Issue 179 by yaosaigeng


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(This Newsletter is not affiliated with the American Diabetes Association)
The Newsletter for Professionals in Diabetes Care

October 29, Issue #179

From the Editor’ Desk:
Last week Steve Freed, Publisher, and I were at the National Community Pharmacist Association
Annual Conference in Seattle. We were just in time to see the record for the most rain in one day in
Seattle. Even though our sightseeing of the city was dampened, we got to see plenty of what was going
on with Diabetes and Pharmacists.

The conference started out with 2 programs, Diabetes Care Certificate Program and Therapeutic
Foot Care Certificate Program. Each of these programs gave the over 300 pharmacists who attended
important knowledge to help all diabetes patients. The diabetes program covered such topics as insulin
pattern management; patient assessments; nutrition, exercise, and sick-day planning; insulin
administration devices, blood glucose monitoring and management. While the foot care program
delivered information on anatomy of the foot; common foot complications and treatment options;
patient evaluation; selection, measurement, and fitting of shoes, inserts, and custom footwear casting.
This training has allowed your local pharmacist to become a spot to refer your patients to. We will soon
have a list of the certified pharmacists for you to send patients to.

While we were in Seattle we had a chance to meet with Dr. Paul Chous. Paul is an optometrist who has
had type 1 diabetes since 1968 and sees only diabetes patients in his practice. Paul has recently
completed a book on Diabetic Eye Disease. Our discussions revealed how little most of us know about
Dilated Eye Exams and the medicines used for dilation. This week we have a stellar summary of Dilated
Eye Exams from Dr. Chous

Starting next week, we will be featuring excerpts from his new book: Diabetic Eye Disease: “Lessons from
a Diabetic Eye Doctor: How to Avoid Blindness and Get Great Eye Care”Keith Campell, RPh, CDE has said “this is
the most informative book on diabetes eye care I have ever read”.

If you want to determine if you are at the forefront of patient care, judge your practice by the standards
discussed by Dr. Timothy S. Hollingshead, in his feature Are We There Yet? After reading this I was
able to see ways to make my practice more effective and professionally rewarding, I am sure you will
benefit also.

This week’ overview:
Item#4: Grafts Help Heal Diabetic Foot Ulcers
Item #8: Pancreatic Beta-cell Loss and Preservation in Type 2 Diabetes
Item #11 Metformin Treatment Leads to Increased Homocysteine, Decreased Vitamin B12 and Folate in
Type 2 Diabetes Patients*

Check out this weeks “  Test Your Knowledge”question. If you get it right on the first try, you will be
entered into a special drawing for your choice of 3 special prizes.

Dave Joffe, Editor-in-Chief

Coca-Cola to Launch Cholesterol-Reducing Orange Juice
See Item #14
Betagenon & Astrazeneca sign collaboration for therapies for type 2 diabetes
 Betagenon AB a Swedish biotechnology company focused on the discovery and early stage development of drug
therapies for treatment of type 2 diabetes. The long-term goal of the collaboration is to enable AstraZeneca to develop
new drugs that restore ability of the beta cells to meet the increased demand of insulin in type 2 diabetics. Betagenon
has access to unique in vivo models in which the beta cells fail to produce and/or secrete enough insulin in a regulate
manner, and which develop diabetes that closely mimics type 2 diabetes in man. These models will be used in the
collaboration to develop a superior drug discovery platform. The terms of the deal were not disclosed.

Studies: Insulin Pump infusion device : If we sent you an Email, please respond by
Friday or we will have to replace you in this study— Please no new participants
Coming soon— a new device to carry your glucose monitor— will it increase
compliance- We will need your help to find out.
If you were selected for the neuropathy study you should have your product by
now— if not then let me know
Tools for your Practice: $25 dollars off coupon for your patients who use Novolog
Click here and we will send you one
 New Product: Pendragon Medical presents first non-invasive “sensorwristwatch”Pendra, to monitor
and predict glucose levels.

                Paris. August 25, 2003 – Swiss medical technology company Pendragon Medical
                Ltd. presented its device Pendra® at the IDF conference. Pendra® continuously
                monitors the blood glucose level every minute without the need for a blood
                sample. It also contains alarm functions to predict critical Hypoglycemia levels.
                Having been approved by the appropriate European regulatory body in May 2003
                as a Type II b Medical Device, Pendra® will be launched in early 2004 in the first
five European markets. More info, click here: Pendra®


This newsletter is the condensed version. If you would like to see the full newsletter go to

This Week’ Items:

1. Cholesterol Drugs Work Best in Evening
Click Here
2. Depression Improves With Weight Loss
 Click Here
3. Good Diabetes Control Benefits Last Many Years
Click Here
4. Grafts Help Heal Diabetic Foot Ulcers
Click Here
5. Younger Adults With Type 2 Diabetes 14 Times More Likely to Suffer Heart Attacks*
Click Here
6. Poorly Controlled Diabetes Can Lead To Liver Problems
Click Here
7. Extended Delay in Progression of Diabetic Nephropathy Seen in Patients who Received Intensive
Diabetes Treatment
Click Here
8. Pancreatic Beta-cell Loss and Preservation in Type 2 Diabetes
Click Here
9 Type 2 Diabetes, Cardiovascular Risk, and The Link to Insulin Resistance
Click Here
10. Cause of Diabetes Affects Response to Treatment
Click Here
11. Metformin Treatment Leads to Increased Homocysteine, Decreased Vitamin B12 and Folate in Type
2 Diabetes Patients*
Click Here
12. Diabetes Can Cause Breast Lumps*
Click Here
13. Steps for your Health
Click Here
14. Coca-Cola to Launch Cholesterol-Reducing Orange Juice
Click Here
15. How to Eat More and Still Lose Weight*
Click Here

ITEMS For The Week:

Item 1
Cholesterol Drugs Work Best in Evening
New research confirms at least one common statin and probably most off the statins may be most effective when taken
at night as opposed to the morning.

Researchers from England studied 83 patients who were taking either 10 milligrams or 20 milligrams of simvastatin,
otherwise known as Zocor. They were taking the drug for primary or secondary prevention of coronary heat disease,
stroke, or peripheral vascular disease.

Patients were randomized to take the drug in the mornings or in the evenings. Fifty-seven patients completed the trial.
Most manufacturers of statins recommend the drugs be taken at night, but doubt has been cast on whether that is the
best time.

Researchers found when patients switched from taking their nighttime pill to the morning, there were significant
increases in total cholesterol and LDL, or the bad, cholesterol.
Authors of the study write, “ Simvastatin is probably best taken at night because concentrations of total cholesterol and
of low density lipoprotein are significantly greater when it is taken in the morning. This finding has implications for
compliance in preventing coronary heart disease.”
British Medical Journal, 2003;327:788


FACT: Obesity doubles for women, more than doubles for men since 1985
The prevalence of obesity among Canadian women has doubled over the last 15 years, new data show. For men it has
more than doubled. The fat isn't just creeping up on Canadians, it's galloping.
Canadian men continue to be fatter than women on average, but women are catching up. Forty per cent of men were
overweight in 2001. From 1985 to 2001, the percentage of women defined as overweight increased to 26 per cent from
19 per cent. Health Canada guidelines define overweight as a body mass index of 25.

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Item 2
Depression Improves With Weight Loss
Severe obesity is associated with a high risk for depression, especially those with diabetes and among young women
with poor body image. However, depression improves with loss of weight.
Dr. John B. Dixon and colleagues from Monash University, in Melbourne, Australia, note that the association between
depression and severe obesity is unclear. In a study reported in the September 22nd issue of the Archives of Internal
Medicine, they examined depression before and after gastric-restrictive weight loss surgery.

The researchers report that 487 consecutive patients completed Beck Depression Inventory (BDI) questionnaires before
and at yearly intervals after surgery, to follow changes with time. The team used paired preoperative and 1-year
postoperative scores from 262 patients to identify predictors of change in BDI scores.
The mean preoperative BDI score for the 487 patients was 17.7. Younger age, female sex, a history of depression, poor
physical function, and poor body image were independently associated with higher depression scores.

"Body mass index, weight, waist, hip, and neck circumference, and waist-hip ratio did not predict higher BDI scores,"
Dr. Dixon and colleagues found. Also, fasting plasma glucose and insulin levels and calculated insulin resistance index
were not predictive of BDI scores.

The investigators observed an association between weight loss and a significant and sustained fall in BDI scores. The
mean scores at 1 and 4 years after surgery were 7.8 and 9.6, respectively.

Female sex, younger age, a greater percentage of excess weight loss, and a poorer preoperative appearance evaluation
were independently associated with greater falls in BDI score at 1 year. There was a significant correlation between fall
in BDI score and improved appearance evaluation (p < 0.001).

Dr. Dixon and colleagues conclude that the findings support the notion of depression as a comorbidity of obesity, and
that those most affected by depression derive the greatest mental health benefit from bariatric procedures. Arch Intern
Med 2003;163:2058-2065.
Did you know: The Diabetes Education Society offers online accredited continuing education programs. Got an
hour, take a course. Visit, take the free sample course and review the Course Catalog. Then
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(800) 659-5808.

Item 3
Good Diabetes Control Benefits Last Many Years
In diabetics, intensive control of blood sugar levels seems to slow the progression of kidney disease many years after
such control has ended, new research shows.
Started in 1981, the Diabetes Control and Complications Trial (DCCT) compared the benefits of intensive and
conventional therapy in 1441 type 1 (i.e., insulin-dependent) diabetics. The intensive therapy consisted of at least three
daily insulin injections with frequent sugar monitoring. In contrast, conventional therapy consisted of no more than two
daily injections and one blood or urine sugar test.

The results from DCCT revealed that intensive therapy was better than conventional therapy at controlling sugar levels
and at slowing the progression of kidney disease. After DCCT ended in 1989, patients in the conventional group were
offered intensive therapy supervised by their own physicians, while those in the treatment group were encouraged to
continue the intensive therapy.

The current study, known as the Epidemiology of Diabetes Interventions and Complications (EDIC) study, represents
eight years of additional follow-up for former DCCT participants. The results are reported in the Journal of the American
Medical Association.

Dr. David M. Nathan, from Massachusetts General Hospital stated that, "Over time, the glycemic levels of the former
control group began to drop, while those of the former intervention group rose, so that during the EDIC study the
levels in each group were no longer substantially different."

Interestingly, although each group now had similar levels, a kidney benefit was still seen in the former intensive
therapy group, Nathan noted.

The new findings complement those reported in 2000, which showed that intensive therapy also provides a persistent
reduction in the risk of diabetic eye disease.

In addition to slowing the progression of kidney disease, intensive therapy reduced the risk of high blood pressure, the
authors point out.

"The take-home message is that early, intensive intervention is very important," Nathan emphasized. "The earlier that
patients can intervene to (control blood sugar) the better effect they're going to get and the better long-term outcomes
they're going to have." Journal of the American Medical Association, October 22/29, 2003.
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Item 4
Grafts Help Heal Diabetic Foot Ulcers
Now, new research has shown that grafts derived from a patient's skin cells can help some diabetic ulcers heal faster,
These findings come from a study, published in the current issue of Diabetes Care, that compared such grafts with
standard gauze dressings in 79 diabetics with ulcers on the top or bottom of their feet.

The grafts were created by taking skin samples from each patient and then growing the skin cells in a lab to form a
sheet that could be used to cover the patient's ulcer.

All of the patients had their ulcers cleaned thoroughly, received antibiotics if needed, and were given casts to relieve
pressure if the ulcer was on the bottom of the foot, lead author Dr. Carlo Caravaggi, from the Ospedale di
Abbiategrasso in Milan, and colleagues note.

Grafting was safe and well tolerated, the authors report. Among patients with ulcers on the top of the foot, 67 percent
of grafted ulcers healed compared with just 31 percent of gauze-treated ulcers. Among patients with ulcers on the
bottom of the foot, however, about 52 percent of ulcers healed regardless of treatment type.

Although grafting appears to be more effective for top-of-foot ulcers, the authors note that it may still be of use for
bottom-foot ulcers, especially when the optimal pressure-relieving cast cannot be used.

Diabetes Care, October 2003.

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DID YOU KNOW:                  Did you know: Prandin and Lopid Interact: Finnish researchers have discovered that 2
drugs commonly used by people with diabetes interact. These drugs are repaglinide (Pranding and gemfibrozil
(Lopid). When the 2 are taken together, repaglinide’ blood sugar-lowering effects become stronger and last longer.
As a result, severe hypoglycemia (too-low blood sugar levels) can occur. Announced results in March 2003
Item 5
Younger Adults With Type 2 Diabetes 14 Times More Likely to Suffer Heart Attacks
Young adults, age 18-44, who get type 2 diabetes are 14 times more likely to suffer a heart attack and up to 30 times
more likely to have a stroke than their peers without diabetes Stroke Risk Increased Up to 30 Times.

Young women account for almost all the increase in heart attack risk, while young men are twice as likely to suffer a
stroke as young women. The study by two researchers at Kaiser Permanente's Center for Health Research (CHR),
funded by the American Diabetes Association, will appear in the November issue of Diabetes Care.

"This means that huge numbers of people are going to get heart disease, heart attacks and strokes years, sometimes
even decades, before they should," says Teresa Hillier, MD, an endocrinologist and investigator at CHR and lead author
of the article. "Young adults are increasingly likely to be overweight and diabetic. Our study is the first to look at the
health outcomes of young adults who get diabetes, and the greatly increased risks of heart attack and stroke are very
To conduct the study, Dr. Hillier and her colleague used electronic medical records to identify 7,844 individuals who
were newly diagnosed with type 2 diabetes from 1996 to 1998 (1,600 were under age 45 and 6,244 were 45 or older).
Other findings included the following:

-- People with early-onset type 2 diabetes are 80% more likely to need insulin therapy within two years than people
with usual-onset type 2 diabetes.

-- People with early-onset diabetes were significantly more obese on average than people with usual-onset diabetes
(BMI 37 vs. 33).(1)

-- Younger adults with diabetes were more than twice as likely as older adults with diabetes to develop any heart
disease compared to their peers without diabetes.

"We are clearly facing a very serious public health problem," says Dr. Hillier. "The CDC is predicting that at least one
out of every three Americans born after 2000 are going to develop diabetes, and the trend we've seen of diabetes
affecting young adults -- and even teenagers -- is going to continue. Young women with diabetes who have a heart
attack are more likely to die from it in the hospital than men, so our finding that young women with diabetes are 14
times more likely to have a heart attack is especially alarming."

(1) Note: a 5'10" man with a BMI of 37 weighs 258 pounds, a 5'5" woman with a BMI of 37 weighs 222 pounds.
Source: Kaiser Permanente

Item 6
Poorly Controlled Diabetes Can Lead To Liver Problems
A case of poorly controlled insulin-dependent diabetes led to liver glycogen deposition and abnormal liver enzymes.
That, from researchers at the 68th Annual Scientific Meeting of the American College of Gastroenterology.

Seth D. Hoffman, MD, and colleagues, Loyola University Medical Center, Maywood, Illinois, United States, discussed the
case of a 22-year-old woman who presented to the emergency department with a 1 month history of increasing
abdominal girth, right upper quadrant pain and a 13.5 kg weight gain. She had been diagnosed with insulin-dependent
diabetes 13 months previously and hospitalised with diabetic ketoacidosis five times in 1 year.

Physical examination revealed anasarca and a mildly tender liver palpable 7 to 8 cm below her midcostal margin.
Laboratory tests demonstrated high serum glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase
(ALT), and normal alkaline phosphatase and bilirubin levels.

Computed tomographic scan of the liver revealed an enlarged liver, and liver biopsy was performed. Biopsy showed
findings consistent with the presence of glycogen and indicated diffuse glycogenosis.

The patient's liver enzymes, oedema and abdominal pain markedly improved after 7 days of tight glycaemic control.

Dr. Hoffman said that in cases of abnormal liver enzymes without hepatitis, other causes must be ruled out and a
normal workup carried out to identify abnormal liver function.

He thinks the present case of liver glycogenosis is uncommon, though 8 to 10 cases have been reported in patients of
all ages with poorly controlled diabetes. He believes that when tight glycaemic control was initiated, the glycogen
deposits were mobilised by insulin.

"Get the diabetes under control," he said, "and the problem resolves."

Dr. Hoffman recommends considering the diagnosis of liver glycogenosis whenever a poorly controlled diabetes patient
has liver enzyme abnormalities.

Eye Disease: Lessons from a Diabetic Eye Doctor: How to Avoid Blindness and Get Great Eye Care
Book Description: Diabetes affects every part of the eye, not just the retina. Presenting critical information about
seven different kinds of diabetic eye disease as well as important steps all diabetics must take to preserve vision, Dr.
Chous clearly and comprehensively guides you through the fundamentals of good diabetes management and great eye
care. Written by an eye doctor, diabetes educator and patient advocate, this book is dedicated to helping you or
someone you love avoid blindness and other complications by taking charge of your diabetes.
More Info:

Item 7
Extended Delay in Progression of Diabetic Nephropathy Seen in Patients who Received
Intensive Diabetes Treatment
Intensive diabetes treatment to sustain near-normal glycemia has an extended benefit of delaying the progression of
diabetic nephropathy.
That, according to the most recent findings of the Epidemiology of Diabetes Interventions and Complications (EDIC)

The EDIC trial, which originated in 1993 after the closeout of the Diabetes Control and Complications Trial (DCCT),
followed 1349 participants of DCCT for the development of microalbuminuria, clinical-grade albuminuria, hypertension,
or an increase in their serum creatinine level. "Follow-up of the DCCT cohort for 8 additional years in the EDIC study
has shown persistent differences in nephropathic outcomes between the former intensive-treatment and conventional-
treatment groups," writes David M. Nathan, MD, Massachusetts General Hospital, Boston, United States, and members
of the combined DCCT/EDIC Research Group. They report results by intention-to-treat analyses of 676 patients in the
original DCCT intensive treatment group and 673 patients in the original DCCT conventional treatment group.

During the EDIC study, new cases of microalbuminuria occurred in 6.8% of the DCCT intensive group compared with
15.8% of the DCCT conventional treatment group. New cases of clinical albuminuria occurred in 1.4% of the DCCT
intensive group compared with 9.4% of the conventional DCCT group.

The investigators note there was no difference in the prevalence of hypertension between groups at the end of the
DCCT (11% for both) but by year 8 of the EDIC follow up they report the prevalence of hypertension was 29.9% in the
intensive group but was 40.3% in the conventional group.

The DCCT/EDIC Research Group found that, since the DCCT baseline through year 8 of the EDIC trial, a doubling of
serum creatinine level occurred in 10 of the intensive treatment group and in 17 of the conventional treatment group.
At EDIC year 8, only 5 patients in the intensive versus 19 in the conventional group reached serum creatinine levels of
2 mg/dL or greater and 4 of the patients in the intensive group compared with 7 in the conventional group required
dialysis and/or kidney transplantation.

"The current results reaffirm that intensive treatment of type 1 diabetes should be initiated as early as is safely possible
in order to provide strong and durable protection from the development and progression of diabetic microvascular
disease," the authors conclude adding, "the protection initiated by intensive treatment appears to outlast the intensive
treatment itself, although the duration of the effect remains to be determined." JAMA 2003;290:2159-2167

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Item 8
Pancreatic Beta-cell Loss and Preservation in Type 2 Diabetes.
Current clinical management of type 2 diabetes is focused on treatment of the signs and symptoms of late-stage
disease rather than addressing potential underlying causes.
In most individuals, the need to respond to progressive states of insulin resistance is met by increasing insulin
production. For insulin-resistant patients, however, the balance between insulin supply and demand may fail from the
progressive loss of pancreatic beta-cell function, eventually leading to type 2 diabetes mellitus.
The aim of this review was to discuss the current concepts underlying potential pancreatic beta-cell failure in the
progression toward type 2 diabetes and therapies that may alter the process.

Data included in this review were identified through a MEDLINE search for articles published from 1966 to April 2003.
Search terms used were beta cell, diabetes, insulin resistance, obesity, cardiovascular disease, thiazolidinediones, and

Evidence of the progressive loss of beta-cell function may include altered conversion of proinsulin to insulin, changes in
pulsed and oscillatory insulin secretion, and quantitative reductions in insulin release. Potential underlying mechanisms
are glucose toxicity, lipotoxicity, poor tolerance of increased secretory demand, and a reduction in beta-cell mass.

CONCLUSION: Current clinical management of type 2 diabetes is focused on treatment of the signs and symptoms of
late-stage disease rather than addressing potential underlying causes, which may be amenable to currently available
therapies, based on a broad understanding of existing data, practice experience, and rational speculation. Clin Ther.
2003;25 Suppl B:B32-46.
FACT: IRS reconsiders blood glucose meters: Because only 6 percent of taxpayers claim medical expenses on
their tax returns, probably due to the fact you can only claim medical expenses that exceed 7.5 percent of their
adjusted gross income. But on May 15th the Internal Revenue Service made it a bit easier for those with diabetes to
reach the cutoff mark of 7.5%. On a May 15, 2003 ruling, IrRS determined that this limitation will no longer apply to
other nonprescription medical care items such as bandages, crutches, and blood sugar checking kits and equipment.
This means that blood glucose meters and strips are now an allowable medical expense. So if you claim medical
expenses on your taxes, don’ forget to include the money spent on your supplies come next April 15th.

Item 9
Type 2 Diabetes, Cardiovascular Risk, and The Link to Insulin Resistance
Early data suggest that, in addition to reducing hyperglycemia, pioglitazone and rosiglitazone effect changes in the
dyslipidemic profile, hemodynamics, vascular inflammation, and endothelial functioning of patients with type 2 diabetes

Patients with type 2 diabetes mellitus frequently have coexistent dyslipidemia, hypertension, and obesity, and are at
risk for microvascular and macrovascular disease complications such as myocardial infarction, stroke, retinopathy, and
microalbuminuria. To optimize cardiovascular health outcomes for patients with type 2 diabetes, strategies to reduce
the risks of microvascular and macrovascular disease are needed in clinical practice.
This article provides an overview of the cardiovascular risk profile of patients with type 2 diabetes and discusses the
cardiovascular consequences of use of the thiazolidinediones (insulin-sensitizing agents) in the treatment of type 2

A literature search of MEDLINE/PubMed was performed to identify relevant articles published from 1966 to April 2003.
Search terms used were diabetes, cardiovascular disease, atherosclerosis, dyslipidemia, obesity, hypertension, blood
pressure, hyperglycemia, inflammation, C-reactive protein, fibrinolysis, plasminogen activator inhibitor type-1,
microalbuminuria, thiazolidinediones, safety, hepatotoxicity, and edema. Bibliographies within the identified articles
were also evaluated for additional relevant articles and information.

Recommendations for cardiovascular risk reduction through preventive and therapeutic strategies that target the
symptoms of insulin resistance may reduce the microvascular and macrovascular sequelae of diabetes and ameliorate
the impact of other components of the metabolic syndrome, including hypertension, hyperglycemia, and obesity. In this
regard, thiazolidinediones are promising therapies.

CONCLUSIONS: Early data suggest that, in addition to reducing hyperglycemia, pioglitazone and rosiglitazone effect
changes in the dyslipidemic profile, hemodynamics, vascular inflammation, and endothelial functioning of patients with
type 2 diabetes. Additional research is needed to further distinguish the cardiovascular benefits of these drugs. Clin
Ther. 2003;25 Suppl B:B4-31

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Item 10
Cause of Diabetes Affects Response to Treatment
Findings have important implications for patient management and selection of treatment.
Individuals with maturity-onset diabetes of the young caused by heterozygous mutations in the hepatocyte nuclear
factor HNF-1a gene have a greater response to sulphonylurea than do patients with type 2 diabetes according to the
findings from a randomised crossover trial.

Ewan R. Pearson, MA, of Peninsula Medical School, Exeter, United Kingdom, and colleagues compared the responses to
the sulphonylurea gliclazide and the biguanide metformin in 18 patients with HNF-1a diabetes and another 18 patients
with type 2 diabetes who were matched for body-mass index (BMI) and fasting plasma glucose.

Patients received 500 mg daily metformin for 1 week, increased to 500 mg twice daily for 1 week then to 1 g twice
daily for 4 weeks or 40 mg daily gliclazide for 1 week, increased to 40 mg twice daily for 1 week then to 80 mg twice
daily for 4 weeks. The groups had a 1-week wash out period before crossing over from one drug regimen to the other.
Patients in the type 2 group had diabetes for a mean duration of 4.8 years and were a mean age of 66 years while
those in the HNF-1a group had diabetes for a mean duration of 18.3 years and were a mean age of 44 years.

The researchers found that patients with HNF-1a diabetes had a 5.2-fold greater response to gliclazide than to
metformin. Among this group the fasting plasma glucose reduction was 4.7 mmol/L for gliclazide compared with 0.9
mmol/L for metformin. Conversely, the patients with type 2 diabetes showed no difference in response to gliclazide and

When compared with the type 2 diabetes group, the HNF-1a group had a 3.9-fold greater response to gliclazide while
the response to metformin was similar in the 2 groups.

Fructosamine assay testing in the patient groups during the last 2 to 3 weeks of taking each drug revealed that
fructosamine was 136 micromol/L lower in the HNF-1a group while taking gliclazide compared with metformin. In the
type 2 diabetes group the fructosamine was 23 micromol/L higher while on gliclazide compared with metformin. The
investigators also noted that the HNF-1a group "had a strong insulin secretory response to intravenous tolbutamide
despite a small response to intravenous glucose, and were more insulin sensitive than those with type 2 diabetes."

The researchers conclude, "the cause of diabetes affects the response to treatment." They suggest that these findings
have important implications for patient management.
Lancet 2003;362:1275-81.
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Item 11
Metformin Treatment Leads to Increased Homocysteine, Decreased Vitamin B12 and Folate in
Type 2 Diabetes Patients
Metformin treatment leads to an increase in homocysteine levels in patients with type 2 diabetes who take insulin.
Adding B6, folic acid and B12 to treatment regimen, might lower homocysteine levels and reduce the risk of CVD.
This comes from a recent report from Bethesda General Hospital, Hoogeveen, Netherlands.

Homocysteine is a sulphur-containing amino acid that has recently been recognised as an independent potential risk
factor for cardiovascular disease in patients with type 2 diabetes. Homocysteine requires folate and vitamin B12 to be
properly metabolised, and serum vitamin B12 levels are known to decrease during metformin treatment. However, the
effect of metformin on homocysteine levels was unclear based on previous studies.

To address this concern, investigators led by M.G. Wulffele performed a placebo-controlled randomised trial to examine
the effects of metformin treatment on serum levels of homocysteine, vitamin B12 and folate in type 2 diabetics.

The patients (N=390) were randomised to receive either metformin (mean dose, 2163 mg/day) or placebo in addition
to insulin for a period of 16 weeks. Among the patients who completed the study (n=353), 171 received metformin
(mean age, 63.2 ± 9.8 years; 95 females) and 182 received placebo (mean age, 58.9 ± 11.1 years, 91 females).

The researchers found that, compared with placebo, metformin was associated with an increase in serum homocysteine
levels (4% [0.2 to 8 µmol L-1]; P=0.039), and decreases in vitamin B12 (-14% [-4.2 to -24 pmol L-1]; P<0.0001) and
folate (-7% [-1.4 to -13 nmol L-1]; P=0.024). In addition, they used structural equation modelling to demonstrate that
metformin therapy did not affect homocysteine directly. Rather, the increase in homocysteine was an indirect effect
mediated by direct effects on folate and vitamin B12.

The researchers comment that, "the clinical significance of such an increase [in homocysteine] is not yet clear but may
not be negligible." In support of this idea, they note a recent analysis demonstrating that a persistent increase in serum
homocysteine of 3 µmol L-1 was associated with an increased risk of coronary heart disease and stroke in nondiabetic
individuals. "There is evidence that such risk increases may be greater amongst diabetic individuals," they add.
J Intern Med 2003 Nov;254:5:455-463

Did YOU KNOW:              Caffeine Shown to Lower Insulin Sensitivity
Data from a study in Feb 2002 Diabetes Care showed that caffeine decreases insulin sensitivity by 15%
in people without diabetes. But it was noted that exercise helps to reduce caffeine-induced insulin
resistance. It was concluded that exercise reduces the detrimental effects of caffeine on insulin action in

Item 12
Diabetes Can Cause Breast Lumps
FINDING A LUMP in your breast can be terrifying and your first thought may be that it is Cancer! Did you know that
diabetes could be the cause?

But breast lumps have many causes. One surprising cause that’ little known— even among doctors— is diabetes and it
is harmless.

Diabetes can cause dense fibrous lumps in the breasts. This condition is called “scierosing lymphocytic lobulitis”or
“diabetic mastopathy. It usually occurs in people who have an autoimmune disease (one in which the immune system
attacks the body’ own tissues).

The typical person with diabetic mastopathy is a premenopausal woman with type 1 and complications. However; men
can get mastopathy, too. So can people wit.h type 2 diabetes and people without any known autoimmune condition.

A person with diabetic mastopathy has one or more hard lumps in one or both breasts. The lumps are not tender and
tend to be irregularly shaped.

If you find a new lump in your breast, you should see a doctor right away. Don’ assume the lump is diabetic
mastopathy, even if you have had diabetic mastopathy before. Cancer can also start as a hard lump. so each new lump
requires testing.

The first test would be a mammogram or an ultrasound scan. If your doctor can’ make a diagnosis after that, tissue
needs to be examined under the microscope. Sometimes, cells and fluid can be removed from the lump with a fine
needle. But it can be difficult to pierce the dense, scarlike tissue of a diabetic mastopathy lump with a needle. So the
doctor may need to surgically remove part or all of the lump and examine it in the lab to make a diagnosis. After a
lump is removed, it often comes back. The number and size of lumps tends to increase as people get older

Diabetic mastopathy lumps are harmless. They do not turn into cancer or increase cancer risk.. However, lumps can be
uncomfortable if several occur in one breast. In that case, the lumps may be removed. You should know about diabetic
mastopathy because many doctors don’ The disease was newly discovered in 1984 and is uncommon. In a case
reported in Diabetes Care in 1998, surgeons removed both of a woman’ breasts because cancer was suspected; the
woman turned out to have diabetic mastopathy. If you have type 1 diabetes and develop a breast lump, ask your
doctor whether diabetic mastopathy might be the cause.
Item 13
Steps for your Health
Latest data show only 15 percent of adults over 18 exercise at least 30 minutes a day, five days a week.

In a national survey, the highest percentage of regular walkers was found among men 65 years and older. Experts are
urging more people to take it on. walk everyday for 30 minutes.”That’ right. In addition to eating low-fat meals, you
need to pound the pavement.

“ you really need is a good pair of shoes, walking improves balance and strengthens bones and muscles. So, not only
are you living longer, but the quality of those years is better.

Walking lowers your risk of diabetes, hypertension, high cholesterol, heart attack, osteoarthritis, obesity and stroke. It is
recommended you work up to walking 30 minutes a day, five days a week.

Studies have shown that you don’ even have to go it all at once. Get 10 minutes in this morning, 10 minutes in this
afternoon and 10 minutes in this evening. So, park far away. And use the stairs.

Brisk walking one mile in 15 minutes burns about the same number of calories as jogging an equal distance in eight and
a half minutes. Need another reason to walk? A recent study in the Annals of Internal Medicine shows regular exercise
among men age 50 to 90 reduced incidence of erectile dysfunction by 30 percent

If you don’ have a program to increase physical activity for your company or practice, then go to

FACT:      Diabetes Masks Signs of Carpal Tunel Syndrome
Carpal tunnel syndrome (CTS) might not be detected by standard testing methods in people with diabetes, according to
researchers in the US and Canada, who urge doctors to evaluate clinical symptoms In a study published in the March
2002 issue of Diabetes Care. Because electrodiagnostic testing often fails to detect carpal tunnel syndrome in people
with diabetes, the researchers recommend that doctors make therapeutic decisions based on symptoms of carpal tunnel
syndrome in individuals with diabetes, independent of electrodiagnostic findings.

Item 14
Coca-Cola to Launch Cholesterol-Reducing Orange Juice
Launching a cholesterol-reducing orange juice this week.
The world's largest soft drink maker will begin rolling out Minute Maid Premium Heart Wise on Monday in the United
States. It expects the drink to be widely available throughout the nation by the Thanksgiving holiday in November.

The product will contain plant sterols, an additive that has been used in cholesterol-fighting margarine and other food
products. Plant sterols have been shown to cut LDL cholesterol levels by about 10 percent when used consistently.

Coca-Cola spokesman Ray Crockett said, "People with moderately high cholesterol will find this product will help them
reduce their cholesterol significantly."

Crockett said the company had conducted a clinical trial to back up the drink's health claims and had obtained approval
from the Food and Drug Administration to market the drink. Results of the clinical test will be available next month.

Atlanta-based Coca-Cola first revealed its plans to launch Heart Wise in an interview with Beverage Digest. John Sicher,
the trade publication's editor, said the drink was on the cutting edge of a new wave of innovative beverages.

"This is real innovation in that it provides a true functional benefit," Sicher said. "It uses a beverage as a delivery
system for an ingredient that will really help people."

Consumers would have to drink two 8-ounce servings of Heart Wise per day to get the suggested daily 2 grams of
sterols needed to lower cholesterol, according to Coca-Cola. Each serving contains about 110 calories.

Diagnostic Tests for Home or Office: Total Cholesterol, Cholesterol Panel, TSH (Thyroid Test),
PSA, and A1c. More Info:
Item 15
How to Eat More and Still Lose Weight
It's the energy density of foods -- not the amount we eat or even the overall fat content -- that most contributes to
weight gain. When it comes to dieting, bigger food is better. That may be surprising to dieters who've struggled to cut
calories by eating less food
This information comes from a study presented at the annual meeting of the North American Association for the Study
of Obesity, Penn State researchers studied how eating salad before a meal could affect total calories a diner ends up

A food has a low energy density if it has few calories relative to its weight. An easy way to choose these low-energy-
dense foods is to choose "big" foods -- those that are bulked up by fiber and water. Chicken and rice soup, for instance,
has a low energy density, with just 0.5 calorie per gram. And it will be just as filling and less fattening as a similar
amount of cheese ravioli, which has 3.2 calories per gram.

Food labels don't tell you about energy density, so you have to do the math yourself to calculate calories per gram.
Foods that have up to 1.5 calories per gram are low energy dense. Foods with 1.5 to four calories per gram are
considered medium, while high-energy-dense foods have four or more.

It might seem obvious that low-energy-dense foods such as chicken soup are less fattening than the same amount of,
say, potatoes au gratin. But there are some surprises. Even a decadent-sounding cream of broccoli soup with cheese
has an energy density of just 0.8. But graham crackers, though low in fat, have a high energy density, with 4.2 calories
per gram.

Here's how to lower the energy density of your diet so you can eat more without increasing your caloric intake:

-Switch to soups: Even creamy soups and rich stews have a lower energy density than many foods.

-Add bulk: Adding vegetables to pasta or casseroles or more veggies to a salad lowers the energy density.

-Beat your food: Smoothies and shakes fill you up longer the longer they are whipped. Substitute: Switch to low-fat
dressings, cheeses and cooking oil in recipes

And the energy-density idea works with indulgence foods, as well. M&M's are considered a high-energy-dense food,
with 4.9 calories per gram. But for about the same calories of a package of M&M's, you could have a slice of chocolate
cake with frosting, at just 3.7 calories per gram, or vanilla pudding made with 2% milk, at just one calorie per gram.
And you'd be left feeling far more satisfied.

The push to focus on the energy density of foods is backed by numerous studies that show hunger tends to be satisfied
by a certain volume of food, regardless of the calorie content. In one Pennsylvania State University study, researchers
found that healthy women instinctively ate about three pounds of food a day. It didn't matter if the foods were high-
calorie or low-calorie -- the women were driven by volume, not calories. Because we are accustomed to a certain
volume of food, when we try to cut back on the amount we eat, we feel hungry -- which is the main reason diets fail.

All of this runs counter to the notion that people who are overweight are just eating too much food. Often those people
are eating normal amounts of food for their size -- they are just choosing energy-dense foods that cause them to
continue to gain weight.

To really make an impact on weight, people need to consume far more "big" foods like fruits, vegetables, salads and
soups. That can include, for instance, adding more vegetables to bulk up casseroles or other dishes to lower the overall
energy density of favorite foods. Dieters should pay attention to basic nutrition and eat a balanced diet, but they should
also work to ease high-energy-dense foods out of their diets.

The problem is that our taste buds don't always like low-energy-dense foods as much as small convenience foods like
snack chips and brownies. But new research shows there are ways to use low-energy-dense foods to help curb
consumption of more fattening foods, without having to give them up altogether.

In the study, diners were allowed to eat as much regular cheese tortellini as they wanted. One group was just given the
tortellini, while other groups were told they had to eat a serving of salad first. The salads included both high-calorie and
low-calorie dressings and cheeses, and the size varied from a 1½ cup to three cups.
Researchers found that when diners pigged out on three cups of salad with low-fat dressing, they ate 107 calories less -
- or about 12% fewer calories for the meal than when they didn't eat a first-course salad.

The first course had such low energy density that it translated into fewer calories, despite the variety effect. But be
warned, the energy density of the salad matters as well. Some diners were given a more energy-dense salad with full-
fat dressing and cheese. They ended up eating 145 calories more -- or about 17% more calories for the whole meal --
than those who ate no salad at all. ADA 2003-10-20

Pearls for Practice: " The lesson for dieters is to binge on a healthy salad or other very low-energy-
dense foods before a meal.
Quote of the Week!

“There is only one success... to be able to spend your life
in your own way...”
                                            ------- Christopher Morley
Your Friends in Diabetes Care
Steve and Dave

Have a question?
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To Enjoy low carb chocolates with no sugar and 1gm of carbohydrate:

Diagnostic Tests for Home or Office: Total Cholesterol, Lipid Panel (Total Cholesterol, LDL,
HDL & Triglycerides, PSA, Thyroid and A1c. More Info

The Diabetes Education Society offers online accredited continuing education programs. Got an hour, take a course.
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