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Objective·To screen the mutations of NEUROD1 gene in families of maturity-onset diabetes of the young (MODY), and investigate the correlation between the mutation and MODY6 and its potential pathogenesis in Chinese.Methods·PCR-direct sequencing was used for screening NEUROD1 mutations from 96 MODY probands who were negative for mutations in the GCK/MODY2, HNF1A/MODY3 and HNF1B/MODY5 genes, and the genotypic frequency of NEUROD1 variations were compared between the 96 MODY probands and 100 non-diabetic control subjects. A de novo modeling method was used to predict the three-dimensional (3D) structures of wild type (WT) and mutated NEUROD1 proteins. Transcriptional activities of both WT and mutant of NEUROD1 on insulin gene were detected by using dual luciferase reporter gene system.Results·Glu59Gln (NM_002500.5, c.175G>C), a heterozygous missense mutation in the NEUROD1 gene, was identified in a MODY pedigree. 3D structural analysis showed that the mutation transformed the negatively charged Glu59 of WT into uncharged mutation Gln59, leading to the loss of Glu59-Arg54 and Glu59-Lys88, two salt bridge bonds, and the formation of Gln59-Arg54, one new hydrogen bond. Transcriptional activity of Glu59Gln mutant for insulin gene was reduced by 36.3% when compared with that of WT (P

Objective: We aimed to examine the relationship between osteocalcin (OC) and the risk of incident diabetes and the risk of incident diabetic kidney disease (DKD).Research Design and Methods: We followed 5,396 participants without diabetes (nondiabetes subcohort) and 1,174 participants with diabetes and normal kidney function (diabetes subcohort) at baseline. Logistic regression and modified Poisson regression models were used to estimate the relative risk (RR) of baseline OC levels with incident diabetes and DKD.Results: During a mean 4.6-year follow-up period, 296 cases of incident diabetes and 184 cases of incident DKD were identified. In the nondiabetes subcohort, higher OC levels were linearly associated with a decreased risk of diabetes (RR for 1-unit increase of loge-transformed OC 0.51 [95% CI 0.35-0.76]; RR for highest vs. lowest quartile 0.65 [95% CI 0.44-0.95]; P for trend < 0.05). In the diabetes subcohort, OC levels were linearly inversely associated with incident DKD (RR for 1-unit increase of loge-transformed OC 0.49 [95% CI 0.33-0.74]; RR for highest vs. lowest quartile 0.56 [95% CI 0.38-0.83]; P for trend < 0.05), even independent of baseline estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. No significant interactions between OC and various subgroups on incident diabetes or DKD were observed.Conclusions: Lower OC levels were associated with an increased risk of incident diabetes and DKD. [ABSTRACT FROM AUTHOR]

Background: This study investigated the performance of the A1CNow+® test (Bayer Diabetes Care, Sunnyvale, CA) in a large population of Chinese patients with diabetes. Subjects and Methods: Hemoglobin A1c (HbA1c) levels in 1,618 Chinese patients with diabetes 10-94 years of age were measured with both the A1CNow+ test, from a fingerstick blood sample, and the high-performance liquid chromatography (HPLC) test, using a venous blood sample, within 24 h. The reportable ranges of the HbA1c values were 4.0-13.0% (A1CNow+) and 4.1-16.8% (HPLC). An error grid analysis (EGA) method was developed to quantify the accuracy of the A1CNow+ results against the HPLC reference results. Results: The A1CNow+ results were highly correlated with the HPLC reference results ( r=0.945, P<0.01). Passing-Bablok regression analysis showed a good linear agreement between the two variables, and the linear regression equation fitted as y=−0.10+1.00 x ( P=0.21). The Bland-Altman difference plot presented that the mean bias of the A1CNow+ results minus the HPLC reference results was −0.09% ( P<0.001); the 95% confidence intervals for the limits of agreement were −1.28% to 1.09%, with 96.5% of the data points lying within this zone. The results of the EGA showed that 80.2% of the A1CNow+ results were accurate, 17.7% were acceptable, 1.9% may lead to inappropriate treatment, and 0.3% may lead to severe clinical consequence. Conclusions: The A1CNow+ test values demonstrated a slight negative bias from the HPLC values. The majority of A1CNow+ test values were accurate when compared with results from the reference method. [ABSTRACT FROM AUTHOR]