Moderate-carbohydrate diet without caloric or lipid restriction for Japanese adult patients with nonalcoholic fatty liver disease: A prospective cohort study.

Aim: Although a low-calorie diet with lipid restriction is recommended in clinical practice guidelines for nonalcoholic fatty liver disease (NAFLD), both compliance and adherence are poor. The present study aimed to evaluate the compliance, adherence, and effectiveness of a moderate-carbohydrate diet without caloric or lipid restrictions.

Methods: Participants comprised 300 patients with NAFLD with elevated ALT levels who received counseling in carbohydrate restriction (150-200 g/day).

Bilateral atrophy of the extensor digitorum brevis muscle might be a useful sign for diagnosing diabetic polyneuropathy in Japanese men who do not sit in the traditional "seiza" style.

Aims/introduction: As the extensor digitorum brevis muscle is a small muscle in the most distal part of the legs, its atrophy (EDBA) might reflect symmetric polyneuropathy (SPN). We aimed to clarify the EDBA-related factors and the usefulness of bilateral EDBA detection for diagnosing SPN, especially diabetic SPN (DSPN).

Materials And Methods: In 1,893 participants from the Japanese general population (investigation I) and 133 established diabetes patients (investigation II), relationships between EDBA and various factors including the traditional sitting style called "seiza'" (kneeling and sitting on one's heels) were investigated.

Clinical Utility of the Meal Tolerance Test in the Care of Patients with Type 2 Diabetes Mellitus.

Objective The measurement of C-peptide immunoreactivity (CPR) is essential for evaluating the pancreatic β-cell function and selecting appropriate therapeutic agents in patients with diabetes mellitus. The meal tolerance test (MTT) is simple to administer physiological insulin-stimulating test. Previous studies have reported that several CPR-related indices are useful markers for predicting insulin requirement in type 2 diabetes.

Clinical polyneuropathy does not increase with prediabetes or metabolic syndrome in the Japanese general population.

Aims/introduction: The prevalence of clinical polyneuropathies (ClinPNs) or nerve conduction abnormality (NCA) in the groups stratified by glucose tolerance, individual components of metabolic syndrome (metabolic syndrome [MetS] components: hypertension, dyslipidemia, obesity) and MetS defined by the International Diabetes Federation consensus was investigated in the Japanese general population. Factors associated with ClinPN and NCA were also identified.

Materials And Methods: A total of 625 examinees of regional medical checkup programs were recruited to this cross-sectional study.

Difference in normal limit values of nerve conduction parameters between Westerners and Japanese people might need to be considered when diagnosing diabetic polyneuropathy using a Point-of-Care Sural Nerve Conduction Device (NC-stat®/DPNCheck™).

Aim/introduction: Studies on a novel point-of-care device for nerve conduction study called DPNCheck have been limited to Westerners. We aimed to clarify Japanese normal limits of nerve action potential amplitude (Amp) and conduction velocity by DPNCheck (investigation I), and the validity of DPNCheck to identify diabetic symmetric sensorimotor polyneuropathy (DSPN; investigation II).

Materials And Methods: For investigation I, 463 non-neuropathic Japanese participants underwent DPNCheck examinations.

The number of microvascular complications is associated with an increased risk for severity of periodontitis in type 2 diabetes patients: Results of a multicenter hospital-based cross-sectional study.

Aims/introduction: To explore the relationships between periodontitis and microvascular complications as well as glycemic control in type 2 diabetes patients.

Materials And Methods: This multicenter, hospital-based, cross-sectional study included 620 patients with type 2 diabetes. We compared the prevalence and severity of periodontitis between patients with ≥1 microvascular complication and those without microvascular complications.

Clinical and functional characterization of the Pro1198Leu ABCC8 gene mutation associated with permanent neonatal diabetes mellitus.

Aims/introduction: The adenosine triphosphate (ATP)-sensitive potassium (KATP) channel is a key component of insulin secretion in pancreatic β-cells. Activating mutations in ABCC8 encoding for the sulfonylurea receptor subunit of the KATP channel have been associated with the development of neonatal diabetes mellitus (NDM). The aim was to investigate clinical and functional characterization of the Pro1198Leu ABCC8 gene mutation associated with permanent NDM (PNDM).

Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese.

In Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals:1.

Genetic associations of type 2 diabetes with islet amyloid polypeptide processing and degrading pathways in asian populations.

Type 2 diabetes (T2D) is a complex disease characterized by beta cell dysfunctions. Islet amyloid polypeptide (IAPP) is highly conserved and co-secreted with insulin with over 40% of autopsy cases of T2D showing islet amyloid formation due to IAPP aggregation. Dysregulation in IAPP processing, stabilization and degradation can cause excessive oligomerization with beta cell toxicity.

Increased arterial stiffness is closely associated with hyperglycemia and improved by glycemic control in diabetic patients.

Aims/introduction: Although arteriosclerotic diseases have been reported to be frequently complicated by diabetes mellitus (DM), a detailed relationship between hyperglycemia and arterial stiffness has not been fully clarified. We investigated the influence of hyperglycemia on arterial stiffness using the cardio-ankle vascular index (CAVI), which is a new method for estimating arterial stiffness.

Materials And Methods: CAVI values of 52 early-staged DM patients (duration <5 years, no microangiopathies) were compared with those of 43 age-matched non-diabetic (NDM) subjects.

Expression of wild-type and mutant S20G hIAPP in physiologic knock-in mouse models fails to induce islet amyloid formation, but induces mild glucose intolerance.

Unlabelled: Aims/Introduction:  Human islet polypeptide S20G mutation (hIAPP(S20G)) is associated with earlier onset type 2 diabetes and increased amyloidogenicity and cytotoxicity in vitro vs wild-type hIAPP (hIAPP(WT)), suggesting that amyloidogenesis may be pathogenic for type 2 diabetes. We compared the contributions of hIAPP(S20G) and hIAPP(WT) toward intra islet amyloid formation and development of type 2 diabetes in a unique physiologic knock-in mouse model.

Materials And Methods:   We replaced the mouse IAPP gene (M allele) with hIAPP(WT) (W allele) and hIAPP(S20G) (G allele) via homologous recombination and backbred transgenic mice against C57Bl/6 strain 5 generations to minimize genetic variation.

Pro198Leu missense polymorphism of the glutathione peroxidase 1 gene might be a common genetic predisposition of distal symmetric polyneuropathy and macrovascular disease in Japanese type 2 diabetic patients.

Unlabelled: Aims/Introduction:  We have previously reported that the Pro198Leu missense polymorphism in the glutathione peroxidase 1 (GPx-1) gene was associated with frequent macrovascular disease (MVD). Our goal was to examine whether the GPx-1 genotype is associated with diabetic neuropathy.

Materials And Methods:   We determined the GPx-1 genotype in 173 Japanese type 2 diabetic patients who received medical interviews, physical examinations, nerve conduction studies, quantitative vibratory perception (QVP), head-up tilt and heart rate variability tests by polymerase chain reaction-restriction fragment-length polymorphism.

Numbness and paresthesia in bilateral toes and soles, and disproportional sweating restricted to face and trunk are suitable symptoms useful for the diagnosis of diabetic symmetric polyneuropathy.

Unlabelled: Aims/Introduction:  In order to diagnose diabetic symmetric polyneuropathy (DSPN) more simply and accurately, we identified symptoms that correlated with neurological functions and existed more frequently in diabetic than non-diabetic subjects.

Materials And Methods:   The relationships between 10 symptoms (numbness or paresthesia in toe and sole, numbness in hand, pain in foot or hand, coldness in legs, painful leg cramp, dizziness on standing, sweating restricted to face/trunk and frequent constipation/diarrhea) and clinical background, defined as DSPN and cardiovascular autonomic neuropathy (CAN) by the criteria proposed in the statement of the American Diabetes Association, and seven quantitative nerve function data were evaluated in 593 diabetic patients in Wakayama Medical University Hospital (WMUH). Furthermore, the prevalence of various symptoms was examined by three questionnaires: a WMUH survey (999 diabetic outpatients), a Nationwide survey (1524 male diabetic outpatients under a primary-care physician) and a Control survey (501 non-diabetic subjects).

Effect of anti-oxidants, Ricetrienol and α-tocopherol, on adipocytokine abnormalities and fatty liver in Otsuka Long-Evans Tokushima Fatty diabetic rats.

Introduction:   We investigated the effect of Ricetrienol, which is an anti-oxidant extracted from rice bran, and α-tocopherol on the adipocytokine abnormalities and fatty liver in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

Materials And Methods:   A total of 18 OLETF rats were bred using a 30% sucrose solution (the diabetic group; DM), whereas another 18 OLETF rats were bred using ordinary water (the non-diabetic obese group; OB) as drinking water, respectively. After the sucrose-fed rats developed diabetes, all of the rats from the diabetic and obese groups were randomly divided into three groups.

Insulin gene mutations and diabetes.

Some mutations of the insulin gene cause hyperinsulinemia or hyperproinsulinemia. Replacement of biologically important amino acid leads to defective receptor binding, longer half-life and hyperinsulinemia. Three mutant insulins have been identified: (i) insulin Chicago (F49L or PheB25Leu); (ii) insulin Los Angeles (F48S or PheB24Ser); (iii) and insulin Wakayama (V92L or ValA3Leu).

Report of the committee on the classification and diagnostic criteria of diabetes mellitus.

Diabetes mellitus is a group of diseases associated with various metabolic disorders, the main feature of which is chronic hyperglycemia due to insufficient insulin action. Its pathogenesis involves both genetic and environmental factors. The long-term persistence of metabolic disorders can cause susceptibility to specific complications and also foster arteriosclerosis.

Regulation of ghrelin signaling by a leptin-induced gene, negative regulatory element-binding protein, in the hypothalamic neurons.

Leptin, the product of the ob gene, plays important roles in the regulation of food intake and body weight through its receptor in the hypothalamus. To identify novel transcripts induced by leptin, we performed cDNA subtraction based on selective suppression of the polymerase chain reaction by using mRNA prepared from the forebrain of leptin-injected ob/ob mice. One of the genes isolated was a mouse homolog of human negative regulatory element-binding protein (NREBP).

Ghrelin inhibits insulin secretion through the AMPK-UCP2 pathway in beta cells.

Ghrelin inhibits insulin secretion partly via induction of IA-2beta. However, the orexigenic effect of ghrelin is mediated by the AMP-activated protein kinase (AMPK)-uncoupling protein 2 (UCP2) pathway. Here, we demonstrate that ghrelin's inhibitory effect on insulin secretion also occurs through the AMPK-UCP2 pathway.

Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 diabetes mellitus.

Recent advances in genome research have enabled the identification of new genomic variations that are associated with type 2 diabetes mellitus (T2DM). Via fine mapping of SNPs in a candidate region of chromosome 21q, the current study identifies potassium inwardly-rectifying channel, subfamily J, member 15 (KCNJ15) as a new T2DM susceptibility gene. KCNJ15 is expressed in the beta cell of the pancreas, and a synonymous SNP, rs3746876, in exon 4 (C566T) of this gene, with T allele frequency among control subjects of 3.

Truncal pruritus of unknown origin may be a symptom of diabetic polyneuropathy.

Objective: Our goal was to ascertain the prevalence of pruritus in diabetic and nondiabetic subjects and the relevance of symptoms, signs, and nerve functions of diabetic polyneuropathy (DPN) of pruritus.

Research Design And Methods: A large-scale survey of 2,656 diabetic outpatients and 499 nondiabetic subjects was performed. In diabetic subjects, the relationship between pruritus and age, sex, diabetic duration, A1C, Achilles tendon reflex (ATR), and abnormal sensation in legs was evaluated.

Chronic kidney disease has a more powerful impact on peripheral arterial disease than metabolic syndrome in Japanese type 2 diabetic patients.

Background: Chronic kidney disease (CKD) and metabolic syndrome have been recognized as risk factors for cardiovascular disease. However, there is no information comparing their impact on macroangiopathy in diabetic patients. Thus, we studied the prevalence of CKD and metabolic syndrome in Japanese type 2 diabetic patients and then compared their impact on peripheral arterial disease (PAD) in type 2 diabetic patients.

SUMO4 Met55Val polymorphism is associated with coronary heart disease in Japanese type 2 diabetes individuals.

The Met55Val polymorphism in the small ubiquitin-like modifier 4 (SUMO4) gene has been associated with susceptibility not only to type 1 diabetes, but also to type 2 diabetes and diabetic nephropathy. We tried to confirm the association with susceptibility to type 2 diabetes and to investigate its role in diabetic vascular complications. The polymorphism was genotyped in two independent Japanese samples (Wakayama and Tokyo) by the TaqMan method.

Functional defect of truncated hepatocyte nuclear factor-1alpha (G554fsX556) associated with maturity-onset diabetes of the young.

A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1alpha (HNF-1alpha) encoding a truncated HNF-1alpha (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1alpha proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1alpha could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA).

Construction of a prediction model for type 2 diabetes mellitus in the Japanese population based on 11 genes with strong evidence of the association.

Prediction of the disease status is one of the most important objectives of genetic studies. To select the genes with strong evidence of the association with type 2 diabetes mellitus, we validated the associations of the seven candidate loci extracted in our earlier study by genotyping the samples in two independent sample panels. However, except for KCNQ1, the association of none of the remaining seven loci was replicated.