Acta Diabetologica最新文献

Background: The interaction and combined effect of the triglyceride-glucose (TyG) index, an alternative parameter of insulin resistance, along with hypertension (HT), on the risk of peripheral arterial disease (PAD), a specific type of atherosclerotic cardiovascular disease, in individuals with type 2 diabetes (T2D) seems straightforward. However, specific research on this topic remains scarce.

Methods: In this cross-sectional study, 2027 adult participants with T2D were devided into four groups based on the mean values of TyG index and various blood pressure parameters along with its category. Binary logistic regression, interaction analysis, combined effect size, and goodness-of-fit of the constructed models were performed.

Results: The TyG index's individual effect and it's combined effect with HT, or higher systolic blood pressure (SBP) or higher mean arterial pressure in patients with T2D correlated with a higher PAD risk respectively (odds ratio [OR], 0.50, [95% confidence interval {CI} 0.28-0.89]; OR, 0.32, [95% CI 0.12-0.90]; OR, 0.35, [95% CI 0.13-0.94]; OR, 0.35, [95% CI 0.12-0.98], respectively). Only an interaction effect exists between the TyG index and SBP (multiplicative interaction{INT_M}: 1.02 [1.002, 1.038]). Combining them can significantly improve the accuracy of predicting PAD (area under the receiver operating characteristic curve {AUC}_MAX = 0.7, AUC_{Model3 + TyG index + SBP}-AUC_Model3 = 0.027). All P values were < 0.05.

Conclusion: This study suggested that TyG index and hypertension, as well as their combined and interaction effect were significantly correlated with the risk of PAD in T2D individuals.

Purpose: To evaluate different quantitative non-invasive retinal biomarkers of microvascular impairment and neurodegeneration in patients affected by mild and moderate non proliferative diabetic retinopathy (NPDR) with or without macular microaneurysms (MAs).

Methods: A cross-sectional case-control study. Ninety-seven eyes with NPDR, 49 with no central MAs and 48 with central MAs, underwent color fundus photography and optical coherence tomography (OCT)/OCT-angiography (OCT-A). Thickness of central macula, retinal nerve fiber layer (NFL), ganglion cell layer (GCL+) and NFL + GCL + was evaluated on OCT. FAZ metrics (ImageJ), perfusion and vessel density (PD/VD), and fractal dimension (FD) (MATLAB) were evaluated on 3 × 3 OCT-A slabs of both superficial and deep capillary plexuses (SCP/DCP). All evaluations were performed on the full image and after subdivision in 4 quadrants.

Results: In the MA group, 77 MAs were detected (45.5% in the DCP). The MA group showed: increased FAZ area and perimeter in the SCP (p < 0.01) and DCP (p = 0.02), and reduced circularity index in the SCP (p = 0.03); reduced VD in the SCP (p < 0.01) and reduced PD, VD (p < 0.01) and FD (p = 0.02) in the DCP; decreased VD and FD in the SCP (p = 0.02 and p = 0.05), and in VD and FD in the DCP in the inferior quadrant (p = 0.04 and p = 0.03); a decrease in VD in the SCP in the nasal quadrant (p = 0.05). No differences have been detected in OCT parameters.

Conclusions: Our results suggest that the presence of central MAs in patients with NPDR may correlate with more pronounced macular microvascular impairment, particularly during the mild and moderate stages of the disease.

Aim: Glucose variation (GV) has emerged as a predictor of morbidity and mortality in persons with diabetes. However, no study has examined whether brain magnetic resonance imaging (MRI) variables mediated the association between mortality and GV.

Materials and methods: This study was a retrospective cohort comprising 3,961 individuals with type 2 diabetes (T2D), whose electronic medical records were retrieved from a medical center between January 2001 and October 2021. GV was quantified using coefficient of variation of fasting plasma glucose (FPG-CV) and glycated hemoglobin (HbA1c). The MRI variables included the presence or absence of cerebrovascular abnormality and white matter hyperintensity (WMH). All deaths and deaths resulting from expanded cardiovascular disease (CVD) were identified through annual record linkage with National Death Datasets. Cox proportional hazards models were applied to evaluate associations of MRI variable or GV with mortality. Mediation analyses were performed to assess the relative contributions of MRI variables for GV on mortality.

Results: Among 3,961 patients, 2,114 patients (53.4%) had cerebrovascular abnormality and 1,888 patients (47.7%) had WMH. The results showed cerebrovascular abnormality and WMHs were significantly associated with all-cause and expanded CVD mortality after considering GV. The largest mediated effects of GV on all-cause and expanded CVD mortality were observed by cerebrovascular abnormality (5.26% and 8.49%, respectively).

Conclusions: Our study suggests cerebrovascular abnormality and WMHs are important predictors of mortality in patients with T2D after considering GV. In addition, MRI variables of cerebrovascular abnormality expressed weak but significant mediation effect on the associations between GV and mortality.

Aims: Assessment of left atrial (LA) function and the left atrioventricular coupling index (LACI) have recently been increasingly recognized as important indices for cardiovascular diseases associated with the presence of prediabetes and diabetes. We aimed to evaluate LA function and the LACI in patients with prediabetes and diabetes via cardiac magnetic resonance (CMR).

Methods: In this retrospective study, we included 35 patients with prediabetes, 32 patients with diabetes, and 84 healthy control participants. The LACI and LA total, passive, and active emptying fractions (LATEmF, LAPEmF, and LAAEmF, respectively) were calculated. The LA reservoir, conduit, and booster pump strains (ε_s, ε_e, and ε_a), and peak positive, peak early negative, and peak late negative strain rates (SRs, SRe, and SRa) were obtained via CMR-feature tracking (CMR-FT). For the statistical analyses, one-way analysis of variance, the Kruskal-Wallis test, and linear regression were conducted, and Pearson's and interclass correlation coefficients were calculated.

Results: Compared with healthy control participants, patients with prediabetes or diabetes presented lower ε_s and ε_e values and a relatively preserved LACI. Patients with diabetes presented considerably reduced SRs, SRe, and LAPEmF. Elevated glycated haemoglobin (HbA1c) levels were independently associated with decreased magnitudes of ε_s, SRs, ε_e, and SRe. No significant associations were found between the LACI and the HbA1c or LA deformation parameters. We observed significant correlations between LATEmF and ε_s, LAPEmF and ε_e and between LAAEmF and ε_a.

Conclusions: CMR-FT provides a potential noninvasive approach for the early detection of alterations in the LA reservoir and conduit function in individuals with prediabetes and diabetes.

Objective: Genome-wide association studies (GWAS) have identified that 6p22.2 region is associated with type 1 diabetes (T1D) risk in the Chinese Han population. This study aims to reveal associations between this risk region and T1D subgroups and related clinical features, and further identify causal variant(s) and target gene(s) in this region.

Methods: 2608 T1D and 4814 healthy controls were recruited from East, Central, and South China. Baseline data and genotyping for rs4320356 were collected. The most likely causal variant and gene were identified by bioinformatics analysis, dual-luciferase reporter assays, expression quantitative trait loci (eQTL), and functional annotation of the non-coding region within the 6p22.2 region.

Results: The leading variant rs4320356 in the 6p22.2 region was associated with T1D risk in the Chinese and Europeans. However, this variant was not significantly associated with islet function or autoimmunity. In silico analysis suggested rs9379874 was the most potential causal variant for T1D risk among thymus, spleen, and T cells, overlapping with the enhancer-related histone mark in multiple T cell subsets. Dual luciferase reporter assay and eQTL showed that the T allele of rs9379874 increased BTN3A1 expression by binding to FOXA1. Public single-cell RNA sequencing analysis indicated that BTN3A1 was related to T-cell activation, ATP metabolism, and cytokine metabolism pathways, which might contribute to T1D development.

Conclusion: This study indicates that a functional variant rs9379874 regulates BTN3A1 expression, expanding the genomic landscape of T1D risk and offering a potential target for developing novel therapies.

Background: Diabetic nephropathy (DN) is a grave complication and the most common renal dysfunction of diabetes mellitus. Genetic factors, including Apolipoprotein E (APOE) isoforms, have been implicated in the pathogenesis of DN.

Methods: A total of 577 type 2 Diabetes mellitus subjects were categorized into diabetes non-nephropathic (Controls: n = 321), diabetes nephropathic (DN: n = 256) groups. Demographic, clinical, and biochemical parameters including age, BMI, lipid profiles (TC, LDL-C, HDL-C, TG), glucose metabolism (plasma glucose, HbA1c, serum insulin), renal function (UACR, PCR), and blood pressure (SBP, DBP) were assessed. APOE variant frequencies were determined using restriction fragment length polymorphism (RFLP) analysis, validated against Hardy-Weinberg equilibrium (HWE), and statistically correlated with each clinical and biochemical parameter.

Results: The DN group had an increased prevalence of hypertension, fatty liver, and dyslipidemia compared to the Control group. Biochemical analyses revealed elevated levels of TC (213.41 mg/dL vs. 189.32 mg/dL), LDL-C (134.46 mg/dL vs. 107.56 mg/dL), and reduced HDL-C (58.13 mg/dL vs. 65.32 mg/dL) in DN cases compared to Controls (all p < 0.0001). The APOE variants distribution showed a significant increase in E2 allele frequency (69.1% vs. 15.3%) and corresponding homozygous genotype (E2/2: 42.2% vs. 5.6%) in DN cohorts.

Conclusion: The study found a higher frequency of E2 allele in the DN group compared to Controls, though no statistically significant risk of DN was linked to this allele. The results suggest a potential association for APOE polymorphisms, requiring broader studies to clarify the role of APOE polymorphisms in DN susceptibility.

Aims: Diabetes mellitus (DM) often leads to wound healing complications, partly attributed to the accumulation of advanced glycosylation end products (AGEs) that impair fibroblast function. Far Upstream Element Binding Protein 1 (FUBP1) regulates cell proliferation, migration, and collagen synthesis. However, the impact of FUBP1 on diabetic wound healing remains unknown. This study is designed to explore the function and mechanisms of FUBP1 in diabetic wound healing.

Methods: Eighteen Sprague-Dawley rats (weighing 220-240 g) were randomly assigned to three groups (n = 6): a control group (NC) of healthy rats, a model group (DM) of untreated diabetic rats, and a treatment group (DM + FUBP1) of diabetic rats accepting FUBP1 treatment. A 10 mm diameter circular full-thickness skin defect was created on the back of each rat. On days 1 and 7, rats in the treatment group received local injections of 5 µg FUBP1 protein at the wound site, whereas the control group and model group were administered saline. Wound healing was documented on days 0, 3, 7, 10, and 14, with tissue samples from the wound areas collected on day 14 for histological analysis, including H&E staining, Masson's trichrome staining, and immunohistochemistry. Western blot analysis was utilized to assess the expression of GSK-3β, Wnt3a, and β-catenin. In vitro, the effects of various concentrations of AGEs on cell viability and FUBP1 expression were examined in human dermal fibroblasts (HDF). Cells were genetically modified to overexpress FUBP1 using lentiviral vectors and were cultured for 48 h in media with or without AGEs. The impacts on fibroblast proliferation, migration, and Wnt/β-catenin signaling were evaluated using CCK-8, scratch assays, and Western blot analysis.

Results: Animal investigation revealed that from day 7 onwards, the wound healing rate of the treatment group was higher than that of the model group but lower than the control group. On day 14, the wound healing rates were as follows: control group (0.97 ± 0.01), model group (0.84 ± 0.03), and treatment group (0.93 ± 0.01). These differences were statistically significant. Histological analysis indicates that FUBP1 promotes granulation tissue formation, re-epithelialization, and collagen deposition in treatment group. Additionally, FUBP1 protein expression decreased in dermal fibroblasts when exposed to AGEs. Overexpression of FUBP1 significantly enhanced fibroblast proliferation and migration, activating the Wnt/β-catenin pathway and mitigating the inhibitory effects of AGEs.

Conclusions: Our results suggest that FUBP1 can be a promising therapeutic target for diabetic wound healing, potentially counteracting the detrimental effects of AGEs on dermal fibroblasts through the Wnt/β-catenin pathway.

Aims: To evaluate glucose metrics, device satisfaction and diabetes impact in adults with type 1 diabetes using different treatment modalities in a real-life setting in Italy.

Methods: This was a multicentre, nationwide, cross-sectional study. Candidates were consecutively evaluated for eligibility during their routine medical visit at the diabetes centre. Researchers collected comprehensive demographic, socioeconomic, anamnestic and clinical data, and administered the Diabetes Impact and Device Satisfaction scale.

Results: From 2021 to 2022, a total of 428 subjects, 45% males, with a median age of 32 years (IQR 23-47) were recruited in 11 participating centres from all over Italy. No differences in age, physical activity, and diabetes impact were found for the different treatment modalities. HCL/AHCL and SAP groups reported higher device satisfaction vs. MDI + SMBG and MDI + CGM (p < 0.001). Subjects treated with HCL/AHCL exhibited significantly higher TIR and significantly lower time spent in hypoglycemia level 1, time spent in hyperglycemia, CV and GMI compared to MDI + CGM, and significantly higher TIR and significantly lower time spent in hypoglycemia level 2, time spent in hyperglycemia, and CV compared to SAP. Significant reduction in hypoglycemia level 2 was also found with PLGM compared to SAP. High education attainment was associated with optimal metabolic control.

Conclusion: Real-life use of advanced technologies for type 1 diabetes is associated with improved glucose metrics and device satisfaction. Education level also contributes to success of treatment.

Background: Following rapid population growth and urbanization, global ultra-processed food consumption levels have increased. Additionally, type 2 diabetes mellitus, a non-communicable disease, is affecting one-tenth of the people worldwide. In this study, we aimed to investigate the association between ultra-processed food consumption and the risk of type 2 diabetes mellitus in different scenarios in a prospective cohort study in the western part of Iran.

Methods: The RaNCD cohort includes 10,047 participants aged 35 to 65; we included participants susceptible to diabetes at enrolment with follow-up data. We used the widely accepted Nova classification to define ultra-processed foods. A multivariable Cox proportional hazards regression model was used as the main model; furthermore, the Cox model with different adjustments and the logistic regression model were used as sensitive analysis to evaluate the association between ultra-processed foods consumption and type 2 diabetes mellitus.

Results: A total of 8827 participants with a mean age of 46.92y, a mean follow-up time of 7.1y, and a mean daily ultra-processed food intake of 87.69 g were included. During the follow-up phases, we included 255 incidences of type 2 diabetes mellitus cases. After adjusting for confounders in the primary model, including age, gender, residence type, socioeconomic status, physical activity, body mass index, and familial history of diabetes despite the elevated hazard ratio of 1.08 (0.75, 1.55) in the fourth quartile compared to the first quartile, the P-value was insignificant (p-value = 0.665); p for trend in the UPF quartiles was also insignificant.

Conclusion: Our study has shed light on the association between ultra-processed food consumption and the risk of type 2 diabetes mellitus. However, further investigations are necessary to confirm or refute the UPFs/T2DM association.