Diabetes Research Update

AUGUST 2021 

Vision impairment tied to cognitive decline

Worse visual acuity, contrast sensitivity, and stereo acuity impairment are associated with an increased risk for cognitive decline in older, community-dwelling individuals, according to a study published online July 16 in JAMA Network Open.  Varshini Varadaraj, M.D., from the Johns Hopkins University School of Medicine and colleagues examined the association between vision and cognition across multiple cognitive domains using several measures of vision. The analysis included 1,202 participants (mean age, 71.1 years) in the Baltimore Longitudinal Study of Aging (mean follow-up, 6.9 years).  The researchers found that worse visual acuity at baseline was associated with greater declines in language and memory domain scores.  Results also showed that greater declines in language, memory, attention, and visuospatial ability scores were associated with worse contrast sensitivity at baseline.   In addition, declines on tests of language and memory were significantly greater for participants with impaired stereo acuity during the study period.  “These results add further evidence to the interrelationship between vision and eye health with healthy brain aging and highlight the need for research into the impact of vision and eye health interventions on cognitive outcomes,” the authors write.   

Health Daily, Ophthalmology news July 22, 2021

Wearable devices can reduce collision risk in blind and visually impaired people

Vibrating wearable device prototype put to test: People who have visual impairments are at a significantly higher risk for collisions and falls.  While some electronic devices are marketed direct-to-consumer claiming to warn wearers of surrounding objects, there has been little evidence of their effectiveness in actual daily mobility settings. This is one of the first randomized-controlled trials to look at the potential benefit of the devices at home and outside of a controlled lab environment. The new study was published July 22 in JAMA Ophthalmology.  

The experimental device used in the trial was created by Dr. Gang Luo and colleagues including lead author Shrinivas Pundlik, PhD, who designed the computer vision algorithm. The device and data recording unit were enclosed in a sling backpack with a chest-mounted, wide-angle camera on the strap, and two Bluetooth-connected wristbands worn by the user. The camera is connected to a processing unit that captures images and analyzes collision risk based on the relative movement of incoming and surrounding objects in the camera’s field of view. If an imminent collision is detected on the left or right side, the corresponding wristband will vibrate while an imminent head-on collision will cause both wristbands to vibrate. Unlike other devices that simply warn of nearby objects whether or not a user is moving toward the objects, this device analyzes relative motion, warning only of approaching obstacles that pose a collision risk. 

The new study included 31 blind and visually impaired adults who use either a long cane or guide dog (or both) to aid their daily mobility. The device was randomized to switch between active mode, in which the users could receive vibrating alerts for imminent collisions, and silent mode, in which the device still processed and recorded images, but did not give users any warning even if potential collisions were detected. The silent mode is equivalent to the placebo condition in many clinical trials testing drugs. Collisions were analyzed by researchers from the recorded videos. The effectiveness of the device was evaluated by comparing collision incidents that occurred during active and silent modes.  

The study found that the collision frequency in active mode was 37 percent less than that in silent mode. Luo and team seek to leverage ongoing improvements in mobile processing power and cameras to make the device smaller and more cosmetically appealing. With additional funding, the team hopes that such a device could be submitted to the U.S. FDA for approval so that it could be commercially available for people with low vision. The clinical trial was funded by a U.S. Army Medical Research and Materiel Command grant, and the device is patented by Mass Eye and Ear.  

ScienceDaily, July 22, 2021

In vivo drug discovery for β-cell proliferation in diabetes

In a study published in Nature Metabolism, researchers at the Karolinska Institutet have developed a novel technique to identify small molecules that can make insulin-producing β-cells divide. Olov Andersson and Jeremie Charbord explain: “Diabetes is characterized by the progressive loss of functionalβ-cells. One possible approach to curing diabetes is to generate new β-cells in situ [in the body] to replenish the pool of β-cells.” 

To screen for chemicals that can induce β-cell proliferation, the researchers developed a novel assay in zebrafish to specifically report β-cell proliferation in vivo in a high-throughput manner. In this way, they identified a kinase inhibitor that potently stimulates β-cell proliferation and confirmed this effect in mouse and human β-cells to make sure the effect is conserved across species. “Our findings suggest a novel concept in which a small molecule…can induce β-cell proliferation—a mechanism that can be leveraged to expand the number of β-cells in diabetes.”  

Medical Xpress, 5/26/2021
https://medicalxpress.com/news/2021-05-vivo-drug-discovery-cell-proliferation.html. For original journal article, see DOI: 10.1038/s42255-021-00391-x

Diabetes vaccine gives promising results in a genetic subgroup

A clinical study led by Linköping University, Sweden, and financed by pharmaceuticals company Diamyd Medical has investigated whether immunotherapy against type 1 diabetes can preserve the body’s own production of insulin. The results suggest that injection of a protein, GAD, into lymph nodes can be effective in a subgroup of individuals. The results have been published in Diabetes Care. 

In type 1 diabetes, the body’s immune system attacks the cells that produce insulin. A highly topical question in research into type 1 diabetes is whether, and if so how, the attack of the immune system can be slowed or even completely stopped. One possible strategy is based on altering the immune defense by injecting a protein that the cells of the immune system react to, in a form of vaccination. One of the proteins against which the immune system often forms antibodies in type 1 diabetes is known as GAD65 (glutamic acid decarboxylase).  

Professor Johnny Ludvigsson has led DIAGNODE-2, a clinical phase 2 study in which researchers investigated the effect of GAD-alum (Diamyd) injections into the lymph nodes of 109 young people with recently diagnosed type 1 diabetes. The participants, aged between 12 and 24 years, were allocated at random to one of two groups. One group received three injections of GAD-alum at intervals of 1 month and vitamin D in tablet form, while the other group (controls) received placebo.  

Previous studies of immunotherapy in diabetes have suggested that genetic factors play a role in how patients respond to the treatment. This led the researchers in DIAGNODE-2 to look at several variants of what are known as “HLA genes.” The HLA variant HLA-DR3-DQ2 exposes the GAD65 protein to cells of the immune system, and Type 1 diabetes patients with this variant often form antibodies against GAD65 at an early stage of the disease. Around half of the participants in the study had the HLA-DR3-DQ2 variant.  

The researchers found that for the complete patient group, there was no difference between treatment and placebo in the degree to which insulin production was preserved. GAD-alum did, however, have a positive effect for the subgroup of patients who had the DR3-DQ2 variant of HLA genes. No undesired effects that could be related to treatment with GAD-alum were seen during the study.  

“Treatment with GAD-alum seems to be a promising, simple and safe way to preserve insulin production in around half of patients with type 1 diabetes, the ones who have the right type of HLA. This is why we are looking forward to carrying out larger studies, and we hope these will lead to a drug that can change the progress of type 1 diabetes,” says Ludvigsson. The study has been financed by Diamyd Medical AB, the Swedish Child Diabetes Foundation, and the Swedish Diabetes Foundation.  

Medical Xpress, 5/24/2021
https://medicalxpress.com/news/2021-05-diabetes-vaccine-results-genetic-subgroup.html. For original journal article, see DOI: 10.2337/dc21-0318

Rare genetic variants confer largest increase in type 2 diabetes risk seen to date

Type 2 diabetes is thought to be driven in part by inherited genetic factors, but many of these genes are yet unknown. Previous large-scale studies have depended on efficient ‘array genotyping’ methods to measure genetic variations across the whole genome. This approach typically does a good job at capturing the common genetic differences between people, though individually these each confer only small increases in diabetes risk. 

Recent technical advances have allowed more comprehensive genetic measurement by reading the complete DNA sequences of over 20,000 genes that code for proteins in humans. Proteins are essential molecules that enable our bodies to function. In particular, this new approach has allowed for the first time a large-scale approach to study the impact of rare genetic variants on several diseases, including type 2 diabetes. 

By looking at data from more than 200,000 adults in the UK Biobank study, researchers from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge used this approach to identify genetic variants associated with the loss of the Y chromosome. This is a known biomarker of biological aging that occurs in a small proportion of circulating white blood cells in men and indicates a weakening in the body’s cellular repair systems. This biomarker has been previously linked to age-related diseases such as type 2 diabetes and cancer. 

In results published in Nature Communications, the researchers identified rare variants in the gene GIGYF1 that substantially increase susceptibility to loss of the Y chromosome, and also increase an individual’s risk of developing type 2 diabetes six-fold. In contrast, common variants associated with type 2 diabetes confer much more modest increases in risk, typically much lower than two-fold. Around 1 in 3,000 individuals carries such a GIGYF1 genetic variant. Their risk of developing type 2 diabetes is around 30%, compared to around 5% in the wider population. In addition, people who carried these variants had other signs of more widespread aging, including weaker muscle strength and more body fat. 

GIGYF1 is thought to control insulin and cell growth factor signaling. The researchers say their findings identify this as a potential target for future studies to understand the common links between metabolic and cellular aging, and to inform future treatments. Ongoing research will aim to understand how the loss of function variants in GIGYF1 lead to such a substantial increase in the risk of developing type 2 diabetes. Their future research will also examine other links between biomarkers of biological aging in adults and metabolic disorders. 

Medical Xpress, 7/7/2021
https://medicalxpress.com/news/2021-07-rare-genetic-variants-confer-largest.html. For original journal article, see DOI: 10.1038/s41467-021-24504-y

“Shocking” early complications from teen-onset type 2 diabetes

Newly published data show alarmingly high rates and severity of early diabetes-specific complications in individuals who develop type 2 diabetes at a young age. This suggests intervention should be early and aggressive among these youngsters, said a researcher. The results for the 500 young adult participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth 2 (TODAY 2) study were published online July 28 in the New England Journal of Medicine by the TODAY study group. At follow-up — after originally participating in the TODAY trial when they were young teenagers — they had a mean age of 26.4 years. At this time, more than two thirds had hypertension and half had dyslipidemia (high fat levels in the blood). Overall, 60% had at least one diabetic microvascular complication (retinal disease, neuropathy, or diabetic kidney disease), and more than a quarter had two or more such complications. “The fact that these youth are accumulating complications at a rapid rate and are broadly affected early in adulthood certainly suggests that aggressive therapy is needed, both for glycemic control and treatment of risk factors like hypertension and dyslipidemia,” study coauthor Philip S. Zeitler, MD, PhD, told Medscape Medical News.  

The TODAY study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. 

Medscape Medical News, 7/29/2021

Trial results show two medications most effective in lowering blood glucose levels in type 2 diabetes patients

Two medications have proven to be most effective in keeping blood glucose levels within a target range while managing type 2 diabetes, a disease that affects more than 32 million Americans. Out of four medications commonly used in conjunction with metformin, liraglutide and insulin were superior to glimepiride and sitagliptin in keeping A1C (a measurement of average blood glucose) levels less than 7%, according to the GRADE study. 

Approximately 1,250 patients out of 5,000 with type 2 diabetes were randomly assigned to each of the four medications in conjunction with ongoing metformin therapy. The comparison included two oral medications, the sulfonylurea glimepiride and the DPP-4 inhibitor sitagliptin, and two injectable medications, insulin glargine and the GLP-1 receptor agonist liraglutide.  The effects of each of the four medications on diabetes complications and side effects were also examined.  

To include a highly diverse population, the GRADE study enrolled patients with a wide range of age, race, and ethnicity. Since minority and ethnic groups are disproportionately impacted by diabetes, 20% Black and 18% Hispanic/Latino Americans were a part of the study. Sponsored by the National Institutes of Health, GRADE followed participants for an average of five years and a maximum of more than seven years.  

While results showed liraglutide and insulin were the most (and similarly) effective in keeping A1C levels less than 7%, glimepiride had a smaller effect and sitagliptin showed the lowest effect, resulting in the highest frequency of developing A1C levels persistently greater than 7%. Insulin glargine was most effective in keeping A1C levels less than 7.5%, a secondary outcome of the study. Presented at the virtual 81st Scientific Sessions of the American Diabetes Association (ADA), the head-to-head comparison provided an informative guide for providers and their patients on how to assess individualized treatment strategies when managing type 2 diabetes.  

Medical Xpress, 7/2/2021

FDA allows automatic ‘generic’ swap for brand-name insulin

U.S. regulators took action on Wednesday, July 28, 2021, that will make it easier to get a cheaper, near-copy of a brand-name insulin at the drugstore. Wednesday’s move by the FDA will allow pharmacists to automatically substitute the cheaper version, just as they do with generic pills for other kinds of drugs. It’s the FDA’s first approval of an “interchangeable” biosimilar, a near-copy of an injected biologic medicine that’s manufactured inside living cells. It could save diabetics and health plans millions of dollars annually and encourage other drugmakers to create more biosimilar medicines. The FDA agreed that Viatris Inc.’s Semglee was interchangeable with widely used Lantus, a fast-acting insulin. Approval of a second such interchangeable biosimilar of a long-acting insulin appears imminent from the same developers, Pittsburgh-based generic giant Viatris and its partner, India’s Biocon. Depending on the pharmacy, Semglee injector pens cost about $150 to $190 without insurance for a typical month’s supply, compared to $340 to $520 for the same supply of brand-name Lantus. 

Medical Xpress, 7/29/2021

Positive safety results reported for UBX1325 in DME, wet AMD

Patients with DME or wet AMD treated with UBX1325 showed positive safety results and “rapid” improvements in several key metrics, according to a press release from Unity Biotechnology. UBX1325, a small molecule inhibitor of Bcl-xL, was assessed in a phase 1 clinical study to determine its safety profile. The therapy is being developed to potentially aid patients in whom anti-VEGF therapy is no longer helpful.  

The first-in-human, open-label, single-ascending dose study enrolled 12 patients with advanced DME or wet AMD. UBX1325 demonstrated a “favorable acute safety profile supporting further clinical development,” the release said. In addition to the positive safety profile, 10 of 12 patients gained ETDRS letters from baseline at 2 weeks, and nine of 12 gained at 4 weeks. (In clinical trials, visual acuity is often measured using a chart called the ETDRS (Early Treatment Diabetic Retinopathy Study) chart.) All six patients who received high doses had a gain in best corrected visual acuity (the best possible vision a person can achieve with corrective lenses) at 2 weeks. Six of 12 patients had a decrease in central subfield thickness (thickness of the centermost portion of the retina), and three of four patients with wet AMD saw an improvement in disease-relevant pathology and a reduction in subretinal/intraretinal fluid. “UBX1325 targets an entirely novel mechanism to eliminate senescent [old] cells in the retinal and choroidal vasculature, a potential root cause of disease progression, and could provide a valuable alternative or adjunctive treatment option to anti-VEGF therapies,” Anirvan Ghosh, PhD, CEO of Unity, said in the release. 

Healio, 7/9/2021

FDA accepts application for faricimab for wet AMD, DME

The FDA has accepted Genentech’s biologics license application under priority review for faricimab to treat neovascular (wet) AMD and DME. The submission was also accepted for diabetic retinopathy, and the European Medicines Agency validated the marketing authorization application for the drug for wet AMD and DME. “If approved, faricimab would be the first in a new class of eye medicines targeting two key pathways that drive retinal disorders, with the potential to offer durable vision outcomes with fewer eye injections than the current standard of care,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in a press release.  

The submission was based on results from four phase 3 studies that showed that faricimab, given at intervals up to 4 months, conferred noninferior vision gains compared with aflibercept administered every 2 months. Approximately 50% of patients who received faricimab were able to extend their treatment time to every 4 months. Faricimab was well tolerated, and no new or unexpected safety signals were identified. Long-term extension studies in wet AMD and DME are underway, as are trials of faricimab’s efficacy and safety in patients with macular edema secondary to central and branch retinal vein occlusion. 

Healio, 7/29/2021


I am not a diabetic or diabetes educator. Reports are excerpted/edited unless otherwise noted. This project is done as a courtesy to the blind/visually impaired & diabetic communities. This update was prepared by Miriam Kaplan, PhD, Editor-in-Chief and Coordinator of The Health Library.   

Disclaimer: Our material is not intended as a substitute for medical care. Our material should be used to formulate questions for discussion with your physician. We hope that the information you find at The Health Library will be useful in communicating with your health professionals. If you have any questions about your unique medical condition, we strongly advise that you see your physician. The Health Library at Vista Center; an affiliate of the Stanford Hospital Health Library. thl@vistacenter.org www.vistacenter.org