[acb-diabetics] many articles

[Patricia LaFrance-Wolf]

1.%%MTD Study Finds Visually Impaired People Get Insulin Pen Dosages Right
7/3/10 Labels on the popular insulin pen used by people with diabetes warn
against

visually-impaired people using pens to measure out and administer their
insulin dosage. A pilot study finds that visually impaired people actually
did

slightly better than their seeing peers.. lead investigator  speculates,
that the reason behind the poor performance of certain individuals in the
sighted

group is that some glossed over important instructions about how to use the
pen. In contrast, individuals with sight problems listened, step by step, to

complete audio instructions before using the pen in the study. [60 subjects]
this study also demonstrates the importance of including people with
disabilities

in research...They were given complete recorded instructions- essentially
the same as those included on printed sheets in the insulin pen packaging,
modified

slightly to include tactile methods for using the pens. Then each
participant measured out 10 doses of insulin and injected them into a rubber
ball.."People

with visual impairment can manage their own insulin accurately when they
have access to nonvisual tools and techniques and complete instructions in a
format

they can use,"

 

2. %% ADA 70: Inhaled Insulin Rivals Conventional Insulin Therapy for T2DM
6/29/10 In patients with T2 inhaled insulin before each meal, plus insulin
glargine

before bedtime, is just as effective at controlling blood sugar as
conventional twice-daily premixed biaspart insulin.  [in addition there is ]
less weight

gain and less hypoglycemia. Oral antidiabetes drugs can provide glycemic
control early on in T2, but progressive beta-cell insufficiency can
eventually

lead to the need for insulin.  This randomized study compared the efficacy
and safety of prandial Technosphere inhaledinsulin with twice-daily biaspart

insulin. Technosphere inhaled insulin is an ultrarapid formulation
containing recombinant human insulin adsorbed onto powder that is delivered
into the

lungs by a small inhaler device. [Adults with T2]  Asked about the issue of
cough, the presenter said that any inhaled powder triggers a cough in some

people." Technosphere .. would be particularly useful in people with T1 and
in insulin- naïve people with T2. It's much less obtrusive to take this
little

inhaler out-( size of a large thumb) and just inhale something, The bigger
population is obviously the T2 population, who says 'Doc, anything but the
needle.

Studies need to look at using this in lieu of injectable insulin in those
people." This study funded by [producer]

 

3.%% M  Daily Glucose Swings Tied to Cognitive Impairment in Elderly
Diabetics (Reuters Health) Jul 07 - Independent of the usual markers of
glycemic control,

the amplitude of daily glucose excursions is linked with cognitive function
in elderly T2. [121 T2 outpatients; age 65-88] "The rapid glucose swings
from

relatively high glucose levels during postprandial periods to low values or
even to asymptomatic hypoglycemia, and its associated neuroglycopenia
[shortage

of brain glucose] may largely contribute to a more rapid decline of
metabolic activity in the brain, The present data open the field to conduct
interventional

studies aimed at treating glycemic disorders not only by reducing HbA1c and
mean hyperglycemia but also by flattening acute glucose fluctuations." the

lead author said.

 

4.%% Cilostazol Reverses Atherosclerosis in Diabetics (Reuters Health) Jul
01 - The phosphodiesterase inhibitor cilostazol induces

regression of carotid atherosclerosis in patients with T2DM. .. the agent
has long been indicated for intermittent claudication ..Both it and aspirin
are

effective in preventing recurrence of atherosclerosis. [329 T2 subjects]
randomized to 81-100mg ASA or cilostazol. All were suspected of having
peripheral

artery disease. At 2 years, regression of the intima-media thickness of the
common carotid artery was significantly greater with cilostazol than with
aspirin.

a "large-scale  trial is needed to establish the usefulness of cilostazol
for primary prevention of CV events in T2

 

5..%% M Heartwire  Severe Hypoglycemia a Marker, Not Cause, of Poor Diabetes
Outcomes? 7/8/10 -  Development of severe hypoglycemia in the ADVANCE  trial

correlated significantly with later CV and microvascular events as well as
development of nonvascular disorders such as cancer, digestive and
respiratory

diseases.. severe hypoglycemic events were a significant predictor of such
outcomes regardless of whether the patients with T2 had been assigned to its

"intensive" or standard glucose-lowering strategy. "There are 2 possible
explanations," the presenter said “One is that severe hypoglycemia directly
causes

the poor outcomes, and the other, "which we propose is more likely, is that
hypoglycemia is a marker of increased vulnerability." [11,140 pts history of

CV  or microvascular disease..]

 

6.%% M Statin Lowers Cardiac Events in Diabetics on Hemodialysis With High
Cholesterol Levels 7/8/10 Atorvastatin [lipitor] significantly decreased
fatal

and nonfatal cardiac events and all-cause mortality in patients with T2 on
hemodialysis who had the highest levels of LDL cholesterol in the study
population.

[1255 subjects] [2nd trial 2776 pts (27% with DM]"So my conclusion in regard
to these data is that statin treatment should be consideredin dialysis
patients

with T2&  elevated LDL cholesterol - more than 145 mg/dL

 

7.%%M Can Will Power Triumph Over the "Fatso" Gene? 7/20/10  Summer weather
is here again, and with it comes the predictable upsurge in ads for how to

look your best in a bikini, tank suit, or Speedo®  and fat -- as usual -- is
a dirty word. For everyone who dismisses excess weight, saying, "It's in my

genes," the bad news is that they're partly right. The good news is that in
this realm, as in many others, genes are not destiny. If ever a gene came by

its nickname naturally, it's FTO. Officially designated  the "fat mass and
obesity associated" gene, A 2007 study [ 39,000 people] found that people
with

2 copies of an FTO variant weighed an average of [6lb] more than did people
with no copies of that variant. . it came as no surprise that FTO variants

were also associated with diabetes. Higher body weight, greater likelihood
of DM-- it seemed obvious. However [another study] of  FTO  risk alleles by

race showed that  the same allele that "conferred an elevated risk of being
obese for both white and Afr-American participants" decreased diabetes risk

21% in Afr Americans. .. So should individuals with these FTO  variants
resign themselves to obesity? In April, a research study published in Arch
of Pediatrics

and Adolescent Medicine  answered this question with a resounding "no."the
study  determined that increased  physical activity could "offset the
genetic

predisposition to obesity associated with the FTO  polymorphism." In this
case, at least, genes are not destiny.

 

8.%%M Gastric Electrical Stimulation Helps Improve Diabetic Gastroparesis
(Reuters Health) Jul 15 - An implanted device that sends electrical current
to

the stomach helps relieve diabetic gastroparesis. [45 pts; median weekly
vomiting frequency went from nearly 20 episodes at baseline to less than 5
after

six weeks.] By one year, vomiting episodes were reduced by at least half in
nearly 70% of patients,,The Enterra Therapy system was approved by the FDA

in 2000 for  DM and idiopathic gastroparesis. It has of two leads that are
sutured into the gastric smooth muscle and connected to a battery that's
implanted

subcutaneously in the upper abdomen.  The system costs approximately
$12,000, and with surgery the price tag comes to about $20,000 -$25,000.
there were

15 serious adverse events including 3  cases that required surgery, one for
an infection of the implant site. research at Texas Tech U sponsored by
Medtronic,

Inc.

 

9.%%  M Glutamine Boosts Nocturnal Hypoglycemia in Young Diabetics (Reuters
Health) Jul 16 - Instead of reducing exercise- related night- time
hypoglycemia

in diabetic kids, glutamine supplementation had the reverse effect - it
increased low blood sugar episodes. [10 T1 adolescents].. mean blood glucose
concentrations

prior to exercise were comparable on glutamine and placebo days, as was the
drop seen after exercise (52.0%). Nevertheless, nocturnal hypoglycemic
events

occurred significantly more often with glutamine than placebo, and the
cumulative probability of hypoglycemia was significantly higher (80% vs
50%).  "The

reason why blood sugar dropped," said a team leader "may be because
glutamine makes the body more sensitive to insulin. Much larger studies,
would of course

be warranted to prove this."

 

10.%% ADA 70: Cell Death Mediator SHP-1 Linked to Progression of Diabetic
Retinopathy [DR]7/1/10  Expression of SHP-1, a protein tyrosine phosphatase
and

a mediator of cell death during hyper- glycemia, may play a role in the
development of DR in patients with long duration of T1DM.  Patients who had
no

retinopathy despite having insulin-dependent DM for 50 years or more had
lower than median levels of SHP-1, whereas patients with long-standing
insulin-

dependent DM who progressed to DR had equal to or higher median levels of
SHP-1, reported the presenter (Joslin Diabetes Center) Patients with high
systolic

BP were also more likely to develop DR. However, hemoglobin A1c levels did
not appear to be a factor.(194 eyes) The study found that most retinopathy
developed

within the first 20 years, with a peak at 3 -4 years. SHP-1 mediates
cross-talk between pathways for cellular death that are induced in
conditions of high

blood glucose, like DM, and between pathways for cellular

survival. "It is interesting that we haven't been able to find the
association between current glycemic control or our best measures of
longitudinal glycemic

control and complication status,"

 

11.%% Medscape Diabetes & Endo.  Avoiding Hypoglycemia: CGM Devices May Be
the Answer 7/7/10 video-  Hi, I'm Dr. Anne Peters, Director of the Clinical

Diabetes Programs at USC joined by Dr. Howard Wolpert, Dir. CGM and Insulin
Pump Program, Joslin Diabetes Center.  first of all: What is continuous
glucose

monitoring?

Dr. W: I think this is going to be the next wave in intensive diabetes
management.  I think it's going to help many of our patients get to goal
much more

readily, particularly people who run into problems with hypoglycemia. These
devices  are actually transcutaneous sensors, ie, sensors that pass through

the skin. The sensor actually is measuring the glucose in the interstitial
fluid underneath the skin, and that's connected up to a transmitter unit.
The

patient has a receiver, which gives them a readout of the glucoses every
5min.   They can actually see the trend of the direction that the glucose is
going.

. these devices have alarms, which are adjustable so they can be preset to
go off at specific hypoglycemic or hyperglycemic thresholds... Obviously,
because

it demands quite a lot of the patient, it's a tool for the patient who's
really motivated and engaged in their DM self- management... Is this an
artificial

pancreas? Dr. W:  Well, I think it's a step along the way. It gives the
patient all the extra info.  t they need to titrate to adjust their insulin
to

get themselves closer to goal, but it's not an automated process. ., it
actually demands quite a lot more of the patient, so I think it's a bit of a
misnomer

to put it in that context. On the other hand, when you look at the long-term
outcome for people with T1who are intensively controlled, we've essentially

licked a lot of the major microvascular complications  [they] can
potentially run into. . what CGM really offers here is an answer to the
hypoglycemic

risk that people who are striving for intensive DM management will run into.
.  part of an analysis of patients who were involved in the Juvenile
Diabetes

Research Foundation CGM trial -- is that we looked at people who derived
benefit from CGM vs those who didn't. . people who are much more stoic in
the

way they deal with frustrations and the demands of the technology do a lot
better than people who tend to get a bit frustrated and angry. .As the
technology

improves, I think a lot of these sorts of teething problems that people run
into using the devices are no longer going to be a problem..

 

12.%% ADA 70: New Insulin Dose Calculation Method Reduces Postprandial
Hyperglycemia in Children 7/2/10 — Children with T1 can have their pizza and
eat

it, too, if they calculate their premeal insulin dose according to
carbohydrate, fat, and protein intake rather than carbo. intake
alone.,Calculating the

insulin requirement according the new method reduces the incidenceof
postprandial hyperglycemia after fat- and protein-rich meals, a team says.
The new

formula was tested it in 42 T1 pts; 6 -20 yr who had been on pump therapy
for at least 3 months. The test meal consisted of a standardized meal of
salami

pizza. . the kids in the study learned the more complicated CFP calculation
quite easily. Commenting on this study D. Maahs, MD, said that delivering
preprandial

insulin is a very important topic in pediatric diabetes..He added that he
was concerned about the apparent increase in hypoglycemia with this method..

Despite these concerns, he said the research is moving in the right
direction.

 

13.%% ADA 70: A Loaf of Bread, A Jug of Wine, and Tight Glucose Control With
Artificial Pancreas 7/2/10  Adults with T1 can eat, drink, and still be in

control of glucose overnight, suggest results of a pilot study. In a test
designed to mimic real-life conditions, 12 adults with T1were fed a large
meal

accompanied by as much as 3/4th of a bottle of white wine and then monitored
for overnight hypoglycemia. Pts on the closed-loop artificial pancreas
system

remained within glucose targets longer and had fewer glucose excursions than
when they were on standard continuous subcutaneous insulin infusion (CSII),

said the presenter. The artificial pancreas system consists of a CSII, or
insulin pump, linked via a control algorithm to a continuous glucose sensor.


In the current study, they attempted to replicate in the hospital several
aspects of daily life, such as the effects on plasma glucose levels of a
good

meal and a few glasses of wine. Alcohol consumption is associated with
delayed hypoglycemia in people with T1. 

 

14.%%  M Internat Journal of Impotence Research  Determinants of Erectile
Dysfunction in T2DM 7/5/10 [555 subjects] Approximately, 6 in 10 men in our
sample

of diabetic men had varying degrees of erectile dysfunction: mild 9% ..and
severe 22.9%. The prevalence of severe ED increased with age, hgher (HbA1c)

levels , hypertension, atherogenic dyslipidemia (low levels of HDL
-cholesterol and high levels of triglycerides) and depression. men with
higher levels

of physical activity were 10% less likely to have ED as compared with those
with the lowest level.

 

15.%% M Gestational Diabetes (GDM) Tends to Recur in Subsequent Pregnancies
7/13/10  Women with a history of GDM have an increased risk for recurrence

in subsequent pregnancies,"Because of the silent nature of GDM, it is
important to identify early those who are at risk and watch them closely
during their

prenatal care," said lead author.. "Well-controlled GDM may prevent
complications that result in fetal and maternal morbidity, such as high BP
during pregnancy,

urinary tract infections, cesarean delivery, big babies, birth trauma, and a
variety of other adverse outcomes, including future diabetes."[65,132 women

with 2 singleton pregnancies &13,096 women with 3..] In the second
pregnancy, the risk for GDM was 41.3% among women with previous GDM vs 4.2%
in women

without previous GDM. Risks for recurrence were higher in Hispanic &
Asian/Pacific Islander women.

 

16.%% MTD Recommended Blood Pressure Level Differs For Heart Patients With
Diabetes 7/9/10 The best BP range for patients with DM and heart disease
appears

to be slightly higher than what is recommended for healthy adults. In fact,
‘ normal’ BP - less than 120 systolic and less than 80 diastolic - may
actually

be risky for those with a combined diagnosis of DM and coronary artery
disease, report researchers. Optimum systolic BP levels should be between
130 &

140 for patients coping with the DM-heart disease combination." "While
lowering BP to less than 140 is very important, it is now clear that in
patients

with diabetes, it is not necessary, and may be harmful to lower BP  too
much," In addition, the study for the first time reveals that this group of
patients

had an increased risk for death when their blood pressure was controlled to
lower than 115 systolic.

 

17.%% MTD In Development Of T2DM, Fat Cells Play Key Role 7/7/10  Cellular
changes in fat tissue - not the immune system - lead to the
"hyperinflammation"

characteristic of obesity-related glucose intolerance and T2 The team looked
at the role of a specific gene known as protein kinase C (PKC)-zeta, which

has been implicated as a key cellular contributor to malignant tumor growth.
Using an animal model, they found that PKC-zeta had a dual role in the
molecular

signaling that leads to inflammation, switching from acting as a regulator
of inflammation to a proinflammation agent in different circumstances."
During

obesity- induced inflammation, [this]molecule begins to promote inflammation
by causing adipocytes [fat cells] to secrete a substance (IL-6) that travels

in large quantities to the liver to cause insulin resistance. "We believe a
similar mechanism of action is at play in malignant tumor development. Now

we are trying to understand how PKC-zeta regulates IL6 to better determine
how we can manipulate the protein to help prevent DM and cancer,"

 

18.%% M Exploring Associations Between Genetic Variants of APOC3, NAFLD, &
Insulin Resistance 5/5/10  Summary - Nonalcoholic fatty liver disease
(NAFLD)

is the most common cause of abnormal liver function in adults in the US The
accumulation of triglycerides in the liver, or hepatic steatosis, seen in
this

disease is associated with hepatic insulin resistance and T2DM.. Development
of NAFLD is thought to occur through a combination of genetic and
environmental

components,  One of these genes encodes apolipoprotein C-3 (APOC3), a
very-low-density protein is thought to delay the [breakdown] of
triglyceride-rich

particles. The team genotyped APOC3  polymorphisms in healthy, nonsmoking,
sedentary Asian Indian men, A subset of patients was also assessed for
insulin

sensitivity and triglyceride clearance.. APOC3  variant carriers
demonstrated marked insulin resistance, reduced plasma triglyceride
clearance, and increased

hepatic triglyceride content as compared with noncarriers.., the authors
also demonstrated that lifestyle changes were capable of counteracting the
genetic

predisposition.

 

19.%% M Adding Ezetimibe to Simvastatin Improves Lipids in T2DM   (Reuters
Health) Jul 12 - T2 diabetics with high cholesterol levels on simvastatin do

better with the addition of ezetimibe. [108pts] Lipid levels were virtually
unchanged in the placebo group, but mean LDL cholesterol fell from 99 to 66

mg/dL in the ezetimibe group and total cholesterol dropped from 162 to 124
mg/dL.  4 pts in the ezetimibe arm had transient sinus bradycardia,[slow
pulse] 

leading the authors to advise that this option "be considered with caution
in subjects with brady-arrhythmias.

 

20.%% M Hyperglycemia During Acute Illness May Predict Increased Risk for
T2DM 7/15/10   Patients with hyperglycemia during an acute illness who are
not

already diagnosed with DM should be considered at increased risk for [its]
development. [5yr Fup;398 pts] "Stress and inflammation during acute illness

seem to reveal an inherent disorder of glucose metabolism which in the
following years leads to development of diabetes."

 

21.%% Eye (2010) 24, July   Effects of conventional argon panretinal laser
photocoagulation on retinal nerve fibre layer and driving visual fields in
diabetic

retinopathy  Conclusions - This pilot study shows that conventional argon
laser panretinal photocoagulation may increase the retinal nerve fibre layer

thickness in the short term, presumably related to laser-induced axonal
injury, with progressive thinning of nerve fibre layer over the long term.

 

22.%% Eye 2010 vol 24 July A preliminary trial to determine whether
prevention of dark adaptation affects the course of early diabetic
retinopathy.  Conclusions 

The study showed that this intervention is safe... results are promising and
consistent with other reports that indicate the retina in DR is suffering

from hypoxia; however, further trials should be undertaken.

 

23.%% M Diabetics Have Alternatives to Rosiglitazone, Experts Say

7/19/10  Clinicians do not lack for alternative therapies if patients with
T2 ask to be switched from rosiglitazone (Avandia) to another glucose-
lowering

medication, according to ADA and 2 other expert groups. The drug is again
under increased scrutiny over CV risks.

 ..published clinical algorithms can guide physicians in selecting the right
drug or combination of drugs. Such algorithms take into account efficacy,

the risk for hypoglycemia, weight gain, and other adverse effects, as well
as cost. "Until further clarification is provided by (FDA), the decision
whether

or not to use any medication must remain that of the treating provider in
direct discussion with the individual patient,"  The statement came 2 days
before

an advisory committee to the FDA voted 20 - 12  to recommend that the FDA
keep Avandia on the market. A majority of members also recommended that the
agency

add a tougher warning about the risk for heart attacks and other
cardiovascular events to the label..

 

24. Delete

25.%% M Type 1 Diabetics Have High Prevalence of Thyroid and Celiac
Autoantibodies (Reuters Health) Jul 14 - Significant proportions of young
patients

with T1 also have thyroid and celiac disease autoantibodies. [30,000 T1
subjects] roughly 20% had positive thyroid antibodies and 11% had celiac
antibodies.

 

26.%% JH Is an Insulin Pump Right For You? 7/22/10  Insulin pumps are used
primarily by people with T1 but more T2 patients are starting to use the
pump.

Am I a good candidate for an insulin pump?  An insulin pump is a small,
computerized device that deliver insulin through a thin tube inserted via a
needle

into the skin of the stomach or thigh. Many people with DM prefer using an
insulin pump because it offers flexibility, convenience, and an insulin flow

that is completely predictable since you program it yourself. The biggest
advantage of the insulin pump is improved blood glucose control. Iin a
4-month

study of 79 diabetics, pump users had an average HbA1c level that was 0.8
percentage points lower than that of people on injected

insulin therapy. Most people with T2 who require insulin have fairly stable
blood glucose levels, requiring just 1- 2injections per day, so a pump isn't

needed. But in hard-to-treat individuals with T2 the insulin pump may be
beneficial. Individuals who are considering insulin pump therapy must be
knowledgeable

about their DM  and committed to regular glucose monitoring. .you have to
make sure to set the delivery rate correctly, check the tubing for
blockages,

change it regularly, and keep the insulin storage chamber full. Since
insulin pumps use rapid-acting insulin, any malfunction can cause a rapid
drop in

insulin levels, so you need to monitor your blood glucose several times a
day. If you think you would benefit from using an insulin pump, discuss it
with

your doctor.

 

27.%% MTD, Key Protein Influences Stem Cell Fate 7/19/10  Take a skin cell
from a patient with T1DM. Strip out everything that made it a skin cell,
then

reprogram it to grow into a colony of pancreatic beta cells. Implant these
into your patient and voila! She's producing her own insulin like a pro.
This

type of personalized therapy is the ultimate goal of most stem cell
research. But to reliably achieve that goal for treating DM and other
diseases, there's

a whole network of genes, proteins and miniscule chemical reactions to
decipher first. A team has discovered that a protein called Tet 1 helps stem
cells

renew themselves and stay pluripotent able to become any type of cell in the
body. "This may be one component of a cocktail to reprogram a specialized

cell to "go back" to the undifferentiated, embryonic stem cell state, Then
you can differentiate it into whatever cell type you want." Tet proteins
activate

a gene called Nanog, which helps stem cells reproduce themselves and keep
their pluripotency. "There are many genes that are important for maintaining

embryonic stem cells' status We will not understand the whole thing until we
identify all the important parts of the network. .

 

28.%% MTD New Treatment For Crippling Diabetic Charcot Foot

7/15/10  Charcot foot can make walking difficult or impossible, and in
severe cases can require amputation. But a surgical technique that secures
foot

bones with an external frame has enabled more than 90% of pts to walk
normally again. The device - a circular external fixator- is a rigid frame
made of

stainless steel and aircraft-grade aluminum. It contains 3 rings that
surround the foot and lower calf. The rings have stainless-steel pins that
extend

to the foot and secure the bones after surgery. Charcot foot can occur in a
diabetic who has neuropathy (nerve damage) in the foot that impairs the
ability

to feel pain. .. the patient doesn't feel the injury, so  he/ she continues
to walk, making the injury worse. Bones fracture, joints collapse and the
foot

becomes deformed.. .patients who are treated with an external fixator often
are able to walk or at least bear some weight on the treated leg. The device

is attached to the leg for 2-3 months.

 

29.%% Nat Reviews Nephrology 6, 2010 Angiotensin II and other components of
the renin–angiotensin– aldosterone system (RAAS) have a central role in the

[development] and progression of diabetic renal disease. Here researchers
describe the roles of RAAS. .[and] renoprotective and cardioprotective
effects

that inhibition of these effectors may have in individuals with DM. This
Review discusses the phenomenon of 'metabolic memory', in which the
beneficial

effects of intensive glycemic control persist after a return to more usual
(often worse) glycemic control. .. preliminary studies indicate that
biochemical

mechanisms such as advanced glycation and molecular pathways involving
epigenetic events [factors other than DNA] might have a role. ..

 

30.%%M Development of Novel Drugs for Ocular Diseases: Possibilities for
Individualized Therapy 7/21/10; Personalized Medicine. 2010;7(4): [note a
comprehensive

review; go to %% for treatments, conclusion, summary; In clinical
ophthalmology, new and old drug regimens are available for the treatment of
major eye

diseases, including glaucoma, and various macular diseases. Traditional
herbal medicine has long been known to play a role in the practice of
personalized

formulations in Asia. Potential preventive and therapeutic effects have been
claimed in individual eye patients. Meanwhile, advanced technologies in
molecular

biology have led to identification of genes associated with many eye
diseases and development of the concept of individual medicine, in which the
genotype

of a person can be used as a basis for disease prediction or prophylactic
treatments. . pharmacogenomic studies have demonstrated the association of
various

genotypes or haplotypes with responses to drug therapies, providing hope for
tailor-made personalized treatments. The combination of genotypic
information

with clinical features for the prescription of treatment modes in eye
diseases is under vigorous research. 

Medical Therapies of Eye Diseases: Overview - Glaucoma, AMD and diabetic
retinopathy are the leading causes of irreversible blindness worldwide.
Glaucoma

and AMD cause progressive degeneration of the optic nerve and retina,
respectively, and medical therapies are the mainstay of treatment for these
conditions.

The development of medical therapies is particularly challenging owing to
presence of the blood -ocular barrier, which maintains the homeostasis of
the

interior of the eye for proper visual function. The blood–ocular barrier is
partly formed by tight junctions between vascular endothelial cells and up

to 98% of low-molecular weight drugs cannot passively diffuse across this
barrier.  Therefore, many pharmacological agents administered systemically
[ie

by mouth] or locally frequently fail to reach sufficient concentrations
intraocularly to achieve therapeutic effects. Despite the intrinsic
difficulties

with drug deliveries into the interior compartments of the eye for
treatment, there has been a tremendous amount of new developments in medical
therapies

over the past 10–15 years. Notable examples include prostaglandin analogs
for lowering of the intraocular pressure in order to prevent the progression

of visual field loss in glaucoma; photodynamic therapy (PDT) for the
treatment of wet- AMD and other types of choroidal neovascularization (CNV),
and intravitreal

triamcinolone acetonide (IVTA) for the treatment of diabetic macular edema
(DME) More recently, antiangiogenesis therapy using anti-VEGF agents has
proven

effective in treating wet-AMD. With these new medical therapies, treatment
outcomes of these potentially blinding conditions have considerably
improved.

 

As effective drug therapies for various eye diseases have become available,
there is also an increased recognition that the treatment response in some

patients might be suboptimal. Patients might be nonresponsive to the therapy
or might develop adverse reactions. This has led to the concept of
personalized

medicine for all specialities in medicine, including ophthalmology. As the
genetic and biologic make-up vary from person to person, treatment responses

can differ considerably among individuals. There is evidence from recent
research to demonstrate that treatment responses are under the influence of
a

multitude of genetic, biochemical, physical and environmental factors. .. it
is important to understand how these personal, intrinsic or external factors

will influence the treatment outcomes. We need to explore the possibility of
identifying and providing individually tailored treatment of eye diseases

for each particular patient.. This article aims to provide an overview of
the .possibility of individualized therapy for patients with eye diseases,
The

possibility of using tailored therapy with herbal medicine will also be
discussed.

Impact of Molecular Biology in Ophthalmology - Recent research and
development for the concept of personalized therapy in treating eye diseases
can largely

be attributed to the advancements made in molecular biology techniques.. As
these diseases are determined by the complex interactions among multiple
genetic

and environmental factors, the identification of genetic determinants
provides insights into the disease pathogenesis, reveals novel therapeutic
targets

or strategies, provides useful biomarkers for diagnosis and facilitates
timely preventative or ameliorative interventions.

%%  Personalized Treatments for Macular Diseases - The macula is located in
the central part of the retina and is responsible for central and color
vision.

Macular diseases are the leading causes of blindness in developed countries.
Medical treatments are now commonly used for treatment, including CNV -
choroidal

neovascularization [abnormal  new vessels ] secondary to AMD or pathologic
myopia, and macular edema of various etiologies, such as DME, branch and
central

retinal vascular occlusions, or uveitis.

 - Diabetic Macular Edema [DME]  is one of the most sight-threatening
complications and occurs in approximately 10% of the DM population. The
prevalence

can be as high as 30% in patients with more than 25 years' history of DM.
Up until the last several years, grid or focal laser photocoagulation
treatment

to the macula has been the standard treatment. However, the long-term result
of grid laser  was unsatisfactory since only 15% of patients demonstrated

visual improvement 3 years post-laser therapy. Medical therapy for DME first
gained popularity in 2001, when the first patient received IVTA for DME
refractory

to grid laser photocoagulation was reported  IVTA reduced macular thickness
and improved visual acuity following treatment. However, recurrence of DME

after IVTA was common after the effects of the drug had worn off in 4-6
months.  There may also be side effects, including an increase in IOP and
cataract

formation. One reason for the limited benefits of grid laser  in DME is the
breakdown of the inner blood–retinal barrier with release of endogenous
permeability 

factors, such as VEGF by the ischemic retina. Anti-VEGF is thus useful in
reducing the amount of vascular hyperpermeability. Anti- VEGF agents
[lucentis,

avastin] improve vision and reduce retinal thickness in DME patients.
However, treatment responses to anti-VEGF therapy are variable. anatomical
reduction

in macular thickness is less when compared with IVTA.  Nonetheless,
preliminary results from ongoing clinical trials using ranibizumab
[lucentis] for DME

are encouraging. Combination therapies with anti-VEGF, corticosteroid and
macular laser photocoagulation can be tailored. Development of personalized
medicine

for DME treatment should include genotyping of the patients.

[genetics] A number of polymorphisms in the VEGF gene are associated with an
increased risk of DME.  Patients with the C634G polymorphism in the VEGF 

gene are likely to have DME and the genotype associated with macular
thickness as measured by OCT. .

DM patients with several specific variations in the VEGF A gene demonstrated
a significantly increased risk of developing blinding retinopathy from
clinically

significant macular edema, severe nonproliferative diabetic retinopathy and
proliferative diabetic retinopathy.  Patients with the C allele of rs3025021

and the G allele of rs10434 were more likely to develop blinding DR.
Further evaluation of the association of VEGF polymorphisms with responses
to treatment,

such as anti-VEGF, will be useful to develop personalized therapy for DME.
Identification of patients with at-risk VEGF  polymorphisms would be useful

to provide guidance for more intensive screening and to be able to offer
earlier treatment for DR. In additional to the VEGF gene, variations in the
endothelial

nitric oxide , manganese superoxide dismutase and erythropoietin (EPO) genes
have also been implicated in the development of DME and DR. Knowing the
pathological

roles of these genes should be useful to develop novel treatments. However,
such biological roles are complex and subject to intriguing personal and
environmental

factors.

[herbs] Personalized Herbal Medicine for Glaucoma & Macular Diseases  Herbal
medicine provides one of the oldest types of healthcare for humans and is

still widely used today.. However, improvements in quality control along
with the advances in clinical research are needed to ascertain their values
for

disease treatment and prevention. For most herbs, the chemical constituents
demonstrating therapeutic effects are not known. Very often different herbs

are added in a certain protocol to formulate a cocktail. In ophthalmology,
herbal medicine is a popular alternative in many communities for eye care
and

even treatment of eye diseases. Molecular biology techniques should help
advance the personalization of herbal medicine for eye diseases. However,
such

studies in ophthalmology are scarce. 

%%Conclusion  From traditional Chinese medicine to modern treatments and
future drug discovery, individualized therapy is always an important
concept.

In ophthalmology, the treatments for eye diseases are prescribed according
to the clinical conditions of the patients. Pharmacogenetic studies have
begun

to shed light on the prospect of personalized medicine. However, there is
still a long way to go before treatments could be tailormade for each
patient.

The main reasons are the complexity in pathogenic mechanisms, intriguing
polygenic associations in various ocular diseases, and the interactions of
multiple

genetic and environmental factors. Vigorous research is going on in all
these areas with important information being revealed everyday. In the near
future,

more new and advanced treatments will be established since new information
on disease pathogeneses will be unraveled, and diseases will be diagnosed
earlier

and more accurately.   Future Perspective   So far, major genes for the
common eye diseases including glaucoma, myopia and diabetic retinopathy are
still

to be identified. Moreover, no treatment is available to reverse the
pathological process or to restore the impaired visual function of these
blinding

diseases. Therefore, regenerative medicine should be greatly affected by
discoveries of novel disease markers and pathways. In the next few years,
rapid

advances in these areas are expected. Exciting advancements of the molecular
mechanisms of the major eye diseases that are attributed to the formulation

of personalized medicine in ophthalmology is envisaged.

%%  Executive Summary .. While effective drug therapies for various eye
diseases are available, treatment responses in patients are found to be
variable,

effective in some but nonresponsive, and even cause adverse reactions, in
others. There is evidence demonstrating treatment responses are under the
influence

of a multitude of genetic, biochemical, physical and environmental factors.
We need to explore the possibility of identifying and providing individually

tailored treatment for eye diseases for each particular patient.   Impact of
molecular biology in ophthalmology  - Since early and even presymptomatic

diagnosis are vital for alleviating complications and inhibiting disease
progression in most forms of glaucoma and macular diseases, the
identification

of genetic determinants aims to reveal novel therapeutic targets or
strategies, provide useful biomarkers for diagnosis and facilitate timely
preventative

or ameliorative interventions. In recent decades, more than 50 causal or
susceptible genes for glaucoma and macular diseases have been identified.
However,

genetic determinants are yet to be identified for over 90% of patients.
Available data on SNPs and copy number polymorphisms have provided useful
information

on the associations between genetic variations and treatment responses. In
the next few years, rapid advancements in the molecular mechanisms of major

eye diseases leading to formulation of personalized medicine are envisaged.
References [181 deleted]

 

31.%% First-Morning Void May Be Best Predictor of Renal Events in Diabetic
Nephropathy 7/22/10  Albumin-to-creatinine ratio (ACR) in a first-morning
void

may be the best predictor of renal events in T2 "From a clinical point of
view, these results are very important, because they imply that collection
of

first morning voids, which is clearly more convenient than collecting a
24-hour urine, can be used for assessment of proteinuria," said lead author
[701

subjects T2] "First, urine ACR represents more than simply proteinuria, and
associations of urine ACR with disease outcomes should be interpreted in the

context of dual contributions of urine albumin excretion and urine
creatinine.

 

32.%%FDA Warns Abbott Diabetes Care About Manufacturing Practices of Its
Glucose Meters 7/21/10 — Abbott Diabetes Care has received a warning letter
from

(FDA) about how it manufactures its

FreeStyle glucose meters. The meters include the FreeStyle Navigator
Continuous Glucose Monitring System , currently unavailable in the US as a
result

of what the company calls a "supply interruption."

In a July 2 letter, the FDA faulted Abbott Diabetes Care, with

violations of quality-control requirements, including how it followed up on
the discovery of empty blister packs and scratches on glucose-meter test
strips.

The FDA also stated that the company lacked enough qualified personnel to
ensure that manufacturing processes met agency standards. The warning letter

stemmed from an FDA inspection of the company's facilities in Alameda, CA
earlier this year. To report adverse events related to these devices,
contact

MedWatch by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at


http://www.fda.gov/medwatch

 

33.%% MTD Novel Anti-Diabetes Mechanism Uncovered By Scripps Research
Institute And Dana-Farber Scientists 7/23/10 scientists  have uncovered a
novel mechanism

that dramatically increases insulin sensitivity and reduces the risk of
developing T2DM and cardiovascular disease. The new study,  focuses on
controlling

a fat-regulating protein known as PPARy, "The field has become interested in
finding drugs that can promote increased insulin sensitization but not
activate

the classical fat cell generating pathway of PPAR?," said the spokesman.
Adipose or fat tissue lies at the center of the metabolic syndrome, a
cluster

of risk factors that increases the possibility of T2, as well as stroke,
coronary artery disease, even certain cancers. PPAR? can be considered the
master

gene of fat cell biology because it drives the conversion of cellular
precursors into fat cells The collaborative studies showed obesity causes a
modification

on PPAR? that leads to alterations in the expression of a number of genes,
including a reduction in the production of an insulin-sensitizing protein
(adiponectin).

This leads to an increase in insulin resistance..While the team found that
PPAR? phosphorylation effects were reversed by both full and partial
agonists,..

"Unfortunately, current drugs that target PPARg increase fat as one of their
unwanted long-term side effects."

 

Abbreviations:Fup-follow up; pt - patients;  DM - diabetes Mellitus; T1DM -
type 1 diabetes mellitus T2DM - type 2; DME - diabetic macular edema; GDM
gestational

diabetes;PDR - proliferative diabetic retinopathy; IVTA  intravitreal
triamcinolone acetonide; FPG - fasting plasma glucose; BP - blood pressure;
CVD -

cardio-vascular disease; MI -myocardial infarction or heart attack ;HTN -
hypertension or high BP; OCT - optical coherence tomography; VA - visual
acuity 

-ADA - Am Diab Ass & ADA Professional.. Online; JH- Johns Hopkins Alerts ;
M- Medscape Web MD; NIH - Nat Institutes of Health;  MTD- Medical News Today


NREndo;Nature Reviews Endocrinology    Definitions via online Medical
dictionaries.  Disclaimer, I am a BSN RN but not a diabetic or diabetic
educator.

Reports are excerpted unless otherwise noted. This project is done as a
courtesy to the blind/visually impaired and diabetic communities. Dawn
Wilcox BSN

RN Coordinator The Health Library at Vista Center; an affiliate of the
Stanford Hospital Health Library.   contact above e-mail or 

thl at vistacenter.org     

            

       

-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://www.acb.org/pipermail/acb-diabetics/attachments/20100802/1a9c1852/attachment-0001.htm>