem cells.

Induced pluripotent stem (iPS) cells were recently established from human fibroblasts. In the present study we investigated the adipogenic differentiation properties of four human iPS cell lines and compared them with those of two human embryonic stem (ES) cell lines. After 12 days of embryoid body formation and an additional 10 days of differentiation on Poly-l-ornithine and fibronectin- coated dishes with adipogenic differentiation medium, human iPS cells exhibited lipid accumulation and transcription of adipogenesis-related molecules such as C/EBPalpha, PPARgamma2, leptin and aP2.