Shohei Matsuno

Cardio-ankle vascular index measures arterial wall stiffness independent of blood pressure

Although brachial-ankle pulse wave velocity (baPWV) is a non-invasive method of detecting arteriosclerosis, it is affected by changes in blood pressure (BP). Cardio-ankle vascular index (CAVI) is a new method for estimating arteriosclerosis, and it has been reported to be less influenced by BP. We investigated the influence of BP changes on CAVI and the correlation of CAVI to clinical factors and carotid arteriosclerosis. CAVI and baPWV in 35 non-diabetic and 33 diabetic subjects were measured in increased BP (after stair climbing) and rested BP (after 10min of rest). Intima-media thickness (IMT) of carotid arteries was measured by ultrasoundsonography. We achieved the following results: CAVI did not show a significant change with a change in BP in both non-diabetic and diabetic subjects. On the contrary, baPWV was significantly influenced by BP changes. Carotid artery IMT had a significant positive correlation with CAVI and baPWV. Multiple regression analysis revealed that significant risk factors of high baPWV were age and systolic BP. On the contrary, significant risk factors of high CAVI were age and hemoglobin A1c, while systolic BP was not relevant. Our findings suggest that CAVI is independent of BP and useful as an indicator of early arteriosclerosis in diabetic subjects.

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. Susceptibility to type 2 diabetes and prevalence of diabetic vascular complications (coronary heart disease, cerebral infarction, retinopathy, and nephropathy) were evaluated by case-control study and multivariate logistic regression analysis, respectively. There were no significant differences in the frequency of alleles or genotypes between patients and controls. The Val allele, however, was associated with higher prevalence of coronary heart disease in patients in both groups (Wakayama, n=423, odds ratio, 1.64; 95% confidence interval, 1.02-2.64; P=0.041; Tokyo, n=451, odds ratio, 1.58; 95% CI, 1.07-2.34; P=0.021, in an additive model, respectively). No significant associations were observed with other diabetic vascular complications. Although association of the polymorphism with susceptibility to type 2 diabetes or nephropathy was not replicated, an association of the polymorphism with risk of coronary heart disease in type 2 diabetes is suggested.

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

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.

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

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).

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

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.

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™)

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).

Fulminant Type 1 Diabetes Mellitus Accompanied by Positive Conversion of Anti-insulin Antibody after the Administration of Anti-CTLA-4 Antibody Following the Discontinuation of Anti-PD-1 Antibody

An 80-year-old woman with malignant melanoma received 20 cycles of anti-programmed death 1 (PD-1) antibody (nivolumab) treatment and showed normal glucose tolerance. Three weeks after switching to anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibody (ipilimumab), her plasma glucose level was elevated to 639 mg/dL, her HbA1c was 7.7%, and her fastening serum C-peptide immunoreactivity was undetectable. Anti-glutamic acid decarboxylase and insulinoma-associated protein-2 antibodies were negative. She was diagnosed with fulminant type 1 diabetes mellitus (F1DM). Remarkably, her anti-insulin antibody was positively converted, and her Sialylated Carbohydrate Antigen, Krebs von den Lungen-6 levels increased after ipilimumab therapy. She possessed F1DM-susceptible Human Leukocyte Antigen-DR4. A fluorescence activated cell sorting analysis showed an altered T-cell population. This case of F1DM highlights specific mechanisms underlying pancreatic beta cell immunity.