Clinical studies in type 2 diabetes (T2D) primarily focused on the single nucleotide polymorphisms (SNPs) located in protein-coding regions. Recently, the SNPs located in noncoding regions have also been recognized to play an important role in disease susceptibility. The super enhancer is a cluster of transcriptional enhancers located in noncoding regions. It plays a critical role in cell-type specific gene expression. However, the exact mechanism of the super enhancer SNPs for T2D remains unclear. In this study, we integrated genome-wide association studies (GWASs) and T2D cell/tissue-specific histone modification ChIP-seq data to identify T2D-associated SNPs in super enhancer, followed by comprehensive bioinformatics analyses to further explore the functional importance of these SNPs. We identified several interesting T2D super enhancer SNPs. Interesting, most of them were clustered within the same or neighboring super enhancers. A number of SNPs are involved in chromatin interactive regulation and/or potentially influence the binding affinity of transcription factors. Gene Ontology (GO) analysis showed a significant enrichment in several well-known signaling pathways and regulatory process, e.g. WNT signaling pathway, which plays a key role in T2D metabolism. Our results highlighted the potential functional importance of T2D super enhancer SNPs, which may yield novel insights into the pathogenesis of T2D.

Objective. To investigate the effect of dapagliflozin (DAPA) on cardiac hypertrophy induced by type 2 diabetes mellitus (T2DM) and its mechanism. Methods. SD rats with T2DM were divided into a T2DM group ( n = 6 ) and DAPA group ( n = 6 ). They were, respectively, fed with the same amount of normal saline and 1 mg/kg DAPA. The control group ( n = 6 ) was also fed with normal saline. The hearts were tested by the application of echocardiography and hemodynamics. Subsequently, fasting blood glucose (FBG), serum total cholesterol (TC), and triglyceride (TG) as well as interleukin- (IL-) 10, IL-6, and tumor necrosis factor (TNF)-α in serum were tested. H&E and Masson staining was performed to observe the degree of cardiac tissue lesions, and expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), calpain-1, p-IκBα, and p65 in myocardial tissue was tested by qRT-PCR and Western blot. Results. Compared with the control group, rats in the T2DM group exhibited significant diabetic symptoms: FBG was significantly elevated, and the levels of TC, TG, IL-6, and TNF-α were significantly increased, while the levels of IL-10 and the calpain activity were evidently decreased. However, DAPA treatment could improve the above changes. At the same time, the damage and fibrosis of the heart tissue in the DAPA group were markedly improved. Additionally, the mRNA expression of ANP and BNP in myocardial tissue of the DAPA group was markedly increased. And DAPA could inhibit the expression of p-IκBα/IκBα in the cytoplasm and p65 in the nucleus as well as the expression of calpain-1 in myocardial tissue. Conclusion. DAPA treatment ameliorates the cardiac hypertrophy caused by T2DM by decreasing body blood glucose, while reducing the expression of calpain-1 in cardiomyocytes and inhibiting the nuclear translocation of NF-κB.

Objective: To evaluate two osteoporosis screening tools, the osteoporosis self-assessment tool for Asians (OSTA) and the osteoporosis screening tool for Chinese (OSTC), in postmenopausal Chinese women with type 2 diabetes mellitus (T2DM). Methods: This retrospective study enrolled postmenopausal female patients with T2DM. Bone mineral density at the lumbar spine (L1-4) and left femoral neck was measured using dual-energy X-ray absorptiometry (DXA). The OSTA and OSTC scores were calculated and compared with bone mineral density at the two anatomical sites. Results: A total of 404 patients with T2DM were enrolled in this study. The detection rates for osteoporosis in the lumbar spine (L1-L4) and left femoral neck by DXA were 22.5% (91 of 404 patients) and 21.8% (88 of 404 patients), respectively; 14.4% (58 of 404 patients) and 18.1% (73 of 404 patients) by OSTA, respectively; and 21.5% (87 of 404 patients) at both sites by OSTC. At the femoral neck, the areas under the curve (AUC) of OSTA and OSTC for predicting osteoporosis were 0.73 and 0.78, respectively. The sensitivity and specificity for OSTA were 64.9% and 72.7%, respectively; and for OSTC, they were 64.2% and 79.5%, respectively.

The roles of gene polymorphisms in diabetes mellitus (DM) have been intensively analyzed earlier, but the results of these studies were conflicting. Hence, we performed this study to better assess the relationship between genetic variations and DM. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess correlations between polymorphisms and DM. A total of 32 studies were finally included in our analyses. Significant associations with the risk of DM were detected for the rs1800871, rs1800872, and rs1800896 polymorphisms. As for complications in DM, significant association with the risk of diabetic nephropathy (DN) was detected for the rs1800871 polymorphism. In addition, we also found that the rs1800896 polymorphism was significantly associated with the risk of diabetic retinopathy (DR). Further stratified analyses on the basis of type of disease demonstrated that the positive results were predominantly driven by the T2DM subgroup. When we stratified data based on ethnicity of participants, we found that the rs1800871 polymorphism was significantly correlated with DM in Caucasians, the rs1800872 polymorphism was significantly correlated with DM in Asians, and the rs1800896 polymorphism was significantly correlated with DM in both Caucasians and Asians. Our findings indicate that rs1800871, rs1800872, and rs1800896 polymorphisms may serve as genetic biomarkers of DM. Moreover, the rs1800871 and rs1800896 polymorphisms may also contribute to the development of complications in DM.

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