Journal of Diabetes Research最新文献

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.

Background: Limited data are available about the epidemiological characteristics and the risk factors for amputation, particularly in developing countries from Asia, especially in China. Objective: We aim to investigate the age features of patients with Type 2 diabetic foot ulcers (DFUs) and analyze the critical influencing factors predicting lower extremity amputation and major amputation. Methods: Data were retrieved from the electric medical record system to identify patients aged > 18 years with Type 2 DFU from January 1, 2017, to December 31, 2023. A logistic regression model was adopted to analyze the risk factors for amputation and major amputation. Results: Nine hundred eighteen patients with Type 2 DFU were eligible for our study, 68.2% of whom were male. In patients with Type 2 diabetes in the hospitals we studied, the prevalence of Type 2 DFU was 1.07%. A majority of patients with DFU were in the 70-79 age group in the winter season, and deaths also peaked in this age group. A total of 38.8% of patients aged 50-59 years underwent amputation. Vascular CTA, complications, history of amputation, and infection sites were the important contributing factors in patients with DFU lower extremity amputation. History of amputation and hemoglobin were the main influencing factors of patients with major amputation resulting from DFU. Conclusion: Most patients with DFU were in the age group of 50-59 years, but the majority of deaths occurred in the 70-79-year age group. Several factors influence the amputation, and those findings provide new insights into the relationship between the severity of narrowed blood vessels and the likelihood of amputation.

Background and Aims: Coronary heart disease (CHD), hypertension (HTN), depression (Dep), and Type 2 diabetes mellitus (T2DM) are often comorbid, resulting in an exacerbated patient condition and worsened prognosis. A lack of systematic metabolomic studies on comorbidities of CHD remains. Therefore, comprehensive metabolomic-based evaluation of comorbidities of CHD is necessary. Methods and Results: In the current study, 169 healthy subjects, 149 CHD subjects, 107 CHD + HTN subjects, 126 CHD + Dep subjects, and 58 CHD + T2DM subjects were recruited. Gas chromatography-mass spectrometry was used for metabolite determination, and multivariate statistical analysis was conducted to identify metabolites that are differentially expressed with the comorbidities of CHD. There were 9, 16, 14, and 10 metabolites identified in the healthy and CHD group, the CHD and CHD + HTN group, the CHD and CHD + Dep group, and the CHD and CHD + T2DM group, respectively. Six metabolic pathways were affected, involving starch and sucrose metabolism; fructose and mannose metabolism; citrate cycle; alanine, aspartate, and glutamate metabolism; fatty acid biosynthesis; and glycolysis. Conclusion: Our study has systematically elucidated the metabolic changes underlying the comorbidities of CHD, thereby providing insight into the mechanisms associated with these alterations.

Background: Young-onset diabetes (YOD) is characterised by unique diagnostic and management challenges more pronounced in resource-limited settings like Sri Lanka. Aims: We aimed to ascertain the prevalence, patterns and characteristics of YOD in Sri Lanka and describe the state of care. Methods: Retrospective review of baseline data of all patients enrolled in the prospective multicentre Database for Young-Onset Diabetes, Sri Lanka (DYOD-SL), was performed, from April 2021 to April 2023. Results: A total of 2531 patient data were included from 28 centres island-wide. Females were 57.6%. The median age was 20 years (interquartile range (IQR) 17, 23), and the age at diagnosis was 15 years (IQR 12, 18). Type 1 diabetes (T1D) was the commonest (57.6%), followed by Type 2 diabetes (T2D) at 34.3%. Younger age at disease onset (p < 0.001), lower BMI (p < 0.001), and diabetic ketoacidosis (DKA) at presentation (p < 0.001) favoured T1D. In the total cohort, the median HbA1c was 9.8% (IQR 7.8, 12.1) with younger patients having poorer control (p = 0.001). Prevalence of nephropathy was 8.1%, retinopathy was 6.6%, neuropathy was 4.1%, moderate-high-risk diabetic foot disease was 1.9%, and macrovascular complications were 0.5%. Hypertension and dyslipidaemia occurred in 2.7% and 14%, respectively. Among patients > 18 years, overweight and obese were 22.2% and 10.4%. Corresponding prevalence in the 5-18-year age group was 20% and 14.7%. Among the insulin users (76%) in the total cohort, the majority (64.7%) were on premixed-based insulin regimens delivered by syringes. Self-monitoring of blood glucose (BG) was reported in 71.3% of the total population. None were on continuous/flash glucose monitoring or insulin pumps. Conclusion: T1D was the commonest subtype of YOD in this hospital-based population. However, T2D was notably higher and is of significant concern. Overall, suboptimal glycaemic control and high rate of complications were noted along with substandard insulin regimens and BG monitoring.