Acta Diabetologica最新文献

Aims: To investigate the relationship between body adiposity and glycemic control in children and adolescents with type 1 diabetes (T1D).

Methods: This cross-sectional study included 364 children and adolescents aged 6-18 years with T1D. Anthropometric indices [BMI, BMI Z-score, waist-to-height ratio (WHtR)] and body composition [fat mass (FM), FM%, fat mass index (FMI)], assessed using bioelectrical impedance analysis, were obtained. Hemoglobin A1c and glucose sensor metrics, including time in range (TIR), were used to assess glycemic control. Associations between variables were analyzed using Spearman's correlation. Logistic regression models were run to identify independent predictors of HbA1c < 7.0% and TIR > 70%, with FMI, WHtR, total daily insulin dose per kg (TDD), treatment modalities, sex, age, diabetes duration, and pubertal stage as independent variables.

Results: Adiposity measures (FMI, FM%, and WHtR) were positively associated with HbA1c and negatively with TIR in both sexes. Logistic regression showed that HbA1c < 7% and TIR > 70% were significantly predicted by FMI [OR(95%CI): 0.822(0.704-0.960), p = 0.013, and 0.807(0.681-0.955), p = 0.012, respectively] and WHtR(x100) [OR(95%CI): 0.927(0.874-0.983), p = 0.013, and 0.923(0.866-0.985), p = 0.015, respectively], independently of TDD, sex, treatment modalities and the other independent variables.

Conclusions: Body adiposity negatively impacts glycemic control in children and adolescents with T1D, independent of sex and insulin treatment modalities. Despite technological advances in diabetes care, excess adiposity is emerging as a key modifiable factor associated with poorer glycemic outcomes and, consequently, poorer long-term health in children and adolescents with T1D.

Background: Women with previous gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes mellitus (T2DM). Although early postpartum screening is recommended, metabolic changes occurring during the first year remain poorly characterized, and Italian guidelines do not include assessment at this time point.

Aim: To evaluate glycaemic and metabolic changes one year after delivery in women with previous GDM and identify clinical and lifestyle predictors of postpartum glucose impairment.

Methods: A cohort of 134 women with prior GDM was assessed at 6-12 weeks (T0) and one year postpartum (T1). Anthropometric, biochemical, nutritional, lifestyle, and quality-of-life parameters were collected. Dietary habits were evaluated using a 3-day food diary and the PREDIMED questionnaire; physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). Logistic regression models were used to identify predictors of altered OGTT at T1.

Results: At baseline, 32.9% of women showed altered OGTT; this increased to 38.8% at one year, while T2DM prevalence rose from 2.2 to 5.2%. Insulin therapy during pregnancy was the only independent predictor of dysglycaemia at T1 (OR 3.5, 95% CI 1.28-9.50, p = 0.015). Women with altered OGTT reported lower SF-36 scores in the domains "role limitations due to physical health" (p = 0.016) and "health change" (p = 0.030). Breastfeeding was associated with more favourable glucose outcomes (p = 0.009).

Conclusions: One-year follow-up after GDM reveals early metabolic and psychosocial differences not detectable in the early postpartum period. Insulin therapy during pregnancy strongly predicts glucose impairment, highlighting the need for extended postpartum surveillance and targeted lifestyle interventions.

Background: Type 1 diabetes mellitus (T1DM) is primarily characterized by insulin deficiency; however, insulin resistance also contributes to poor metabolic outcomes and microvascular complications. The estimated glucose disposal rate (eGDR) is a simple, validated surrogate for insulin resistance. This study evaluated the utility of eGDR in predicting microvascular complications and metabolic syndrome (MetS) among Iraqi patients with type 1 diabetes mellitus (T1DM).

Methodology: A cross-sectional study was conducted between November 2024 and July 2025 at the diabetic center in Baghdad Medical City and Al-Mustansiriyah University, a total of 263 adults with T1DM (> 1 year duration) were enrolled. Clinical, anthropometric, and biochemical parameters were collected, and eGDR was calculated. Participants were stratified into quartiles of eGDR. Logistic regression analysis and ROC analysis were performed to evaluate the predictive role of eGDR.

Results: The mean age of participants was 25 ± 4.82 years, with an average diabetes duration of 8.62 ± 2.3 years. Suboptimal glycemic control was observed (HbA1c 9.11% ± 1.73). MetS was present in 36.9% of participants, while retinopathy, neuropathy, and nephropathy were detected in 4.6%, 5.7% and 4.6% respectively. Lower eGDR values were significantly associated with higher waist circumference, elevated HbA1c, and hypertension. eGDR independently predicted microvascular complications, with ROC analysis showing excellent discrimination for nephropathy (AUC 0.976), neuropathy (AUC 0.926), and retinopathy (AUC 0.914). The Predictive ability for MetS was moderate (AUC 0.731).

Conclusion: eGDR is a promising predictor of microvascular complications and MetS in T1DM.Its simplicity and low cost make it a practical clinical tool for early risk stratification, particularly in resource-limited settings.

Background: Mitochondrial failure is a cornerstone of diabetic organ damage. While it is well understood that shattered mitochondria (excessive fission) and aggressive cleanup (mitophagy) drive this deterioration, the upstream genetic "switches" that trigger these processes remain unclear. This study investigates whether a specific regulatory chain the TFAP4-UBC9-SUMO1 axis orchestrates this mitochondrial breakdown in diabetic tissues.

Methods: We analyzed transcriptomic data from four independent cohorts (GEO datasets: GSE1009, GSE4745, GSE6880, and GSE133598) covering diabetic renal and cardiac tissues. By integrating differential expression analysis with functional enrichment tools (GO, KEGG, and GSEA), we mapped the molecular landscape connecting cellular stress to mitochondrial dynamics and metabolic remodeling.

Results: Our analysis revealed a synchronized stress response across all datasets rather than isolated gene changes. Diabetic tissues exhibited a distinct upregulation of pathways related to protein SUMOylation, mitochondrial organization, and ER stress. Specifically, the data showed a convergence of signals indicating chronic "Protein processing in the endoplasmic reticulum" and sustained "Mitophagy," accompanied by broad shifts in lipid and energy metabolism. These signatures suggest that the machinery responsible for SUMO-modifying proteins is hyperactive and tightly linked to mitochondrial clearance programs.

Conclusion: The transcriptomic evidence supports a model where TFAP4 acts as a transcriptional driver that boosts UBC9 and SUMO1 expression. This upregulation likely fuels the SUMO-dependent modification of DRP1, locking mitochondria in a state of hyper-fission and forcing the cell into excessive self-eating (mitophagy). The TFAP4-UBC9-SUMO1 axis thus represents a critical, yet overlooked, engine of mitochondrial depletion and offers a promising new target for halting diabetic complications.

Background/objectives: Employing rigorous epidemiological approaches, we performed a systematic evaluation of Sodium Glucose Cotransporter-2 (SGLT-2) inhibitors for managing digestive system disorders and symptoms associated with Glycogen Storage Disease Type Ib (GSD Ib).

Methods: Electronic searches were conducted in three databases, with the latest update on 27 October 2025 (PROSPERO reference: CRD420251021881). Two reviewers independently screened records by title and abstract for full-text review. Eligible studies meeting the predefined criteria were assessed for quality using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for observational studies and the Methodological Index for Non-Randomized Studies (MINORS) for clinical trials, followed by data extraction.

Results: Meta-analysis or descriptive synthesis was performed for six common GSD Ib-related digestive symptoms. Multiple studies reported improvement in abnormal gastrointestinal patterns following SGLT-2 inhibitor therapy. Meta-analysis further demonstrated symptomatic relief in moderate-to-severe IBD, recurrent oral mucosal lesions, and anemia, with pooled remission rates (95% CI) under the two models being: 81.1% (68.4%-89.5%) and 85.3% (63.6%-99.2%) for IBD; 81.5% (73.6%-87.4%) and 83.5% (75.7%-90.3%) for oral lesions; and 60.5% (52.6%-68.0%) and 63.8% (48.0%-78.3%) for anemia. Regarding safety, hypoglycemia was the most frequently reported adverse event, followed by urinary tract and genital infections.

Conclusions: The efficacy analysis demonstrated beneficial effects of SGLT-2 inhibitors on six GSD Ib-related digestive disorders and its extra-digestive manifestations, showing potential for improving abnormal gastrointestinal patterns, moderate-to-severe inflammatory bowel disease, recurrent oral mucosal lesions, and anemia.

Cohen syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the VPS13B gene, classically presenting with developmental delay, distinctive craniofacial features, neutropenia, truncal obesity, and progressive retinal dystrophy. Metabolic abnormalities, including insulin resistance and diabetes mellitus, have been increasingly recognized, but early-onset diabetes with diabetic ketoacidosis remains uncommon. We report a 28-year-old Chinese woman with early-onset insulin-resistant diabetes complicated by recurrent diabetic ketoacidosis and nephropathy. She presented with intellectual disability, characteristic facial dysmorphism, truncal obesity with slender limbs, neutropenia, and visual impairment. Diabetes was diagnosed at 24 years of age, with negative islet autoantibodies and preserved C-peptide levels. Whole-exome sequencing identified two novel compound heterozygous VPS13B variants, including a synonymous variant with predicted splice-disrupting effects and a nonsense variant, confirming the diagnosis of Cohen syndrome. This case expands the mutational and metabolic spectrum of Cohen syndrome and highlights the importance of considering syndromic causes and genetic testing in patients with atypical early-onset diabetes.

Aims: Neonatal diabetes mellitus (NDM) occurs before 6-12 months of age and is commonly caused by activating mutations in KCNJ11 (KCNJ11-NDM) or ABCC8. Because of brain expression of these mutant ATP-dependent potassium channels, a spectrum of divergent neurodevelopmental difficulties have been described, including developmental delay, epilepsy, and neonatal diabetes (DEND). However, information on anxiety, social responsiveness, and grit is limited.

Methods: Individuals with KCNJ11-NDM (N = 12) and their unaffected siblings (N = 12) were recruited through the University of Chicago Monogenic Diabetes Registry and participants or their parent/caregiver completedthe Screen for Adult/Child Anxiety Related Disorder (SCAARED/SCARED), the Social Responsiveness Scale, Second Edition (SRS-2), and the Grit Scale.

Results: Mean SRS-2 scores were significantly different between KCNJ11-NDM and sibling controls (P = <0.001 ), with 7/10 affected participants, and 0 /11 siblings, having scores suggestive of autism spectrum disorder (ASD). Differences in anxiety (P = 0.69) and grit (P = 0.46) were not significant when compared to sibling controls; however, 58% (7/12) of KCNJ11-NDM participants and 40% (4/10) of sibling controls had scores indicating an anxiety disorder by either self- or parent-report.

Conclusions: Our results agree with previous studies suggesting significant difficulties with social functioning in KCNJ11-NDM, with 7/10 participants having scores suggestive of ASD, strongly reinforcing the need for early neurodevelopmental screening to allow for prompt support. Our report adds to the knowledge of this population in finding robust grit scores but with a high level of anxiety in both KCNJ11-NDM and unaffected siblings. Although families affected by KCNJ11-NDM may have a high risk of anxiety disorders, it is encouraging that affected and unaffected children exhibit robust self-resiliency that will help support functioning through the challenges of life. Study of additional individuals will help to clarify specific challenges, long-term outcomes, and best approaches for monitoring and support.

Aims: Continuous glucose monitoring (CGM) benefits pregnant women with type 1 or type 2 diabetes, but its role in gestational diabetes (GDM) remains uncertain. We aimed to compare the effects of CGM with self-monitoring of blood glucose (SMBG) on glycemic, maternal, and neonatal outcomes in women with GDM.

Methods: We compared CGM with SMBG in women with GDM through a systematic search across randomized controlled trials (RCTs) in PubMed, Cochrane Library, Embase, and Scopus. We evaluated glycemic, maternal and neonatal outcomes using a random-effects model.

Results: Eleven RCTs (n = 1225) met inclusion criteria. The use of CGM increased the likelihood of achieving appropriate maternal weight gain (RR 1.37, 95% CI 1.02 to 1.82; I² = 0%) and reduced mean neonatal birth weight (MD - 122.79 g, 95% CI - 189.78 to - 55.79; I² = 0%). CGM use did not change maternal time in range (TIR), time above range (TAR), time below range (TBR), glycated hemoglobin, gestational hypertension, cesarean delivery, macrosomia, preterm delivery, neonatal hypoglycemia, or neonatal intensive care unit admissions.

Conclusions: In women with GDM, the use of CGM improved the likelihood of appropriate maternal weight gain and lowered neonatal birth weight compared with SMBG, but it did not improve overall glycemic control or other maternal and fetal outcomes.

Trial registration: PROSPERO CRD420251044960 (registered 2025).