Acta Diabetologica最新文献

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.

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.

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/1.73m² 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.

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.

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.

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 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.

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, I²: 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.

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.