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Diabetes in control issue 324

DIABETES IN CONTROL.com Newsletter
The Newsletter for Professionals in Diabetes Care
August 9, 2006 Issue #324

***********************************
Top Diabetes Stories:
***********************************

Early-Onset of Type 2 Diabetes Linked to Early Death*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4012
Cholesterol/Blood Pressure Combo Not Being Treated*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4011
Free Fat Acids Independently Associated With Cardiovascular Mortality*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4008
Chromium Improves Glycemic Control When Sulfonylurea Is Insufficient*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4007
Physicians Miss Signs of Chronic Kidney Disease*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4003
Compound in Dairy Products Targets Diabetes*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4002
Walking Makes a Difference in Controlling Type 2 Diabetes*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4001
Treatment Guidelines Favor Early Metformin Then Insulin for Type 2 Diabetes*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4000

*********************************
From the editor’s desk
*********************************

If you are going to AADE in LA the be sure to check out Whats Happening a at the Diabetes in Control booth #500 In
addition to the Conferences most unique giveaways we will be having raffles for all kinds of prizes.
Fill out raffle and drop off at our booth to win.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=3976

Our good friend Kevin McMahon at Diabetech has been using a unique wireless glucose meter device to transmit real-
time wireless readings automatically to a specific team of interested caregivers. He is now working with Stephen W
Ponder, M.D,
on a new clinical trial using this technology. If you want to recommend any patients or learn more go to
http://www.clinicaltrial.gov/ct/show/NCT00322478
.
There seems to be so much to learn and so little time to do it. This week we are bringing the best in new technology and
education. Working with the Network for Continuing Medical Education we are happy to bring you an MP3 or Podcast
recording of The Role of the Endocannabinoid System in the Regulation of Energy Homeostasis.
This 35 minute audio education program is moderated by Stephen N. Davis, MD, FRCP, Chair, Division of
Diabetes, Endocrinology, and Metabolism, Vanderbilt University School of Medicine
. Click here to be taken to
download either the Podcast or MP3. Register and then go to:
http://www.cvmetabolic.org/endo/20060720archive.asp

Sheri Colberg, Ph.D., FACSM shares more of her new best seller, The 7 Step Diabetes Fitness Plan. This week read:
But What If You Already Have Diabetes? You will want to print this one out and give it to your patients.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4013

dLife for August 13, 7PM ET on CNBC:
dLife explores relationships and intimacy. The dating life with diabetes; dealing with erectile dysfunction; and talking to
your partner. Plus, Super Bowl Champion Kendall Simmons on and off the field. Check your local listings for details and
tune in to dLifeTV.

We can make a difference!
***********************************
This week’s overview:
***********************************

Item #3: Reduced Blood Flow Velocity Precedes Diabetic Microvascular Disease
Item #4: Intensive Versus Moderate Statin Therapy
Item #7: Pioglitazone HCl Plus Glimepiride Tablets (Duetact) for Type 2 Diabetes
Item #8: Study Backs Pill Use for Neonatal Diabetes
Item #9: Traditional Chinese Medicine Hones Diabetes Treatment
Item #14: Diabetes Prevalence Outstrips National Growth Rate and More
Item #15: Diabetes Drug Adherence Lower for African Americans
Check out this weeks “Test Your Knowledge” question.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4014
Dave Joffe, Editor-in-Chief

==================================

NEWS FLASH:

Novo Nordisk sues Pfizer over Exubera - Danish drugmaker says Pfizer violated inhaled insulin patents.
Novo Nordisk is
alleging that the new product Exubera violates patents on inhalable insulin for diabetics. "We're trying
to protect our intellectual property," said Novo Nordisk general counsel Jim Shehan. "We've been a leader in diabetes
for 80 years. For us to keep that leadership position it's essential that our intellectual property rights are respected."
==============================
Tools for Your Practice:
Improving your Practice Manual

The Improving your Practice Manual is a step-by-step guide for initiating an improvement process
in your practice setting; it provides tools for testing and implementing changes and measuring
success. The Manual’s Improvement Sequence is processes. A seven-step process that should aid
motivated practitioners in changing their chronic care.
To read more about this tool or download it, click here.
http://www.improvingchroniccare.org/tools/pacic.htm
To download the complete Improving your Practice Manual, click here.
http://www.improvingchroniccare.org/improvement/sequencing/text version ICIC Improving Your Practice Manual.doc
============================
New Product: New Diabetes Drug:
Duetact™ - FDA Approves Once Daily Duetact™ (pioglitazone HCl and glimepiride) for the Treatment of
Type 2 Diabetes. New product offers two commonly used doses in a single tablet, giving physicians and
patients convenient dosing options. Dosing options will be 30mg/2mg. and 30mg./4mg. See this weeks Item
#7 for more information.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4006
===================================

This Week’s Items:
1. Early-Onset of Type 2 Diabetes Linked to Early Death*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4012
2. Cholesterol/Blood Pressure Combo Not Being Treated*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4011
3. Reduced Blood Flow Velocity Precedes Diabetic Microvascular Disease
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4010
4. Intensive Versus Moderate Statin Therapy
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4009
5 Free Fat Acids Independently Associated With Cardiovascular Mortality*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4008
6. Chromium Improves Glycemic Control When Sulfonylurea Is Insufficient*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4007
7. Pioglitazone HCl Plus Glimepiride Tablets (Duetact) for Type 2 Diabetes
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4006
8. Study Backs Pill Use for Neonatal Diabetes
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4005
9. Traditional Chinese Medicine Hones Diabetes Treatment
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4004
10. Physicians Miss Signs of Chronic Kidney Disease*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4003
11. Compound in Dairy Products Targets Diabetes*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4002
12. Walking Makes a Difference in Controlling Type 2 Diabetes*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4001
13. Treatment Guidelines Favor Early Metformin Then Insulin for Type 2 Diabetes*
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4000
14. Diabetes Prevalence Outstrips National Growth Rate and More
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=3999
15. Diabetes Drug Adherence Lower for African Americans
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=3998

__________________________________________________________________________
Items For The Week:
Item 1
Early-Onset of Type 2 Diabetes Linked to Early Death
The onset of type 2 diabetes before age 20 was associated with an increased risk of early kidney failure and death
between ages 25 to 55, according to researchers.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4012
In a longitudinal study of 1,856 diabetic Pima Indians, including 96 with youth-onset diabetes, the rate of end-stage renal disease was five to eight times higher than those of the same age with older-onset diabetes (ages 25 to 44), reported investigators in the July 26 issue of the Journal of the American Medical Association. Death rates for participants with early-onset diabetes were three times higher than in non-diabetics and slightly higher than among those with older-onset disease, said Meda Pavkov, M.D., Ph.D., and colleagues, of the National Institute of Diabetes and Digestive and Kidney Diseases. Among the 1,856 diabetic participants (767 male and 1,089 female), 96 had youth-onset type 2 diabetes and 1,760 had older-onset type 2 diabetes (ages 20 to 55 years). Pima Indians have extremely high rates of type 2 diabetes, and the prevalence of the disease in Pima youth had doubled between 1967 and 1998, the researchers wrote. The sex-adjusted kidney failure rate for youth-onset diabetes was 8.4 times higher than for those with onset at ages 25 to 34 years, five times higher than for onset at ages 35 to 44 years, and four times higher for onset at 45 to 54, Dr. Pavkov said. The age-sex-adjusted incidence of diabetic end-stage renal disease was 25.0 cases per 1,000 person-years in youth-onset diabetes. In older-onset (25 to 34 years), the incidence was 5.4 cases per 1,000 person-years; incidence rate ratio 4.6. Age-specific renal-failure incidence rates were higher in participants with youth-onset diabetes at all ages, the researchers reported. Between ages 25 and 55, the age-sex-adjusted death rate from natural causes was 15.4 deaths per 1,000 person-years in participants with youth-onset diabetes, and 7.3 deaths per 1,000 person-years in individuals with older-onset diabetes. To further explore differences in youth-onset and older-onset groups, death rates were compared with those of 4,189 nondiabetic participants. As expected, the nondiabetic subjects had the lowest death rates. Compared with nondiabetic participants, the death rate was 3.0 times as high in individuals with youth-onset diabetes and 1.4 times as high in individuals with older-onset diabetes. More than half of the diabetic participants died from diabetic nephropathy, cardiovascular disease, or infections, regardless of the age of onset of diabetes. By contrast, the most prevalent cause of death in the nondiabetic participants was alcoholic liver disease, the researchers reported. The longer duration of diabetes by middle age in those diagnosed younger than 20 years, and not the age at onset per se, is largely responsible for the higher rate of serious complications, Dr. Pavkov said. An equivalent duration of type 2 diabetes in a young person is as damaging to the kidneys as it is in an older person, he added. Because youth-onset type 2 diabetes leads to substantially increased complications rates and mortality in middle age, "efforts should focus on preventing or delaying the onset of diabetes, delaying the onset of diabetic nephropathy, or both," the researchers concluded. Practice Pearls
? ? When talking with young patients, obese or otherwise at risk for early-onset type 2 diabetes, advise them that they are at risk for kidney disease in middle age and that compliance with health recommendations is imperative. Journal of the American Medical Association:Pavkov ME, et al, "Effect of Youth-Onset Type 2 Diabetes Mellitus on Incidence of End-Stage Renal
Disease and Mortality in Young and Middle-aged Pima Indians,"
JAMA 2006;296:241-426.


====================================================
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Item 2
Cholesterol/Blood Pressure Combo Not Being Treated
A large number of adults with both high blood pressure and high cholesterol are not receiving treatment, a study
shows.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4011
High blood pressure, or hypertension, and high cholesterol (a.k.a., hypercholesterolemia), are two important modifiable risk factors for heart and circulatory disease. Dr. Nathan D. Wong, director of the Heart Disease Prevention Program at the University of California, Irvine, noted that, "We were surprised that, despite well-publicized guidelines and treatments available for hypertension and hypercholesterolemia, less than a third are being treated for both conditions and only one-tenth are controlled to recommended levels." Based on a study of 2,864 adult men and women, he and his colleagues estimate that roughly one-fifth (18 percent) of U.S. adults overall have both elevated cholesterol and blood pressure; however, this increases to approximately 50 percent in those 60 years of age and older. Yet, less than one-third (29 percent) of such persons with both elevated cholesterol and blood pressure are actually being treated, Wong and his colleagues report in the American Journal of Cardiology. "Worst of all," Wong said, only 9 percent have their blood pressure and cholesterol lowered to goal levels. Not surprisingly, combined high blood pressure and high cholesterol was most often seen in adults with heart and circulatory disease, diabetes, metabolic syndrome -- a cluster of heart disease and diabetes risk factors such as obesity and elevated blood sugar, blood pressure, and cholesterol -- or a combination of these. This study shows that treatment and control of combined hypertension and hypercholesterolemia are "suboptimal," concludes the study team. "The very important message," Wong concluded, "is that many persons with hypertension also have hypercholesterolemia (and vice versa), and that we have to do a better job at identifying when both of these are present and treating both of these conditions, as their coexistence dramatically increases the risk of cardiovascular disease." American Journal of Cardiology, July 15, 2006. ================================

DID YOU KNOW:

Big Rise in Kids With Type 1 Diabetes: The UK has one of the world's fastest-growing rates of Type 1 diabetes in
children, researchers warned last week. A study of 57 countries found the annual increase was four per cent compared
to 2.8 worldwide and 3.2 across Europe. Around 20,000 under 14s have the disease which requires lifelong insulin.
Simon O'Neill, of Diabetes UK, said: It's extremely worrying - previously the annual increase was three per cent." It is
not known exactly what causes Type 1. Mr O'Neill said: "The large increase in a short period cannot solely be caused
by genetic factors. Therefore, environment and infections must play a part." The Finnish study ranked the UK fifth
behind Finland, Sardinia, Sweden and Kuwait.
================================
Item 3
Reduced Blood Flow Velocity Precedes Diabetic Microvascular Disease
A slowing of blood flow in the middle cerebral arteries, may signal the onset of microvascular disease in elderly patients
with type 2 diabetes, a potential mechanism of cerebrovascular disease in these patients.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4010
Dr. Vera Novak, at Beth Israel Deaconess Medical Center in Boston, and associates studied blood flow in the brains of
28 type 2 diabetics and 23 controls. The mean age was 62.3 years.
The researchers used transcranial Doppler ultrasound at rest and during hyperventilation to reduce carbon dioxide to 25 mm Hg for 3 minutes to assess cerebral blood velocity. Measurements were taken again after breathing 5% carbon dioxide and 95% air for 3 minutes to increase carbon dioxide level to 45 mmHg. The investigators then compared changes on ultrasound with changes in white matter hyperintensity on MRI. Compared with controls, diabetics had a lower mean blood flow velocity and higher cerebrovascular resistance at baseline, defined as mean blood pressure divided by mean cerebral blood flow velocity. Diabetics also had hypocapnia, hypercapnia and impaired carbon dioxide reactivity compared with controls. Baseline blood flow velocity positively correlated with systolic blood pressure, but was negatively associated with periventricular white matter hyperintensity, hemoglobin A1c levels and the presence of inflammatory markers, Dr. Novak's team reports in the July issue of Diabetes Care. This study provides "further evidence that type 2 diabetics is associated with microvascular disease that may reduce cerebral blood flow in elderly people. Interventions to treat microvascular disease and to enhance cerebral blood flow may play a role in preventing cerebrovascular complications of diabetes," the researchers conclude. The jury is still out on whether reduced cerebral blood flow is a cause or an effect of white matter disease, the investigators note. ================================ Advertisement The "New" 60 second foot exam. As part of the ADA recommended annual Comprehensive Diabetic Foot Exam (CDFE), PressureStatTM provides a simple, cost-effective, and dynamic method of foot pressure identification, measurement and monitoring. Stop by Booth 500 at the AADE conference for a Free
Foot Analysis and a chance to win a PressureStat Starter Kit.
Fill out the entry form and bring to the Diabetes in Control booth #500.
http://www.diabetesincontrol.com/forms/pressurestat.php
================================
Item 4
Intensive Versus Moderate Statin Therapy
Intensive lipid lowering with high-dose statin therapy provides a significant benefit over standard-dose therapy for
preventing predominantly non-fatal cardiovascular events.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4009
Debate exists regarding the merit of more intensive lipid lowering with high-dose statin therapy as compared with standard-dose therapy. So this study was done to conduct a meta-analysis that compares the reduction of cardiovascular outcomes with high-dose statin therapy versus standard dosing. The PubMed was searched for randomized controlled trials of intensive versus standard-dose statin therapy enrolling more than 1,000 patients with either stable coronary heart disease or acute coronary syndromes. Four trials were identified: the TNT (Treating to New Targets) and the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid-Lowering) trials involved patients with stable cardiovascular disease, and the PROVE IT–TIMI-22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction-22) and A-to-Z (Aggrastat-to-Zocor) trials involved patients with acute coronary syndromes. We carried out a meta-analysis of the relative odds on the basis of a fixed-effects model using the Mantel-Haenszel method for the major outcomes of death and cardiovascular events. A total of 27,548 patients were enrolled in the 4 large trials. The combined analysis yielded a significant 16% odds reduction in coronary death or myocardial infarction (p < 0.00001), as well as a significant 16% odds reduction of coronary death or any cardiovascular event (p < 0.00001). No difference was observed in total or non-cardiovascular mortality, but a trend toward decreased cardiovascular mortality (odds reduction 12%, p = 0.054) was observed. From the results it was conculed that intensive lipid lowering with high-dose statin therapy provides a significant benefit over standard-dose therapy for preventing predominantly non-fatal cardiovascular events. J Am Coll Cardiol, 2006; 48:438-445, doi:10.1016/j.jacc.2006.04.070 (Published online 11 July 2006). ================================ Start your own walking program
New StepTracker Available at special prices. See the results of the Step Program Study. http://www.diabetesincontrol.com/programs/steps/index.shtml Purchase your own pedometers and receive the Steps to Health Program at no charge. http://www.rx4betterhealth.com/steptracker/ The Only Pedometer on the Market That Comes With a Program for Success!
DID YOU KNOW:
Key Fat and Cholesterol Cell Regulator Identified, Promising Target: Researchers have identified how a
molecular switch regulates fat and cholesterol production, a step that may help advance treatments for metabolic
syndrome, the constellation of diseases that includes high cholesterol, obesity, type II diabetes, and high blood
pressure. Read and print the full news article.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4015
==========================

Item 5
Free Fat Acids Independently Associated With Cardiovascular Mortality
Levels of free fat acids are associated with mortality in patients with coronary artery disease.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4008
Senior investigator Dr. Winfried Maerz, of the Medical University of Graz states that "Free fat acids are an independent
predictor of cardiovascular death in subjects at intermediate risk.”
Dr. Maerz and colleagues came to this conclusion after examining data from 3315 Caucasian subjects in an ongoing study of coronary artery disease. The patients were followed for a median of 5.38 years and all subjects underwent coronary angiography at baseline. At follow-up, 513 patients had died, the researchers report in the July issue of the Journal of Clinical Endocrinology and Metabolism. Compared with subjects with the lowest levels of free fat acids, those with the highest levels had an adjusted hazard ratio for death from any cause of 1.58 and for death from cardiovascular causes of 1.83. In the more than 2500 subjects with stable or unstable cardiovascular disease, the predictive value of free fat acids was similar to that in the entire cohort. However, in the participants without cardiovascular disease, the association did not reach significance. Free fat acids were higher in subjects with unstable cardiovascular disease and increased with the severity of heart failure. "Although our study does not ultimately prove causality," concluded Dr. Maerz, "we suggest that looking at free fatty acids may hold a great potential for stratification and even for the treatment of coronary heart disease." J Clin Endocrinol Metab 2006;91:2542-2547. Advertisement
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Item 6
Chromium Improves Glycemic Control When Sulfonylurea Is Insufficient
Chromium picolinate (CrPic) supplementation improves glycemic control in patients with type 2 diabetes not adequately
controlled while taking sulfonylurea, according to the results of a randomized, double-blind study.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4007
"CrPic supplementation has been suggested to improve glycemia, but there are conflicting reports on efficacy," write
Julie Martin, MS, RD, from the University of Vermont in Burlington, and colleagues. "To provide a comprehensive
clinical evaluation of chromium, we conducted a randomized, double-blind, placebo-controlled trial in subjects with type
2 diabetes and over a 10-month period of observation, used established techniques to assess changes in insulin
sensitivity, body composition, and glycemic control."
After baseline evaluation, 37 subjects with type 2 diabetes were treated with a sulfonylurea (glipizide gastrointestinal therapeutic system, 5 mg/day) with placebo for 3 months. These subjects were then randomized in a double-blind fashion to receive for 6 months either the sulfonylurea plus placebo (n = 12) or the sulfonylurea plus 1000 µg of chromium as CrPic (n = 17). End points included body composition, insulin sensitivity, and glycemic control at the end of the 3-month single-blind placebo phase and at study end. The group receiving sulfonylurea/placebo fared worse than the sulfonylurea/CrPic group in terms of increase from baseline in body weight (2.2 kg; P < .001 vs 0.9 kg; P = .11), percent body fat (1.17%; P < .001 vs 0.12%; P = .7), and total abdominal fat (32.5 cm2; P < .05 vs 12.2 cm2; P < .10) from baseline. Compared with the sulfonylurea/placebo group, the sulfonylurea/CrPic group had significant improvements in insulin sensitivity corrected for fat-free mass (28.8; P < .05 vs 15.9; P = .40), glycated hemoglobin levels (HbA1c; -1.16%; P < .005 vs -0.4%; P = .30), and free fatty acids (-0.2 mmol/L; P < .001 vs -0.12 mmol/L; P < .03). "This study demonstrates that CrPic supplementation in subjects with type 2 diabetes who are taking sulfonylurea agents significantly improves insulin sensitivity and glucose control," the authors write. "Further, CrPic supplementation significantly attenuated body weight gain and visceral fat accumulation compared with the placebo group. The mechanisms for these findings are not precisely known, but clinical research studies addressing dietary intake, skeletal muscle fat oxidation, and insulin signaling are ongoing." Diabetes Care. 2006;29:1826-1832. ===========================
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===========================
Item 7
Pioglitazone HCl Plus Glimepiride Tablets (Duetact) for Type 2 Diabetes
FDA approves new combination product for Type 2 diabetes.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4006
On July 28, the FDA approved pioglitazone HCl (Actos) plus glimepiride 30-mg/2-mg and 30-mg/4-mg tablets (Duetact, both made by Takeda Pharmaceuticals North America, Inc) for use as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes who are already receiving a combination of the 2 components or whose diabetes is not adequately controlled with a sulfonylurea alone. The 2 active ingredients have complementary modes of action — pioglitazone directly targets insulin resistance while glimepiride acts primarily to increase the amount of insulin produced by the pancreas. According to a company news release, the "duet act" product is expected to be available later this year. The combination tablets should be administered no more than once daily at either of the tablet strengths to avoid exceeding maximum dosages for pioglitazone (45 mg/day) and glimepiride (8 mg/day). Starting doses should be chosen based on the patient's current regimen of pioglitazone and/or a sulfonylurea; those currently receiving pioglitazone monotherapy should receive an initial dose of 30 mg/2 mg, which can be adjusted after assessing therapeutic response. Patients transitioning from glimepiride monotherapy to combination therapy may be initiated at either the 30-mg/2-mg or 30-mg/4-mg strength. The FDA notes that because no exact dosage relationship exists between glimepiride and other sulfonylurea agents, patients currently receiving a different sulfonylurea alone or in combination with pioglitazone should be limited to a starting dose of 30 mg/2 mg of pioglitazone plus glimepiride. As with other thiazolidinediones, pioglitazone is associated with a risk for fluid retention that may exacerbate or lead to heart failure. Patients receiving pioglitazone should be observed for signs and symptoms of heart failure, and therapy should be discontinued if any deterioration in cardiac status occurs. Combination therapy with pioglitazone is not recommended for patients with moderate to severe heart failure. Because of the potential risk for pioglitazone-induced hepatotoxicity, serum alanine aminotransferase (ALT) levels should be evaluated prior to initiation of therapy and periodically thereafter at appropriate intervals. Liver function tests should also be obtained for patients with symptoms suggestive of hepatic dysfunction (eg, nausea, vomiting, abdominal pain, fatigue, anorexia, or dark urine). Patients with ALT levels at 1 to 3 times the upper limit of normal should be evaluated more frequently pending a return to normal or pretreatment values. Therapy should be discontinued if ALT levels exceed 3 times the upper limit of normal or if the patient has jaundice. The FDA notes that use of thiazolidinediones, such as pioglitazone, can cause ovulation in some premenopausal anovulatory women, thereby increasing their risk for pregnancy. Adequate contraception is therefore recommended for women of childbearing age receiving pioglitazone/glimepiride combination therapy. Dr. Bernstein will be doing another live teleconference call soon. If you would
like to ask a question or just register for the free teleconference call, just go to
www.askdrbernstein.com and register. There were over 600 people on the last
call. More info at http://www.diabetes911.net


================================
Item 8
Study Backs Pill Use for Neonatal Diabetes
The small number of diabetics who were diagnosed early in infancy may be spared a lifetime of insulin shots, according
to new research.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4005
Investigators two years ago pinpointed a genetic cause for about half of all cases of neonatal diabetes, uncovering a flaw that prevents the body from producing insulin. The revelation led researchers to test pills taken for decades by older diabetics. The results show those pills can circumvent the mutation and allow patients to start producing insulin for the first time. About 1,500 to 2,000 Americans with neonatal diabetes rely on daily insulin injections to survive, said lead researcher Ewan Pearson, a lecturer at the University of Dundee in Scotland. The study found that 44 of 49 patients with the genetic mutation were able to safely switch to pills and get better control of the disease. ``Anybody who was diagnosed before six months of age should go and have a genetic test for the mutation," Pearson said in a telephone interview. ``If they have it, there is a 9 in 10 chance they could come off insulin." The study, along with the report of another genetic mutation that may explain as many as 12 percent of neonatal diabetes cases, appears in today's New England Journal of Medicine. While almost 21 million Americans have diabetes, more than 90 percent have type 2, which tends to develop during adulthood. They often take drugs called sulfonylureas to boost insulin production. Neonatal diabetes is very rare, occurring in just 1 in 100,000 births. Patients traditionally are treated with daily insulin shots like those with type 1 diabetes, which is generally diagnosed in children and accounts for 5 to 10 percent of all diabetes cases. The researchers used sulfonylureas in the study. The treatment restored insulin secretion and led to greater control of the diabetes, wrote Mark A. Sperling, an endocrinologist at Children's Hospital of Pittsburgh, in an editorial accompanying the study. Pearson ER et al. "Switching from Insulin to Oral Sulfonylureas in Patients with Diabetes Due to Kir6.2 Mutations." N Engl J Med 2006;355:467-77. FACT:
Research Finds That Diabetes Disease-Management Programs Improve Quality of Care; But Patients'
Health Outcomes Another Story:
With diabetes disease-management programs becoming more commonly used
among physician groups, the question arises: Just how effective are they at improving patient care? Read and print the
full news article.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4016
===============================

Item 9
Traditional Chinese Medicine Hones Diabetes Treatment
A herbal remedy Berberine used for thousands of years in traditional Chinese medicine may have a role to play in
fighting Type 2 diabetes.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4004
A team of Chinese, South Korean and Australian scientists working at the Garvan Institute in Sydney, Australia, found
that a plant extract known as berberine helps insulin work better in diabetic mice, thereby easing the symptoms of the
disease.
Berberine is found in the roots and bark of several medicinal plants, including goldenseal and barberry. (Huanglian is the Chinese name of a berberine-containing plant.) Insulin is normally secreted into the bloodstream after we eat, to help push incoming sugar into our tissues, particularly muscle and fat cells. For people with Type 2 diabetes, the process goes awry: Either they don't produce enough insulin or the body tissues don't respond to the hormone. The new research, published in the journal Diabetes, suggest that berberine helps insulin do its job. "Our studies in animal models of diabetes show that berberine acts, in part, by activating an enzyme in the muscle and liver called AMPK that is involved in improving sensitivity of the tissue to insulin," the lead researcher, Dr. David James, said in an e-mail interview. What's more, "berberine assists with the removal of circulating fats [in the bloodstream], thereby helping to reduce body weight," he said. Dr. James noted that medications are available to treat insulin resistance, but many patients find the drugs cause unpleasant side effects. "Our hope is that berberine will provide a better alternative." So, does this mean that diabetics should now be using herbal remedies such as goldenseal? Not necessarily, Dr. James said. The amount of berberine in these products can vary greatly. For their study, the researchers used a purified form of the compound. And a lot more studies are needed before a berberine-based drug can be recommended to patients. ================================
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Item 10
Physicians Miss Signs of Chronic Kidney Disease
Primary care physicians are not recognizing kidney disease in high-risk patients as often as they should." A lot of
primary care physicians need to bone up on the signs of chronic kidney disease, according to investigators.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4003
When randomly selected family practitioners and internists, were asked which diagnostic tests they would order for a hypothetical patient with symptoms and lab values consistent with chronic kidney disease, 59% of FPs and 78% of internists got it right. This contrasted with 97% of nephrologists who got it right when asked the same questions. "We, as physicians, can certainly do better," the investigators wrote in the August issue of American Journal of Kidney Diseases. "Millions of people have kidney disease, but a substantial number may not have their disease recognized," they added. "Simply put, our study shows that . Using a list generated by the American Medical Association, the investigators mailed questionnaires to a random sampling of primary care physicians, general internists, and nephrologists. The questionnaires described a hypothetical patient on a new-patient visit, and asked what tests they would order and whether they would make referrals to a nephrologist at the visit. The patient was described as a 50-year-old woman, 5'2" and 154 pounds. All physicians received the same description of the patient, with identical test values, signs, and symptoms, except for two patient characteristics, which varied to test the investigators' assumptions that certain factors could influence recommendations for further testing and referrals. The two characteristics were the patient's race, which could be either African American or Caucasian, and comorbidities, which could include hypertension alone or hypertension plus diabetes. Clues pointing to a diagnosis of chronic kidney disease included persistent proteinuria over a four month period, and lab findings consistent with -- but not spelled out as -- Kidney Disease Outcomes Quality Initiative (KDOQI) stage three chronic kidney disease progressing to stage 4 within four months. The glomerular filtration rate was specified as progressing over four months from 30 to 59 mL/min/1.73 m2 [0.50 to 0.98 mL/s] to 15 to 29 mL/min/1.73 m2 [0.25 to 0.48 mL/s]. "Physicians were provided with enough clinical information in the scenario to use either the Cockroft-Gault or the modified Modification of Diet in Renal Disease equations to calculate the patient's estimated glomerular filtration rate themselves, but they were not provided with actual estimated glomerular filtration rate using either calculation," the authors noted. The participants were also furnished with information about the patient's lab values from a previous visit to another physician four months earlier. Respondents include 126 nephrologists (39% response rate), 89 FPs (28%), and 89 general internists (28%). The investigators found that FPs recognized chronic kidney disease less often that either internists or nephrologists (adjusted percentage, 59%; 95% confidence interval, 47% to 69%). More internists than FPs nailed the diagnosis (78%; 95% CI, 67% to 86%), as did an even higher percentage of nephrologists (adjusted percentage, 97%; 95% CI, 93% to 99%, P< 0.01). In addition, while 76% and 81% of FPs and internists, respectively, said they would recommend referrals for the patient in the scenario, virtually all of the nephrologists (99%) would have done so, they reported. "In this study of physicians sampled randomly from across the United States, our findings suggest that efforts to raise physicians' awareness of progressive chronic kidney disease and disseminate recently developed clinical practice guidelines have not been as effective as hoped," Dr. Boulware and colleagues wrote. They also found that primary care physicians with more than 10 years of clinical practice experience were least likely to recognize chronic kidney disease and also least likely to recommend referral. They wrote that "these findings strongly confirm other studies indicating that more recently trained physicians are more aware of current treatment guidelines and potentially deliver better quality care." They suggested that care of patients with chronic kidney disease could be enhanced through better dissemination of clinical practice guidelines, and better collaboration among primary care physicians and nephrologists, including joint practice guidelines focused on optimal diagnosis and management of patients with the condition. In addition, of the basis of their findings, they suggested that physicians with more years in practice should be targeted for dissemination of information regarding the identification and appropriate referral of patients with chronic kidney disease. "Many of these primary care doctors are in absolutely the best position to diagnose and treat chronic kidney disease," said Neil R. Powe, M.D., of Johns Hopkins, a co-author. "These health care professionals need to work with nephrologists to begin to eliminate the disagreement over how these patients should be treated and when they should be referred," he said. Practice Pearls
? ? Explain to interested patients that chronic kidney disease is a growing problem, and is exacerbated by conditions such as hypertension and diabetes. ? ? Explain that specific clinical signs combined with patient characteristics may warrant additional diagnostic tests American Journal of Kidney Diseases: Boulware LE et al. "Identification and Referral of Patients With Progressive CKD: A National Study." Am J
Kidney Dis. 48; 2:192-204.

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Item 11
Compound in Dairy Products Targets Diabetes
A possible new way to treat diabetes without synthetic drugs.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4002
Fatty acids commonly found in dairy products have successfully treated diabetes in mice, according to a researcher at Penn State. The compounds, known as conjugated linoleic acids (CLA), also have shown promising results in human trials, signaling a new way of potentially treating the disease without synthetic drugs. "The compounds are predominantly found in dairy products such as milk, cheese and meat, and are formed by bacteria in ruminants that take linoleic acids -- fatty acids from plants -- and convert them into conjugated linoleic acids, or CLA," said Jack Vanden Heuvel, professor of molecular toxicology in Penn State's College of Agricultural Sciences and co-director of Penn State's Center of Excellence in Nutrigenomics. Researchers first became interested in CLA when it was shown to inhibit a variety of cancers such as breast, skin and colon in mice, and further research showed effects on circulating cholesterol and inflammation. These effects are the same as the newest generation of synthetic drugs used to treat diabetes in humans. These synthetic drugs act by triggering a set of nuclear receptors called PPAR. In addition to being targets for a variety of clinically effective drugs, PPARs belong to a large family of proteins, and their biological purpose is to sense fatty acids and fatty acid metabolites within the cell, said Vanden Heuvel. When the synthetic drugs interact with these protein receptors, it turns the receptor "on," making it an active form of the protein, which then interacts with DNA and regulates gene expression. This increases the enzymes that process fatty acids and also increases the tissues' sensitivity to insulin. "We wondered if CLA was using the same mechanism, in which case it could be used as an anti-diabetes drug," Vanden Heuvel said. To test the idea, he used CLA on mice prone to adult onset (Type-2) diabetes. Results indicated that the mice had an improvement in insulin action, and a decrease in circulating glucose. Also, the mechanism was indeed similar to that of the drugs. "Anti-diabetes drugs act the same way. They mimic the natural activators of the receptors by getting into the cell and interacting with the PPARs to regulate glucose and fat metabolism," said Vanden Heuvel. Early human trials indicate that when administered for longer than eight weeks, CLA improves the body's misregulation of insulin and lowers the level of glucose in the blood in patients with adult onset, or Type-2 diabetes, the most common form of this disease. However, Vanden Heuvel cautioned that while having a diet that is high in dairy and meat products, and thereby CLA, might have a health benefit, one also must be aware of other lipids present in these products, such as trans fatty acids. Instead, he suggested that in addition to a well-balanced diet, it is advantageous to incorporate CLA as a dietary supplement, or to seek out new products that enrich foods such as butter, margarine and ice cream with CLA. "Adult-onset diabetes is fast becoming an epidemic and is largely associated with poor diet and nutrition and other lifestyle issues," Vanden Heuvel said. The reason for the increase in diabetes may have to do with the ratio of so-called "good" and "bad" fats, with the average American diet containing too much of the "bad" fats. CLA, whose effect is very similar to fish oil, a source of "good" fat, could prove beneficial against Type-2 diabetes. "And compared to the synthetic drugs used to treated this disease, CLA does not cause weight gain and may in fact decrease overall body fat," said Vanden Heuvel, who has been granted a patent on the new method of treating diabetes with CLA. Penn State Center of Excellence in Nutrigenomics http://nutrigenomics.psu.edu/ . ================================
DID YOU KNOW:

Sleep Deprivation Doubles Risks of Obesity in Both Children and Adults: Research has found that sleep
deprivation is associated with an almost a two-fold increased risk of being obese for both children and adults. Read
and print the full news article.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4017
================================

PLEASE CLICK HERE TO UPDATE YOUR PROFILE!!!
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Item 12
Walking Makes a Difference in Controlling Type 2 Diabetes
How much walking is needed to produce the best effects for controlling Type 2 diabetes?
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4001
Walking or doing other aerobic exercise for 38 minutes - about 2.2 miles or 4400 steps - showed a significant effect for
those with diabetes, even if they didn't lose weight. They improved their hemoglobin A1C by 0.4%, reduced their risk of
heart disease, and improved their cholesterol and triglyceride levels. They saved $288 a year in health care costs.
The number of walkers with diabetes who needed insulin therapy dropped by 25%, and those on insuling therapy
reduced their dosage by an average 11 units per day. They had great improvement in hemoglobin A1C levels of 1.1%,
improved cholesterol, triglycerides, blood pressure, and reduced risk of heart disease. They reduced their medical costs
by over $1200 per year.
Those who didn't walk saw their health care costs go up by over $500 in the two-year study period. Their insulin use
went up, as did cholesterol, triglycerides, and blood pressure. There is a huge cost in failing to walk and exercise,
especially for those with diabetes.
Exercise and walking have also been shown to reduce the risks of developing Type II diabetes. Whether you have
diabetes or not, it is never too soon or too late to begin a walking or exercise program.
Anals of Internal Medicine, July 2006

Learn about the new Steps-To-Health Program. A program like no other. It will motivate your patients to increasing
their physical activity while they are having fun. http://www.steps-to-health.org/
==============================
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Item 13
Treatment Guidelines Favor Early Metformin Then Insulin for Type 2 Diabetes
Metformin should be prescribed along with lifestyle intervention as soon as patients are diagnosed with type 2 diabetes
and if A1c cannot be brought down to below 7%, within 2-3 months, then insulin as the second-line drug.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4000
That comes from the authors of a new consensus algorithm endorsed by the American Diabetes Association.
Based on evidence gleaned from well-controlled trials and the expert opinions of diabetes specialists, the document stresses the importance of promptly diagnosing type 2 diabetes and achieving an A1c level as close to the nondiabetic range as possible (less than 6%) or, at a minimum, to less than 7%. The statement was published in the August issue of the journal Diabetes Care (2006;29:1–10). Insulin also features prominently in the document as an intervention to be considered expeditiously in patients who veer from a tightly targeted glycemic goal. A hemoglobin A1c level of 7% or greater “should serve as a call to action to initiate or change therapy,” the consensus panel said. Delays in achieving control typically occur when medications are reserved for patients who have not responded to efforts to promote exercise, dietary adjustments, and weight loss, the panel said. “For most individuals with type 2 diabetes, lifestyle interventions fail to achieve or maintain metabolic goals.” The algorithm also advocates adding basal insulin, a sulfonylurea, or a thiazolidinedione (glitazone) within 2–3 months of the initiation of therapy or “at any time” that A1c levels are 7% or greater. The strong recommendation to consider insulin as a second-line drug “was a little surprising, since few people do it,” said consensus panel member Dr. Mayer B. Davidson, of Charles R. Drew University of Medicine and Science, Los Angeles. But such a change in clinical practice could be “very effective,” he said in an interview. The guidelines contain detailed advice for initiating and adjusting insulin regimens, the complexity of which may contribute to delays in aggressive therapy that could optimize patient outcomes. If a combination of lifestyle changes, metformin, and a second-line drug fail to achieve glycemic control, the algorithm endorses adding another of the second-line choices (basal insulin, a sulfonylurea, or glitazone) or intensifying insulin therapy. “Although three oral agents can be used, initiation and intensification of insulin therapy is preferred based on effectiveness [and] expense,” the authors noted in the algorithm approved by the Professional Practice Committee of the American Diabetes Association (ADA) and an ad hoc committee of the European Association for the Study of Diabetes. Consensus panel members deplored the lack of “high-quality evidence” comparing diabetes drugs head to head, adding that “there are insufficient data at this time to support a recommendation of one class of glucose-lowering agents or one combination of medications over others with regard to … complications.” They therefore focused on the effectiveness of drug classes in lowering glycemic levels as the “overarching principle” guiding their choice of first- and second-line agents. Pramlintide, exenatide, a-glucosidase inhibitors, and the glinides were not included in the algorithm “owing to their generally lower overall glucose-lowering effectiveness, limited clinical data, and/or relative expense,” although the authors acknowledged that they might be “appropriate choices in selected patients.” Diabetes experts within and outside the ADA applauded the guidelines committee led by Dr. David M. Nathan, director of the diabetes center at Massachusetts General Hospital and professor of medicine at Harvard Medical Center, both in Boston. “Aggressive control of glucose is incredibly important in the care of our patients,” said Dr. Hellman, clinical professor of medicine at the University of Missouri-Kansas City. He also agreed with the new algorithm's emphasis on aggressive treatment of type 2 diabetes in the first year after diagnosis, including the early integration of insulin into the treatment regimen. The most important message to primary care physicians is to hit the disease hard, early on, he emphasized. “Deterioration is more common when physicians wait a long time to gradually accelerate the treatment.” Indeed, “heightened uncertainty regarding the most appropriate means of treating this widespread disease,” was one of the driving forces behind the development of the algorithm, the authors noted. “Although numerous reviews on the management of type 2 diabetes have been published in recent years, practitioners are often left without a clear pathway of therapy to follow,” they wrote. Diabetes Care (2006;29:1–10).Aug, 2006
================================
FACT:

Size Matters: Smaller Bowls and Spoons May Curb Consumption: Picking out the perfect bowls and spoons
sounds like a concern solely for brides-to-be, but a new study of eating habits suggests that selecting right-sized serving
utensils may help dieters avoid unconscious overeating. Read or print the full news article.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4018
================================
Item 14
Diabetes Prevalence Outstrips National Growth Rate and More
The US Centers for Disease Control and Prevention (CDC) reported a 50% increase in the prevalence of diabetes from
1997 to 2004
.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=3999
An analysis of data from the National Health Interview surveys has revealed that although the estimated US population
increased by approximately 8% during 1997 to 2004, the prevalence of diabetes increased by 50% during this period
(10.1 to 15.2 million). The increase in diabetes cases corresponded with a 41% increase in the estimated number of
diabetes-related visits to physician offices and hospital outpatient departments.
An analysis of 2005 data from the School Health Profiles questionnaire has revealed that although nearly all high
schools in 25 states and 10 large urban school districts provided some level of nutrition/dietary behavior and physical
activity/exercise instruction, only half to three quarters of schools taught all 15 nutrition topics and even fewer (one to
two thirds) taught all 12 physical activity topics as recommended by the CDC.
Moreover, fewer than half of lead health education teachers in the schools had received staff development on nutrition
and physical activity within the preceding 2 years.
According to the CDC, studies have indicated that teachers who receive staff development are more likely to effectively
cover a broader range of these topics, which have been shown to improve dietary behavior, increase physical activity,
reduce sedentary behavior, and decrease the prevalence of overweight among students.
The CDC recommends that health education on nutrition and physical activity topics be included in schools as part of a
coordinated program that includes healthy meal and snack choices; a physical education program based on
recommendations from the National Association for Sport and Physical Education in Moving Into the Future: National
Standards for Physical Education
; opportunities for safe and enjoyable physical activity; school health services and
counseling regarding dietary behavior and physical activity; and a health promotion program for school staff members.

MMWR. 2006;55(30):817-840. August 4 issue of the Morbidity and Mortality Weekly Report

Learn about the Steps To Health, a program to increase physical activity that has gone through 8 years of
clinical studies to show its effectiveness.
http://www.steps-to-health.org

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Item 15
Diabetes Drug Adherence Lower for African Americans
African-Americans with type 2 diabetes appear to be less likely than whites to take prescribed medications.
http://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=3998
One reason African Americans with type 2 diabetes tend to have comparatively poor clinical outcomes may be cultural, investigators reported. African-Americans with type 2 diabetes appear to be less likely than whites to take prescribed medications, In a retrospective study comparing medication compliance among Medicaid-insured patients who were given first-time prescriptions for oral antidiabetic agents, African Americans had a 12% lower adherence rate than whites, they found. "That's an unacceptable difference, particularly because African Americans tend to have higher rates of diabetes and disease-related complications," said Rajesh Balkrishnan, Ph.D., a professor of pharmacy, a co-author. "Adherence rates for these types of medications should be better than 90% regardless of who takes them," he added. "Such low rates of adherence may be related to lower socioeconomic status and to lower levels of education." A study published by the Institute of Medicine in 2002 found that African Americans, Hispanics, and Native Americans have a burden of illness and mortality from diabetes that are between 50% and 100% higher than among whites. Other studies haves shown that African Americans with diabetes have worse glycemic control than others, Shenolikar and colleagues wrote. To see whether the disparities in outcomes could be due in part to medication compliance, Shenolikar and colleagues here and at Wake Forest in Winston-Salem, N.C., looked at Medicaid-insured patients with a new, first-time prescription for oral diabetes medications. The cohort included 1,527 African Americans, 1,128 white patients, and 514 patients of other racial/ethnic backgrounds. They determined medication adherence by looked at the ratio between prescriptions and refills, working under the assumption that a refill implied that the patient had taken the drug prescribed. The outcome was expressed as a medication possession ratio, which was calculated as the number of days that the patient possessed a prescription divided by the number of days between refills. The authors used multivariate regression analyses to determine the difference in adherence rates adjusting for other covariates, including demographic characteristics (such as age and gender), clinical confounders (such as use of healthcare services over the previous 12 months), type of therapy, total number of medications, and number of comorbidities. They found that whites had a significantly higher adherence rates than blacks. That is, whites took their medication 59% of the time, compared with African Americans, who took their medications 54% of the time. In multivariate analyses, the difference translated into a 12% lower compliance rate among African American. The investigators also found that compliance was dependent on the type of medication prescribed, with those assigned to Glucophage (metformin) having a 62% lower compliance rate than patients assigned to sulfonylureas (P<0.05), and a 63% lower rate compared with patients assigned to thiazolidinediones. "Many commercial insurers pay for educators to teach patients the importance of taking their medications as prescribed," Dr. Balkrishnan said. "Medicaid needs to do the same thing. While it invests a lot of money in providing services, it does little to educate its recipients about those services and how to use them. People need to understand the importance of taking their medications." ? ? Explain to patients the importance of compliance when taking medications for type 2 diabetes. ? ? Explain that oral medications, combined with diet changes and exercise, may prevent or delay the need for insulin injections, and can reduce the risk for complications such as blindness, heart disease, kidney failure, and vascular and neurologic problems leading to amputations.
Shenolikar RA et al. "Race and Medication Adherence in Medicaid Enrollees with Type-2 Diabetes." J Natl Med Assoc. 2006. 98;7:1071-7.


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26.4 brief comms.cds

brief communications rhesus or cynomolgus macaques successfullyyielded product from both batches. Sequenc-ing and phylogenetic analyses indicate thatthose for CHAT 6039 were from cynomolgusmacaques (Fig. 1). chimpanzee cellular components in two OPVCHAT stocks, together with the positive iden-sequences, provides no support for thehypothesis that these materials were responsi-ble for the ent

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