Acta Diabetologica[JOURNAL]
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200 papers
Integrative analysis of placental metabolic reprogramming and microbiome alterations in gestational diabetes mellitus (GDM).
Yousefi F, Salehi B, Ghorbani N … +2 more , Yaghmayee S, Eslami M
Acta Diabetol · 2026 Jun · PMID 41504923 · Publisher ↗
Gestational diabetes mellitus (GDM) significantly impacts placental metabolism and microbial composition, leading to transformations at the maternal–fetal interface. In response to hyperglycemia, the placenta undergoes e...
Gestational diabetes mellitus (GDM) significantly impacts placental metabolism and microbial composition, leading to transformations at the maternal–fetal interface. In response to hyperglycemia, the placenta undergoes extensive metabolic reprogramming, including disturbances in lipid metabolism, reduced efficiency in fatty acid oxidation, altered amino acid transport, and adaptations in glycolysis. These metabolic changes are associated with inflammatory cytokine activity, mitochondrial stress, and endoplasmic reticulum dysfunction, collectively driving placental lipotoxicity and disruptions in nutrient transfer. Research underscores the critical role of regulatory pathways such as AMPK, PI3K/AKT, and PPARα–CPT1 in mediating these metabolic shifts, with specific metabolites, such as linoleic and α-linolenic acids, identified as promising biomarkers for GDM. The gut–placenta microbiome axis plays a key role in the development of GDM. Microbial imbalances, marked by a reduction in beneficial genera such as Bifidobacterium, Akkermansia, and Roseburia, coupled with an increase in pro-inflammatory species like Bacteroides and Desulfovibrio, influence both endocrine signaling and immune function. Notably, microbial metabolites like short-chain fatty acids have a complex impact by improving insulin sensitivity but potentially contributing to metabolic dysfunction when present in excessive amounts. Furthermore, research indicates that alterations in maternal microbiota can be transmitted vertically to the neonate, with long-term implications for metabolic health. Emerging omics-based research, integrating transcriptomics, proteomics, lipidomics, and metabolomics, provide a systems-level view of the molecular mechanisms driving GDM. These findings emphasize the intricate relationship between placental metabolic reprogramming and microbial dynamics in influencing maternal and fetal health outcomes and highlight novel opportunities for biomarker discovery and therapeutic intervention.
Ectopic fat distribution and its correlation with insulin resistance indices in non-obese individuals with type 2 diabetes.
Han Q, Xue M, Li F … +7 more , Wang W, Yuan X, Chen X, Pan H, Liu M, Liu S, Lou Q
Acta Diabetol · 2026 Apr · PMID 41504922 · Publisher ↗
BACKGROUND: This study examined the links between regional adiposity and insulin resistance in non-obese adults with type 2 diabetes. METHODS: This post-hoc analysis utilized data from a randomized controlled trial invol...
BACKGROUND: This study examined the links between regional adiposity and insulin resistance in non-obese adults with type 2 diabetes. METHODS: This post-hoc analysis utilized data from a randomized controlled trial involving participants with type 2 diabetes who were recruited from a hospital in East China between December 2018 and January 2019. Pancreatic fat content (PFC), liver fat content (LFC), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were quantified using the IDEAL-IQ water–fat separation technique. Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA2-IR), Matsuda index, Raynaud’s insulin sensitivity index, triglyceride-glucose (TyG) index, and estimated glucose disposal rate (eGDR). Associations were examined using univariate and multivariate linear regression analyses. RESULTS: Data from 84 participants were analyzed. After adjusting for age, gender, duration of diabetes, HbA1c, BMI, and LDL-C, linear regression analysis demonstrated significant correlations between LFC and VAT with HOMA2-IR (β = 0.053, P = 0.011; β = 0.007, P < 0.001 ) and the TyG index (β = 0.034, P = 0.032; β = 0.006, P < 0.001 ). Additionally, VAT and SAT showed correlations with Raynaud’s insulin sensitivity index (β= -0.037, P = 0.018; β= -0.035, P = 0.021 ) and the Matsuda index (β= -0.903, P = 0.027; β= -0.781, P = 0.048 ). CONCLUSIONS: In non-obese individuals with type 2 diabetes, LFC, VAT, and SAT were significantly associated with insulin resistance, with VAT showing the strongest link. These findings suggest that assessing regional fat distribution can identify insulin resistance in non-obese type 2 diabetes, enabling early risk stratification and targeted intervention.
Decoupling weight loss from organoprotective benefits in GLP-1RA, dual agonists, and SGLT2I therapy: A narrative review.
Bhaduri G, Bhattacharyya S, Mukherjee S … +1 more , Gokalani R
Acta Diabetol · 2026 Apr · PMID 41504921 · Publisher ↗
Over the past decade, incretin-based therapies and SGLT2 inhibitors have redefined management of type 2 diabetes (T2D) and obesity. While their glucose-lowering and weight-reducing properties are well established, growin...
Over the past decade, incretin-based therapies and SGLT2 inhibitors have redefined management of type 2 diabetes (T2D) and obesity. While their glucose-lowering and weight-reducing properties are well established, growing evidence highlights benefits that extend beyond these metabolic endpoints. Large cardiovascular outcome trials, renal protection programs, and liver disease studies demonstrate that reductions in cardiovascular events, kidney failure, and steatohepatitis are only partly explained by changes in body weight or glycated hemoglobin. Instead, these agents may exert direct disease-modifying actions through anti-inflammatory, antifibrotic, hemodynamic, and endothelial pathways. This narrative review synthesizes evidence from major randomized trials and large prospective cohorts published between 2010 and 2025, prioritized based on hard clinical endpoints and relevance to organ-protection outcomes. Trials such as SURPASS-CVOT, SOUL, SELECT, SUSTAIN-6, LEADER, REWIND, EMPA-REG OUTCOME, DAPA-CKD, EMPA-KIDNEY, and ESSENCE collectively illustrate protection across cardiovascular, renal, and hepatic systems. Importantly, trials conducted predominantly in individuals with higher baseline body weight demonstrated more pronounced weight loss, whereas other pivotal trials involving participants with lower baseline weight showed comparable organoprotective benefits despite far smaller weight changes—highlighting that these effects extend beyond the advantages conferred by weight reduction alone. Emerging data also suggest possible benefits in neurological and respiratory domains. Recognition of these broader effects has important implications for chronic disease management and the development of future therapeutic paradigms.
In memory of Agostino Consoli.
Giaccari A, Formoso G
Acta Diabetol · 2026 May · PMID 41504920 · Publisher ↗
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Efficacy and safety of orforglipron in type 2 diabetes mellitus and obesity: a GRADE-assessed meta-analysis and trial sequential analysis with subgroup evaluations by diabetic status, obesity status, and dose regimens.
Jamal A, Khan S, Qadri M … +14 more , Shah A, Iftikhar H, Fatima E, Ahmad M, Sikandar M, Jawed I, Muneeb M, Mohmand MS, Bacha Z, Khan BW, Jamal T, Khalid AA, Khan MI, Zulkaif M
Acta Diabetol · 2026 Apr · PMID 41498807 · Publisher ↗
BACKGROUND: Orforglipron, an oral non-peptide GLP-1 receptor agonist, is being evaluated for type 2 diabetes mellitus (T2DM) and obesity. A quantitative synthesis of efficacy and safety across doses and phenotypes is nee...
BACKGROUND: Orforglipron, an oral non-peptide GLP-1 receptor agonist, is being evaluated for type 2 diabetes mellitus (T2DM) and obesity. A quantitative synthesis of efficacy and safety across doses and phenotypes is needed. OBJECTIVE: To assess the efficacy and safety of orforglipron versus placebo in adults with T2DM and/or obesity, including prespecified subgroup analyses by dose and metabolic phenotype, along with certainty evaluation using GRADE and trial sequential analysis (TSA). METHODS: Following PRISMA 2020, randomized controlled trials comparing orforglipron with placebo were combined using random-effects meta-analysis to determine mean differences (MD) or risk ratios (RR) with 95% confidence intervals. Heterogeneity (I²), influence (leave-one-out analysis), dose groups (3, 6, 24, 36 mg), and phenotype subgroups (obese/non-diabetic vs. non-obese/diabetic) were analyzed; TSA evaluated the required information size and monitoring boundaries. RESULTS: Five trials (n = 2,672; orforglipron 1,413; placebo 1,259) were included. Orforglipron reduced HbA1c (primary MD − 1.07%, 95% CI − 2.00 to − 0.13; I²=100%; sensitivity MD − 1.45%, 95% CI − 1.49 to − 1.41; I²=0%), body weight (primary MD − 5.25 kg, 95% CI − 6.72 to − 3.77; I²=96%; sensitivity MD − 4.21 kg, 95% CI − 4.40 to − 4.02; I²=0%), BMI (MD − 1.99 kg/m², 95% CI − 2.97 to − 1.01; I²=97%), and systolic blood pressure (primary MD − 3.90 mmHg, 95% CI − 6.44 to − 1.35; I²=91%; sensitivity MD − 2.56 mmHg, 95% CI − 4.64 to − 0.48; I²=22%). Fasting plasma glucose decreased significantly overall (MD − 25.77 mg/dL, 95% CI − 58.70 to − 7.18; very high heterogeneity; dose-response evident). Diastolic blood pressure was neutral (primary MD − 0.32 mmHg, 95% CI − 2.36 to 1.71; sensitivity MD + 0.68 mmHg, 95% CI − 0.02 to 1.39). Heart rate increased (primary MD + 6.38 bpm, 95% CI + 2.99 to + 9.77; high heterogeneity). Hypoglycemia (RR 1.05, 95% CI 0.23 to 4.86) and serious adverse events (RR 1.10, 95% CI 0.75 to 1.62) did not differ from placebo. TSA supported strong evidence for weight, BMI, and SBP; additional data is needed for DBP, heart rate, hypoglycemia, and SAEs. CONCLUSIONS: Reported as primary pooled effects, orforglipron improves HbA1c, weight, BMI, SBP, and fasting plasma glucose, with a class-consistent increase in heart rate and no excess in hypoglycaemia or serious adverse events versus placebo. Sensitivity analyses generally reduced heterogeneity without reversing conclusions. TSA indicates conclusions for weight, BMI, and SBP are robust; longer-term comparative trials should refine DBP and safety signals.
J-shaped associations of serum urate with all-cause and cause-specific mortality in diabetes: mediation by kidney function.
Li Y, Zhu H, Xu Z … +7 more , Ye W, Li B, Guo D, Wu Y, Yu M, Ji L, Xu J
Acta Diabetol · 2026 Mar · PMID 41379162 · Publisher ↗
AIMS: Aimed to investigate the associations of serum urate with all-cause and cause-specific mortality in diabetes and to assess whether estimated glomerular filtration rate (eGFR) mediates these associations. METHODS: W...
AIMS: Aimed to investigate the associations of serum urate with all-cause and cause-specific mortality in diabetes and to assess whether estimated glomerular filtration rate (eGFR) mediates these associations. METHODS: We analyzed 18,809 UK Biobank participants with diabetes, free of CVD or cancer at baseline, followed for a median of 13.5 (12.8-14.4) years. Cox and Fine-Gray models estimated mortality risks, restricted cubic splines assessed nonlinear associations, and Aalen additive hazards models evaluated mediation. RESULTS: During follow-up, 2984 deaths occurred (739 CVD, 1065 cancer). Compared with the lowest urate quartile (< 4.6 mg/dL), participants in the highest quartile (> 6.3 mg/dL) had significantly higher risks of all-cause mortality (HR = 1.329, 95% CI 1.190-1.485), CVD mortality (HR = 1.391, 95% CI 1.115-1.736), cancer mortality (HR = 1.258, 95% CI 1.042-1.518), and other-cause mortality (HR = 1.245, 95% CI 1.042-1.487). A J-shaped association was observed, with all-cause mortality rising above 5.4 mg/dL of urate. Sex-stratified analyses revealed higher inflection points in males than females (7.2 mg/dL vs. 5.7 mg/dL). Mediation analysis indicated that eGFR explained 36.4% of the association between urate and all-cause mortality, with an indirect effect of 10 (95% CI 4.5-15.2) events per 1,000 person-years. CONCLUSIONS: Elevated serum urate, even within the normal range, was independently associated with all-cause and cause-specific mortality in diabetes, partly mediated by reduced eGFR. These findings support considering subclinical hyperuricemia in risk stratification, especially among individuals with early-stage diabetes and preserved metabolic and renal function.
Metabolic effects of pioglitazone and sodium-glucose cotransporter 2 inhibitors in familial partial lipodystrophy.
Soyaltin U, Simsir IY, Akinci B
Acta Diabetol · 2026 Mar · PMID 41369773 · Publisher ↗
OBJECTIVE: We aimed to evaluate the potential metabolic benefits of pioglitazone, a PPARG agonist, and sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with familial partial lipodystrophy (FPLD). METHODS: Th...
OBJECTIVE: We aimed to evaluate the potential metabolic benefits of pioglitazone, a PPARG agonist, and sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with familial partial lipodystrophy (FPLD). METHODS: This retrospective medical chart study included 38 adult patients with FPLD (18 treated with pioglitazone and 20 with SGLT2 inhibitors). RESULTS: Treatment with pioglitazone reduced HbA1c from 8.6% (6.2-9.2) to 7.0% (5.9-8.8) at month 6 (p = 0.004) and 7.0% (6.1-8.7) at month 12 (p = 0.107). Triglycerides decreased by 25% (6-55%) at month 6 (p = 0.001) and 16% (4-44%) at month 12 (p = 0.008). A modest reduction in ALT was observed at month 12 (p= 0.046). Treatment with SGLT2 inhibitors reduced HbA1c from 8.7% (7.9-10.2) at baseline to 8.1% (7.4-9.4) at month 6 (p = 0.003) and 7.9% (7.3-8.9) at month 12 (p = 0.003). Median triglyceride levels decreased by 11% (0-33%) at month 6 (p = 0.013), while changes at month 12 were not significant. No meaningful changes were observed in weight, ALT, or AST. CONCLUSIONS: We observed modest metabolic improvements following treatment with pioglitazone and SGLT2 inhibitors in patients with FPLD.
Advances in diabetic wound healing: from pathophysiology to emerging therapies.
Swain SS, Karri VVSR, Uddin ME … +3 more , Gowthamarajan K, Bhaskaran M, Subramaniyan V
Acta Diabetol · 2026 Mar · PMID 41369772 · Publisher ↗
Diabetic wounds (DWs), particularly those affecting the lower extremities, represent a significant clinical challenge due to their chronic nature and high risk of complications, including infection and amputation. Despit...
Diabetic wounds (DWs), particularly those affecting the lower extremities, represent a significant clinical challenge due to their chronic nature and high risk of complications, including infection and amputation. Despite advances in diabetes management, conventional wound care strategies often fail to achieve satisfactory healing outcomes, largely due to the complex pathophysiology of DWs, are involving impaired angiogenesis, chronic inflammation, and compromised immune responses. The data on the conventional and emerging therapies used in the management of DWs were searched using PubMed, Scopus, and Web of Science databases to locate literature published. Studies have shown that conventional wound care interventions like debridement, dressing, and infection control mostly provide symptomatic treatment without eliminating underlying cellular and molecular diabetic wound pathophysiology. Recent years have witnessed the emergence of novel therapeutic approaches, including stem cell therapy, gene therapy, nanotechnology-based interventions, and tissue engineering. These strategies improve angiogenesis, alter the polarization of macrophages, and stimulate tissue repair, which can offer new hope for enhancing wound healing in diabetic patients. This review synthesizes current literature on the pathophysiology of diabetic wound healing, evaluates the limitations of traditional therapies, and provides a comprehensive overview of cutting-edge treatments that holds an effective diabetic wound management.
Correction: Treatment with non-automated insulin pumps or multiple daily injections during pregnancy and post-delivery in women with type 1 diabetes: A secondary analysis of the copenfast trial.
Christiansen K, Nørgaard SK, Nørgaard K … +4 more , Clausen TD, Damm P, Mathiesen ER, Ringholm L
Acta Diabetol · 2026 Mar · PMID 41348219 · Full text
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Once-weekly administration of insulin in the real-world management of type 2 diabetes. A Delphi-like consensus.
Candido R, Buzzetti R, Consoli A … +5 more , Irace C, Torre E, Trevisan R, Fadini GP, T2D once-Weekly Insulin Expert Panel Group
Acta Diabetol · 2026 Feb · PMID 41335333 · Full text
BACKGROUND: Despite major advancements in diabetes management, insulin therapy continues to have a prominent role in glycemic control, aiding numerous patients. However, treatment-associated unmet needs pose a hindrance...
BACKGROUND: Despite major advancements in diabetes management, insulin therapy continues to have a prominent role in glycemic control, aiding numerous patients. However, treatment-associated unmet needs pose a hindrance to therapy acceptance and adherence, negatively affecting patient outcomes due to less effective glycemic management. METHOD: A consensus study was conducted using a Delphi-like methodology, with the aim of highlighting and discussing the potential benefits and challenges with the introduction of once-weekly basal insulin icodec in the management of diabetes. RESULTS: The consensus firmly highlights the transformative approach and the timely adoption of once-weekly basal insulin for patients affected by type 2 diabetes. Once-weekly insulin icodec was broadly supported as a viable alternative to daily basal insulin, particularly for insulin-naïve individuals and those on basal-only regimens. Key advantages included reduced injection burden, improved adherence, and potential cost savings. The therapy was also seen as a way to counteract therapeutic inertia and improve quality of life. Although some implementation challenges were noted, namely patient selection and titration, most experts endorsed educational efforts and digital tools to support adoption. The panel supported the progressive replacement of daily with weekly basal insulin. CONCLUSION: The advent of once-weekly insulin icodec therapy is an unprecedent breakthrough in diabetes care. Compared with once-daily insulin analogues, it offers a simplified, secure, enhanced, and sustained glycemic control, counteracting therapeutic inertia, expectedly improving adherence to insulin therapy. Insulin icodec can not only enable personalized treatment and positively impact the clinical outcome, but also improve patient satisfaction and overall quality of life.
A perspective on clinical profile and quality of care of "Octogenarians" living with type 1 diabetes in Italy, AMD Annals Initiative.
Da Porto A, Candido R, Manicardi V … +4 more , Rocca A, De Cosmo S, Russo G, AMD Annals Study Group
Acta Diabetol · 2026 Feb · PMID 41307692 · Publisher ↗
BACKGROUND AND AIMS: Thanks to the efforts made in the last century many patients with Type 1 Diabetes (T1D) are reaching and surpassing the age of 75, however, data on their clinical characteristics, prevalence of diabe...
BACKGROUND AND AIMS: Thanks to the efforts made in the last century many patients with Type 1 Diabetes (T1D) are reaching and surpassing the age of 75, however, data on their clinical characteristics, prevalence of diabetes complications and quality of care are lacking. METHODS: This multicenter, observational, retrospective study includes data from participants with T1D aged over 75 years, regularly evaluated in the year 2023 in 296 Diabetes Clinics in Italy included in the Associazione Medici Diabetologi (AMD) Annals Initiative. Socio-demographic characteristics, data on glycemic, lipid, and blood pressure control, data on the current insulin therapy regimen, the use of insulin pumps, as well as data on the prevalence of microvascular and macrovascular complications of diabetes was evaluated. Additionally, we evaluated some indicators of quality of care. RESULTS: We included 2443 participants with mean age of 79.9 ± 3.9 years, in prevalence (54.9%) female. The mean duration of diabetes was 34.1 ± 17.5 years. Participants were evaluated regularly in person at the diabetes clinic on average 2.7 ± 2.1 times per year. 5% of participants were treated with insulin pumps. Mean glycated hemoglobin (HbA1c) was 7.8 ± 1.1. In comparison to standard therapy, better glycemic control was seen in participants on insulin pumps. Despite the high prevalence of diabetic retinopathy (33.3%) and chronic kidney disease (CKD) (39%) only a small portion of participants presented with end-stage complication, with 2.3% of participants having Proliferative Retinopathy (0.4% vision loss), 0.3% being on dialysis, and 2.5% having a history of amputation or foot ulcer. Cardiovascular disease was detected in 17.8% of participants. 77% of participants with previous CV event were treated with anti-platelet therapy. 68% of participants with proteinuria were treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. LDL target of < 100 mg/dl was achieved in almost 2/3 of participants. Overall quality of care, expressed as Q-Score, was 27.4 ± 8.2. CONCLUSION: Our data show that a consistent number of T1D participants regularly followed up by Italian diabetes centers reached an advanced age. The overall quality of care for participants regularly followed was good, within a lower-than-expected burden of end-stage renal disease, visual loss, and diabetic foot. Management of CV risk factors could be improved, as well as the use of technology in this setting.
Influence of GLP1 receptor rs6923761 and rs761387 genetic variants on oral semaglutide response in patients with type 2 diabetes.
Candido R, Toffoli B, Baccichetto G … +5 more , Marchese F, Carpenè S, Gaiotti S, Fabris B, Bernardi S
Acta Diabetol · 2026 Feb · PMID 41307691 · Full text
AIMS: Glucagon-like peptide-1 receptor (GLP-1R) has become one of the most promising ligand-receptor systems to target for type 2 diabetes mellitus (T2DM) treatment. Over the last two decades, several GLP-1 receptor agon...
AIMS: Glucagon-like peptide-1 receptor (GLP-1R) has become one of the most promising ligand-receptor systems to target for type 2 diabetes mellitus (T2DM) treatment. Over the last two decades, several GLP-1 receptor agonists (GLP-1RAs) have been developed and semaglutide is the first and only GLP-1RA available as an oral formulation. GLP1R single nucleotide polymorphisms may affect GLP-1R response to oral semaglutide. Here we aimed to evaluate the impact of rs6923761 and rs761387 GLP1R polymorphisms on the response to oral semaglutide. METHODS: This is a retrospective cohort study including adult patients with T2DM who had been treated with oral semaglutide for at least one year. Patients were enrolled between November 2023 and April 2024, and then genotyped. RESULTS: We selected 210 adult patients with a median age of 71 years. Their median BMI was 29.1 kg/m2, HbA1c was 7.2% (55 mmol/mol), duration of diabetes was 12 years. After a median follow-up of 18 months, oral semaglutide reduced HbA1c by −0.3% (−3 mmol/mol), BMI by −1.1 kg/m2, SBP by −5 mmHg, total cholesterol by -8 mg/dL, triglycerides by -6.5 mg/dL. In addition, a reduction of ACR by −44.02 mg/g was observed in patients with baseline ACR > 30 mg/g, along with a decrease of liver transaminases in patients with baseline levels ≥ 35 U/L. Multivariate linear regression did not show any significant association between rs6923761 or rs761387 GLP1R genotypes and changes in HbA1c, BMI, SBP and DBP. CONCLUSIONS: Our findings confirm the effectiveness of oral semaglutide in improving metabolic control and providing cardiorenal protection in different clinical scenarios. Conversely, they fail to show a clear benefit of GLP1R genotyping to guide treatment decisions, at least in patients with HbA1c < 7.5% (< 58 mmol/mol). Further studies are needed to confirm and extend our findings.
Red cell distribution width positively correlates with 10-year risk of cardiovascular disease among people with type 1 diabetes as assessed by the Steno Type 1 Risk Engine.
Naskret D, Pilacinski S, Niedzwiecki P … +2 more , Kulecki M, Zozulinska-Ziolkiewicz D
Acta Diabetol · 2026 Feb · PMID 41283907 · Full text
INTRODUCTION: We evaluated the association between Red Cell Distribution Width (RDW) and predicted 10-year cardiovascular disease (CVD) risk, as estimated by the Steno Type 1 Risk Engine (ST1RE), in individuals with type...
INTRODUCTION: We evaluated the association between Red Cell Distribution Width (RDW) and predicted 10-year cardiovascular disease (CVD) risk, as estimated by the Steno Type 1 Risk Engine (ST1RE), in individuals with type 1 diabetes (T1D). METHODS: We conducted a retrospective analysis of 342 adults with T1D duration > 5 years, (163 women, 179 men) from a tertiary Diabetes Center electronic database. Participants were stratified into tertiles of RDW: Group 1 (G1: < 12.6), Group 2 (G2: 12.6-13.2), and Group 3 (G3: >13.2). RESULTS: Higher RDW was associated with older age and longer diabetes duration. The prevalence of microvascular complications did not differ across RDW tertiles. Predicted 10-year CVD risk (ST1RE 10Y) increased with higher RDW: median (IQR) 4.5 (3.2-6.1) in G1, 4.5 (2.9-7.2) in G2, and 6.2 (3.5-12.0) in G3 (p < 0.01). In multiple linear regression, RDW was positively associated with ST1RE 10Y, (β = 1.13;95% CI, 0.57-1.70; p < 0.01; R = 0.36). In multivariable logistic regression, RDW was independently associated with moderate/high versus low ST1RE 10Y risk (OR = 1.87;95%CI, 1.28-2.75; p = 0.001). Models were adjusted for presence of hypertension, dyslipidemia, diabetic kidney disease, BMI value and hsCRP concentration. CONCLUSION: Our results suggest that RDW is independently associated with predicted 10-year CVD risk in individuals with T1D. These findings support RDW as a potential marker for cardiovascular risk stratification. However, external validation is required before clinical application.
Quality of life and health literacy in individuals with diabetes-related wounds.
Romeira NIG, Barroso LPD, Roque M … +3 more , de Aquino Pereira J, Apolinário PP, Lima MHM
Acta Diabetol · 2026 Feb · PMID 41283906 · Publisher ↗
AIMS: To evaluate quality of life (QoL) and health literacy (HL) in Brazilian individuals with Diabetes Mellitus type 2 (DM2) and diabetes-related foot ulcers (DFU). METHODS: An observational, cross-sectional study was c...
AIMS: To evaluate quality of life (QoL) and health literacy (HL) in Brazilian individuals with Diabetes Mellitus type 2 (DM2) and diabetes-related foot ulcers (DFU). METHODS: An observational, cross-sectional study was conducted at a tertiary outpatient clinic in Southeastern Brazil. A total of 100 adult study participants, aged ≥ 18 years, who were diagnosed with type 2 DM and presented with at least one DFU were included. Instruments included a sociodemographic and clinical questionnaire, the Diabetic Foot Ulcer Scale-Short Form (DFS-SF), and the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA-18). DFUs were classified using the Wound, Ischemia, and foot Infection (WIfI) system. Statistical analyses included comparison, correlation, and multiple linear regression tests. RESULTS: Based on the present study, the level of diabetes HL among the study participants was inadequate. Taking into consideration the sample size, exploratory regression analyses suggest that hypertension and a moderate-to-high amputation risk (WIfI classification) were both significantly associated with poorer QoL, with respect to leisure activities and a greater perceived dependency during daily activities, respectively. Participants expressed considerable concern regarding their foot health and the challenges associated with foot ulcer management. A connection between neuropathy and increased anxiety regarding foot conditions was also found. CONCLUSIONS: Older age, longer disease duration, hypertension, and neuropathy were associated with poorer QoL in DM patients with DFU. Although no overall association was found between HL and the DFS-SF domains, adequate HL was associated with higher scores in the "Bothered by ulcer care" domain. These findings highlight the multi-faceted impact of clinical and demographic factors on QoL in this population, and warrant further investigation using larger, longitudinal cohorts.
Interleukin-17 A and diabetic kidney disease: emerging evidence on its pathogenic role and targeted modulation.
Qu B, Xie T, Xie Y … +4 more , Guang Z, Han Y, Li M, Tong X
Acta Diabetol · 2026 Mar · PMID 41283905 · Publisher ↗
Diabetic kidney disease (DKD), a significant microvascular complication of diabetes, is a multifactorial condition and a primary cause of both chronic kidney disease (CKD) and end-stage renal disease (ESRD). Interleukin-...
Diabetic kidney disease (DKD), a significant microvascular complication of diabetes, is a multifactorial condition and a primary cause of both chronic kidney disease (CKD) and end-stage renal disease (ESRD). Interleukin-17 A (IL-17 A), an essential pro-inflammatory cytokine, is gaining recognition for its role in the development of DKD, highlighting its potential as a new therapeutic target. The pathogenic roles of IL-17 A may be mediated through several mechanisms, including the amplification of inflammatory responses, disruption of immune homeostasis, promotion of renal fibrosis, inhibition of mitochondrial autophagy, and perturbation of gut microbiota balance. Importantly, IL-17 A appears to exert both deleterious and potentially protective effects, reflecting a complex regulatory role in disease progression. However, the current evidence supporting these dual functions remains limited and context-dependent. Comparative analyses with other cytokines, such as IL-6, IL-1β, TNF-α, IL-22, and other IL-17 family members, are needed to position IL-17 A within the broader cytokine network and clarify its relative pathogenic and therapeutic significance. In this review, we critically examine the mechanistic basis of IL-17 A-mediated therapeutic strategies for DKD, drawing on recent advances from both established and emerging research. Furthermore, we identify key unresolved questions and propose future directions to guide ongoing and prospective investigations in this evolving field.
Characteristics of above 65-year-olds with type 1 diabetes in the Finnish diabetic nephropathy study.
Franzén EMC, Eriksson MI, Satuli-Autere S … +7 more , Ylinen A, Jansson Sigfrids F, Nicklén J, Öhman H, Groop PH, Thorn LM, FinnDiane Study Group
Acta Diabetol · 2026 Feb · PMID 41251706 · Full text
AIMS: Ageing in people with type 1 diabetes is identified as a research gap. Therefore, the aim of our study is to characterize above 65-year-olds with type 1 diabetes, and to identify potential protective factors or fac...
AIMS: Ageing in people with type 1 diabetes is identified as a research gap. Therefore, the aim of our study is to characterize above 65-year-olds with type 1 diabetes, and to identify potential protective factors or factors related to increased risk of mortality in this age group. METHODS: This observational study includes 864 participants aged 55 years or older with type 1 diabetes (age at onset below 40) from the Finnish Diabetic Nephropathy Study, grouped according to age into three categories: 55-60, 60-65, and > 65 years old. Multivariable logistic regression analysis was used to identify factors independently associated with age above 65. Cox regression analysis was conducted to assess how these factors impact survival. RESULTS: Factors that were independently associated with age above 65 years included: higher diabetes onset age, higher pulse pressure, lower mean arterial pressure, absence of current smoking and diabetic kidney disease, history of severe diabetic retinopathy and cardiovascular events, lower daily insulin dose, lower HbA, and lowerApoB-100 concentrations. Of these factors, the ones associated with mortality in above 65-year-olds during follow-up were presence of diabetic kidney disease, higher HbA, and history of cardiovascular events. CONCLUSION: Above 65-year-olds were characterized by both factors generally related to positive and negative health outcomes. Additionally, different factors were found to be associated with reaching older age and with survival beyond the age of 65.
Depression is associated with lower adherence to cardioprotective medications in adults with type 1 diabetes.
Lithovius R, Mutter S, Parente EB … +4 more , Harjutsalo V, Groop PH, Thorn LM, Sandholm N
Acta Diabetol · 2026 Feb · PMID 41251705 · Full text
AIMS: To investigate the association between depression and refill adherence to cardioprotective medications in a representative cohort of type 1 diabetes adults. METHODS: This Finnish Diabetic Nephropathy (FinnDiane) su...
AIMS: To investigate the association between depression and refill adherence to cardioprotective medications in a representative cohort of type 1 diabetes adults. METHODS: This Finnish Diabetic Nephropathy (FinnDiane) sub-study included 1,588 adults with type 1 diabetes who had purchased antihypertensive or lipid-lowering drugs within ± 0.5 years from study baseline. The proportion of days covered (PDC) method was used to calculate overall refill adherence over a 10-year follow-up. Adherence was classified into good (> 80%), intermediate (≥ 50 and < 80%), and poor (< 50%). Participants were considered to have depression, if they had a diagnosis of depression or had purchased antidepressive agents at any time point from 1995 until the end of follow-up, identified from national registries. Multinomial logistic regression analysis, adjusted for age, sex, duration of diabetes, education level, HbA, BMI, diabetic kidney disease, smoking, and alcohol consumption was performed. RESULTS: Of the cohort 37% had depression during the study period. Those individuals with depression were more often women (P = 0.0001), and had lower adherence to cardioprotective medication (P = 0.02) than those without depression. Individuals with depression had 72% higher odds ([95% CI 1.09, 2.70], P = 0.02) of having poor versus good adherence, compare to those without depression. The results persisted after excluding antidepressants potentially used for neuropathic pain (OR 1.61 [95% CI 1.02, 2.55], P = 0.04). CONCLUSIONS: Healthcare professionals should assess presence of depression and monitor medication adherence at regular consultations, and whenever needed, should implement strategies to manage the depression in order to enhance adherence, which might ultimately lead to improved cardiovascular outcomes in type 1 diabetes.
METTL14-dependent regulation of HMGB1 attenuates inflammation in diabetic retinopathy.
Huang Z, Guan J, Zhang X … +6 more , Hu Q, Huang J, Sang W, Wang X, Jiang B, Sun D
Acta Diabetol · 2026 Feb · PMID 41247402 · Publisher ↗
BACKGROUND: Diabetic retinopathy (DR) is a frequent complication of diabetes, characterized by progressive vision loss, with chronic inflammation being an important contributor in its development. N6-methyladenine (m6A)...
BACKGROUND: Diabetic retinopathy (DR) is a frequent complication of diabetes, characterized by progressive vision loss, with chronic inflammation being an important contributor in its development. N6-methyladenine (m6A) is a crucial RNA modification within eukaryotes, playing an essential role in different bodily functions and disease states. Nonetheless, the precise mechanism underlying m6A modification in DR remains elusive. METHODS: BV2 cells were stimulated with high glucose (HG) and mice were injected intraperitoneally with streptozotocin (STZ) to induce inflammation. RT-qPCR, Western blot, ELISA, immunofluorescence, CCK-8, Wound Healing, and RIP assays were used to evaluate the effects of methyltransferase-like 14 (METTL14) in these models. RESULTS: Our study indicated significantly decreased levels of METTL14 in HG stimulated BV2 cells and in STZ models. In addition, METTL14 levels were reduced in peripheral venous samples of DR patients. Meanwhile, the inflammatory factors were inhibited by up-regulation of METTL14 in HG stimulated BV2 cells and STZ models. Mechanistically, METTL14 overexpression inhibited high mobility group box 1 (HMGB1), thereby suppressing nuclear factor kappa-B (NF-κB) signaling pathway activation. CONCLUSION: This study suggested that METTL14 may influence inflammation in DR by modulating the HMGB1/NF-κB pathway, providing valuable insights into potential therapeutic approaches for DR.
Letter to the editor on management of AHCL in an adolescent with DM1 and frequent episodes of ketoacidosis: from resistance to therapeutic adaptation.
Guerra F, Zagaroli L, Zamarra GB … +2 more , Postiglione S, Delvecchio M
Acta Diabetol · 2026 Apr · PMID 41247401 · Publisher ↗
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Trends in prevalence of chronic kidney disease and risk management among US adults with diabetes, 2001 to 2020.
Qu Q, Su H, Chen H … +3 more , Liao S, Zhang H, Li X
Acta Diabetol · 2026 Feb · PMID 41240072 · Publisher ↗
AIMS: To examine trends in prevalence of chronic kidney disease (CKD) and risk management among US adults with diabetes between 2001 and 2020. METHODS AND RESULTS: This serial cross-sectional study included 4200 adults w...
AIMS: To examine trends in prevalence of chronic kidney disease (CKD) and risk management among US adults with diabetes between 2001 and 2020. METHODS AND RESULTS: This serial cross-sectional study included 4200 adults with diabetes (representing approximately 29.0 million persons) from the National Health and Nutrition Examination Survey (2001 to 2020). Age-adjusted prevalence of CKD G3a among adults with diabetes decreased from 6.6% to 3.0% by 2005-2008, then plateaued. CKD G4-G5 increased from 0.5% to 1.7% by 2009-2012, then decreased to 0.7% by 2017-2020. The prevalence of any CKD decreased from 34.1% to 25.3% by 2009-2012, then increased to 30.6% by 2017-2020. Correspondingly, albuminuria decreased from 28.4% to 21.2% by 2009-2012, then increased to 27.4% by 2017-2020. Among adults with concomitant CKD, proportion of adults achieving blood pressure (BP) < 140/90 mmHg increased from 64.6% to 75.1% by 2005-2008, then decreased to 59.5% by 2017-2020. Low-density lipoprotein cholesterol < 100 mg/dL, non-high-density lipoprotein cholesterol < 130 mg/dL, antidiabetic medication use and antihyperlipidemic medication use increased from 30.4%, 22.8%, 58.6%, and 33.8% to 46.4%, 45.6%, 74.2%, and 38.8%, respectively. Recommended antidiabetic medication use decreased from 37.6% to 24.2% by 2009-2012, then increased to 59.2% by 2017-2020. CONCLUSIONS: After a decade of decline, the prevalence of any CKD and albuminuria increased among US adults with diabetes, while CKD G3a plateaued. CKD G4-G5 peaked during 2005-2012 and decreased thereafter. Lipid control and use of antidiabetic and antihyperlipidemic medications among adults with concomitant CKD increased in the past 2 decades, whereas BP control decreased. This study provided updated trends in the prevalence of chronic kidney disease (CKD) in diabetes and in risk factor control and medication use in diabetes and CKD by using a nationally representative sample of the whole US noninstitutionalized population. Among US adults with diabetes, the prevalence of CKD decreased in earlier years but increased in recent years, while improvements in medication use for diabetes and lipids were observed, though blood pressure control declined.
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