[Diabetes-Talk] Diabetes Research Update 8-2018

[Sally Maguire]

From: The Health Library [mailto:thl at vistacenter.org] 
Sent: Tuesday, August 28, 2018 11:17 AM
To: The Health Library <thl at vistacenter.org>
Subject: Diabetes Research Update 8-2018

 

Health Library at Vista Center for the Blind and Visually Impaired: DIABETES Research Update AUGUST  2018  Contents: 

1. Legacy effect -intensive A1c control 

2. T2D with no other risks, not tied to excess mortality 

3. New drugs show promise in DME

4. Benefits early RX of diabetic retinopathy (DR)

5. Smart contact lens read blood sugar 

6. OCTA find retinal NV in DR

7. T2D bariatric surg tops in risk reduction 

8. Laser, anti-VEGF similar for DME

9. Machine learning for DR   

10. Age T1D diagnosis mortality risk

11. SGLT-2 T2D risk of amputation

12. No best second-line RX for T2D 

13. Blue light toxic to retina 

1. No legacy effect from intensive  HbA1c control: The Veterans Adm Diabetes Trial in patients who had longstanding uncontrolled type 2 diabetes did not find a "legacy effect" of fewer future cardiovascular (CV) events in the 15-year follow-up. At 10 yrs compared with patients in the standard treatment group, those in the intensive glucose-lowering group had fewer CV events (myocardial infarction, stroke, CV death, congestive heart failure, and amputation) but this did not extend out to 15yrs. H Gerstein, McMaster U said  Presented -American Diabetes Association (ADA) 2018. Medscape 6/28/18  

2. T2D, without other risks, not tied to excess mortality:Action points - People with type 2 diabetes who were free of other risk factors (elevated glycated hemoglobin level -HbA1c elevated low-density LDL, albuminuria, smoking, and elevated BP) did not appear to have any excess mortality risk.  However despite the lack of any of these risk factors, people with T2D persistently had a higher risk or heart failure vs diabetes-free controls. A Rawshani, Sweden and colleagues found the above results using data from 270,000 subjects with T2D in a cohort study.  Of the 5 risk factors, a higher HbA1c outside of the target range was the top predictor for both stroke and acute MI, while smoking was the strongest predicting factor for mortality.  Support includes Swedish Research Council. Dr R disclosed no relevant relationships with industry. Co-authors disclosed multiple such  relationships .Source Reference: Rawshani A et al N Engl J Med 2018; MPToday 8/15/18 

3. New drugs show promise in DME- A dual-target monoclonal antibody outperformed anti-VEGF therapy in patients with diabetic macular edema  Targeting VEGF-A and angio-poietin-2 (Ang-2) the bispecific antibody led to a 10-letter inprovement in BCVA in substantially more patients than did ranibizumab (lucentis) irrespective of anti-VEGF RX history, R Singh, Cleveland Clinic said. The randomized, phase II trial, compared 2 dose levels of RG7716 and lucentis in 229 patients. The 3.6-letter difference between the higher dose of RG7716 and lucentis was statistically significant. The agent showed no new or unexpected safety signals. A second study suggested an integrin inhibitor (risuteganib) could complement anti-VEGF agents in the RX of DME. Only about half of patients respond well to anti-VEGF which suggests inflammation or other factors might play a greater role in the nonresponsive  patients, said P Kaiser, also of C Clinic.    Risuteganib targets oxidative stress and inflammation. This study randomized 80 patients to 5 dose regimes of bevacizumab (Avastin).  Patients got the most benefit from risuteganib when it was preceded by the single dose of avastin. A 40% improvement in BCVA vs a previous evaluation of risuteganib monotherapy. The first study was supported by Hoffmann-LaRoche. Singh disclosed relationships with 6  companies. The risuteganib study was supported by Allegro Pharma.  Dr K disclosed relationships with many companies. Source Ref: Singh RP, et al and Kaiser PK, et al ASRS 2018; MPToday 7/27/18

4. ASRS: Benefits with early treatment of diabetic retinopathy (DR) -Almost 60% of patients with nonproliferative diabetic retinopathy (NPDR) had at least a two-step improvement in retinopathy score when treated with an anti-VEGF agent (aflibercept-eylea) a randomized trial showed.  By comparison, 6% of patients in a sham-injection control group had the same improvement in the Diabetic Retinopathy Severity Scale (DRSS), and a fourth of them developed vision- threatening complications. The findings added to evidence that earlier intervention in DR can help preserve vision for more patients. C Wykoff Houston said. ”I think we all can agree that patients with center-involved macular disease with visual acuity loss, as well as those with high-risk proliferative DR, warrant intervention." He added that the threshold for other stages such as nonproliferative disease can be more ambiguous. This ambiguity was the basis for the randomized Panorama trial. Investigators in 5 countries enrolled 402 patients with NPDR without DME and a DRSS score of 47 or 53. Patients were randomized to 2 dosing schedules of intravitreal eylea or sham injection. The decision to initiate RX for patients with DRSS scores of 47 or 53 should continue to be individualized, said Wykoff. M Elman, Maryland, reported findings from the phase 3, randomized Ride & Rise trials. The 250 patient group with moderate/ severe NPDR, about 80% attained a 2-step improvement in disease severity with either of two doses of lucentis. The rates were 10-15% in the patients with mild/mod NPDR and 31-36% in the subgroup with PDR.  Panorama was supported by Regeneron. Wykoff disclosed relationships many pharma companies. Genentech supported RIDE and RISE. Elman disclosed relationships with Genentech/Roche, Regeneron and a few other companies. MPToday 7/25/2018 

5. Smart contact lens market: The smart contact lens contains a wireless chip and miniaturized sensor for monitoring physiological parameters such as glucose levels in tears of a diabetic patient or intraocular pressure in glaucoma patients. These sensors are embedded inside the 2  layers of soft lenses and a tiny hole in the outer layer allows tears to flow into the sensor which measures the  parameters and data is transmitted to the wireless device for storage, via hair-thin antenna. US FDA recently approved a smart contact lens to continuously monitor IOP in patients of glaucoma,the major cause of irreversible blindness. Triggerfish is a single use lens worn for 24 hrs by glaucoma patients.  It's sensor helps ophthalmologists identify the best time to measure the IOP  which can eventually damage the vision of a patient. Google Inc. is developing a smart contact lens with Alcon, an eye care division of Novartis AG, which can detect blood glucose levels from the tears and is expected to launch in the global market in the next 5-6 years.  The technology is expected to transform the way of management of chronic diseases such as diabetes and glaucoma.  A  company in Korea is  developing a combination of smart contact lens and eyeglass which can be used to monitor diabetes and dispense medication on-demand.  Source: Future market insights  8/1/18  

6. Characteristics of neovascular ization (growth of new abnormal vessels-NV) in early stages of proliferative diabetic retinopathy (PDR) by optical coherence tomography angiography (OCTA): 35 eyes were included in the study. Conclusions: OCTA allowed identification of the origins and morphologic (structure) patterns of NV in PDR. The new classification of retinal NV may be useful to better understand pathophysiological (developmental) mechanisms and to guide efficient therapeutic strategies. American J Ophthmal. Aug 2018

7. In T2D, bariatric surgery is tops for microvascular (small blood vessels) risk reduction - lowered risk OF diabetic retinopathy, neuropathy, & nephropathy maintained for several years. This was a retrospective review of electronic medical records of type 2 diabetes patients under going bariatric surgery versus controls who did not, 16.9% of adults in the bariatric surgery group developed microvascular disease 5 yrs postop vs 34.7% who had only usual diabetes care said D Arterburn, Kaiser Permanente Wash and colleagues.  Significant reductions in the above complications in addition to the composite index of microvasc disease were seen at 1, 3, 5, and 7 yrs following surgery. The bariatric procedures included gastric bypass, sleeve gastrectomy, or adjustable gastric banding. An accompanying editorial by C le Roux, Ireland and P Schauer, Cleveland Clinic said. "We can now consider surgery a treatment of diabetes beyond glycemia,"  Support by Nat Institute of Diabetes and Digestive and Kidney Diseases  Le Roux reported relationships with Science Foundation Ireland, and many companies. Source Reference: Arterburn D and Le Rou C.Schauer P  et al Ann Intern Med 2018;

8. Laser, Anti-VEGF therapy similar for DME:  Patients with proliferative diabetic retinopathy (PDR) had similar 5-year vision outcomes when treated with intravitreal ranibizumab (Lucentis) or panretinal photocoagul ation (PRP), a randomized study showed.  Both treatments led to mean visual improvement of about 3 letters and a mean visual acuity of 20/25 vs 20/32 at baseline. Vision-impairing diabetic macular edema (DME) occurred significantly more often in patients treated with PRP. The superior vision outcome with lucentis seen at 2 years failed to hold up to the end of the trial, J Gross, S Carolina, reported. Visual field loss progressed in both groups during years 2- 5. Vitreous hemorrhage occurred in almost 50% of both groups."  He added that the  findings support either ranibizumab or PRP as viable RX for proliferative diabetic retinopathy. "Patient-specific factors - including cost, and frequency of visits - should be considered when choosing treatment for PDR ." The study included 394 study eyes and 305 patients. PDR remains the leading cause of blindness among working-age adults in the US. Sponsored by Jaeb Center for Health Research with support from the NEI and Genentech. Gross disclosed relationships with Jaeb Center. Genentech, Regeneron, and Ohr. Source Ref: Gross JG et al ASRS 2018;Gross JG et al  JAMA Oph 2018; MPToday 7/25/18 

9. Evaluating machine learning models for diabetic retinopathy:  Retinal fundus images from DR screening programs were each graded by the algorithm, US board-certified ophthalmologists, and retinal specialists. Of the 193 discrepancies between adjudication by retinal specialists and majority decision of ophthalmologists, the most common were missing microaneurysm, artifacts, and misclassified hemorrhages. Conclusions:  A small set of adjudicated DR grades allows substantial improvements in algorithm performance. The resulting algorithm's performance was on par with that of individual US Board-Certified ophthalmologists and retinal specialists. Oph Aug 2018

10. Younger age of T1D diagnosis tied to higher mortality risk: A large nationwide cohort study found that, women who had been diagnosed with type 1 diabetes by the age of 10 lost an average of 17.7 yrs off their life while men lost around 14.2 life-years. A Rawshani, Sweden, and team wrote that those who developed T1D at a later age also had significantly elevated risks for mortality and heart-related conditions. Those diagnosed between the age 26 -30 had about 3 times higher risk for all-cause mortality vs 4 times in those diagnosed before age 10.  The team  explained: "The longer the duration of diabetes, the greater the glycemic load and thus the damage. Another possible explanation for our findings is that patients with a younger age of onset have a more severe and rapid loss of ß-cells, which contributes to increased glycemia."  In the study 27,196 patients were matched to 135,178 diabetes-free controls with a median follow-up of 10 years. Earlier initiation of herapies such as statins, and GLp-1 agonists requires further research, but is another potential strategy to reduce the risk of cardio vascular disease.  funded by the Swedish Heart and Lung Foundation. Dr R reported a financial relationship with Novo Nordisk; Source Ref: Rawshani A, et al  Lancet 2018;392; commentary Ref: Basina M, Maahs D Lancet 2018;392: MPToday 8/9/18

11. Clinical trials suggest that canagliflozin (invokana) a sodium-glucose cotransporter 2 (SGLT-2) inhibitor for treating T2D may be associated with lower extremity amputation  H-Y Chang, Johns Hopkins said.  The retrospective cohort study had 953,906 patients who were new users of SGLT-2 inhibitors, DPP-4 inhibitors and  GLP-1 agonists. Follow-up was for a median range of 99 -127 days. Lower extremity amputations crude incident rates ranged from 4.9 for patients using metformin, sulfonylureas and thiazolidinediones to 10.53 per 10,000 person-years for new users of SGLT-2 inhibitors.  Data showed that new users of SGLT-2 inhibitors had a higher risk of amputation than those on  DPP-4 inhibitors  and GLP-1 agonists “Because all SGLT-2 inhibitors share similar mechanisms of action, a warning for amputations as a class effect was applied to all SGLT-2 inhibitors after review of clinical trial data,” they added that  given the uncertainty of the true nature of the association between SLGT-2 inhibitors and amputation, clinicians and patients will have to navigate RX choices balancing the l risks against the benefits . Dr Chang reports no relevant financial disclosures. Please see study for all other authors’ relevant financial disclosures. Healio 8/13/18

12. No Best Second-Line Therapy for Type 2 Diabetes: Neither sulfonylureas, dipeptidyl peptidase (DPP)-4 inhibitors, nor thiazolidinediones (TZDs) proved more effective at lowering glycated hemoglobin (HbA1c) when added to metformin. N Shah, Stanford and colleagues analyzed data on more than 246 million patients from the US France, and S Korea from 1975 to 2017. Major limitations of the study   is the lack of (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists.  Support includes National Library of Medicine. Shah reported having no relevant conflicts of interest; two study co-authors were employees of Janssen R and Development, and other co-authors disclosed financial relationships including AstraZeneca.Source Reference: Vashisht R, et al JAMA Network Open 2018; MPT 8/24/18 

13. Chemists discover how blue light from digital devices speeds blindness. The process can lead to (AMD). A Karunarathne, U Toledo  said. Macular degeneration is the death of photo-receptor cells in the retina. Those cells need molecules called retinal to sense light and trigger a cascade of signaling to the brain. Photoreceptors are useless without retinal, which is produced in the eye."   His lab found that blue light exposure causes retinal to trigger reactions that generate poisonous chemical molecules in photoreceptor cells which do not regenerate in the eye.  No activity is sparked with green, yellow or red light.  The team found that a molecule (alpha tocoferol) a vitamin E derivative and a natural antioxidant in the eye and body, stops the cells from dying. However, as a person ages or the immune system is suppressed, people lose the ability to fight against the attack. The lab is measuring light coming from TV, cell phone and tablet screens to get a better understanding of how cells in the eyes respond to everyday blue light exposure. Dr JPayton, UT said. "Some cell phone companies are adding blue-light filters to the screens, and I think that is a good idea."  To protect your eyes from blue light, Dr K advises wearing sunglasses that filter both UV and blue light outside and avoid looking at your cell phones or tablets in the dark. Journal Ref: K Ratnayake, JPayton et al; Scientific Reports, 2018; 8 (1) SciDaily AER 8/14/18 

ASRS:  American Society of Retina Specialists

Terms: DM- diabetes Mellitus; T1D- type 1, T2D - type 2; DME - diabetic macular edema; BP -blood pressure; Incident diabetes= new onset DM;  treatment-naïve -never before treated; CGM - continuous glucose monitor; VA-visual acuity. ADA - American Diabetes Association; AJN- Amer J Nursing; AJO – Amer Journal Oph; FDA-US Food Drug Administration; MMN-Medscape Med News; MPT - Med Page Today; NEI - National Eye Institute; Nature Com- munications Definitions -online Med dictionaries. Note - I am a BSN RN but not a diabetic or DM educator. Reports are excerpted/ edited unless otherwise noted. (explanations by thl are in brackets) This project is done as a courtesy to the blind/visually impaired & diabetic communities. Dawn Wilcox BSN RN Editor, Coordinator Health Library; Miriam Kaplan PhD- Contributing Editor. 

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.  <mailto:thl at vistacenter.org> thl at vistacenter.org or  <mailto:dewilcox at pacbell.net> dewilcox at pacbell.net 

Vista Center empowers individuals who are blind and visually impaired to embrace life to the fullest through evaluation, counseling, education and training. www.vistacenter.org <https://mandrillapp.com/track/click/30489975/www.vistacenter.org?p=eyJzIjoidXh3ZVBaYUJ2dGNDY1B5NzhfSldNZ0hfakFnIiwidiI6MSwicCI6IntcInVcIjozMDQ4OTk3NSxcInZcIjoxLFwidXJsXCI6XCJodHRwOlxcXC9cXFwvd3d3LnZpc3RhY2VudGVyLm9yZ1wiLFwiaWRcIjpcImUyMTcwMDQ0ZWRkMjQyNmI4ZTU2ZTBlOGUzNGQzYjlmXCIsXCJ1cmxfaWRzXCI6W1wiMTkyMGQxN2ExNjJjMWE4ZjZkYWIzMWMyOGY4N2JlNGMzYzQ3MzI3ZFwiXX0ifQ>     

 



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