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

Pioglitazone Slows Carotid Thickening in Diabetics

NEW YORK (Reuters Health) May 13 - Independent of its ability to improve glycemic control, pioglitazone therapy decreases carotid intima-media thickness (IMT) in patients with type 2 diabetes, according to a report in the May 17th issue of Circulation.

"We are encouraged by these results because the benefits seen with pioglitazone could, theoretically, lead to an overall reduction in the incidence of heart attack and stroke for people with type 2 diabetes," study co-author Dr. Thomas Forst, from the Institute for Clinical Research and Development in Mainz, Germany, said in a statement.

The findings stem from a study funded by Takeda Pharmaceuticals, which markets pioglitazone under the trade name Actos.

The study involved 173 patients with type 2 diabetes who were randomized to receive pioglitazone or glimepiride-based treatment for 24 weeks.

During the study period, patients in each group experienced similar improvements in glycemic control, based on HbA1c levels. However, only pioglitazone-treated subjects showed a significant reduction in carotid IMT at 12 and 24 weeks.

Insulin resistance improved significantly in the pioglitazone group, but not in the glimepiride group.

Further analysis showed that the drop in carotid IMT correlated with the improvement in insulin resistance, but was independent of changes in glycemic control, the authors note.

"Our results support the growing body of evidence for an anti-atherogenic effect of PPAR-gamma activators that reach beyond glycemic control and might imply prognostic benefits for patients treated with this class of drugs and especially for patients with type 2 diabetes," the authors conclude.

Circulation 2005;111:2525-2531.

Danish Study Outlines Risk Factors for Diabetic Maculopathy

By Earl R. Nichols FT. LAUDERDALE, FL -- May 9, 2005 -- According to a large Danish database, there does not appear to be a significant difference in the risk of developing diabetic maculopathy between patients with type 1 or type 2 diabetes, or type 2 patients who are insulin-dependent and who are not insulin-dependent. The risk is more or less similar, at 25.4 cases (a 5--year incidence rate of 11.9%) per thousand patient-years for patients with type 1 diabetes and 31.8 cases (a 5--year incidence rate of 14.7%) per thousand patient-years for those with type 2 diabetes. M. L. Laursen, MD, department of ophthalmology, Odense University Hospital, Odense, Denmark, presented the results in a poster session here at the Association for Research in Vision and Ophthalmology Annual Meeting. The longitudinal observational study was conducted at one diabetes clinic between 1997 and 2001 and examined a total of 1218 patients -- 696 with type 1 diabetes and 522 with type 2 diabetes. Patients had their eyes examined regularly using two-field, non-stereoscopic photography of the fundus. Over the course of the 5-year follow-up period, 47 patients with type 1 diabetes and 39 patients with type 2 diabetes developed maculopathy. Slightly more patients with insulin-dependent type 2 diabetes went on to develop maculopathy, but the difference was not significant when compared with those who were not insulin-dependent. Patients with type 1 diabetes were significantly younger than those with type 2 disease and had had diabetes for longer compared to type 2 diabetics (17.0 years vs. 9 years). When the database began collecting information, the patients were 40.3 years old in the type 1 diabetes group and 57.5 years old in the type 2 group. Those with type 1 disease were more likely to have normal body mass index, while those with type 2 disease were more likely to be overweight or obese. The main factors predicting which patients with type 1 diabetes were most likely to develop maculopathy were elevated triglycerides (risk ratio [RR] 1.29), haemoglobin 1Ac (RR 1.28) and vibration perception threshold, which is a measure of muscle and nerve fiber reactivity (RR 1.21) The factors most likely to be associated with progression to maculopathy among type 2 diabetics were duration of disease (RR 1.08), diastolic blood pressure (RR 1.20) and vibration perception threshold (RR 1.26) Other factors that were associated with a greater risk of developing maculopathy included elevated low-density lipoprotein cholesterol level and elevated total cholesterol level. Men were more likely to develop maculopathy than women (RR 1.61 and 1.44, respectively). Vibration perception threshold may be the most important of all these factors since it is known that mixed sensory autonomic neuropathy is the most common clinical subtype of diabetic neuropathy and that this may in turn reflect abnormalities in choroidal blood flow, which is highly innervated and regulated by the autonomic nervous system, the authors concluded. [Presentation title: Incidence of and Risk Factors for Diabetic Maculopathy in a Danish Photographic Screening Programme. Poster 393/B367]

Intense Insulin Therapy Does Not Improve Outcome After MI

NEW YORK (Reuters Health) May 03 - Intense metabolic control using insulin does not improve mortality and morbidity in type 2 diabetic patients after acute myocardial infarction, according to the results of a multicenter European study.

Insulin does not seem to be the only solution, but tight glucose control by any means is very important." Dr. Lars Ryden from the Karolinska Institute, Stockholm, told Reuters Health. He advises clinicians to "use all available tools to keep blood glucose...down."

Dr. Ryden and colleagues in the Diabetes and Insulin-Glucose Infusion in Acute MI 2 (DIGAMI 2) study compared three glucose management strategies in more than 1200 diabetic patients after suspected acute myocardial infarction.

These included acute insulin-glucose infusion followed by long-term insulin-based treatment; acute insulin-glucose infusion followed by standard glucose control; and routine management according to local practice.

Although blood glucose levels were lower with the first two strategies after the first 24 hours, the authors report, glucose control over time (blood glucose and glycosylated hemoglobin levels) did not differ among the three treatment approaches, Dr. Ryden's group reports in the April issue of the European Heart Journal.

Mortality also did not significantly differ among the three treatment groups. Secondary events (stroke, myocardial reinfarction, etc.) tended to be higher in the most intensive treatment program, but the differences did not reach statistical significance.

Although the three different treatment strategies had similar effects on mortality, "hyperglycemia remained one of the most important prognostic predictors," the investigators note.

"Future development of tools that will allow frequent and precise (non-invasive) measurement of blood glucose levels and, eventually, of an automated system for insulin-titrated tight blood glucose control will be of utmost importance," writes Dr. Greta Van den Berghe from Catholic University of Leuven, Belgium in a related editorial.

"We anxiously await the development and validation of such devices," Dr. Van den Berghe concluded.

Eur Heart J 2005;26:639-641,650-661.

Insulin Identified as Trigger for Type 1 Diabetes

WEDNESDAY, May 11 (HealthDay News) -- Insulin, the hormone most closely linked to diabetes, has turned out to be the cause of the inherited form of the blood sugar disease, researchers report.

For reasons that remain unclear, in patients with type 1 diabetes the body's immune T-cells react against insulin-producing cells in the pancreas -- effectively shutting them down and triggering disease onset.

After eight long years of painstaking----------------------------------------------(read online)

>Diabetic Neuropathies

Introduction

The diabetic neuropathies are heterogeneous, affecting different parts of the nervous system that present with diverse clinical manifestations. They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor distal symmetric polyneuropathy (DPN) and the autonomic neuropathies. DPN is a diagnosis of exclusion. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons. 1 ) Nondiabetic neuropathies may be present in patients with diabetes. 2 ) A number of treatment options exist for symptomatic diabetic neuropathy. 3 ) Up to 50% of DPN may be asymptomatic, and patients are at risk of insensate injury to their feet. As >80% of amputations follow a foot ulcer or injury, early recognition of at-risk individuals, provision of education, and appropriate foot care may result in a reduced incidence of ulceration and consequently amputation. 4 ) Autonomic neuropathy may involve every system in the body. 5 ) Autonomic neuropathy causes substantial morbidity and increased mortality, particularly if cardiovascular autonomic neuropathy (CAN) is present. Treatment should be directed at underlying pathogenesis. Effective symptomatic treatments are available for the manifestations of DPN and autonomic neuropathy.

This statement is based on two recent technical reviews,[1,2] to which the reader is referred for detailed discussion and relevant references to the literature.---- cont online

Impact of MI, Diabetes on Overall Health Differs Between the Sexes

By Megan Rauscher

NEW YORK (Reuters Health) May 02 - In men myocardial infarction increases the risk of death from heart disease more so than diabetes, but in women diabetes is a greater mortality threat, according to results of a Finnish study reported May 3rd in the Journal of the American College of Cardiology.

"In general, diabetes is bad news for women," Dr. Gang Hu from National Public Health Institute and University of Helsinki told Reuters Health. "More aggressive management of diabetes to prevent cardiovascular disease may be needed, particularly in women," the researcher warned.

In the study, the investigators compared the effects of diabetes and MI on the risk of death in two cohorts of patients: a baseline cohort, which included 2416 patients with prior diabetes or MI who were followed for 12 years; and a follow-up cohort, which included 4315 patients who were diagnosed with incident diabetes or MI during follow-up and were further followed for 7.7 years after diagnosis.

Most previous studies only had a "single baseline measurement for the disease status of diabetes and MI," Dr. Hu pointed out.

In the baseline cohort, men with prior MI had a 20% to 80% increased risk of death from CHD or any cause, whereas women with prior MI had a 43% to 45% decreased risk of CHD or total mortality compared with men and women with prior diabetes.

In the follow-up cohort, men and women with incident MI had a greater risk of dying from heart disease, with hazard ratios of 2.15 and 1.65, respectively, compared with men and women with incident diabetes.

Total mortality, however, was similar between subjects with incident diabetes and MI during follow up, Dr. Hu said.

For people with incident MI, CHD is "the major cause of death," Dr. Hu explained, whereas people with incident diabetes may be at increased risk of dying from CHD, stroke, cancer, kidney disease, infection and other causes. Thus, total mortality is similar between subjects with incident diabetes and MI, which highlights the importance of diabetes on overall health, the researcher added.

In a statement, Dr. Christiane E. Angermann, from the University of Wurzburg in Germany said this study provides "yet another strong argument for the necessity to consider gender-related differences between men and women regarding the impact of risk factors, while designing guidelines not only for diagnosis and therapy, but also, and in particular, for the prevention of cardiovascular disease."

J Am Coll Cardiol 2005;45:1413-1418.

FDA OKs Lilly-Amylin Drug for Type 2 Diabetes

Fri Apr 29, 2005 5:38 PM BST

By Toni Clarke

NEW YORK (Reuters) - U.S. regulators have approved a diabetes drug derived from lizard saliva for patients who have not responded to other treatments, the drug's developers, Eli Lilly and Co. and Amylin Pharmaceuticals Inc., said on Friday.

The U.S. Food and Drug Administration approved exenatide, an injectable drug to be sold under the brand name Byetta, as an additional therapy for patients with Type II diabetes -- the most common form -- whose blood sugars are not sufficiently controlled by two oral medications.

Analysts expect the drug could eventually generate sales of about $1 billion to $2 billion.

Shares of Amylin fell 8 percent to $16.73 in midday trade on the Nasdaq, after earlier touching a two-year low of $16.01. Analysts, however, said the news was positive for Amylin.

The companies, which had sought approval only to market Byetta only in combination with other diabetes drugs, said that the FDA also gave conditional approval for Byetta as a stand-alone treatment, subject to further clinical trials.

Jamaison Schuler, a spokesman for Eli Lilly, said the FDA's decision to conditionally approve the drug as a stand-alone treatment is "wonderful news" as the companies had not sought such approval and indicates the agency sees promise in the drug for this use.

Some analysts, as well as Lilly, said that investors may be misinterpreting the conditional approval as a negative move.

Exenatide is Amylin's second product on the commercial market. It already sells Symlin, another diabetes treatment.

Exenatide, which is a synthetic version of saliva of the Gila monster lizard that lives in the Arizona desert, is the first of a new class of drugs known as incretin mimetics. It mimics hormones, released in the human gut in response to food, that help regulate glucose levels.

Trials of 1,446 patients showed about a 1 percent reduction in blood sugar levels in patients who took Byetta along with other oral diabetes medications, including widely used metformin and a class of older drugs called sulfonylureas.

Most patients also experience weight loss. Weight gain is seen as a risk factor for diabetes.

Patients can inject Byetta as an alternative to taking insulin, which can cause hypoglycemia, or worrisome drops in blood sugar levels that can cause fainting.

Because Byetta is not closely linked with hypoglycemia Shao said patients would not have to monitor their blood glucose levels as constantly as insulin users must.

"I'll especially recommend this drug for obese diabetics who are making their best effort to control their diets but are still not losing weight," said Dr. Stuart Weiss, an assistant professor at New York University Medical School.

Shares of Lilly, which has many drugs on the market, were unchanged at $58.00 on the New York Stock Exchange.

More than 15 million people in the United States have type II diabetes. Diabetics are unable to produce enough insulin or cannot process their insulin properly, resulting in dangerously high blood-sugar levels, which can lead to heart disease, blindness and amputations if not treated.

Amylin Chief Operating Officer Daniel Bradbury said the company has not yet set a price for the drug. He said it could face future competition from Danish drug maker Novo Nordisk, which is working on a rival medicine called Liraglutide.

Novartis AG, Merck & Co. Inc. and Bristol-Myers Squibb are also testing diabetes drugs in a different class that try to prolong the gut's natural insulin secretions.

(Additional reporting by Ransdell Pierson in New York and Susan Heavey in Washington.)

© Reuters 2005. All rights reserved

Prevention of Type 2 Diabetes With Troglitazone in the Diabetes Prevention Program

Abstract and Introduction
Abstract

The Diabetes Prevention Program (DPP) was a randomized clinical trial of prevention of type 2 diabetes in high-risk people. Troglitazone, an insulin-sensitizing agent, was used initially but was discontinued during the trial. Troglitazone therapy was compared with other DPP interventions, considering both the short-term "in-trial" results and the longer-term results after troglitazone were discontinued. From 1996 to 1998, participants were randomly assigned to treatment with metformin ( n = 587), troglitazone ( n = 585), double placebo ( n = 582), or intensive lifestyle intervention (ILS) ( n = 589). Because of concern regarding its liver toxicity, the troglitazone arm was discontinued in June 1998, after which follow-up of all participants continued. During the mean 0.9 year (range 0.5-1.5 years) of troglitazone treatment, the diabetes incidence rate was 3.0 cases/100 person-years, compared with 12.0, 6.7, and 5.1 cases/100 person-years in the placebo, metformin, and ILS participants ( P < 0.001, troglitazone vs. placebo; P = 0.02, troglitazone vs. metformin; P = 0.18, troglitazone vs. ILS). This effect of troglitazone was in part due to improved insulin sensitivity with maintenance of insulin secretion. During the 3 years after troglitazone withdrawal, the diabetes incidence rate was almost identical to that of the placebo group. Troglitazone, therefore, markedly reduced the incidence of diabetes during its limited period of use, but this action did not persist. Whether other thiazolidinedione drugs used for longer periods can safely prevent diabetes remains to be determined.
Introduction

The Diabetes Prevention Program (DPP) was a randomized clinical trial of prevention of type 2 diabetes in people at high risk of diabetes.[1] Enrollment began in 1996 with randomization to four treatment groups. Three treatments were standard healthy lifestyle recommendations plus placebo, metformin, or troglitazone. The fourth treatment was intensive lifestyle (ILS), which consisted of no drugs and the same lifestyle recommendations given to the pharmacologic groups, but the lifestyle advice was given with much more behavioral support. The details of these treatments and the results of three of the interventions have been described,[1-3] and the protocol is available at http://www.bsc.gwu.edu/dpp/protocol.htmlvdoc .

In planning the DPP (from 1994 to 1996), the research group considered testing several drugs affecting insulin secretion and sensitivity. Metformin and troglitazone, two drugs of different classes with different actions, were chosen. Metformin had been used worldwide in treating type 2 diabetes for several decades but was not approved in the U.S. until 1994. Troglitazone, an insulin-sensitizing thiazolidinedione, showed promise in improving insulin sensitivity and glucose tolerance.[4] Its use was started in the DPP in 1996 as an investigational drug. It was then approved in the U.S. for diabetes treatment in 1997 but was withdrawn from the DPP in 1998 and from the U.S. market in 2000 because of liver toxicity. In this study, we report the results of troglitazone treatment both before and after its discontinuation during the DPP.
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Diabetic Neuropathies

Introduction

The diabetic neuropathies are heterogeneous, affecting different parts of the nervous system that present with diverse clinical manifestations. They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor distal symmetric polyneuropathy (DPN) and the autonomic neuropathies. DPN is a diagnosis of exclusion. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons. 1 ) Nondiabetic neuropathies may be present in patients with diabetes. 2 ) A number of treatment options exist for symptomatic diabetic neuropathy. 3 ) Up to 50% of DPN may be asymptomatic, and patients are at risk of insensate injury to their feet. As >80% of amputations follow a foot ulcer or injury, early recognition of at-risk individuals, provision of education, and appropriate foot care may result in a reduced incidence of ulceration and consequently amputation. 4 ) Autonomic neuropathy may involve every system in the body. 5 ) Autonomic neuropathy causes substantial morbidity and increased mortality, particularly if cardiovascular autonomic neuropathy (CAN) is present. Treatment should be directed at underlying pathogenesis. Effective symptomatic treatments are available for the manifestations of DPN and autonomic neuropathy.

This statement is based on two recent technical reviews,[1,2] to which the reader is referred for detailed discussion and relevant references to the literature. READ NEXT ONLINE

Metformin May Cut Risk of Cancer in Diabetics

NEW YORK (Reuters Health) Apr 21 - Patients with type 2 diabetes who are prescribed metformin appear to be at lower risk of cancer than those not treated with metformin, according to a pilot observational study reported in the British Medical Journal Online First on April 21.

Lead author Dr. Josie M. M. Evans and colleagues at the University of Dundee in Scotland explain that metformin activates the enzyme AMP activated protein kinase, which in turn is regulated by the tumor suppressor LKB1. They therefore theorized that metformin use may reduce risk of cancer.

To test their hypothesis, they performed a case-control study in which a diabetes clinical information system was linked with a database of dispensed prescriptions.

Between 1993 and 2001, nearly 12,000 patients had been newly diagnosed with type 2 diabetes, including 923 who were later diagnosed with cancer. These were matched to 1846 diabetic subjects without cancer by age, year of diagnosis and gender.

During the year prior to the cancer diagnosis, 36.4% of cases and 39.7% of controls had been given a prescription for metformin (odds ratio 0.86). The odds ratio for any exposure to metformin since 1993 was 0.79.

There appeared to be a dose-response relationship between metformin and cancer, as the odds were further reduced by increasing duration of metformin treatment and total amount of metformin dispensed.

The research team is now in the planning phase of a large cohort study linked to a cancer registration database, they note.

BMJ Online First 2005.

Caffeine Boosts Insulin Resistance Regardless of Exercise, Weight Loss

By Anne Harding

NEW YORK (Reuters Health) Mar 18 - Caffeine intake has a negative effect on insulin sensitivity in men with and without type 2 diabetes, and this effect persists even with regular exercise and loss of adiposity, Canadian researchers report.

"Through mechanisms that have yet to be firmly established, caffeine attenuates any of the beneficial effects of exercise or weight loss on insulin resistance," Dr. Robert Ross of Queens University in Kingston, Ontario, told Reuters Health. While the clinical implications remain unclear, Dr. Ross added, the findings are a "red flag" for clinicians and are particularly important for obese patients and those with diabetes, who already are at greater metabolic risk.

Dr. Ross and his team performed hyperinsulemic-euglycemic clamp procedures in 23 men before and after a three-month exercise program. The men were given 5 mg/kg of caffeine or placebo in a double-blind, randomized fashion. Subjects included eight sedentary lean men, seven obese men with type 2 diabetes and eight obese men without diabetes.

Before the exercise program, caffeine reduced insulin sensitivity by 33% in the lean and obese men and 37% in the men with type 2 diabetes compared to placebo. After the exercise program, insulin sensitivity fell 23% after caffeine intake in the lean men, 26% in the obese men, and 36% in the diabetic men. The post-exercise difference was not statistically significant.

The findings, published in the March issue of Diabetes Care, seem to contradict recent reports that coffee intake is associated with a reduction in type 2 diabetes risk, Dr. Ross noted. However, coffee contains several other substances that may affect glucose metabolism, such as antioxidants, potassium and magnesium. "When you give somebody caffeine without all of the other substances that are in coffee you have a very different situation," he added.

"What is clear," he continued, "is that caffeine has a very powerful physiological effect."

Diabetes Care 2005;28:576-572.