Objective
To investigate the relationship between dyslipidemia and diabetic retinopathy in non-insulin-dependent diabetes mellitus（NIDDM） patients．
Methods
In 55 health controls，60 NIDDM patients with DR and 75 NIDDM patients without DR，the plasma total cholesterol（TC），triglycerides（TG），high-density lipoprotein（HDL）and HDL subfractions，fasting plasma glucose（FPG），fasting plasma insulin（FINS）and glycosylated hemogolbin（HbA 1C）were measured，and the plasma lowdensity lipoprotein （LDL） and very lowdensity lipoprotein（VLDL）were caculated．
Results
In NIDDM patients with DR，the TC，LDL，FPG，HbA 1C and duration of NIDDM were higher or longer than those in NIDDM patients without DR．Moreover，the TC，LDL，FPG、FINS、HbA 1C and dutation of NIDDM were increased or lengthened in NIDDM patients with proliferative DR as compared with those with backgroud DR．The correlation analysis showed the severity of DR was positively correlated with TC，LDL，HbA 1C and duration of NIDDM．
Conclusion
Dyslipidemia may play some role in the onset and development of DR．
(Chin J Ocul Fundus Dis,1998,14:21-23)
Objective To assess the effectiveness and safety of biphasic insulin aspart 30 given three times a day in the management of type 2 diabetes. Methods Such databases as CENTRAL, MEDLINE, PubMed and CNKI were searched on computer; additionally, the relevant conference proceedings from associations like American Diabetes Association, and the references of all selected literatures were also hand-searched. The randomized controlled trials (RCTs) on biphasic insulin aspart 30 given three times a day in treating type 2 diabetes were screened according to inclusive and exclusive criteria, without concerning the limitation of languages and blind methods. After data extraction and quality evaluation, Meta-analysis was performed by using RevMan 4.2 software. Results Ten trials involving 1 415 patients were included. The sub-group analysis showed that compared with the group of given biphasic insulin aspart 30 twice a day (the bid group), the group of given biphasic insulin aspart 30 three times a day (the tid group) was superior in decreasing HbAlc (Plt;0.000 01). Compared with the group of thrice preprandial injection of Novolin R plus one injection of Novolin N at bedtime (the qid group), Meta-analysis showed that, a) As to the average fasting glucose levels: the tid group was not superior to the qid group (P=0.65); b) As to the average 2-hour postprandial glucose levels: the tid group was superior to the qid group (P=0.0003); c) As to the therapeutic time: the tid group was not superior to the qid group (P=0.38); d) As to the insulin doses: the tid group was superior to the qid group (P=0.000 1); e) As to the insulin costs: the tid group was inferior to the qid group (P=0.02); and e) As to the incidence of hypoglycaemia: the tid group was superior to the qid group (P=0.000 2). Compared with the oral antidiabetic drugs, the results of Meta-analyses showed: the tid group was superior in decreasing HbAlc (P=0.001). Conclusion The limited current evidence shows that biphasic insulin aspart 30 given three times a day, as a simple insulin intensified scheme, is safe and effective for type 2 diabetes, and is worth recommending in clinic. However, all these findings should be further confirmed with more large sample and well-designed RCTs.
Objective To study the interferencing and anti-tumor effects of lentiviral vector of siRNA targeting IGF1R and EGFR gene of the liver cancer cell. Methods The complementary DNA containing both sense and antisense Oligo DNA of the targeting sequence was designed, synthesized and connected to the pLVTHM vector, named pLVTHM-IGF1R, into whom the EGFR-siRNA expression frame containing H1 promotor synthesized by RT-PCR was cloned to generate pLVTHM-IGF1R-EGFR-siRNA. The 293T cells were cotransfected by 3 plasmids of pLVTHM-IGF1R-EGFR-siRNA, psPAX2 and pMD2G to enclose LVTHM-IGF1R-EGFR-siRNA, which was amplified in large amount and purified by caesium chloride density gradient centrifugation for measurement of virus titer. SMMC7721 cells infected by LVTHM-IGF1R-EGFR-siRNA were infection group, the untreated SMMC7721 cells and blank vector plasmid LVTHM were two control groups (SMMC7721 cell group and blank vector group). The effect of LVTHM-IGF1R-EGFR-siRNA on IGF1R and EGFR expressions of SMMC7721 cells were detected by RT-PCR and Western blot. The antitumor potential of LVTHM-IGF1R-EGFR-siRNA to SMMC7721 cells was evaluated by Cell Counting Kit-8 assay for cell growth and TUNEL for apoptosis respectively. Results LVTHM-IGF1R-EGFR-siRNA was constructed successfully. Functional pfu titers of LVTHM-IGF1R-EGFR-siRNA was 4.58×109 pfu/ml. Protein and mRNA expression of IGF1R and EGFR of infection group were less than those of blank vector group and SMMC7721 cell group （P＜0.05）, LVTHM-IGF1R-EGFR-siRNA was more effective to inhibit the proliferation and promote apoptosis of SMMC7721 cells （P＜0.05）. Conclusion LVTHM-IGF1R-EGFR-siRNA expressing IGF1R-EGFR-siRNA can inhibit the expression of IGF1R and EGFR, and may be used for further investigation of gene therapy of liver cancer.
ObjectiveTo explore therapeutic mechanisms and clinical application prospects of novel weight-loss medications in patients with obesity complicated by cardiovascular-kidney-metabolic (CKM) syndrome, aiming to provide theoretical support and therapeutic strategies for personalized precision management of CKM syndrome. MethodsRecent domestic and international studies were retrospectively reviewed, focusing on the mechanisms of action, clinical research outcomes, and application progress of novel weight-loss medications, including glucagon-like peptide 1 (GLP-1) receptor agonists, dual glucose-dependent insulinotropic peptide (GIP)/GLP-1 receptor agonists, triple GIP/GLP-1/glucagon receptor agonists, and amylin analogues. Special emphasis was placed on their comprehensive effects on cardiovascular, renal, and metabolic parameters. ResultsNovel weight-loss medications have demonstrated significant weight reduction and multisystem benefits through precise regulation of central appetite pathways, insulin sensitivity, and lipid metabolism. Among these medications, GLP-1 receptor agonists (e.g., semaglutide) and dual receptor agonists (e.g., tirzepatide) have been confirmed in phase Ⅲ clinical trials to effectively reduce cardiovascular event risks, slow renal function deterioration, and markedly improve glycemic control in obese patients with CKM syndrome. Triple receptor agonists (e.g., retatrutide) and combination medication regimen (e.g., CagriSema regimen) have further enhanced weight-loss efficacy, providing novel therapeutic avenues for obesity-related diseases. Additionally, these medications usually require combined application with traditional chronic disease medications, such as sodium-glucose linked transporter 2 inhibitors and renin-angiotensin-aldosterone system blockers, to achieve comprehensive therapeutic outcomes in CKM syndrome patients. However, further studies are needed to address long-term safety in real-world settings, optimization of drug formulations, and application in precision medicine. ConclusionsNovel weight-loss medications offer promising strategies for personalized precision treatment of obesity with CKM syndrome due to their significant weight-loss efficacy and multisystem synergistic effects. Although current clinical trials demonstrate substantial therapeutic potential, the complexity of CKM syndrome and individual patient variability necessitate additional in-depth research to facilitate broader clinical adoption and optimization of these medications.
Objective Through studying a diabetic patient accompanied with pancreatic cancer by means of evidence-based clinical practice, to find out the relationship between diabetes mellitus and cancer and whether the long-acting insulin glargine increases the risk of cancer or not, which is regarded as a disputable hot issue at present. Methods Such databases as The Cochrane Library (Issue 3, 2010), OVID-EBM Reviews (1991 to Sept. 2010), MEDLINE (1950 to Sept. 2010) and CNKI (2000 to Sept. 2010) were retrieved to collect high quality clinical evidence, and the best therapy was formulated in accordance with the willingness of patients themselves. Results Eight randomized controlled trials (RCTs), four meta-analyses and one RCT meta-analysis were included. The evidence indicated that: a) Diabetes mellitus was kind of related to the occurrence of malignancies; b) There was no evidence at present showing the relationship between long-acting insulin glargine and cancer; c) Strictly controlling of blood sugar did not increase the risk of tumorigenesis, but hyperglycemia causing cancer was proofless; and d) Whether the diabetic patient with cancer should stop taking long-acting insulin glargine or not should require suggestions from specialists rather than patients themselves. Conclusion No evidence at present shows that tumorigenesis is related to diabetes mellitus, long-acting insulin glargine and strict controlling of blood sugar. It is necessary to require more evidence to decide whether the therapy should be adjusted or not for the diabetic patient with cancer who is in the process of glargine therapy.
ObjectiveTo observe and compare the cytological and biological differences between human normal and degenerated nucleus pulposus (NP), and to investigate the repair effect of insulin-like growth factor 1 (IFG-1) and platelet derived growth factor (PDGF) on human degenerated NP.MethodsHuman degenerative and normal NP tissues were obtained from operative patients, a portion of which were processed into tissue sections and HE staining was performed to observe the morphological changes of nucleus pulposus cells (NPCs) before and after degeneration of NP. Immunohistochemistry staining was used to determine the expression levels of collagen type Ⅰ, collagen type Ⅱ, B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax) proteins. Another portion of tissues were isolated and cultured and NPCs morphology was observed under inverted microscope. Western blot analysis was used to detect collagen type Ⅱ protein expression. Then, the gene transfection experiments were launched, including 4 groups, with group A designed as degenerated NPCs only, and groups B, C, and D of degenerated NPCs transfected with IGF-1 gene lentiviral particles, PDGF gene lentiviral particles, and lentiviral particles carrying IGF-1 and PDGF double genes, respectively. At 21 days after transfection, the cell morphology of each group was observed under inverted microscope, the positive rates of IGF-1 and PDGF of each group were measured by flow cytometry, and the expression of collagen type Ⅱ protein was detected by using immunohistochemistry staining and Western blot.ResultsHE staining showed that there were a large number of notochordal cells and a small number of chondrocytes in the central NP tissue of normal group, while the NPCs in degeneration group were significantly reduced, and a large proportion of fibrocartilage tissues were found in NP tissue. Immunohistochemistry staining showed that the percentages of collagen type Ⅰ and Bax protein-positive cells in degeneration group were significantly higher than those of normal group, while the percentages of collagen type Ⅱ and Bcl-2 protein-positive cells were significantly lower than those of normal group (P<0.05). Western blot showed that the relative expression level of collagen type Ⅱ protein in degeneration group was significantly lower than that in normal group (t=65.493, P=0.000). At 21 days after gene transfection, compared with group A, the cell viability of groups B, C, and D increased and the morphology became more regular. Flow cytometry showed that the percentages of IGF-1-positive cells in groups B and D were significantly higher than that in group A, and the percentages of PDGF-positive cells in groups C and D were significantly higher than that in group A (P<0.05). Immunohistochemistry staining showed that the positive stainings of collagen type Ⅱ in groups A, B, C, and D was (±), (+), (+), and (++), respectively. Western blot showed that the relative expression of collagen type Ⅱ protein in groups A, B, C, and D increased by degrees, and the differences between groups were significant (P<0.05).ConclusionBoth IGF-1 and PDGF can reverse the degeneration of intervertebral discs NPCs and they have synergistic effects, providing experimental basis for its application in clinical treatment approaches for degenerative disc disease.
Purpose
To investigate the status of proliferation and activation of vascular endothelial cells in preretinal neovascular membranes from patients with insulin dependent diabetetes mellitus(IDDM)by means of immunohistochemical techniques.
Methods
Status of vascular endothelial cells in 18 preretinal neovascular membranes from 18 patients with IDDM was studied by double-immunofluorescence technique and the alkaline phosphataes-anti-alkaline phosphatase(APAAP)technique and compared the findings with the main clinical features of the patients.
Results
Of 18 vascularized membranes,16(88.9%)contained proliferating endothelial cells (positive for proliferating vascular endothelial cell marker EN 7/44) and 14 (77.8%) were positive for endothelial cell activation marker anti-VCAM-1;furthermore,by using a double staining technique,we found that in 14 of the 16 cases(87.5%) the proliferating vascular endothelial cells were activated (expressing VCAM-1).
Conclusion
The proliferation and activation of the vascular endothelial cells of the newly formed vessels in preretinal neovascular membranes suggests the significance of the vascular endothelial cells in the pathophysiology and the progress of proliferative diabetic retinopathy.
(Chin J Ocul Fundus Dis,1998,14:141-143)
Objective To explore the association between triglyceride glucose-waist circumference (TyG-WC) index and the risk of stroke among the middle-aged and older people, and compare the differences among TyG-WC, triglyceride glucose (TyG), and waist circumference (WC) in the prediction of stroke. Methods The data of adults aged 45 years or older enrolled in the China Health and Retirement Longitudinal Study registry in 2011 were collected, and the endpoint was self-reported or physician-diagnosed new stroke event by 2015. According to the baseline TyG-WC tertile, individuals were divided into three groups: TyG-WC tertile 1, tertile 2, and tertile 3 groups. Multiple logistic regression analyses were performed to analyze the associations of TyG-WC, TyG, and WC with the risk of stroke. The area under the curve (AUC) of receiver operating characteristic (ROC) curve, integrated discrimination improvement (IDI) score, and net reclassification improvement (NRI) score were calculated to evaluate the predictive value of TyG-WC, TyG, and WC in stroke. Results A total of 5847 participants were finally included, with 1949 in each group. After 4 years of follow-up, there were 252 cases of new stroke. There was significant difference in the incidence of stroke among the three groups (TyG-WC tertile 1 group: 2.57%, TyG-WC tertile 2 group: 4.16%, TyG-WC tertile 3 group: 6.21%; P<0.05). The results of multiple logistic regression analyses showed that the risk of new stroke in the third tertile group of TyG-WC and WC was higher than that in the first tertile group, respectively [TyG-WC: odds ratio (OR)=1.465, 95% confidence interval (CI) (1.033, 2.078), P=0.032; WC: OR=1.717, 95%CI (1.190, 2.478), P=0.004], while TyG was not the risk factor of stroke (P>0.05). The ROC curve analysis showed that the AUC of WC (0.566) was slightly higher than that of TyG-WC (0.556) and TyG (0.527). The IDI of TyG-WC (0.25%) was slightly higher than that of WC (0.22%), and the both were higher than that of TyG (0.07%). The NRI of WC (25.04%) was slightly higher than that of TyG-WC (19.68%), and the both were high than that of TyG (12.02%). Conclusions Compared with TyG, higher TyG-WC and WC are associated with the increased risk of new stroke among the middle-aged and older people. The predictive value of TyG-WC and WC for the risk of new stroke in the middle-aged and elderly is similar, and is better than that of TyG.
ObjectiveTo observe expressions of E3 ubiquitin ligase—mitsugmin53 (MG53) protein, MG53 mRNA, and insulin receptor substrate 1 (IRS-1) mRNA in skeletal muscle of non-obese type 2 diabetic mellitus (T2DM) rats after gastric bypass operation (GBP), and to investigate possible mechanism of GBP in improving insulin resistance.MethodsTwenty-four healthy male GK rats were randomly divided into diabetic operation group, diabetic sham operation group, and diabetic control group, 8 rats in each group; besides, 8 male Wistar rats were served as normal control group. The expressions of MG53 protein in skeletal muscle tissue were detected by using Western blot method on week8 after operation. The mRNA levels of IRS-1 and MG53 in skeletal muscles tissue were measured by RT-PCR methods on week 8 after operation.Results① The expressions of MG53 protein and MG53 mRNA in the diabetic sham operation group and diabetic control group were significantly higher than those in the diabetic operation group and the normal control group on week 8 after operation (P<0.05), respectively, which had no significant differences between the diabetic operation group and the normal control group (P>0.05), and between the diabetic sham operation group and the diabetic control group (P>0.05) on week 8 after surgery. ② Compared with the normal control group, the expression of IRS-1 mRNA was significantly decreased in the diabetic operation group, the diabetic sham operation group, and the diabetic control group (P<0.05), while there were no significant differences between the diabetic operation group, diabetic sham operation group, and the diabetic control group on week 8 after operation (P>0.05).ConclusionExpression of E3 ubiquitin ligase—MG53 protein in skeletal muscle tissue in T2DM rats following GBP is decreased, thus reduces the IRS-1 ubiquitin-degradation, increase the expression of IRS-1 protein in insulin signaling pathway of skeletal muscle tissue, and improve insulin resistance of skeletal muscle.
Objective To construct, validate and evaluate a nomogram prediction model based on triglyceride-glucose index for predicting the risk of type 2 diabetes mellitus (T2DM) in patients with obstructive sleep apnea (OSA). Methods A total of 414 patients diagnosed with OSA who were hospitalized in the Second Affiliated Hospital of Kunming Medical University from July 2013 to July 2023 were retrospectively analyzed. They were randomly divided into training set (n=289) and validation set (n=125) at a ratio of 7:3 using R software. In the training set, univariate logistic regression, best subsets regression (BSR) and multivariate Logistic regression were used to determine the independent predictors of OSA combined with T2DM and construct a nomogram. The area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow goodness of fit test, decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the discrimination, calibration and clinical applicability of the nomogram prediction model. Finally, the internal validation of the nomogram prediction model was carried out on the validation set. Results In the training set, the results of univariate logistic regression, BSR and multivariate logistic regression analysis showed that hypertension (OR=2.413, 95%CI 1.276-4.563, P=0.007), apnea hypopnea index (OR=1.034, 95%CI 1.014-1.053, P=0.001), triglyceride-glucose index( OR=12.065, 95%CI 5.735-25.379, P<0.001), triglyceride/high density lipoprotein cholesterol (OR=0.736, 95%CI 0.634-0.855, P<0.001) were independent predictors of T2DM in OSA patients. A nomogram prediction model was constructed based on the above four predictors. In the training set and validation set, the AUC, sensitivity, and specificity of the nomogram prediction model for predicting the risk of T2DM in OSA patients were 0.820 (95%CI 0.771-0.869), 75.7%, 75.9% and 0.778 (95%CI 0.696-0.861), 74.5%, 73.0%, respectively, indicating that the nomogram had good discrimination. The calibration curve showed that the nomogram had a good calibration for predicting T2DM in OSA patients. DCA and CIC also showed that the nomogram prediction model had certain clinical utility. Conclusions A simple, fast and effective nomogram prediction model with good discrimination, calibration and clinical applicability was successfully constructed, validated and evaluated. It can be used to predict the risk of T2DM in OSA patients and help clinicians to identify patients with high risk of T2DM in OSA patients.
