Lifestyle Changes Effective In Protecting Against Type II Diabetes

24 Jan 2007

Changing to a healthier lifestyle appears to be at least as effective as taking prescription drugs in reducing the risk of developing Type 2 diabetes, says a new BMJ study.

Type 2 diabetes is a growing problem - in England around 1.3 million people have diabetes and around 5% of total NHS resources are used for the care of people with diabetes.

Researchers from Leicester reviewed studies which measured the effects of different interventions - lifestyle, diabetes drug and anti-obesity drug - on people with impaired glucose tolerance (1).

They found that lifestyle changes, e.g. switching to a healthier diet and increasing exercise to be at least as effective as taking prescription drugs. On average, lifestyle changes helped to reduce the risk of developing type 2 diabetes by around half. Lifestyle changes were also less likely to have adverse side-effects.

However, the researchers say that both lifestyle changes and prescription drug taking must be sustained in order to prevent the development of Type 2 diabetes.

The authors say that as global rates of Type 2 diabetes are likely to double by 2030, interventions to prevent the condition will have an important role to play in future health policies. The study findings have large implications for public health policy, however, the authors note that if lifestyle changes are to be truly effective more needs to be done to support people to adopt healthier lifestyles.

###

(1) People with impaired glucose tolerance have a high risk of developing type II diabetes

Contact: Emma Dickinson
BMJ-British Medical Journal

Article URL: http://www.medicalnewstoday.com/medicalnews.php?newsid=61209

Positive Opinion For Type 2 Diabetes Treatment, JANUVIA - First In New Class Of Oral Treatments Known As DPP-4 Inhibitors, European Union

JANUVIA (sitagliptin), Merck, Sharp & Dohme's treatment for patients with type 2 diabetes, today received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Evaluation Agency (EMEA) in Europe. The CHMP opinion recommends that JANUVIA be approved in the European Union for the treatment of type 2 diabetes. Following the conclusion of the CHMP review, the opinion for JANUVIA will be transmitted to the European Commission (EC). If the EC adopts the opinion, JANUVIA will be the first and only prescription medication in a new class of drugs known as dipeptidyl peptidase-4 (DPP-4) inhibitors, which enhance the body's own ability to lower blood sugar (glucose) when it is elevated. The decision will be applicable to the 27 countries that are members of the European Union, including the United Kingdom, Germany, France, Italy and Spain. JANUVIA is currently approved in eleven countries including the United States and Mexico. Marketing authorization from the European Commission is expected in early April after the adoption of the opinion.

The CHMP, comprised of regulators from all European Union countries, gave the positive opinion following a review of comprehensive data supporting the efficacy and safety and tolerability profile of JANUVIA. The submission package consisted of studies involving approximately 4,000 patients with type 2 diabetes treated with JANUVIA.

JANUVIA has been investigated in patients with type 2 diabetes to improve glycaemic control in combination with metformin when diet and exercise, plus metformin, do not provide adequate glycaemic control. JANUVIA has also been studied as add on therapy with PPARγ agonists in patients with type 2 diabetes mellitus in whom use of a PPARγ agonist (e.g. a thiazolidinedione) is appropriate. In addition, JANUVIA has been studied as monotherapy in many patients.

In a clinical study, JANUVIA plus metformin, compared to treatment of a sulfonylurea (SU) plus metformin, showed comparable glucose lowering efficacy. In this study patients taking JANUVIA plus metformin lost weight (-1.5 kg) compared to patients taking glipizide plus metformin who gained weight gain (+1.1 kg). Hypoglycaemia (when blood sugar becomes too low) was more common in patients treated with glipizide plus metformin (32 percent) compared to patients treated with JANUVIA plus metformin (4.9 percent). In the overall phase III clinical programme the incidence of hypoglycaemia in patients taking JANUVIA was similar to patients taking placebo (1.2 percent, JANUVIA vs. 0.9 percent, placebo). In clinical trials of up to 2 years in duration, patients have received treatment with JANUVIA alone or in combination with metformin, a sulfonylurea (with or without metformin) or a PPARγ agent. In these trials, the rate of discontinuation due to adverse experiences considered drug-related was 0.8 percent with JANUVIA and 1.5 percent with other treatments. No adverse reactions considered as drug- related were reported in patients treated with JANUVIA occurring in excess (> 0.2 % and difference > 1 patient) of that in patients treated with control. Reported adverse events included nausea (common), somnolence, upper abdominal pain, diarrhoea and hypoglycaemia (uncommon).* JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.

About JANUVIA

JANUVIA (sitagliptin) is an oral, once daily, potent and highly selective DPP-4 inhibitor. DPP-4 inhibitors work by enhancing a natural body process that lowers blood sugar, the incretin system. When blood sugar is elevated, incretins work in two ways to help the body regulate high blood sugar levels: they trigger the pancreas to increase the release of insulin and signal the liver to reduce its production of glucose. DPP-4 inhibitors enhance the body's own ability to control blood sugar levels by increasing the active levels of these incretin hormones in the body, helping to decrease blood sugar levels in patients with type 2 diabetes.

Expanding Clinical Trial Program for JANUVIA

MSD's clinical development program for JANUVIA is robust and continues to expand with 43 studies completed or under way, and four more studies set to begin this year. There are about 6,700 patients in the Company's clinical studies with about 4,700 of these patients being treated with JANUVIA. Additionally, about 1,100 patients have been treated with JANUVIA for more than a year.

About Merck

Merck & Co., Inc., which operates in many countries as MSD (Merck Sharp & Dohme), is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Forwarding-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward- looking statement, whether as a result of new information, future events, or otherwise. Forward- looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.

-- JANUVIA - Patient and Caregiver Web Site
-- JANUVIA - Health Care Professional Web Site

* Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); and very rare (< 1/10,000).

(R) JANUVIA is a registered trademark of Merck & Co., Inc., which operates in many countries as MSD (Merck, Sharp & Dohme).

A Happy New Year to one an` all.
May the year ahead bring all that you desire and more.
If that includes a substantial lottery win my address is available on
request.

Best Wishes
Tony

PCD Europe

Primary Care Diabetes EUROPE (PCD Europe)

PCD Europe (www.pcdeurope.org) exists to provide a focal point for primary care clinicians and their patients. Its purpose is to promote high standards of care throughout Europe. Emphasis is placed on incorporating evidence based medicine into daily practice as well as promoting diabetes education and research in primary care.

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Fruit Yogurt Could Play An Important Role In Diabetes Management

 

Yogurt enriched with fruit or made from soy could play an important dietary role for people living with Type 2 diabetes and high blood pressure, suggests new findings by University of Massachusetts Amherst researchers.
Led by Kalidas Shetty, the UMass Amherst scientists screened extracts from a sampling of dairy and soy yogurts for properties that could help keep diabetes and hypertension in check, such as the activity level of enzymes that help moderate blood glucose levels. The researchers found that fruit-enriched yogurts-especially those made with blueberries or made from soy-contain active natural compounds that may curb some aspects of diabetes, the researchers report in an upcoming issue of the Journal of Food Biochemistry.............Continued ONLINE

WELCOME TO DIABETES HEALTH ONLINE

Welcome to DiabetesHealthOnline

Recommended reading on what you need to know about diabetes.

DIEBETES MINE

DiabetesMine 

 

For journalist Amy Tenderich, being diagnosed with diabetes changed her life -- twice. The news itself transformed the way she regarded everyday things like meals and exercise. But when she sought information on how others cope with the disease, how people interpret new research and try new therapies, she became frustrated. So she created her own resource -- www.diabetesmine.com -- and in its short existence, her work has propelled her to the forefront of an online community of diabetics, healthcare experts, and researchers.

UNDERSTANDING TYPE 2 DIABETES

Barry J. Goldstein, MD, PhD   

The Growing Epidemic of Type 2 Diabetes

Type 2 diabetes mellitus is a progressive metabolic disease that is becoming increasingly common in the United States. The number of Americans with type 2 diabetes more than doubled from 1980 to 2004.^[1] According to the American Diabetes Association (ADA), approximately 20.8 million children and adults in the United States — 7% of the population — have diabetes. Although an estimated 14.6 million people have been diagnosed with diabetes, approximately 6.2 million are unaware that they have the disease.^[2] The potential causes of this growing epidemic include an aging population, lifestyle changes, limited physical activity, obesity, and high caloric intake. Type 2 diabetes is a costly healthcare burden and a major cause of morbidity and mortality. In terms of medical expenditures and lost productivity, the cost of type 2 diabetes was estimated to be about $132 billion in 2002.^[3]

Insulin resistance accounts for more than 90% of all type 2 diabetes cases.^[4] The National Health and Nutrition Examination Survey (NHANES) estimated that one third of the US population between the ages of 40 and 74 years is insulin-resistant.^[5] Insulin resistance is at the core of the pathogenesis of the metabolic syndrome and leads not only to insulin-stimulated glucose uptake with glucose intolerance or frank diabetes, but also to high triglycerides, low high-density lipoprotein cholesterol (HDL-C), high blood pressure, and increased cardiovascular risk.^[6] Elevated blood glucose levels are diagnostic of type 2 diabetes. Clinical studies have demonstrated that diabetes itself is one of the major risk factors for coronary heart disease and micro- and macrovascular complications.^[7-9]

Obesity, a growing epidemic in both adults and children, is a metabolic abnormality that is highly associated with the development of type 2 diabetes. The NHANES data indicated that the prevalence of obesity is also on the rise. In 2003 and 2004, 17.1% of US children and adolescents were overweight.^[10] These data indicated that the age-adjusted prevalence of overweight and obesity among adults has increased from a level of 23% in NHANES III to a new level of approximately 32%.^[11] These high incidences of overweight among children and obesity among adults remain a major public health concern, because they can lead to subsequent type 2 diabetes and cardiovascular disease. A recent study showed that individuals with onset of diabetes in youth (especially at younger than 20 years of age) had a 3-fold higher death rate than nondiabetic participants, compared with a 1.4-fold increased rate in individuals with onset of diabetes occurring at an older age.^[12]

Pathophysiology of Type 2 Diabetes: A Dual-Defect Disease

Type 2 diabetes is a dual-defect disease characterized by insulin resistance and impaired beta-cell function. Glucose derived from dietary carbohydrate and hepatic glucose production is tightly regulated by insulin. Type 2 diabetes results from an imbalance between insulin sensitivity and insulin secretion.^[13] In the diabetic condition, glucose production fails to be adequately regulated by insulin, leading to hepatic glucose overproduction and diminished glucose uptake by muscle tissue. In addition, accelerated gastric emptying and excessive lipolysis in adipose tissue also contribute to developing type 2 diabetes.^[13] Over time, pancreatic beta cells fail to maintain their high rate of insulin secretion, leading to glucose intolerance, insulin resistance, and overt type 2 diabetes.^[13] Various clinical syndromes are associated with insulin resistance, including obesity, type 2 diabetes, cardiovascular disease, essential hypertension, polycystic ovary syndrome, nonalcoholic fatty liver disease, certain types of cancer, and sleep apnea.

Treatment Goals and Options for Type 2 Diabetes

Glycemic control remains fundamental to treating diabetes. The UK Prospective Diabetes Study (UKPDS) demonstrated that intensive glycemic control with antidiabetes drugs reduces microvascular complications.^[8] The availability of sensitive and inexpensive home glucose monitors has made it possible for patients with type 2 diabetes to monitor long-term glycemic control. Diabetes treatment guidelines recommend vigorously lowering glucose levels to attain near-normal glycemia in order to reduce micro- and macrovascular complications. The most recent recommendations of the ADA suggest that although the glycated hemoglobin (A1C) goal for patients with all forms of diabetes is < 7%, the goal for an individual patient is an A1C as close to normal (< 6%) as possible, because this level can be safely achieved without significant hypoglycemia.^[14] The American College of Endocrinology recommends a similar A1C goal of ≤ 6.5%.^[15,16]

Patients with type 2 diabetes have various treatment options available to control their glucose levels. In addition to therapeutic lifestyle changes that include diet and exercise, several classes of medications with different mechanisms of action are currently available. Advances in our understanding of the pathophysiology of diabetes, identification of the targets of antidiabetes medications, and pivotal clinical trials have all contributed to the development of antidiabetes treatment strategies — both monotherapy and combination therapy.^[17-20]

The goal of pharmacotherapy is to control hyperglycemia and delay the comorbidities that are associated with diabetes. For type 2 diabetes, drugs that increase circulating insulin levels or decrease insulin resistance are used. Important considerations include the additional effects of medications on biomarkers of cardiovascular risk, and safety and tolerability issues. The following drugs effectively control glucose levels by differing mechanisms of action.^[21]

Sulfonylureas: Sulfonylureas (glipizide, glyburide, glimepiride) reduce glucose levels by stimulating insulin release from the pancreas. However, they tend to cause hypoglycemia and can become less effective over time.^[22]

Meglitinides: Meglitinides (nateglinide, repaglinide) are insulin secretagogues and act by stimulating insulin release from the pancreas. They have a short half-life and restore insulin levels following meals. However, compliance is an issue because they must be taken 3 times a day with main meals.

Biguanide: Biguanide (metformin) primarily acts by inhibiting hepatic glucose production and controlling glucose levels. Although it tends to cause less weight gain, gastrointestinal side effects may be significant. Additionally, this agent may not be effective in the long-term control of this chronic disease state.

Alpha-glucosidase inhibitors: Alpha-glucosidase inhibitors (acarbose, miglitol) delay the postprandial digestion of complex carbohydrates and thus inhibit postprandial hyperglycemia. These agents are associated with severe gastrointestinal side effects and are limited by their relatively weak efficacy in lowering A1C levels.

Thiazolidinediones (TZDs): TZDs (rosiglitazone, pioglitazone) bind and activate peroxisome proliferator-activating receptor-gamma, thereby improving insulin sensitivity and reducing hepatic glucose levels. Additionally, these agents have been shown to improve estimates of beta-cell function and provide sustained glycemic control. Unlike sulfonylureas, TZDs do not cause hypoglycemia or stimulate insulin release. However, TZDs may cause fluid retention and weight gain.

Combinations: A variety of combination therapies are used to treat type 2 diabetes with 2 agents with complementary mechanisms of action. Many of these combinations have demonstrated clinical success by improving glycemic control to recommended goals while offering better tolerability profiles, in many cases due to a reduced dose of 1 or both agents. Sulfonylureas have been used in combination with insulin-sensitizing medications, including metformin and TZDs, and have demonstrated significantly improved glycemic control.^[8,23] TZDs, such as rosiglitazone and pioglitazone, in combination with metformin have been shown to improve glycemic control, insulin sensitivity, and beta-cell function.^[24,25]

Insulin: Insulin is required for the management of type 1 diabetes and in many patients at the more advanced stages of type 2 diabetes. Insulin is administered in long-acting (basal), short-acting (mealtime), and premix (long- and short-acting) formulations. Relatively peakless long-acting recombinant insulin analogs have been helpful in restoring basal insulin needs (glargine, detemir). New forms of rapid-acting insulin — called insulin analogs (lispro, aspart, glulisine) — have a faster onset and shorter duration of action than regular insulin. They are used to lower mealtime glucose excursions. Inhaled insulin, which only contains rapid-acting human insulin, is also available. This is also used for mealtime glucose control and is taken before a meal.

Incretin mimetics and dipeptidyl peptidase (DPP)-IV inhibitors: Incretins, including glucagon-like peptide (GLP)-1, are hormones secreted in the gut in response to the absorption of glucose and they have multiple glycoregulatory actions. GLP-1 levels are reduced in patients with type 2 diabetes. Exenatide, an agent that mimics the effects of naturally occurring GLP-1, has been proven effective in improving glucose control by restoring the impaired glucose-dependent insulin secretion by the islet beta cells and suppressing islet alpha-cell glucagon secretion, 2 effects that contribute to hyperglycemia in diabetes. Exenatide also slows gastric emptying, leading to a better match between food absorption and insulin secretion, which leads to improved postprandial glucose control. Exenatide administration is associated with moderate weight reduction. Side effects include nausea, especially during the first week or two of use. The drug is administered via injection twice daily, and it is costly. Longer-acting GLP-1 agonists are in development and may provide an improvement over exenatide because they would only need to be injected once daily or weekly.

Another approach to enhance the action of GLP-1 in the body, currently under US Food and Drug Administration (FDA) review, is via the DPP-IV inhibitors. DPP-IV is the enzyme responsible for the degradation of GLP-1 in the bloodstream, and blocking the action of DPP-IV significantly prolongs the blood levels of this incretin. Levels of another incretin, glucose-dependent insulinotropic polypeptide, are also enhanced when DPP-IV is inhibited. Two new oral medications, vildagliptin and sitagliptin, have shown similar glycemic benefits as exenatide via beta-cell-stimulated insulin secretion, islet alpha-cell glucagon suppression, and slowing of gastric emptying. Unfortunately, these agents have not shown a significant effect on weight reduction.

What Does the Future Hold?

Perhaps the most important goal in the management of diabetes is preventing long-term complications. One approach is the primary prevention of diabetes altogether. To that end, a number of prevention studies have shown that oral antidiabetic agents or lifestyle interventions can significantly reduce the progression of impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) to overt diabetes. Other studies have shown reduced primary or secondary cardiovascular events in patients with type 2 diabetes who were using various interventions, including statins, antihypertensives, and TZDs.^[26] In patients with established cardiovascular disease, pioglitazone showed some improvement of secondary cardiovascular endpoints in the Prospective Pioglitazone Clinical Trial In Macrovascular Events Study, but outcomes data in patients treated at earlier stages of the development of atherosclerosis are lacking. Due to increasing evidence that the prevention of diabetes and its complications may ultimately be a therapeutic possibility, several large-scale studies are under way that will help establish the best clinical approach to this goal. Clinical outcomes include the impact of intensive glycemic control on progression to diabetes, the benefits of early intervention, reduction of cardiovascular complications, and the improvement of beta-cell function.

The Diabetes Reduction with Ramipril and Rosiglitazone Medication (DREAM) study is designed to determine whether rosiglitazone and/or ramipril can delay or prevent the development of type 2 diabetes in those who have IGT and/or IFG who are at high risk of developing diabetes.^[27] The Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study is assessing the effect of valsartan and short-acting nateglinide in prediabetes patients.^[28] The Actos Now for Prevention of Diabetes (ACT NOW) trial is evaluating the effect of pioglitazone in subjects with IGT and metabolic syndrome for improvement in insulin sensitivity, beta-cell function, body composition, and cardiovascular risk factors.^[29] The A Diabetes Outcome Progression Trial (ADOPT) is designed to provide data on the differentiating effects of rosiglitazone, glyburide, and metformin on glycemic control, beta-cell function, and macrovascular disease risk.^[30] These large-scale clinical trials may have a significant impact when their findings are reported over the next several years.

Conclusions

Type 2 diabetes is a major health problem in the United States. Consequently, the incidence of diabetes complications and cardiovascular diseases is also increasing and has a negative impact on public health and the economy. Therefore, it is important to control the growing epidemic of type 2 diabetes. Younger people are especially at risk for the long-term complications of diabetes when they acquire the disease at an early age. Glycemic control is one of the most important risk factors to contain the progression of type 2 diabetes and its associated microvascular complications, and glucose itself is likely to play a key role in macrovascular disease as well. In addition to therapeutic lifestyle changes, several pharmacologic options are available for the treatment of type 2 diabetes. Antidiabetes drugs effectively control glucose levels. Intensive glycemic control may be shown to help delay the progression of type 2 diabetes as well as to offer additional benefits, such as improved beta-cell function. Ultimately, we anticipate that type 2 diabetes and its complications will be effectively managed with a comprehensive treatment strategy that includes therapeutic lifestyle modifications and pharmacologic therapy aimed at glycemic control as well as reduction in cardiovascular risk.

Increased Statin Dose Can Benefit Diabetics With Heart Disease

NEW YORK (Reuters Health) May 26 - Treating diabetics who have clinical signs of coronary heart disease with a high dose of atorvastatin (80 mg daily), rather than the normal dose of 10 mg daily, can lower the rate of major cardiovascular events by 25%, according to a report in the June issue of Diabetes Care.
In the main analysis of data from the Treating to New Targets (TNT) study, increasing the atorvastatin dose was shown to provide significant clinical benefits for patients with stable coronary heart disease. The focus of this subanalysis, conducted by Dr. James Shepherd of the University of Glasgow and colleagues, was to determine if this benefit applied to patients with heart disease and diabetes as well.
The study involved 1501 patients with baseline LDL-C levels of less than 130 mg/dL who were randomized to atorvastatin at a dose of 10 or 80 mg per day and followed for a median of 4.9 years. The primary endpoint was the time to a first major cardiovascular event, including death from heart disease, non-fatal MI, resuscitated cardiac arrest or stroke.
The final LDL-C levels reached in the 10- and 80-mg atorvastatin groups were 98.6 and 77.0 mg/dL, respectively.
The primary event rate in the higher dose atorvastatin group was 13.8%, significantly lower than the 17.9% rate noted in the lower dose group (p = 0.026). In addition, the higher dose was also linked to a delay in the occurrence of cerebrovascular events and any cardiovascular event.
Side effects were similar in both groups and no persistent elevations in liver enzymes were noted, the report indicates.
"Pending a definitive trial, these data suggest that the use of high-dose statin to achieve an LDL cholesterol level considerably lower than 100 mg/dL may be appropriate for patients with diabetes and coronary heart disease, irrespective of their initial LDL cholesterol level, age, duration of diabetes, or glycemic control," the authors conclude.
Diabetes Care 2006.

Novel Type 2 Diabetes Screening Program Helps Identify at-Risk Youth

Feb. 27, 2006 (Reno, Nevada) A new screening checklist may help identify children at risk for type 2 diabetes, according to a new study presented here at the annual meeting of the American College of Preventive Medicine. The checklist combined elevated body mass index (BMI) with other traditional risk factors, such as race/ethnicity, family history of type 2 diabetes, acanthosis nigrans, and hypertension."Our goal was to identify children ages 10 to 18 with type 2 diabetes, prediabetes, or metabolic syndrome, and to provide an intensive family-based healthy lifestyle program for children diagnosed with diabetes or prediabetes," said Elizabeth Tilson, MD, MPH, medical director of Community Care of Wake/Johnston Counties, North Carolina, a quality improvement program for Medicaid patients. Implementing the program required a collaborative community effort, involving private practitioners, the local health department, medical society, hospital, YMCA, and other agencies. Dr. Tilson and colleagues developed a screening checklist tool based on the American Academy of Pediatrics and American Diabetes Association guidelines with some modifications. Participating physicians were to screen all children aged 10 to 18 years for elevated BMI. Children with a BMI higher than the 85th percentile were assessed for the risk factors of race/ethnicity, family history of type 2 diabetes, acanthosis nigrans, and hypertension (defined as systolic blood pressure higher than the 90th percentile for age and height). If a child had one or more risk factors present in addition to a BMI higher than the 85th percentile, he or she was referred for a fasting blood glucose test and an oral glucose tolerance test. "Any child with a BMI higher than the 95th percentile was referred for a fasting blood glucose and a glucose tolerance test, even if no other risk factors were present because a BMI in this percentile is a strong risk factor for prediabetes or diabetes, Dr. Tilson said.A total of 89 physicians in 37 different practices used the new screening tool between July 2004 and December 2005. They referred a total of 747 children aged 10 to 18 years for laboratory tests during this 18-month period. At the start of the program, physicians referred fewer than 10 at-risk children per month for laboratory testing. By June 2005, however, physicians were referring about 50 children per month. Of the 747 children referred, 606 (81%) received fasting blood glucose and glucose tolerance tests. Considering the logistics of obtaining these tests in children, Dr. Tilson commented, "We were really excited about this. We thought 81% showed that the program was quite effective."Of the children who received laboratory tests, 272 (45%) had abnormal results. A majority of those children met criteria for metabolic syndrome with 3 or more factors present, such as elevated systolic blood pressure, triglycerides, and high-density lipoprotein levels, and impaired fasting blood glucose. Three children were diagnosed with type 2 diabetes (defined as a fasting blood glucose level higher than 126 mg/dL). "Of the kids that had abnormal lab results, keep in mind that the mean age of these children was 12. We are really dealing with a syndrome that used to only be seen in adults," Dr. Tilson stressed during her presentation.Children diagnosed with prediabetes or diabetes underwent a 12-week lifestyle intervention with their families, including educational classes and exercise coordinated with the YMCA and other organizations.Dr. Tilson identified several barriers to screening in private practice. "One barrier is actually parent refusal," she told Medscape. "Some parents don't want to acknowledge that their child is overweight or they aren't interested in any lifestyle interventions." She also cited time pressure on physicians. "The screening tool we have put together is to make [screening] as easy as possible in a busy clinic," Dr. Tilson said.Dr. Tilson added that physicians may not be identifying children at moderate risk for diabetes. "Physicians see so many kids that have BMIs off the chart greater than the 95th percentile so when we see kids with BMIs between the 85th and 95th percentile, we've been desensitized to referring them," she told Medscape.Commenting on Dr. Tilson's presentation, Neal Kohatsu, MD, MPH, president of the American College of Preventive Medicine, told Medscape, "The screening program is a thoughtful integration of medicine and public health. It involved working with other community constituencies to help identify populations at risk, so it was novel in that regard." He added, "I definitely think that this program could apply to many other settings where underserved children and minority populations are targeted. [The study results] would be useful information in developing a community-based diabetes screening program."The study was independently funded. The authors report no pertinent financial disclosures.Preventive Medicine 2006: Session 24 Submitted Abstracts Session. Presented February 24, 2006.Reviewed by Peggy Keen, PhD, FNP

Medical Monofilament Sensory Nerve Testers For Diabetics

Monofilaments: History and Importance

The history of the use of various filaments to test for the presence or absence of sensation dates back to the 1800’s when Von Frey used horsehairs for testing patients’ sensation thresholds. In 1960, Dr. Josephine Semmes and Dr. Sidney Weinstein developed a more sophisticated set of medical grade sensory testing monofilaments.1 Their premise was that an increased diameter of a monofilament would be accompanied by a required increased force needed to create a bend in the monofilament when it was applied to the surface to be tested. They created a progressive scale of monofilaments for neurologic sensory testing. Monofilaments are assigned numbers that range from 4.17 to 6.10. The higher the number, the stiffer the filament. The formula utilized is as follows: Marking = (log10 Force(in mg) x 10). The 5.07 monofilament has been accepted as the medical standard for screening of the minimum level of protective sensation in the foot. The reproducible buckling stress force required to bend the 5.07 monofilament is 10 grams of force.2



The problem with the original Semmes - Weinstein monofilaments was primarily related to cost. The same is true of many of the more recent versions of this product with a plastic handle designed to hold the monofilament. These devices have primarily been distributed only to health care professionals. Another clinical tool often used by health care professionals for sensory testing is the 128 C Tuning Fork used for testing vibratory perception. Again, cost, lack of ease of use and limited distribution are problems with this instrument. In fact, a number of studies have shown that the monofilament is a tool equal to that of the tuning fork as a way to diagnose loss of sensation.
TEST DEMO

Walnuts May Improve Lipid Profile in Type 2 Diabetes

Dec. 1, 2004 — Adding walnuts to a low-fat diet improves lipid profile for patients with type 2 diabetes, according to the results of a randomized study published in the December issue of Diabetes Care.

"Walnuts are distinguished from other nuts by virtue of their higher polyunsaturated fat content (and importantly their ?-linolenic acid [ALA] content) combined with antioxidants in the form of ?-tocopherol," write Linda C. Tapsell, PhD, from the National Centre of Excellence in Functional Foods, University of Wollongong in New South Wales, Australia, and colleagues. "There are mechanistic explanations for the influence of dietary polyunsaturated fatty acid (PUFA) on insulin action and energy metabolism, and cohort studies of women in the U.S. have demonstrated a reduced risk of developing type 2 diabetes with dietary PUFA replacing trans or saturated fatty acids (SFAs)."

In this parallel design trial, 58 adults with type 2 diabetes were randomized to one of three dietary advice groups, each with 30% energy as fat: low fat, modified low fat, and modified low fat inclusive of 30 g of walnuts per day. Mean age was 59.3 ± 8.1 years.

Patients received dietary advice at baseline, with monthly follow-up and telephone calls bimonthly for support. All groups were advised to consume fish and five daily portions of fruits and vegetables. Body weight, percent body fat, blood lipids, glycosylated hemoglobin (HbA1c), total antioxidant capacity, and erythrocyte fatty acid levels were measured at baseline and at three and six months, and analysis was by intent-to-treat.

Erythrocyte biomarkers of dietary intake confirmed higher dietary polyunsaturated fat-to-saturated fat ratio and intakes of ?-3 fatty acids in the walnut group. Compared with the two other treatment groups, the walnut group had a significantly greater increase in high-density lipoprotein (HDL) cholesterol-to-total cholesterol ratio (P = .049) and in HDL (P = .046). The walnut group also had a 10% reduction in low-density lipoprotein (LDL) cholesterol, reflecting a significant effect by group (P = .03) and time (P = .04).

The three groups were similar in changes in body weight, percent body fat, total antioxidant capacity, and HbA1c levels.

Study limitations include open recruitment; participation of only 50% of volunteers, limiting generalizability of the results; and lower baseline cholesterol levels in the walnut group.

"Structured 'whole of diet' advice that included 30 g of walnuts/day delivering substantial amounts of polyunsaturated fatty acid improved the lipid profile of patients with type 2 diabetes," the authors conclude.

The Australian Research Council and the California Walnut Commission funded this study.

Diabetes Care. 2004;27:2777-2783

Measurements in the Diabetic Foot

Abstract and Introduction
Abstract

Diabetic foot syndrome is complex, affects up to 20% of patients with diabetes at least once in their lifetime, and is responsible for the vast majority of amputations in the United States and in Europe. Since its clinical history evolves from an initial nonulcerative phase, to an acute ulcerative phase, an eventual recurrence, and a chronic post-ulcerative phase, measurements related to such a complex condition should explore and exhaustively describe all aspects of the pathology. In the pre-ulcerative phase, evaluation and quantification of risk factors for the development of ulceration are the most important aspects. In this phase, neuropathy and peripheral vascular disease are addressed. In the ulcerative phase, measurements related to the ulcer, including size, location, involvement of deep structures, presence of ischemia, and infection, are all relevant to establish a therapeutic program and a prognosis of the pathologic condition. In the post-ulcerative phase, emphasis should be placed on determining the risk of recurrences and evaluating postural loads and gait imbalances secondary to the outcomes of the acute phase. Such evaluation is important in the prescription of orthesis and shoes that have a protective role with the at-risk foot and thus reduce the risk of recurrences. Measurements in the diabetic foot are of paramount importance to create a quantitative paradigm and reduce empiricism in clinical practice in the management of such a complex pathology.
Introduction

From 4S to FIELD and PROactive: 10 years of CV Trials in People With Diabetes

Abstract and Introduction
Abstract

The last ten years have seen a rapid expansion in the evidence-base for the reduction of cardiovascular risk in people with diabetes. Following the landmark Scandinavian Simvastatin Survival Study (4S), several other studies have shown the benefits of statins in people with diabetes, but much less data are available for the benefit of fibrates, and the main evidence to date comes from subgroup analysis of the Veterans Affairs High Density Lipoprotein Cholesterol Intervention Trial (VA-HIT). The Hypertension in Diabetes Study (HDS), nested within the United Kingdom Prospective Diabetes Study (UKPDS), proved that tight control of hypertension reduced microvascular and macrovascular events in people with diabetes, and the Heart Outcomes Prevention Evaluation (HOPE) and MICRO-HOPE studies suggested a benefit in reducing cardiovascular events with angiotensin-converting enzyme (ACE) inhibition, additional to blood pressure lowering effects. With regards to glycaemic therapy, the UKPDS has shown the benefit of metformin in reducing myocardial infarctions. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) studies will be presented later this year and will give information on the role of fenofibrate and pioglitazone respectively in reducing cardiovascular events in people with diabetes.
Introduction

The brave new world of type 2 diabetes management embarked upon in the last decade has been truly monumental. It is easy to forget the compartmentalisation of care that preceded this with the diabetologist's primary role being the improvement of glycaemic control. The importance of viewing diabetes not so much as a disease of too much sugar associated with microvascular disease to a state of premature cardiovascular death which is associated with hyperglycaemia and microvascular disease was heralded as recently as 1996 when the evidence was still lacking.[1] This review describes some landmark cardiovascular studies over the last 10 years in type 2 diabetic patients in the fields of lipids, hypertension and glycaemic control and discusses the use of specific drugs such as statins and ACE inhibitors.
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Physicians Should Treat All Cardiovascular Risk, Not Just Metabolic Syndrome

Aug. 25, 2005 — A joint statement from the Professional Practice Committee of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), published in the September issue of Diabetes Care, advises physicians not to diagnose or treat the metabolic syndrome. Rather, the statement suggests that they should treat all cardiovascular (CV) risk.

"The term 'metabolic syndrome' refers to a clustering of specific cardiovascular disease (CVD) risk factors whose underlying pathophysiology is thought to be related to insulin resistance," write Richard Kahn, PhD, from the ADA in Alexandria, Virginia, and colleagues. "While there is no question that certain CVD risk factors are prone to cluster, we found that the metabolic syndrome has been imprecisely defined, there is a lack of certainty regarding its pathogenesis, and there is considerable doubt regarding its value as a CVD risk marker."

In recent decades, investigators identified clustering of certain CVD risk factors including obesity, type 2 diabetes, hyperlipidemia, and hypertension. Hyperinsulinemia was also linked to hyperlipidemia, obesity, and hypertension; and a cluster of CVD risk factors seemed to underlie type 2 diabetes. In association with insulin resistance, risk factor clustering led to the description of a unique pathophysiologic condition termed the "metabolic" or "insulin resistance" syndrome.

On Jan. 28, 2005, the authors performed a Medline search using the keywords "syndrome X" or "insulin resistance syndrome" or "metabolic syndrome," identifying 4,646 citations, including 3,948 studies performed on human subjects. Definitions for "metabolic syndrome" have been proposed by the World Health Organization (WHO) and the Third Report of the National Cholesterol Education Program's Adult Treatment Panel (ATP III), as well as by other organizations.

This review critically examined the evidence underlying the definition of the metabolic syndrome, as well as its pathogenesis, association with CVD, and impact of treatment. The primary focus was on articles addressing the metabolic syndrome as defined by ATP III, with a view toward answering three main questions: (1) How clear is the existing definition of the metabolic syndrome for diagnostic purposes?; (2) Does the treatment of metabolic syndrome differ from treatment of its individual components?; and (3) What additional research is needed to improve current knowledge of this syndrome?

"Until much needed research is completed, clinicians should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of the 'metabolic syndrome,'" the authors write. "Our analysis indicates that too much critically important information is missing to warrant its designation as a 'syndrome.'"

Until additional studies address unanswered questions, the authors recommend that patients with diabetes or clinical CVD should be excluded from the case definition of metabolic syndrome; that adults with any major CVD risk factor should be evaluated for the presence of other CVD risk factors; that patients with CVD risk variables over normal limits should be counseled regarding lifestyle modification; that those with markers indicating overt disease (such as blood pressure higher than 140/90 mmHg or fasting plasma glucose level at 7.0 mmol/L or more) should be treated according to established guidelines; and that all CVD risk factors should be individually and aggressively treated.

"Providers should avoid labeling patients with the term 'metabolic syndrome,' as this might create the impression that the metabolic syndrome denotes a greater risk than its components, or that it is more serious than other CVD risk factors, or that the underlying pathophysiology is clear," the authors conclude. "Until randomized controlled trials have been completed, there is no appropriate pharmacological treatment for the metabolic syndrome, nor should it be assumed that pharmacological therapy to reduce insulin resistance will be beneficial to patients with the metabolic syndrome."

Diabetes Care. 2005;28:000-000

Canadian Study Demonstrates New Approach To Achieving Diabetes Control

Insight study reveals leading research on the benefits of using insulin earlier HAMILTON, ONTARIO -- June 16, 2005 -- Results of an all-Canadian study announced June 13 at an international diabetes congress demonstrate that patients with type 2 diabetes can safely achieve target blood sugar (glycemic) levels faster and more frequently when insulin glargine (a basal, long-acting insulin) is added to therapy, versus using oral agents alone. In addition to achieving better glycemic control, patients using insulin glargine expressed increased satisfaction with their treatment and experienced improved quality of life. The INSIGHT study (Implementing New Strategies with Insulin Glargine for Hyperglycemia Therapy), presented at the 65th American Diabetes Association Annual Meeting and Scientific Sessions by lead investigator, Dr. Hertzel Gerstein, a professor of medicine and director of endocrinology and metabolism at McMaster University in Hamilton, demonstrated that early addition of insulin glargine therapy (in combination with oral agents or alone) safely achieved better glycemic and metabolic outcomes than adding oral agents. These results were achieved with no increased risk of hypoglycemia (low blood sugar levels) compared to oral medications. "Often, insulin therapy is considered as a last resort during late-stage disease," said Dr. Gerstein. "What INSIGHT has shown is that basal insulin therapy with insulin glargine can be safely and effectively introduced early in the course of diabetes. These results may help change the way that type 2 diabetes is managed in the future." All patients in the study had an A1C (target glycemic level) between seven and 11 per cent. This is above the recommended target of seven per cent or less, established by the Canadian Diabetes Association in the 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. When insulin glargine was added to their treatment, patients were able to achieve lower and steady blood glucose levels more quickly and more often. Diabetes in Canada According to Health Canada, it is estimated that 2.25 million Canadians have either type 1 or type 2 diabetes. Diabetes is the seventh leading cause of death in Canada, and Canadian adults with diabetes are twice as likely to die prematurely, compared to persons without diabetes. The Canadian Diabetes Association states that the aggressive management of diabetes is critical in order to delay or altogether prevent complications such as heart disease, stroke, permanent vision loss, renal disease, damage to the limbs and erectile dysfunction in men. Aggressive treatment is critical, especially for patients with an A1C level of nine per cent or less. Health Canada recognizes that the growth of diabetes is at epidemic levels and estimates that at least 30 per cent of adults with diabetes are unaware they have the condition. Health Canada also states that healthcare costs for managing diabetes and its complications amount to more than $9 billion annually. About Insulin Glargine Insulin glargine is approved for once-daily administration in patients over the age of 17 with type 1 or type 2 diabetes who require basal insulin to control abnormally high blood sugar levels. Insulin glargine can be used with oral diabetes medications and/or short-acting insulin to help control diabetes. About the INSIGHT Study The INSIGHT study is an all-Canadian study comparing the percentage of people who reached a target glycemic level (A1C) of 6.5 per cent or less, in two consecutive readings, when insulin glargine was added to their current therapy, versus those on adjusted oral therapy alone. The study, involving 19 endocrinologists and 34 general practitioners, was conducted at 53 study sites including British Columbia, Alberta, Manitoba, Ontario, Quebec, Prince Edward Island, Nova Scotia and Newfoundland. A total of 405 patients with type 2 diabetes were enrolled to participate in this open-label, randomized, two-arm parallel study that consisted of a two-week screening phase and a 24-week treatment phase. SOURCE: McMaster University

Energy Expenditure Promises Benefits for Diabetics

NEW YORK (Reuters Health) May 25 - Physical activity that expends more than 10 metabolic equivalents (METs) per hour per week will provide health advantages and reduced medical costs for patients with type 2 diabetes, according to Italian researchers. However, full benefits are not achieved unless more than 20 METs per hour per week are expended.

Senior author Dr. Pierpaolo De Feo and colleagues, from the University of Perugia note

that the results confirm that general recommendations of at least 30 minutes of moderate-intensity physical activity on most days are "also valid for type 2 diabetic subjects and demonstrate a significant dose-response relationship."

The findings, which appear in the June issue of Diabetes Care, are based on an analysis of data from 179 type 2 diabetic subjects who participated in a physical activity intervention. The subjects were divided into six groups based on the number of METs expended per hour per week.

The two groups that performed no more than 10 METs of exercise per hour per week experienced no change in HbA1c, blood pressure, total cholesterol, triglycerides, or heart disease risk. By contrast, the other four groups experienced improvements in all of these parameters.

In order to also achieve an improvement in body weight, waist circumference, heart rate, fasting glucose, serum LDL and HDL cholesterol, more than 20 METs per hour per week of activity was needed, the investigators note.

The groups with more than 10 METs per hour per week of exercise experienced a reduction in per capita yearly medication costs. The group with the lowest activity level (no METs) experienced a rise in costs and the group with the next lowest level (1 to 10 METS per hour per week) had no change in costs.

In a related editorial, Dr. James O. Hill, from the University of Colorado, Denver, comments that the results "provide an optimistic message about physical activity and type 2 diabetes. It isn't necessary for your patients to do a lot of strenuous exercise to reap health benefits. Even small increases in physical activity can help, and it seems possible to produce these changes in the majority of your patients."

Diabetes Care 2005;28:1295-1302,1524-1525.

Dairy Products May Lower Risk of Type 2 Diabetes in Men CME

May 10, 2005 — Men who have a high dairy intake have a lower risk of type 2 diabetes mellitus (DM), according to the results of a prospective study published in the May 9 issue of the Archives of Internal Medicine. The editorialist reviews the purported benefits of milk and dairy products.

"Diet and lifestyle modifications can substantially reduce the risk of type 2 diabetes," write Hyon K. Choi, MD, from Massachusetts General Hospital in Boston, and colleagues. "While a strong inverse association has been reported between dairy consumption and the insulin resistance syndrome among young obese adults, the relation between dairy intake and type 2 diabetes is unknown."

The investigators prospectively examined the relationship between dairy intake and incident cases of type 2 DM in 41,254 male participants with no history of DM, cardiovascular disease, and cancer when enrolled in the Health Professionals Follow-up Study.

During 12 years of follow-up, there were 1,243 incident cases of type 2 DM. Dairy intake was associated with a modestly lower risk of type 2 DM. Compared with men in the lowest quintile of dairy intake, the relative risk (RR) for type 2 DM in men in the top quintile of dairy intake was 0.77 (95% confidence interval [CI], 0.62 - 0.95; P for trend = .003), after adjustment for body mass index (BMI), physical activity, dietary factors, and other potential confounders.

For each serving-per-day increase in total dairy intake, there was a 9% lower risk for type 2 DM (multivariate RR, 0.91; 95% CI, 0.85 - 0.97). The corresponding RR was 0.88 (95% CI, 0.81 - 0.94) for low-fat dairy intake and 0.99 (95% CI, 0.91 - 1.07) for high-fat dairy intake. BMI did not affect this association (< 25 vs >/= 25 kg/m2; P for interaction, .57).

"Dietary patterns characterized by higher dairy intake, especially low-fat dairy intake, may lower the risk of type 2 diabetes in men," the authors write.

Study limitations include observational design, potential for unmeasured confounding, self-reporting of DM with possible underdiagnosis, and study population limited to men 40 years old and older with no history of type 2 DM.

The National Institutes of Health supported this study in part. The authors report no financial disclosures.

In an accompanying editorial, Janet C. King, PhD, from Children's Hospital Oakland Research Institute in California, calls this study "a further reminder of the potential importance of dairy intake and the continuing value of research in this area." She notes that milk contains amino acids, vitamins, minerals, and additional bioactive components.

"Many of these components protect individuals from exogenous stresses, toxins, and pathogens; encourage adaptation to the environment; and promote metabolic regulation, while other milk components cause negative effects in susceptible individuals," Dr. King writes. "Research shows that the role of dairy foods in health is very complex and probably varies with the genotype and phenotype of the individual."

Dr. King reports no financial conflicts of interest.

Arch Intern Med. 2005;165:975-976, 997-1003