A Multidisciplinary Approach of Type 1 Diabetes: The Intersection of Technology, Immunotherapy, and Personalized Medicine
Abstract
:1. Introduction
2. The Role of Smart Technology in T1D: CGM, Insulin Pumps, and AI Systems
- Fasting glucose levels should be maintained between 3.9 and 7.8 mmol/L (70–140 mg/dL) [40].
- For children under 7 years of age, a tighter time interval is recommended, ensuring that at least 50% of CGM readings fall within 3.9–7.8 mmol/L (70–140 mg/dL) or 70% within the range of 3.9–10 mmol/L (70–180 mg/dL) [41].
- ISPAD recommends maintaining HbA1c levels below 53 mmol/mol (<7.0%) to prevent long-term microvascular and macrovascular complications [40].
2.1. Continuous Glucose Monitoring (CGM) Systems
- Professional CGM: data are recorded over several days and can be accessed only by healthcare providers, typically for retrospective analysis [46].
- Personal CGM: Users can view glucose levels in real time, allowing for immediate intervention. This category includes the following:
2.2. Continuous Subcutaneous Insulin Delivery (CSII) Systems
- Basal insulin infusion: a continuous supply of small amounts of rapid-acting insulin throughout the day and night to maintain stable glucose levels;
- Bolus insulin delivery: a single, larger dose of insulin given at mealtimes or to correct high blood glucose levels [51].
- Traditional tube pumps: these pumps feature an insulin reservoir connected to the body via a thin tube, which leads to a cannula (needle or catheter) inserted under the skin.
- Patch pumps: These devices are directly attached to the skin and do not require tubing. Insulin is delivered via a short cannula that penetrates the skin.
- Closed-loop pumps (artificial pancreas systems): these fully automated systems combine an insulin pump with a CGM sensor, continuously adjusting insulin doses based on real-time glucose data.
- Integrated CGM pumps: while not entirely automated, these pumps work in conjunction with CGM sensors and can suggest insulin dose adjustments based on glucose trends.
- Mechanical pumps: these are simpler devices that provide fixed and programmable insulin delivery, often used in specific clinical scenarios [46].
2.3. Glucose-Responsive Insulin Delivery System and Artificial Intelligence (AI) in Diabetes Management
2.4. Supporting Adolescents in T1D Self-Management: Education and Digital Tools
2.4.1. The Role of Digital Storytelling in Diabetes Education
2.4.2. Mobile Technology and IT Innovations in T1D Management
2.4.3. The Role of Telemedicine in T1D Management
- Reduced patient-physician interaction: personal contact is a key element in establishing trust and improving patient adherence, which may be compromised in virtual care settings [124].
- Technological barriers: some patients and healthcare providers struggle with limited digital literacy, affecting their ability to effectively utilize telemedicine platforms [123].
2.5. Expanding Diabetes Technology Worldwide: Challenges and Opportunities
3. Future Solutions in the Therapy of T1D
3.1. Wearable Biosensors: Non-Invasive Continuous Monitoring
- Real-time glucose tracking via smartphone applications;
- Automated alerts when glucose levels exceed pre-set thresholds;
- Data storage and analysis to enhance long-term glycemic management.
3.2. Optical Coherence Tomography (OCT) for Glucose Monitoring
- Completely non-invasive, eliminating the need for needles or skin punctures;
- High imaging precision enables real-time tracking of glucose fluctuations;
- Enhanced patient comfort is particularly beneficial for pediatric patients [142].
3.3. Bioimpedance-Based Glucose Monitoring
- Bioimpedance offers a stable and precise estimation of glucose levels, particularly within an optimal frequency range below 40 kHz [145].
- CGM devices based on bioimpedance include sensors, analytical algorithms, and measurement circuits, offering a potential alternative to traditional CGM systems [138].
3.4. Immunotherapy: Modulating the Immune Response in T1D
- Proinsulin peptide (PPI) vaccines: Proinsulin peptide vaccines train the immune system to tolerate beta cells instead of attacking them. By exposing the immune system to proinsulin fragments, these vaccines help induce immune tolerance, potentially preventing or delaying T1D onset. Clinical stage: phase I/II trials are ongoing to assess efficacy and safety [17].
- Regulatory T-cell (Treg) therapy: Tregs are a specialized subset of immune cells responsible for suppressing autoimmune reactions. In Treg therapy, patient-derived Tregs are extracted, expanded in a laboratory, and reinfused to restore immune balance. This approach reduces beta cell destruction and modulates immune responses, helping preserve endogenous insulin production. Clinical stage: multiple Phase I/II clinical trials are investigating Treg therapy in newly diagnosed T1D patients [147].
- Monoclonal antibodies (teplizumab therapy): Teplizumab is a monoclonal antibody therapy that targets CD3 on T-cells, effectively by blocking key immune pathways involved in the attack on beta cells, delaying disease progression in newly diagnosed individuals, and reducing inflammation and modulating the immune system’s response to beta cells. Clinical stage: Teplizumab has received FDA approval for delaying the onset of T1D in at-risk individuals. Ongoing studies continue evaluating long-term efficacy [16,148].
- Antigen-specific therapy— Zinc Transporter Protein 8 (ZnT8) targeting: ZnT8 is an autoantigen present in prediabetic and diabetic patients, making it a critical target for immunotherapy. ZnT8-based treatments help regulate immune responses, potentially protecting beta cells from further autoimmune damage. Early diagnosis strategies using ZnT8 autoantibodies can also improve predictive screening for T1D risk. Clinical stage: preclinical and early-stage Phase I trials [149,150];
- Immune modulators: Immune modulation aims to modify the immune response to maintain beta cell function and prevent or delay the onset of the disease. Abatacept, a T-cell co-stimulation blocker, reduces inflammation and lowers the likelihood of autoimmune destruction. Other immunomodulatory drugs are currently being tested to improve beta cell survival and enhance long-term glycemic control. Clinical stage: phase II/III trials are evaluating the efficacy in delaying T1D progression [151].
3.5. Stem Cell Therapy
- Embryonic stem cells (ESCs) are pluripotent cells capable of differentiating into any cell type, including beta cells. These cells have shown great potential for beta cell regeneration but raise ethical concerns and a risk of immune rejection [153];
- Induced pluripotent stem cells (iPSCs) are reprogrammed adult cells that mimic ESCs, offering a patient-specific approach. These cells are generated from the patient’s own cells, reducing the risk of immune system rejection and provide an ethically viable alternative to embryonic stem cells [154];
- Mesenchymal stem cells (MSCs) are found in bone marrow, adipose tissue, and umbilical cord blood. These cells exhibit anti-inflammatory and immunomodulatory properties, making them valuable in autoimmune diseases like T1D. Also, they differentiate into multiple cell types, including insulin-producing beta cells [155,156].
3.6. Gene Therapy
- Gene transfer for beta-cell regeneration uses viral vectors (e.g., adenoviruses, lentiviruses) to introduce essential transcription factors like PDX1 and MAFA. These factors play a critical role in beta cell development and regeneration, restoring insulin production in individuals with T1D [135].
- CRISPR-Cas9 gene editing is a revolutionary gene-editing technique that enables precise genetic modifications. This gene can correct mutations in the insulin gene to ensure proper insulin production. Also, it allows the introduction of protective sequences to shield beta cells from autoimmune destruction [157].
- Gene therapy for localized immunosuppression delivers therapeutic genes that produce immunosuppressive proteins (e.g., IL-10 and TGF-beta). Also, it protects beta cells from autoimmune attacks without compromising the body’s immune defense against infections [157].
- Alpha-to-beta cell conversion introduces specific genes like ARX and PDX1 to reprogram glucagon-producing alpha cells into insulin-producing beta cells. This technique offers an alternative source of functional beta cells, restoring natural insulin production [18].
3.7. Contact Lenses for CGM
3.8. Microbiome and Personalized Medicine
3.9. The Role of Probiotics in T1D Management
3.10. Nanomedicines Based on Trace Elements in Diabetes Management
- Blood glucose regulation: trace element nanoparticles help lower blood glucose levels, reducing hyperglycemia.
- Improved insulin sensitivity: these nanoparticles enhance cellular responsiveness to insulin, allowing for better glucose uptake and utilization.
- Enhanced insulin secretion: certain trace element-based nanomedicines stimulate pancreatic β-cells to produce and release insulin more efficiently.
- Alleviation of glucose intolerance: by modulating glucose absorption and utilization, these nanoparticles help prevent postprandial glucose spikes.
- Lipid profile improvement: studies have shown that trace element nanoparticles can positively influence lipid metabolism, reducing the risk of dyslipidemia in diabetes.
- Anti-inflammatory and antioxidant properties: nanoparticles derived from trace elements exhibit anti-inflammatory and antioxidant effects, which are crucial in preventing β-cell damage and mitigating diabetes-related oxidative stress [137].
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
T1D | Type 1 diabetes |
CGM | Continuous glucose monitoring |
AI | Artificial intelligence |
CRISPR | Clustered Regularly Interspaced Short Palindromic Repeats |
WHO | World Health Organization |
IDF | International Diabetes Federation |
ISPAD | International Society for Pediatric and Adolescent Diabetes |
CSII | Continuous subcutaneous insulin infusion |
FDA | Food and Drug Administration |
IT | Information technology |
MAFA | Musculoaponeurotic fibrosarcoma oncogene homolog A |
PDX1 | Pancreatic and duodenal homeobox 1 |
ARX | Aristaless-related homeobox |
DKA | Diabetic ketoacidosis |
SGLT2 | Sodium-Glucose Co-Transporter 2 |
TREG | Regulatory T-cell |
GDPR | General Data Protection Regulation |
HIPAA | Health Insurance Portability and Accountability Act |
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Company Name | Country | Example of CGM Device | Functional Principle | Clinical Relevance and Mechanism |
---|---|---|---|---|
F. Hoffmann-La Roche | Switzerland | Accu-Chek CGM System | Utilizes a subcutaneous sensor to measure glucose in interstitial fluid, transmitting data wirelessly to a receiver or smartphone. | Provides real-time glucose tracking and alerts users to prevent hypo- or hyperglycemia. |
A. Menarini Diagnostics | Italy | GlucoMen Day CGM | Employs a minimally invasive continuous glucose sensor that connects via Bluetooth for real-time monitoring. | Enhances glucose control by reducing the frequency of blood glucose finger sticks. |
B. Braun Melsungen AG | Germany | Omnitest CGM | Uses an enzymatic biosensor to detect glucose levels in the interstitial fluid, providing continuous data. | Supports proactive insulin adjustments by offering trend insights. |
Echo Therapeutics, Inc. | USA | Symphony CGM | Implements a transdermal biosensor for non-invasive glucose measurement. | Aims to eliminate discomfort associated with invasive CGM devices. |
Johnson & Johnson | USA | Animas Vibe CGM | Integrates a real-time glucose sensor with an insulin pump for automated insulin adjustments. | Improves glycemic control through a semi-automated insulin delivery system. |
Medtronic plc | USA | Guardian Connect CGM | Uses a thin subcutaneous sensor to provide continuous glucose readings to a linked device. | Provides predictive alerts for hypo- and hyperglycemia, improving glycemic stability. |
GlySens Incorporated | USA | GlySens ICGM System | Features a fully implantable CGM that transmits glucose data continuously. | Reduces the need for sensor replacements, allowing long-term glucose monitoring. |
Senseonics Holdings, Inc. | USA | Eversense Implantable CGM | Utilizes an implantable fluorescence-based glucose sensor that communicates with a wearable transmitter. | Offers extended wear time (up to 6 months) for reduced device maintenance. |
Abbott Laboratories | USA | FreeStyle Libre | Uses a filament sensor placed under the skin that is scanned manually for glucose readings. | Eliminates routine fingerstick testing while providing retrospective glucose data. |
LifeScan IP Holdings LLC | USA | OneTouch CGM System | Employs a subcutaneous electrochemical sensor that transmits glucose levels to a connected app. | Facilitates real-time glucose monitoring with digital tracking for better self-management. |
Terumo Corporation | Japan | Terumo CGM | Implements an enzymatic reaction-based sensor for continuous glucose tracking. | Ensures high accuracy in glucose detection, aiding in insulin dosing decisions. |
Application Name | Key Benefits | References |
---|---|---|
Bant app | Enhances blood glucose monitoring and self-management. | [5,97] |
Webdia app | Reduces HbA1c levels in children. | [87] |
MyT1DHero app | Improves communication between parents and adolescents; enhances adherence to self-care. | [23,98] |
Ana Alsukary app created in Saudi Arabia | Helps children understand their diabetes and adjust their lifestyle. | [24] |
Young with Diabetes app (YWD) | Reduces feelings of loneliness; enhances T1D knowledge and self-management skills. | [88,92,99] |
Diapplo app | Partially meets children’s educational needs. | [100] |
Mobile Diabetes Advice for Dads (mDAD) | Assists fathers in understanding and supporting diabetes management. | [89] |
SweetGoals app | Supports young adults in complying with their medical regimen. | [101] |
Mobile Diab | Aids in T1D treatment for adolescents. | [86,102,103] |
CanDIT (Canadian Diabetes Incentives and Technology) app | Highly accepted tool for providing diabetes-related information. | [103] |
iSpy app and glycemic control tools | Encourages glucose monitoring, assists with data collection, and supports healthy nutrition and medication dosing. | [104,105] |
Category | Therapy | Development Stage | Key Benefits | Challenges/Risks | Reference |
---|---|---|---|---|---|
Emerging Therapies (In Clinical Trials, Awaiting Approval) | Beta Cell Regeneration Therapies (Stem Cell-Derived β-Cells) | Phase 1/2 clinical trials | Potential to restore natural insulin production | Risk of immune rejection, ethical concerns | [133] |
Advanced Artificial Pancreas (Next-Gen Hybrid Closed-Loop Systems) | Late-stage development | AI-driven glucose prediction, dual hormone systems | Requires extensive validation, high costs | [125] | |
Combination Immunotherapy Approaches | Phase 1/2 trials | Aims to protect β-cells from autoimmune destruction | Long-term effects and patient selection still uncertain | [134] | |
Experimental Therapies (Preclinical or Early Research) | CRISPR Gene Editing for T1D Cure | Preclinical stage | Potential to correct genetic predisposition to autoimmunity | Ethical and technical challenges, long-term safety unknown | [135] |
Bioartificial Pancreas (Encapsulated Insulin-Secreting Cells) | Animal models | Implantable alternative to insulin therapy | Durability and immune rejection issues | [12] | |
Gut Microbiome Modulation for Autoimmune Prevention | Early human studies | May prevent autoimmune response and preserve β-cells | Needs further validation, long-term effects unknown | [136] | |
Nanomedicine-Based Insulin Delivery | Preclinical stage | More efficient insulin absorption, reduced injections | No human trials yet, safety concerns | [137] |
Probiotic Type | Key Details | Type of Study (Participants) | Duration of Treatment | Key Findings | Reference |
---|---|---|---|---|---|
Multispecies Probiotic (Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis, Saccharomyces boulardii) | Commonly found in fermented foods; supports gut health and immune modulation. | Randomized, double-blind, placebo-controlled clinical trial (91) | 6 months | Significant reduction in HbA1c, fasting glucose, and total cholesterol | [167,168] |
Multispecies Probiotic (Lactobacillus casei, Bifidobacterium bifidum) | Frequently used in probiotic supplements; aids in gut microbiome stability. | Randomized controlled trial (60) | 12 weeks | Significant improvement in glycemic control and lipid profile. | [166] |
Lactobacillus rhamnosusGG | Well-researched strain for gut health; found in dairy-based probiotic products. | Randomized controlled trial (33) | 6 months | No significant effect on β-cell function or HbA1c levels. | [169] |
Multispecies Probiotic (Bifidobacterium longum, Lactobacillus bulgaricus, Streptococcus thermophilus) | Used in dairy products and probiotic formulations; supports digestion and metabolism. | Randomized, double-blinded, placebo-controlled pilot study (50) | 12 weeks | Significant reduction in fasting blood glucose levels. | [170] |
Synbiotic Supplement (Probiotics + Prebiotics) | Combination of beneficial bacteria and dietary fibers for gut health. | Randomized controlled trial (130) | 6 months | Study protocol; results pending. | [171] |
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Batir-Marin, D.; Ștefan, C.S.; Boev, M.; Gurău, G.; Popa, G.V.; Matei, M.N.; Ursu, M.; Nechita, A.; Maftei, N.-M. A Multidisciplinary Approach of Type 1 Diabetes: The Intersection of Technology, Immunotherapy, and Personalized Medicine. J. Clin. Med. 2025, 14, 2144. https://doi.org/10.3390/jcm14072144
Batir-Marin D, Ștefan CS, Boev M, Gurău G, Popa GV, Matei MN, Ursu M, Nechita A, Maftei N-M. A Multidisciplinary Approach of Type 1 Diabetes: The Intersection of Technology, Immunotherapy, and Personalized Medicine. Journal of Clinical Medicine. 2025; 14(7):2144. https://doi.org/10.3390/jcm14072144
Chicago/Turabian StyleBatir-Marin, Denisa, Claudia Simona Ștefan, Monica Boev, Gabriela Gurău, Gabriel Valeriu Popa, Mădălina Nicoleta Matei, Maria Ursu, Aurel Nechita, and Nicoleta-Maricica Maftei. 2025. "A Multidisciplinary Approach of Type 1 Diabetes: The Intersection of Technology, Immunotherapy, and Personalized Medicine" Journal of Clinical Medicine 14, no. 7: 2144. https://doi.org/10.3390/jcm14072144
APA StyleBatir-Marin, D., Ștefan, C. S., Boev, M., Gurău, G., Popa, G. V., Matei, M. N., Ursu, M., Nechita, A., & Maftei, N.-M. (2025). A Multidisciplinary Approach of Type 1 Diabetes: The Intersection of Technology, Immunotherapy, and Personalized Medicine. Journal of Clinical Medicine, 14(7), 2144. https://doi.org/10.3390/jcm14072144