Search

Background: Enhanced marrow adiposity is frequently linked with a decline in bone density. The underlying mechanisms responsible for bone loss in diabetes are not well understood. In this investigation, we employed an alloxan-induced diabetes rabbit model to unravel the association between marrow fat content and bone resorption, utilizing magnetic resonance spectroscopy. Methods: Forty 4-month-old male New Zealand rabbits were randomly allocated into two groups: a control group and an alloxan-induced diabetic group, each consisting of 20 rabbits. Biochemical analyses covered plasma glucose, enzyme levels, lipid profiles, blood urea nitrogen, creatinine levels, and markers of bone turnover. Quantification of bone marrow adipose tissue utilized both MR spectroscopy and histological examinations. Dual-energy X-ray absorptiometry and microcomputed tomography were employed to determine bone density and trabecular bone microarchitectures. The expression levels of marrow adipocyte markers (peroxisome proliferator-activated receptor-gamma2, CCAAT/enhancer-binding protein-α, and fatty acid binding protein 4) and markers of bone resorption [tartrate-resistant acid phosphatase (TRACP) and cathepsin K] were assessed using RT-PCR. Results: Diabetic rabbits exhibited significant increases in marrow fat fraction (MFF) over time (MFF increased by 13.2% at 1.5 months and 24.9% at 3 months relative to baseline conditions, respectively). These changes were accompanied by the deterioration of trabecular microarchitectures. Marrow adipogenesis was evident through a 31.0% increase in adipocyte size, a 60.0% rise in adipocyte number, a 103.3% increase in the percentage of adipocyte area, and elevated mRNA expressions of marrow adipocyte markers. Osteoclast markers (TRACP and cathepsin K RNA and serum TRACP5b levels) were elevated in diabetic rabbits. MFF exhibited a robust correlation with trabecular bone microarchitectures. A significant positive correlation was identified between ΔMFF and serum ΔTRACP5b levels. Moreover, MFF at 3 months showed a strong positive correlation with serum TRACP5b levels (r = 0.763), as well as with the mRNA expression of osteoclast markers, including TRACP (r = 0.784) and cathepsin K (r = 0.659), all with p < 0.001. Conclusions: Rabbits with type 1 diabetes experience an expansion of marrow adiposity, and this enhanced marrow adiposity is associated with increased osteoclast activity. [ABSTRACT FROM AUTHOR]

Introduction: Studies assessing longitudinal changes in the prevalence of autoimmune thyroiditis (AIT) among the pediatric population are limited. During the COVID-19 era, several papers proposed a rise in AIT cases. Our study aimed to analyze the prevalence of thyroid autoimmunity (TA) over a 10-year period spanning pre-pandemic and pandemic years in a population who are regularly screened for thyroid disturbances. Materials and methods: This single-center retrospective cohort study analyzed data from 1,361 children and young adults with type 1 diabetes (T1D) treated between 2013 and 2022 in Hungary's largest pediatric endocrinology center. Results of anti-thyroid autoantibodies (anti-thyroid peroxidase/ATPO/and antithyroglobulin/ATG/), thyroid function tests (TFTs) and thyroid ultrasound examinations were obtained. Annual prevalence rates of TA and ultrasound-proven thyroiditis were calculated. Mean (± SD) follow-up period was 4.7 (± 2.8) years. Results: The overall prevalence of TA among our T1D children was 22.8% ([20.3;25.5], 310 cases) with significantly more girls affected (p<0.001). From 2013 to 2022, TA prevalence rose from 15.9% to 20.6% (p=0.041). The increase was detected during the pre-pandemic years but not in the COVID-19 era. Ultrasound-confirmed thyroiditis was present in 80.0% of examined TA cases. Ultrasound positivity rate was stable during the study period. Among our children with TA, 28.5% exhibited clinically relevant thyroid-stimulating hormone (TSH) abnormalities (most commonly subclinical hypothyroidism) and/or were prescribed thyroid medication. Children with AIT had a significantly elevated risk of thyroid dysfunction compared to those with only thyroid autoantibody positivity (p<0.001). Conclusion: Our results show a rise in the prevalence of thyroid autoimmunity among T1D children over the past decade, but our data do not support the assumed role of SARS-CoV-2 in the development of the disease. [ABSTRACT FROM AUTHOR]

Introduction: For people living with diabetes, effective glucose monitoring is a key component in diabetes care, helping to reduce disease burden, complications, and healthcare utilization. Sensor-based glucose monitoring systems, which can provide more comprehensive information about glucose levels than capillary-based self-monitoring of blood glucose (SMBG), are becoming established among people living with diabetes. The objective of this study was to assess the cost-effectiveness of glucose monitoring with FreeStyle Libre systems, compared with SMBG, from the perspective of a Canadian private payer. Methods: The analysis used the validated, person-level microsimulation model DEDUCE (Determination of Diabetes Utilities, Costs, and Effects). Analyses were conducted separately for populations of people with type 1 and type 2 diabetes mellitus (T1DM; T2DM), with time horizons of 40 and 25 years, respectively. T2DM treatment was assumed to be 84% non-insulin, 10% basal insulin, and 6% multiple daily injections of insulin. The effect of FreeStyle Libre was modeled as reductions versus SMBG in glycated hemoglobin level (T1DM, − 0.42%; insulin-treated T2DM, − 0.59%; non-insulin-treated T2DM, − 0.3%) and in acute diabetic events (hypoglycemia and diabetic ketoacidosis). Costs (in 2023 Canadian dollars (Can$)) and utilities were discounted at 1.5%. Outcomes were assessed as costs and quality-adjusted life years (QALYs). Results: In both populations, FreeStyle Libre was dominant to SMBG, providing more QALYs at a lower cost (T1DM: + 1.25 QALYs, − Can$32,287 costs; T2DM: + 0.48 QALYs, − Can$8091 costs). Reductions were seen in the cumulative incidence of all complications (except blindness in the T1DM analysis). FreeStyle Libre was dominant to SMBG in all scenarios tested. Probabilistic sensitivity analysis showed that FreeStyle Libre had a 100% probability of being dominant to SMBG for T1DM and a 91% probability of being dominant for T2DM. Conclusion: This economic analysis shows that, from a Canadian private payer perspective, FreeStyle Libre is cost-effective compared with SMBG for all people living with diabetes. Plain Language Summary: Glucose monitoring is important for people living with diabetes. Effective glucose monitoring can reduce the risk of hypoglycemia (low blood sugar), diabetic ketoacidosis (a potentially life-threatening complication which occurs when the body has low insulin and high blood sugar levels), and long-term complications. This can be done using finger sticks and test strips or sensor-based devices such as the FreeStyle Libre systems. In this study, we modeled the effect of FreeStyle Libre use in persons living with type 1 or type 2 diabetes mellitus in Canada using the DEDUCE economic model. In both analyses, FreeStyle Libre use was predicted to lead to better outcomes (measured as quality-adjusted life years—a measure of health which combines life expectancy with quality of life) for people living with diabetes while reducing costs. [ABSTRACT FROM AUTHOR]

Objective: Conduct a cross-sectional study to investigate the periodontal conditions and oral health behaviours among adult subjects with type one diabetes mellitus and compare them with those of a group of age- and gender-matched without diabetes. Furthermore, we also intend to evaluate the potential indicators of the risk for the development of periodontal disease. Methods: The evaluation was undertaken with patients with diabetes (n = 70) from a patients’ cohort of the the Hospitalar Center of Tâmega e Sousa and subjects without diabetes (n = 69). Results: The prevalence of periodontal disease showed significant differences between groups. Gingivitis reached a prevalence of 37.1% in patients with type one diabetes mellitus and periodontitis 55.7%. These systemically compromised patients exhibited a higher prevalence of Plaque Index, Bleeding on Probing and Periodontal Probing Depth and a reduced number of teeth when compared to the control group. The stage II was the most prevalent in the diabetes population, followed by the stage IV and most of diabetes subjects presented grade C progression. Conclusions: There is a higher prevalence of periodontal disease in type one diabetes mellitus individuals when compared to the controls. Age, Bleeding on Probing and number of cigarettes per day are associated with higher risk of periodontal disease in type one diabetes mellitus patients. Clinical relevance: Our study provides evidence about the prevalence of periodontal disease among type 1 diabetes mellitus and creates awareness regarding the factors that potentially contribute to worsening periodontal tissues. Furthermore, informing diabetic patients about the importance of early diagnosis and prevention of periodontal disease and the importance of reducing/quitting smoking. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Serum lactate levels have been recognized as a robust marker for predicting disease severity and survival in many critically ill children but consensus is lacking regarding its utility in diabetic ketoacidosis. This study aimed to investigate the relationship between initial lactate levels and disease severity in pediatric patients presenting with diabetic ketoacidosis. Methods: This single-center retrospective descriptive study involved pediatric patients with diabetic ketoacidosis in the pediatric emergency department between January 2022 and April 2023. Patients were diagnosed using the International Society for Pediatric and Adolescent Diabetes 2022 guidelines. Results: Among the 112 patients included in the study, 41 (36.6%) were classified as mild, 42 (34.8%) as moderate and 32 (28.6%) as severe acidosis. A statistically significant difference was observed between the time to resolution and clinical severity of diabetic ketoacidosis (p < 0.001). Elevated lactate levels of 2.5 mmol/L or above were detected in 37.5% (42/112) of our patients and a significant increase in clinical severity was observed as lactate levels increased (p < 0.001). Correlation analysis revealed no significant relationship between lactate levels and time to resolution of diabetic ketoacidosis or length of intensive care unit stay. Multivariate analysis demonstrated a significant association between lactate levels and severity of acidosis (p: 0.046). Conclusion: Although there is an association between the severity of acidosis and lactate levels in diabetic ketoacidosis, contrary to expectations, this relationship was not found to be associated with adverse outcomes. An important point not to be overlooked by pediatricians is that elevated lactate levels in diabetic ketoacidosis may not always herald poor outcomes. [ABSTRACT FROM AUTHOR]

Aim: To measure the impact of type 1 and 2 diabetes mellitus (T1D and T2D) on the QoL of a person's family members/partner and assess if there is any difference in family impact. Methods: A cross‐sectional study, recruited online through patient support groups, involved UK family members/partners of people with diabetes completing the Family Reported Outcome Measure‐16 (FROM‐16). Results: Two hundred and sixty‐one family members/partners (mean age = 57.9 years, SD = 13.8; females = 68.2%) of people with diabetes (mean age = 57.7, SD = 20.6; females = 38.3%; T1D n = 100; T2D n = 161) completed the FROM‐16. The overall FROM‐16 mean score was 10.47, SD = 7.8, suggesting a moderate effect on the QoL of family members of people with diabetes. A quarter (24.5%) of family members experienced a 'very large effect' or 'extremely large effect' on their QoL. The family impact of T1D (mean FROM‐16 = 12.61, SD = 7.9) was greater than that of T2D (mean = 9.15, SD = 7.5, p < 0.01), with being 'female' and 'parents of children and adolescents' rendered as significant predictors of greater impact. Family members of T2D had a lower risk of experiencing a high family impact (FROM‐16 score >16) compared with T1D (RR 0.561, 95% CI 0.371–0.849). Conclusions: Compared to T2D, family members of T1D experience a greater impact on their QoL, particularly those caring for children and adolescents. These findings have clinical and resource implications, indicating a need to assess this impact as a part of routine diabetes care to support impacted family members. The FROM‐16 could assess this impact in routine practice and further facilitate referral of family members to appropriate support services. [ABSTRACT FROM AUTHOR]

Aim: Intraindividual body weight variability (BWV), that is, the degree of weight fluctuations over time, is associated with an increased risk of cardiovascular diseases (CVDs) in multiple settings. The impact of BWV on cardiovascular risk in type 1 diabetes (T1D) remains unclear, despite the issues relative to weight management in individuals with this condition. Materials and methods: Using data from the Swedish National Diabetes Register, we identified individuals with T1D and without CVD at baseline with at least three measurements of body weight taken over three consecutive years. We estimated BWV as quartiles of the standard deviation of weight measures and explored its longitudinal association with the incidence of CVD during a 12.7 ± 4.6 year follow‐up through adjusted Cox regression models. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke and all‐cause mortality. We modelled the function of risk in relation to the magnitude of BWV, testing also whether weight trends, that is, increasing, stable or decreasing, age, sex and glycaemic control modified the association between BWV and the outcome. Results: Among the 36 333 individuals with T1D in the register, we identified 19 373 individuals with at least three measures of body weight and without CVD at baseline. Participants with the highest BWV had a 42% increased risk of reaching the primary endpoint compared to those with the lowest BWV (hazard ratio [HR] = 1.42, 95% confidence interval [CI]: 1.24–1.62). In addition, high BWV was significantly associated with a 51% increased risk of all‐cause mortality (HR = 1.51, 95% CI: 1.28–1.78), a 37% increased risk of peripheral artery disease (HR = 1.37, 95% CI: 1.06–1.77) and a 55% increased risk of hospitalization for heart failure (HR = 1.55, 95% CI: 1.20–2.01). BWV showed a quasi‐linear association with the primary endpoint. No interaction was observed when comparing subgroups for weight trends, sex or degree of glycaemic control. In the subgroup of elderly individuals, the association of BWV with the primary endpoint was no longer significant. Conclusions: High BWV is associated with an increased risk of CVD and all‐cause mortality in individuals with T1D, independently of canonical risk factors. Weight trends, sex and glycaemic control do not modify such association while older age attenuates it. [ABSTRACT FROM AUTHOR]

Background: Baihu Jia Renshen Decoction (BJRD) is used for diabetes mellitus (DM) management in clinics. Objective: To elucidate the potential mechanism of BJRD in treating type 1 DM (T1DM). Methods: T1DM models were established via intraperitoneal injection of streptozotocin (STZ). Rats were subsequently randomly divided into the normal control (NC), model (MOD), insulin (INS), INS + BJRD-medium dose (MID), and INS + BJRD-high dose (HIGH) groups. The rats' body weight was measured. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs) in the muscle and adipose tissues. Quantitative real-time polymerase chain reaction was utilized to verify the DEG levels. Results: Body weights of MOD, INS, MID, and HIGH groups were significantly reduced as compared to those of NC group. Compared with NC group, MOD group showed significant Hspa1b and Notch3 downregulation and Camkk2 level elevation. Compared with MOD group, INS group showed further downregulation of the Hspa1b level, whereas MID group exhibited an increase. The Camkk2 levels in INS, MID, and HIGH groups were further reduced. The Notch3 levels did not significantly change in INS and MID groups, whereas that of HIGH group increased. Additionally, compared with NC group, MOD group demonstrated upregulation of the Myl1, Mylpf, Acacb, and Pygm levels and downregulation of Fasn level. Compared with MOD group, Myl1, Mylpf, and Pygm levels in INS, MID, and HIGH groups were down-regulated, whereas Fasn and Acacb levels were up-regulated. Conclusion: BJRD may influence pancreatic β-cell function, thereby enhancing the function of the skeletal muscle and adipose tissues in a T1DM rat model. [ABSTRACT FROM AUTHOR]

Objective: Earlier work suggests Myoinositol (MI) and D‐chiro‐ inositol (DCI) imbalance in urine and plasma of diabetic patients, and their potential for monitoring insulin resistance. This study aimed to assess levels of Myoinositol (MI) and D‐chiro‐ inositol (DCI) in saliva of children with type 1 diabetes mellitus (DM‐1) and controls, to verify if concentrations of MI and DCI are similarly altered in saliva, exploring their potential for monitoring DM‐1. Design, Patients and Measurements: This cross‐sectional clinical study enroled 45 patients (DM‐1, n = 25; Controls, n = 20). Children aged 3–12 years with fasting blood glucose levels > 126 mg/dL, and HbA1c levels > 7%. Saliva was collected, and salivary measurements included pH, flow rates and concentrations of MI, DCI and glucose, employing high‐performance liquid chromatography. Periodontal health was assessed using bleeding and plaque indices. Results: Children with DM‐1 showed elevated MI (p = 0.001), reduced DCI (p = 0.001), and increased MI‐DCI ratio (p = 0.001). The MI‐DCI ratio was elevated by 16‐fold among diabetic children. Plaque (p = 0.003) and gingival bleeding (p = 0.001) were higher in DM‐1 than controls. The MI increased the odds of an outcome of DM‐1 by 174%, while DCI reduced the odds by 63%, highlighting their strong and opposing effects on DM‐1. Conclusions: Children with DM‐1 express higher MI and lower DCI levels, while non‐diabetic children show an inversion of these concentrations. Inositol imbalance in saliva of diabetic children resembles previous results in urine, and represents a possible venue for monitoring this disease, paving the way for future investigations into salivary inositols. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) and neurodegenerative diseases/disturbances are worldwide health problems. The most common chronic conditions diagnosed in persons 60 years and older are type 2 diabetes mellitus (T2DM) and cognitive impairment. It was found that diabetes mellitus is a major risk for cognitive decline, dementia, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Different mechanisms of associations between these diseases and diabetes mellitus have been suggested. For example, it is postulated that an impaired intracellular insulin signaling pathway, together with hyperglycemia and hyperinsulinemia, may cause pathological changes, such as dysfunction of the mitochondria, oxidative stress inflammatory responses, etc. The association between diabetes mellitus and neurodegenerative diseases, as well as the mechanisms of these associations, needs further investigation. The aim of this review is to describe the associations between diabetes mellitus, especially type 1 (T1DM) and type 2 diabetes mellitus, and selected neurodegenerative diseases, i.e., Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. Suggested mechanisms of these associations are also described. [ABSTRACT FROM AUTHOR]

Introduction: Type 1 diabetes mellitus (T1DM) is a chronic metabolic disorder primarily managed through insulin therapy, which is crucial for achieving optimal glycemic control in children and adolescents. Therapeutic education is essential, equipping patients and their families with the knowledge and skills necessary for effective self-management. This familial support plays a critical role in the success of therapy and in fostering an environment conducive to the child's self-management of the condition. A core objective of therapeutic education is the prevention of complications associated with T1DM. Children and adolescents are made aware of the importance of consistent disease management by receiving information about the potential consequences of prolonged metabolic dysregulation. Methods: The study employed a diagnostic survey method with a proprietary questionnaire consisting of a demographic section and 28 closed-ended questions. The survey was conducted between February and May 2024 at the Pediatric Diabetes and Pediatrics Clinical Department of the Polikarp Brudziński Independent Public Children's Clinical Hospital in Warsaw. A total of 100 valid responses were included. Data were analyzed using frequency analysis for categorical variables, descriptive statistics for quantitative data, and Pearson's Chi-squared test for relationship analysis. Results: Most parents (76%) initiated knowledge acquisition in diabetology departments. Group and individual training sessions were attended by 58% of respondents. Training frequency was predominantly daily (88%), and 92% of parents stressed the importance of consistent education. The vast majority (96%) of participants rated the training as well prepared, with 100% affirming that the education was adapted to their needs. Conclusions: Therapeutic education for children with T1DM is highly effective, particularly when integrating individual and group training sessions. Regular daily exercise is associated with higher levels of knowledge and skills in diabetes management. This emphasizes the importance of structured and frequent educational programs to optimize disease control, enhance familial support, and prevent complications, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes mellitus (T1DM) in pediatric patients often leads to emotional distress, impacting self-management. The PAID-Peds survey measures diabetes-related emotional burden but lacks a validated Spanish version. This study aimed to validate the Spanish PAID-Peds survey in children and adolescents with T1DM and correlate it with diabetic metabolic control parameters. Methods: A cross-sectional study was conducted from October 2022 to December 2023, recruiting 636 patients aged 8–17 years from three Spanish hospitals. Psychometric properties were assessed using Cronbach's alpha for reliability and confirmatory factor analysis for construct validity. Associations between PAID-Peds scores and clinical measures, such as HbA1c, were examined. Results: The final sample consisted of 538 participants (84.59% response rate). The PAID-Peds survey showed high internal consistency (Cronbach's alpha = 0.90). The confirmatory factor analysis indicated a satisfactory model fit (χ2 = 812.28, p < 0.001; RMSEA = 0.08). Weak correlations were found between PAID-Peds scores and HbA1c (r = 0.14, p < 0.001). Conclusions: The Spanish PAID-Peds survey is a reliable tool for assessing emotional burden in pediatric T1DM patients. Integrating it into clinical practice may improve early identification of emotional distress, aiding in better diabetes management. Further research should explore its application over time and in intervention studies. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the fluctuations in glucose levels measured using CGM-metrics during the four distinct seasons of the year in individuals with type 1 diabetes mellitus (T1DM) using an intermittently scanned CGM (isCGM) device or sensor augmented pump (SAP). Research design and methods: This retrospective, single-center study enrolled 93 individuals with T1DM who were equipped with an isCGM device or SAP at Kobe University Hospital. The subjects had a median age of 47.0 years [interquartile range, 37.0–62.0 years], 25 individuals (26.9%) were male, median body mass index was 22.0 kg/m2 [20.8–23.8 kg/m2], and median hemoglobin A1c level was 7.4% [6.9–8.0%]. CGM data were reviewed from January to December 2019, and the mean sensor glucose (SG) value, time above range (TAR), time in range (TIR), time below range (TBR), and standard deviation (SD) of SG were calculated for each season (spring, March–May; summer, June–August; autumn, September–November; winter, December–February). Results: Seasonal fluctuations were detected for mean SG, TAR, TIR, and SD, with TIR being lower and mean SG, TAR, and SD being higher in cold seasons (spring or winter) than in warm seasons (summer or autumn). Conclusion: Seasonal fluctuations in CGM metrics should be taken into account in future studies performed to evaluate the favorable impact of CGM on glycemic management in individuals with T1DM. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate whether glycoprotein and lipoprotein lipidomics profiles could enhance a clinical predictive model for carotid subclinical atherosclerosis in patients with type 1 diabetes (T1D). Additionally, we assessed the influence of cardiac autonomic neuropathy (CAN) on these predictive models. Methods: We conducted a cross-sectional study including 256 patients with T1D. Serum glycoprotein and lipoprotein lipidomics profiles were determined using 1H-NMR spectroscopy. Subclinical atherosclerosis was defined as carotid intima-media thickness (cIMT) ≥ 1.5 mm. CAN was identified using the Clarke score. Predictive models were built and their performance evaluated using receiver operating characteristic curves and cross-validation. Results: Subclinical atherosclerosis was detected in 32% of participants. Patients with both CAN and atherosclerosis were older, had a longer duration of diabetes, and were more likely to present with bilateral carotid disease. Clinical predictors such as age, duration of diabetes, and smoking status remained the strongest determinants of subclinical atherosclerosis [AUC = 0.88 (95%CI: 0.84–0.93)]. While glycoprotein and lipoprotein lipidomics profiles were associated with atherosclerosis, their inclusion in the clinical model did not significantly improve its diagnostic performance. Stratification by the presence of CAN revealed no impact on the model's ability to predict subclinical atherosclerosis, underscoring its robustness across different risk subgroups. Conclusions: In a cohort of patients with T1D, subclinical atherosclerosis was strongly associated with traditional clinical risk factors. Advanced glycoprotein and lipoprotein lipidomics profiling, although associated with atherosclerosis, did not enhance the diagnostic accuracy of predictive models beyond clinical variables. The predictive model remained effective even in the presence of CAN, highlighting its reliability as a screening tool for identifying patients at risk of subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]

Introduction: Appropriate glycemic control is paramount for people with type 1 diabetes (PwT1D) by the effective delivery of exogenous insulin. However, glycemic variability and the risk of severe hypoglycemia must be reliably controlled. Methods: COMET-T is a prospective, multicenter, observational study conducted in Germany, Austria, and Switzerland during 2021–2022 to assess the effectiveness and safety of insulin glargine 300 U/ml (Gla-300) after switching from other basal insulins. Out of 135 PwT1D, data of 94 patients were analyzed. The primary endpoint was the change in time in range (TIR) approximately 12 and 24 weeks after switching to Gla-300. Secondary endpoints were: change in HbA1c, fasting plasma glucose (FPG), coefficient of variation (CV%) of plasma glucose, body weight (BW) and insulin dose. Results: Patients had mean age of 48.6 ± 16.5 years, included 39.4% males and had 18.2 ± 15.5 years T1D duration. From baseline (54.3%), TIR changed at week 12 (mean change 0.3% [± 14.3]; p = 0.8383) and at week 24 (+ 4.5% [± 14.9], p = 0.078). At week 24, TIR significantly increased in patients with body mass index > 30 kg/m2 (8.4% [± 12.8] p = 0.0057) and patients who previously received insulin detemir (10.5%; [± 12.93]; p = 0.0005). At week 24, there was a significant reduction in the HbA1c value (8.1 ± 0.6% vs. 7.7 ± 0.9%; p < 0.001), a reduction in the CV% of plasma glucose (36.1 ± 12.4% vs. 32.8 ± 9.6%, p = 0.056), and increase in bolus insulin dose (26.5 ± 16.3 vs. 27.9 ± 16.6 U/day; p = 0.042). FPG, BW, and basal insulin doses were not significantly changed. Conclusions: Although switching to Gla-300 in poorly controlled PwT1D did not significantly reduce TIR, it significantly decreased HbA1c values and glycemic variability without changes in BW and basal insulin dose. [ABSTRACT FROM AUTHOR]

Background: The etiology of type 1 diabetes (T1D) remains an area of active research, with genetic and environmental factors being investigated. This meta-analysis aimed to determine if rotavirus vaccination influences the onset of T1D in children. Methods: Following PRISMA 2020 guidelines, two researchers independently searched multiple databases, including PubMed and Google Scholar, for studies published in English from 2006 to September 2024. They used the search terms "rotavirus vaccination" and "type 1 diabetes", and assessed study quality using the ROBINS-E tool. The analysis pooled hazard ratios (HRs) from selected studies using a fixed-effects model, with statistical significance set at p < 0.05 and heterogeneity evaluated using the I2 statistic. Results: A systematic search identified 90 records, of which 5 studies met the inclusion criteria. These studies, encompassing a total population of 4,427,291 children from developed countries, suggest a protective effect of rotavirus vaccination against T1D. The pooled HR was 0.87 (95% CI: 0.78–0.98), indicating a 13% lower risk of T1D in vaccinated children compared to unvaccinated ones (p = 0.03). Moderate heterogeneity was noted (χ2 = 10.02, df = 4, p = 0.04, I2 = 60%). Conclusions: This analysis suggests that rotavirus vaccination may reduce the risk of T1D in children from high-income Western countries. While these findings are promising, they may not be generalizable to settings outside similar advanced healthcare systems. Further research is needed to confirm the protective effects of rotavirus vaccination against T1D across diverse populations. [ABSTRACT FROM AUTHOR]

Thyroid dysfunctions are common in type 1 diabetes mellitus (T1DM) pregnancies, impacting embryogenesis and fetal neurodevelopment. This study investigates the effects of subclinical hypothyroidism and BDNF (Brain-derived neurotrophic factor) telomere length in T1DM mothers and their newborns. In a recent study, researchers found an inverse relationship between TSH (thyroid-stimulating hormone) levels and telomere length in the cord blood of newborns. This was prospective cohort analysis of 70 mothers and their newborns with T1DM. The study measured leukocyte telomere length (LTL) in maternal and neonatal samples. Subclinical hypothyroidism during the first trimester was characterized by TSH levels ranging from 2.5 to 5.0 mIU/L alongside normal free thyroxine (FT4) concentrations. In this study, we proved that maternal telomere length predicts telomere length in the newborn. Furthermore, we investigated the influence of maternal hypothyroidism on telomere length in the newborn. Maternal hypothyroidism in the first trimester of pregnancy has a strong influence on the shortening of newborn telomeres. BDNF has a positive effect on maternal and newborn telomere length. These results can have an important impact on the subsequent development of a child born to a diabetic mother. Health and disease associated with telomere length later in life may be programmed at birth. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic neuropathy is the most common long-term complication of diabetes mellitus, widely studied in the adult population, but its prevalence in children and adolescents has not yet been clearly defined. Materials and Methods: Diabetic patients over 11 years old and with at least 5 years of diabetes were subjected to specific tests for the screening of diabetic peripheral neuropathy (DPN) and for the diagnosis of cardiac autonomic neuropathy (CAN). Additionally, all data related to the patients' average hemoglobin (HbA1c) levels over the last year and the past 5 years and the monitoring and insulin delivery technology used were collected. Results: Tests were performed on a total of 81 patients. DN diagnostic tests identified 17 patients with signs of neuropathy (21.0%), specifically 11 with DPN (13.6%) and 7 with CAN (8.6%). Data showed that the 5-year HbA1c of those diagnosed with DPN was significantly higher compared to those without a diagnosis. The analysis also highlighted that an average HbA1c level over 5 years greater than 8.5% increases the risk of DPN by 10 times. Conclusions: This article confirms that diabetic neuropathy begins to develop even in pediatric patients, that various nerve conduction systems may be affected, and that poorer glycometabolic control is associated with an increased risk of developing DN. These results highlight the importance of early screening and prevention through tight glycometabolic control. [ABSTRACT FROM AUTHOR]

Aim: To test whether an audit and feedback‐based intervention improved HbA1c 12 months after transfer to type 1 diabetes adult care. Methods: Multi‐centre, quasi‐experimental pre‐post study of an AF‐based intervention targeting paediatric diabetes teams, which encouraged the implementation of an evidence‐informed structured transition process at five paediatric diabetes centres in Ontario, Canada. Participants entered the study at their final paediatric visit. A parallel control cohort was ascertained using population‐based administrative datasets. The primary outcome was HbA1c 12 months after transfer. The main exposure was the study period: pre‐implementation (June 2018–May 2019); early‐implementation (June 2019–September 2020); and late‐implementation (October 2020–September 2021). Multivariable linear regression models were fit separately in each cohort. Results: There were 449 and 2844 individuals in the intervention and control cohorts, respectively. Twelve months after transfer, participants in the late‐implementation intervention cohort had an HbA1c that was, on average, 0.41% lower than participants in the pre‐implementation period (p = 0.016). Among the control cohort, there was no significant difference in the HbA1c 12 months after transfer between study periods. Conclusions: We found an effect of the intervention on glycaemic management one year following transfer to adult care. Future work will focus on refining and testing the effectiveness of the intervention in an expanded number of study sites and in collaboration with adult diabetes care providers. [ABSTRACT FROM AUTHOR]

The hybrid closed-loop (HCL) system, Medtronic MiniMed™ 770G, has been available for use by Japanese individuals with type 1 diabetes mellitus since 2021. The aim of this study was to evaluate the effect of its use on glycemic variability and quality of life (QOL) in this population. This multicenter, open-label, prospective observational study included 14 Japanese individuals with type 1 diabetes mellitus treated with MiniMed™ 640G. Participants who switched to the 770G system were evaluated for time in range (TIR) and other glycemic outcomes at baseline and at 3 and 12 months post-transition. QOL was assessed using the Diabetes Therapy-Related QOL (DTR-QOL) scale. The mean baseline glycated hemoglobin was 7.52 ± 1.05%, and body mass index (BMI) was 21.78 ± 3.07 kg/m2. By study completion, individuals used the HCL system approximately 80% of the time in a day. TIR showed improvement, with an increased achievement ratio of TIR > 70% at 12 months. Hypoglycemia occurrence was minimal at 12 months. In addition, all-time sensor glucose measurements decreased after 12 months, and there were no significant changes in BMI or daily insulin dose. DTR-QOL scores did not significantly differ, possibly owing to increased total alarms and sensor calibration times. Transitioning to the Medtronic MiniMed™ 770G system led to an improved achievement ratio of TIR > 70% and reduced hyperglycemia at 12 months. However, no significant change in QOL was observed, probably because of the increased number of total alarms. [ABSTRACT FROM AUTHOR]

Introduction: Type 1 diabetes is often accompanied by autoimmune thyroid disease. We aimed to investigate the clinical characteristics of Japanese patients with acute-onset type 1 diabetes and thyroid autoantibodies, focusing on decreased endogenous insulin secretion. Materials and methods: We examined 80 patients with acute-onset type 1 diabetes, classifying them into two groups with and without thyroid autoantibodies and compared the clinical characteristics of the two groups. A fasting serum C-peptide immunoreactivity (CPR) of less than 0.1 ng/mL was defined as insulin depletion. Results: In patients with thyroid autoantibodies, the median fasting serum CPR levels at the fourth year after the onset of type 1 diabetes were significantly lower than in those without thyroid autoantibodies (p = 0.02). The cumulative incidence of insulin depletion at 5 years of duration after diagnosis of type 1 diabetes was significantly higher in thyroid autoantibody-positive group than in thyroid autoantibody-negative group (p = 0.01). In the Cox proportional models adjusted for selected baseline factors (age, sex, and BMI), the presence of thyroid autoantibodies did not increase the risk of insulin depletion within 5 years after the onset. However, in bivariate Cox proportional hazards models that investigated the association between thyroid autoantibodies and each baseline factor, the presence of thyroid autoantibodies significantly increased the risk of insulin depletion. Conclusions: Our study showed that Japanese patients with acute-onset type 1 diabetes and positive for thyroid autoantibodies had a higher risk of insulin deficiency within 5 years after the onset than those without thyroid autoantibodies. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the economic value of intermittent-scanning continuous glucose monitoring (isCGM) with self-monitoring of blood glucose (SMBG) in adults with type 1 diabetes (T1D). Methods: Participants were placed on either an isCGM or SMBG arm for 84 days, in a randomized, crossover setup with a 28-day washout period. Clinically relevant hypoglycemia (<54 mg/dL) and severe hypoglycemia (SH) risks were calculated by analyzing the data from isCGM. The effectiveness variable was quality-adjusted life years (QALYs), and costs included medical costs related to the SMBG device. In addition, we performed a sensitivity analysis using a tornado diagram to confirm the robustness of the results. Patients: A total of 93 Japanese T1D adults (51.4 ± 15.3 years old, male 47.3%, and HbA1c 7.3 ± 0.7%) treated with multiple daily insulin injection (MDI). Results: Compared to the SMBG arm, clinically relevant hypoglycemia and SH risks over daytime (2.7 ± 1.7 vs. 2.4 ± 1.6 times; P = 0.008 and 3.1 ± 3.2 vs. 2.2 ± 2.7; P = 0.001) and night-time periods (2.1 ± 1.6 → 1.7 ± 1.2; P < 0.001 and 5.1 ± 4.0 → 4.2 ± 3.8; P = 0.013) were reduced with isCGM treatment. The isCGM system was associated with an incremental gain in quality-adjusted life expectancy (QALE) of 0.8 QALYs compared with the SMBG arm (74.6 vs. 73.8 QALYs). The resulting incremental cost-effectiveness ratio was JPY 4,398,932 (US$41,212) per QALY gained, which is well below the generally accepted cost-effectiveness threshold. SH during the daytime period was the primary driver of the incremental QALE. Conclusion: The findings suggest that isCGM use for Japanese T1D adults treated with MDI is cost saving relative to SMBG. [ABSTRACT FROM AUTHOR]

Hypertension, cardiovascular disease and kidney failure are associated with persistent hyperglycaemia and the subsequent development of nephropathy in people with diabetes. Diabetic nephropathy is associated with widespread vascular disease affecting both the kidney and the heart from an early stage. However, the risk of diabetic nephropathy in people with type 1 diabetes is strongly genetically determined, as documented in familial transmission studies. The search for the underlying genes has been extensive, using specific hypotheses, sibling linkage studies and genome-wide association studies (GWAS). The role of the angiotensinI-converting enzyme/kininase II (ACE) gene and genetic variability in ACE levels as a susceptibility and prognostic factor for diabetic nephropathy has been well documented in people with type 1 diabetes. The ACE gene insertion/deletion polymorphism, which is associated with plasma and tissue ACE levels, has been the most studied genomic variant in diabetic nephropathy. Recently, this polymorphism has also been associated with longevity in people with type 1 diabetes. The ACE I/D polymorphism has also been associated with vascular, extra-renal complications including myocardial infarction and lower-limb amputation in this population. Other genes and loci have been identified in linkage studies and GWAS, such as the COL4A3 gene or a region on chromosome 3q with the adiponectin gene. Replication was not always attempted and was rarely achieved, even for GWAS. Overall, effect sizes remain modest and no major gene has been identified, despite the strength of the genetic effect in transmission studies. We searched bibliographic databases for studies reporting genomic variants associated with diabetic nephropathy and meta-analyses of such studies. We selected important relevant studies for further discussion in this narrative review. This brief review attempts to summarise the current knowledge on the genetics of diabetic nephropathy and associated cardiovascular disease in people with type 1 diabetes, and discusses some conceptual and methodological issues relevant to the interpretation of past studies and the design of future ones. [ABSTRACT FROM AUTHOR]

Background: This study aims to examine the alterations and clinical significance of CD8+ regulatory T cell subsets in the peripheral blood of individuals with type 1 diabetes mellitus (T1DM). Methods: From January 2020 to December 2023, a study was conducted involving 40 individuals with T1DM, who visited the Department of Endocrinology at the First Affiliated Hospital of Nanjing Medical University (T1DM group). For comparison, 40 healthy individuals who underwent routine physical examinations at the same hospital during this period were selected as the control group. Peripheral blood mononuclear cells were isolated, and CD8+ T cells were labeled with CD3, CD25 and FoxP3 to analyze their subset frequencies using flow cytometry. The study examined differences in subset frequencies between the two groups and explored correlations between subset frequency, disease duration, and age of onset. Results: The frequencies of CD8+ CD25+, CD8+ FoxP3+, CD8+ CD25+ CD3+ and CD8+ FoxP3+ CD3+ subsets in peripheral blood mononuclear cells did not significantly differ between the healthy control group and the T1DM group (P > 0.05). In the T1DM group, the expression level of CD25 on CD8+ T cells showed no correlation with the age of onset or disease duration, and FoxP3 levels were also unrelated to the age of onset, with no statistical differences (P > 0.05). However, within the T1DM group, FoxP3 levels progressively decreased with longer disease duration, demonstrating a statistically significant negative correlation (Pearson r = -0.331, P < 0.05). In the T1DM group, the level of CD3+ CD8+ T cells expressed CD25, and there was no correlation between Foxp 3 level and age of onset, not statistically significant (P > 0.05), but the level of Foxp 3 in the T1DM group decreased with the duration of the disease, (Pearson r= − 0.363, P < 0.05). Conclusion: The levels of CD8+FoxP3+ regulatory T cells in peripheral blood mononuclear cells of patients with T1DM show a significant correlation with disease duration, suggesting that these cells may play a critical role in the progression of T1DM. [ABSTRACT FROM AUTHOR]

Background/Objectives: The objective of this study was to compare trends in the incidence of deliveries and in obstetric interventions and outcomes in women with and without type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM). Methods: This was an observational study using the Spanish National Hospital Discharge Database (2016–2022). Results: A total of 1,995,953 deliveries were recorded between 2016 and 2022 (6495 mothers with T1DM, 5449 with T2DM, and 124,172 with GDM). The incidence of T1DM and GDM increased over time, although it remained stable in women with T2DM. Women with T2DM were more likely to have obstetric comorbid conditions (72.93%) than women with GDM (63.04%), women with T1DM (59.62%), and women who did not have diabetes (45.3%). Pre-eclampsia, previous cesarean delivery, and arterial hypertension were the most prevalent conditions in all types of diabetes. The highest frequency of cesarean delivery was recorded for women with T1DM (55.04%), followed by women with T2DM (44.94%), and those with GDM (28.13%). The probability of cesarean delivery was 2.38, 1.79, and 1.19 times greater for T1DM, T2DM, and GDM, respectively, than for women who did not have diabetes. The adjusted rate for severe maternal morbidity was significantly higher for women with T1DM (RR 2.31; 95%CI 2.02–2.63) and T2DM (RR 1.58; 95%CI 1.34–1.87) than for women without diabetes. Conclusions: The incidence of deliveries in women with T2DM remained unchanged between 2016 and 2022; the incidence of deliveries increased in women with T1DM and GDM. The prevalence of comorbidity and obstetric factors increased over time in women with T1DM and GDM. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aimed to compare the effect of the real-time continuous glucose monitoring (rt-CGM) and flash glucose monitoring (FGM) on glycemic control in adults with type 1 diabetes mellitus (T1DM). Methods: A systematic literature search of all relevant studies comparing the clinical effectiveness of rt-CGM and FGM in adults with T1DM on Cochrane Library, PubMed, Embase, Web of Science, and Scopus from January 2015 to June 2023 was performed. The primary endpoints were glycated hemoglobin (HbA1c) and TIR (time in range). Secondary endpoints included time below range [TBR (<3.9 mmol/L) and (<3.0 mmol/L)], time above range [TAR (>10.0 mmol/L) and (>13.9 mmol/L)], mean glucose, and glycemic variability (GV) [standard deviations (SD) and coefficient of variation (CV)]. Results: Six studies with 1516 TIDM patients, including three randomized controlled trials and three observational studies, were enrolled in this meta-analysis. Compared to FGM, rt-CGM led to greater glycemic control, represented by higher TIR (%, 3.9 ∼ 10 mmol/L) (SMD = 0.59, 95% CI: 0.37 ∼ 0.81, p < 0.001), decreased TBR (%, <3.9 mmol/L) (SMD = −1.45, 95% CI: −2.33 ∼ −0.57, p = 0.001), decreased TAR [(%, >10.0 mmol/L) (SMD = −0.38, 95% CI: −0.71 ∼ −0.04, p = 0.03) and (%, >13.9 mmol/L) (SMD = −0.42, 95% CI: −0.79 ∼ −0.04, p = 0.03), respectively], lower mean glucose (SMD = −0.18, 95% CI: −0.31 ∼ −0.06, p = 0.003), decreased SD (SMD = −0.70, 95% CI: −1.09 ∼ −0.31, p < 0.001), and decreased CV (SMD = −0.76, 95% CI: −1.05 ∼ −0.47, p < 0.001). However, there was no difference in lowering HbA1c and TBR (%, <3.0 mmol/L) between groups. Conclusion: The rt-CGM outperformed FGM in improving several key CGM metrics among adults with T1DM, but there is no significant difference in HbA1c and TBR (<3.0 mmol/L). [ABSTRACT FROM AUTHOR]

Participation in a paediatric, complex randomized controlled trial (RCT) might add to the family burden when a child is diagnosed with a severe disease. Although important, there are only a limited number of papers describing this aspect of research from the family point of view. This study explored parents' and children's experiences of participation in a research study shortly after the child had been diagnosed with type 1 diabetes. Sixteen parents (nine mothers, seven fathers) and nine children were interviewed by an independent researcher about their inducement, the decision-making process within the family which led to their participation, and their experience of having done so. The result showed that the parents wanted to contribute to improve treatment for children with diabetes in general but also specifically for their own child. Older children were more involved in the decision making than the younger children. Study information needs to be communicated clearly and effectively since decision-making based on information of a clinical trial directly after the child's diabetes onset proved difficult. Being randomized to the intervention group in this specific study was considered somewhat burdensome. However, parental participants in both intervention and control group claimed that they would recommend participation in research studies to other parents in a similar situation, and so did the children. There was no difference between the mothers' and fathers' experiences. Implications: Parents' expectations: A predominant driving force for the parents was the expectation that the study outcome could lead to something good for both their own child and other children with type 1 diabetes. Children's perspective on participation: Older children appreciated being involved in the decision-making process and valued their role in potentially helping others with diabetes. However, younger children were less involved and often relied on their parents for decision-making. Personal benefits: Both children and parents considered it important to gain something for themselves; by participating, they could benefit from more advanced technology and more rigorous follow-ups. Importance of control group: It was important for the families' motivation for completing the study that the researchers conveyed that the control group was as important for the outcome of the study as the intervention group. Future treatments: The parents felt that participation in the clinical trial could eventually lead to new treatments that could help their own child. Perceived safety: The fact that the clinical trial was considered well-planned and safe and implied no risk for the child made it easier to agree to participation. Effective communication: Since the onset of diabetes is emotionally stressful, and diabetes treatment itself is demanding, effective communication about the content of such a clinical trial is necessary, otherwise families may not understand what they are agreeing to. Burden on the intervention group: This clinical trial was somewhat burdensome for the intervention group to participate in; nevertheless, all of the families remained committed to their reasons for participating and completed the study [ABSTRACT FROM AUTHOR]

Objectives: Achieving an ideal glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM) is both a difficult and challenging process. We aim to highlight the expected factors contributing to inadequate glycemic control in children and adolescents with T1DM in a sample of Iraqi children and adolescents. Methods: This was a descriptive cross-sectional study that recruited 247 T1DM patients aged < 18 years & disease duration ≥ 1 year. Data collected included socio-demographic & clinical characteristics with recent HbA1c value. Each patient was examined for signs of puberty and any lipodystrophy at insulin injection sites. Factors studied using Independent-Samples T-Test, One way ANOVA & Multivariable logistic regression. Results: Of the 247 patients, 108 (43.7%) were males, and 139 (56.3%) were females. The mean & SD of the age of patients was 10.13 ± 3.85 years. The Mean & SD of the recent HbA1c level was 9.43 ± 2.56. HbA1c ≤ 7.5 was achieved in 27.1% of patients. Using Multivariable logistic regression to study the association between variable factors and inadequate glycemic control, showed a significant association with higher odds in terms of the older age of the patient, maternal illiteracy, presence of recurrent diabetic ketoacidosis (DKA) episodes, absence of carb counting, and presence of lipodystrophy. Higher HbA1c was also associated significantly with puberty, rural residency, poor socioeconomic status, DKA presentation, and using regular + NPH insulin regimen. Conclusions: In the current study, inadequate glycemic control was induced by many factors, Strategies should be applied to control these factors to minimize the prospective risks of macro-vascular complications linked to T1DM in children & adolescents. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the relationship between cutaneous microcirculation reactivity, retinal circulation, macrocirculation function, and specific adhesion molecules in young patients with uncomplicated type 1 diabetes. Fifty-five patients with type 1 diabetes mellitus (T1DM), aged 8 to 18 years, were divided into subgroups based on skin microcirculation reactivity. The cutaneous microcirculatory vessels were considered reactive if post-test PORH coverage increased compared to pre-test coverage. Optical coherence tomography (OCT) was conducted to detect early retinopathic changes. Macrocirculation was described using pulsatility indices (PIs) determined for common carotid (CCA) and peripheral arteries of the upper and lower limbs. The ankle–brachial index was also assessed. There were no significant differences in retinal circulation and macrocirculation between the studied subgroups. However, there were significant differences between the various subgroups concerning the age at onset of diabetes and the sP-selectin levels but not ICAM-1 and sVCAM-1. The sP-selectin differences remained true after adjusting for age at onset. The sP-selectin level was significantly higher in the subgroup of patients with non-reactive cutaneous microcirculation. The results of our study indicate that sP-selectin may be considered as an immunological marker for cutaneous abnormalities, which serve as an early indicator of endothelial dysfunction in young patients with type 1 diabetes in the absence of classical complication. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR), a hallmark of type 2 diabetes mellitus, develops in a significant number of patients with type 1 diabetes mellitus (T1DM) despite the use of insulin therapy to control glycemia. However, little is currently understood regarding the underlying mechanisms of IR in T1DM, especially within the context of chronic insulin treatment. Recent evidence suggests an important influence of glucolipotoxicity in skeletal muscle on insulin sensitivity in T1DM. Thus, this review summarizes our current knowledge regarding impairments in skeletal muscle lipid, glucose, and oxidative metabolism in the development of IR in insulin‐treated T1DM. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate diabetes self-care among diabetic children and adolescents and compare with glycaemic control. Summary of Diabetes Self-Care Activities (SDSCA) questionnaire was distributed to patients aged 10–18 years with types 1 and 2 diabetes mellitus (DM) at paediatric diabetes clinics in Malaysia. Haemoglobin A1c levels were measured after questionnaire completion. A total of 106 patients completed the questionnaire with a mean age of 13.91 (± SD 2.48) years. Mean haemoglobin A1c and SDSCA score were 9.78 (± SD 2.43)% and 19.09 (± SD 5.81), respectively. Type 1 DM patients had significantly higher haemoglobin A1c (10.11 95% CI [9.62, 10.59] vs 8.38 95% CI [7.13, 9.62]). Total score was higher in type 1 DM although not statistically significant (19.32 95% CI [18.21, 20.43] vs 18.08 95% CI [14.28, 21.87]). Blood glucose testing score was significantly higher in type 1 DM (5.24 95% CI [4.82, 5.66] vs 3.50 95% CI [2.23, 4.77]). There was statistically significant negative correlation between score in diet subcategory and haemoglobin A1c. In conclusion, self-care activities among diabetic children and adolescents are still suboptimal. Self-care activities on blood glucose testing are significantly better in type 1 DM. Diet section correlated well with glycaemic control necessitating further research. [ABSTRACT FROM AUTHOR]

The growing prevalence of overweight/obesity, the persistence of inadequate glycemic control among the majority of affected individuals, and the still unacceptably high risk of cardiovascular morbidity and mortality among population with type 1 diabetes mellitus (T1D), impose an urgent need for the introduction of non-insulin glucose-lowering agents in the therapeutic armamentarium. Given that their antihyperglycemic mechanism of action is independent of endogenous insulin secretion and that the observed cardio-renal benefits are unrelated to their glucose-lowering properties, one can speculate that the use of sodium-glucose co-transporter-2 inhibitors (SGLT2is) could provide benefits in T1D, similar to the ones observed among individuals with type 2 diabetes mellitus, chronic kidney disease (CKD), and heart failure. Available evidence from randomized controlled trials suggests that treatment with SGLT2is as adjunct to insulin in T1D results in modest reductions in glycated hemoglobin and body weight. Additionally, SGLT2is ameliorate albuminuria, and thus delay or prevent the development of CKD in T1D. However, use of SGLT2is is associated with an increased risk of diabetic ketoacidosis (DKA) in T1D. This commentary aims at providing a framework for practical recommendations regarding the potential use of SGLT2is in adults with T1D, based on the individual's risk level for DKA development, the presence of inadequate glycemic control and related cardio-renal complications. [ABSTRACT FROM AUTHOR]

Aims: To conduct a meta‐analysis of randomized controlled trials (RCTs) to evaluate the effect of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) on glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) metrics as an adjunct to insulin therapy in adults with type 1 diabetes mellitus (T1D). Methods: A systematic literature search was conducted through Medline (via PubMed), Cochrane Library, and Google Scholar up to 27 May 2024. Dual‐independent study selection, data extraction, and quality assessment were performed. Results were summarized using random‐effects meta‐analysis. Results: Six RCTs were identified, involving a total of 378 individuals with T1D. The use of GLP‐1RAs in addition to standard insulin therapy was associated with a significant reduction in HbA1c (mean difference [MD] −0.21%, 95% confidence interval [CI] −0.36 to −0.06; p = 0.007) and a similar time in range (TIR) compared to placebo (MD −0.22%, 95% CI −2.39 to 1.95; p = 0.84). GLP‐1RA therapy resulted in a significantly higher time below range (MD 1.13%, 95% CI 0.50 to 1.76; p < 0.001) and a lower time above range compared with placebo (MD −1.83%, 95% CI −2.51 to −1.15; p < 0.001). Nonsignificant differences were noted for the secondary outcomes, including the mean amplitude of glucose excursion, continuous overall net glycaemic action for 60 min, mean daily glucose, coefficient of variation, and mean standard deviation of weekly glucose levels. Conclusion: Our findings suggest that, in individuals with T1D, add‐on therapy with GLP‐1RAs does not confer significant benefits in terms of CGM metrics and is associated with a longer time below the target glycaemic range. [ABSTRACT FROM AUTHOR]

Copyright of Saudi Medical Journal is the property of Saudi Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

For many autoimmune diseases, including type 1 diabetes mellitus (T1DM), efforts have been made to modify the disease process through pharmacotherapy. The ultimate goal must be to develop therapies with curative potential by achieving an organ without signs of parenchymal cell destruction and without signs of immune cell infiltration. In the case of the pancreas, this means regenerated and well-preserved beta cells in the islets without activated infiltrating immune cells. Recent research has opened up the prospect of successful antibody combination therapy for autoimmune diabetes with curative potential. This goal cannot be achieved with monotherapies. The requirements for the implementation of such a therapy with curative potential for the benefit of patients with T1DM and LADA (latent autoimmune diabetes in adults) are considered. [ABSTRACT FROM AUTHOR]

Background: This study investigates the therapeutic mechanisms of Cai's Herbal Tea in Type 1 Diabetes Mellitus (T1DM) mice, focusing on its effects on mitochondrial change and autophagy via the AMP-activated protein kinase (AMPK)—mammalian target of rapamycin (mTOR) pathway. Methods: The composition of Cai's Herbal Tea was analyzed by Ultra-High Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry (UHPLC-Q/TOF-MS). C57BL/6 mice and Min6 pancreatic beta cells were divided into control, diabetic mellitus (DM)/high glucose (HG), and treatment groups (low, medium, and high doses of Cai's Tea, and Metformin). Key physiological parameters, pancreatic islet health, Min6 cell morphology, viability, and insulin (INS) secretion were assessed. Small Interfering RNA-AMPK (si-AMPK) was utilized to confirm the pathway involvement. Results: Cai's Herbal Tea improved body weight, pancreatic islet pathological injury, and INS secretion whereas reduced total triglycerides, fasting blood sugar, and Interferon gamma (INF-γ) in T1DM mice, particularly at higher doses. In Min6 cells, Cai's Tea mitigated HG-induced damage and proinflammatory response, enhancing cell viability and INS secretion. Notably, it reduced swelling and improved cristae structure in treated groups of mitochondria and promoted autophagy via the AMPK-mTOR pathway, evidenced by increased LC3II/LC3I and P-AMPK/AMPK ratios, and decreased P-mTOR/mTOR and P62 expressions in pancreatic islet β-cells. Furthermore, these effects were converted by si-AMPK interference. Conclusion: Cai's Herbal Tea exhibits significant therapeutic efficacy in T1DM mice by improving mitochondrial health and inducing autophagy through the AMPK-mTOR pathway in pancreatic islet β-cells. These findings highlight its potential as a therapeutic approach for T1DM management. [ABSTRACT FROM AUTHOR]

Copyright of Medicina Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background/Objectives: Structured therapeutic patient education is the key to improving biopsychosocial outcomes in people with type 1 diabetes mellitus. This study aimed to determine the effects of structured therapeutic education on glycemic control and emotional well-being in people with type 1 diabetes mellitus. Methods: This is a systematic review with a meta-analysis (PROSPERO ID: CRD42023390079). Searches were performed in Scopus, MEDLINE, Web of Science, CINAHL, APA PsycInfo, APA PsycArticles, and the Psychology Database (June–August 2024). The eligibility criteria included randomized controlled trials published in English or Spanish within the past 10 years. Data extraction and risk of bias evaluations were independently conducted by two reviewers. The outcomes analyzed included glycated hemoglobin, time in range, emotional well-being, self-management behaviors, and adherence to treatment. Meta-analyses were performed using RevMan with random and fixed effects models. Results: Seventeen studies met the eligibility criteria. There was a significant improvement in glycemic control, stress, anxiety, and treatment satisfaction, although the results for the other emotional outcomes were mixed. Conclusions: Structured therapeutic patient education improves glycemic control and selected emotional outcomes in individuals with type 1 diabetes mellitus. Further trials are needed to refine the characteristics of the intervention and broaden the applicability of the findings to diverse populations. [ABSTRACT FROM AUTHOR]

Background/Objectives: The gut microbiota is linked to the pathogenesis of type 1 diabetes mellitus (T1DM), while supplementation with probiotics may result in positive alterations in the composition of the gut microbiome. This research aimed to map the changes in the gut microbiome and blood markers of streptozotocin-induced diabetic rats after a dietary intervention with free or immobilized cells of the presumptive probiotic Pediococcus acidilactici SK on pistachio nuts. Methods: Twenty-four male Wistar rats were studied and divided into four groups (healthy or diabetic) which received the free or the immobilized P. acidilactici SK cells on pistachio nuts for 4 weeks. Blood, fecal, and intestinal tissue samples were examined. Results: The diabetic rats exhibited an elevated concentration of HDL-c, while the inflammatory IL-1β levels were significantly lower in the diabetic animals that received the immobilized cells compared to the group that received the free cells. The dietary intervention with immobilized cells led to decreased counts of fecal staphylococci and enterococci in the diabetic animals, while the diet with both free and immobilized P. acidilactici SK cells rendered levels of these populations in normal values in the feces and intestinal tissue of the diabetic animals. Noticeably, the Lactobacillus and Bifidobacterium genera were elevated after the supplementation with immobilized P. acidilactici SK cells on pistachio nuts. Conclusions: Dietary supplementation with P. acidilactici SK cells (in free or in immobilized form) beneficially affected the gut microbiota/microbiome of streptozotocin-induced diabetic rats, leading to the alleviation of dysbiosis and inflammation and control over their lipid levels. [ABSTRACT FROM AUTHOR]

Background. Patients with a diagnosis of type 1 diabetes mellitus (T1DM) experience high levels of stress (stressful events and perceived stress) and psychological distress (symptoms of depression and anxiety) compared to people without diabetes. High levels of chronic and perceived stress in people with T1DM are associated with poor glycemic control. The relationship between perceived stress and glycemic control appears to be most pronounced in adults who are likely to experience disproportionate amounts of stress. The purpose of this study was to consider factors that may negatively impact glycemic levels in people with a diagnosis of type 1 diabetes mellitus. Materials and methods. Perceived stress, diabetes distress, morning salivary cortisol, inflammatory biomarkers, and hemoglobin A1c (HbA1c) were measured in this quantitative, cross-sectional phase of a larger, mixed methods research. People with T1DM completed self-report surveys, provided blood and salivary samples to examine effect sizes of relationships among variables of interest. Results. Most people with T1DM did not adhere to recommendations for HbA1c. Reports of diabetes distress were strongly associated with reports of perceived stress and demonstrated a large and potentially clinically meaningful relationship (r = 0.78, p < 0.001). Medium-to-large effects were noted between perceived stress and HbA1c. Cortisol and IL-8 may mediate the relationship between perceived stress and HbA1c in people with T1DM. Patients who provided salivary samples had lower average HbA1c levels (M = 8.55, SD = 1.54) than those who did not (M = 10.96, SD = 2.53). Of the inflammatory biomarkers, only IL-8 was associated with HbA1c levels with a moderate effect size (r = 0.351). Exploratory analysis also revealed that IL-8 may mediate the relationship between perceived stress and HbA1c. Conclusions. Understanding the causes of elevated glycemic levels in T1DM patients may help tailor diabetes management interventions to improve health outcomes. [ABSTRACT FROM AUTHOR]

Background: Proximal renal tubular dysfunction occurs during diabetic ketoacidosis (DKA) in type 1 diabetes. However, only a few studies have reported on the multiple proximal renal tubular functions simultaneously. Moreover, to the best of our knowledge, distal renal tubular function has not yet been investigated. Methods: Patients with newly diagnosed type 1 diabetes mellitus were classified into those with DKA and those without DKA, and their proximal and distal renal tubular functions were investigated. The diagnostic criteria for DKA were blood glucose > 200 mg/dL, blood pH < 7.3 or HCO3– < 15 mEq/L, and urine ketone body positivity. Results: Six patients with DKA and five patients without DKA were included. In patients with DKA, urinary β2-microglobulin levels were significantly higher, while blood pH, HCO3–, and tubular reabsorption of phosphorus were significantly lower than in those without DKA. There were no significant differences in blood glucose, HbA1c, serum phosphorus, urinary N-acetyl-beta-glucosaminidase, and urinary amino acid excretion between patients with and without DKA. Elevated NH3 levels and impaired urinary acidification were not observed in patients with and without DKA. Conclusions: In patients with newly diagnosed type 1 diabetes mellitus complicated with DKA, multiple proximal renal tubular dysfunctions occur simultaneously, suggesting transient Fanconi syndrome. Distal renal tubular acidosis was unlikely. The diagnostic criteria for DKA are appropriate also in the view of proximal renal tubular dysfunction and are considered suggestive of pathophysiological factors that may cause proximal renal tubular dysfunction. [ABSTRACT FROM AUTHOR]

Background: Diabetes care incorporates multiple integrated elements like self-care practices, patient education and awareness, societal support, equitable access to healthcare facilities and trained healthcare professionals, commitment from the diabetes associations and government policies. There is a dearth of research exploring the barriers experienced by both People with Type 1 diabetes (PwT1D) and People with Type 2 diabetes (PwT2D) in accessing the holistic elements of diabetes care. This study thus aimed at exploring the perceived barriers among PwT1D and PwT2D in accessing diabetes care services in urban and rural areas of Nepal. Method: This study was a qualitative research using phenomenological approach where an in-depth interview with 23 participants on insulin was conducted. This included 15 PwT1D and 8 PwT2D, residing in the capital and rural areas and attending the hospitals and clinic in the urban and semi-urban regions in Nepal. A semi-structured questionnaire was used for the interview. The interviews were transcribed verbatim and deductive thematic analysis was done. Results: Majority were female participants and most had received a formal education and were visiting the hospitals located in capital city. Mean age for PwT1D was (27.86 ± 1.85) years whereas the median age for PwT2D was [47.5 (IQR, 16.5)] years. Seven themes were generated from the study representing key barriers from patient's perspective. These were: Theme (1) Double stigma: Diabetes diagnosis and insulin use, Theme (2) Non-adherence to insulin and Self-Monitoring of Blood Glucose (SMBG), Theme (3) Logistic challenges in rural areas: Scarcity of healthcare professionals and other healthcare facilities, Theme (4) Dissatisfaction with healthcare services, Theme (5) Patients seeking alternative treatment strategies over allopathic treatment, Theme (6) Limitations of health insurance scheme and Theme (7) Limited role of national diabetes organizations. Conclusion: There is a need in raising awareness among general public especially on T1DM to address the issue of diabetes stigma. An effort in implementation of policies supporting diabetes care and refinement of National Health Insurance Scheme is equally essential. Similarly, strengthening of Health Care System by ensuring availability of insulin, laboratory facilities and trained healthcare professionals in rural areas should be focused to address the inequity in access to healthcare in rural and urban sectors. [ABSTRACT FROM AUTHOR]

Introduction and aim. Orthorexia nervosa is described as an obsession with consuming solely healthy foods accompanied by restrictive behaviors. Patients with chronic conditions frequently require dietary interventions alongside medication to manage symptoms and slow down disease progression. However, when dietary restrictions are taken to extremes, individuals may develop orthorexia nervosa, resulting in malnutrition and weight loss. This poses risks during treatment, where maintaining a balanced diet is vital. In this review we aim to display the prevalence of orthorexia nervosa in patients suffering from selected chronic diseases. Material and methods. A literature review was performed to investigate the prevalence of orthorexia nervosa among individuals with type 1 diabetes, inflammatory bowel disease, celiac disease, rheumatoid arthritis, and cancer. Description of the State of Knowledge. The occurrence of orthorexia reaches up to 7% in the general population, 72% in patients with type 1 diabetes mellitus, 77% in case of inflammatory bowel disease, 71% among individuals suffering from celiac disease, 75% in those with rheumatoid arthritis, and 50% in case of cancer. Orthorexia nervosa predominantly affects females who are younger, have higher levels of education, select organic foods, prepare their own meals, and have other concurrent chronic illnesses. The distress associated with diagnosis is considered the primary factor contributing to the development of this condition. Orthorexia ultimately leads to malnutrition, weight loss, impaired social functioning, and poses a risk of complications during the management of patients suffering from chronic diseases. Conclusion. The prevalence of orthorexia nervosa in patients suffering from the exhibited chronic illnesses is significantly higher compared to the general population. Therefore, early detection of this condition and intervention are necessary to improve patient management. Further research is needed to assess the frequency of orthorexia among individuals suffering from other chronic diseases. [ABSTRACT FROM AUTHOR]

Background: Existing studies predominantly focused on the relationship between periodontitis and type 2 diabetes mellitus (T2DM), with limited data on the association between periodontitis and type 1 diabetes mellitus (T1DM). This study aimed to examine the impact of T1DM and periodontitis on the subgingival microbiome and levels of advanced glycation end-products (AGEs). Methods: Samples were collected from four groups: T1DM, periodontitis (P), T1DM with periodontitis (DP), and periodontally and systemically healthy controls (Control). Subgingival microbiome composition and AGE levels were assessed using 16S rRNA gene sequencing and enzyme-linked immunosorbent assay (ELISA), respectively. Correlations between clinical indexes, microbiome composition, and AGEs were analyzed using Spearman correlation coefficient. Results: Alpha and beta diversity analyses revealed significant differences in bacterial diversity between the DP group and other groups. Linear discriminant analysis effect size (LEfSe) analysis identified specific bacteria influencing each group: Acinetobacter, Leptotrichia, Raoultibacter, and Veillonella in the Control group; Tannerella, Porphyromonas, Filifactor, and Treponema in the P group; and Lactobacillales in T1DM individuals. Prevotella and Selenomonas were notably influential in the DP group. PICRUSt2 analysis showed pathways alterations were concentrated in cell motility, translation, cell growth and death and metabolism in the DP and P groups. Spearman correlation analysis indicated a positive correlation between AGEs and periodontitis or diabetes-related parameters and AGEs were positively correlated with Haemophilus and Arachnia. Conclusions: The findings suggested that the composition and function of the subgingival microbiome in the P group with or without T1DM were significantly different. Additionally, AGEs were involved in the development of periodontitis even in absence of hyperglycemia. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Pediatric Disease / Türkiye Çocuk Hastalıkları Dergisi is the property of Turkish Journal of Pediatric Disease and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Type 1 diabetes mellitus (T1DM), a complex chronic disease with an intricate etiology and pathogenesis, involves the recognition of self-antigens by pancreatic islet autoantigen-specific T cells and plays crucial roles in both early- and late-stage destruction of beta cells, thus impacting disease progression. Antigen-specific T cells regulate and execute immune responses by recognizing particular antigens, playing broad roles in the treatment of various diseases. Immunotherapy targeting antigen-specific T cells holds promising potential as a targeted treatment approach. This review outlines the pathogenesis of diabetes, emphasizing the pivotal role of pancreatic islet autoantigen-specific T cells in the progression and treatment of T1DM. Exploring this avenue in research holds promise for identifying novel therapeutic targets for effectively managing diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Williams-Beuren syndrome is a contiguous gene syndrome caused by microdeletion of the locus 7q11.23. It is a clinically recognizable condition whose cardinal features include growth deficiency, variable degrees of neurodevelopmental disorders, congenital cardiac defects, outgoing personality, and typical facies. Case Series Presentation: This retrospective study analyzed 38 consecutive patients in a single center for rare diseases, diagnosed by Preus criteria modified by the Sugayama scoring system, comprising 17 male and 21 female individuals aged 1 month to 55 years. Cases were divided into two groups concerning (a) exclusive clinical diagnosis or (b) clinical diagnosis followed by a laboratory cytogenetic or cytogenomic test; except for hypertension, no significant difference was seen among both groups. The most frequent findings were intellectual deficiency, developmental delay, typical facies, and overfriendliness, all above 80% of the total sample. On the other hand, supravalvar aortic stenosis was found in only 32.4%, while other congenital heart diseases were seen in 56.7% of the sample. Unusual features included one individual with 13 pairs of ribs, another with unilateral microphthalmia, and three with unilateral renal agenesis. Comorbidities comprised 9 cases of hypothyroidism and 1 case each of precocious puberty, segmental vitiligo, type 1 diabetes mellitus, and congenital adrenal hyperplasia. Conclusion: Preus criteria modified by the Sugayama scoring system are still efficient and helpful for clinical diagnosis. This is the second report on microphthalmia and the first study describing the association between vitiligo, type 1 diabetes mellitus, and congenital adrenal hyperplasia in individuals with Williams-Beuren syndrome. [ABSTRACT FROM AUTHOR]

Aim: The aim was to investigate whether COVID‐19 increases new incidence of hypertension (HTN), chronic kidney disease (CKD) and diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) up to 40 months post‐infection. Materials and Methods: Three groups of patients from the Montefiore Health System in the Bronx (1 March 2020 to 1 July 2023) were studied: T1D patients hospitalized for COVID‐19 (H‐COVID‐19, n = 511), T1D patients with COVID‐19 but not hospitalized for COVID‐19 (NH‐COVID‐19, n = 306) and T1D patients without a positive COVID‐19 test on record (non‐COVID‐19, n = 1547). COVID‐19 patients were those with a positive polymerase‐chain‐reaction test on record, and non‐COVID‐19 patients were either tested negative or not tested on record. Cumulative incidences and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were computed with adjustment for competing risks. Results: Compared to non‐COVID‐19 patients, both H‐COVID‐19 (unadjusted 19.72% vs. 3.14%, p < 0.001; aHR = 7.55 [3.33, 17.06], p < 0.001) and NH‐COVID‐19 (10.26% vs. 3.14%, p = 0.004; aHR = 5.08 [2.19, 11.78], p < 0.001) patients were more likely to develop new HTN. Compared to non‐COVID‐19 patients, both H‐COVID‐19 (11.41% vs. 1.14%, p < 0.001; aHR = 9.76 [4.248, 22.25], p < 0.001) and NH‐COVID‐19 (7.69% vs. 1.14%, p < 0.001; aHR = 6.54 [2.91, 14.67], p < 0.001) patients were more likely to develop new CKD. Compared to non‐COVID‐19 patients, both H‐COVID‐19 (4.09% vs. 1.06%, p < 0.001; aHR = 12.24 [4.09, 36.59], p < 0.001) and NH‐COVID‐19 (3.06% vs. 1.06%, p = 0.035; aHR = 12.94 [4.09, 40.89], p < 0.001) patients were more likely to develop new DKA at follow‐up. Conclusion: T1D patients with COVID‐19 are at higher risk of developing new HTN, CKD and DKA compared to T1D patients without COVID‐19. [ABSTRACT FROM AUTHOR]

Background and Objectives: Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease with T cell-mediated pathogenesis of pancreatic β-cell destruction, leading to insulin deficiency. MicroRNAs such as miR-223 and miR-106b, along with PTEN, have been reported to participate in the pathophysiology of diabetes and its complications. The current study has explored the expression of miR-223, miR-106b, and PTEN and their association with various clinical and biochemical parameters in subjects diagnosed with T1DM. Materials and Methods: Sixty T1DM patients (two groups as uncomplicated/ with microalbuminuria) and fifty healthy volunteers, age- and sex-matched, were enrolled in this study. The fasting venous blood samples were collected, and PTEN and miRNAs (miR-223 and miR-106b) levels were measured by ELISA and real-time PCR, respectively. Results: The PTEN levels of patients with microalbuminuria were significantly lower than those of patients without microalbuminuria, while those of miR-223 and miR-106b were significantly increased in the T1DM group compared with the healthy control group (p < 0.001). ROC analysis indicated that PTEN, miR-223, and miR-106b could be potential biomarkers for diagnosing T1DM with high specificity but with variable sensitivities. Also, PTEN and miR-223 were negatively correlated with r =−0.398 and p < 0.0001, indicating that they were interrelated in their role within the T1DM pathophysiology. Conclusions: In the current study, it has been shown that the circulating levels of PTEN, miR-223, and miR-106b are significantly changed in T1DM patients and may back their potential to be used as non-invasive biomarkers for the diagnosis and monitoring of T1DM. Low PTEN protein expression was related to high miR-223 expression, indicating involvement of these miRNA in the regulation of PTEN. Further studies should be performed to clarify the exact mechanisms and possible clinical applications of these molecules. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze the potential pathogenic connection between metabolic factors, photoreceptor cell rearrangements, retinal microvascular perfusion, and functional parameters through multifocal electroretinography (mfERG) in type 1 diabetes mellitus (DM1). Methods: This prospective observational cohort study enrolled DM1 patients (40.5 ± 9.1 years) with mild nonproliferative diabetic retinopathy followed for 4 years. Patients were subjected to multimodal imaging, which included color fundus photography, optical coherence tomography (OCT), OCT angiography, adaptive optics (AO), and mfERG. OCTA slabs were analyzed using ImageJ software (software version 2.3.0/1.53f) to calculate perfusion density (PD) at both superficial (SCP) and deep (DCP) capillary plexuses, as well as flow deficit percentage (FD%) at the choriocapillaris (CC). To calculate cone metrics on AO at the parafovea, including cone density (CD), linear dispersion index (LDi), and heterogeneity packing index (Hpi%) in the parafovea, the images were post-processed using a MATLAB algorithm. The mfERG P1 implicit time (IT) and N1-P1 response amplitude density (RAD) from R1 (foveal area), R2 (parafoveal area), and the unified rings R1 + R2 were evaluated. Results: A total of 22 patients (22 eyes) were enrolled. No significant differences were noted in central mfERG amplitude and implicit time-averaged values (p > 0.05, all). The main factor influencing R1 IT was HbA1c, while R1 RAD was affected by Hpi and CC FD%. R1 + R2 IT was influenced by Hpi, LDi (p > 0.001, all), and modifications in the perfusion density in the SCP (p < 0.001) and DCP (p = 0.03) at the parafovea. In contrast, R1 + R2 RAD were associated with HbA1c (p = 0.02) and Hpi (p < 0.001). Conclusions: Microvascular changes and glucometabolic factors are key elements influencing the long-term morphofunctional alterations at the photoreceptor level in DM1. [ABSTRACT FROM AUTHOR]