Acta Diabetologica最新文献

Background: Osteomyelitis (OM) associated with diabetic foot ulceration (DFU) is a growing public health challenge worldwide. Since 2012 the number of patients presenting with DFU per year to our centre has doubled.

Objective: This study aims to evaluate outcomes from outpatient antibiotic therapy (OPAT) in the management of OM in DFU patients.

Methods: A retrospective analysis was performed of medical notes, radiology, and vascular laboratory reports for all DFU patients with OM treated from April 2016 to April 2020. Variables analyzed included age, gender, site of OM, WIfI Score (Wound Ischaemia and foot Infection Score), probe-to-bone test (PTB), imaging (X-ray/magnetic resonance imaging (MRI), co-morbidities (peripheral arterial disease (PAD), chronic kidney disease (CKD), hypertension (HTN), smoking, ischemic heart disease (IHD), and dyslipidaemia. Outcomes evaluated were healing, recurrent DFU, and freedom from amputation at 12 months.

Results: 185 patients were admitted with 264 infected digits (Male 223; Female 41). The mean age was 66 years. Only 168 (63.6%) were fully healed at 12 months. Of the 96 patients who failed to heal, 43 underwent a repeat course of prolonged antibiotics without improvement. Factors associated with treatment failure were PAD, poorly controlled HbA1c and Deep or Extensive Ulcer or Gangrene.

Conclusion: Extended outpatient antibiotic therapy (with an inpatient multidisciplinary approach) is an effective treatment for digital OM in DFU with a success rate of 63%. In recurrence, repeating prolonged antibiotics is unlikely to achieve healing. PAD, poorly controlled HbA1c and Deep or Extensive Ulcer or Gangrene are predictors of treatment failure.

Cystic fibrosis (CF)-related diabetes (CFRD), characterized by partial to complete impaired insulin secretion, is the most common extra-pulmonary complication of CF. Actually, insulin is the only approved therapy for its management. Advanced hybrid closed loop (AHCL) systems are the gold standard therapy for type 1 diabetes and have been proposed for other insulin-dependent forms of diabetes, including CFRD. With AHCL systems, people with CFRD can better manage several typical disease-related issues, such as minimal insulin requirements, its variability due to exacerbations or concomitant steroid therapies, nutritional behaviors, the co-existence of CF complications as intestinal malabsorption or liver disease. SmartGuard, the AHCL system for Medtronic Minimed 780G, requires a minimum of 8 units per day to operate. In this paper, we expose a case of two young women with CFRD with total daily insulin requirements < 8 UI, using off-label SmartGuard system over a 3 years of follow-up period, suggesting an evaluation of its use also in people with minimal insulin needs, considering its beneficial impact in glucose control and quality of life.

Background: Diabetic Kidney Disease (DKD) is a complex disease associated with circadian rhythm and biological clock regulation disorders. Melatonin (MT) is considered a hormone with renal protective effects, but its mechanism of action in DKD is unclear.

Methods: We used the GSE151325 dataset from the GEO database for differential gene analysis and further explored related genes and pathways through GO and KEGG analysis and PPI network analysis. Additionally, this study used a type 2 diabetes db/db mouse model and investigated the role of melatonin in DKD and its relationship with clock genes through immunohistochemistry, Western blot, real-time PCR, ELISA, chromatin immunoprecipitation (ChIP), dual-luciferase reporter technology, and liposome transfection technology to study DEC1 siRNA.

Results: Bioinformatics analysis revealed the central position of clock genes such as CLOCK, DEC1, Bhlhe41, CRY1, and RORB in DKD. Their interaction with key inflammatory regulators may reveal melatonin's potential mechanism in treating diabetic kidney disease. Further experimental results showed that melatonin significantly improved the renal pathological changes in db/db mice, reduced body weight and blood sugar, regulated clock genes in renal tissue, and downregulated the TLR2/MyD88/NF-κB signaling pathway. We found that the transcription factor DEC1 can bind to the TLR2 promoter and activate its transcription, while CLOCK's effect is unclear. Liposome transfection experiments further confirmed the effect of DEC1 on the TLR2/MyD88/NF-κB signaling pathway.

Conclusion: Melatonin shows significant renal protective effects by regulating clock genes and downregulating the TLR2/MyD88/NF-κB signaling pathway. The transcription factor DEC1 may become a key regulatory factor for renal inflammation and fibrosis by activating TLR2 promoter transcription. These findings provide new perspectives and directions for the potential application of melatonin in DKD treatment.

Aims: Diabetic retinopathy (DR) is a severe complication of diabetes mellitus (DM), and it is challenging to diagnose DR at an early stage by conventional methods. The aim of the present work is to propose an innovative approach to monitor the process of DR from scratch.

Methods: The plasma metabolites changed with DM were obtained by time-dependent metabolomics and lipidomics; the change of retinal function was measured by b-wave amplitude and total Ops-wave amplitude in electroretinography (ERG). Multivariate statistical analysis, logistic regression and correlation analysis were employed to identify metabolic markers from metabolites for the monitoring of DR and investigate the relationship between metabolic markers and retinal function.

Results: The metabolic markers LPE18:0, LPC15:0, SM d14:2/26:0, SM d12:0/28:2 and MG 21:0 associated with DR can be utilized as metabolic markers to monitor the process of DR; The decrease in myo-inositol and LPC22:5 and increase in xylonic acid and TAG10:0/16:0/18:1 indicated retinal dysfunction.

Conclusions: The levels of metabolic markers can be used as an indicator of the onset of DR or as a means of monitoring changes in retinal function.

Aims: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene-gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM).

Methods: SNPstats online software ( https://www.snpstats.net/start.htm ) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus ( http://shesisplus.bio-x.cn/SHEsis.html ) online software was used for haplotype analysis.

Results: A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13-2.01), 1.44 (1.10-1.89) and 1.25 (1.01-1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18-0.79) and 0.37 (0.16-0.80) for codominant and recessive models, respectively. No significant gene-gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68-0.98), P = 0.047.

Conclusions: Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk.

Aims: Inflammation plays a crucial role in the interconnection between diabetes and cancer. Our study seeks to investigate the predictive value of inflammatory indices concerning overall survival (OS) among diabetic cancer patients.

Methods: We analyzed data from the National Health and Nutrition Examination Survey between 1999 and 2020. Using four immune-related markers, we employed the log-rank method, multivariate Cox regression, and subgroup analysis to explore the predictive capacity of these markers for OS among adult individuals with diabetes and cancer.

Results: Our study identified four systemic immune-inflammatory indices that demonstrated significant predictive potential for OS among diabetic cancer patients, namely systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (all p values < 0.05). Notably, these inflammatory biomarkers still maintain their predictive value after adjusting potential confounding factors. The analysis using restrictive cubic splines revealed significant non-linear relationships between inflammatory biomarkers and OS.

Conclusion: The findings presented in this study underscore the potential of inflammatory markers as prognostic indicators and their crucial role in enhancing risk assessment for diabetic patients with cancer.

Aims: Estimated glucose disposal rate (eGDR), a noninvasive and convenient measure of insulin resistance, has been demonstrated to be associated with mortality in both type 1 and type 2 diabetes. We aimed to explore whether eGDR is associated with cardiovascular disease (CVD) risk and mortality in prediabetic adults.

Methods: A nationwide population-based cohort of prediabetic individuals from the National Health and Nutrition Examination Survey 1999-2018 with available data on eGDR was included and categorized into eGDR ≥ 8 (reference), 6-7.99, 4-5.99, and < 4 mg/kg/min groups. Cox proportional hazards model was used to estimate the associations of eGDR with mortality.

Results: A total of 4725 prediabetic adults, 60.12% men, mean age 48 years were included. The odds ratio and 95% confidence interval (CI) for CVD risk were 1.74 (1.08-2.78), 2.90 (1.79-4.67), and 4.58 (2.15-9.76) for the eGDR 6-7.99, 4-5.99, and < 4 mg/kg/min groups, respectively, compared with the reference group. There were 410 deaths (116 CVD-related) during a median follow-up of 107 months in 4,332 participants without baseline CVD. The hazard ratios and 95%CI for the eGDR 6-7.99, 4-5.99, and < 4 mg/kg/min groups were 1.70 (1.23-2.35), 2.01 (1.45-2.77), and 1.84 (1.11-3.04), respectively, for all-cause mortality (P for trend < 0.0001), and 3.84 (2.04-7.21), 4.01 (2.01-8.00), and 2.88 (1.03-8.06), respectively, for CVD mortality (P for trend = 0.01). Smoking status significantly modified the associations between eGDR and all-cause or CVD mortality.

Conclusions: Increased insulin resistance, as indicated by a lower eGDR, is associated with increased risks of all-cause and CVD mortality in U.S. prediabetic adults.

Aims: Diabetic kidney disease (DKD) significantly impairs quality of life in individuals with diabetes mellitus (DM). The influence of the Dietary Inflammatory Index (DII) on DKD, which is associated with adverse health outcomes, is not well-understood.

Methods: We analyzed 2712 subjects from the National Health and Nutrition Examination Survey (NHANES) spanning 2011-2018, aiming to elucidate the relationship between DII and DKD.

Results: DKD was diagnosed in 1016 participants (37.46%). Elevated DII levels were significantly associated with an increased DKD risk, as evidenced by multivariate logistic regression (Odds Ratio [OR] = 1.40, 95% Confidence Interval [CI] 1.12-1.75, P < 0.05). Further analysis after adjusting for covariates highlighted a notable non-linear correlation between DII and DKD risk, at DII values below 0.45, the risk of DKD increases with higher DII levels, whereas it stabilizes beyond this point. Subgroup analysis additionally revealed that diabetic men have a significantly higher DKD risk compared to women (P < 0.05).

Conclusion: Our study indicates a pronounced link between higher DII scores and increased risk of DKD among DM patients. These findings underscore the paramount importance of dietary management in DM treatment, stressing the need for interventions focused on reducing dietary inflammation to decelerate DKD progression.

Aims: Diastolic dysfunction represents the earliest and most common manifestation of diabetic cardiomyopathy. Nitric oxide (NO), a potent vasodilator and anti-inflammatory mediator released from the subendocardial and coronary endothelium, favors left ventricular distensibility and relaxation. In type 2 diabetes (T2D), the NO bioavailability is reduced due to the oxidative stress and inflammatory state of the endothelium, because of chronic hyperglycemia. The aim of the present research is to evaluate the relationship between endothelial function and diastolic function in subjects with T2D.

Method: Subjects with T2D and age and sex-matched healthy controls were consecutively recruited. All participants underwent flow-mediated dilation (FMD) to assess endothelial function, and echocardiography to evaluate diastolic function.

Results: Thirty-five patients (6 women, 29 men) and 35 healthy controls were included in the final analysis. FMD was significantly lower in T2D than controls (4.4 ± 3.4 vs. 8.5 ± 4.3%, p = 0.001). T2D presented different abnormalities in diastolic function compared to controls: lower E/A (early to late diastolic transmitral flow velocity), lower septal and lateral e' (early diastolic myocardial tissue velocity at septum and lateral wall), and higher E/e' (surrogate of filling pressure). In subjects with T2D, we observed a significant correlation between FMD and E/e' (r = -0.63, p = 0.001), lateral e' (r = 0.44, p = 0.03), and septal e' (r = 0.39, p = 0.05).

Conclusions: Our observational study demonstrated a link between FMD and diastolic dysfunction in subjects with type 2 diabetes.

Aims: Streptozotocin (STZ) is widely used to study diabetic complications. Owing to the nonspecific cytotoxicity of high-dose STZ, alternative models using moderate-dose or a combination of low-dose STZ and a high-fat diet have been established. This study aimed to investigate the effects of these models on muscle function.

Methods: The muscle function of two STZ models using moderate-dose STZ (100 mg/kg, twice) and a combination of low-dose STZ and high-fat diet (50 mg/kg for 5 consecutive days + 45% high-fat diet) were examined using in vivo electrical stimulation. Biochemical and gene expression analysis were conducted on the skeletal muscles of the models immediately after the stimulation.

Results: The contractile force did not differ significantly between the models compared to respective controls. However, the moderate-dose STZ model showed more severe fatigue and blunted exercise-induced glycogen degradation possibly thorough a downregulation of oxidative phosphorylation- and vasculature development-related genes expression.

Conclusions: Moderate-dose STZ model is suitable for fatigability assessment in diabetes and careful understanding on the molecular signatures of each model is necessary to guide the selection of suitable models to study diabetic myopathy.