Background: Osteoporosis and cardiovascular diseases (CVDs) are 2 major public health problems. Osteoporosis and CVDs may be linked but the association between lipid profile and osteoporosis is still controversial. The purpose of this study was to examine the associations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) with osteoporosis. Methods: Using inpatients’ and outpatients’ electronic medical records (EMR) and dual X-ray absorptiometry (DXA) database stored at The Second Hospital of Jilin University, we included 481 individuals with complete and valid lipid and bone mineral density (BMD) data in 2017. Serum samples were used to measure TC, LDL-C, HDL-C and TG. Femoral neck and total hip BMD were measured by DXA; osteoporosis was defined as femoral neck or total hip T-score ≤ -2.5. Multivariable logistic regression models were used to test the associations of TC, LDL-C, HDL-C and TG with osteoporosis. Results: The mean age for included individuals was 62.7 years (SD = 8.6 years); 60.1 % of them were female. Each standard deviation (SD) increase in TC (Odds Ratio [OR]: 1.48; 95 % Confidence Interval [CI]: 1.06–2.07) and TG (OR: 1.67; 95 % CI: 1.16–2.39) were associated with increased risk of osteoporosis; LDL-C and HDL-C levels were not associated with osteoporosis. Age, sex and body mass index (BMI) did not interact with the relationships of TC and TG with osteoporosis (all P > 0.10). Conclusions: Higher TC and TG levels were associated with greater risk of osteoporosis in this cross-sectional study.

Introduction: With the shortage of donor organs for islet transplantation, insulin-producing cells have been generated from different types of stem cell. Human fetal pancreatic stem cells have a better self-renewal capacity than adult stem cells and can readily differentiate into pancreatic endocrine cells, making them a potential source for islets in diabetes treatment. In the present study, the functions of pancreatic islets derived from human fetal pancreatic progenitor cells were evaluated in vitro and in vivo. Methods: Human pancreatic progenitor cells isolated from the fetal pancreas were expanded and differentiated into islet endocrine cells in culture. Markers for endocrine and exocrine functions as well as those for alpha and beta cells were analyzed by immunofluorescent staining and enzyme-linked immunosorbent assay (ELISA). To evaluate the functions of these islets in vivo, the islet-like structures were transplanted into renal capsules of diabetic nude mice. Immunohistochemical staining for human C-peptide and human mitochondrion antigen was applied to confirm the human origin and the survival of grafted islets. Results: Human fetal pancreatic progenitor cells were able to expand in medium containing basic fibroblast growth factor (bFGF) and leukemia inhibitor factor (LIF), and to differentiate into pancreatic endocrine cells with high efficiency upon the actions of glucagon-like peptide-1 and activin-A. The differentiated cells expressed insulin, glucagon, glucose transporter-1 (GLUT1), GLUT2 and voltage-dependent calcium channel (VDCC), and were able to aggregate into islet-like structures containing alpha and beta cells upon suspension. These structures expressed and released a higher level of insulin than adhesion cultured cells, and helped to maintain normoglycemia in diabetic nude mice after transplantation. Conclusions: Human fetal pancreatic progenitor cells have good capacity for generating insulin producing cells and provide a promising potential source for diabetes treatment.

Background. Long noncoding RNAs (lncRNAs) were previously found to be closely related to the pathogenesis of diabetes. Objectives. To reveal the differentially expressed lncRNAs and messenger RNAs (mRNAs) involved in type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) and predict the lncRNA target genes to derive their expression profiles for the diagnosis of T2DM and LADA and their differential diagnosis. Methods. Twelve venous blood samples were collected from T2DM patients, LADA patients, and nondiseased subjects to obtain total RNAs. After removing rRNA from total RNAs to establish the desired library for sequencing, quality control and quantification analyses were carried out. The fragments per kilobase of exon model per million reads mapped (FPKM) of lncRNAs were calculated to construct the gene expression profiles of lncRNAs and mRNAs. Fold changes (fold change: 2.0) and p values (p value: 0.05, FPKM ≥ 0.1) were calculated, and then differentially expressed lncRNAs and mRNAs were screened. To obtain the significantly coexpressed lncRNA-mRNA pairs, the lncRNA target genes were deduced according to the association between adjacent sites. Results. Compared to nondiseased controls, 68,763 versus 28,523 lncRNAs and 133 versus 1035 mRNAs were significantly upregulated and significantly downregulated, respectively, in T2DM patients. For LADA patients, 68,748 versus 28,538 lncRNAs and 219 versus 805 mRNAs were significantly upregulated and significantly downregulated, respectively, relative to nondiseased controls. Compared to T2DM patients, 74,207 versus 23,079 lncRNAs and 349 versus 137 mRNAs were significantly upregulated and significantly downregulated, respectively, in LADA patients. Based on the correlation analysis, seven lncRNA-mRNA pairs (BTG2, A2M, HECTD4, MBTPS1, DBH, FLVCR1, and NCBP2) were significantly coexpressed, and two lncRNAs (ENST00000608916 and ENST00000436373) were newly discovered. Conclusion. Significant differences in lncRNA expression were discovered among the three groups. Furthermore, after predicting lncRNA expression profiles, GO/KEGG pathway analysis could deduce the target gene function.

This randomised controlled trial assessed the effectiveness and safety of weekly 56.5 μg teriparatide (SAL056) compared to alendronate in postmenopausal women in China with osteoporosis at high risk of fractures over 48 weeks. This phase 3, multicentre, randomised, open-label, active-controlled, parallel-group, non-inferiority trial enrolled postmenopausal women aged 45–80 years with osteoporosis at 37 centres in China. Participants were randomised (1:1) to receive either subcutaneous teriparatide 56.5 μg weekly or 70 mg oral alendronate weekly for 48 weeks, with the primary efficacy assessment at Week 48. Between November 2021 and September 2023, 493 patients were enrolled (243 in the teriparatide group and 250 in the alendronate group). The primary endpoint, lumbar spine bone mineral density (BMD) at L1–L4, showed a significantly greater increase in the teriparatide group compared to the alendronate group at Week 48 (5.01% vs. 4.20%, mean difference 0.80%, P = 0.025). Sensitivity analysis confirmed these results. At Weeks 24 and 48, teriparatide also resulted in higher hip BMD than alendronate (1.50% vs. 1.46%, P > 0.05 and 3.27% vs. 1.67%, P < 0.001). Procollagen type 1 N-terminal propeptide (P1NP) levels in the teriparatide group increased transiently at Week 12, then declined toward baseline by Weeks 24 and 48, and a decrease in serum cross-linked c-terminal telopeptide of type I collagen (S-CTX) levels from baseline to the end of treatment. Meanwhile, in the alendronate (a typical bone resorption inhibitor) group, CTX level remained continuously suppressed from the baseline. Clinical fracture rates were lower in the teriparatide group than in the alendronate group at Weeks 24 (1.2% vs. 2.8%, P > 0.05) and 48 (1.7% vs. 4.0%, P > 0.05). Teriparatide was generally safe and well tolerated. Teriparatide (56.5 μg once weekly) was more effective than alendronate in treating postmenopausal osteoporosis with a high fracture risk, significantly increasing L1–L4 BMD over 48 weeks. It was safe, well tolerated, and had a safety profile similar to that of Teribone®. This study demonstrates that once-weekly teriparatide significantly improves bone mineral density and reduces fracture risk in postmenopausal osteoporosis patients. As a patient-friendly alternative to daily injections, it may enhance adherence and inform clinical guidelines, representing a promising strategy for patients and healthcare systems.

Background: Previous research has demonstrated that fasting C-peptide (FCP) serves as a protective element against diabetic retinopathy. But the protective effect of elevated FCP levels against diabetic retinopathy (DR) remains uncertain when these levels exceed specific thresholds. This research aimed to investigate the intrinsic link between FCP concentration and DR in individuals with T2DM. Methods: A total of 1661 individuals diagnosed with type 2 diabetes participated in this observational analysis, where DR was assessed as the primary outcome and categorized according to FCP levels. Curve fitting analysis and two-part linear regression models were applied to assess the relationship between DR and FCP, and exploratory analysis was conducted to identify the threshold. Results: Our study found a non-linear relationship between the two, as well as a threshold effect at an FCP of 4.11 ng/mL. Below the critical value, each 1 ng/mL increase in FCP levels was associated with a 24% lower risk of DR (OR: 0.74, 95% CI: 0.64– 0.86). Above the cutoff, the relationship did not reach statistical significance (OR: 1.52, 95% CI: 0.87– 2.66). Conclusion: There was a nonlinear relationship between FCP level and DR risk, which was negatively correlated at first but stabilized at a lower level when FCP> 4.11 ng/mL.

Diabetic nephropathy (DN) is a common chronic complication of diabetes mellitus (DM), and dapagliflozin, a representative drug of sodium-glucose co-transport protein 2 inhibitors (SGLT2i), is a novel hypoglycemic agent for the treatment of type 2 diabetes mellitus (T2DM), which has been shown to reverse microalbuminuria in early type 2 diabetic nephropathy (T2DN), but the mechanism of action remains to be elucidated. In this study, five patients with early T2DN treated in our hospital from October 2020 to May 2021 were selected for the study and were treated with insulin combined with dapagliflozin to lower glucose, and the initial insulin treatment was named as DN group, and the addition of dapagliflozin was named as DN-DAPA group, and another five patients with a healthy physical examination at the same period were selected as the blank control group (NC group). Patients' morning urine samples were collected and processed using iTRAQ unlabeled quantitative proteomics technology. Bioinformatics analysis was performed to obtain 193 differentially expressed proteins. 91 expressions were up-regulated and 72 expressions were down-regulated in the DN group compared with the NC group, and 11 expressions were up-regulated and 26 expressions were down-regulated in the DN-DAPA group compared with the DN group. Five significantly co-expressed protein molecules were screened at P < 0.05 and [logFC] >1.5: SOD1, SLC25A6, S100A13, PPP2R2A, CXCL12. Therefore, these differential proteins are associated with early T2DN injury. Molecularly, dapagliflozin improves mitochondrial oxidative stress and reduces urinary microalbumin excretion in early T2DN patients by inhibiting PPP2R2A and CXCL12/ S100A13 pathways to reverse early T2DN.