AI Blood Test Could Detect Early Eye Nerve Damage in People with Type 2 Diabetes
Key Takeaways:
- An AI tool called Pro-DRN uses a blood sample to flag people with type 2 diabetes at high risk of diabetic retinal neurodegeneration (DRN), before any damage shows on the retina.
- It was trained on 1,218 participants and validated in 502 people from UK Biobank, identifying 71 proteins linked to DRN – with ACTA2, COL6A3 and HSPG2 the strongest predictors.
- As retinal nerves are among the first tissues affected by diabetes, the test could also hint at wider nerve damage and help target earlier monitoring and future treatments.
A simple blood test to catch nerve damage early
Scientists have developed an AI-assisted prediction tool that can identify people with type 2 diabetes who are at high risk of developing diabetic retinal neurodegeneration (DRN) before symptoms appear. The findings were published in the journal PLOS Medicine.
The work was led by Wei Wang, MD, PhD, associate professor at the Guangdong Provincial Clinical Research Center for Ocular Diseases. According to the authors, the damage that diabetes inflicts on the delicate nerves of the eye appears to leave a detectable molecular trail in the bloodstream long before it becomes visible in the eye itself.
“Our study suggests that early retinal nerve damage in diabetes leaves measurable signals in the blood,” write the authors. “These findings suggest that a simple blood test analyzed with artificial intelligence may help identify people with diabetes who are at highest risk of early retinal nerve damage, well before visible damage appears on the retina.”
Why the retinal nerves matter in diabetes
Type 2 diabetes affects more than half a billion people worldwide, and it carries an increased risk of long-term complications, including progressive neurodegeneration – the gradual deterioration of nerve tissue over time.
The nerves of the retina are among the earliest tissues to be affected. As this damage advances, it can eventually lead to severe visual impairment and the loss of sight. The difficulty for clinicians is one of timing: current diagnostic methods can only detect DRN once the retina has already sustained irreversible damage. By the time the problem is visible, the window for early, protective intervention has often closed.
How the Pro-DRN tool was built
To address this, Wang and colleagues developed a machine learning algorithm called Pro-DRN. They drew on data from 1,218 participants in the Guangzhou Diabetic Eye Study, all of whom had been diagnosed with type 2 diabetes but had not yet developed DRN at the point of enrolment.
The model combined two distinct streams of information. The first was proteomics data – a detailed read-out of the proteins circulating in participants’ blood samples. The second was a series of yearly retinal images, capturing the state of the eye over a six-year follow-up period. By matching the molecular signals in the blood against how each person’s retina changed year on year, the algorithm learned which blood-borne patterns preceded the onset of nerve damage.
The proteins behind the predictions
The analysis surfaced 71 proteins associated with the development of DRN. Of these, three stood out as the most consistent drivers of accurate prediction: ACTA2, COL6A3 and HSPG2. These are key structural components involved in maintaining the integrity of the nerve and muscle tissue in the eye, which helps explain why disturbances in their levels might signal nerve tissue under strain.
Crucially, the team did not rely on a single dataset. The results were validated in an independent cohort of 502 people from UK Biobank, where the core effects and protein signals were reproduced – an important check that the findings were not simply a quirk of the original group.
From research tool to clinical aid
Pro-DRN has been made available as an interactive, web-based risk assessment tool that clinicians can use to support early DRN screening and to monitor how a person’s risk evolves over time. People identified as being at high risk could then benefit from more frequent check-ups and from early interventions aimed at preventing or slowing progressive neurodegeneration, rather than waiting for damage to become apparent.
A window into the wider nervous system
The potential significance of the test reaches beyond the eye. Because DRN is one of the first signs of nerve degeneration brought on by diabetes, detecting it early could also signal the onset of nerve injury elsewhere in the body.
Such damage can contribute to cognitive impairment, dementia and peripheral neuropathy – the latter causing loss of sensation and motor control in the hands, feet and other extremities. Viewed this way, a single eye-focused test could offer valuable insight into the overall health of a person’s nervous system.
New possibilities for treatment and trials
The discoveries also open up two further avenues. The proteins identified as being involved in DRN progression could be investigated as potential targets for the development of new therapies. In addition, the AI-based tool could prove useful for selecting and stratifying participants in clinical trials that are evaluating neuroprotective strategies designed to prevent or delay nerve damage – helping ensure such studies enrol the people most likely to show a measurable benefit.
Looking ahead
For the researchers, the broader ambition is a shift in how diabetic eye care is approached – from reacting to damage that has already occurred towards anticipating who is most vulnerable.
“Pro-DRN may help move diabetic eye care from detecting established damage toward earlier, molecularly informed risk stratification, so that closer monitoring and future neuroprotective interventions can be directed to the people most likely to benefit,” Wang and colleagues write.
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Weight Loss Drugs Linked to Lower Risk of Peptic Ulcer Disease in Adults with Diabetes
Key Takeaways:
- A large US study involving more than 66,000 adults found that people with type 2 diabetes using GLP-1 receptor agonists had significantly lower odds of developing peptic ulcer disease.
- Researchers observed a 44 percent lower likelihood of peptic ulcer disease among GLP-1 users overall, with a 56 percent lower risk seen in people who switched from metformin to a GLP-1 medication instead of insulin.
- The findings add to growing evidence that GLP-1 receptor agonists may have anti-inflammatory and gastrointestinal protective effects beyond blood sugar control and weight management.
Study suggests potential gut benefits of GLP-1 medications
Medications commonly prescribed for type 2 diabetes and obesity management may provide an additional benefit beyond blood sugar control and weight reduction. A large nationwide study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) has found that people with type 2 diabetes who used GLP-1 receptor agonists were significantly less likely to develop peptic ulcer disease compared with those who did not use these medications.
The findings were published in Clinical Gastroenterology and Hepatology and were based on electronic health record data from more than 66,000 adults participating in the National Institutes of Health’s All of Us Research Program. The programme is considered one of the most diverse biomedical research datasets in the United States.
“Peptic ulcer disease remains a significant cause of illness and hospitalization, particularly among people with type 2 diabetes, yet large-scale clinical studies examining how newer diabetes medications affect ulcer risk have been lacking,” said Trisha Pasricha, MD, MPH, a gastroenterologist at BIDMC. “Our study was designed to address that gap and to better understand whether GLP1 receptor agonists are associated with meaningful differences in ulcer risk in this population.”
Understanding peptic ulcer disease in diabetes
Peptic ulcers are painful open sores that develop in the lining of the stomach or upper part of the small intestine. Symptoms can include ongoing abdominal pain, nausea, indigestion, and bloating. In more severe cases, ulcers can lead to complications such as gastrointestinal bleeding or perforation.
Globally, around four million people experience ulcer-related complications each year.
People living with type 2 diabetes are known to have a higher risk of developing peptic ulcer disease. Researchers believe this increased vulnerability may stem from a combination of chronic inflammation, metabolic stress, impaired tissue repair, and greater exposure to medications associated with ulcer formation, particularly nonsteroidal anti-inflammatory drugs (NSAIDs).
Because of this elevated risk, researchers sought to investigate whether GLP-1 receptor agonists, which were first approved for diabetes treatment approximately two decades ago and are now widely used for both diabetes and obesity care, might influence ulcer risk.
GLP-1 use associated with lower ulcer risk
The researchers found that the use of GLP-1 medications was associated with substantially lower odds of being diagnosed with peptic ulcer disease.
Across the full study population, people with type 2 diabetes using GLP-1 receptor agonists had a 44 percent lower likelihood of receiving a peptic ulcer diagnosis compared with people not using these medications. The association remained even after adjusting for factors including age, sex, body mass index, medication use, and other clinical variables.
The investigators also carried out a more focused comparison involving people who had discontinued metformin, which remains the standard first-line therapy for type 2 diabetes. Researchers examined participants who then transitioned either to a GLP-1 medication or to insulin therapy.
In this head-to-head analysis, people who switched to a GLP-1 receptor agonist had a 56 percent lower risk of developing peptic ulcer disease compared with those who switched to insulin.
Researchers point to possible anti-inflammatory effects
Although GLP-1 receptor agonists are not currently prescribed for ulcer prevention, researchers believe the findings may reflect broader biological effects of the medications.
“Although these medications are not prescribed with ulcer prevention in mind, there is growing evidence that GLP1 receptor agonists may have broader biological effects, including anti-inflammatory properties and roles in gastrointestinal mucosal protection,” said senior author Pasricha, who is also an assistant professor of medicine at Harvard Medical School. “Those effects may help explain why we observed different ulcer risks compared with insulin.”
GLP-1 receptor agonists are best known for improving blood glucose control, supporting weight loss, and reducing cardiovascular risk in people with type 2 diabetes and obesity. However, a growing body of research suggests these drugs may also reduce inflammation and support tissue repair within the gastrointestinal tract.
The authors noted that more research is needed to determine whether these effects directly improve the stomach and small intestine’s ability to resist injury, particularly in people with diabetes who may already have impaired protective mechanisms.
Findings strengthened by known risk factors
The investigators also observed that medications already known to increase ulcer risk behaved as expected within the dataset. NSAIDs, corticosteroids, and blood thinners were all associated with increased ulcer risk, supporting the reliability of the study’s methodology.
Taken together, the researchers said the findings strengthen the observed association between GLP-1 receptor agonist use and lower rates of peptic ulcer disease.
Study authors and funding
Co-authors of the study included Philippa Seika, Jocelyn Chang, Su Min Hong, Sarah Ballou, Vikram Rangan, Chethan Ramprasad, Johanna Iturrino, Judy Nee, and Subhash Kulkarni of BIDMC; Christian Denecke of Charité Universitätsmedizin; and Anthony Lembo of Cleveland Clinic.
The study was funded by the American Gastroenterological Research Foundation’s Research Scholar Award, the National Institute on Aging, the Diacomp Foundation, a Pilot Grant from the Harvard Digestive Disease Core, and the Walter Benjamin Fellowship from the Deutsche Forschungsgemeinschaft.
The authors reported no conflicts of interest.
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Algorithm-Guided Insulin Dosing Improves Blood Sugar Control in Type 2 Diabetes
Key Takeaways:
- An algorithm paired with continuous glucose monitoring significantly increased time in target glucose range compared with standard self-monitoring approaches
- The tool provides personalised weekly insulin dose recommendations based on recent glucose data, helping to simplify titration
- Early findings suggest strong patient acceptability and potential to enhance diabetes management at scale, though larger trials are needed
A data-driven approach to insulin adjustment
A novel algorithm developed by researchers at the University of Virginia Center for Diabetes Technology has demonstrated encouraging results in supporting people living with Type 2 Diabetes to better manage their blood glucose levels.
The system works in combination with a continuous glucose monitor and provides tailored recommendations for insulin dose adjustments. Rather than relying solely on manual interpretation of glucose readings, the algorithm analyses patterns over time and offers structured, data-informed guidance.
In a clinical trial involving 30 participants, individuals were randomly assigned to one of two approaches over a 16-week period:
- Algorithm-guided insulin adjustment using continuous glucose monitoring data
- Traditional self-monitoring of blood glucose with independent dose adjustment
The results showed a marked improvement in glycaemic control among those using the algorithm. Participants in this group increased their average time spent within a safe blood glucose range from 54.1% to 75.3%. By contrast, those relying on self-monitoring alone saw a more modest increase from 50.2% to 55.3%.
Moving beyond traditional insulin management
The findings highlight the growing role of digital health tools in diabetes care. According to Marc D. Breton, the study’s lead author:
“These results clearly show that diabetes technology and advanced algorithms can be leveraged to great effects, well beyond the classical paradigm of automated insulin delivery. As continuous glucose monitoring and connected medical devices become ubiquitous, we have the opportunity to provide highly personalized advice and monitoring to people with diabetes and guide their use of insulin and medications. Showing the impact of these technologies in early insulin therapy (only one dose a day) opens the door to helping the vast majority of people using insulin, well beyond what we were able to achieve with automated insulin delivery.”
This perspective reflects a broader shift towards personalised, technology-enabled care. Rather than fully automated systems alone, there is increasing interest in decision-support tools that augment clinical judgement and patient self-management.
Addressing the challenges of insulin titration
For many people living with type 2 diabetes, treatment often begins with oral or non-insulin therapies. However, as the condition progresses, insulin may become necessary to maintain adequate glycaemic control.
Adjusting insulin doses – a process known as titration – can be complex and burdensome. It typically requires frequent monitoring, interpretation of glucose patterns, and iterative dose changes. Importantly, there is no universally standardised titration protocol, which can create variability in care and outcomes.
To address this, Anas El Fathi developed the algorithm with the aim of streamlining and improving this process. The system evaluates two weeks of continuous glucose monitoring data and generates weekly recommendations for insulin dose adjustments, offering a structured and personalised approach.
Strong acceptance and clinical potential
The study also explored how well the technology was received by participants. According to Ralf Nass:
“From a medical point of view, it was fascinating to see that the algorithm was not only better than the standardized insulin titration recommendations, but also how well the technology was accepted by the participants with type 2 diabetes. This type of technology has the potential to help physicians enable their patients to achieve better glycemic control faster by using a personalized approach.”
This combination of improved outcomes and user acceptability is particularly important, as adherence and engagement remain key challenges in long-term diabetes management.
Future directions – towards more personalised diabetes care
While the results are promising, the researchers emphasise that further validation is required. Larger and longer clinical trials will be needed to confirm the effectiveness of the algorithm across more diverse populations.
Looking ahead, the integration of more advanced data-driven approaches may further enhance personalisation. Breton noted:
“It is only the very beginning of these efforts. With early demonstration behind us, we can focus on robust approaches that will be effective with more varied populations. Integrating recently developed data-driven methodologies, especially digital twins, to further improve our capacity to tailor diabetes managements to individuals is likely to once more revolutionize diabetes care.”
Such developments could represent a significant step forward in precision medicine for people living with diabetes.
Study publication and funding
The findings have been published in the peer-reviewed journal Diabetes Technology & Therapeutics, with the article available as open access.
The research team included El Fathi, Nass, Carol J. Levy, Camilla Levister, Grenye O’Malley, Nirali A. Shah, Shaziah Hassan, Cheryl Quainoo, Chaitanya L.K. Koravi, Taylor N. Nguyen, Giulio Matteo Santini, Emma Emory, Carlene Alix, Dillon K. Flanagan, David Fulkerson, Mary Clancy Oliveri, Christian Laugesen, Jonas K. Lineolov, Peter W. Hansen and Breton.
The clinical trial was supported by a grant from Novo Nordisk.
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GLP-1 Receptor Agonists Linked to Lower Mortality After Diabetic Foot Ulcers, Nationwide French Study Finds
Key Takeaways:
- Nearly one in seven people experienced death within one year of a first diabetic foot ulcer, highlighting the severity of risk following ulcer onset.
- Treatment with GLP-1 receptor agonists was independently associated with improved survival, including after major lower-limb amputation.
- Multidisciplinary care and early specialist involvement were associated with better outcomes, reinforcing the importance of structured follow-up.
Background and study aims
Diabetic foot ulcers remain one of the most serious complications of diabetes, often signalling advanced disease and a high burden of comorbidity. Despite advances in diabetes care, mortality following a first diabetic foot ulcer continues to be substantial.
This nationwide observational study set out to identify factors associated with one-year mortality after a first recorded diabetic foot ulcer using data from the French National Health Data System (SNDS). A secondary objective was to examine mortality within one year following major lower-limb amputation in the same population.
Study design and data sources
Researchers conducted a retrospective cohort analysis using the SNDS, a comprehensive national database that captures hospital admissions, outpatient care, prescribed medications, and long-term disease registrations across France.
Adults with a first incident diabetic foot ulcer recorded between January 2017 and December 2018 were included. Case identification combined hospital discharge diagnoses and community care records, allowing capture of people diagnosed both in hospital and in outpatient settings. All individuals were followed for 12 months after ulcer identification.
To examine associations with mortality, the researchers used Cox proportional hazards models. These models adjusted for a wide range of variables, including demographic characteristics, clinical comorbidities, diabetes treatments, major amputation, and access to specialist care.
Mortality and amputation outcomes
In total, 133,791 people with a first diabetic foot ulcer were identified. Within one year of diagnosis, 14.6% died, underlining the high short-term mortality associated with this complication. During the same period, 3.5% underwent a major lower-limb amputation.
Outcomes following amputation were particularly poor. Among those who had a major amputation, 28.8% died within one year, indicating a markedly elevated risk compared with people who did not undergo amputation.
Factors associated with increased mortality
Several factors were independently associated with a higher risk of death within one year of a first diabetic foot ulcer. These included male sex, increasing age, and ulcers identified during a hospital admission rather than in the community.
Clinical and treatment-related predictors of higher mortality included insulin use, major lower-limb amputation, and a range of comorbid conditions. Cardiovascular disease, cancer, dementia, end-stage kidney disease, and liver disease were all strongly associated with poorer survival.
Similar patterns were observed when analysing mortality after major amputation, suggesting that underlying health status and disease severity play a central role in outcomes across the care pathway.
Protective factors and the role of GLP-1 receptor agonists
Several factors were associated with a lower risk of death. Use of lipid-lowering therapy emerged as a protective factor, as did prior contact with specialist healthcare professionals. People who had consulted diabetologists, ophthalmologists, or podiatrists before ulcer onset experienced better survival, pointing to the benefits of ongoing, multidisciplinary diabetes care.
Notably, treatment with glucagon-like peptide-1 receptor agonists was independently associated with reduced mortality at one year. This association persisted both in the overall cohort and among people who underwent major lower-limb amputation, suggesting a consistent survival benefit linked to this class of medication.
Interpretation and implications for care
The findings confirm that one-year mortality after a diabetic foot ulcer remains unacceptably high and is closely linked to age, comorbidity burden, and disease severity. Importantly, the inclusion of community-identified ulcers highlights that people with diabetic foot disease are highly vulnerable even outside hospital settings.
The observed association between GLP-1 receptor agonist use and improved survival adds to growing evidence that these therapies may offer benefits beyond glycaemic control. Alongside pharmacological treatment, structured follow-up and early involvement of specialist services appear to play a critical role in improving outcomes.
Conclusions
This nationwide study shows that mortality following a first diabetic foot ulcer is substantial, particularly among people with advanced comorbidities and those requiring major amputation. Glucagon-like peptide-1 receptor agonists and coordinated, multidisciplinary care were associated with better survival and should be prioritised in high-risk populations.
Together, these findings underscore the urgent need to strengthen preventive strategies, optimise care pathways, and ensure timely access to specialist diabetes and foot care services for people living with diabetes who are at risk of ulceration.
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Study Suggests GLP-1 Medications May Reduce Frailty Progression in Older Adults
Key Takeaways:
- Older adults with type 2 diabetes who begin SGLT-2 inhibitors or GLP-1 receptor agonists show slower frailty progression over one year compared with those starting other diabetes therapies.
- The analysis, based on a large national Medicare dataset, suggests these medications may offer benefits beyond glycaemic and cardiovascular control, potentially supporting strength, mobility, and functional independence.
- The protective effect was not fully explained by fewer cardiovascular or safety events, indicating a possible direct influence of these drug classes on frailty itself.
Emerging evidence that newer diabetes drugs may protect against frailty
A new study has found that older adults living with type 2 diabetes who initiate treatment with sodium–glucose cotransporter-2 (SGLT-2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists experience significantly slower progression of frailty over a 12-month period compared with those starting alternative diabetes medications. The findings point to a potential added advantage of these therapies in helping older adults maintain physical resilience, strength, and independence, complementing their established effects on blood glucose regulation and cardiovascular risk reduction.
Study overview and methods
The research, published in Diabetes Care and titled “Sodium–Glucose Cotransporter-2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, and Frailty Progression in Older Adults With Type 2 Diabetes”, examined a large national cohort of older adults in the United States who had recently begun different classes of diabetes medication.
The investigators analysed a 7 per cent sample of Medicare claims data, enabling real-world tracking of over one year of health outcomes. Frailty progression was assessed using a validated claims-based Frailty Index (CFI), which ranges from 0 to 1 and reflects the cumulative presence of age-related health deficits. Higher CFI scores indicate more severe frailty.
Key findings – slower frailty progression with SGLT-2 and GLP-1 therapies
Older adults newly prescribed a GLP-1 receptor agonist, such as semaglutide (Ozempic) or liraglutide (Victoza), demonstrated a mean CFI change of –0.007 (95 per cent CI: –0.011 to –0.004) compared with matched new users of DPP-4 inhibitors. Those initiating SGLT-2 inhibitors, including empagliflozin (Jardiance) and dapagliflozin (Farxiga), experienced a mean change of –0.005 (95 per cent CI: –0.008 to –0.002).
These figures represent a statistically significant slowing in frailty progression over the study period. In contrast, people beginning sulfonylureas did not show a meaningful difference relative to DPP-4 inhibitor users.
Importantly, the study found that cardiovascular events and other safety-related health issues explained only a small proportion of the protective association. This suggests that these classes of medications may exert a more direct biological effect on mechanisms related to frailty, such as inflammation, physical function, or metabolic stress.
Why frailty matters in older adults with type 2 diabetes
Frailty is common among older adults and especially prevalent in people living with type 2 diabetes. Previous research indicates that 10–15 per cent of adults over the age of 65 meet criteria for frailty, with substantially higher rates among those with diabetes. Multiple factors contribute to this increased vulnerability, including chronic low-grade inflammation, accelerated muscle loss, cardiovascular disease, and the overall physiological strain of managing a long-term condition.
Frailty is linked to an elevated risk of falls, disability, hospital admission, diminished quality of life, and reduced survival. Because frailty is difficult to reverse once it becomes established, clinicians and researchers have prioritised strategies that can delay or slow its progression. The study’s findings therefore hold particular significance for geriatric diabetes care.
Clinical implications – a possible shift in medication decision-making
The results may encourage clinicians to consider the broader health trajectory of older adults when selecting diabetes medications, especially as SGLT-2 inhibitors and GLP-1 receptor agonists are increasingly used for combined glycaemic, cardiovascular, and renal protection.
Chanmi Park, MD, MPH, the study’s lead author and Assistant Scientist I at the Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife, highlighted this point:
“While SGLT-2 inhibitors and GLP-1 receptor agonists are primarily prescribed for blood sugar control and heart protection, our findings show they may also help older adults with diabetes stay stronger and less vulnerable to health setbacks. Because frailty is common, serious, and hard to reverse, this could meaningfully change how clinicians think about medication choices for ageing patients.”
A promising step towards more holistic diabetes care
The study adds to a growing body of literature suggesting that newer diabetes medications may offer multidimensional benefits. By potentially supporting physical resilience in addition to metabolic and cardiovascular health, SGLT-2 inhibitors and GLP-1 receptor agonists could become central tools in promoting healthier ageing for people living with type 2 diabetes.
Further research will be needed to better understand the biological mechanisms at play and to determine whether similar benefits appear in more diverse patient populations and longer-term studies.
CCH insight:
The results of this study are very encouraging from the perspective of GLP-1 medications and muscle mass/strength. There are currently concerns in some quarters about potential excess loss of muscle mass and sarcopenia accompanying weight loss from these drugs. However, this study points towards a positive impact on physical strength and function from GLP-1 therapy.
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