articles

[Guest guest]

1. ARV0 2008 papers on Macular Edema and vitrectomy

Undiagnosed peripheral ischemia is thought to be the root cause of

persistent diabetic macular edema (DME) in some patients. In this

study, patients were

evaluated with Optomap wide-field angiography. [14 eyes of 7 patients

with diabetes who had clinically significant macular edema.]

Approximately one quarter

of the retina was deemed ischemic in those who had DM retinopathy and

macular edema. The study authors concluded that future strategies used

to treat macular

edema should also address the peripheral ischemic component. Eliott et

al; presented data on the use of the I-vation implant containing

triamcinolone

acetonide for patients with DME. 31 patients were randomized to receive

the implant in either the slow-release or fast-release version.

Conclusion: the

I-vation implant resulted in overall meaningful improvements in retinal

thickness and vision without serious adverse events at 18 months.

Yee and colleagues - presented their data on the use of topical

nepafenac to treat nonpseudophakic cystoid macular edema. Although the

pathogenesis of

macular edema due to DM has been closely linked with the release of

vascular growth factors in response to ischemia, macula edema may also

have components

of chronic inflammation. Nepafenac is a selective cyclooxygenase (COX)-2

inhibitor and has been shown to have excellent retinal penetration. [11

patients

] prescribed topical nepafenac 3 times daily.. Mean vision improved

from 20/50 to 20/30, and mean central retinal thickness improved from

392 mcm at baseline

to 299 mcm at 3 months. the authors concluded that topical nepafenac may

have a role in macular edema cases other than pseudophakic cystoid

macular edema.

Vitrectomy - Hu and colleagues evaluated cataract progression after

25-gauge vitrectomy and the incidence of cataract removal over a 2-year

period. (Cataract

progression is a well-known complication after vitrectomy surgery, and

is thought to be due to the use of intraocular gases, the increase in

oxidative

stress on the lens, and the mechanical damage caused by

instrumentation.) [57 patients] The patient population underwent

25-gauge vitrectomy for a variety

of indications. During the 2 years of follow-up, 81% of patients had

documented postoperative cataract progression and 42% underwent cataract

extraction.

These findings would indicate that cataract progression following

25-gauge vitrectomy surgery may be lower than after conventional

20-gauge vitreoretinal

surgery. The authors hypothesized that this difference may be due to

shorter operative times, less complete anterior vitreous gel removal,

less instrument

exchange, and less manipulation of anterior structures.

2.%% Heartwire - Too Few Diabetes Trials are Seeking Answers to Issues

Important to Patients, Including Hard CV End Points 6/4/08

- Too many randomized controlled trials of DM drugs are designed with

surrogate end points and not with the kinds of end points that actually

matter to

patients. That's the conclusion of a new analysis. " There's an ethical

obligation to justify the research enterprise by saying that at least a

fraction

of this will provide information that will fundamentally change the

lives of the people who are suffering from this condition, " the senior

author said

.. " If a large majority of your research is either for knowledge's sake

or for marketing purposes, that corrupts the evidence base and makes you

wonder

whether you really are doing the right thing. " The new study comes hot

on the heels of regulatory discussions and congressional investigations

into blockbuster

drugs like ezetimibe [zetia] and rosiglitazone [avandia] and the trials

conducted to assess them. Both drugs sparked fresh debates over the role

of surrogate

end points in major clinical trials. In the case of rosiglitazone, the

drug appears to lower hemoglobin A 1c but may increase the risk of both

MI and

death, while the entire glitazone class appears to increase the risk of

heart failure. " We really know very little about the effects of these

new diabetes

drugs and even about some of the older drugs on patient outcomes . It's

very difficult for patients and physicians to make decisions about the

benefits

of these agents without knowing how they will make patients feel,

whether they will ext end their lives, or whether they will prevent

complications effectively. "

[436 randomized controlled trials of DM interventions] They found that

" patient-important " outcomes- -including cardiovascular events, death,

pain, function,

and quality of life--were chosen as primary outcomes in just 18% of

trials. .the bulk of trials used either surrogate outcomes, such as

glycated hemoglobin

or cholesterol levels, or physiological/lab outcomes (eg, insulin

levels, C-peptide levels, etc). Of note, trials of patients with T2 were

significantly

less likely than trials of T1 or T1 & 2 combined to report outcomes

important to patients... He acknowledges that surrogate markers play an

important role

in expediting the drug- approval process, but he thinks the " stringent "

rules for validating a surrogate marker are frequently bypassed. " It is

unfortunate,

because everyone wants to have newer, more potent, and safer agents, and

it would slow the whole process down if we were to demand that for every

one of

these agents we want patient-important outcomes to be measured. Yet when

we don't do it, we find ourselves crashing into a wall, realizing that

we may

have caused harm to people by again trying to rush to have these

innovative agents on the market. " He and his colleagues hope that their

study will spur

researchers, clinical trialists, and diabetes health-advocacy groups to

come together and reach some consensus about the types of outcomes

needed in clinical

trials of diabetes interventions.

3.%% MW -Sirolimus Linked to New-Onset Diabetes Following Renal

Transplant (Reuters Health) Jun 03 - For kidney transplant recipients,

use of the anti-rejection

drug sirolimus may increase the risk of DM , . " Patients who develop DM

after transplantation have roughly the same risk of transplant failure

as patients

who develop acute transplant rejection, " researchers state. [20,124

nondiabetic adult recipients of a first kidney transplant;2600 were

prescribed sirolimus

in combination with other immunosuppressants; 3-year follow-up] ..

treatment with sirolimus in any combination was associated with

increased risk for

new-onset diabetes compared with the reference group (patients treated

with cyclosporine A and MMF/AZA).J Am Soc Nephrol 2008.

4.%% NIHPRESS Digest - 6/4/2008 (#2008-75) Long-term Pesticide Exposure

May Increase Risk of Diabetes Licensed pesticide applicators who used

chlorinated

pesticides on more than 100 days in their lifetime were at greater risk

of DM, according to researchers. The associations between specific

pesticides and

incident DM ranged from a 20 to 200 % increase in risk, said scientists

with the NIH's National Institute of Environmental Health Sciences and

the National

Cancer Institute . " The results suggest that pesticides may be a

contributing factor for DM along with known risk factors such as

obesity, lack of exercise

and having a family history of diabetes, " they said " Although the amount

of DM explained by pesticides is small, these new findings may extend

beyond the

pesticide applicators in

the study, " Some of the pesticides used by these workers are used by

the general population, though the strength and formulation may vary.

Other insecticides

in this study are no longer available on the market, however, these

chemicals persist in the environment and

measurable levels may still be detectable in the general population and

in food products. For example, chlordane, which was used to treat homes

for termites,

has not been used since 1988, but can remain in treated homes for many

decades. New cases of diabetes were reported by 3.4% of those in the

lowest pesticide

use category compared with 4.6 % of those in the highest category. . the

strongest relationship was found for trichlorfon, with an 85 % increase

in risk

for frequent and infrequent users and nearly a 250 % increase for those

who used it more than 10 times. Trichlorfon is an organophosphate

insecticide classified

as a general-use pesticide that is moderately toxic. Previously used to

control cockroaches, crickets, bedbugs, fleas, flies and ticks, it is

currently

used mostly in turf applications, such as maintaining golf courses.

" This is one of the largest studies looking at the potential effects of

pesticides

on DM incidence in adults, " said a co-author in the paper appearing in

the May issue of the " Amer Journal of Epidemiology. " " It clearly shows

that cumulative

lifetime exposure is important and not just recent exposure., " [30,000

subjects].. Among the 50 different pesticides the researchers looked

at, they

found seven specific pesticides -- aldrin, chlordane, heptachlor,

dichlorvos, trichlorfon, alachlor and cynazine -- that increased the

likelihood of

diabetes among study participants who had ever been exposed to any of

these and an even greater risk as cumulative days of lifetime exposure

increased.

5.%% First Data on Aliskiren in Diabetic Nephropathy Heartwire 6/5/08

-The first trial of a new antihypertensive agent, the direct renin

inhibitor aliskiren

(Tekturna), in patients with DM nephropathy shows that addition of the

drug to conventional treatment over a 6 -month period reduces

proteinuria by 20%

The findings also suggest that aliskiren may be renoprotective, and

reducing proteinuria is associated with benefit in relation to

cardiovascular disease

in these patients, the team said. But others questioned these

conclusions, saying that proteinuria is merely a surrogate end point.

" They've shown that

the addition of aliskiren to losartan gives benefit in terms of reducing

proteinuria, but we have no idea how that will translate into long-term

benefit

for patients, and we have no idea what the long-term safety [of

aliskiren] is.. " It's just a question of how many patients will be able

to continue on maximum

doses of an ACE inhibitor or an ARB--or both in many cases--and then add

in aliskiren, "

6.%% MW -Evidence Limited for Screening Most Adults for Type 2 Diabetes

June 5, 2008 -The US Preventive Services Task Force (USPSTF) has issued

a statement

that limited evidence exists to recommend screening adults for T2DM but

screening may be helpful in those with hypertension. " More than 19

million Americans

are affected by T2, which is undiagnosed in one third of these persons, "

write the researchers. In addition, more than 54 million adults have

prediabetes.

Debate continues over the benefits and harms of screening and then

treating adults who have asymptomatic DM or prediabetes. " Specific

recommendations of

the USPSTF with regard to screening for T2 in adults are as follows:

Because high BP is a recognized risk factor for cardiovascular

complications in people

with T2, blood pressure should be measured. Asymptomatic adults with no

symptoms of T2 or evidence of possible complications of diabetes but

with sustained

BP greater than 135/80 mm Hg (treated or untreated) should be screened

for T2DM. For asymptomatic adults with sustained BP of 135/80 or lower,

no recommendation

has been made regarding screening for T2. ADA recommends screening with

fasting plasma glucose, defining DM as a fasting plasma glucose level of

126 mg/dL

or greater, and confirming an abnormal result with a repeated screening

test on a separate day. .screening interval of every 3 years.

Information about

the 10-year risk for coronary heart disease must be considered when

deciding if screening would be helpful on an individual basis.. Further

work is also

needed to examine the effect of screening and diagnosis on patient

self-efficacy, motivation for lifestyle change, and the potential

psychological effects

of labeling. " Ann Intern Med. 2008;148

7.%% NY Times June 7, 2008 Tight Rein on Blood Sugar Has No Heart

Benefits - Two large studies involving more than 21,000 people found

that people with

T2DM had no reduction in their risk of heart attacks and strokes and no

reduction in their death rate if they rigorously controlled their blood

sugar

levels. The results provide more details and bolster findings reported

in February, when one of the studies, by the NIH, ended prematurely. At

that time,

researchers surprised DM

experts with the announcement that study participants who were

rigorously controlling their blood sugar actually had a higher death

rate than those whose

blood sugar control was less stringent. Now the federal researchers are

publishing detailed data from that study. Researchers in the second

study, involving

participants from 20 countries, are also publishing their results on

blood sugar and cardiovascular disease. That study did not find an

increase in deaths,

but neither did it find any protection from cardiovascular disease with

rigorous blood sugar control. Thus both studies failed to confirm a

dearly held

hypothesis that people with T2 could be protected from cardiovascular

disease if they strictly controlled their blood sugar. It was a

hypothesis that seemed

almost obvious. Cardiovascular disease accounts for 65% of deaths among

people with T2. And since DM is characterized by high levels of blood

sugar, the

hope was that if people with DM could just get their blood sugar as

close to normal as possible, their cardiovascular disease rate would be

nearly normal

as well. The two studies and a similar but smaller one by the VA were

presented at ADA 68th 2008. Diabetes researchers say that the message is

that patients

should obtain at least moderate control of blood sugar to protect

against eye, kidney and nerve disease. But for heart disease, they say,

the only proven

method of preventing complications is to give statins to control

cholesterol, drugs to control BP and aspirin to control blood clotting,

and to encourage

people to lose weight and exercise. .. Although the studies' failure to

prove the blood sugar/cardiovascular disease hypothesis was a huge

disappointment,

the result may reflect how difficult it is to change outcomes in people

like the study participants, said Dr. Judith Fradkin, chief of the

diabetes division

at the National Institute of Diabetes and Digestive and Kidney Diseases.

They were middle age or older and had had diabetes for years. " You're

trying to

intervene in people in whom a lot of the damage may already have been

done, " Younger and newly diagnosed patients may be a different story,

she said,

adding, " That's the great unanswered question. "

8.%% MW - ADVANCE: Intensive Glucose Control Reduces Diabetic

Nephropathy 6/8/08 - Intensive glucose control significantly reduces

the risk for nephropathy,

according to the results of a 5-year trial to assess the effects of

intensive glucose control and BP lowering on vascular complications of

T2DM. The Action

in Diabetes and Vascular Disease: Preterax and Diamicron Modified

Release Controlled Evaluation (ADVANCE) study is the world's largest

diabetes trial,

enrolling 11,140 patients with T2in 20 countries. " Clinicians, diabetes

specialists, and indeed the patients whom they look after, urgently need

a guidance

as to the level of glycemic control that we can safely aim for, " Simon

Heller, study coauthor said. [Patients were at least 55; had been

diagnosed with

T2 at age 30 years or older, and had a history of, or at least 1 risk

factor for, vascular disease.] Participants were randomly assigned to

receive a placebo

or a fixed dose of perindopril and indapamide to lower BP, and to

undergo intensive control or standard control of blood glucose.

Regardless of initial

blood pressure, the blood pressure-lowering regimen in this population

reduced their relative risk of death due to cardiovascular disease by

18% . Patients

randomized to the intensive-glucose -control group (n = 5571) received

gliclazide; other glucose-control

agents were prescribed as needed to achieve the ADVANCE target HbA1c of

6.5% or less. Conclusion: " [W]e would not conclude that glucose makes no

difference,

but we would say that attempting to get very very tight glucose control

may not give you added benefit for cardiovascular disease. On the other

hand,

remember that 50% of all the people who enter a dialysis program in the

west have DM as the cause of their kidney disease. So...you don't have

to get so

tight in the control to get a better effect on cardiovascular [events],

but you do if you want to really reduce kidney disease, which is a very

important

endpoint. " N Engl J Med. 2008;358.

9.%% MW -Diabetic Ulcer Gel Gets Black Box Warning 6/9/08 A black box

warning has been added to the safety labeling for becaplermin

gel (Regranex , & ) to warn of the increased risk for

cancer mortality in patients who use 3 or more tubes of the product, the

(FDA) announced

Friday. The action follows an FDA safety review that was initiated after

a postmarketing retrospective cohort study revealed an overall increase

in the

number of cancer deaths in becaplermin-exposed patients compared with

similar patients who had not been exposed. The agency has now concluded

that the

risk for cancer mortality was 5-fold higher in patients exposed to 3 or

more tubes of becaplermin, .. " the adjusted rate ratio for overall

cancer incidence

among becaplermin-treated patients was 1.2 . For patients who had been

exposed to 3 or more tubes of the gel, the adjusted mortality rate ratio

was 5.2

" In announcing this label change, FDA still cautions health care

professionals to carefully weigh the risks and benefits of treating

patients with Regranex.

Regranex is not recommended for patients with known malignancies. "

Becaplermin 0.01% gel is a recombinant form of human platelet-derived

growth factor

that is indicated for the treatment of lower extremity diabetic

neuropathic ulcers with an adequate blood supply that extend into the

subcutaneous tissue

or beyond.

10.%% MW -Saxagliptin Once Daily Improves Key Clinical Measures of

Glucose Control June 9, 2008 - A phase 3 trial has demonstrated that

once-daily administration

of saxagliptin for 24 weeks reduces HbA1c, fasting plasma glucose (FPG),

and postprandial glucose (PPG) levels in patients with type 2 diabetes

mellitus.

The senior author announced at ADA 68th 2008 [401 patients;

double-blind, placebo-controlled trial] were randomly assigned to

receive a placebo or 2.5,

5.0, or 10.0 mg of saxagliptin once a day for 24 weeks. A second cohort

of 66 patients in an open-label trial received 10 mg of saxagliptin once

a day.

" Saxagliptin is a [dipeptidyl peptidase (DPP-4)] inhibitor, [it] is an

enzyme that inactivates certain hormones, most importantly incretins.

And incretins...have

a key role in maintaining and helping to provide glucose homeostasis. So

saxagliptin, by inhibiting DPP-4, will then slow the inactivation of the

important

hormones...thereby hopefully prolonging their beneficial effect, " he

said. In the present trial, mean baseline HbA1c for all 4 groups was

7.9% to 8.0%.

HbA1c was significantly reduced compared with placebo in patients who

received saxagliptin once daily FPG levels also decreased in all 3

treatment groups

compared with placebo " In this study, at all doses we saw clinically

relevant changes for A1c , FPG, and benefits to PPG, " he summarized.

Adverse events

were experienced by 71.6% of the placebo group, 75.5% of saxagliptin

patients in the main study, and 60.6% of the open-label group. The most

common adverse events were upper respiratory tract infections, headache,

urinary

tract infection, nasopharyngitis, sinusitis, and back pain. Dr. Chen is

employed by and owns shares of Bristol-Myers Squibb Company.

11.%% Sitagliptin May Be Safe, Effective in Patients With Diabetes and

Renal Disease June 6, 2008 - Sitagliptin was generally well tolerated

and provided

effective glycemic control in patients with type 2 diabetes and moderate

to severe renal insufficiency. " Because of safety and tolerability

issues, there

are limited antihyperglycaemic

treatment options for patients with T2 who have chronic kidney disease

(CKD), " researchers write. " Sitagliptin is primarily renally eliminated

with approximately

80% of the oral dose excreted unchanged in the urine. " The goal of this

study was to evaluate the safety and efficacy of sitagliptin in patients

with T2

and moderate creatinine clearance (CrCl; = 30 to < 50 mL/minute) or

severe renal insufficiency (CrCl < 30 mL/minute), including those with

end-stage renal

disease (ESRD) requiring dialysis. [91 patients ] At baseline, mean

glycated hemoglobin value was 7.7% For patients continuously treated

with sitagliptin,

the mean change in glycated hemoglobin value from baseline to 54 weeks

was -0.7%.. hypoglycemia occurred in 4.6% of the sitagliptin group vs

23.1% of the

placebo/glipizide group. " In this study, sitagliptin was generally well

tolerated and provided effective glycaemic control in patients with T2

and moderate

to severe renal insufficiency, including patients with ESRD on

dialysis, " the study authors write. Merck & Co, Inc, supported this

study and employs 8

of the study authors. Diabetes Obes Metab. Published online June 1,

2008.

12.%% MW - Takeda New Diabetes Drug Seen Good but Not Great

Reuters Health Information 2008. C 2008 Reuters Ltd. Jun 05 - The drug,

called alogliptin or SYR-322, is under regulatory review and data will

be presented

at ADA 68th2008. Japan's largest drug maker has grown globally on the

strength of its diabetes pill Actos, which will lose U.S. patent

protection in 2011.

With alogliptin, which belongs to a new class of diabetes drugs called

DPP-4 inhibitors, Takeda hopes to not only compete with Merck's drug

Januvia, the

only DPP-4 on the U.S. market, but also offset some of the drop-off in

Actos sales that will come with generic competition. Abstracts of the

data have

been released, prompting most Tokyo-based analysts to tentatively

pronounce alogliptin to be roughly the same as Januvia in terms of

safety and efficacy.

But some analysts saw the glass as being half-full, touting

alogliptin's likely approval later this year, the probable development

of an alogliptin/Actos

combination pill and other combination medicines. Alogliptin could be

used in combination with insulin, while Januvia cannot. Other analysts

also stressed

the apparent lack of side-effects in the alogliptin data. " The good

thing is there appears to be no skin toxicity and renal toxicity for

this product.

13.%% MNTD - When It Comes To Type 1 Diabetes, Weight Gain May Be

Healthy 9 Jun 2008 Gaining body fat may be a good thing, at least for

people with

T1 say researchers. Their study, presented at ADA 68th 2008 followed 655

patients with T1 for 20 years and found

that patients who gained weight over time were less likely to die.

Researchers measured patients' body mass index (BMI) and waist

circumference and assessed BMI every two years. Results showed that

patients whose BMI increased

the most during the study (2 to

11 points or about 10 to 55 pounds) were one-third less likely to die

than those who had smaller increases in BMI, indicating that weight gain

may protect

people with T1 from premature death. " Although weight gain in adulthood

is typically associated with increased mortality, this may not be the

case for

those with T1, " said Trevor Orchard, M.D.,professor of epidemiology

" Gaining a reasonable amount of weight may be a sign patients are

getting enough insulin

and appropriately controlling their disease, which may partly explain

why those who gained weight over time had lower mortality rates, " The

team also looked at BMI ranges and found no difference in mortality

between those

with a BMI in the overweight range (BMI 25-30) and the normal range (BMI

20-25). Conversely, they found that having a BMI in the underweight

(less than

20) or obese range (BMI 30 +) was a strong predictor of mortality. " These

results are not a firm recommendation to people with T1 to put on

weight, but

it does raise the possibility that weight recommendations in T1may be

somewhat different than those for the general population, and emphasizes

the complex

relationship between body fat and mortality in diabetes, "

14.%% MNTD - The Relationship Between Type 2 Diabetes And Sleep Apnea 9

Jun 2008 The International Diabetes Federation (IDF) Task Force on

Epidemiology

and Prevention has warned that recent research demonstrates that T2DM

and obstructive sleep apnea (OSA) are closely related, and that both

disorders have

significant implications on public health and on individuals. These were

the conclusions of a meeting of diabetes and sleep experts who examined

the impacts

of untreated OSA, the most common form

of sleep disordered breathing. The resulting IDF statement was released

at ADA 68th2008 " While T2 is recognized as a serious global epidemic,

the severe

health consequences of untreated sleep apnea, especially in people with

diabetes, are not. Health policy makers and the general public must be

made aware

of the link between [these]

so that we can begin to address the significant economic burden and

debilitating health consequences to individuals and the community, "

said Professor P Zimmet, co-chair Recent studies suggest that up to 40%

of people with OSA have diabetes.. although the mechanisms linking OSA

with DM

are not yet fully understood, the consequences of both conditions cannot

be ignored. It has been shown that the prevalence of CVD increases

progressively

with the increasing severity of OSA and that people with DM and/or OSA

face serious cardiovascular problems and earlier death. Undiagnosed OSA

may interfere

with lifestyle treatment for diabetes. The IDF Task Force statement

includes recommendations for screening, treatment and further research.

While people

with OSA should be routinely

screened for metabolic disease and T2; people with DM should be screened

for OSA particularly when they present classical symptoms such as

witnessed apneas,

heavy snoring or daytime sleepiness and poor workplace performance.

Recommendations for treatment of OSA include weight reduction in

overweight and obese

people, reduction in alcohol intake and CPAP treatment. Although further

research is needed, the treatment of OSA may improve glycaemic control

and will

certainly benefit people as it improves their quality of life, BP

control and risk of cardiovascular disease.

15.%% MNTD -Potential For Sensitive Blood Test To Identify Type 1

Diabetes 8 Jun 2008 Knowing who has, or will develop T1DM is of immense

clinical significance,even

as the number of cases of the much more common T2DM skyrocket.

Collaborators from Antigen Express and and scientists in UK and Italy

are now one step closer

to a reliable, highly sensitive diagnostic test that will identify T1 in

time for early intervention. [ADA 68th 2008] A key hallmark in the

etiology of

T1is T cell recognition of islet cell antigens. Several proteins are

associated with development of T1, in particular insulin and glutamic

acid decarboxylase

65 (GAD65). Unfortunately, a highly sensitive, specific assay for T

cells reactive to insulin or GAD65 is still under development, and not

available as

a diagnostic or prognostic tool to clinicians. Currently, TI can only be

diagnosed by the presence of antibodies when the disease is already well

underway.

The team

approached the lack of an assay through a novel approach. Investigators

linked an antigenic peptide derived from GAD65 to the Ii-Key fragment,

which enhances

binding of antigenic peptides directly to MHC Class II receptors on the

cell surface. .Cells from patients with T1demonstrated a distinct

profile of cytokine

production compared to cells from healthy volunteers. . the interferon

response to whole GAD65 was significantly greater in DM subjects

compared to controls

T1 diabetics also showed a increase in interferon response to GAD65

Ii-Key peptides. " The cytokine expression profile we observe is helpful

from a diagnostic

perspective and gives hope that Ii-Key/GAD65 hybrids may have utility as

agents to suppress autoimmunity. " T cell reactivity to GAD65 is of

particular

interest in individuals who develop DM later in life, as this helps to

differentiate them from the more common T2. . a validated

diagnostic based on GAD65 could put those patients on the right

treatment regimen earlier.

16.%% MNTD - Kidney Cell Suicide In Diabetes Patients 6/7/08

Diabetes is the leading cause of renal failure that requires dialysis.

The disease generates such a hostile environment that it forces the

kidney cells

to kill themselves, progressively reducing the renal functions of the

kidneys. A research group has studied the causes and consequences of the

cell suicide

of renal cells. DM slowly destroys the kidney up to the point where the

renal function has to be taken on by dialysis (artificial kidney) or a

transplanted

kidney. It is the leading cause of end stage renal failure that requires

dialysis. The destruction of the kidney comes from the loss of its

cells, which

recent studies have demonstrated to be caused by apoptosis, a process

that, for cells, involves death by suicide. Cells suicide when their

environment

does not " please " them, when their surroundings

feel hostile or stressful. The Spanish team has spent years studying the

causes and the consequences of kidney cell suicide, specializing in

" psycho-cellulology " .

The affected kidneys exhibited an abnormal expression of 112 genes that

regulate the cell suicide. Among these genes, the team identified a

protein of

the Tumour Necrosis Factor (TNF) family, called TRAIL, as the key to the

cell suicide in diabetes affected kidneys. In these kidneys, large

quantities

of TRAIL can be found that surprisingly do not come from the increased

glucose levels that define the disease, but from the inflammation that

accompanies

the renal damage. Inflammation and higher glucose levels favour renal

damage; the inflammation raises the TRAIL levels while the

hyperglycaemia generates

a stressful environment that, in the presence of TRAIL, leads to cell

suicide. The role played by inflammation in the cell suicide suggests

that the treatment

of diabetic nephropathies requires a multiple attack to control the

glucose levels while also acting on the renal inflammation and lethal

proteins like

TRAIL.

17.%% MNTD - Global View Supports Concept Of Using Vitamin D In Reducing

Disease Risks For Type 1 Diabetes 5 Jun 2008

Sun exposure and vitamin D levels may play a strong role in risk of T1DM

in children, according to new findings. This association comes on the

heels of

similar research findings by the same group regarding vitamin D levels

and several major cancers. The team found that populations living at or

near the

equator, where there is abundant sunshine (and ultraviolet B irradiance)

have low incidence T1DM

Conversely, populations at higher latitudes, where available sunlight is

scarcer, have higher incidence rates. These findings add new support to

the concept

of a role of vitamin D in reducing risk of this disease. Ultraviolet B

(UVB) exposure triggers photosynthesis of vitamin D3 in the skin. This

form of vitamin

D also is available through diet and supplements. T1 is the second most

common chronic disease in children, second only to asthma. About 15,000

new cases

are diagnosed in the US each year, where this disease is the main cause

of blindness in young and middle-aged adults and is among the top

reasons for kidney

failure and transplants in youth and midlife. " This research suggests

that childhood T1 may be preventable with a modest intake of vitamin D3

(1000 IU/day)

for children, ideally with 5 to 10 minutes of sunlight around noontime,

when good weather allows, Infants less than a year old should not be

given more

than 400 IU per day without consulting a doctor. Hats and dark glasses

are a good idea to wear when in the sun at any age,

and can be used if the child will tolerate them. " Article adapted by

Medical News Today from original press release. Source: Kim

University of

California - San Diego

18. %% MNTD -Discovery Of New Signal Pathway Important To Diabetes

Research 4 Jun 2008 Scientists have discovered that cells

in the pancreas cooperate - signal - in a way hitherto unknown. The

discovery can eventually be of significance to the treatment of

diabetes. Scientists

have known for a long time that glucose is regulated with the help of

hormones in the pancreas, which is to say that pancreatic beta cells

produce insulin,

which reduces sugar levels, and that alpha cells produce glucagon, which

boosts them. This glucose balance must be kept within a very narrow

interval,

and we need both insulin and glucagon to remain in good health. " A

person with low blood sugar levels feels poorly and faint; a person with

excessively

high blood sugar levels gets diabetes, " says the leader of this study.

This team focused onglucagon secretion, and discovered that alpha cells

also secreted

glutamate, which facilitates glucagon release and makes it more

efficient. They are working on the hypothesis that when glucose levels

are raised in a

healthy person, the beta cells become active and start to release

insulin, which reduces sugar concentrations in the blood, upon which the

alpha cells

then start to secrete glucagon and glutamate. In this context, glutamate

acts as a positive signal that tells the alpha cells that it is time to

accelerate

the production of glucagon to prevent glucose levels from falling too

low. " It's this signal pathway that is our discovery,.This interaction

between beta

cells and alpha cells is crucial for normal blood sugar regulation. " The

discovery also means that when the beta cells fail to produce insulin

properly,

as is the case in diabetes, the alpha cells' signal path is also

blocked, which upsets

the glucose balance even more. " Maybe we'll be able to achieve better

blood sugar regulation in DM patients if we target more the

glucagon/glutamate rather

than just the insulin " , he says Cell Metabolism, 4 June 2008.

19.%% MNTD -Researchers Identify Gene That Regulates Glucose Levels 4

Jun 2008 a collaborative study has identified a gene that regulates

glucose levels. " Elevations

of blood glucose are diagnostic of DM. This finding demonstrates there

are gene variants that are important for day-to-day regulation of

glucose, but they

do not appear to play a significant role in disease risk, " says

co-senior author. The study determined that this variant is not

associated with an increased

risk for T2. " The identification of these variants increases our basic

biologic knowledge about regulation of glucose and may also be useful in

future

genetic studies to help discriminate between genetic variants that do or

do not contribute to disease susceptibility, " [5,000 participants] The

results

determined that a gene on chromosome 2 that encodes for the enzyme

glucose-6-phosphatase catalytic 2 (G6PC2) is associated with fasting

glucose levels.

" Genetic variation

of G6PC2 may be responsible for reducing insulin secretion and causing

the glucose concentration to increase. " ..the finding points to the

importance of

studying not just diseases like DM, but also the regulation of

phenotypes like blood glucose. " Genetics is identifying a whole new set

of genes, proteins

and pathways that are related to diabetes and blood sugar control. Our

next challenge is to figure out

how these genes work, " he says Also Appears In: Genetics,

20.%% MW - Hemoglobin A1C Levels Strongly Linked to Subsequent Mortality

in Diabetes 6/9/08 - Hemoglobin A1C (A1C) levels are strongly associated

with

subsequent mortality in both men and women without a previous diabetes

diagnosis, according to the results of the largest study to date of A1C

levels and

subsequent mortality risk. " Only a few prospective studies have examined

the associations between A1C among subjects initially free of DM

subsequent risk

of mortality, " write the researchers. A1C levels have also been

associated with mortality in patients with T1DM and nondiabetic chronic

kidney disease

and with incident cardiovascular disease. " [ 47,904 participants] For

participants without a previous diagnosis DM, HRs for all-cause

mortality steadily

increased from the A1C reference category to the highest category (

7.0%) In addition, A1C was associated with mortality from circulatory,

endocrine, nutritional,

metabolic, and immune diseases as well as from other and unknown causes.

" It confirms previous findings that A1C levels are strongly associated

with subsequent

mortality in both men and women without a prior diabetes diagnosis. "

21.%% MW - Liraglutide Effectively Controls Glucose, Reduces Weight in

Type 2 Diabetes June 9, 2008 ADA 68th2008 - A year-long study at more

than 100

centers has shown that liraglutide achieves better blood glucosecontrol

and body weight reduction than glimepiride for patients with T2DM. Both

drugs

were given once daily as monotherapy. Lead investigator said " In this

case we've looked at 2 different methods of stimulating beta cell

insulin secretion:

the standard method, which uses sulfonylurea [glimepiride], vs the new

glucagon-like peptide (GLP)-1 receptor agonist stimulation. A different

mechanism, and that gives you different responses, " [746 subjects with

T2; randomized,

double-blind trial;mean baseline HbA

1c in all 3 groups was 8.2%.] The 1.8-mg dose of liraglutide was more

effective than the 1.2-mg dose. The ADA HbA1c target of less than 7.0%

was reached

by 51% of patients in the 1.8-mg group, 43%

in the 1.2-mg group, and 28% in the glimepiride group.Fasting plasma

glucose (FPG) levels were significantly reduced for each liraglutide

group compared with the glimepiride group.A significant decrease in body

weight occurred in both liraglutide groups " All of the GLP-1 drugs tend

to retard

gastric emptying and appear to have a direct

effect on appetite,..also the absence of hypoglycemia may eliminate some

of the food-seeking behavior that you see. There were no reports of

major hypoglycemic

events in liraglutide-treated patients,

and the occurrence of minor hypoglycemia was significantly less with

liraglutide than with glimepiride. " [This treatment] preserves the

normal natural

coupling between the stimulus - glucose levels - and the secretion of

insulin. It does not work on the insulin-secretion

mechanism directly. It works on an amplifier side channel, " he

explained. " We're dialing up, or down, the response to a change in

blood glucose, but

we're not causing a change spontaneously... " Liraglutide is an instant

drug. It's once a day. It uses one of nature's tricks, it binds to

albumen, the

main protein in plasma, and that's why it lasts such a long time, "

Abbreviations: DM - diabetes Mellitus;T1DM - type 1 diabetes mellitus

T2DM - type 2; BP - blood pressure; MI [myocardial infarction or heart

attack] ;HTN

- hypertension; ADA - Amer Diabetes Asso; AFB - Amer Foundation for the

Blind ; FDA Federal Drug Administration; JH - s Hopkins ; MW

Medscape Web MD;

NIH - National Institutes of Health; VA - Veterans Administration. MNTD-

Medical News Today

Definitions - Dorlands 31st Ed and Google. 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 Coordinator The Health Library at

Vista Center

contact above e-mail or thl@...