Retrospective database analysis of cancer risk in patients with type 2 diabetes mellitus in China

<p><b>Objective:</b> To investigate the association between type 2 diabetes (T2D) and the risk of overall cancer and site-specific cancers in a Chinese population.</p> <p><b>Research design and methods:</b> Tianjin Urban Employee Basic Medical Insurance database (2003–2014) was used to identify patients with newly onset T2D in 2009, patients with prevalent T2D prior to 2009, and general individuals without T2D. Overall and site-specific cancer incidence rates and incidence rate ratios relative to general population were calculated for both incident and prevalent T2D cohorts. Multivariate Cox proportional hazards models adjusting for baseline characteristics and potential bias were conducted. Subgroup analyses based on gender and age were further conducted.</p> <p><b>Results:</b> For the year 2009, 21,208 patients with onset T2D (mean age 58.8 years; 48.1% female), 28,248 patients with prevalent T2D (mean age 63.7 years; 50.2% female) and 744,339 general individuals (mean age 43.2 years; 47.7% female) were identified. Controlling for confounders, diabetic patients had an overall 56%–59% higher risk of developing cancer, among which the highest risks by site were liver (adjusted hazard ratio [aHR] = 1.80–2.48), colorectal (aHR = 2.41–2.69) and stomach (aHR = 2.02–2.51) cancers (all <i>p</i> < .05). Patients with prevalent T2D had increased cancer risk in the pancreas (aHR = 4.52, <i>p</i> < .001). Female diabetic patients had increased risk in the kidneys (aHR = 3.22–3.31, <i>p</i> < .01). Patients aged between 50 and 59 years had the highest relative risk (90% higher), while the relative risk was the lowest among patients ≥70 (45% higher).</p> <p><b>Conclusion:</b> Type 2 diabetes was associated with increased overall cancer risk led by liver, colorectal and stomach cancers. Patients with longer diabetes duration were associated with higher pancreatic cancer risk and female diabetic patients had a higher risk of kidney cancer.</p

Primer sequences of osteogenic markers.

<p>Primer sequences of osteogenic markers.</p

Physicochemical properties of CAH/B2 scaffolds.

<p><b>A.</b> SEM view of CAH/B2 scaffold at a magnification of 100×, <b>B.</b> SEM view of CAH/B2 scaffold at a magnification of 200×. SEM analysis showed that micro-pores were generated in the CAH scaffold, the average pore diameter in the scaffold being 100–110 µm. <b>C.</b> In vitro release behavior of BMP-2 from the CAH scaffold. Col/B2 served as a control. The release velocity of BMP-2 was delayed in the CAH/B2 group compared with release from Col/B2. The cumulative BMP-2 released from the CAH/B2 and the Col/B2 groups almost reached a plateau at 21 and 14 days, respectively. <b>D.</b> SEM view of MSCs cultured on a CAH/B2 scaffold at a magnification of 100×.</p

Characterization of CAH/B2 scaffolds.

<p><b>A.</b> EDX analysis of CAH specimen. B. XRD pattern of CAH specimen.</p

Histology analysis.

<p>Coronal sections through the midlines of defects are shown. (A–E): lower magnification, Bar = 1 mm, yellow arrow: new bone formed; (A′–E′): higher magnification, Bar = 0.25 mm. (A, A′): Blank; (B, B′): CAH; (C, C′): CAH+M; (D, D′): CAH/B2+M. (E, E′)Col/B2+M. Blue arrow: new bone, Yellow arrow: host bone, *:interface between new bone and host bone.</p

Biocompatibility and effects of the CAH/B2 scaffold on osteoblastic differentiation.

<p><b>A.</b> MTS assay of MSCs cultured with CAH and CAH/B2 scaffolds. The cells were also cultured in plates as a control. Data represent the mean+SD of n = 5 samples. No statistically significant differences were seen between groups. <b>B.</b> Effects of CAH/B2 on in vitro ALP activity. ALP activity in the CAH/B2 group was higher than in the CAH group. One-way analyses of variance suggest that there are significant differences among three groups. The significant post hoc test results are identified by symbol *. N = 5. P<0.001: CAH vs. CAH/B2. <b>C.</b> The level of calcium deposition in 3-week cultures was evaluated by AR-S. The values indicated are means ± SD, (n = 5) p<0.005 as compared with that deposition in the CAH group. <b>D.</b> qRT-PCR analysis of osteoblast marker genes, showing that MSCs cultured on a CAH/B2 scaffold exhibited increased Col I, OCN and OPN gene expression. Data represent the mean + SD of n = 5 samples. P<0.05.</p

Summary of changed miRNAs during bone aging.

<p>Summary of changed miRNAs during bone aging.</p

miRNA expression validated by qRT-PCR in MSCs and bone.

<p>qPCR results were normalized to U6 snRNA expression levels. Values showed that these miRNAs were significantly different between 2m and 25m samples.</p

Biological functions of corresponding miRNAs are involved in aging and osteoblastic differentiation.

<p>Biological functions of corresponding miRNAs are involved in aging and osteoblastic differentiation.</p

Identification and Characterization of MicroRNAs by High Through-Put Sequencing in Mesenchymal Stem Cells and Bone Tissue from Mice of Age-Related Osteoporosis

<div><p>The functional deficiencies of bone marrow-derived mesenchymal stem cells (MSCs) may contribute to the aging process and age-related diseases, such as osteoporosis. Although it has been reported that microRNAs (miRNAs) played an important role in mechanisms of gene regulation of aging, and their expression profiles in MSCs osteogenic differentiation were established in recent years, but it is still elusive for the dynamic patterns of miRNAs in aging process. Importantly, the miRNAs in aged bone tissue had not been yet reported so far. Here, we combined high through-put sequencing with computational techniques to detect miRNAs dynamics in MSCs and bone tissue of age-related osteoporosis. Among the detected miRNAs, 59 identified miRNAs in MSCs and 159 in bone showed significantly differential expressions. And more importantly, there existed 8 up-regulated and 30 down-regulated miRNAs in both MSCs and bone during the aging process, with the majority having a trend of down-regulation. Furthermore, after target prediction and KEGG pathway analysis, we found that their targeted genes were significantly enriched in pathways in cancer, which are complex genetic networks, comprise of a number of age-related pathways. These results strongly suggest that these analyzed miRNAs may be negatively involved in age-related osteoporosis, given that most of them showed a decreased expression, which could lay a good foundation for further functional analysis of these miRNAs in age-related osteoporosis.</p></div