Journal of Diabetes Research最新文献

Background: Emerging evidence suggests cell exfoliation could be operating under the control of cell metabolism. It is unclear if there are associations between the concentration of exfoliated kidney proximal tubule cells (PTCs) in urine with glycemic control and complications. Our study is aimed at exploring this. Methods: Urine samples were collected from 122 adult study participants and stored at -80°C. Exfoliated PTCs were extracted from thawed urine using a validated specific immunomagnetic separation method based on anti-CD13 and anti-SGLT-2 antibodies. The number of PTCs was assessed using brightfield microscopy. Study participants were grouped into those with no diabetes mellitus (DM) and those with DM. Individuals with DM were further subgrouped into those with and without retinopathy. Adjusted Poisson regression analysis was conducted for the DM cohort, investigating associations between demographic, clinical, and biochemical parameters with mean urinary exfoliated PTCs. Results: The adjusted Poisson regression analysis noted sex to have a significant association with mean number of urinary exfoliated PTCs, with a lower incidence rate in males compared to females (incidence rate ratio (IRR) 0.56, 95% CI 0.35-0.89, p = 0.014). Each 1% increase in glycated haemoglobin (HbA1c) was associated with an increase of 1.03 times in mean exfoliated PTCs (IRR 1.03, 95% CI 1.01-1.04, p = 0.007), and DM patients with retinopathy had an increase of 1.68 times in mean exfoliated PTCs compared to those without retinopathy (IRR 1.68, 95% CI 1.07-2.62, p = 0.024). No significant associations were observed with albuminuria or estimated glomerular filtration rate (eGFR). Conclusions: Our results indicate increased shedding of PTCs into the urinary tract in patients with poorer glycemic control, particularly those with diabetic retinopathy and in females.

Introduction: Diabetic nephropathy (DN) and diabetic retinopathy (DR) are serious complications of type 2 diabetes mellitus (T2DM). The reported estimates of prevalence and progression of DN and DR vary widely across studies. We undertook a systematic review and meta-analysis to determine the extent to which these variations in prevalence and progression of DN and DR may relate to different ethnic groups and socioeconomic status (SES). Methods: We searched the databases Ovid MEDLINE, Global Health, APA Psych Info, Embase, and PubMed for publications from 2005 to September 2023, based on T2DM and DN or DR, which included patient's ethnicities and SES. Prevalence estimates were summarized by meta-analysis using random effects models for each microvascular complication, stratified by ethnicity and SES. Data on progression was summarized narratively. Results: Twenty-seven studies were included. The overall prevalence of DN was 18% (95% CI: 14%, 22%) with no differences noted by ethnic group. Low economic status and low education levels were associated with a 4% increased risk of DN compared to higher levels. Higher prevalence of DR was noted among the Afro-Caribbeans, 28% (95% CI: 11%, 46%), compared to the White/Caucasian 19% (95% CI: 11%, 27%), and Asian/Indo Asians 25% (95% CI: 9%, 41%). Low-SES populations have a higher prevalence of DR than high-SES populations. The average prevalence was 16% (95% CI: 11%, 22%) among the high economic status group, compared to 25% (95% CI:20%, 30%) for the low economic status. Our study showed that Black ethnicity was associated with a higher risk of progression to end-stage renal disease (ESRD) and diabetic maculopathy compared to other ethnicities. People with high SES had a lower rate of DR progression than those with low SES, odds ratio (OR) (0.63, 95% CI: 53%, 74%). Conclusion: Ethnicity and SES may be associated with differential risk of development and progression of DN and DR. The available evidence was limited by the number of studies and small samples for certain ethnic/socioeconomic groups.

Introduction: The aim of present study was to evaluate the impact of perimenopause on insulin resistance. Specifically, insulin sensitivity was assessed in a perimenopausal mouse model treated with 4-vinylcyclohexene diepoxide (VCD), together with the changes in exosomal miRNA and hepatic mRNA expression profiles. Methods: Homeostasis model assessment of insulin resistance (HOMA-IR) was utilized to assess the status of insulin resistance, and insulin action was evaluated during menopausal transition. RNA sequencing (RNA-seq) analysis was used to identify altered expression profiles of exosomal miRNAs and hepatic mRNAs. Differentially expressed miRNA (DEM)-differentially expressed gene (DEG) network analyses were also conducted. Furthermore, altered expression levels of these exosomal miRNAs and genes were validated in plasma exosomes and liver tissue of perimenopausal mice. Results: HOMA-IR in VCD-treated mice was significantly increased, and hepatic glycogen was significantly decreased. Key exosomal miRNAs (miR-17-3p, miR-134-5p, miR-700-5p, and miR-6899-3p) and hepatic genes (G6pdx, Ptpn2, Lepr, Kras, and Braf) may be associated with impaired insulin signaling during perimenopause. Conclusion: The perimenopausal period acts as a potential factor in introducing insulin resistance as evidenced by impaired insulin action and altered expression profiles of exosomal miRNAs and hepatic genes. The present study contributes to the understanding that abnormal cargos carried by plasma exosomes, such as miRNAs, may be related to altered expression of the corresponding genes in the liver and abnormal insulin response.

Aim: To describe the demographic and clinical characteristics of patients with Charcot neuro-osteoarthropathy (CNO) and to examine for differences between participants with Type 1 diabetes mellitus (DM) (T1DM) and Type 2 diabetes mellitus (T2DM). Materials and Methods: Multicenter observational study in eight diabetic foot clinics in six countries between January 1, 1996, and December 31, 2022. Demographic, clinical, and laboratory parameters were obtained from the medical records. Analyses were performed using parametric or nonparametric statistical tests for variables with normally or nonnormally distributed values, respectively. Comparisons of the qualitative data were performed using the chi-square test. Results: Seven hundred seventy-four patients with DM and CNO were included. The mean age at diagnosis of CNO was 54.5 ± 11.7 years, and the median (interquartile range (IQR)) diabetes duration at diagnosis of CNO was 15 (10-22) years. Among participants, 71.8% (n = 546) were male and 83.2% (n = 634) had T2DM. Neuropathy was present in 91.7% (n = 688), retinopathy in 60.2% (n = 452), and nephropathy in 45.2% (n = 337). Subjects with T1DM, compared to T2DM, were diagnosed with CNO at a younger age (46.9 ± 11.0 vs. 57.9 ± 10.2 years, p < 0.001), had longer diabetes duration (median value (IQR): 29.0 (21.0-38.0) vs. 14.0 (8.0-20.0) years, p < 0.001), and had more often microvascular complications (neuropathy, 95.2% in T1DM vs. 87.4% in T2DM, p = 0.006; retinopathy, 83.3% vs. 55.4%, p < 0.001; and nephropathy 67.5% vs. 40.5%, p < 0.001). Conclusions: CNO is predominant in males, occurs in long-standing DM, and is often accompanied by microvascular complications. People with T1DM, compared to those with T2DM, are affected at a younger age, have longer diabetes duration, and have more often microvascular complications.

Background: Shenlian (SL) decoction, a renowned traditional Chinese formula for diabetes mellitus, has also been employed to treat intestinal disorders. Previous studies have demonstrated the efficacy of SL decoction in regulating blood glucose and intestinal bacteria. Nevertheless, further analysis is required to elucidate the mechanistic link between SL decoction-mediated improvement of intestinal function and treatment of Type 2 diabetes mellitus (T2DM). Methods: Firstly, the active ingredients of SL decoction were sourced from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, with putative targets of active ingredients being predicted using the same database. Secondly, the Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were employed to screen the aforementioned targets that act on T2DM, and protein-protein interaction (PPI) networks were constructed in accordance with the results. Thirdly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), which resulted in a comprehensive analysis of the association between SL decoction for the treatment of T2DM and the modulation of intestinal functions. Finally, the effect of the SL decoction on predicted lipopolysaccharide (LPS)-related targets, as well as intestinal function markers, was validated through in vivo experimentation. Results: A total of 36 active ingredients and 145 potential targets of SL decoction were predicted. GO enrichment analysis indicated that the principal biological processes by which the SL decoction acted against T2DM were responses to LPSs, while KEGG enrichment analysis identified the nuclear factor kappa B (NF-κB) signaling pathway and toll-like receptor signaling pathway as the key pathways involved. The in vivo experiments showed that SL decoction improved glycolipid metabolism indexes, inflammatory factor levels, and LPS levels in db/db mice. The immunohistochemical results demonstrated that the SL decoction restored the expression of Occludin, Claudin-1, and ZO-1 in the intestine and inhibited the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MYD88), and NF-κB in both the intestine and pancreas. Furthermore, it may influence the levels of short-chain fatty acids (SCFAs) in feces. Conclusions: This research investigated the multigene pharmacological mechanism of SL decoction against T2DM using network pharmacology and in vivo experiments. SL decoction treatment of T2DM may reverse inflammation by inhibiting LPS-related pathway activation and improving intestinal function.

Aims: The study was aimed at assessing the role of the MiniMed780G system of glycemic control before, during, and after Ramadan among people with Type 1 diabetes (PwT1D). Methods: This is a single-center retrospective analysis of MiniMed780G system users aged 14 years and above whose glycemic profiles were collected from February 21 to May 20, 2023, which corresponds to the Hijri months of Sha'ban, Ramadan, and Shawwal 1444/1445. Data was collected, processed, and analyzed in the framework of the Medtronic Galaxy service of the One Hospital Clinical Service (OHCS) program in Dallah Hospital, Riyadh, Saudi Arabia. Data from 43 PwT1D (24 females, mean age 30 ± 11 years with 14 ± 8 years from diabetes onset) using the MiniMed780G system were collected. Results: Overall, the 3-month (Sha'ban, Ramadan, and Shawwal) mean sensor glucose (SG), time in range (TIR) (70-180 mg/dL), time below range (TBR) (54-69 mg/dL and < 54 mg/dL), time above range (TAR) (180-250 mg/dL and > 250 mg/dL), and glucose management indicator (GMI) showed no statistical differences within the three periods. No differences in insulin total daily dose have been detected, and no diabetic ketoacidosis (DKA) or severe hypoglycemia events occurred. Conclusion: The use of the MiniMed780G system is safe with favorable glycemic outcomes across nonfasting and fasting months.

This study explores a novel healthcare model employed in the primary care setting integrating a carbohydrate-reduction dietary approach and health coaching for managing prediabetes (PD) and Type 2 diabetes (T2D) in New Zealand. Using qualitative methods, we conducted focus groups with 46 patients and individual interviews with health coaches and general practitioners across two regions. Five major themes emerged from inductive thematic analysis: reduced carbohydrate lifestyles, health coaching, implementation, empowerment, and sustainability. Patients reported significant health improvements, including weight loss, reduced medication burden, and increased energy. Challenges included resistance from some medical professionals and negative public perceptions. Health coaching played a crucial role in patient care, providing individualised support and enhancing health literacy. The study found that this model both improved patient outcomes and also alleviated the burden on healthcare professionals by managing time-intensive aspects of patient care. Barriers to the adoption of this model include scepticism about low-carbohydrate diets and the need for more education and awareness among healthcare professionals. The findings suggest that this healthcare model has the potential to transform the management of PD and T2D in primary care, shifting patients from lifelong medication dependence to significant health improvements and potential disease remission or reversal.

Background: Diabetic liver injury is a serious complication due to the lack of effective treatments and the unclear pathogenesis. Ferroptosis, a form of cell death involving reactive oxygen species (ROS)-dependent lipid peroxidation (LPO), is closely linked to autophagy and diabetic complications. Therefore, this study is aimed at investigating the role of autophagy in regulating ferroptosis by modulating the degradation of acyl-CoA synthetase long-chain family member 4 (ACSL4) in diabetic hepatocytes and its potential impact on diabetic liver injury. Methods: Initially, ferroptosis and autophagy were assessed in liver tissues from streptozotocin-induced diabetic rats and in palmitic acid (PA)-treated LO2 cells. Subsequently, the study focused on elucidating the regulatory role of autophagy in mediating ferroptosis through the modulation of ACSL4 expression in PA-treated LO2 cells. Results: The results demonstrated that ACSL4-mediated ferroptosis and inhibition of autophagy were observed in diabetic hepatocytes in vivo and in PA-treated LO2 cells. Additionally, the ferroptosis inhibitor was able to mitigate the PA-induced cell death in LO2 cells. Mechanistically, the stability and expression level of the ACSL4 protein were upregulated and primarily degraded via the autophagy-lysosome pathway in PA-treated LO2 cells. The use of the autophagy inhibitor 3-methyladenine (3-MA) and the inducer rapamycin further demonstrated that autophagy regulated ferroptosis by mediating ACSL4 degradation, highlighting its critical role in diabetic liver injury. Conclusions: These results elucidate the roles of ferroptosis, autophagy, and their interactions in the pathogenesis of diabetic liver injury, offering potential therapeutic targets. Furthermore, they shed light on the pathogenesis of ferroptosis and other diabetic complications.

Type 1 diabetes (T1D) is an autoimmune chronic disorder that damages beta cells in the pancreatic islets of Langerhans and results in hyperglycemia due to the loss of insulin. Exogenous insulin therapy can save lives but does not stop disease progression. Thus, an effective therapy may require beta cell restoration and suppression of the autoimmune response. However, currently, there are no treatment options available that can reverse T1D. Within the National Clinical Trial (NCT) database, a majority of over 3000 trials to treat T1D are devoted to insulin therapy. This review focuses on noninsulin pharmacological therapies, specifically immunomodulators. Many investigational new drugs fall under this category, such as the recently FDA-approved CD3 monoclonal antibody teplizumab to delay the onset of T1D. In total, we identified 39 different immunomodulatory investigational drugs. FDA-approved teplizumab for Stage 2 T1D is discussed along with other immunomodulators that have been tested in Phase 3 clinical trials or higher, including otelixizumab (another anti-CD3 monoclonal antibody), daclizumab (an anti-CD25 monoclonal antibody), ladarixin (CXCR1/2 inhibitor), and antithymocyte globulin (ATG). Immunomodulators also play roles in islet transplantation and cellular therapies like FDA-approved Lantidra. Several immunomodulators involved in Phase 3 clinical studies of islet transplantation are also discussed, including alemtuzumab, basiliximab, etanercept, and reparixin, some already FDA-approved for other uses. These include alemtuzumab, basiliximab, etanercept, and reparixin, some of which have been FDA-approved for other uses. This review provides background, mechanism of action, results of completed trials, and adverse effects as well as details regarding ongoing clinical trials for each of these immunomodulators. Trial Registration: ClinicalTrials.gov identifier: NCT03875729, NCT01030861, NCT00129259, NCT00385697, NCT01280682; NCT03929601, NCT04598893, NCT05757713, NCT00678886, NCT01123083, NCT00064714, NCT00468117, NCT04628481, NCT01106157, NCT02215200, NCT00331162, NCT00679042, NCT01220856, NCT01817959.

Background: Olfactory dysfunction and cognitive impairment (CI) have been associated with Type 2 diabetes (T2DM), but the mechanisms underlying this association are broadly unknown. This systematic review tends to investigate the relationship between the onset of olfactory dysfunction and CI in patients with T2DM and to explore the potential role of olfactory dysfunction as an early diagnosis biomarker of CI. Methods: We conducted a systematic review consulting PubMed and Scopus. The articles considered eligible included patients with T2DM and cognitive and olfactory test. Results: The search identified a total of 145 articles, of which 13 were finally selected. The majority of these studies discovered a correlation between olfactory dysfunction and CI in individuals with T2DM. Additionally, other biomarkers such as functional magnetic resonance imaging demonstrated changes in brain regions associated with the sense of smell in T2DM patients. Conclusions: Olfactory dysfunction could be a biomarker for early diagnosis of CI in T2DM. However, these alterations are highly heterogeneous and more studies that include neuroimaging need to be conducted.