Type 1 diabetes mellitus is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to the vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. We, therefore, investigated a VDR gene polymorphism in type 1 diabetes. We examined the VDR gene Bsm I polymorphism in 203 type 1 diabetic patients and 222 controls, and the association between the VDR gene polymorphism and type 1 diabetes and their onset pattern. We found a significantly higher frequency of B allele in type 1 diabetics overall, compared with controls (P = 0.0010). Moreover, there was a significant difference in B-allele frequency between acute-onset type 1 diabetics and controls (P = 0.0002), whereas this difference was not observed between slow-onset type 1 diabetics and controls. Regardless of the existence of islet-associated autoantibody, we found a significant difference in B-allele frequency between acute-onset type 1 diabetics and controls. In conclusion, we found an association between a VDR gene polymorphism and acute-onset type 1 diabetes. Assessment of this VDR gene polymorphism may contribute to prediction of the onset pattern in individuals with a high risk of type 1 diabetes.

OBJECTIVE -The development of diabetic nephropathy is considered to be associated with oxidative stress. NADPH oxidase and the receptor for advanced glycation end products (RAGE) have attracted attention as mechanisms of generating oxidative stress. We studied the relation between the genotypes of the NADPH p22phox C242T and RAGE G1704T polymorphisms and the development of diabetic nephropathy in type 2 diabetic patients.RESEARCH DESIGN AND METHODS -Using a retrospective review of clinical data, we allocated 181 Japanese type 2 diabetic patients to one of two groups: patients without diabetic nephropathy (group N; n ϭ 108) and patients developing diabetic nephropathy (group D; n ϭ 73) for 10 years or more. The p22phox C242T and RAGE G1704T polymorphisms were examined by Taqman PCR methods.RESULTS -The frequency of the p22phox CC genotype was significantly higher in group D than in group N (90 vs. 79%; P ϭ 0.0427). The frequency of the RAGE GT ϩ TT genotype was significantly higher in group D than in group N (26 vs. 13%; P ϭ 0.0313). The frequency of the combination of p22phox CC and RAGE GT ϩ TT genotypes was significantly higher in group D than in group N (22 vs. 8%; P ϭ 0.0057). In multiple logistic regression analysis, systolic blood pressure, HbA 1c , triglycerides, and the combination of polymorphisms were shown to be independent variables.CONCLUSIONS -These results suggest that assessment of the combination of NADPH p22phox C242T and RAGE G1704T polymorphisms may be useful in identifying the risk for developing diabetic nephropathy in type 2 diabetic patients. Diabetes Care 27:303-307, 2004D iabetic nephropathy is the main cause of end-stage renal disease. Although poor glycemic control for a long period of time is a major factor in the development of diabetic nephropathy, hypertension, hyperlipidemia, and genetic factors are also associated with its development. The molecular mechanisms that underlie the pathogenesis of diabetic nephropathy remain unclear. Recent studies have highlighted the hyperglycemia-induced production of reactive oxygen species (ROS) as one of the mechanisms involved in the development of diabetic microangiopathy, via the following pathological pathways: activation of protein kinase C (PKC), formation of advanced glycation end products (AGEs), and activation of transcription factors such as nuclear factor-B (NF-B) (1). It has been proposed that genes associated with oxidative stress contribute to the risk of diabetic nephropathy (2-4). Recently, NADPH oxidase and the receptor for AGEs (RAGE) have received attention as mechanisms of generating oxidative stress. NADPH oxidase is a membraneassociated enzyme for superoxide production in vascular smooth muscle cells and endothelial cells (5). It has been reported that the NADPH oxidase p22phox C242T polymorphism is associated with vascular superoxide production in human blood vessels from coronary artery disease (CAD) patients (6). In addition, it has been suggested that AGEs might play a role in the pathogenesis of diabetic nephropathy ...

OBJECTIVE -Natural killer T-cells (NKT cells) are believed to play an important role in the regulation of immune response, and a numerical and functional deficit of NKT cells has been reported to be associated with the pathogenesis of autoimmune diseases. Thus far, it has been shown that subjects with type 1 diabetes have a lower frequency of NKT cells than nondiabetic subjects. In this study, we measured the frequency of peripheral V␣24 ϩ V␤11 ϩ T-cells, which include human NKT cells, in Japanese diabetic patients.RESEARCH DESIGN AND METHODS -Peripheral blood samples were obtained from 164 Japanese diabetic patients and 67 healthy subjects. The diabetic patients were classified into four categories as follows: islet-associated autoantibody-positive (Ab ϩ ) and -negative (Ab -) classic type 1 diabetes, latent autoimmune diabetes in adults (LADA), and type 2 diabetes. We measured the frequency of peripheral V␣24 ϩ V␤11 ϩ CD3 ϩ triple-positive cells.RESULTS -Unexpectedly, a higher frequency of V␣24 ϩ V␤11 ϩ T-cells was observed in Ab ϩ and Ab -patients compared with LADA patients (P ϭ 0.0294 and P ϭ 0.0021), type 2 diabetic patients (P Ͻ 0.0001 and P Ͻ 0.0001), and healthy subjects (P ϭ 0.0046 and P ϭ 0.0001). Moreover, an inverse correlation between V␣24 ϩ V␤11 ϩ T-cell frequency and disease duration was observed in Ab ϩ ( ϭ Ϫ0.455; P ϭ 0.0023) and Ab -( ϭ Ϫ0.432; P ϭ 0.0162) patients.CONCLUSIONS -Our findings indicate that a high frequency of V␣24 ϩ V␤11 ϩ T-cells is a unique finding in recent-onset classic type 1 diabetes, and measurement of V␣24 ϩ V␤11 ϩ T-cell frequency may be useful to assess the disease activity of classic type 1 diabetes.

Aim To examine the association between a decrease in the frequency of going out and oral function in independent older adults living in the urban area of Tokyo. Methods The participants analyzed were 785 older adults from the “Takashimadaira Study” (344 men and 441 women, age 77.0 ± 4.6 years). This study investigated the following items: decrease in frequency of going out; basic characteristics (sex, age); physical factors, such as oral function (difficulty chewing, difficulty swallowing, dry mouth); body pain; the Japan Science and Technology Agency Index of Competence; physical activities; psychological factors, such as the Geriatric Depression Scale‐15 score; and social and environmental factors, such as the presence or absence of participation in organization activities. Results To investigate the factors associated with a decrease in frequency of going out, logistic regression analysis showed an association with age (OR 1.08, 95% CI 1.03–1.13), difficulty chewing (OR 2.41, 95% CI 1.52–3.83), dry mouth (OR 1.68, 95% CI 1.07–2.64), body pain (OR 1.78, 95% CI 1.14–2.78), Japan Science and Technology Agency Index of Competence scores (OR 0.91, 95% CI 0.84–0.99), physical activities (OR 0.99, 95% CI 0.98–1.00), Geriatric Depression Scale‐15 scores (OR 1.13, 95% CI 1.05–1.21) and organization activities (OR 1.94, 95% CI 1.22–3.07). Covariance structural analyses showed that both “difficulty chewing” and “dry mouth” significantly affected “decrease in frequency of going out.” In addition, decrease in frequency of going out was significantly affected by “ Geriatric Depression Scale‐15 scores” through oral function. Conclusions The relationship between oral function and decrease in frequency of going out was clarified, after the multifaceted factors were adjusted. Geriatr Gerontol Int 2019; 19: 792–797.

Human serum paraoxonase (PON1) exists in 2 major polymorphic forms: Q (glutamine) or R (arginine) at codon 192. The PON1192 activity polymorphism is substrate dependent. The PON1Q192 isoform has a higher rate of in vitro hydrolysis of diazoxon, sarin, and soman, whereas the PON1R192 isoform has higher activity for the hydrolysis of paraoxon and chlorpyrifos oxon. Both isoforms hydrolyze phenyl acetate at approximately the same rate. The present study described and evaluated a kinetic method of arylesterase activity determination with a modified fixed incubation method that used the oxidative coupling of phenol with 4-aminoantipyrine of phenyl acetate as the substrate. Our improved method shows that arylesterase activity is lower with the PON1R192 isoform than with the PON1Q192 isoform. The average activities of serum of individuals of a specific PON1Q192 genotype showed higher arylesterase and lower paraoxonase activity than the PON1R192 genotype. The ratio of paraoxonase/arylesterase activity showed a clear separation of all three PON1192 genotypes with no overlap between the groups (QQ: < 5.0, QR: 5.0-11.0, RR: > 11.0). PCR has suggested that the PON1192 phenotypes correspond to the PON1192 genotypes. Therefore, when conducting epidemiological or mechanistic studies that examine the role of PON1 in organophosphorus or lipid metabolism, this ratio is more useful and informative than a PCR-based genotype alone. J Atheroscler Thromb, 2003; 10: 337-342.