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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]

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., (© 2022 by the American Diabetes Association.)

Diabetes mellitus is a prevalent disease result in several complications, including bone problems. Previous studies have shown that microRNA (miR)-26a regulates glucose metabolism and plays a protective role in diabetes. However, whether miR-26a also affects bone quality in diabetes remains unknown. In the present study, we evaluated the potential effects of miR-26a on bone in diabetic mice. We administrated miR-26a in streptozotocin-induced diabetic mice. The metabolic parameters, bone quality, osteoblast and osteoclast markers, and insulin signaling activation were measured. miR-26a ameliorated insulin resistance and glucose tolerance, improved bone microarchitecture and quality, increased osteoblasts and bone formation, decreased osteoclasts, and promoted the insulin signaling pathway in diabetic mice. These effects were abolished in insulin receptor-compromised Col1a1-Insr +/- mice. In conclusion, miR-26a could ameliorate bone-specific insulin resistance and bone quality in diabetic mice, which depended on the insulin receptors on osteoblasts. Our findings highlight the potential of miR-26a as a therapeutic target for diabetes mellitus-related bone metabolism and diseases., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)