[Diabetes-Talk] Diabetes Research Update 9-2018

[Sally Maguire]

From: The Health Library [mailto:thl at vistacenter.org] 
Sent: Tuesday, September 25, 2018 4:36 PM
To: The Health Library <thl at vistacenter.org>
Subject: Diabetes Research Update 9-2018

 

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

1. New 2D artificial retina flexible   

2. FDA -flesh-eating infection warning  SGLT2s 

3. Glycemia - minority T1D youth:

4. Diabetic retinopathy vision function

5. SGLT2 vaginal yeast infections 

6. Big data confirm T2D  treatment       

7. Potential new way to treat blinding diseases

8. AI detects DR authorized by FDA

9. Air quality and development of T2D

10.SGLT-2s tops for recuced heart failure risk 

11. Inequality use of high-tech devices    Medicare

12. Anti-VEGF  effective persistent DME 

 1.A new generation of artificial retinas based on 2D materials: Scientists
have successfully developed and tested the world’s first ultrathin
artificial retina that could vastly improve on existing implantable
visualization technology for the blind.  Diseases such as diabetic
retinopathy, macular  degeneration, and retinitis pigmentosa  can damage or
destroy retinal tissue, leading to vision loss or complete blindness.
Silicon-based retinal implants have restored a modicum of vision to some
individuals.  N Lu, U Texas says that these devices are rigid, flat and
fragile, making it hard for them to replicate the natural curvature of the
retina which often results in blurry  or distorted images and can cause
long-term strain or damage to surrounding eye tissue, including the optic
nerve.  She and her team used 2D materials, including graphene, molybdenum,
thin layers of gold, alumina and silicon nitrate to create a flexible, high-
density and curved sensor array. The device, which resembles the surface of
a flattened soccer ball conforms to the size and shape of a natural retina
without mechanically disturbing it.  In lab and animal studies,
photo-detectors on the device readily absorbed light and passed it through a
external circuit board. The soft circuit board housed all of the electronics
needed to process light, stimulate the etina and acquire signals from the
visual cortex.  The prototype artificial retina is biocompatible and
successfully  mimics the structura features of the human eye. The team says
it could be an important step in the quest to develop the next generation of
soft bio-electronic retinal prostheses. Funding  includes Nat Science
Foundation and Office of Naval Research. Presented at American Chemical
Society meeting 8/20/18.

 2. FDA slaps flesh-eating infection warning on SGLT2 diabetes drugs:
Thirteen SGLT2 drugs will need new warnings, a distinction for a diabetes
drug class that's gained popularity since its first entrant, Invokana, won
approval in 2013.  In the past five years, the FDA has identified a dozen
cases of a rare flesh-eating infection in patients taking SGLT2 diabetes
drugs. The condition (Fournier’s gangrene, or necrotizing fasciitis of the
perineum) can be caused by diabetes itself, but the agency is requiring
SGLT2 drugmakers to add a warning about the risk to their labels.  The 13
drugs have been linked to cases of Fournier’s. The new warning is not likely
to slow down SGLT2 sales growth, which has been fueled in part by
heart-helping data from Jardiance, the first diabetes drug to show it could
cut the risk of CV events and death. The FDA reported that 7 cases of the
condition occurred in men and the rest in women, and on average the
condition emerged about 9 months after they started taking an SGLT2
inhibitor. All of the patients were hospitalized and one died.  To determine
whether the condition was linked to the drugs, the FDA searched its adverse
event database going back to 1984. It found just 6 cases of Fournier’s
gangrene, all in men. “This contrasts with the findings for Fournier’s
gangrene with the SGLT2 inhibitors where more cases were reported over a
shorter timeframe, and cases involved both males and females,” the document
said. Spokespeople for Merck, Johnson & Johnson’s Janssen, Lilly and
AstraZeneca said that the companies are discussing the labeling update with
the FDA.  Fiercepharma.com 8/30/18

 3. Glycemia trajectories worse among minority T1D youth:  Minority youth
with type 1 diabetes were at higher risk of increasing blood glucose levels
compared with whites.  These increased risks only applied to males.  A
Kahkoska U North Carolina and team found in a longitudinal cohort study of
people younger than 20 with T1D, black participants had 8-fold higher odds
of having moderate baseline HbA1c levels with  major increases over time,
compared to non-Hispanic white youth. The team said that physical
environment, food security, and barriers to health care, may create
race-based groups of people for whom glycemic control is challenged by
inconsistencies in  the availability of resources or support for T1D
management.  Source Ref: Kahkoska A et al JAMA Network Open 2018. Funded by
NIH and Nat Institute of  Diabetes and Digestive and Kidney Diseases;
MPToday  9/8/18    

 4. Impact of incidence and progression of Diabetic Retinopathy (DR) on
vision-specific functioning (VF): Population-based cohort study of 518
patients. Incident DR was defined  as “none or minimal” DR at baseline and
at least mild nonproliferative DR at follow-up;  Conclusions: DR,
particularly vision-threatening stages, has a substantial negative impact on
people's overall vision-dependent functioning and specific activities such
as cooking, seeing street signs, and reading the newspaper. Our findings
reinforce the need for strategies to prevent or delay the development of DR.
Ophthalmology Sep 2018

 5. Vaginal candidiasis (VC) more likely with real-world use of SGLT2
inhibitors than in clinical trials: H Yokoyama, Japan, and colleagues
enrolled 114 women with type 2 diabetes.  At baseline, 17 women tested
positive for VC. At 6 month 74 subjects remained in the study (9 colonized
at baseline). 36.9 percent had positive cultures and 15.8% developed
candidiasis symptoms.  At 6 months, Candida presence was significantly
associated with older age  and being postmenopausal. These rates of vaginal
Candida colonization and symptomatic vaginitis found in real-world practice
appeared to be higher as compared to the findings in clinical trials, the
team wrote.  They added that when older subjects, despite postmenopausal
loss of estrogenic stimulation inhibitor treatment, are exposed to high
urine glucose excretion when they have diabetic microvascular impairment,
Candida colonization is likely to occur. Published in Journal of Diabetes
Investigation. The authors report no relevant financial disclosures.
Healio.com 9/10/18

 6. Big data confirm Type 2 Diabetes treatment approach - The findings
derived from analysis real-world data from more than 246 million patients in
8 healthcare systems in 3 countries. Prior analysis found that metformin was
the most commonly prescribed medication for diabetes; it was prescribed 75%
of the time as a first RX and remained the only medication 29% of the time.
The current study limited the analysis of second line diabetes drugs to
sulfonylureas, DPP-IV inhibitors and thiazolidinediones (TZD.) The team
found that comparisons of sulfonylureas with TZDs and of DPP-IV inhibitors
with TZDs show no difference in reaching HbA1c levels of 7% or less. None of
the drugs raised the risk for kidney disorders, however, sulfonylureas were
associated with a small increased risk for myocardial infarction and eye
disorders compared with DPP-4 inhibitors.  M S Kirkman, U North Carolina
commented  "For now, clinicians need to continue to individualize therapy
beyond metformin, taking into account outcomes of importance to patients,
such as cost, side effects, hypoglycemia, and weight gain, and incorporating
what we know from cardiovascular outcome trials for patients with known CV
disease." "This study is an example of a large multinational open
collaborative research network, which can produce evidence at scale and is
made feasible via the adoption of a common data model and open-source
analytical tools." said lead investigator N Shah, Stanford. Support included
National Library of Medicine. Co-authors reported financial arrangements
with over 12 companies. Dr K's institution has received support from Novo
Nordisk and Theracos. JAMA Network Open 2018; Healio 8/24/18; Medscape
8/31/2018  

 7. A potential new way to treat some of the most common blinding diseases
Many eye diseases, including diabetic retinopathy and macular degeneration,
exhibit increased permeability (leaking) of blood vessels in the macular
(central) portion of the retina leading to fluid accumulation and vision
loss. Therapies targeting a specific cytokine, vascular endothelial growth
factor (VEGF) have transformed clinical care ; however, not all patients
respond well. A new report in American J of Pathology shows that inhibiting
a signaling molecule (atypical protein kinaseC aPKC), genetically or  with
drugs, reduces increased vessel permeability  and blocks inflammation.
Blocking aPKC may help protect vision in patients with these eye diseases.
Good vision requires retinal neurons to send signals to the brain. Retinal
neurons must be protected. This is maintained, in part, by the
blood-retinal-barrier (BRB). The BRB helps control entry of water,
nutrients, and ions to the retina. However, injury or chronic disease can
weaken the BRB and increase vascular permeability.  A variety of molecular
factors can affect permeability, including VEGF and the inflammatory
cytokine tumor necrosis factor alpha (TNF?). Both of these eventually
activate aPKC signaling, to change the permeability of the endothelial cells
(inner lining ) of blood vessels.  "Our data reveal aPKC as an interesting
target...  developing aPKC inhibitors may provide a new therapeutic option
for blinding eye diseases," said D Antonetti U Michigan  "Our research may
help patients with diabetic retinopathy,  and may also lead to new
treatments for uveitis, as well as for retinal vein and artery occlusions."
Commentary, E  Pearsall Harvard noted that although there are still many
questions about the etiology of inflammation, and whether it has a causative
role in eye disease, additional pre-clinical studies necessary to bring
small molecule aPKC inhibitors into clinical use are eagerly anticipated.
Materials provided by Elsevier.  SciDaily 9/13/2018 

 8. AI that detects DR authorized by FDA. Researchers have developed a
system that uses artificial intelligence to successfully detect diabetic
retinopathy, according to a clinical trial in primary care offices. The
trial compared the performance of IDx-DR to the gold standard diagnostic for
DR. "The AI system's primary role is to identify those people with diabetes
who are likely to have dr that requires further evaluation by an eye-care
provider," lead investigator Dr M Abràmoff said.  More than 24,000 people
lose their sight to DR each year in the US.  Diabetes affects the blood
vessels in the retina, causing them to leak and distort vision.  AI assisted
the operator in getting good-quality retinal images using a robotic camera.
After 4 images were obtained, the AI system made a clinical diagnosis in 20
seconds.  Like expert clinicians, the AI detects the characteristic lesions
of DR, including microaneurysms, hemorrhages and lipoprotein exudates (mass
of leaked fatty-acids + protein) Nature Digital Medicine, 9/3/18; AER 9/4/18

9. Is air pollution a risk factor for Type 2 Diabetes?  In continuation of
the debate regarding genetic vs environmental risks in developing T2D, there
is further evidence that air pollution may play a role. A study this summer
from Al-Aly et al utilized data from the VA healthcare system and the EPA’s
air quality data on small particulate matter (PM2.5) to analyze over 1.7
million people    Based on the amount of PM2.5 in a person’s city of
residence,  Exposure to this air pollutant contributed to an estimated 14%
of new diabetes diagnoses in 2016. Etiology (cause) is likely a combination
of effects on adipose (fat) tissue, glucose uptake and alterations of the
immune system. Further longitudinal studies are needed to determine clear
causality, as other associated risks including  socioeconomic status, access
to healthy foods, and neighborhood walkability. If pollution is truly
influencing the number of people developing a condition like T2D,
governments around the world may have to pay more attention to environmental
policy in order to improve population health.  MPToday 08.29.2018 

 10. SGLT-2s tops for heart failure risk reduction: In a systematic review
and meta-analysis, SGLT-2sshowed the largest reduction for heart failure
risk versus other medications for type 2 diabetes when compared with
placebo, reported R Retnakaran, Toronto, and colleagues.  In two pooled
analyses restricted to only GLP-1 agonists and DPP-4 inhibitors, neither
treatment classes were tied to a significant heart failure risk reduction.
The researchers also found no significant association between heart failure
risk in these trial participants with a lowering of HbA1c over time,
measured with a meta-regression analysis. "These findings suggest that
specific drug classes, rather than glycemic targets, should be the focus of
heart failure prevention efforts," commented A DeVore and J Green, both of
Duke University who praised Retnakaran et al's study in an accompanying
editorial. The meta-analysis included data on 87,162 subjects  with T2D from
trials done between 2013-2017.  However, it is also important to note that
this heart failure benefit doesn't come without added risks, as drugs
containing canagliflozin carry a boxed warning for leg and foot amputation
risk, as well as a FDA warning on acute kidney injury risk, and most
recently a warning for Fournier's gangrene with SGLT-2 inhibitors.   Support
by intramural funds.  Dr. R reports grants and  fees from several pharma
companies.  Editorial authors reported funding for clinical research
inculding American Heart Association and Novartis. Source Ref: Retnakaran R
et al, DeVore, Green et al JACC Heart Fail 2018. 

11. Inequality in use of high-tech devices to help people see:  A new study
shows a steep inequality in usage of low vision devices proven to improve
functioning and quality of life.  Low vision devices such as magnifiers can
help with reading cell phones and menus, telescopic lenses can keep people
in the driver’s seat and special glasses can be programmed to read out loud
and recognize faces.  However  Medicare does not cover the cost of the
devices, which is much like its policy of limited coverage of eyeglasses.
Researchers at U Michigan and Harvard focused on nationally representative
survey data from about 3,000 Medicare beneficiaries 65 and older who
reported vision impairment. Compared with whites, adults from minority
racial/ethnic groups were less likely to report using low-vision devices.
However, they found no difference in the use of vision rehab, an evaluation
of activities of daily living and implementation of a plan to improve
functioning – a service that is covered by Medicare. If the findings are
confirmed, it may suggest that policy makers could consider coverage of low
vision devices under Medicare to address racial disparities.  Source:
University of Michigan AER 9/11/18

12. Anti-VEGF effective in persistent diabetic macular edema (DME) following
intravitreous aflibercept, bevacizumab, or ranibizumab (eylea, avastin,
lucentis): The Diabetic Retinopathy Clinical Research Network  conducted a
comparative effectiveness trial evaluating the prevalence of persistent DME
and its effect on visual acuity in eyes treated with above drugs.  546
patients were included in the post hoc analysis. Persistent DME at 24wks in
the bevacizumab group was 65.6%; aflibercept 31.6% and ranibizumab 41.5%.
The mean change in visual acuity was significantly greater among eyes
without persistent DME than in those with DME in the aflibercept and
ranibizumab groups, but not in the bevacizumab group. At 2 years of
follow-up after the initial 24 weeks, the prevalence of persistent DME eyes
that developed chronic persistent DME was 68.2% with bevacizumab, 44.2% with
aflibercept, and 54.5% with ranibizumab.  This study is important in helping
us understand the response of DME to anti-VEGF treatment. All 3 anti-VEGF
agents were found to help in persistent DME resolution to some degree, with
worthwhile gains in vision and minimal risk for vision loss. This study
highlights the importance of continuous RX  for persistent DME after 3 or
more injections rather than switching therapies, owing to the gradual
resolution of DME and improvement in visual acuity.  JAMA Ophthal. 2018;136:
Medscape 9/12/18   

 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; AJO – Amer Journal
Oph; FDA- US Food &Drug Administration; MMN-Medscape Med News; MPToday - Med
Page Today; NEI - National Eye Institute; Nature Com- munications
Definitions -online Med dictionaries.   Disclaimer, 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. The 

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