Acta Diabetologica[JOURNAL]
Sun
200 papers
miR-125a-5p promotes normal angiogenesis in diabetic foot ulcers by targeting GSTM5.
Huang F, Zhou Y, Wu H … +1 more , Ma F
Acta Diabetol · 2026 Mar · PMID 41091197 · Publisher ↗
BACKGROUND: Reduced angiogenesis is a key factor in impaired healing diabetic foot ulcers. It is critical to identifying the relevant genes that regulate angiogenesis or the relevant mechanisms that accelerate angiogenes...
BACKGROUND: Reduced angiogenesis is a key factor in impaired healing diabetic foot ulcers. It is critical to identifying the relevant genes that regulate angiogenesis or the relevant mechanisms that accelerate angiogenesis, which is essential for the treatment of Diabetic foot ulcers (DFU). METHODS: Direct targeting of miR-125a-5p to Glutathione S-Transferase M5 (GSTM5) was demonstrated by dual luciferase assays. MiR-125a-5p and GSTM5 were induced or silenced by HGM in endothelial cells in vitro, and the results were compared with a blank control to determine the mechanism of miR-125a-5p and GSTM5 expression levels on DFU. RESULTS: Initial analysis revealed distinct expression patterns of miR-125a-5p and GSTM5 between acute and chronic DFU patients. Their regulatory roles were investigated by comparing differential expression profiles in these two patient groups. We found that low expression of both in chronic DFU patients was positively correlated with changes in angiogenic markers. Inhibition of miR-125a-5p and GSTM5 in endothelial cells in vitro yielded the same results, demonstrating the promote angiogenesis of their expression on angiogenesis. CONCLUSION: MiR-125a-5p promotes normal angiogenesis in diabetic foot ulcers by targeting GSTM5.
The close relationship between inflammation and insulin resistance: a comparative perspective from a new angle.
Wang X, Yang R, Li J … +5 more , Liang Y, Jin C, Xu Y, Wu X, Zou M
Acta Diabetol · 2026 Mar · PMID 41091196 · Full text
BACKGROUND: Excess weight is a progressive metabolic epidemic, and inflammation plays an important role in the progression of disease. Insulin resistance (IR) is an important feature of obesity, but it does not reflect s...
BACKGROUND: Excess weight is a progressive metabolic epidemic, and inflammation plays an important role in the progression of disease. Insulin resistance (IR) is an important feature of obesity, but it does not reflect systemic inflammation. Currently, there is a lack of effective clinical tools for early risk stratification and intervention in physically active people. METHODS: This was a prospective cohort of 72,262 overweight but physically active persons in the UK Biobank. The TyG was combined with hsCRP, waist circumference (WC), or body mass index (BMI) as indices of IR. Adjusted Cox regression, interaction tests, restricted cubic splines (RCS) analysis, Kaplan-Meier analysis, and Harrell's C-index were used to examine the relations and time-dependent predictive power. RESULTS: During 12.7 years of follow-up, 1,477 participants developed metabolic dysfunction-associated fatty liver disease (MAFLD). RCS analysis suggested TyG-hsCRP had a nonlinear positive correlations with all-cause mortality. Compared to the lowest quartile group, the corrected hazard ratio (HR) (95% confidence interval [CI]) of new-onset MAFLD in maximum quartile groups for TyG-hsCRP was 1.94(1.62-2.32), for TyG-WC was 1.78(1.44-2.18), for TyG-BMI was 1.36(1.12-1.65), and for TyG was 1.41(1.15-1.72). The relation between C-index of TyG-hsCRP and MAFLD was higher than that of other TyG indices. Similar results were observed in all-cause mortality. CONCLUSION: TyG-hsCRP is superior to other indices for identifying risk of MAFLD and all-cause mortality in overweight but physically active people. Our findings suggest the importance of inflammatory metabolism and provide evidence for effectively early anti-inflammatory treatments.
Nutrient intake order on metabolic outcomes in type 2 diabetes: a systematic review and meta-analysis.
Saldarriaga-Callejas LM, Ratan P, Pasqualotto E … +2 more , Bovi T, Trevisan T
Acta Diabetol · 2026 Mar · PMID 41081830 · Publisher ↗
INTRODUCTION AND OBJECTIVE: Macronutrient sequence has been proposed as a practical strategy to improve postprandial glycemia in individuals with type 2 diabetes (T2D). However, current evidence remains inconclusive. Thi...
INTRODUCTION AND OBJECTIVE: Macronutrient sequence has been proposed as a practical strategy to improve postprandial glycemia in individuals with type 2 diabetes (T2D). However, current evidence remains inconclusive. This meta-analysis aims to provide an updated evaluation of the impact of a carbohydrate-last (CL) strategy, compared to carbohydrate-first or unordered (CF) intake, on metabolic parameters in adults with T2D. METHODS: A systematic search was conducted in PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) evaluating nutrient intake order in T2D. Outcomes were analyzed using mean difference (MD) with 95% confidence intervals (CI) under a random-effects model. Heterogeneity was assessed using Cochrane's Q test and I² statistics. Analyses were conducted using R, version 4.4.2. RESULTS: Seventeen studies involving 389 participants were included, with 114 (29%) in a parallel design and 192 (49%) in a crossover design receiving CL. In the pooled analysis, the CL group had significantly lower postprandial glucose at 60 min (MD: -42.73 mg/dL; 95% CI: -55.51, -29.96; p < 0.01) and 120 min (MD: -13.00 mg/dL; 95% CI: -21.07, -4.94; p < 0.01), higher postprandial glucagon-like peptide-1 (GLP-1) levels (MD: 8.21 pmol/L; 95% CI: 2.34, 14.09; p < 0.01), delayed gastric emptying half-time (MD: 28.14 min; 95% CI: 16.06, 40.23; p < 0.01), and reduced glycated hemoglobin (HbA1c) at follow-up (MD: -0.16%; 95% CI: -0.31, -0.01; p = 0.04). CONCLUSION: Carbohydrate-last eating pattern has been shown to improve postprandial glycemia, enhance GLP-1 secretion, and delay gastric emptying, with a minimal effect on HbA1c in individuals with mild T2D. Further research is needed to confirm its applicability in advanced disease stages and to establish long-term metabolic benefits.
Therapeutic potential of copper II oxide in treating diabetic wounds: an emerging approach for enhanced healing.
Bogadi S, Uddin ME, Karri VVSR … +6 more , Begum R, Kader MA, Abullais SS, Reza MS, Alexiou A, Papadakis M
Acta Diabetol · 2026 Jan · PMID 41055721 · Publisher ↗
Diabetes is the most serious consequence of Type 2 Diabetes Mellitus, which affects almost all vital organs in the human body. According to the World Health Organization, 537 million adults worldwide are affected by diab...
Diabetes is the most serious consequence of Type 2 Diabetes Mellitus, which affects almost all vital organs in the human body. According to the World Health Organization, 537 million adults worldwide are affected by diabetes and its complications. By 2030, this figure is expected to reach 643 million, and by 2045, it will reach 783 million. Up to 25% of diabetic patients experience the equivalent foot Ulcer (Diabetic wound). Infections result in hospitalization in more than 50% of wounds, and 20% of infections necessitate amputations. In India, people with DWs account for 80% of all non-traumatic amputations performed yearly. The rise in blood sugar levels, reflected by a chronic hyperglycemic state, is a significant contributor to the failure of the healing process. This is because the extremities do not get enough blood, which reduces oxygen. In diabetic wounds, oxidative stress plays a critical role in stabilizing Hypoxia hypoxia-inducible factor (HIF-1 α). Numerous researchers have looked into the theory that oxidative stress in a specific area causes delayed chronic diabetic wounds. Some of the existing remedies, such as hyperbaric oxygen inhalation therapy (HBO) and other topical gaseous oxygen (TGO) administration, have certain drawbacks, such as the inability to stop oxidative stress in particular regions of the wound that cannot synthesize oxygen in the target site. Therefore, it is crucial to reduce oxidative stress in chronic diabetic wounds. In this review, we focus on metal oxide-related nanoparticles such as copper II oxide, which act as an anti-oxidant activity property by lowering the oxidative stress and stabilizing Hypoxia Inducible Factor (HIF), which in turn encourages proangiogenic factors and vascular endothelial growth factors to aid in wound healing.
Blunted cortisol and altered antioxidant defense as biomarkers of systemic stress in hyperglycemic Zebrafish.
Minz R, Sharma PK
Acta Diabetol · 2026 Mar · PMID 41055720 · Publisher ↗
BACKGROUND/AIM: Emerging evidence links hyperglycemia, a "hallmark of diabetes mellitus" not only to peripheral metabolic dysfunction but also to its detrimental impact on brain health, often contributing to stress-relat...
BACKGROUND/AIM: Emerging evidence links hyperglycemia, a "hallmark of diabetes mellitus" not only to peripheral metabolic dysfunction but also to its detrimental impact on brain health, often contributing to stress-related pathologies such as depression and cognitive decline. Zebrafish, with their well-characterized vascular system and behavioral assays, offer a unique model to study the impacts of sucrose-induced hyperglycemia. This study aims to investigates the effects of sucrose-induced hyperglycemia on stress mechanisms in type 2 diabetes using the zebrafish. METHODS: Male zebrafish were divided into two groups: control, and 55.5mM sucrose immersed. Over two weeks, these were subjected to behavioural assays- the novel tank test (NTT) and the light/dark test (LDT). The NTT assessed anxiety-related behaviour by measuring the time spent in different vertical zones of a novel tank, while the light/dark test evaluated anxiety responses based on the time spent in illuminated versus dark compartments. Trajectory body coordinates and tail kinematics were quantified using ZebraZoom software to asses locomotor metrics status. Cortisol levels were measured to assess HPA axis function. Antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT), were quantified to evaluate oxidative stress. RESULTS: The results revealed that zebrafish exposed to sucrose exhibited significant hyperglycemia (**p < 0.01) and behavioural changes compared to those on control. Specifically, in the NTT, the hyperglycemic group demonstrated heightened anxiety-like behaviour, spending more time at the bottom zone of the tank. In the light/dark test, male zebrafish showed increased anxiety by spending more time in the dark compartment. Hyperglycemic zebrafish showed a significant blunting of the cortisol response, indicating impaired stress regulation. Additionally, SOD activity was increased, while CAT activity was decreased, suggesting an imbalance in antioxidative defense mechanisms. CONCLUSION: The zebrafish system effectively models the negative impacts of sucrose-induced hyperglycemia, providing valuable insights into the stress mechanisms associated with type 2 diabetes. These findings demonstrate that hyperglycemia alters both endocrine stress response and antioxidant systems, potentially serving as biomarkers of systemic stress.
In women with pre-existing diabetes, the contribution to pregnancy outcomes of gestational weight gain as defined by IOM guidelines, differs when adjustment for gestational age is used.
Xie X, Liu J, López A … +4 more , García-Patterson A, Adelantado JM, López E, Corcoy R
Acta Diabetol · 2026 Jan · PMID 41055719 · Publisher ↗
AIMS: To investigate the association between gestational weight gain (GWG) as per Institute of Medicine 2009 (IOM) and pregnancy outcomes in women with gestational (GDM) or preexisting diabetes mellitus (PDM), when apply...
AIMS: To investigate the association between gestational weight gain (GWG) as per Institute of Medicine 2009 (IOM) and pregnancy outcomes in women with gestational (GDM) or preexisting diabetes mellitus (PDM), when applying or not a correction for gestational age (IOM-CGWG and IOM-GWG respectively). METHODS: We conducted a retrospective analysis of pregnant women with either GDM or PDM attended in our center. Exposure variables: IOM-GWG and IOM-CGWG. OUTCOME VARIABLES: Maternal and fetal/neonatal clinical outcomes. STATISTICS: Logistic regression with adjustment for other potential independent variables. RESULTS: In women with GDM, correction for gestational age did not affect the distribution of weight gain or the association with clinical outcomes (pregnancy-induced hypertension, preeclampsia, cesarean delivery, large-for-gestational age newborns (LGA), macrosomia and small-for-gestational age newborns (SGA)). In women with PDM, correction for gestational age, caused a shift in the distribution to a higher rate of excessive weight gain. In the adjusted analysis, IOM-GWG was significantly associated with cesarean delivery, preterm birth, LGA, macrosomia, SGA and neonatal respiratory distress. With IOM-CGWG, the association with preterm birth disappeared while an association with PIH emerged. Population-attributable and preventive fraction were substantial for both women with GDM and PDM. CONCLUSIONS: We conclude that the associations of IOM-GWG and IOM-CGWG are substantial in both women with GDM and PDM, indicating an area for potential intervention. In women with PDM, the modification of associations when gestational age is accounted for is relevant, highlighting the importance of considering this variable.
Italian guidelines for the treatment of type 1 diabetes.
Pintaudi B, Bruttomesso D, Girelli A … +17 more , Indelicato L, Mannucci E, Pizzini A, Anelli V, Romeo EL, Schiaffini R, Spandonaro F, Migliore A, Orso M, D'Angela D, Polistena B, Speese K, Stara R, Targher G, Vitale M, Candido R, for Associazione Medici Diabetologi (AMD), Società Italiana di Diabetologia (SID), Italian Society for Pediatric Endocrinology, Diabetology (SIEDP)
Acta Diabetol · 2026 May · PMID 41051486 · Publisher ↗
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Non-invasive biomarkers for diabetic complications: insights from corneal and retinal imaging.
Xiao M, Chen Y, Yan X … +3 more , Wang L, Cheng H, Chen W
Acta Diabetol · 2026 Mar · PMID 41051485 · Publisher ↗
BACKGROUND: Diabetes-related complications, such as diabetic peripheral neuropathy (DPN) and chronic kidney disease (CKD), severely affect quality of life. Early detection is crucial. This study investigates ocular imagi...
BACKGROUND: Diabetes-related complications, such as diabetic peripheral neuropathy (DPN) and chronic kidney disease (CKD), severely affect quality of life. Early detection is crucial. This study investigates ocular imaging parameters as potential biomarkers for these conditions using corneal confocal microscopy (CCM) and optical coherence tomography angiography (OCTA). METHODS: This cross-sectional study included 76 type 2 diabetes patients (139 eyes) from Fujian Medical University Union Hospital. Participants underwent CCM to assess corneal nerve fiber density (CNFD), branching density (CNBD), and nerve fiber length (CNFL). OCTA and OCT were used to evaluate macular and peripapillary retinal vascular densities (VD) and retinal nerve fiber layer (RNFL) thickness. Laboratory tests measured sural nerve conduction velocity (SSNCV), urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). DPN and CKD were categorized using Toronto consensus criteria and UACR thresholds, respectively. Statistical analyses included Spearman correlation and ROC curve evaluations. RESULTS: Significant reductions in CNFD, CNBD, and CNFL were observed in the DPN + group compared to DPN- (P < 0.001, P = 0.005, P < 0.001). Corneal nerve parameters correlated positively with SSNCV (r = 0.419-0.430, P < 0.001). ROC analysis demonstrated CNFD as the most sensitive marker for detecting DPN (AUC = 0.7179, 95% CI: 0.6328-0.8031). Retinal superficial VD in the superior macular region showed the highest diagnostic performance for CKD (AUC = 0.7140, 95% CI: 0.6057-0.8223), with significant correlations between retinal VD parameters and UACR. CONCLUSIONS: Corneal nerve parameters measured by CCM and retinal vascular parameters assessed by OCTA are promising non-invasive biomarkers for early detection and monitoring of diabetic neuropathic and microvascular disorders.
Preliminary real-world observational data on A8 TouchCare use in adults with type 1 diabetes.
Borella ND, Corsi A, Scaranna C … +2 more , Trevisan R, Lepore G
Acta Diabetol · 2025 Dec · PMID 41051484 · Publisher ↗
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Metrics in pregnancy: is it the time for new glycaemic goals for pregnant women with type 1 diabetes? An experience with advanced hybrid closed loop.
Bitterman O, Fresa R, Napoli A
Acta Diabetol · 2026 Mar · PMID 41051483 · Publisher ↗
INTRODUCTION: Recommended pregnancy specific Time in Range (TIR) 63-140 mg/dl is a quite wide range and, even if the goal of > 70% is achieved, the specific targets for fasting and mean glycaemia, which are much lower th...
INTRODUCTION: Recommended pregnancy specific Time in Range (TIR) 63-140 mg/dl is a quite wide range and, even if the goal of > 70% is achieved, the specific targets for fasting and mean glycaemia, which are much lower than 140 mg/dl, could not be complied. This case series aimed to explore the performance of an Advanced Hybrid closed Loop (AHCL) in pregnancy on a stricter glycaemic range. METHODS: We collected retrospective data about recommended glucose metrics and an hypothetic TITR 63-95 mg/dl, more suitable for fasting periods, from 11 type 1 diabetes patients, using Medtronic MiniMed™ 780G, with glucose target 100 mg/dl and Active Insulin Time 2 h, from preconceptional phase until delivery. RESULTS: TIR 63-140 mg/dl quickly improved throughout pregnancy, with progressively improving HbA1c and no significant changes in Time Below Range (TBR). TITR 63-95 mg/dl was 26% in the 1st trimester, 20% in the 2nd and 30% in the 3rd, corresponding to 6, 5 and 7 h per day, less than the hypothetic 8/24 hours of fasting. TAR > 140 reduced more compared to TAR > 95, reflecting a greater improve in postprandial values than in fasting. CONCLUSIONS: Although the AHCL Medtronic MiniMed™ 780G helped improving glycaemic control during pregnancy, our patients spent very few hours in the range 63-95 mg/dl, probably because they did not reach fasting glucose goals. A stricter TIR may be hypothesized for pregnant women too, as an additional goal along with TIR 63-140 mg/dl, but studies are needed to explore the consequences on maternal and fetal outcomes.
Development and validation of a risk predictive nomogram for carotid intima-media thickening in patients with type 2 diabetes.
Zheng Y, Tuo L, Xiao J … +2 more , Ling R, Yan L
Acta Diabetol · 2026 Jan · PMID 40965634 · Publisher ↗
AIM: Carotid intima-media thickness (CIMT) serves as a valuable cardiovascular risk marker in type 2 diabetes mellitus (T2DM). We aimed to develop and validate a nomogram incorporating novel indicators, including the tri...
AIM: Carotid intima-media thickness (CIMT) serves as a valuable cardiovascular risk marker in type 2 diabetes mellitus (T2DM). We aimed to develop and validate a nomogram incorporating novel indicators, including the triglyceride-glucose (TyG) index, to predict CIMT thickening in T2DM. METHODS: In this retrospective study of 804 patients with T2DM, we employed least absolute shrinkage and selection operator regression followed by stepwise regression for predictor selection. Six machine learning models were evaluated, with model selection based on the area under the receiver operating characteristic curve (AUROC). The optimal model was used to develop the nomogram, assessed using AUROC, calibration curves, decision curve analysis (DCA), and SHapley Additive exPlanations (SHAP) for feature importance. RESULTS: Independent predictors of CIMT thickening in T2DM included age, body mass index, current smoking status, regular exercise habits, glycated hemoglobin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and TyG index. Logistic regression demonstrated excellent predictive performance and was selected for nomogram development. The predictive model showed strong discriminative ability and good calibration in both the training and testing datasets. DCA confirmed its clinical utility across relevant risk thresholds, with SHAP analysis identifying age as the most influential predictor. CONCLUSIONS: This study developed and validated a nomogram integrating routine clinical parameters and novel indicators, including the TyG index, to assess the risk of CIMT thickening in T2DM patients. This nomogram provides an evidence-based tool to help clinicians identify high-risk patients and guide early therapeutic interventions.
Low bone morphogenic protein-2 in diabetes patients with peripheral neuropathy is a correlated risk factor for the development of Charcot arthropathy.
Cassuto J, Folestad A, Ålund M … +2 more , Asteberg S, Göthlin J
Acta Diabetol · 2026 Jan · PMID 40960630 · Full text
AIMS: Diabetes patients with peripheral neuropathy run increased risk of developing Charcot arthropathy (Charcot), often associated with foot fractures. Bone morphogenic proteins (BMPs) are among the most important regul...
AIMS: Diabetes patients with peripheral neuropathy run increased risk of developing Charcot arthropathy (Charcot), often associated with foot fractures. Bone morphogenic proteins (BMPs) are among the most important regulators of bone homeostasis and fracture repair but have not been investigated in the pathophysiology of Charcot. The current study aims to address this issue. METHODS: Sixteen patients diagnosed with active Charcot were treated with total contact cast (TCC) and monitored during 24 months (M) with repeated plain radiographs and magnetic resonance imaging (MRI). Plasma was sampled at 9 occasions and analyzed for BMP-1, BMP-2, BMP-3, BMP-4, BMP-6, BMP-7 and BMP-9 as well as for basal laboratory data. Fifteen diabetes patients with peripheral neuropathy and fifteen healthy participants without diabetes served as controls. RESULTS: All Charcot patients had pathologically low BMP-2 level at inclusion which remained suppressed throughout the 2-year follow-up as defined by being lower than 2 standard deviations (SD) of BMP-2 in healthy controls (p < 0.001) and in diabetes patients with neuropathy without Charcot (p < 0.002). BMP-2 did not differ between the control groups. BMP-7 in Charcot patients increased significantly 6-12 months following TCC treatment. Other BMPs showed no significant differences between the groups at any point during the follow-up. CONCLUSIONS: Low BMP-2 in diabetes patients with neuropathy is associated with increased risk of developing Charcot fractures due to the critical role of BMP-2 for the initiation of bone repair. BMP-7 appears to partly compensate for the lack of response by other osteogenic BMPs during fracture repair in Charcot patients.
Retinopathy and nephropathy in type 1 diabetes: role of HbA1c and blood pressure variability.
Fatulla P, Ludvigsson J, Imberg H … +2 more , Nyström T, Lind M
Acta Diabetol · 2025 Dec · PMID 40960629 · Full text
AIMS: To examine the association between within-person variability in glycated hemoglobin A1c (HbA1c) and blood pressure (BP) with retinopathy and nephropathy in type 1 diabetes (T1D). METHODS: This nationwide cohort inc...
AIMS: To examine the association between within-person variability in glycated hemoglobin A1c (HbA1c) and blood pressure (BP) with retinopathy and nephropathy in type 1 diabetes (T1D). METHODS: This nationwide cohort included 9,358 individuals from the Swedish National Diabetes Register with T1D <5 years at inclusion (1998-2017) and ≥8 years follow-up. Variability in HbA1c, systolic BP (SBP), and diastolic BP (DBP) was calculated as updated SDs. Associations with microvascular complications were analyzed using logistic regression with generalized estimating equations, adjusted for demographic and clinical covariates. RESULTS: Mean age at inclusion was 14.2 years, mean diabetes duration 1.2 years, and 44% were female. Over 10.7 years' follow-up, retinopathy developed in 33% and nephropathy in 9.3%. SBP variability was significantly associated with pre-proliferative or proliferative retinopathy (aOR 1.13, 95% CI 1.00-1.27) and proliferative retinopathy/ laser photocoagulation (1.23, 1.04-1.45), as well as with any albuminuria (1.15, 1.08-1.23) and macroalbuminuria (1.29, 1.15-1.45). DBP variability was associated with any albuminuria (1.11, 1.03-1.19) and macroalbuminuria (1.28, 1.10-1.50). HbA1c variability was associated with any retinopathy (1.14, 1.08-1.20) and any albuminuria (1.12, 1.03-1.21). CONCLUSIONS: Beyond mean levels, higher variability in HbA1c and BP is associated with retinopathy and nephropathy. Stable BP control in patients with established retinopathy may be important to prevent progression to sight-threatening stages.
Modified cut-off value of the urine albumin-to-creatinine ratio is helpful for identifying patients at high risk for chronic kidney disease in prediabetes.
Liu J, Yang L, Wu J … +3 more , You L, Yan L, Ren M
Acta Diabetol · 2026 Jan · PMID 40960628 · Publisher ↗
BACKGROUND: Prediabetes is associated with higher risk of chronic kidney disease (CKD), however studies investigating the prognostic index for incident CKD in patients with prediabetes are lacking. Thus, the present stud...
BACKGROUND: Prediabetes is associated with higher risk of chronic kidney disease (CKD), however studies investigating the prognostic index for incident CKD in patients with prediabetes are lacking. Thus, the present study aims to find the risk factors for CKD in prediabetic population. METHODS: We included 1220 prediabetic participants without CKD in the REACTION study and examined the associations of clinical indicators with CKD incidence with 3.6 years of follow-up using logistic regression analyses. To explore the nonlinear relationship between the Urine Albumin-To-Creatinine Ratio (UACR) and the hazard ratio (HR) of CKD, a Restricted Cubic Spline (RCS) analysis was conducted. Logistic regression analysis was employed to assess the association between UACR categories and the risk of CKD incidence. RESULTS: There were 78 (6.4%) individuals developed CKD, and elevated UACR was observed in patients who developed CKD. UACR was an independent risk factor of CKD after adjusting for covariates and RCS presented an association between elevated UACR and higher risk of CKD incidence. UACR cutoff points of 7.54 mg/g overall was associated with the risk of CKD progression. In comparison to a UACR range of 0-7.54 mg/g (B1), those who falling within the ranges of 7.54-14.95 (B2), 14.95-22.36 (B3), and 22.36-30 (B4), exhibited a significantly increased risk of CKD development. eGFR below the threshold of 81.64 mL/min/1.73m was significantly associated with an increased risk of CKD characterized by impaired glomerular filtration. CONCLUSION: In conclusion, the novel UACR cutoff of 7.54 mg/g serves as an effective tool to identify individuals at high risk of developing CKD-ACR during the prediabetes stage.
Expression of long non-coding RNAs MALAT1, MEG3, and XIST in gestational diabetes mellitus: a cross-sectional study.
Dey BK, Banerjee S, Adhikary P … +4 more , Chowdhury S, Roy S, Roy SB, Bhattacharjee R
Acta Diabetol · 2026 Jan · PMID 40928673 · Publisher ↗
BACKGROUND AND AIMS: Gestational diabetes mellitus (GDM) is defined as glucose intolerance first identified during pregnancy that does not meet the criteria for overt diabetes. Its pathophysiology shares key features wit...
BACKGROUND AND AIMS: Gestational diabetes mellitus (GDM) is defined as glucose intolerance first identified during pregnancy that does not meet the criteria for overt diabetes. Its pathophysiology shares key features with type 2 diabetes mellitus (T2D), including insulin resistance and inflammation. Emerging evidence suggests that long non-coding RNAs (lncRNAs) are implicated in T2D. This study investigates the gene expression of lncRNAs in GDM and explores their association with insulin resistance and proinflammatory cytokines. MATERIALS AND METHODS: This cross-sectional study included 25 GDM and 36 non-GDM (NGDM) participants from a tertiary care antenatal clinic. GDM was diagnosed using a 75 g oral glucose tolerance test (OGTT) based on the International Association of Diabetes and Pregnancy Study Groups criteria. MALAT1, MEG3, and XIST were selected for analysis due to their reported involvement in T2D. Their gene expression levels were quantified using real-time PCR, while serum concentrations of proinflammatory cytokines (TNF-α, IL-6, IL-1β) and glycemic markers (C-peptide, fasting insulin) were measured using ELISA. RESULTS: MALAT1, MEG3, and XIST were significantly downregulated in the GDM group compared to the NGDM group (p < 0.01). In the GDM group, all three lncRNAs showed a significant negative correlation with Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) (MALAT1: r = -0.44, p = 0.03; MEG3: r = -0.46, p = 0.04; XIST: r = -0.45, p = 0.04). Additionally, MALAT1 gene expression negatively correlated with IL-6 (r = -0.49, p = 0.03) and TNF-α (r = -0.48, p = 0.04). MEG3 and XIST gene expression negatively correlated with IL-1β (r = -0.51 and - 0.50, p = 0.03 for both) and TNF-α (r = -0.47 and - 0.52, p = 0.04 and 0.03, respectively). CONCLUSION: MALAT1, MEG3, and XIST are downregulated in GDM, and their gene expression levels are negatively correlated with insulin resistance and select proinflammatory cytokines. These findings suggest a potential role for lncRNA downregulation in GDM pathogenesis, warranting further investigation.
Incidence and causes of major amputation in patients with diabetic foot ulcers: data from a retrospective study.
Meloni M, Uccioli L, Andreadi A … +9 more , Giurato L, Ruotolo V, Romano M, Minasi A, Bellizzi E, Bonanni FR, Salvi M, Bellia A, Lauro D
Acta Diabetol · 2026 Jan · PMID 40906200 · Full text
AIM: The study aimed to evaluate the rate and causes of major amputation in patients with diabetic foot syndrome. METHODS: The current study is a retrospective observational study including consecutive patients referred...
AIM: The study aimed to evaluate the rate and causes of major amputation in patients with diabetic foot syndrome. METHODS: The current study is a retrospective observational study including consecutive patients referred to a tertiary-level diabetic foot service from January 2020 to November 2023 due to a new diabetic foot problem requiring hospital admission. All patients had been managed by a multi-disciplinary diabetic foot team (MDFT) through a pre-set limb salvage protocol including the management of peripheral arterial disease, infection, foot offloading, and comorbidities. At 1 year of follow-up, the following outcomes measures were evaluated: rate of major amputation, clinical characteristics of amputees, and causes of major amputation. RESULTS: Overall, 1226 patients referring for a diabetic foot problem and requiring hospitalization were screened for the study. Among them, 30 (2.4%) patients experienced major amputation. Amputees had 69.9±10.7 years, the majority were male (73.3%) with a prevalence of type 2 diabetes (93.3%) and a long diabetes duration (25.2±9.8 years). They showed several comorbidities such as ischaemic heart disease (83.3%), heart failure (46.7%), end-stage-renal-disease (26.7%), and in addition high rate of peripheral arterial disease (PAD) (86.7%), infected wounds (98.3%), and osteomyelitis (90%). Major amputation was mainly related to untreatable limb ischemia (failure of revascularization procedure) in 56.7% of cases, calcaneus osteomyelitis and necrotizing fasciitis in 16.7% of cases, and tarsal osteomyelitis in 10% of cases. CONCLUSIONS: The rate of major amputation was very low in this population managed by a MDFT. PAD was the main cause of major amputation.
The impact of type 2 diabetes on aging: multidimensional approaches to preserve cognitive health.
Lucia S, Fornaro S, Federici M … +1 more , Rumiati RI
Acta Diabetol · 2025 Dec · PMID 40892247 · Full text
The growing prevalence of type 2 diabetes (T2D) among older adults represents a major public health concern, given its association with accelerated cognitive decline and increased risk of neurodegenerative diseases. Seve...
The growing prevalence of type 2 diabetes (T2D) among older adults represents a major public health concern, given its association with accelerated cognitive decline and increased risk of neurodegenerative diseases. Several diabetes-related mechanisms, including chronic hyperglycaemia, oxidative stress, vascular dysfunction, and insulin resistance in the brain, negatively impact key cognitive domains, including memory and executive functions. These neuropathophysiological alterations are also linked to structural brain changes, contributing to vulnerability to dementia. This narrative review examines both established and emerging strategies aimed at counteracting the cognitive impact of T2D in aging populations. Traditional interventions, especially structured physical activity programs, have consistently demonstrated benefits for global cognitive functioning. In parallel, new pharmacological treatments, such as GLP-1 receptor agonists (e.g., semaglutide), not only improve glycemic control but may also exert neuroprotective effects. Multidomain approaches integrating metabolic management, nutritional optimization, physical exercise, and social engagement, such as those tested in the J-MIND-Diabetes study, have yielded promising outcomes in preserving cognitive functions. We argue that combining pharmacological and behavioral strategies holds significant potential for supporting cognitive health in elderly individuals with T2D. Such multimodal interventions may enhance resilience to cognitive decline, improve quality of life, and promote healthy brain aging in this at-risk population.
Serum lipids changes following cocoa intake in type 2 diabetes patients: a graded dose-response systematic review and meta-analysis of clinical trials.
Anari R, Mohseni H, Motamed S … +2 more , Anari E, Amani R
Acta Diabetol · 2025 Dec · PMID 40886195 · Publisher ↗
INTRODUCTION: Hyperlipidemia, a prevalent comorbidity among type 2 diabetes patients, is a potential risk factor for cardiovascular diseases. It is unclear whether cocoa has beneficial impacts on the serum lipids of pati...
INTRODUCTION: Hyperlipidemia, a prevalent comorbidity among type 2 diabetes patients, is a potential risk factor for cardiovascular diseases. It is unclear whether cocoa has beneficial impacts on the serum lipids of patients with diabetes. METHODS: PubMed, Scopus, and Embase databases were systematically reviewed for clinical trials on cocoa intake and blood lipids in type 2 diabetes until January 1, 2024, and the reference list of relevant articles was searched manually. Two reviewers extracted data and determined the risk of bias (RoB) using the Cochrane tool. The random effect model was applied to calculate standardized mean differences (SMDs). Finally, the certainty and clinical importance of the evidence were checked (PROSPERO registration code: CRD42021224931). RESULT: Eleven RCTs with 506 participants were included. Different forms of cocoa and various intervention durations were applied. Only two RCTs had a low RoB. Findings showed a significant reduction in serum triglyceride (SMD: - 0.57, 95% CI - 1.05, - 0.10, I: 82.7%), but not in other blood lipids. There was a severe heterogeneity in results justified with discrepancies in age, designs, durations, interventions, body mass index, baseline blood lipids, and risk of bias. The results showed low certainty and unimportant lipid changes. CONCLUSION: Although cocoa may slightly change serum lipids in diabetes, its recommendation for lipids control has fair clinical benefits. Due to the lack of certainty of findings and an inadequate number of studies, further well-designed trials considering possible sources of heterogeneity with low RoB are highly recommended.
Serum uric acid to HDL-Chol ratio (UHR) is associated with insulin resistance/sensitivity in individuals without diabetes.
Rubino M, Massimino M, Mancuso E … +7 more , Averta C, Palummo A, Perticone M, Succurro E, Sciacqua A, Mannino GC, Andreozzi F
Acta Diabetol · 2026 Jan · PMID 40864241 · Full text
BACKGROUND: The uric acid-to-HDL cholesterol ratio (UHR) is a promising non-insulin-based marker for metabolic risk, associated with type 2 diabetes, hypertension, hepatic steatosis, and cardiovascular disease. However,...
BACKGROUND: The uric acid-to-HDL cholesterol ratio (UHR) is a promising non-insulin-based marker for metabolic risk, associated with type 2 diabetes, hypertension, hepatic steatosis, and cardiovascular disease. However, its utility in individuals with altered glucose tolerance remains unclear. METHODS: We investigated the relationship between UHR and insulin sensitivity in two independent cohorts. Sample 1 (n = 1555) from the CATAMERI study, was stratified based on oral glucose tolerance test (OGTT) results, and Sample 2 (n = 332) from the EUGENE2 project, with insulin sensitivity measured via euglycemic-hyperinsulinemic clamp. RESULTS: In Sample 1, UHR showed positive correlations with BMI, triglycerides, 2-hour plasma glucose, HOMA-IR, fasting plasma insulin (p < 0.0001 for all) and with HbA1c (p < 0.001), and negative correlations with Matsuda index (p < 0.0001) and total cholesterol (p = 0.019). Multivariable linear regression identified HOMA-IR (β = 0.100), Matsuda index (β=-0.146), InsAUC30/GluAUC30 (β = 0.120), and Stumvoll 1st-phase insulin secretion (β = 0.121) as independent UHR predictors. In Sample 2, bivariate analyses, adjusted for age, sex, and BMI, confirmed positive correlations between UHR and HbA1c (p < 0.001), 2-hour post-load glucose (p = 0.001), BMI, triglycerides, and fasting insulin (p < 0.0001 for all) and a negative correlation with Clamp M (glucose disposal, p = 0.0003). Finally, multivariable regression of Clamp M variability (adjusted for age, sex, and BMI) demonstrated significant negative associations with UHR (β= -0.230) and BMI (β= -0.375). CONCLUSION: These findings suggest that UHR, derived easily and inexpensively from routine clinical measurements, is a promising indicator of metabolic risk in individuals without diabetes. Its accessibility positions it as a potential tool for early diabetes prevention strategies, potentially reducing reliance on the OGTT.
The L-type amino acid transporter inhibitor, BCH, inhibits myotube BCAA uptake and mitochondrial function without altering myotube insulin sensitivity during insulin resistance in C2C12 myotubes.
Travis KB, Ragland KJ, Spry ER … +3 more , Zaman T, Lundin PM, Vaughan RA
Acta Diabetol · 2026 Jan · PMID 40856815 · Publisher ↗
INTRODUCTION: Branched-chain amino acids (BCAA) are essential nutrients involved in protein synthesis. BCAA are absorbed via the L-type amino acid transporter (LAT1) in skeletal muscle where the majority of BCAA are meta...
INTRODUCTION: Branched-chain amino acids (BCAA) are essential nutrients involved in protein synthesis. BCAA are absorbed via the L-type amino acid transporter (LAT1) in skeletal muscle where the majority of BCAA are metabolized. Higher circulating BCAA levels have been shown to correlate with insulin resistance. Some speculate that enhanced BCAA metabolism/disposal or reduced BCAA uptake may limit BCAA-mediated anabolic signaling and possibly improve insulin sensitivity. AIMS: This study investigated the effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), a LAT inhibitor, on metabolism and insulin sensitivity in a myotube model of insulin resistance. Because BCAA-mediated anabolic signaling has been linked with insulin resistance, we assessed if reduced BCAA uptake via LAT inhibition would improve insulin sensitivity. METHODS: C2C12 myotubes were cultured in the presence and absence of insulin resistance and treated with and without BCH. Myotube metabolism was assessed via oxygen consumption, and associated gene and protein expression were assessed using qRT-PCR and Western blot, respectively. LC/MS was performed to assess the effect of each condition on extracellular BCAA accumulation. RESULTS AND CONCLUSIONS: BCH treatment and insulin resistance both increased extracellular BCAA levels which was associated with reduced protein expression/activity of BCAA catabolic enzymes. Additionally, BCH and insulin resistance were both independently associated with reduced mitochondrial function which occurred without significant changes in mitochondrial biogenesis signaling. Importantly, BCH did not alter myotube viability or insulin sensitivity, suggesting reduced metabolism was not a function of reduced viability. These observations demonstrate that reduction of BCAA uptake may not improve insulin resistance and may promote mitochondrial dysfunction.
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