Vitamin D and Insulin-Dependent Diabetes: A Systematic Review of Clinical Trials.

(1) Background: Vitamin D supplementation after type 1 diabetes mellitus (T1DM) onset has led to conflicting results on beta-cell preservation. Aim: This paper presents a systematic review to verify whether randomized prospective controlled trials (RCTs) demonstrate that improved vitamin D status confers protection on T1DM. (2) Methods: A systematic review was conducted up until 18 January 2024 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching MEDLINE, MEDLINE In-Process, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, using keywords "vitamin D", "type 1 diabetes", and "children". (3) Results: Following the above-mentioned search process, 408 articles in PubMed and 791 in Embase met inclusion criteria. After removing duplicates, 471 articles remained. After exclusion criteria, 11 RCTs remained. Because of major heterogeneity in design and outcomes, no meta-analyses were conducted, allowing only for qualitative analyses. There was no strong evidence that vitamin D supplementation has lasting effects on beta-cell preservation or glycemic control in new-onset T1DM. (4) Conclusions: More rigorous, larger studies are needed to demonstrate whether vitamin D improves beta-cell preservation or glycemic control in new-onset T1DM. Because T1DM may cause osteopenia, it is advisable that patients with new onset T1DM have adequate vitamin D stores.

Vitamin D efficacy in type 1 and type 2 diabetes.

It is well known that vitamin D has a profound effect on calcium and bone metabolism, but its influence on other organs (extraskeletal effect) has been proposed. Consistently, vitamin D deficiency is associated with an increased incidence of various diseases, including type 1 and type 2 diabetes, as reported by many observational studies. However, there has been no consensus on whether vitamin D deficiency is a causative factor in the incidence of diabetes mellitus. There have been no randomized controlled trials (RCTs) aimed at preventing the onset of type 1 diabetes with vitamin D intake. In addition, the results of RCTs evaluating the preventive effect of vitamin D supplementation on type 2 diabetes development have been inconsistent. The recent observational studies, randomized controlled trials, and meta-analyses are confirming that vitamin D or active vitamin D administration is effective in preventing the incident of type 1 and type 2 diabetes.

Practice of complementary and alternative medicine use in North Indian children with type 1 diabetes: an exploratory study.

Purpose: Intermittent or concurrent use of Complementary and Alternative medicines (CAM) with insulin may have adverse effects in children with Type 1 Diabetes (T1DM). This study explores the practices of CAM use in children with T1DM. Methods: An exploratory study was conducted among parents of children with T1DM attending a tertiary-level diabetes clinic. Data were collected using a structured pre-tested questionnaire. Results: Two-hundred parents were invited; 183 (91.5%) completed the study. The mean age of the children was lower among CAM users than others (7.9 ± 4.3 vs 9.3 ± 4.3 years, p 0.032). The two groups were similar in gender, family income, parental education, and age at diagnosis. Sixty-seven (36.6%) had used CAM. The parents' reasoning for CAM use was to cure diabetes (62.7%), to improve glycemic control (28.3%), or considering it harmless (17.9%). The most commonly used CAMs were Ayurveda (32.8%) and homeopathic preparations (31.3%). The time interval between diagnosis and CAM use ranged from 1 day to 4 years. The duration of CAM use varied widely; 50.7% used CAM for < 1 month. Only 10 CAM users had HbA1C estimated during CAM use; their mean HbA1C was 12.4 ± 3.6%. Twenty-seven CAM users (40.2%) reported poorer glycemic control; 26.8% had no effect, and the rest had undefined effects due to too short duration of use. Conclusion: CAM, mostly herbal, is frequently used among children with T1DM in North India and has detrimental effects on glycemic control. This information should be used during diabetes education to avoid medical emergencies related to sub-optimal insulin dosing. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00663-9.

Nutritional Management of Athletes with Type 1 Diabetes: A Narrative Review.

Type 1 diabetes mellitus (T1DM) represents a complex clinical challenge for health systems. The autoimmune destruction of pancreatic beta cells leads to a complete lack of insulin production, exposing people to a lifelong risk of acute (DKA, coma) and chronic complications (macro and microvascular). Physical activity (PA) has widely demonstrated its efficacy in helping diabetes treatment. Nutritional management of people living with T1DM is particularly difficult. Balancing macronutrients, their effects on glycemic control, and insulin treatment represents a complex clinical challenge for the diabetologist. The effects of PA on glycemic control are largely unpredictable depending on many individual factors, such as intensity, nutrient co-ingestion, and many others. Due to this clinical complexity, we have reviewed the actual scientific literature in depth to help diabetologists, sport medicine doctors, nutritionists, and all the health figures involved in diabetes care to ameliorate both glycemic control and the nutritional status of T1DM people engaging in PA. Two electronic databases (PubMed and Scopus) were searched from their inception to January 2024. The main recommendations for carbohydrate and protein ingestion before, during, and immediately after PA are explained. Glycemic management during such activity is widely reviewed. Micronutrient needs and nutritional supplement effects are also highlighted in this paper.

The use of dietary supplements, and the association between supplemental vitamin D and glycaemic control in adult individuals with type 1 diabetes.

AIMS: To assess the dietary supplement use in adult individuals with type 1 diabetes, and to study the association between vitamin D supplementation and glycaemic control in an observational cross-sectional study. METHODS: The study subjects were participants of the Finnish Diabetic Nephropathy Study. Data were included from all individuals with type 1 diabetes with estimated glomerular filtration rate ≥60 mL/min/1.73 m2, who had completed a diet questionnaire. In the questionnaire, the participants reported dietary supplement use for the past 30 days. A thorough investigation with an assessment of the blood panel was conducted at the study visit. RESULTS: Data were available from 1181 individuals (43% men, mean ± SD age 45 ± 13 years). Altogether 62% of the sample reported supplement use; 56% reported some vitamin or mineral and 27% reported non-vitamin and non-mineral supplement use. Supplement use was more frequent among women and those supplementing had better overall health. In the study sample, of the vitamins and minerals, vitamin D (45%) and magnesium (31%), respectively, were the most frequently reported. In the multivariable models, vitamin D supplementation was associated with better glycaemic control. Starting from a daily dose of ≥30 µg, there was evidence of improving glycaemic control with higher doses of supplemental vitamin D (e.g., for 30 µg: B [Wald Confidence Internal], p-value, -2.76 [-5.03 to -0.49], 0.017). CONCLUSIONS: Supplement use was frequent in this sample of adult individuals with type 1 diabetes. Due to potential drug-supplement interactions, the attending physicians should be aware of their patients' supplement use. The causality between vitamin D supplementation and glycaemic control should be assessed in a randomized controlled trial.

Effect of Calcium and Vitamin D Supplementation (Dairy vs. Pharmacological) on Bone Health of Underprivileged Indian Children and Youth with Type-1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (n = 203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8 ±â€¯307.8, B-983.2 ±â€¯352.9, C-792.8 ±â€¯346.8. TBLHBMD-A-± 0.2, B-0.8 ±â€¯0.2, C-0.6 ±â€¯0.2, p < 0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7 ±â€¯1.1, B-0.6 ±â€¯1.4, C- -0.7 ±â€¯1.1; Girls- A-1.1 ±â€¯1.1, B-0.9 ±â€¯3.4, C- -1.7 ±â€¯1.3, p < 0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9 ±â€¯28.6, B-15.3 ±â€¯16.5, C-7.6 ±â€¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.

Mitochondrial bioenergetics, metabolism, and beyond in pancreatic ß-cells and diabetes.

In Type 1 and Type 2 diabetes, pancreatic ß-cell survival and function are impaired. Additional etiologies of diabetes include dysfunction in insulin-sensing hepatic, muscle, and adipose tissues as well as immune cells. An important determinant of metabolic health across these various tissues is mitochondria function and structure. This review focuses on the role of mitochondria in diabetes pathogenesis, with a specific emphasis on pancreatic ß-cells. These dynamic organelles are obligate for ß-cell survival, function, replication, insulin production, and control over insulin release. Therefore, it is not surprising that mitochondria are severely defective in diabetic contexts. Mitochondrial dysfunction poses challenges to assess in cause-effect studies, prompting us to assemble and deliberate the evidence for mitochondria dysfunction as a cause or consequence of diabetes. Understanding the precise molecular mechanisms underlying mitochondrial dysfunction in diabetes and identifying therapeutic strategies to restore mitochondrial homeostasis and enhance ß-cell function are active and expanding areas of research. In summary, this review examines the multidimensional role of mitochondria in diabetes, focusing on pancreatic ß-cells and highlighting the significance of mitochondrial metabolism, bioenergetics, calcium, dynamics, and mitophagy in the pathophysiology of diabetes. We describe the effects of diabetes-related gluco/lipotoxic, oxidative and inflammation stress on ß-cell mitochondria, as well as the role played by mitochondria on the pathologic outcomes of these stress paradigms. By examining these aspects, we provide updated insights and highlight areas where further research is required for a deeper molecular understanding of the role of mitochondria in ß-cells and diabetes.

Acceptability of a Self-Led Mindfulness-Based Intervention for Teens with Type 1 Diabetes: Pilot Randomized Controlled Trial.

BACKGROUND: Diabetes distress among adolescents with type 1 diabetes has been associated with suboptimal diabetes outcomes, including lower quality of life, increased diabetes self-management challenges, and suboptimal glycemic outcomes. OBJECTIVE: This study examined the feasibility and acceptability of a scalable self-led mindfulness-based intervention to reduce diabetes distress in adolescents with type 1 diabetes. METHODS: Adolescents (N=25) aged between 14 and 18 years diagnosed with type 1 diabetes completed a baseline assessment. Participants were randomized to receive a 10-week self-guided mindfulness-based stress reduction workbook program (e-book or paper option) immediately (n=15) or after a 10-week wait (n=10). During the intervention period, participants completed weekly assignments and feedback surveys. At 10 weeks and 20 weeks, follow-up assessments were completed. RESULTS: Findings indicated that participants did not find the original intervention feasible or acceptable. Adolescents reported barriers to completing the weekly material, such as that they forgot or that the material was not sufficiently related to their diabetes management. Adolescents also reported that a digital format rather than a workbook or e-book may be more acceptable. Results from weekly surveys provided the foundation for recommendations for future iterations of the mindfulness-based intervention for adolescents with type 1 diabetes. CONCLUSIONS: Participant feedback informed recommendations for self-led mindfulness programs for youth with type 1 diabetes. Adolescents indicated that a shorter, digital mindfulness-based intervention focused on diabetes-specific behaviors may be more helpful. TRIAL REGISTRATION: ClinicalTrials.gov NCT05115175; https://clinicaltrials.gov/study/NCT05115175.

Peripheral fatigue regulation during knee extensor exercise in type 1 diabetes and consequences on the force-duration relationship.

PURPOSE: This study aimed to examine if peripheral fatigue is adjusted during knee extensor (KE) exercise in order not to surpass a critical threshold patient with type 1 diabetes (T1D) and the consequences of this mechanism on the force-duration relationship. METHODS: Eleven T1D individuals randomly performed two different sessions in which they performed 60 maximum voluntary contractions (MVC; 3 s contraction, 2 s relaxation). One trial was performed in the non-fatigued state (CTRL) and another after fatiguing neuromuscular stimulation of the KE (FNMES). Peripheral and central fatigue were quantified by the difference between pre and post exercise in quadriceps voluntary activation (ΔVA) and potentiated twitch (ΔPtw). Critical torque (CT) was determined as the average force of the last 12 contractions, whereas W' was calculated as the area above the CT. RESULTS: Although FNMES led to a significant decrease in potentiated twitch (Ptw) before performing the 60-MVCs protocol (p < 0.05), ΔVA (∼ -7.5%), ΔPtw (∼ -39%), and CT (∼816 N) post-MVCs were similar between the two conditions. The difference in W' between CTRL and FNMES was correlated with the level of pre-fatigue induced in FNMES (r2 = 0.60). In addition, W' was correlated with ΔPtw (r2 = 0.62) in the CTRL session. CONCLUSION: Correlative results in the present study indicate that regulating peripheral fatigue mechanisms at a critical threshold limit W'. Additionally, peripheral fatigue during KE exercise is limited to an individual threshold in T1D patients.

Association between type 1 diabetes and systemic lupus erythematosus: a Mendelian randomization study.

OBJECTIVES: Observational studies have shown that there is a bidirectional relationship between type 1 diabetes (T1D) and systemic lupus erythematosus (SLE); the causality of this association remains elusive and may be affected by confusion and reverse causality. There is also a lack of large-scale randomized controlled trials to verify. Therefore, this Mendelian randomization (MR) study aimed to investigate the causal association between T1D and SLE. METHODS: We aggregated data using publicly available genome-wide association studies (GWAS), all from European populations. Select independent (R2 < 0.001) and closely related to exposure (P < 5 × 10-8) as instrumental variables (IVs). The inverse-variance weighted (IVW) method was used as the primary method. We also used MR-Egger, the weighted median method, MR-Robust, MR-Lasso, and other methods leveraged as supplements. RESULTS: T1D had a positive causal association with SLE (IVW, odds ratio [OR] = 1.358, 95% confidence interval [CI], 1.205 - 1.530; P < 0.001). The causal association was verified in an independent validation set (IVW, OR = 1.137, 95% CI, 1.033 - 1.251; P = 0.001). SLE had a positive causal association with T1D (IVW, OR = 1.108, 95% CI, 1.074 - 1.144; P < 0.001). The causal association was verified in an independent validation set (IVW, OR = 1.085, 95% CI, 1.046 - 1.127; P < 0.001). These results have also been verified by sensitivity analysis. CONCLUSION: The MR analysis results indicated a causal association between T1D and SLE. Therefore, further research is needed to clarify the potential biological mechanism between T1D and SLE. Key Points • Observational studies have shown that there is a bidirectional relationship between T1D and SLE. • We evaluated causal effects between T1D and SLE by Mendelian randomization analyses. • The MR analysis results indicated a causal association between T1D and SLE.

Virtual reality's impact on children with type 1 diabetes: a proof-of-concept randomized cross-over trial on anxiety, pain, adherence, and glycemic control.

AIMS:  Assess the effectiveness of virtual reality (VR) technology, in reducing pain and anxiety, and improving adherence and glycemic control among children with type 1 diabetes (T1D). METHODS: Children with T1D, managed with continuous glucose monitoring and insulin pumps, were recruited for a randomized cross-over trial. Children were randomized to one of two interventions for diabetes management: group 1 used VR glasses first and group 2 listened to vocal-guided affective imagery first (audio). After 1 month, the interventions were crossed over. The outcome measures included pain and anxiety assessment, adherence, glycemic control, and patient-reported outcome measures (PROMs) of VR satisfaction and effectiveness. RESULTS:  Forty children, mean age 11.4 ± 1.8 years, were participated. During the VR part, the monthly mean pain score compared to the baseline improved in both groups by 30% (p = 0.03). A 14% reduction in the state anxiety score was observed from baseline to 1 month in both groups (p = 0.009). Glycemic control measures including time in range, time above range, and glucose management indicator improved in both groups during VR part (p < 0.004 for all), compared to audio part. After one month, the patient-reported outcome measure (PROM) of satisfaction and effectiveness was sixfold higher after 1 month in group 1 compared to group 2 (p = 0.002). Adherence improved for both groups. CONCLUSIONS: VR was shown to be effective in reducing pain and anxiety, improving adherence, PROM, and glycemic control among children with T1D. We suggest incorporating VR technology in pediatric diabetes clinics to facilitate and improve coping and management of diabetes. TRIAL REGISTRATION: Trial registration number and date of registration for prospectively registered trials:ClinicalTrials.gov Identifier: NCT05883267, May 10th, 2023.

Ayurveda for a Type 1 Diabetes Patient with Peripheral Arterial Occlusive Disease: A Case Report.

INTRODUCTION: The effect of Ayurvedic therapy in type 2 diabetes (T2D) is well documented. For people with type 1 diabetes (T1D), there is little evidence on the applicability of Ayurvedic therapy. This case illustrates the course of Ayurvedic treatment in a person with T1D accompanied by peripheral arterial occlusive disease (PAOD). CASE PRESENTATION: The patient had insulin-dependent T1D since the age of 6 years. At 39 years of age, he developed progressive bilateral PAOD of the femoral arteries. He presented claudication symptoms at a walking distance of 150 m. Ten surgical interventions for recanalization have been performed. The PAOD put heavy psychological strains on the patient. He developed moderate depression with anxiety and complained of tinnitus and sleep disturbances. Through an initial outpatient Ayurvedic treatment mainly focused on dietary, lifestyle changes and phytotherapeutics, and a subsequent 6-week inpatient Ayurvedic treatment in India, a weight reduction of 12 kg, a reduction in insulin requirement to 65% of baseline, as well as a walking performance without restriction at a medium load could be achieved. The depression and inner tension retreated, and one-sided tinnitus and existing sleep disturbances dissolved completely. The lasting effect was still perceptible 5 months after the inpatient stay. CONCLUSIONS: For this person with T1D with PAOD, outpatient and inpatient Ayurvedic therapy could generate a significant improvement of his situation. The case demonstrates that people with T1D can benefit from using individualized Ayurvedic therapy. This case motivates to invest in Ayurvedic research for people with T1D and complications.Die Wirkung der ayurvedischen Therapie bei Typ-2-Diabetes (T2D) ist gut dokumentiert. Für Menschen mit Typ-1-Diabetes (T1D) gibt es kaum Belege für die Anwendbarkeit der ayurvedischen Therapie. Dieser Fall veranschaulicht den Verlauf einer ayurvedischen Behandlung bei einer Person mit T1D, begleitet von einer peripheren arteriellen Verschlusskrankheit (pAVK).Der Patient hatte seit seinem 6. Lebensjahr einen insulinabhängigen 'T1D'. Im Alter von 39 Jahren entwickelte er eine fortschreitende bilaterale periphere arterielle Verschlusskrankheit (pAVK) der Oberschenkelarterien. Bei einer Gehstrecke von 150 m zeigte er Claudicatio-Symptome. Es wurden 10 chirurgische Eingriffe zur Rekanalisation durchgeführt. Die pAVK stellte für den Patienten eine starke psychische Belastung dar. Er entwickelte eine mittelschwere Depression mit Angstzuständen und klagte über Tinnitus und Schlafstörungen. Durch eine erste ambulante ayurvedische Behandlung, die sich hauptsächlich auf Ernährungs-, Lebensstiländerungen und Phytotherapeutika konzentrierte, und eine anschließende 6-wöchige stationäre ayurvedische Behandlung in Indien wurde eine Gewichtsreduktion um 12 kg, eine Reduzierung des Insulinbedarfs auf 65% des Ausgangswerts sowie eine bedeutende Verbesserung der Gehstrecke erreicht. Die Depression und die innere Anspannung verschwanden, und der einseitige Tinnitus und bestehende Schlafstörungen lösten sich vollständig auf. Der nachhaltige Effekt war noch 5 Monate nach dem stationären Aufenthalt spürbar.Für diese Person mit T1D mit pAVK konnte eine ambulante und stationäre ayurvedische Therapie eine deutliche Verbesserung der Situation bewirken. Der Fall zeigt, dass Menschen mit T1D von einer individualisierten ayurvedischen Therapie profitieren können. Dieser Fall motiviert dazu, in die ayurvedische Forschung für Menschen mit T1D und Komplikationen zu investieren.

The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition.

BACKGROUND: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive. PURPOSE: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms. METHODS: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms. RESULTS: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice. CONCLUSION: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D.

Harnessing the benefits of glycine supplementation for improved pancreatic microcirculation in type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is predominantly managed using insulin replacement therapy, however, pancreatic microcirculatory disturbances play a critical role in T1DM pathogenesis, necessitating alternative therapies. This study aimed to investigate the protective effects of glycine supplementation on pancreatic microcirculation in T1DM. Streptozotocin-induced T1DM and glycine-supplemented mice (n = 6 per group) were used alongside control mice. Pancreatic microcirculatory profiles were determined using a laser Doppler blood perfusion monitoring system and wavelet transform spectral analysis. The T1DM group exhibited disorganized pancreatic microcirculatory oscillation. Glycine supplementation significantly restored regular biorhythmic contraction and relaxation, improving blood distribution patterns. Further-more, glycine reversed the lower amplitudes of endothelial oscillators in T1DM mice. Ultrastructural deterioration of islet microvascular endothelial cells (IMECs) and islet microvascular pericytes, including membrane and organelle damage, collagenous fiber proliferation, and reduced edema, was substantially reversed by glycine supplementation. Additionally, glycine supplementation inhibited the production of IL-6, TNF-α, IFN-γ, pro-MMP-9, and VEGF-A in T1DM, with no significant changes in energetic metabolism observed in glycine-supplemented IMECs. A statistically significant decrease in MDA levels accompanied by an increase in SOD levels was also observed with glycine supplementation. Notably, negative correlations emerged between inflammatory cytokines and microhemodynamic profiles. These findings suggest that glycine supplementation may offer a promising therapeutic approach for protecting against pancreatic microcirculatory dysfunction in T1DM.

Formononetin, a bioactive isoflavonoid constituent from Astragalus membranaceus (Fisch.) Bunge, ameliorates type 1 diabetes mellitus via activation of Keap1/Nrf2 signaling pathway: An integrated study supported by network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Type 1 diabetes mellitus (T1DM) results from insulin deficiency due to the destruction of pancreatic ß-cells. Previously, our studies showed that inhibition of Keap1/Nrf2 signaling pathway promoted the onset of T1DM, which suggests that finding drugs that can activate the Keap1/Nrf2 signaling may be a promising therapeutic strategy for the T1DM treatment. Astragalus membranaceus (Fisch.) Bunge is a common traditional Chinese medicine that has been frequently applied in Chinese clinics for the treatment of diabetes and other diseases. Formononetin (FMNT), one of the major isoflavonoid constituents isolated from this herbal medicine, possesses diverse pharmacological benefits and T1DM therapeutic potential. However, the exact molecular mechanisms underlying the action of FMNT in ameliorating T1DM have yet to be fully elucidated. AIMS OF THE STUDY: This study is to investigate the regulation of FMNT on the Keap1/Nrf2 signaling pathway to ameliorate T1DM based on network pharmacology approach combined with experimental validation. MATERIALS AND METHODS: A mouse-derived pancreatic islet ß-cell line (MIN6) was used for the in vitro studies. An alloxan (ALX)-induced T1DM model in wild-type and Nrf2 knockout (Nrf2-/-) C57BL/6J mice were established for the in vivo experiments. The protective effects of FMNT against ALX-stimulated MIN6 cell injury were evaluated using MTT, EdU, apoptosis and comet assays. The levels of blood glucose in mice were measured by using a blood monitor and test strips. The protein expression was detected by Western blot analysis. Furthermore, the binding affinity of FMNT to Keap1 was evaluated using cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, and solvent-induced protein precipitation (SIP) assay. The interaction pattern between FMNT and Keap1 was assessed by molecular docking and molecular dynamics simulation techniques. RESULTS: Network pharmacology analysis revealed that FMNT exerted its therapeutic effect against T1DM by mainly regulating oxidative stress response-associated signaling molecules and pathways, such as Nrf2 regulating anti-oxidant/detoxification enzymes and Keap1-Nrf2 signaling pathway. The in vivo results showed that FMNT significantly deceased the ALX-induced high blood glucose levels and conversely increased the ALX-induced low insulin contents. In vitro, FMNT markedly protected MIN6 cells from ALX-induced cytotoxicity, proliferation inhibition and DNA damage and reduced the ALX-stimulated cell apoptosis. FMNT also inhibited ALX-induced overproduction of intracellular ROS to alleviate oxidative stress. In addition, FMNT could bind to Keap1 to notably activate the Keap1/Nrf2 signaling to upregulate Nrf2 expression and promote the Nrf2 translocation from the cytoplasm to the nucleus, resulting in enhancing the expression of antioxidant proteins HO-1 and NQO1. Inhibition of Keap1/Nrf2 signaling by ALX was also markedly abolished in the cells and mice exposed to FMNT. Moreover, these effects of FMNT in ameliorating T1DM were not observed in Nrf2-/- mice. CONCLUSIONS: This study demonstrates that FMNT could bind to Keap1 to activate the Keap1/Nrf2 signaling to prevent intracellular ROS overproduction, thereby attenuating ALX-induced MIN6 cell injury and ameliorating ALX-stimulated T1DM. Results from this study might provide evidence and new insight into the therapeutic effect of FMNT and indicate that FMNT is a promising candidate agent for the treatment of T1DM in clinics.

Oral gavage delivery of Cornus officinalis extract delays type 1 diabetes onset and hyperglycemia in non-obese diabetic (NOD) mice.

Type 1 diabetes (T1D) is an autoimmune disease initiated by genetic predisposition and environmental influences, which result in the specific destruction of insulin-producing pancreatic ß-cells. Currently, there are over 1.6 million cases of T1D in the United States with a worldwide incidence rate that has been increasing since 1990. Here, we examined the effect of Cornus officinalis (CO), a well-known ethnopharmacological agent, on a T1D model of the non-obese diabetic (NOD) mouse. A measured dose of CO extract was delivered into 10-week-old NOD mice by oral gavage for 15 weeks. T1D incidence and hyperglycemia were significantly lower in the CO-treated group as compared to the water gavage (WT) and a no handling or treatment control group (NHT) following treatment. T1D onset per group was 30%, 60% and 86% for the CO, WT and NHT groups, respectively. Circulating C-peptide was higher, and pancreatic insulitis was decreased in non-T1D CO-treated mice. Our findings suggest that CO may have therapeutic potential as both a safe and effective interventional agent to slow early stage T1D progression.

The relationship between emotional self-awareness, emotion regulation, and diabetes distress among Italian and Dutch adults with type 1 diabetes.

Objective: Evidence suggests that many adults with type 1 diabetes (T1D) experience clinically relevant levels of diabetes distress, indicating coping difficulties. Studies have primarily focused on emotion regulation as a possible construct to be addressed in psychological interventions to alleviate diabetes distress. This study extends the literature by investigating the cross-sectional association between emotion regulation, diabetes distress and the construct of emotional self-awareness as an additional variable to be considered in potentially reducing diabetes distress. Methods: Via an online survey, data was collected on emotional self-awareness dimensions (attention to feelings, clarity of feelings), emotion regulation strategies (cognitive reappraisal, expressive suppression, mood repair) and diabetes distress, along with self-reported clinical and sociodemographic information. Multiple linear regression with stepwise backward method was used to examine associations, controlling for country. Results: N = 262 Italian and Dutch adults with T1D (80.5% women, M = 38.12 years, SD = 12.14) participated. Clarity of feelings was significantly negatively associated with diabetes distress, resulting in a medium effect size (ß = -0.22, p < 0.001). Likewise, mood repair was negatively related to diabetes distress, showing a small effect size (ß = -0.26, p < 0.001). Conclusion: These findings shed light on the importance of a dimension of emotional self-awareness, namely clarity of feelings. This represents the ability to identify one's emotional states and discriminate between them. Thus, it should be considered in psychological interventions, such as mentalization-based treatment, that might contribute to alleviating T1D-related distress.

A Nutritional Approach to Optimizing Pump Therapy in Type 1 Diabetes Mellitus.

Achieving optimal glucose control in individuals with type 1 diabetes (T1DM) continues to pose a significant challenge. While continuous insulin infusion systems have shown promise as an alternative to conventional insulin therapy, there remains a crucial need for greater awareness regarding the necessary adaptations for various special circumstances. Nutritional choices play an essential role in the efficacy of diabetes management and overall health status for patients with T1DM. Factors such as effective carbohydrate counting, assessment of the macronutrient composition of meals, and comprehending the concept of the glycemic index of foods are paramount in making informed pre-meal adjustments when utilizing insulin pumps. Furthermore, the ability to handle such situations as physical exercise, illness, pregnancy, and lactation by making appropriate adjustments in nutrition and pump settings should be cultivated within the patient-practitioner relationship. This review aims to provide healthcare practitioners with practical guidance on optimizing care for individuals living with T1DM. It includes recommendations on carbohydrate counting, managing mixed meals and the glycemic index, addressing exercise-related challenges, coping with illness, and managing nutritional needs during pregnancy and lactation. Additionally, considerations relating to closed-loop systems with regard to nutrition are addressed. By implementing these strategies, healthcare providers can better equip themselves to support individuals with T1DM in achieving improved diabetes management and enhanced quality of life.

Outpatient screening for anxiety and depression symptoms in adolescents with type 1 diabetes - a cross-sectional survey.

BACKGROUND: The daily demands of type 1 diabetes management may jeopardize adolescents' mental health. We aimed to assess anxiety and depression symptoms by broad-scale, tablet-based outpatient screening in adolescents with type 1 diabetes in Germany. METHODS: Adolescent patients with type 1 diabetes mellitus (n = 2,394; mean age 15.4 y [SD 2.0]; 50.7% male) were screened for anxiety (GAD-7) and depression symptoms (PHQ-9) by self-report questionnaires and linked to clinical data from the DPV patient registry. Logistic regression was used to estimate the contribution of clinical parameters to positive screening results. RESULTS: Altogether, 30.2% showed a positive screening (score ≥ 7 in either test), and 11.3% reported suicidal ideations or self-harm. Patients with anxiety and depression symptoms were older (15.7 y [CI 15.5-15.8] vs. 15.3 y [CI 15.2-15.4]; p < 0.0001), had higher HbA1c levels (7.9% [CI 7.8-8.0] (63 mmol/mol) vs. 7.5% [CI 7.4-7.5] (58 mmol/mol); p < 0.0001), and had higher hospitalization rates. Females (adjusted odds ratio (aOR) 2.66 [CI 2.21-3.19]; p < 0.0001), patients > 15 years (aOR 1.40 [1.16-1.68]; p < 0.001), who were overweight (aOR 1.40 [CI 1.14-1.71]; p = 0.001), with HbA1c > 9% (> 75 mmol/mol; aOR 2.58 [1.83-3.64]; each p < 0.0001), with a migration background (aOR 1.46 [CI 1.17-1.81]; p < 0.001), or smoking (aOR 2.72 [CI 1.41-5.23]; p = 0.003) had a higher risk. Regular exercise was a significant protective factor (aOR 0.65 [CI 0.51-0.82]; p < 0.001). Advanced diabetes technologies did not influence screening outcomes. CONCLUSIONS: Electronic mental health screening was implemented in 42 centers in parallel, and outcomes showed an association with clinical parameters from sociodemographic, lifestyle, and diabetes-related data. It should be integrated into holistic patient counseling, enabling early recognition of mild mental health symptoms for preventive measures. Females were disproportionally adversely affected. The use of advanced diabetes technologies did not yet reduce the odds of anxiety and depression symptoms in this cross-sectional assessment.

Perspectives of women living with type 1 diabetes regarding preconception and antenatal care: A qualitative evidence synthesis.

INTRODUCTION: Pregnant women with type 1 diabetes may have an increased risk of complications for both the baby and themselves. Educational programmes, preconception planning, strict glycemic control and comprehensive medical care are some of the antenatal interventions that have been proposed to improve the outcomes of pregnant women with type 1 diabetes. While some evidence-based recommendations about antenatal care are included in clinical practice guidelines (CPGs), the views, and experiences of women with type 1 diabetes about these interventions are not well known. AIM: To understand and synthesize the perceptions of women with type 1 diabetes about the interventions before pregnancy. METHOD: A qualitative evidence synthesis (QES) was carried out with a framework analysis guided by the Cochrane Qualitative and Implementation Methods Group approach. Three online databases (Medline, Embase and Web of Science) were searched. We included qualitative articles that were published from 2011 to 2021 and which were available in English or Spanish. FINDINGS: Ten references met the inclusion criteria of the study and were included. Three main themes were identified: (a) acceptability of antenatal care, (b) feasibility and implementation consideration and (c) equity and accessibility difficulties. CONCLUSION: Continuity of care, coordination between health professionals and services, and a more holistic approach are the key aspects women say need to be considered for more acceptable, feasible and equitable preconception and antenatal care. PATIENT OR PUBLIC CONTRIBUTION: This QES was carried out as part of the CPGs on diabetes mellitus type 1, carried out as part of the Spanish Network of Health Technology Assessment Agencies. In this CPG, the representatives of the patient associations are Francisco Javier Darias Yanes, from the Association for Diabetes of Tenerife, who has participated in all the phases of the CPG; Aureliano Ruiz Salmón and Julián Antonio González Hernández (representatives of the Spanish Diabetes Federation (FEDE) who have participated as collaborator and external reviewer, respectively.