#47 - 🧠 T1D genes are active in your brain

Hey readers! 👋

Welcome back to another packed week in the T1D world. This week we're diving into some fascinating research connecting diabetes genetics to the brain (yes, really), a new NEJM trial on teplizumab, pump tech that listens for blockages with sound waves, and an implant that keeps beta cells alive by making its own oxygen. Grab your coffee and let's get into it. ☕

Genetic Risk for Type 1 Diabetes Extends to Brain Cells, Study Finds - Yale researchers discovered that genetic risk variants for T1D are active not just in immune and pancreatic cells, but also in brain cells called microglia. - Yale School of Medicine

The study used UK Biobank data and Mendelian randomization to identify overlap between T1D risk signals and cognitive traits. Importantly, the researchers stress this reflects shared biological pathways, not direct causation, and environmental factors still play a major role. It's a reminder that T1D is more systemic than we sometimes think, and understanding these connections could open new avenues for research.

Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes - A phase 3 trial of 328 children and adolescents showed that teplizumab preserved beta-cell function, with a 59% higher C-peptide level at 78 weeks compared to placebo. - NEJM

Here's where it gets nuanced: despite that significant biochemical preservation, the trial didn't find meaningful differences in insulin dose, HbA1c, time in range, or hypoglycemia events. The safety profile was reassuring, with mostly mild side effects and no long-term immunosuppression. This is an important data point for teplizumab's story. Preserving beta cells matters, but the clinical translation remains an open question that future studies will need to address.

Enhancing Type 1 Diabetes Polygenic Risk Prediction Through Neural Networks - A neural network using just 67 known T1D-associated genetic variants achieved an AUC of 0.903 in predicting T1D risk, with a 98.9% negative predictive value for the lowest-risk group. - PubMed

This kind of risk stratification tool could eventually help identify who needs closer monitoring, especially when paired with autoantibody screening programs. The model was validated in both UK Biobank and a German cohort, showing strong performance across populations.

Towards Insulin Independence in Type 1 Diabetes: Prospects for Prevention and Cure - This comprehensive review covers the current landscape from teplizumab's ability to delay onset by 2-3 years, to stem-cell-derived beta-cell therapies like VX-880 that have achieved insulin independence in early trials. - PLoS Medicine

The paper also discusses CRISPR-engineered islets and autologous iPSC-derived transplants that could eventually remove the need for chronic immunosuppression. These are still early-stage efforts, but the convergence of prevention and regeneration strategies is genuinely encouraging.

Gene Therapy and Safer Islet Transplants: Advances in Type 1 Diabetes Research - Two notable developments: KRIYA-839, a gene therapy delivering insulin-producing genes to muscle cells, is entering its first clinical trial, while tegoprubart, a targeted anti-rejection drug, has enabled transplant recipients to stop insulin therapy with an average HbA1c of 35 mmol/mol (5.35%). - Diabetes UK

Implant Treats Type 1 Diabetes by Oxygenating Insulin-Producing Cells - Cornell engineers built an implantable device that generates its own oxygen supply to keep encapsulated insulin-secreting cells alive, without immunosuppression. - Cornell Chronicle

Still in rat models, but the approach of solving the oxygen problem, one of the biggest barriers to cell encapsulation, is clever. The team is planning pig studies and human stem-cell trials next.

Medtrum Touts Meal Logging Tech for Automated Insulin Delivery - Medtrum's TouchCare Nano AID system introduces Auto Meal Handling, which lets users simply log that they're eating instead of counting carbs, achieving 75% time in range in a six-month study of 95 participants. - Drug Delivery Business

For anyone who's ever stared at a plate trying to estimate carbs, this is a welcome direction. No increase in hypoglycemia was observed, which is the key safety benchmark.

Twiist Loop Algorithm - Twiist's AID system predicts glucose every 5 minutes with a 6-hour forecast, showing a 6% improvement in time in range and a 90% reduction in severe hypoglycemia in clinical studies. - Twiist

iiSure Technology - Twiist's acoustic measurement tech detects insulin pump occlusions up to nine times faster than competing systems, potentially reducing unexplained highs and DKA risk. - Sequel Med Tech

Eversense 365 CGM System - The only one-year implantable CGM, offering 365 days of continuous readings with a removable transmitter, gentle daily adhesives, and coverage by most insurance plans for as low as $199/year. - Eversense

That's a wrap for this week! As always, we're here to keep you informed without the hype. If something caught your eye or you have thoughts to share, just hit reply. We read every message. 💬

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