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1.
Gerontol Geriatr Med ; 10: 23337214241260938, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39091995

RESUMEN

Objectives: To determine the prevalence of diabetic retinopathy and undiagnosed diabetes among Delaware nursing home and assisted care facility residents. Methods: This cross-sectional study involved the statistical analysis of comprehensive eye examination records of 2,063 nursing home residents residing in 18 facilities and 4 assisted living facilities in Delaware from 2005 to 2009. Descriptive statistical analyses were conducted to identify the rates of retinal dot and blot hemorrhages and existing systemic diabetes diagnoses. Results: The mean age of nursing home and assisted care facility residents was 77 years (range 9-104), and 64.4% were over the age of 80. Most residents were female (61.1%) and white (72.5%). 3.6% of the 2,063 nursing home residents had blot or dot hemorrhages in one or both eyes. 32.8% had a type 1 or type 2 diabetes diagnosis. Of the ones with a positive dot and blot hemorrhage finding, 56.8% had a diagnosis of diabetes, and 43.2% did not. Discussion: There was a high prevalence of dot and blot hemorrhages without a systemic diagnosis of diabetes, indicating a need for regular eye care among residents.

2.
Pak J Med Sci ; 40(7): 1410-1414, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39092054

RESUMEN

Objective: To explore the effect of Atorvastatin combined with Irbesartan in the treatment of early diabetic nephropathy (DN). Methods: Clinical data from 153 patients with early DN, admitted to Huzhou Central Hospital from January 2020 to December 2022, was retrospectively selected. Patients were divided into two groups based on the treatment they received: patients received Irbesartan treatment alone were assigned to Irbesartan group (n=74); patients received Irbesartan combined with Atorvastatin were assigned to combined group (n=79). Levels of renal function indicators, renal fibrosis indicators, micro inflammatory status indicators, and incidence of adverse reactions were compared between the two groups before and after the treatment. Results: After the treatment, indicators of renal function, renal fibrosis and micro-inflammation in both groups significantly decreased compared to pretreatment levels (P<0.05), and were significantly lower in the combined group compared to Irbesartan group (P<0.05). There was no significant difference in the incidence of adverse reactions between the groups (P>0.05). Conclusions: Compared with Irbesartan alone, Atorvastatin combined with Irbesartan is more effective in the treatment of early DN. Combined treatment regimen is able to effectively reduces the micro-inflammatory state, improve renal function and fibrosis, and is not associated with the increased risk of adverse reactions.

3.
Pak J Med Sci ; 40(7): 1378-1383, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39092062

RESUMEN

Objectives: This study was aimed to determine the various factors which could serve as predictor of saving of lower limb from amputation in patients with diabetic foot ulcer (DFU). Method: This three-year retrospective study was conducted in the Diabetes and Endocrinology Unit of Hayatabad Medical complex Peshawar, Pakistan. Demographic, clinical, laboratory and radiological information of the diabetic patients with DFU admitted between January 2020 to December 2022 was retrieved from the hospital files. Information regarding initial and final decision regarding amputation and the outcome of the ulcer was also recorded. Results: A total of 502 patients of diabetes mellitus (DM) with DFU were included in the study, of whom there were 279 (55.6%) males and 223 (44.4%) females. The mean age of the study population, mean duration of DM and mean HbA1c were 55.2 ± 9.8 years, 13.7 ± 6.7 years and 11.2 ± 2.4 %, respectively. Patients who had an amputation of their lower limbs had an increased age (p= 0.034), raised total leucocyte count (TLC) (p= <0.001), higher HbA1c (p= 0.025), had osteomyelitis (p= <0.001), and had a higher-grade ulcer (p= <0.001). On binary logistic regression analysis, ulcer grade (OR=7.4, p= <0.001), osteomyelitis (OR=11.8, p= <0.001), and initial decision of no amputation at the time of admission (OR=33.6, p=<0.001) were independently associated with the lower limb salvage. Conclusion: DFU which were of grade I to II, had no evidence of osteomyelitis and for which an initial decision was of no amputation were more likely to be salvaged.

4.
Front Pharmacol ; 15: 1379821, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39092227

RESUMEN

Diabetic kidney disease (DKD) is characterized by complex pathogenesis and poor prognosis; therefore, an exploration of novel etiological factors may be beneficial. Despite glycemic control, the persistence of transient hyperglycemia still induces vascular complications due to metabolic memory. However, its contribution to DKD remains unclear. Using single-cell RNA sequencing data from the Gene Expression Omnibus (GEO) database, we clustered 12 cell types and employed enrichment analysis and a cell‒cell communication network. Fibrosis, a characteristic of DKD, was found to be associated with metabolic memory. To further identify genes related to metabolic memory and fibrosis in DKD, we combined the above datasets from humans with a rat renal fibrosis model and mouse models of metabolic memory. After overlapping, NDRG1, NR4A1, KCNC4 and ZFP36 were selected. Pharmacology analysis and molecular docking revealed that pioglitazone and resveratrol were possible agents affecting these hub genes. Based on the ex vivo results, NDRG1 was selected for further study. Knockdown of NDRG1 reduced TGF-ß expression in human kidney-2 cells (HK-2 cells). Compared to that in patients who had diabetes for more than 10 years but not DKD, NDRG1 expression in blood samples was upregulated in DKD patients. In summary, NDRG1 is a key gene involved in regulating fibrosis in DKD from a metabolic memory perspective. Bioinformatics analysis combined with experimental validation provided reliable evidence for identifying metabolic memory in DKD patients.

5.
Front Endocrinol (Lausanne) ; 15: 1422674, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39092282

RESUMEN

Objective: This study aims to conduct a comprehensive investigation of the serum amino acid profiles of individuals with type 2 diabetes (T2D) and its related complications. Methods: Patients with T2D were enrolled in this study. Sixteen kinds of common amino acids in the fasting circulating were assessed through liquid chromatography-mass spectrometry (LC-MS). Subsequently, correlation, regression analyses, and receiver operating characteristic (ROC) curves were conducted to assess the associations between amino acids and clinical indicators. Results: Thirteen different kinds of amino acids were identified in diabetic patients, as compared with normal controls. The Glutamine/Glutamate (Gln/Glu) ratio was negatively correlated with BMI, HbA1c, serum uric acid, and the triglyceride-glucose (TyG) index, while it was positively correlated with HDL-C. Logistic regression analyses indicated that Gln/Glu was a consistent protective factor for both T2D (OR = 0.65, 95% CI 0.50-0.86) and obesity (OR = 0.79, 95% CI 0.66-0.96). The ROC curves demonstrated that Gln/Glu, proline, valine, and leucine provided effective predictions for diabetes risk, with Gln/Glu exhibiting the highest AUC [0.767 (0.678-0.856)]. In patients with T2D, Gln was the only amino acid that displayed a negative correlation with HbA1c (r = -0.228, p = 0.017). Furthermore, HOMA-ß exhibited a negative correlation with Glu (r = -0.301, p = 0.003) but a positive correlation with Gln/Glu (r = 0.245, p = 0.017). Notably, logistic regression analyses revealed an inverse correlation of Gln/Glu with the risk of diabetic kidney disease (OR = 0.74, 95% CI 0.55-0.98) and a positive association with the risk of diabetic retinopathy (OR = 1.53, 95% CI 1.08-2.15). Conclusion: The Gln/Glu ratio exhibited a significant association with diabetes, common metabolic parameters, and diabetic complications. These findings shed light on the pivotal role of Gln metabolism in T2D and its associated complications.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ácido Glutámico , Glutamina , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Glutamina/sangre , Masculino , Femenino , Persona de Mediana Edad , Ácido Glutámico/sangre , Anciano , Estudios de Casos y Controles , Biomarcadores/sangre , Adulto , Glucemia/análisis , Glucemia/metabolismo , Complicaciones de la Diabetes/sangre
7.
Cureus ; 16(7): e65888, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39092383

RESUMEN

In ophthalmology, intravitreal therapies are currently not personalized/customized and are not adjusted to the individual vitreous volume. With reference to the recently published calculation formula for a more accurate estimation of the vitreous body, we determined the dose of intravitreal medication for different vitreous volumes and compared them with the average volume. Using the axial length of the eye, the formula for the vitreous volume exact (VIVEX) can provide a more accurate indication of the vitreous volume in individual cases than an assumed standard volume of 4 mL. The concentration of active substances in small eyes may be twice as high as that in normal-sized emmetropic eyes. In contrast, large eyes may show less than half of the recommended drug concentration. The calculated concentrations of the investigated intravitreal drugs in small and large eyeballs showed impressive differences with large deviations from the recommended doses. Further systematic studies should follow to find out whether this has any impact on the effectiveness or side effects of the injected drugs.

8.
Eur J Ophthalmol ; : 11206721241267029, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39094553

RESUMEN

BACKGROUND: This retrospective cohort study aimed to assess the characteristics of patients enrolled in the national diabetic retinopathy (DR) screening program and evaluate the selected program's quality elements in the first five years after implementation. METHODS: Patients who underwent DR screening between February 2018 and June 2022 at the University Medical Centre Ljubljana were included. General patient characteristics (age, sex, type and therapy of diabetes mellitus (DM), duration of DM, blood HbA1c levels), best corrected visual acuity, stage of DR, presence of sight-threatening diabetic retinopathy (STDR), and selected quality indicators (quality of photographs, re-screening interval, time to treatment) were recorded and evaluated. RESULTS: A total of 34 654 screening examinations were performed on 13 513 patients with diabetes. The majority (77.3%) had Type 2 diabetes, with a mean DM duration of 9.74 ± 9.87 years. In 55.9% of patients, DM duration was less than ten years, and the mean HbA1c was 7.33% ± 1.49. DR signs were noted in 29.1% of patients and 0.89% of patients exhibited STDR. After establishing the diagnosis of STDR, treatment was initiated in 3.43 ± 1.98 months. CONCLUSION: Implementing the DR screening program provides valuable insights into managing diabetic retinopathy nationwide. It allows for the early detection of sight-threatening DR and facilitates timely and effective treatment, which could help prevent severe visual impairment.

9.
Curr Eye Res ; : 1-7, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39086188

RESUMEN

PURPOSE: To investigate the value of proprotein-converting subtilisin kexin type 9 (PCSK9) levels in type 2 diabetes mellitus (T2D) patients with different stages of diabetic retinopathy (DR) and to compare these findings with a healthy control group without diabetes mellitus (DM). METHODS: A total of 135 patients, 100 of whom were patients with T2D and 35 of whom were in the health control group, were included in this prospective study. T2D patients were divided into three groups: the first group included 34 people with T2D without DR, the second group had 32 people with non-proliferative DR (NPDR), and the third group had 34 people with proliferative DR (PDR). Serum PCSK9 levels were analyzed and compared between the groups. RESULTS: Forty-nine percent of the participants were female, and the mean age was 64 ± 9.1 years, with no statistically significant results between the four groups in terms of age and sex. The mean serum PCSK9 value was significantly different (p = 0.01) when all groups were evaluated, and statistically significant change was observed with the progression of DR. When serum PCSK9 levels were evaluated in all T2D patients (groups 1, 2, and 3), a medium-level correlation was observed with low-density lipoprotein (p < 0.05). CONCLUSION: Serum PCSK9 values differed significantly in diabetic patients compared to the control group. One should be clinically cautious about the usefulness of circulating PCSK9 concentrations as an indicator of the risk of diabetic retinopathy.

10.
Semin Ophthalmol ; 39(6): 460-467, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39087722

RESUMEN

PURPOSE: To evaluate the responses of different optical coherence tomography (OCT) patterns of diabetic macular edema (DME) to intravitreal injection therapy. METHODS: In this retrospective, comparative, and multicenter study, patients who had previously untreated DME, who received intravitreal ranibizumab (IVR) or aflibercept (IVA) and/or steroid treatment with the pro re nata (PRN) treatment regimen after a 3-month loading dose, and had a 12-month follow-up in the MARMASIA Study Group were included. Morphological patterns of DME were divided into four groups based on OCT features diffuse/spongious edema (Group 1), cystoid edema (Group 2), diffuse/spongious edema+subretinal fluid (SRF) (Group 3), and cystoid edema+SRF (Group 4). Changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA) at months 3, 6, and 12, and the number of injections at month 12 were compared between the DME groups. RESULTS: 455 eyes of 299 patients were included in the study. The mean baseline BCVAs [Logarithm of the Minimum Angle of Resolution (logMAR)] in groups 1, 2, 3, and 4 were 0.54 ± 0.24, 0.52 ± 0.25, 0.55 ± 0.23, and 0.57 ± 0.27, respectively. There was no significant difference between the baseline mean BCVAs between the groups (p = .35). The mean BCVAs were significantly improved to 0,47 ± 0,33 in group 1, 0,42 ± 0,33 in group 2, 0,47 ± 0,31 in group 3, and 0,45 ± 0,43 at month 12. There was no significant difference between the groups in terms of BCVA change at month 12 (p = .71). The mean baseline CMTs in groups 1, 2, 3, and 4 were 387,19 ± 128,19, 447,02 ± 132,39, 449,12 ± 109,24, and 544,19 ± 178,61, respectively. At baseline, the mean CMT was significantly higher in Group 4 than in the other groups (p = .000). The mean CMTs were significantly decreased to 325,16 ± 97,55, 334,94 ± 115,99, 324,33 ± 79,20, and 332,08 ± 150,40 in four groups at month 12 respectively (p > .05). The groups had no significant difference in mean CMT at month 12 (p = .835). The change in CMT was significantly higher in Group 4 than in the other groups at month 12 (p = .000). The mean number of intravitreal anti-VEGF injections at month 12 was 4.51 ± 1.57 in Group 1, 4.63 ± 1.54 in Group 2, 4.88 ± 1.38 in Group 3, and 5.07 ± 1.49 in Group 4. The mean number of anti-VEGF injections in Group 1 and Group 2 was significantly lower than in Group 4 (p = 0,014 and p = 0,017). CONCLUSIONS: In real life, there was no significant difference between the DME groups in terms of visual improvement at month 12. However, better anatomical improvement was achieved in Group 4 than in the other DME groups.


Asunto(s)
Inhibidores de la Angiogénesis , Retinopatía Diabética , Inyecciones Intravítreas , Edema Macular , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Edema Macular/tratamiento farmacológico , Edema Macular/diagnóstico , Edema Macular/fisiopatología , Edema Macular/etiología , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/fisiopatología , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Agudeza Visual/fisiología , Proteínas Recombinantes de Fusión/administración & dosificación , Masculino , Femenino , Ranibizumab/administración & dosificación , Persona de Mediana Edad , Estudios de Seguimiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Pronóstico , Mácula Lútea/patología , Mácula Lútea/diagnóstico por imagen , Glucocorticoides/administración & dosificación
11.
Acta Diabetol ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090426

RESUMEN

AIMS: Diabetic retinopathy (DR) results from complex genetic and metabolic interactions. Unraveling the links between blood metabolites and DR can advance risk prediction and therapy. METHODS: Leveraging Mendelian Randomization (MR) and Linkage Disequilibrium Score Regression (LDSC), we analyzed 10,413 DR cases and 308,633 controls. Data was sourced from the Metabolomics GWAS server and the FinnGen project. RESULTS: Our research conducted a comprehensive MR analysis across 486 serum metabolites to investigate their causal role in DR. After stringent selection and validation of instrumental variables, we focused on 480 metabolites for analysis. Our findings revealed 38 metabolites potentially causally associated with DR. Specifically, 4-androsten-3beta,17beta-diol disulfate 2 was identified as significantly associated with a reduced risk of DR (OR = 0.471, 95% CI = 0.324-0.684, p = 7.87 × 10- 5), even after rigorous adjustments for multiple testing. Sensitivity analyses further validated the robustness of this association, and linkage disequilibrium score regression analyses showed no significant genetic correlation between this metabolite and DR, suggesting a specific protective effect against DR. CONCLUSIONS: Our study identifies 4-androsten-3beta,17beta-diol disulfate 2, a metabolite of androgens, as a significant protective factor against diabetic retinopathy, suggesting androgens as potential therapeutic targets.

12.
J Diabetes Investig ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090828

RESUMEN

Diabetic striatopathy, a rare hyperglycemia complication, is characterized by chorea/ballism and striatal anomalies on neuroimaging, usually managed with glycemic control and haloperidol. However, practical strategies for haloperidol-resistant cases are scarce. We describe a 76-year-old Japanese woman with diabetic striatopathy who initially presented with polydipsia, polyuria, and lower-extremity weakness. Despite pronounced hyperglycemia (725 mg/dL), her blood glucose levels were reduced through saline infusion and intravenous insulin. Subsequently, she developed whole-body ballism concomitant with striatal hyperintensity on T1-weighted magnetic resonance imaging, which initially responded to haloperidol. Upon discontinuation of haloperidol, her symptoms relapsed and did not improve with the reintroduction of haloperidol. Dopamine transporter single photon emission computed tomography revealed diminished bilateral striatal uptake, suggesting presynaptic dopaminergic dysfunction. This finding prompted the initiation of L-dopa, which significantly improved her symptoms. This case underlines the need to consider presynaptic dopaminergic dysfunction in diabetic striatopathy patients unresponsive to standard treatments, highlighting the effectiveness of L-dopa in such scenarios.

13.
J Cell Biochem ; : e30634, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39091188

RESUMEN

In this study, we investigate the effect of neuregulin 4 (NRG4) on podocyte damage in a mouse model of diabetic nephropathy (DN) and we elucidate the underlying molecular mechanisms. In vivo experiments were conducted using a C57BL/6 mouse model of DN to determine the effect of NRG4 on proteinuria and podocyte injury, and in vitro experiments were performed with conditionally immortalized mouse podocytes treated with high glucose and NRG4 to assess the protective effects of NRG4 on podocyte injury. Autophagy-related protein levels and related signaling pathways were evaluated both in vivo and in vitro. The involvement of the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was detected using chloroquine or AMPK inhibitors. The results showed that the AMPK/mTOR pathway was involved in the protective roles of NRG4 against high glucose-mediated podocyte injury. Also, NRG4 significantly decreased albuminuria in DN mice. PAS staining indicated that NRG4 mitigated glomerular volume and mesangium expansion in DN mice. Consistently, western blot and RT-PCR analyses confirmed that NRG4 decreased the expression of pro-fibrotic molecules in the glomeruli of DN mice. The immunofluorescence results showed that NRG4 retained expression of podocin and nephrin, whereas transmission electron microscopy revealed that NRG4 alleviated podocyte injury. In DN mice, NRG4 decreased podocyte apoptosis and increased expression of nephrin and podocin, while decreasing the expression of desmin and HIF1α. Overall, NRG4 improved albuminuria, glomerulosclerosis, glomerulomegaly, and hypoxia in DN mice. The in vitro experiments showed that NRG4 inhibited HG-induced podocyte injury and apoptosis. Furthermore, autophagy of the glomeruli decreased in DN mice, but reactivated following NRG4 intervention. NRG4 intervention was found to partially activate autophagy via the AMPK/mTOR signaling pathway. Consequently, when the AMPK/mTOR pathway was suppressed or autophagy was inhibited, the beneficial effects of NRG4 intervention on podocyte injury were diminished. These results indicate that NRG4 intervention attenuates podocyte injury and apoptosis by promoting autophagy in the kidneys of DN mice, in part, by activating the AMPK/mTOR signaling pathway.

14.
Hum Antibodies ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39093067

RESUMEN

BACKGROUND: Many studies have examined the role of inflammation in the development of diabetic neuropathy (DPN). OBJECTIVE: Evaluate the relation of the serum level of Transforming Growth Factor-ß and Tumor Necrosis Factor-α and development of diabetic peripheral neuropathy DPN. METHODS: In a case-control study, randomly selected 140 diabetic patients were included, the randomly selected patients were divided equally and matched into a case group who have diabetic peripheral neuropathy and diabetic neuropathy-free patients as a control group. For both groups whole blood sample was examined to compare for (TGF-ß), and (TNF-α) levels determination by ELISA technique. RESULTS: The age of the study samples ranged from 25 to 80 years with a male ratio of 1.45:1 although the sex differences between both groups were not significant. The mean levels of (TNF-α) and (TGF-ß) was significantly higher among cases group than that of controls group (254.86 ± 75.9 vs158.01 ± 50.600) for TNF-α and for TGF- ß (312.85 ± 62.27 vs. 217.82 ± 52.95) respectively. Both TNF-α and TGF-ß have high sensitivity and specificity in detection of DPN. The sensitivity of TNF-α was 95.7% and specificity of 61.4% area under the ROC curve (AUC) of 0.870 ± 0.029, while the sensitivity of TGF-ß was 91.4%, and specificity of 67.1 with good area under the ROC curve (AUC) of 0.891 ± 0.026 (P=0.000). CONCLUSIONS: TNF-α and TGF -ß are significantly elevated levels in patients with DPN, these cytokines could be used as indicators for the development of DPN.

15.
Arch Med Sci Atheroscler Dis ; 9: e122-e128, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086621

RESUMEN

Artificial intelligence is growing quickly, and its application in the global diabetes pandemic has the potential to completely change the way this chronic illness is identified and treated. Machine learning methods have been used to construct algorithms supporting predictive models for the risk of getting diabetes or its complications. Social media and Internet forums also increase patient participation in diabetes care. Diabetes resource usage optimisation has benefited from technological improvements. As a lifestyle therapy intervention, digital therapies have made a name for themselves in the treatment of diabetes. Artificial intelligence will cause a paradigm shift in diabetes care, moving away from current methods and toward the creation of focused, data-driven precision treatment.

16.
Curr Genomics ; 25(3): 153-157, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-39086997

RESUMEN

Diabetic Kidney Disease (DKD) remains the leading cause of Chronic and End Stage Kidney Disease (ESKD) worldwide, with an increasing epidemiological burden. However, still, the disease awareness remains low, early diagnosis is difficult, and therapeutic management is ineffective. These might be attributed to the fact that DKD is a highly heterogeneous disease, with disparities and variability in clinical presentation and progression patterns. Besides environmental risk factors, genetic studies have emerged as a novel and promising tool in the field of DKD. Three decades ago, family studies first reported that inherited genetic factors might confer significant risk to DKD development and progression. During the past decade, genome-wide association studies (GWASs) screening the whole genome in large and multi-ethnic population-based cohorts identified genetic risk variants associated with traits defining DKD in both type 1 and 2 diabetes. Herein, we aim to summarize the existing data regarding the progress in the field of genomics in DKD, present how the revolution of GWAS expanded our understanding of pathophysiologic disease mechanisms and finally, suggest potential future directions.

17.
J Orthop Translat ; 48: 25-38, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39087140

RESUMEN

Background: Diabetic bone healing remains a great challenge due to its pathological features including biochemical disturbance, excessive inflammation, and reduced blood vessel formation. In previous studies, small intestine submucosa (SIS) has been demonstrated for its immunomodulatory and angiogenic properties, which are necessary to diabetic bone healing. However, the noticeable drawbacks of SIS such as fast degradation rate, slow gelling time, and weak mechanical property seriously impede the 3D printing of SIS for bone repair. Method: In this study, we developed a novel kind of 3D-printed scaffold composed of alginate, nano-hydroxyapatite, and SIS. The morphological characterization, biocompatibility, and in vitro biological effects of the scaffolds were evaluated, and an established diabetic rat model was used for testing the in vivo biological effect of the scaffold after implantation. Results: The in vitro and in vivo results show that the addition of SIS can tune the immunomodulatory properties and angiogenic and osteogenic performances of 3D-printed scaffold, where the macrophages polarization of M2 phenotype, migration and tube formation of HUVECs, as well as osteogenic expression of ALP, are all improved, which bode well with the functional requirements for treating diabetic bone nonunion. Furthermore, the incorporation of alginate substantially improves the printability of composites with tunable degradation properties, thereby broadening the application prospect of SIS-based materials in the field of tissue engineering. Conclusion: The fabricated 3D-printed Alg/HA/SIS scaffold provides desirable immunomodulatory effect, as well as good osteogenic and angiogenic performances in vitro and in vivo, which properties are well-suited with the requirement for treating diabetic bone defects. Translational potential of this article: The incorporation of SIS and alginate acid not only provides good printability of the newly fabricated 3D-printed Alg/HA/SIS scaffold, but also improves its immunoregulatory and angiogenic properties, which suits well with the requirement for treating diabetic bone disease and opens up new horizons for the development of implants associating diabetic bone healings.

18.
Artículo en Inglés | MEDLINE | ID: mdl-39088648

RESUMEN

Intrarenal dopamine plays a protective role against the development of diabetic nephropathy during the early stages of the disease. In streptozotocin-induced diabetic mice with a renal-specific catechol-O-methyl transferase knockout, intrarenal dopamine was found to suppress glomerular hyperfiltration, reduce oxidative stress and inflammation, and inhibit fibrosis. However, while dopamine activation in streptozotocin-induced diabetic models has been shown to provide renal protection, the role of dopamine in models of naturally induced diabetes mellitus is still unclear. In the present study, we administered 10 mg/kg p.o. benserazide, a peripheral decarboxylase inhibitor, to Spontaneously Diabetic Torii rats daily, in order to investigate the activation of the renal dopaminergic system during diabetic nephropathy progression. Our findings show that peripheral dopamine decreased urinary 8-iso-prostaglandin F2a and suppressed increases in plasma cystatin C levels. This study demonstrates that a reduction in peripheral dopamine can exacerbate renal dysfunction, even in the early stages of diabetic nephropathy characterized by glomerular hyperfiltration, thereby clarifying the pivotal role of endogenous peripheral dopamine in modulating oxidative stress and kidney performance.

19.
BMC Endocr Disord ; 24(1): 133, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090718

RESUMEN

BACKGROUND: The purpose of this systematic review and meta-analysis was to synthesize the current literature to determine the safety and efficacy of using subcutaneous insulin compared to an intravenous (IV) insulin infusion in managing diabetic ketoacidosis (DKA). METHODS: We searched Ovid-Medline, EMBASE, SCOPUS, BIOSIS and CENTRAL from inception to April 26, 2024. Randomized controlled trials (RCTs) and observational studies that assessed the use of subcutaneous compared to intravenous insulin for the treatment of mild to moderate DKA were included. Data extraction and quality assessment were performed by two independent reviewers and disagreements were resolved through further discussion or by a third reviewer. The Cochrane Risk of Bias tool version 2.0 was used to evaluate the RCTs and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS)-I tool was used to evaluate the observational studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Meta-analyses were conducted using random-effects models. We followed the PRISMA guidelines for reporting our findings. RESULTS: Six RCTs (245 participants) and four observational studies (8444 patients) met our inclusion criteria. Some studies showed a decreased length of stay (Mean Difference [MD] in days: -0.39; 95% CI: -2.83 to 2.08; I2: 0%) among individuals treated with subcutaneous insulin compared to intravenous insulin. There was no difference in the risk of all-cause mortality, time to resolution of DKA (MD in hours: 0.17; 95% confidence interval [CI]: -3.45 to 3.79; I2: 0%) and hypoglycemia (Risk Ratio [RR]: 1.02; 95% CI: 0.88 to 1.19; I2: 0%) between the two groups. CONCLUSION: Treatment of DKA with subcutaneous insulin may be a safe and effective alternative to IV insulin in selected patients. The limited available evidence underscores the need for further studies to explore optimal dosing, patient selection criteria and long-term outcomes.


Asunto(s)
Cetoacidosis Diabética , Hipoglucemiantes , Insulina , Humanos , Cetoacidosis Diabética/tratamiento farmacológico , Insulina/administración & dosificación , Hipoglucemiantes/administración & dosificación , Inyecciones Subcutáneas , Adulto , Sistemas de Infusión de Insulina , Infusiones Intravenosas , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
Ren Fail ; 46(2): 2387428, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39099183

RESUMEN

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), and its pathogenesis has not been clarified. Current research suggests that DKD involves multiple cell types and extra-renal factors, and it is particularly important to clarify the pathogenesis and identify new therapeutic targets. Single-cell RNA sequencing (scRNA-seq) technology is high-throughput sequencing of the transcriptomes of individual cells at the single-cell level, which is an effective technology for exploring the development of diseases by comparing genetic information, reflecting the differences in genetic information between cells, and identifying different cell subpopulations. Accumulating evidence supports the role of scRNA-seq in revealing the pathogenesis of diabetes and strengthening our understanding of the molecular mechanisms of DKD. We reviewed the scRNA-seq data this time. Then, we analyzed and discussed the applications of scRNA-seq technology in DKD research, including annotation of cell types, identification of novel cell types (or subtypes), identification of intercellular communication, analysis of cell differentiation trajectories, gene expression detection, and analysis of gene regulatory networks, and lastly, we explored the future perspectives of scRNA-seq technology in DKD research.


Asunto(s)
Nefropatías Diabéticas , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Humanos , Nefropatías Diabéticas/genética , Análisis de la Célula Individual/métodos , Transcriptoma , Secuenciación de Nucleótidos de Alto Rendimiento , Redes Reguladoras de Genes , Fallo Renal Crónico/genética , Perfilación de la Expresión Génica
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