To estimate the remaining life of existing RC bridge decks damaged by alkali silica reaction (ASR), multi-scale numeri-cal analysis with chemo-hygral model is integrated with visual inspection data ...at site. First, the applicability of the poro-mechanical models for ASR expansion in the multi-scale frame are examined with the experiments of the real scale RC slabs and the model is validated to bring about fair prediction of the 3D anisotropic expansion and the fatigue life of the slabs. Second, visually inspected cracks on bottom surfaces of RC decks are converted to space-averaged strains, and the magnitude of ASR is estimated from the vertical deformation, based on which the internal pre-stress and the damage fields are re-produced by numerical predictor-corrector cycles, and the remaining life of ASR damaged RC bridge decks is fairly estimated. By conducting sensitivity analyses in terms of ASR-gel volumes and cracks, allowable error range of site inspection data is clarified to meet the requirement of asset management.
Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide ...association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP rs791595; risk allele = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17, GPSM1 rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15 and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.
Background and Objectives: Few studies exist on resistant starch in rice grains. The Okinawa Institute of Science and Technology Graduate University (OIST) has developed a new rice (OIST rice, OR) ...rich in resistant starch. This study aimed to clarify the effect of OR on postprandial glucose concentrations. Methods and Study Design: This single-center, open, randomized, crossover comparative study included 17 patients with type 2 diabetes. All participants completed two meal tolerance tests using OR and white rice (WR). Results: The median age of the participants was 70.0 59.0-73.0 years, and the mean body mass index was 25.9+-3.1 kg/m2. The difference in total area under the curve (AUC) of plasma glucose was -8223 (95% confidence interval CI: -10100 to -6346, p<0.001) mg·min/dL. The postprandial plasma glucose was significantly lower with OR than with WR. The difference in the AUC of insulin was -1139 (95% CI: -1839 to -438, p=0.004) muU·min/mL. The difference in the AUC of total gastric inhibitory peptide (GIP) and total glucagon-like peptide-1 (GLP-1) was -4886 (95% CI: - 8456 to -1317, p=0.011) and -171 (95% CI: -1034 to 691, p=0.673) pmol·min/L, respectively. Conclusions: OR can be ingested as rice grains and significantly reduced postprandial plasma glucose compared to WR independent of insulin secretion in patients with type 2 diabetes. OR could have escaped absorption not only from the upper small intestine but also from the lower small intestine.
Edema occurs in various disorders. One of those is remitting seronegative symmetrical synovitis with pitting edema, a rare syndrome whose pathophysiology is not clearly understood. We report herein a ...case of refractory edema diagnosed as remitting seronegative symmetrical synovitis with pitting edema.
A 82-year-old Asian male was admitted to the Department of General Internal Medicine with a 2-month history of symmetrical swelling of both hands. Despite treatment with loop diuretic furosemide 40 mg daily, his condition did not respond to the medication and his quality of life deteriorated. An examination of the joints showed tenderness suggestive of synovitis with restricted movements in bilateral proximal interphalangeal joint. Laboratory findings revealed hyperglycemia, elevated erythrocyte sedimentation rate 118 mm/hour, and elevated C-reactive protein 6.58 mg/dL. Plain radiographs of both hands showed soft tissue swelling, changes consistent with osteoarthritis, and no erosions. The diagnosis of bilateral remitting seronegative symmetrical synovitis with pitting edema was made. Treatment with prednisolone 15 mg daily was instituted.
Although remitting seronegative symmetrical synovitis with pitting edema is rare, it should be remembered as a disease that causes edema in the elderly.
We studied the cross-sectional relationship between GA and HbA1c in 142 type 2 diabetic patients who had an HbA1c level <7.5% for at least one year without fluctuation by more than 0.5%. We also ...followed the changes of GA and HbA1c in 18 type 2 diabetic patients for 16 weeks as they progressed from untreated severe hyperglycemia (HbA1c≥9.0%) to good glycemic control (HbA1c≤6.5%) by intensive insulin treatment. The annual mean levels of GA and HbA1c in the stably controlled patients showed a weak, but significant, correlation (r = 0.23, p<0.001) in the 142 diabetic patients. However, the GA/HbA1c ratio ranged widely from 2.0 to 4.0 showing a normal distribution (2.9 ± 0.34, M ± SE), although patients with conditions affecting albumin turnover or RBC lifespan were excluded from the study. The GA/HbA1c ratio was significantly higher when patients were in hyperglycemic than when glycemic control was good (3.5 ± 0.15 vs. 2.9 ± 0.07, M ± SE, p<0.01). GA decreased more rapidly than HbA1c during intensive insulin therapy, but the percent reduction of HbA1c eventually corresponded with that of GA by 16 weeks after the start of treatment. These results demonstrate that, although unknown influences on GA or HbA1c may exist, GA may be a useful marker for monitoring short-term variations of glycemic control during treatment of diabetic patients.
OBJECTIVE: Urinary liver-type fatty acid-binding protein (L-FABP) is a promising indicator of tubular but not glomerular damage. The aim of this study was to evaluate the clinical usefulness of ...urinary L-FABP as a prognostic biomarker in impaired diabetic nephropathy in type 2 diabetes. RESEARCH DESIGN AND METHODS: This investigation involved a cross-sectional and longitudinal analysis of the relationship between urinary L-FABP levels and progressive nephropathy. Urinary L-FABP was measured with enzyme-linked immunosorbent assay. In the cross-sectional analysis, the association of urinary L-FABP, with the severity of diabetic nephropathy, was investigated in 140 patients with type 2 diabetes and in 412 healthy control subjects. Of the patients in the former study, 104 have been followed for 4 years. The progression of diabetic nephropathy was defined as progressive albuminuria, end-stage renal disease, or induction of hemodialysis. RESULTS: Urinary L-FABP levels were progressively increased in subjects with normo-, micro-, or macroalbuminuria and further increased in patients with end-stage renal disease. In the longitudinal analysis, high urinary L-FABP levels were associated with the increase in albuminuria, progression to end-stage renal disease, or induction of hemodialysis. This was particularly demonstrated in the subgroup of patients without renal dysfunction (n = 59), where high urinary L-FABP levels were associated with the progression of diabetic nephropathy. CONCLUSIONS: Urinary L-FABP accurately reflected the severity of diabetic nephropathy in type 2 diabetes, and its level was high in the patients with normoalbuminuria. Moreover, higher urinary L-FABP was a risk factor for progression of diabetic nephropathy.
Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX , SLC30A8, and KCNJ11 With Susceptibility to Type 2 Diabetes in a Japanese Population
Shintaro Omori 1 , 2 ,
Yasushi Tanaka 2 ,
Atsushi Takahashi 3 ,
...Hiroshi Hirose 4 ,
Atsunori Kashiwagi 5 ,
Kohei Kaku 6 ,
Ryuzo Kawamori 7 ,
Yusuke Nakamura 8 and
Shiro Maeda 1
1 Laboratory for Diabetic Nephropathy, SNP Research Center, RIKEN, Yokohama, Kanagawa, Japan
2 Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, Kawasaki,
Kanagawa, Japan
3 Laboratory for Statistical Analysis, SNP Research Center, RIKEN, Tokyo, Japan
4 Health Center, Keio University School of Medicine, Tokyo, Japan
5 Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
6 Division of Endocrinology and Metabolism, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan
7 Department of Medicine, Metabolism and Endocrinology, School of Medicine, Juntendo University, Tokyo, Japan
8 Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Address correspondence and reprint requests to Shiro Maeda, Laboratory for Diabetic Nephropathy, SNP Research Center, RIKEN,
1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. E-mail: smaeda{at}src.riken.jp
Abstract
OBJECTIVE —Recently, several genes have been shown to be associated with an increased risk of type 2 diabetes by genome-wide association
studies in white populations. To further investigate the involvement of these polymorphisms in conferring susceptibility to
type 2 diabetes, we examined the association of 14 single nucleotide polymorphisms (SNPs) within 11 candidate loci with type
2 diabetes in a Japanese population.
RESEARCH DESIGN AND METHODS —We analyzed 14 SNPs (rs4402960 in IGF2BP2 , rs10811661 in CDKN2A/B , rs1111875 and rs7923837 in HHEX , rs13266634 in SLC30A8 , rs1113132 and rs11037909 in EXT2 , rs9939609 and rs8050136 in FTO , rs7756992 in CDKAL1 , rs1801282 in PPARG Pro12Ara, rs5219 in KCNJ11 Glu23Lys, rs7480010 in LOC387761 , and rs9300039 in Ch11) in 1,630 Japanese subjects with type 2 diabetes and in 1,064 control subjects by using an invader
assay or a TaqMan assay.
RESULTS —Among the 11 loci examined, 6 were significantly associated with type 2 diabetes in our population by a logistic regression
analysis, similar to previously reported results (rs4402960, P = 0.00009; rs10811661, P = 0.0024; rs5219, P = 0.0034; rs1111875, P = 0.0064; rs13266634, P = 0.0073; rs7756992, P = 0.0363). In this population, the remaining five loci were not significantly associated with type 2 diabetes. In addition,
we identified significant association of the SNPs in FTO gene with BMI in the control subjects.
CONCLUSIONS —We have identified 6 of the 11 loci that were identified by genome-wide association studies in white populations, and these
loci are considered strong candidates for type 2 diabetes susceptibility across different ethnicities.
SNP, single nucleotide polymorphism
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 27 December 2007. DOI: 10.2337/db07-0979.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0979 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received July 14, 2007.
Accepted December 12, 2007.
DIABETES
Multiple factors, regarding mechanical properties, load levels, and environmental conditions, affect the fatigue lifetime of reinforced concrete (RC) bridge decks. For the mechanical behavior, ...previous research predicts the fatigue lifetime of RC decks as a function of their punching shear capacity, where they give less attention to other modes of failure due to experimental limitations of fatigue loading and the restriction of girders spacing in the past design practice. Nowadays, multi-scale simulation can deal with fatigue loading problems, which secures examining complex situations that cannot be easily reproduced in the laboratories of fatigue tests. In this study, various RC decks with wide range of dimensions, material properties, reinforcement ratio, and load levels are analyzed by the validated multi-scale simulation. Then, artificial neural network (ANN) based model is also proposed based on wide-range of studied cases, which estimates the fatigue life of newly constructed RC decks, where it can be the basis of performance-based design. After that, the impact of deck’s properties on fatigue life is evaluated based on the built ANN model, which matches the conceptual design of RC decks. Finally, coupling of an empirical equation and ANN model is proposed, which may support conceptual decision-making.
Abstract We evaluated the efficacy and safety of sitagliptin after 3 months’ treatment in Japanese type 2 diabetic patients and examined changes in clinical factors. Baseline HbA1c, PPG, BMI, and ...duration of diabetes may be predictors of HbA1c reduction when using sitagliptin in Japanese type 2 diabetic patients.
In order to evaluate the relationship between clinical markers of glycemia and glucose excursion, we performed 48-hour continuous glucose monitoring (CGM) in 43 diabetic patients. For the clinical ...markers, HbA1c, glycoalbumin (GA), and 1,5-anhydroglucitol (1,5-AG) were measured, and for the parameters of glucose excursion from CGM, average glucose (AG), standard deviation of glucose (SD), the area under the curve for glucose levels >180 mg/dL (AUC>180), and the difference between the maximum and minimum glucose levels during 48 hours (ΔG48hr) were analyzed. All patients were treated without any changes of the dosages of oral anti-diabetic agents or insulin for at least the previous 3 months with coefficient of variation (CV) of HbA1c less than 4 %. In results, while HbA1c did not show any single correlation with AG, SD, AUC>180, or ΔG48hr, both GA and 1,5-AG were significantly related to all these parameters. Furthermore, GA significantly correlated to all CGM parameters, and SD significantly correlated to GA in multiple regression analyses. These results suggest that GA may be a different marker from HbA1c for diabetic complications, because GA, but not HbA1c, may reflect not only short-term average glucose but also fluctuation of glucose.
PDF
