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1. Stroke Disparities in US Regions May Be Due in Part to Diabetes Variation

(Reuters Health) Jun 27 - Regional differences in diabetes prevalence may

contribute

to the geographic disparity in stroke mortality seen in the US, independent

of hypertension. [ population- based cohort 21,959 black and white subjects

over 45years old. The team observed a significantly higher prevalence of DM

in both black and white study subjects living in the " Stroke Buckle " -- the

coastal plain region of North Carolina, South Carolina, and Georgia -

compared with the rest of the US. The same was true for black and white

study subjects

living in the Stroke Belt (remainder of NC, SC, GA, plus Alabama,

Mississippi, Tennessee, Arkansas and Louisiana), In black residents of the

Belt, variations

in socioeconomic status, particularly education and income, appeared to

explain much of the regional variations in DM the researchers report. Among

black

and white residents of the Buckle and whites in the Belt, regional

differences remained significant when controlling for socioeconomic status

and relevant

risk factors. There were no significant regional differences with regard to

diabetes awareness, treatment or control. These findings suggest that

efforts

directed at reducing diabetes in the Belt, and especially in the Buckle,

" may be an important additional interventional strategy to reduce the

disparity

in stroke mortality associated with the Stroke Belt, especially because the

combination of DM and hypertension may be more potent with regard to stroke

risk mortality as compared to hypertension alone. " Stroke 2008;39.

2.%% WebMD: FDA Urged to Toughen Diabetes Drug Tests

Expert Panel Recommends More Extensive Safety Testing of New Drugs July 3,

2008 -- Drug companies should be required to conduct stricter safety tests

before

marketing new diabetes drugs, expert advisors tell the FDA. An expert

committee has urged the agency to require companies to screen DM drugs for

heart

attack risk before they can be approved, or to require longer safety testing

after the

drugs are on the market. The move comes after Avandia , a drug for

T2DM , has come under scrutiny because of evidence it may raise heart attack

risks by as much as 40%. " We heard they wanted us to have greater certainty

and assurance before approval about the cardiovascular effects of the drugs,

and that they wanted us to ensure

that the question was ultimately answered either before approval or after

approval, " says , who directs the FDA's Office of New Drugs.

" It's

a higher level of understanding and a higher level of assurance that you've

excluded unacceptable cardiovascular risk. "

The FDA put new warnings on Avandia last year. It was allowed to stay on the

U.S. market despite calls -- including from some FDA officials -- that it

be pulled from sales. The experts' recommendations only apply to new T2

drugs. Agency officials say they will have to decide whether to require

longer

safety studies before approval,

more detailed follow-up trials once drugs are on the market, or both.

" It really will ultimately require us to look at each individual drug, " All

drugs have risks. But FDA officials have not yet determined what would

qualify

as an " unacceptable risk " for diabetes drugs. says some heart risk

could be deemed acceptable if a drug is shown to be highly beneficial. Drugs

with only " marginal " benefit likely won't be allowed on the market if

testing shows they raise cardiovascular risks, he says.

3.%% Prevention of Type 2 Diabetes Mellitus With Angiotensin

-Converting-Enzyme Inhibitors Am J Health-Syst Pharm. 2008;65(10):

7/01/2008 Summary: ACE inhibitors have established their role in

hypertension, primary and secondary prevention of cardiovascular events, and

prevention

of progression to and worsening of renal function. However, their ability to

preserve pancreatic function and prevent new-onset diabetes is also coming

to the forefront. .

Diabetes affects more than 20.8 million adults throughout the US.

90% have T2DM, and one third of persons with T2 remain undiagnosed. In

some instances, the development and appearance of diabetes-associated

complications

precede the formal diagnosis of diabetes. Various strategies for preventing

progression from impaired fasting glucose to diabetes have been evaluated,

including lifestyle modifications, biguanides, and thiozolidinediones.

Translational research implicates a correlation between angiotensin II and

progression to T2 and the potential role of angiotensin -converting-enzyme

(ACE)

.. .Conclusion: ACE inhibitors may preserve pancreatic function and prevent

new-onset DM, especially for patients who are hypertensive with impaired

glucose

tolerance. Large studies investigating the effect of ACE inhibitors on the

prevention of diabetes as a primary outcome are needed to determine the use

for this indication.

4.%% Ask the Experts about Insulin Therapy in Type 2 Diabetes

Insulin: A Last Resort? Medscape Diabetes & Endocrinology. 2008; 6/30/2008

Question - Why is insulin often considered a last resort in the treatment

of T2DM? Response from L. Pearson, MS, RN, CDE Even though the

United Kingdom Prospective Diabetes Study showed that as many as 60% of

people

with T2 eventually will need insulin to manage their blood glucose to

target, insulin is not used to its maximum benefit. Time, fear, lack of

knowledge,

and psychological resistance on the part of both the patient and the

provider all play a part. For providers, when the need to add another agent

to manage

blood glucose arises, the time involved in teaching the patient about the

new medication and the time to titrate the agent are issues. It takes longer

to teach self-administration of insulin

compared with self-administration of a pill. However, the new insulin pens

have made teaching insulin administration much easier, as have the simple

algorithms,

such as Treat-to-Target, and the once-daily titration schedule for

long-acting insulins. Concerns also arise about hypoglycemia and weight gain

in patients

who may already be overweight. Although these are valid concerns, the new

insulin analogs have significantly reduced the likelihood of hypoglycemia -

especially

nocturnal hypoglycemia -- as well as weight gain. Patients should be

educated about hypoglycemia and should also meet with a nutritionist to

adjust food

intake to reduce the likelihood of weight

gain. Psychological resistance to insulin is another reason for viewing

insulin as a last resort. In psychological insulin resistance, the patient's

wish

to " stay off the needle " is combined with provider concerns, as described

above. Often, provider and patient never even talk about these issues, and

the

result is a delay in initiating insulin to the detriment of the patient's

health. Lack of knowledge on the part of

both the patient and the provider contributes to the delay. This is a

conversation that needs to be had early on in the diagnosis of DM ,

emphasizing that

diabetes is a progressive disease. The goal is not to stay off insulin, but

rather to control the blood glucose in an effort to prevent or delay the

complications

associated with DM.

5.%% MW -High Intrahepatic Triglyceride Content a Marker of Insulin

Resistance Reuters Health Jun 27 - An international team of investigators

reports that

elevated intrahepatic triglyceride (IHTG) content is inversely correlated

with plasma insulin concentration and positively associated with impaired

insulin

action. [42 nondiabetic obese subjects] with an IHTG content ranging from

1%-46%, to

determine the relationship between IHTG and insulin action in the liver,

muscle and fat. " The ability of insulin to suppress fatty acid release from

adipose

tissue and to stimulate glucose uptake by skeletal muscle were also

inversely correlated with IHTG content. "

Multivariate analyses showed that IHTG content predicted insulin action in

liver, skeletal muscle, and adipose tissue. This was independent of BMI and

percent body fat. " Nonalcoholic fatty liver disease should be considered

part of a multi-organ system

derangement in insulin sensitivity, " they conclude. " IHTG is an important

marker of insulin resistance which is a precursor for DM. " To best manage

the

patient with elevated IHTG content, " we recommend a weight loss diet .

..Moderate weight loss, about 5% of initial body weight, markedly decreases

intrahepatic

triglyceride content. " Gastroenterology 2008;134:.

6.%% MW - Outpatient Parenteral Antimicrobial Therapy For A Diabetic Patient

With A Foot Infection June 27, 2008 Clinical Case #1: A Diabetic Patient

With A Foot Infection - A 35-year-old diabetic man decides to take up

exercising and joins a local fitness center. He begins to make progress with

endurance

using a treadmill but notes a rash between his toes. He tries to clean and

dress it and even tries some powder for tinea pedis but a sore develops and

his foot swells. It then becomes red and painful with a dull ache. After he

notices pus in the wound and has a chill, he decides to go to the emergency

department of a local hospital He says he is taking his pills for diabetes

but his blood sugars have gone up to nearly 300 the last few days and he has

been thirsty. He has no other medical problems

that he knows of. On examination, both feet have reduced pinprick sensation

but good pulses. The right foot is swollen, hot, and red with some purulent

drainage and a foul odor. Capillary refill is adequate. He is admitted to

the hospital when laboratory studies show glucose levels of 351, BUN of 35,

creatinine

of 2.6, WBC of 18,900, and hemoglobin of 12. He is started on

piperacillin/tazobactam, but response is slow with fever, continued high

blood glucose, and

persistent swelling and pain. Culture of the drainage shows

Escherichia coli and a methicillin-resistant Staphylococcus aureus (MRSA)

infection plus, eventually, a Bacteroides species (spp). Vancomycin is

added

to his antimicrobial regimen.

The odor noted on examination suggested an active anaerobe that needed

coverage, although it did not grow until late. The empiric therapy with

piperacillin/tazobactam

encompasses this spectrum, but some pathogens may be overlooked, especially

MRSA strains, which need added antimicrobial coverage with an active agent

such as vancomycin. A number of antibiotic options are available to cover

all 3 types of bacteria identified in this patient. A combination of drugs

is

often used initially, then narrowed or expanded when culture

and susceptibility information become available.

The initial choice of antibiotic was not broad enough. The patient improves

slowly over the next 5 days and tolerates the medications well with good

glucose

control once insulin is started. After a week in the hospital, he is feeling

well and bored. He keeps asking when he can go home. He is told that he will

need another week or 2 of intravenous (IV) antibiotic therapy because of

possible bone involvement. He is evaluated for outpatient parenteral

antimicrobial

therapy (OPAT). The expansion of OPAT is driven mainly by the need for cost

containment . Approximately 7.6 million individuals currently receive care

from 17,700 home care providers. The practice of administering IV

antimicrobial therapy in the home or in alternate

care settings has grown rapidly since it was first described in 1974.

The OPAT can be delivered in many different settings. Common models for OPAT

include an office or clinic, hospital-based infusion centers, emergency

departments,

visiting nurse services to the home, and patient self-administration. The

most common method of OPAT delivery in the US is a combination with a nurse

infusing a patient and then training the patient in self- administration.

Although this home-based OPAT is sometimes offered as an extension of an

infusion

center, it is often coordinated by a commercial home infusion company. Such

companies, usually organized around pharmacy services, provide a nurse and

pharmacist with training

and expertise in IV therapy, IV antibiotics, added home care needs, and

dealing with the insurance companies. Hospitals often have their own

programs or

partners to facilitate early discharge because of diagnosis-related group

(DRG) system limitations on payments. The health maintenance organization

(HMO)

structure is well suited to the provision of OPAT.Outpatient antibiotic

infusion therapy services can also be incorporated into existing operations

such

as oncology clinics, emergency departments, and even wound care. Regardless

of organizational structures, the success of OPAT programs depends on

effective communication and coordination among the team members. The team

consists of the prescribing physician, nurse specialist, pharmacist,

patient,

and often other personnel. Although the growth of OPAT has been stimulated

primarily by cost savings, a number

of other factors have made it successful. These include the development of

antimicrobial agents that can be administered once daily, technologic

advances

in vascular access and infusion devices, increased acceptance of such

therapy by both patients and healthcare personnel,. Another important factor

is that

the patient gains an improved quality of life and sense of control.

Antimicrobial resistance is also less of a problem at home than in the

hospital. Many

OPAT patients are able to go back to work or school while on

therapy.

Some patients may be started on OPAT without hospitalization but others

should not. The 2004 OPAT guidelines recommend that patients with a sepsis

syndrome

or infections such as meningitis, endocarditis, septic arthritis, or severe

pneumonia should be

hospitalized for at least the initiation of parenteral antimicrobial therapy

because of the risk that the patient's medical condition may suddenly worsen

or that hospital-based procedures may be needed.

7.%% MW - Dawning of a New Age in Type 2 Diabetes Care: An Expanding Role

for Injectable Agents June 30, 2008; [most of this presentation retained

since

there was so little research this week ] Confronting PPG With Incretins:

New Agents With Additional Glucose-Lowering Power and Beneficial Secondary

Effects

[slides with text] Pratley MD I'm going to talk about a little bit

of a different aspect about diabetes here. I'm going to talk a little bit

initially

about the importance of postprandial glucose control in T2DM. But I've got

the honor, the privilege of talking about 1 of the new areas, incretin

hormone

physiology, pharmacology, and therapeutic strategies that leverage

glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4)

inhibitors.

This is a very exciting area in diabetes, and the purpose is to help us

change how we treat diabetes. Audience Response Questions- About half of you

are

rarely prescribing DPP-4 inhibitors. And then the rest are

sometimes or frequently. So it's an interesting kind of split. Some of you

are very comfortable with these, and some haven't yet moved into how they

fit

into the treatment paradigm. .. When we talk about glucose control, most of

us focus on A1C, getting patients to goal, however we want to define that

goal.

It's important to keep in mind that the A1C is really a function of both the

fasting glucose levels, which are easy enough to measure in either our lab

or to have our patients measure them at home, but also the postprandial

glucose. And that's where it becomes a little bit more murky. many patients

spend

most of their day in the postprandial state. And I think this is something

that we often overlook. So (ADA) recommendations are to get patients to an

A1C

less than 7%, but really what we're talking about as an A1C goal for

individual patients as close to normal as possible without significant

complications.

The American

Association of Clinical Endocrinologists (AACE) has tighter A1C goals. The

postprandial glucose goals are a little bit disparate. For the ADA, a

postprandial

goal of less than 180 is the target. For AACE, we're looking for less than

140, so really a normal postprandial glucose level.

Role of Fasting Plasma Glucose and Postprandial Glucose in A1C

Slide 11. What this demonstrates is that, as your A1C levels are lower, the

relative contribution of postprandial glucose to the A1C is proportionately

higher. So at higher A1C levels above 10%, the contribution of fasting

glucose is proportionately greater. What this illustrates is that, across

the board,

we need to worry about both fasting glucose levels and postprandial glucose

levels. But as people come close to goal, it's more of a postprandial

phenomenon.

Now, in type 2 diabetes, there are a couple of fundamental abnormalities in

the control of glucose production. In the fasting state, what we see are

elevated

levels of glucose production overnight. And this is the data in nondiabetic

individuals. Postprandially, what should happen in the control group here is

endogenous glucose production should be shut off very rapidly, because

you're getting glucose in from the meal. And that happens in normal

glucose-tolerant

people but not so much in patients with T2. On the left side of the panel is

the demonstration that glucose that's

entering this system doesn't really differ between diabetic and nondiabetic

patients. It's really their ability to shut off endogenous glucose

production

that contributes to postprandial and fasting hyperglycemia in T2...We're

dealing with 2 abnormalities. One is fasting hyperglycemia that contributes

to

levels of chronic toxicity and leads to tissue lesions. These are glycation

of proteins, DNA, and other macromolecules. And at the same time, we're

dealing

with

hyperglycemia that occurs with every meal, this postprandial hyperglycemia.

And that's been associated with increases in reactive oxygen species,

oxidative

stress, and changes in endothelial function. So there's both a chronic

toxicity and an acute toxicity associated with hyperglycemia. And it's the

interaction

of those 2 phenomena that really lead to the complications of diabetes.

So which is worse for you? Fasting hyperglycemia or postprandial

hyperglycemia? Obviously, that's a loaded question.

Slide 15. But there's good evidence that postprandial hyperglycemia is a

good predictor of developing mortality. These are patients who are not yet

diagnosed

with DM. you can see across the spectrum of both fasting glucose levels,

the 2-hour glucose level was

a significant predictor of mortality. So at low fasting glucose levels and

even higher fasting glucose levels, where we consider these patients to be

diabetic,

it was the postprandial glucose, the 2-hour glucose, that was the strongest

predictor of developing mortality. And this is principally cardiovascular

mortality.

Slide 16. The same is actually also true for microvascular complications.

[study] they found that postprandial glucose levels were directly related to

retinopathy and the development of nephropathy. So it's not only

macrovascular disease that we have to worry about, but it's the

microvascular disease,

as well. Again, it's what's happening in the mealtime period with the

oxidated stress that's probably very important.

Role of Incretin - Slide 17. So we're used to thinking of T2as an

insulin-resistant state. And it's also a state where there is relative

insulin deficiency.

You don't get diabetes unless you have a defect in beta-cell function that

is inadequate to compensate for the insulin resistance. But we can add a new

player into the mix, and that is impaired incretin action. So what is the

incretin pathway? The incretin hormones are gut hormones. They're derived

from

the K cells in the proximal gut and the L cells in the distal gut in

response to a nutrient challenge. Glucose-dependent insulinotropic

polypeptide (GIP)

is derived from the K cells, GLP-1 from the L cells. The secretion of GIP

and GLP is really rapid following a meal. And both of these hormones are

secreted

as active hormones, and they're rapidly inactivated by an enzyme called

dipeptidyl peptidase-4 or DPP-4. This enzyme is protease that basically

circulates.

Now, GLP and GIP act at target tissues through specific G protein-coupled

receptors. .. GLP, as it turns out, has a number of actions that make it

very

useful to addressing hyperglycemia in T2. We talked about the acute effects

on beta-cell function, where it improves insulin secretion .. It has effects

on glucagon. So glucagon secretion from the alpha cell is increased and is

not suppressed after meals. It turns out that GLP-1 helps to suppress this

inappropriate

glucagon secretion. This contributes, in large part, to the effects of GLP-1

on lowering glucose levels. There's also evidence that GLP-1 may improve

insulin

resistance, and GLP-1 also slows gastric emptying. So, it slows glucose

influx from the gastrointestinal (GI) tract.. the net effect of GLP-1 on all

these

factors that contribute to hyperglycemia is quite potent.

Slide 23. The problem with diabetes, of course, is that the incretin effect

is dampened. First of all, the patients with diabetes have

an impairment in insulin secretion. It's blunted. It's a little bit delayed

compared to the normal glucose-tolerant people. It's also markedly less in

comparison to the intravenous challenge, so that the incretin effect, this

difference, is markedly less in patients with diabetes than it is in the

nondiabetic

subjects. ..What is very clear is that GLP-1 doesn't work as well in

patients with T2 compared to normal glucose-tolerant individuals. There is

an impairment,

a GLP-1

resistance, if you will, kind of like insulin resistance.

GLP-1 Receptor Agonists and DPP-4 Inhibitors

Slide 25. we can get around this in the same way that we get around insulin

resistance by giving insulin by enhancing GLP-1 levels. There are 2 ways to

go about this. We can give a GLP-1 receptor agonist. These are activators in

the GLP-1 receptor, like exenatide or Byetta

.. Or there are other human GLP-1 agonists, like liraglutide, which is bound

to a fatty acid group. So this is very similar to the detemir insulin that

is available. The other way to enhance GLP-1 levels is to inhibit the

breakdown of GLP-1. So this is the concept behind the DPP-4 inhibitors. A

number

of these DPP-4 inhibitors are

in development. Sitaglipitin, or Januvia,

is the one that is available on the market now.

Just to summarize the physiology of the incretins, the incretin effect is

that insulin secretion is greater with oral than with intravenous glucose.

We

think that it's largely due to the effects of GLP-1 and GIP, which are

released from the gut. Besides insulin secretion, GLP has several effects,

including

inhibiting glucagon release, slowing gastric emptying, satiety effects that

may lead to weight loss, and potentially

increasing beta-cell mass. Incretins are rapidly metabolized and inactivated

in circulation by dipeptidyl peptidase-4. And either because of impaired

secretion

of GLP-1 or impaired effect of GLP-1, the incretin effect is markedly

diminished in patients with type

2 diabetes.

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@...

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