Guest guest Posted April 9, 2008 Report Share Posted April 9, 2008 1. PERISCOPE: Pioglitazone Prevents Atherosclerosis Progression in Diabetics Heartwire 2008. © 2008 Medscape Mar 31, 2008 - A new study of pioglitazone (Actos) suggests that it can prevent progression of atherosclerosis and produce meaningful improvements in cardiovascular risk factors over 18 months, as compared with glimepiride (Amaryl) Experts say results of the Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation (PERISCOPE) trial, presented here at the American College of Cardiology 2008 Scientific Sessions, raise new questions about how best to lower blood sugar levels in T2DM. Dr Nissen (Cleveland Clinic), who presented the results during a late-breaking trial session , called the results a " huge surprise. " " What we saw was that the people who got one of the most widely used therapies--glimepiride, a sulfonylurea--had unequivocal progression of coronary atherosclerosis by [intravascular ultrasound] IVUS, while pioglitazone had a little less plaque at the end of the study, and the difference between the two therapies was highly statistically significant. . . . To our knowledge, this is first time that a diabetes study has been shown to slow progression of coronary atherosclerosis. " He emphasized that while no one study should change clinical practice, that the PERISCOPE results come in the wake of PROACTIVE, which showed a significant 16% reduction in its secondary end point of death, MI, and stroke with pioglitazone. " I think the totality of information suggests this is a beneficial therapy, but PERISCOPE alone doesn't answer all the questions. " But commenting on the study for heartwire, Dr Blumenthal ( Hopkins) warned against making too much of a small imaging study on top of a larger clinical trial that failed to meet its primary end point. " We need more supportive data. Right now the totality of evidence is not enough to change guidelines, " he said. " The chance of this having a significant impact on clinical practice is the same as a snowball's chance in Hades. " In PERISCOPE, 543 patients with T2 underwent coronary IVUS and then were randomized to receive either glimepiride or pioglitazone for 18 months, at which time IVUS studies were repeated. According to study investigators, mean percent atheroma volume decreased by 0.16% in pioglitazone- treated subjects but increased by 0.73% in glimepiride-treated patients. Both agents lowered glycohemoglobin and fasting insulin levels, although pioglitazone's effects on these end points were statistically greater. Pioglitazone also produced statistically meaningful changes in HDL and triglyceride levels. Adverse events in the trial were clearly different between the 2 drugs. More patients taking glimepiride developed hypoglycemia and angina, while patients taking pioglitazone were more likely to develop edema, gain weight, or suffer bone fractures. Commenting on the study, Dr S Yusuf highlighted the fracture results, which occurred in 3% of the pioglitazone-treated patients. " This was a significant excess in fractures with pioglitazone, and no matter how good a surrogate end point, even if it is truly related to the outcome you're interested in, which may be CV events, it doesn't tell you the totality of the benefit/risk, " he said. Following Nissen's presentation, one of the session moderators, Dr Greg Brown , asked Nissen if the PERISCOPE results have " changed [his] opinion about the glitazone class, " referring to the 2007 hullabaloo over rosiglitazone[avandia] , sparked in large part by a meta-analysis that Nissen coauthored. Nissen called this a " fair question " but emphasized that, while technically in the same class, rosiglitazone and pioglitazone affect different genes. " They both affect a gene that is involved in lowering blood sugar, but they have otherwise extraordinarily different effects. We have to study each of these compounds individually. " JAMA 2008; 2.%% MNTD - Reduced Lung Capacity Accelerates With Diabetes 27 Mar 2008 People who have diabetes encounter a faster loss of lung capacity than those who do not have DM, a finding that may have implications for the potential use of inhaled insulin, according to a study appearing in the April issue of Diabetes Care. The lung research, part of a larger investigation known as the Atherosclerosis Risk in Communities (ARIC) study, confirmed previous suggestions that the lung is a target organ for diabetic injury and that lung abnormalities accelerate once DM takes hold. Previous research by the same authors established that decreased lung capacity precedes and may predict a diagnosis of diabetes. The new study is accompanied by an editorial that concludes that diminished lung function may contribute to DM morbidity and mortality. Specifically, the study found that people with T2 experienced a more rapid decline in forced vital capacity, the measure of how well the lungs fill with air, than people without DM. Though all people experience a decline in forced vital capacity as they age, diabetics appear to undergo a more rapid loss that appears before the diabetes diagnosis and accelerates after the disease sets in. This could be because high blood sugar levels stiffen the lung tissue, or because the fat tissue in the chest and abdomen may confine the lungs more in people with DM, explained the researchers. They concluded the study with advice to clinicians to " pay heightened attention to pulmonary function in their patients with T2. [and] that the loss of pulmonary function could add to diabetic morbidity and mortality, and raised concerns about the potential use of inhaled insulin, since it may " trigger or exacerbate pulmonary dysfunction. " 3.%%MNTD - Implantable Device Designed For Type-2 Diabetes Patients Who Are Overweight And Do Not Respond To Current Oral Anti-Diabetic Treatments 28 Mar 2008 New York-Presbyterian Hospital/Weill Cornell Medical Center is recruiting patients for a national clinical research study of an investigational implantable device designed to help those with T2 who are overweight and do not respond to current oral anti-diabetic treatments. The Tantalus® System is designed to sense naturally occurring electrical activity of the stomach in real time and automatically apply electrical stimulation when a person eats. The device is implanted though a minimally invasive laparoscopic procedure that can be performed in an outpatient setting. " Even with current medications and lifestyle changes, controlling T2 in patients who are overweight can be difficult. This new treatment potentially offers new hope for patients who have been unsuccessful in managing their diabetes and weight, " says Dr. Louis Aronne, clinical site principal investigator, director of the Comprehensive Weight Control Program at [the medical center] An earlier, smaller study published in the Journal of Obesity Surgery found that the device reduced hunger and body weight in morbidly obese patients. Improvements in blood pressure were also seen. " The primary objective of the current study is to evaluate the safety and efficacy of the Tantalus in treating overweight patients with type-2 diabetes. The device's impact on weight loss, blood pressure and other clinical and metabolic parameters will also be studied, " http://www.med.cornell.edu 4.%% MW -Diabetics More Likely to Have Carpal Tunnel Surgery (Reuters Health) Apr 01 - Patients with T2DM are more than 4 times more likely to undergo carpal tunnel decompression surgery than are people without DM, according to an Australian study. " Our article, " the senior investigator told Reuters Health, " confirms that DM patients have decompression surgery for carpal tunnel syndrome much more frequently than people without diabetes. " [1248 diabetic participants in an observational study; 67 had carpal tunnel decompression during 12,109 patient-years of follow-up. This amounted to an incidence of 5.5 per 1,000 patient-years, a rate that was at least 4.2 times that in the general population. In examining demographic and other factors for possible reasons for this high rate in diabetics, he continued, " our data suggest that the decision to go ahead with the procedure is influenced by obesity/overweight, which is likely to increase the severity of the symptoms associated with carpal tunnel syndrome. " They also found evidence, he added, " that being in a stable relationship was important, perhaps because of the greater financial resources and psychological support for an operation in this situation. " Diabetes Care 2008;31:498-500. 5.%% ADA - Dying to Be Thin 4/1/08 Some women with T1DM lose weight by intentionally skipping or reducing their usual insulin doses. The practice is dangerous because the blood becomes too acidic, and damage to the stomach, eyes, and nerves can occur. An estimated one-third of women with T1 reduce or forego insulin doses in order to lose weight, according to studies. Data indicates that women who do not take the appropriate amount of insulin are more prone to suffering kidney and foot damage and more likely to die at a younger age. In a recent study, researchers monitored 234 women with T1 who had taken part in another study in the 1990s. They found that 30 % of the women in the original survey said they under-dosed on insulin at some point. The follow-up study revealed 10 deaths among women who had limited their insulin, compared to 16 among the larger group who had not skimped on insulin. Other studies have found higher rates of eating disorders among women who have type 1 diabetes compared to other women. News summaries © 2007 Information, Inc. 6.%% ADA - Optimizing Treatment Reduces CVD Risk in Patients With Diabetes 4/1/08 Physicians should consider a number of factors when deciding what treatment options are best for patients with diabetes, according to Lamendola, MSN, ANP, research coordinator at Stanford University School of Medicine. Among the factors doctors should consider are how long the patient has had DM, whether or not they have high BP, and their LDL and HDL cholesterol goals, she said at the ACC2008. She noted that LDL goals should be less than 100 mg/dL, though patients with overt cardiovascular disease should shoot for getting their LDL levels below 70 mg/dL. Lamendola added that physicians should prescribe statins to their patients to help them reduce their LDL cholesterol level. " Begin a dose that is going to give you at least a 40 % reduction, and if not at target goal, increase the statin or add combination therapy, " HDL goals, meanwhile, should be greater than 40 mg/dL for men and greater than 50 md/dL for women. Triglycerides should be less than 150 md/dL. News summaries © 2007 Information, Inc. Endocrine Today (03/30/08) 7.%% ADA -The (Person With Diabetes) Beyond a Foot Ulcer 4/1/08 Italian researchers studied the role of depressive symptoms in the healing and recurrence of foot ulcers in people with T2DM. [cohort observational study 80 individuals with T2;60 years and older. individuals who healed had much lower scores on the geriatric depression scale, while those with scores of 10 had a much greater risk of not healing at 6months. More than 50 % of the patients had a recurrent ulcer, and those individuals had significantly higher total cholesterol levels, higher scores on the Greenfield index of disease severity and geriatric depression scale, and a greater prevalence of cerebrovascular disease. The researchers concluded that there is an association between depressive symptoms and impaired healing and ulcer recurrence in older patients with T2. News summaries © Jour of Amer Podiatric Medical Association (04/01/08) Vol. 98, No. 2, 8.%% ADA - Medications Plus Dental Materials May Equal Infection for (People With Diabetes) 4/1/08 Many people with DM are unaware that their condition could result in complications with their dental care. Medications dispensed at the dentist's office sometimes conflict with those taken by patients with DM--a factor that a new study. says makes communicating with a dental provider particularly important. Patients are advised to seek a dentist sensitive to the care of people with diabetes and regularly inform the dental provider with updated medical information. Patients with DM are advised to eat meals before they visit the dentist and to bring along their glucose monitoring devices. An Academy of General Dentistry spokesperson says the dentist must be informed of the patient's insulin status, including their daily dosage and whether or not they have taken the medication on that day. " It is imperative that [people with diabetes] inform their dentist of their needs in order to anticipate medication interactions and physical reactions to treatment, " he adds. News summaries © Science Daily (03/24/08) 9.%% ADA - Resveratrol in Grape Skins Could Stop [Diabetes] Complications Such as Heart Disease, Retinopathy, and Nephropathy 4/1/08 British researchers have discovered that a natural component of grape skins could prevent cellular damage leading to heart disease, retinopathy,and nephropathy in people with DM. Resveratrol, found in grape skins, peanuts, and red wine, has been detected by researchers as a compound that assists cells in preventing electron leaks. These leaks cause the circulation of free radicals, hazardous by-products of mitochondrial damage, that are linked to increased glucose levels in patients with DM. The circulation of free radicals results in conditions leading to heart disease, retinopathy, and nephropathy. Resveratrol's role in preventing free-radical production consists of promoting the cellular enzyme production that prevents electron leakage. The researchers said: " Resveratrol or related compounds could be used to block the damaging effects of glucose, which in turn might fight the often life-threatening complications that accompany diabetes. " The research is published in the journal Diabetes, Obesity, and Metabolism. News summaries © 10.%% JH Nutrition and Diabetes -- Taking the Mystery Out of Mealtime s Hopkins Comprehensive Diabetes Center, When you were diagnosed with diabetes, one of your first questions probably was: What should I eat? An excellent question, because more than any other health problem, DM requires careful attention to your diet, including what foods you choose and how much and when you eat them. Here is some nutritional information you’ll want to know and share with your friends with diabetes. Q. Nutrition guidelines recommend specific amounts of carbohydrates, fats, and proteins. I feel like I need to plan every meal with a kitchen scale and calculator. Is there a simpler way to get the right portions and mix of nutrients? A. “Mealtime should not be stressful,” says nutritionist Bravo, R.D., L.D.N., a diabetes educator at the JH. To simplify meal planning, she recommends meeting with a registered dietitian to develop a dietary plan that meets your needs. If you have T1DM getting the right amount of carbohydrates will be a big concern. If you have T2DM, you might need to lose a few pounds, so limiting calories will be a priority. Limiting the amount of saturated fat and cholesterol is important, too, because T1 & 2 increase the risk of heart disease. Instead of weighing or measuring food and crunching numbers when you plan meals, a dietitian can show you how to control your intake of carbohydrates, calories, and fat by visualizing portions. For instance, one serving of cooked pasta is the size of an ice cream scoop, a serving of meat is no bigger than a deck of cards, and a serving of butter resembles one die. Q. Should I use meal-replacement shakes or bars to lose or control my weight if I have DM? What advantages or disadvantages do they offer? A. Meal preparation doesn’t get much easier than grabbing a chilled can from the fridge, stirring a packet of powder in a glass of water, or unwrapping a meal bar. Meal-replacement products eliminate guesswork, too. Their labels tell you exactly how many calories and what nutrients they contain. However, some people find these products too chalky or chewy. More important, some say that meal-replacement shakes and bars don't satisfy their appetite as well as regular food, and they end up snacking between meals to quell the hunger. So if you have no problem with the taste and texture of meal replacement products and they satisfy your hunger, feel free to use them as a weight-control tool. 11.%% MW -Treatment With Pregabalin May Reduce Pain of Diabetic Neuropathy 4/2/08 - In patients with painful diabetic peripheral neuropathy (DPN), treatment with pregabalin at various doses was effective in reducing pain, according to the results of 7 randomized controlled trials across a range of doses. " The antiepileptic agents, gabapentin and pregabalin have attained widespread usage in the treatment of painful DPN, " write the reseachers. " These agents bind to the auxiliary a2-d subunit of the voltage sensitive calcium channel thereby decreasing Ca2+ influx at nerve terminals and modulating neurotransmitter release. " Pregabalin treatment was associated with significant reductions in pain and pain-related sleep interference caused by DPN (150, 300, & 600 mg/day 3 times daily vs placebo. When administered twice daily, only the 600-mg/day dosage was effective (P = .001). The reductions in pain and sleep interference reductions associated with pregabalin appeared to correlate positively with dosage, with the greatest effect seen in patients treated with 600 mg/day of pregabalin. Dizziness, somnolence, and peripheral edema were the most frequently reported treatment-emergent adverse events. " The dose-related increase in efficacy was accompanied by a dose-related increase in incidence of most adverse events. " Pfizer Global Pharmaceuticals funded this study, Diabetes Care. Published online March 20, 2008. 12.%% MW - Soy Intake May Benefit Patients With Type 2 Diabetes and Nephropathy 4/3/2008 — Intake of soy protein had beneficial effects on cardiovascular risk factors and kidney-related biomarkers in patients with type 2 diabetes and nephropathy, according to the results of a longitudinal, randomized trial just published. The researchers write " To determine the effects of long-term soy consumption on cardiovascular risks, we measured C-reactive protein (CRP) and kidney function indexes among T2 patients with nephropathy. " [41 patients 18men ;duration 4years] The soy protein group (n = 20) was assigned to a diet of 35% animal proteins, 35% textured soy protein, and 30% vegetable proteins, whereas the control group was assigned to a similar diet containing 70% animal proteins and 30% vegetable proteins. Duration of the study was 4 years. The soy protein group fared better than the control group regarding effects on cardiovascular risk factors. Mean change in the soy protein vs control groups for fasting plasma glucose levels was –18 vs 11 mg/dL; for total cholesterol levels,–23vs 10 ± mg/dL for low-density lipoprotein (LDL) cholesterol levels, the soy protein group also had greater decreases in serum CRP levels " Longitudinal soy protein consumption significantly affected cardiovascular risk factors and kidney-related biomarkers among T2 patients with nephropathy, " the study authors write. " As diabetic nephropathy is a progressive disease, we expected that the conditions of these patients would have gotten worse after 4 years, but because of medical and dietary control, their conditions improved in some respects. " Diabetes Care. 2008;31 13.%% MW - Cardiorespiratory Fitness, BMI Linked to Risk of Type 2 Diabetes in Women (Reuters Health) Apr 02 - Low cardiorespiratory fitness, as measured by a treadmill exercise test, and high body mass index (BMI) are independently associated with incident T2DM in women, according to study findings. " Because women newly diagnosed with diabetes have a higher relative risk for cardiovascular disease death than men with DM, it is important to investigate the associations among obesity, physical activity, and the risk of developing T2 in women. " [observational cohort of 6249 women;age 20-79 free of cardiovascular disease, cancer, and DM at baseline.] " CRF (cardiorespiratory fitness) was assessed as the duration of a symptom-limited maximal treadmill exercise test, " the team reports, and the women were categorized into thirds -- low, middle and high -- based on age-specific treadmill time. After adjusting for a number of covariables including BMI, women in the middle and upper thirds of CRF had significantly lower risks of diabetes compared to the least fit third In an analysis examining the combined effects of CRF and BMI on diabetes risk, the researchers found that while fitness had a protective effect in overweight/obese individuals, it did not eliminate their increased risk. " These findings underscore the critical importance of promoting regular physical activity and maintaining normal weight for diabetes prevention, " the lead researcher said. " Our next step, " he added, " is to examine the association between cardiorespiratory fitness, body mass index, and all-cause mortality in women who have impaired fasting glucose and undiagnosed diabetes to clarify if lower fitness and higher body weight have great impact on survival in these high-risk women. " Diabetes Care 2008;31 14.%% Poor Glycemic Control Linked to Development of Microalbuminuria in T1DM Apr 4, 2008 — Poor glycemic control is linked to the development of microalbuminuria in childhood-onset T1DM, according to the results of a prospective observational study. The risk for progression to macroalbuminuria was similar to that in adult-onset disease, but because it occurs in young adult life, the study authors suggest that early intervention in adolescents with normal BP might help improve prognosis. " In adults with T1 microalbuminuria is an early marker of structural renal disease and a risk factor for the development of macroalbuminuria, " write the researchers. The goal of this study was to describe independent predictors for the development of microalbuminuria and progression to macroalbuminuria in patients with childhood-onset T1DM. [527 participants with T1;mean age of 8.8. Mean follow-up 9.8 years] After 10 years of diabetes, the cumulative prevalence of microalbuminuria was 25.7% This increased to 50.7% after 19 years of diabetes and a total of 5182 patient-years of follow-up. The only modifiable adjusted predictor for microalbuminuria was elevated HbA1c levels. " In childhood onset T1DM, the only modifiable predictors were poor glycaemic control for the development of microalbuminuria and poor control and microalbuminuria (both persistent and intermittent) for progression to macroalbuminuria, " the authors write. 15.%% Reduced Diabetic, Hypertensive, and Cholesterol Medication Use With Walking Med Sci Sports Exerc. 2008;40(3) ©2008 Amer College of Sports Medicine 3/27/2008 [32,683 female;8112 male; 2.8% and 7.4% reported antidiabetic, 14.3%/29.0% antihypertensive, and 7.3% /21.5% reported LDL cholesterol-lowering medication use, respectively. .The longest usual weekly walk was a better discriminator of medication status than the total cumulative distance per week, particularly in men. Conclusion: These results are consistent with the hypothesis that antidiabetic, antihypertensive, and LDL cholesterol-lowering medication use may be reduced substantially by walking more intensely and farther each week, and by including longer walks. 16.%% Ask the Experts - Exercise, Insulin, and Type 2 Diabetes Medscape Diabetes & Endocrinology. 2008; 3/31/2008 Question Is there a guide for reducing the insulin dose during exercise for people with T2 who are on basal/bolus insulin therapy? Response from L. Pearson, MS,RN,CDE Director, Diabetes Care, Fairview Health Services, Minneapolis Exercise is a key component of a healthy diabetes treatment regimen, but when insulin is involved -- even in a person with T2-- precautions should be taken. Before embarking on an exercise program, the(ADA) emphasizes that a person with T2DM should be evaluated for cardiovascular disease or other conditions that might contraindicate certain types of exercise. It is important that the exercise program be individualized on the basis of findings of the evaluation as well as the therapy regimen. There are other variables that need to be considered: How often does the person currently exercise? If he or she is not very active, the likelihood of hypoglycemia is greater. The length of time the person is active and the level of intensity will affect blood glucose response as well. Other medications, such as sulfonylureas or pramlintide, need to be considered. Basically, if the person is on a basal/bolus insulin regimen, the primary concern is the prevention of hypoglycemia. The ADA recommends checking blood glucose before, after, and then several hours after exercise because hypoglycemia can occur hours after exercise. For exercise that continues for 30 minutes or more, carbohydrate (CHO) intake or the rapid-acting or short-acting insulin may need to be adjusted. If the blood glucose level is less than 100 mg/dL, the person should take 15 g of CHO before starting the activity. If the person is planning to exercise for 1 hour or longer, blood glucose should be checked during exercise. .. .It is important to keep good records of all blood glucose values, the duration and intensity of the activity, and CHO intake, and to use the information to guide adjustments in the future. The response will be different for everyone on the basis of the level of insulin resistance and physical fitness. Additional recommendations that can help your patients reduce the incidence of hypoglycemia include: Don't exercise when insulin is peaking; Avoid injecting into the arms or legs; use the abdomen to ensure more even absorption of insulin; If exercising late in the day, have a snack before bedtime to avoid a delayed hypoglycemic reaction during the night; and Don't forget hydration; fluids should be replenished during exercise, especially when exercise lasts for more than 1 hour and there is significant perspiration. 17.%% MW -Sodium-Glucose Transporter 2 Inhibitors: New Therapeutic Targets, New Therapeutic Options in the Treatment of Type 2 Diabetes Mellitus Mar 31, 2008 .... Over the last 10 years, key clinical trials, have demonstrated the importance of glucose lowering as well as BP and lipid management in reducing the burden of diabetes complications. Despite recent advances in therapy, complication rates remain high. Therefore, there is a real need to develop new drugs for the treatment of DM. Such agents should ideally have a low propensity to cause hypoglycemia, and should ideally promote weight loss or at least not contribute to weight gain. It is likely that T2DM is a heterogeneous disease, and it is important to remember that the etiology and pathophysiology are complex and incompletely understood.. it is unlikely that any single mechanism will eventually explain all cases of T2 or suggest a therapeutic advance that will be suitable for all patients with the condition. The Role of the Kidney in Normal Glucose Homeostasis - The kidney plays a vital role in the normal control of blood glucose, mainly because glucose in the blood is freely filtered by the glomerulus and has to be reabsorbed. The kidney also contributes to gluconeogenesis, [to create glucose] and can make up to about 5to10% of overall glucose production in humans. At a threshold of about (180 mg/dL), the capacity to reabsorb glucose is exceeded and glucosuria [sugar in the urine] develops Glucosuria thus occurs in the presence of hyperglycemia, and has been used to demonstrate the presence of DM and monitor glycemic control long before the routine measurement of capillary blood glucose became possible. it was only after demonstration in the 18th century that DM was associated with increased glucose in the blood as well as the urine, Most glucose reabsorption occurs in the proximal tubules of the nephron, [basic kidney cell] , the primary transporters responsible for the renal reabsorption of glucose are the 2 sodium-dependent glucose transporters SGLT1 and SGLT2. SGLT1 is a high-affinity, low-capacity glucose/galactose transporter found in the gut, brain, skeletal muscle, liver, lungs, and kidneys. It is the main sodium- dependent glucose transporter in the gastrointestinal tract, and is necessary for the normal absorption of dietary glucose.. Glucosuria also results in loss of energy in the urine. In patients with a blood glucose 50% above the renal threshold, this could result in the loss of nearly 600 kcal energy per day -- in the urine. Indeed, it has been shown that a significant amount of the weight gain seen with improved glucose control with insulin therapy in T2 is due to the stopping of [sugar loss in the urine] ; thus, paradoxically, glucosuria may be of possible benefit in patients with DM. The Potential of SGLT2 Inhibition in the Treatment of DM - It has been known since the 19th century that phlorizin, originally isolated from the bark of apple trees, could induce glucosuria in humans. Phlorizin is a competitive inhibitor of both SGLT1 and SGLT2, Giving phlorizin to partially pancreatectomized DM rats induces glucosuria and lowers blood glucose. It has significant limitations,..it inhibits both SGLT1 and SGLT2, causing both malabsorption of glucose and galactose as well as glucosuria.. More recently, it has been possible to develop compounds that are more selective for the SLGT2 transporter. An early example, T-1095 (RWJ394718) has been shown to induce glucosuria in rodent models of DM and lower blood glucose, However, this compound also had significant activity against the SGLT1 transporter, Although T-1095 has not proceeded to clinical development, it has demonstrated proof of principle, such that many pharmaceutical companies are now developing SGLT2 inhibitors as potential treatments for T2DM Several compounds have been shown to be effective in animal models, and some have now proceeded to clinical development. Sergliflozin, is reported to show 7-fold selectivity for human SGLT2 vs SLGT1 in cell culture systems, and has been shown to induce glucosuria in healthy mice, rats, and dogs, and lower postprandial blood glucose in rats with DM in rats (Fi Sergliflozin (GW869682X) is now being developed .. preliminary data showed increased urinary glucose excretion, modest weight loss, and no evidence of hypoglycemia in overweight and obese subjects over 14 days of treatment. In subjects with T2.. so there is a potential for clinically significant weight loss in addition to glucose lowering. Another potential benefit would be small increases in sodium excretion; this would be analogous to the mild diuretic effect seen with thiazide diuretics, and might theoretically result in modest reductions in arterial blood pressure. Potential Drawbacks - Healthcare providers may have concerns about the effects of inducing glucosuria on the kidneys, but the lack of evidence of renal damage in patients with familial renal glucosuria provides some reassurance. Increases in urinary glucose excretion may lead to polyuria [many urinations] and increased thirst, but this has not been reported as a major problem in the trials to date. Another theoretical problem in relation to the genitourinary tract is increased risk for either bacterial or fungal infection. Only assessment in the context of clinical trials will tell us whether SGLT2 inhibitors increase the risk for such infections The final concern that may be whether some patients would experience salt-wasting, as has been described in one individual with an SLGT2 mutation. It is also important to consider the likelihood of other unpredicted adverse effects, In summary, SGLT2 inhibitors have significant potential in the treatment of T2 as a class of drugs that can effectively lower blood glucose while avoiding weight gain, hypoglycemia, and edema -- all of which are common and represent significant barriers to the effective treatment of this disabling condition. 18.%% MW- Treatment With Pregabalin May Reduce Pain of Diabetic Neuropathy Apr 2, 2008; In patients with painful diabetic peripheral neuropathy (DPN), treatment with pregabalin at various doses was effective in reducing pain, according to the results of 7 randomized controlled trials across a range of doses. " The antiepileptic agents, gabapentin and pregabalin have attained widespread usage in the treatment of painful DPN, " write the reseachers. Dosages used in these trials were 150,300, and 600 mg/day, administered 3 times daily or twice daily; treatment durations ranged from 5 to 13 weeks. Pregabalin treatment was associated with significant reductions in pain and pain-related sleep interference caused by DPN (150, 300, and 600 mg/day administered 3 times daily vs placebo. Dizziness, somnolence, and peripheral edema were the most frequently reported treatment-emergent adverse events. " Treatment with pregabalin across its effective dosing range is associated with significant, dose-related improvement in pain in patients with DPN, " the study authors write. " The dose-related increase in efficacy was accompanied by a dose-related increase in incidence of most adverse events. " Pfizer Global Pharmaceuticals funded this study, provided consulting fees to the lead study author, and employs the other 2 study authors. Diabetes Care.online March 20, 2008. 19.%% Cromolyn May Reverse Insulin Analog-Induced Lipoatrophy Reuters Health Information 2008. Apr 03 - Mast cell stabilizing therapy with topical cromolyn can reverse early injection-site lipoatrophy induced by human insulin analogs, and prevent further lesions’ The problem of local lipoatrophy [loss of subcutaneous fat] is uncommon, " and the kinetic advantages of insulin analogs to patients with diabetes outweigh this small risk, " Dr. B. Goldfine from the Joslin Diabetes Center told Reuters Health. " However, we would be pleased if our therapy provided a means to treat the lesions in those that develop this rare complication. " [3 women and 2 men with severe local atrophy] Subcutaneous biopsies from acute and chronic injection sites showed increased numbers mast cells with active degranulation in all cases and prominent eosinophils in three cases, the investigators report. " Topical cromolyn sodium was applied twice a day to atrophic areas and prophylactically to new sites of insulin administration, " they explain. None of the patients developed new lipoatrophic lesions after using topical cromolyn, the researchers note, and four of the five showed significant improvement of lipoatrophy, with complete resolution after only 4 weeks in one patient. " Physicians are choosing to use our findings and treat empirically with the cromolyn without biopsy, " Dr. Goldfine said. " This is not an unreasonable approach. " Future long-term studies,will help determine whether these patients will need to use topical cromolyn permanently to prevent lipoatrophy lesions, or whether after some period of treatment with cromolyn, discontinuation with or without an additional form of intervention may halt the process. " Diabetes Care 2008;31 20.%% MW - Neurotrophic Factor Improves Glucose Tolerance, Beta-Cell Mass in Mice Mar 28 - Experiments in vitro and in mice show that glial cell line-derived neurotrophic factor (GDNF) increases beta-cell mass and improves glucose tolerance, according to a study Although GDNF is not known to be involved in pancreatic beta-cell growth and survival, the researchers noted that previous studies had raised the possibility that neurotrophic factors might be involved with those processes, perhaps through islet repair. They therefore studied GDNF's role in regulating beta-cell survival in pancreatic cell lines and in transgenic mice that overexpress GDNF in pancreatic glia, and also investigated the results in terms of glucose tolerance. Using both an insulin-secreting line of mouse pancreatic cells and isolated mouse pancreatic beta cells, the researchers showed that these cells express receptors for GDNF, and that GDNF reduces apoptosis and promotes survival of beta cells. The part of the study involving transgenic mice showed that such mice had significantly larger beta-cell mass, more islets per unit of pancreatic tissue, larger individual islets and higher insulin content, when compared to wild-type mice. Compared with wild-type mice, the transgenic mice were found to have improved glucose homeostasis, with no difference in insulin sensitivity. Furthermore, compared with wild-type mice, the transgenic mice were significantly resistant to DM induced by repeated administration of streptozotocin. " We are hoping that with further research, GDNF, or small molecules similar to GDNF, can be used to improve beta cell survival post transplantation, " they told Reuters Health. " In addition, understanding the role of neurotrophic factors in influencing beta cell mass can give us new insights into the mechanisms of development of diabetes and help in developing new strategies for prevention and treatment. " He added that one of the next steps will be to test GDNF's effects on human islets. Gastroenterology 2008;134 21.%% Low Testosterone Levels Common in Diabetic Men (Reuters Health) Mar 28 - Regardless of the type, DM is associated with low testosterone levels in men, according to a report. Moreover, as insulin resistance rises, levels of testosterone fall. " As testosterone deficiency may contribute to impaired performance, mood, and libido, as well as have an adverse impact on cardiovascular risk, these findings demonstrate the presence of a significant and unrecognized problem among men with DM, " the lead author said in a statement. " Our findings of insulin resistance as a potential determinant of reduced testosterone levels may represent an important avenue for intervention, " Prior research has indicated that men with T2DM are often deficient in testosterone. The current study is the first to document a similar association with T1DM. [648 men with diabetes,] low levels of total testosterone were noted in 43% of men with T2 and in 7% of men with T1. 57% of T2 diabetics and 20.3% of T1 had a reduced calculated free testosterone level, the report indicates. Similar rates were noted in each group after adjusting for age and body mass index. In both types of DM, an inverse association between insulin resistance and testosterone levels was observed.. " While there is a strong rationale for testosterone replacement, the balance of benefits and risks is currently unknown and still to be defined by large and long-term clinical trials the team concludes.J Clin Endocrinol Metab 2008. [ACC 2008]American College of Cardiology 2008 Scientific Sessions Abbreviations: DM - diabetes Mellitus;T1DM - type 1 diabetes mellitus T2DM - type 2; ADA - Amer Diabetes Asso; AFB - Amer Foundation for the Blind ;BP - blood pressure;FDA Federal Drug Administration; HTN - hypertension;JH - s Hopkins ; MW Medscape Web MD; NIH - National Institutes of Health; VA - Veterans Administration. MNTD- Medical News Today Definitions - Dorlands 31st Ed and Google. Disclaimer, I am a BSN RN but not a diabetic or diabetic educator. Reports are excerpted unless otherwise noted. This project is done as a courtesy to the blind/visually impaired and diabetic communities. Dawn Wilcox Coordinator The Health Library at Vista Center contact above e-mail or thl@... LaFrance-Wolf 5120 Myrtus Avenue Temple City, CA 91780 Quote Link to comment Share on other sites More sharing options...
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