Transcutaneous electrical nerve stimulation as adjunct to primary care management for tennis elbow: pragmatic randomised controlled trial .


Objective To investigate the effectiveness of supplementing information and advice on analgesia and exercise from a general practitioner with transcutaneous electrical nerve stimulation (TENS) as a non-drug form of analgesia to reduce pain intensity in patients with tennis elbow.

Design Pragmatic randomised controlled trial in primary care.

Setting and 38 general practices in the West Midlands, UK.

Participants 241 adults consulting with a first or new (no consultation in previous six months) clinical diagnosis of tennis elbow.

Interventions Participants were randomly allocated to either primary care management alone, consisting of a consultation with a general practitioner followed by information and advice on exercises, or primary care management plus TENS to be used once a day for 45 minutes over six weeks (or until symptom resolution) for pain relief.

Outcome measures The primary outcome was self reported intensity of elbow pain (0-10 rating scale) at six weeks. Primary and secondary outcomes were measured at baseline and at six weeks, six months, and 12 months by postal questionnaire. Analysis was by intention to treat.

Results 121 participants were randomised to primary care management plus TENS and 120 to primary care management only (first episode, n=197 (82%); duration <1-3 months, n=138 (57%)). Adherence to exercise and TENS recommendations reported at six weeks was low; only 42 participants in the primary care management plus TENS group met a priori defined adherence criteria. Both intervention groups showed large improvements in pain and secondary outcomes, especially during the first six weeks of follow-up. However, no clinically or statistically significant differences were seen between groups at any follow-up timepoint. At the primary endpoint (six weeks), the between group difference in improvement of pain was −0.33 (95% confidence interval −0.96 to 0.31; P=0.31) in favour of the primary care management only group, with adjustment for age, sex, and baseline pain score.

Conclusions This trial does not provide evidence for additional benefit of TENS as an adjunct to primary care management of tennis elbow. Poor adherence to interventions is evidence of the challenges of implementing self management treatment strategies in primary care.


Source: BMJ


Effects of a Fixed-Dose Combination Strategy on Adherence and Risk Factors in Patients With or at High Risk of CVD.

Importance   Most patients with cardiovascular disease (CVD) do not take recommended medications long-term. The use of fixed-dose combinations (FDCs) improves adherence in several clinical areas. Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment.

Objective   To assess whether FDC delivery of aspirin, statin, and 2 blood pressure–lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors, systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C).

Design, Setting, and Participants   The UMPIRE trial, a randomized, open-label, blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010–July 2011 in India and Europe. The trial follow-up concluded in July 2012.

Interventions   Participants were randomly assigned (1:1) to an FDC-based strategy (n=1002) containing either (1) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol or (2) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide or to usual care (n=1002).

Main Outcomes and Measures   Adherence to medication (defined as self-reported use of antiplatelet, statin, and ≥2 BP-lowering medications) and changes in SBP and LDL-C from baseline.

Results   At baseline, mean BP was 137/78 mm Hg, LDL-C was 91.5 mg/dL, and 1233 (61.5%) of 2004 participants reported use of antiplatelet, statin, and 2 or more BP-lowering medications. Median follow-up was 15 months (interquartile range, 12-18 months). The FDC group had improved adherence vs usual care (86% vs 65%; relative risk [RR] of being adherent, 1.33; 95% CI, 1.26-1.41; P < .001) with concurrent reductions in SBP (−2.6 mm Hg; 95% CI, −4.0 to −1.1 mm Hg; P < .001) and LDL-C (−4.2 mg/dL; 95% CI, −6.6 to −1.9 mg/dL; P < .001) at the end of the study. Although there was consistency of effects across predefined subgroups, evidence existed of larger benefits in patients with lower adherence at baseline. In this subgroup of 727 participants (36%), adherence at the end of study was 77% vs 23% (RR, 3.35; 95% CI, 2.74-4.09; P < .001 for interaction), SBP was reduced by 4.9 mm Hg (95% CI 7.3-2.6 mm Hg; P = .01 for interaction), and LDL-C was reduced by 6.7 mg/dL (95% CI, 10.5-2.8 mg/dL; P = .11 for interaction). There were no significant differences in serious adverse events or cardiovascular events (50 [5%] in the FDC group and 35 [3.5%] in the usual care group; RR, 1.45; 95% CI, 0.94-2.24; P=.09) between the groups.

Conclusions and Relevance   Among patients with or at high risk of CVD, use of an FDC strategy for blood pressure, cholesterol, and platelet control vs usual care resulted in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C.


Source: JAMA

Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies.


Objective To determine whether individual fruits are differentially associated with risk of type 2 diabetes.

Design Prospective longitudinal cohort study.

Setting Health professionals in the United States.

Participants 66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies.

Main outcome measure Incident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires.

Results During 3 464 641 person years of follow-up, 12 198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.96 to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts).

Conclusion Our findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.


In three prospective cohorts of US men and women, we found that the associations with risk of type 2 diabetes differed significantly among individual fruits: greater consumption of blueberries, grapes, apples, bananas, and grapefruit were significantly associated with a reduced risk of type 2 diabetes. Most of these associations were quite consistent among three cohorts. Additionally, differences in the glycemic index/glycemic load values of fruits did not account for the association of specific fruits with risk of type 2 diabetes. Moreover, greater fruit juice consumption was associated with an increased risk, and substitution of whole fruits for fruit juice was associated with a lower risk, except for strawberries and cantaloupe.

Results in relation to other studies

In eight previous prospective studies, the association between total fruit consumption and risk of type 2 diabetes was examined,2 3 4 5 6 7 8 9 and the results were mixed. Similar to previous analyses in the Nurses’ Health Study3 and the Finnish Mobile Clinic Health Examination Survey study,2 the current findings supported an inverse association between total fruit consumption and risk of type 2 diabetes, but not in other studies.4 5 6 7 8 9 In contrast to total fruit consumption, evidence on consumption of individual fruits or fruit groups with risk of type 2 diabetes is limited and incomplete. In four prospective studies, consumption of citrus fruit was not associated with a lower risk of type 2 diabetes.5 6 7 8 Apple consumption was inversely associated with risk in the Women’s Health Study29 and in the Finnish study,30 but not in the Iowa Women’s Health Study.31 In addition, greater consumption of berries was associated with a lower risk in the Finnish study,2 but not in the Iowa Women’s Health Study.31 In our previous analyses that focused on anthocyanin rich fruits, intakes of blueberries, strawberries, and apples were associated with a lower risk of type 2 diabetes.32 Consistently, in a clinical trial, increased consumption of berries improved glycemic control among people with diabetes.33 Our current investigation extended the evidence in this regard and found novel, inverse associations for grapes, bananas, and grapefruit.

The different associations of individual fruits with diabetes risk may be due to the heterogeneous composition of these foods. Firstly, blueberries, apples, and red or black grapes contain high levels of anthocyanins.12 In mice with diabetes, bilberry extract rich in anthocyanins can activate adenosine monophosphate-activated protein kinase, enhance glucose uptake and utilization in white adipose tissue and skeletal muscle, and reduce glucose production in the liver.34 Our previous analyses also showed that levels of anthocyanin intake were inversely associated with risk of type 2 diabetes.32 In the current study, further adjustment for anthocyanins did not substantially change the associations for individual fruits, suggesting that the inverse associations of individual fruits are likely due to other constituents of these foods. Both red and white grapes contain high levels of resveratrol in skin.35 In mice, a high fat diet with 0.04% resveratrol increased insulin sensitivity at 24 months compared with the same diet without resveratrol.36 However, randomized controlled trials examining the effects of supplementation of resveratrol on glucose metabolism have generated inconsistent results.37 38 39 Prunes, peaches, plums, apricots, and apples contain chlorogenic acid,40 41 42 43 which may potentially mediate the beneficial effects of coffee consumption on diabetes risk.44 In rats, chlorogenic acid reduces glucose dependent insulinotropic peptide secretion by slowing glucose absorption in the intestine.45Moreover, chlorogenic acid increases muscle glucose uptake in mice with diabetes.46Finally, grapefruits contain high amounts of naringin.12 In rats, naringin inhibits dipeptidyl peptidase 4 similarly to sitagliptin, a dipeptidyl peptidase 4 inhibitor used for the treatment of diabetes.47 Inhibition of dipeptidyl peptidase 4 increases glucagon-like peptide 1, which subsequently leads to improved glucose tolerance.48 In contrast to these specific fruits mentioned above, cantaloupe was associated with an increased risk of type 2 diabetes in the current analysis. Melons have lower levels of phytochemicals than the aforementioned fruits.12 None the less, little evidence exists regarding the effects of melons on glucose metabolism. Although other fruits may also be beneficial for glucose metabolism, significant associations between other specific fruits and risk of type 2 diabetes were not found in the current and previous investigations.5 6 7 8

The glycemic index/glycemic load values of fruits did not seem to be the factor that determined their association with type 2 diabetes in the current study, although in a clinical trial, increased consumption of low glycemic index fruits improved glycemic control among people with diabetes.33 In recent meta-analyses, a higher dietary glycemic index/glycemic load was associated with a greater risk of type 2 diabetes.4950 In the Nurses’ Health Study and Health Professionals Follow-up Study, the associations between dietary glycemic index and risk of type 2 diabetes were positive, although the associations for dietary glycemic load were not significant.51 52 53 None the less, the contribution of total fruit consumption to dietary glycemic load was rather small (about 10%) in these populations. Of individual fruits, the top three contributors to dietary glycemic load were bananas (3-4%), apples (2%), and grapes (1%). In contrast, the relatively high glycemic load values of fruit juices13 along with reduced levels of beneficial nutrients through juicing processes11 12 (for example, the glycemic load values per serving are 6.2 for raw oranges and 13.4 for orange juice, and fibre levels per serving are 3.1 g and 0.5 g, respectively) may explain the positive associations between fruit juice consumption and risk of type 2 diabetes. Moreover, the difference in the viscosity of foods is also an important factor affecting postprandial blood glucose dynamics. Fluids pass through the stomach to the intestine more rapidly than solids even if nutritional content is similar.54 For example, fruit juices lead to more rapid and larger changes in serum levels of glucose and insulin than whole fruits.55 56 Although these mechanisms may potentially explain the diverse associations for individual fruits, further research is apparently needed to confirm our findings on specific fruits in relation to type 2 diabetes and to further elucidate underlying mechanisms.

Strengths and limitations of this study

The present study has several limitations. Firstly, measurement errors were inevitable in the estimates of fruit consumption, especially for individual fruits with lower consumption levels.17 18 Adjustment for energy intake and use of cumulatively averaged intake levels can reduce the magnitude of measurement errors to some extent.26 Generally, random errors in exposure assessments attenuate true associations toward the null. Secondly, the possibility of false positive findings may exist because we examined the associations of multiple fruits in the current investigation without adjusting for multiple comparisons based on a priori hypotheses. Meanwhile, most associations were consistent across three cohorts, and the associations for blueberries, grapes, and apples remained statistically significant even after applying the Bonferroni correction, a conservative method correcting for multiple comparisons. Thirdly, in our food frequency questionnaires, intakes of some individual fruits (apples and pears; peaches, plums, and apricots) were combined because these fruits have similar nutrient profiles. Therefore we could not determine whether the associations for these combined fruits can be ascribed to a specific individual fruit. Fourthly, we cannot exclude the possibility of recall bias in the assessments of diet based on the food frequency questionnaires. However, the prospective study design and exclusion of participants with chronic diseases at baseline should minimize such bias. Fifthly, although in the multivariable analysis we considered a multitude of lifestyle and dietary factors, including other individual fruits, residual or unmeasured confounding may still exist. Finally, our study populations primarily consist of health professionals with European ancestry. Thus our findings may not be generalized to other populations.


Our findings suggest that there is significant heterogeneity in the associations between individual fruits and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, was significantly associated with a lower risk of type 2 diabetes, whereas greater fruit juice consumption was associated with a higher risk. The differences in the associations between individual fruits were not accounted for by variation in the glycemic index/glycemic load values of individual fruits. Overall, these results support recommendations on increasing consumption of a variety of whole fruits, especially blueberries, grapes, and apples, as a measure for diabetes prevention.

What is already known on this topic

  • Total fruit consumption is not consistently associated with a lower risk of type 2 diabetes
  • The possible heterogeneity among individual fruits regarding the associations with risk of type 2 diabetes has not been examined
  • The associations with risk of type 2 diabetes are different among individual fruits
  • Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas increased consumption of fruit juices has the opposite association
  • In addition, the associations of individual fruits are not determined by their glycemic index or glycemic load values

What this study adds



Source: BMJ


More Than Just Reassurance on Tiotropium Safety.

Since its registration in 2002, a dry-powder formulation of tiotropium delivered by a HandiHaler inhalation device has consistently been recommended in clinical-practice guidelines as first-line maintenance bronchodilator therapy for chronic obstructive pulmonary disease (COPD). This recommendation is based on the efficacy of tiotropium in improving lung function, exercise capacity, and quality of life and in reducing moderate and severe COPD exacerbations.

The safety reputation of tiotropium as delivered by dry-powder inhalation remained relatively unblemished until its successor, tiotropium delivered by a soft-mist Respimat inhaler, underwent clinical trials. Despite the clear efficacy of the Respimat formulation, post hoc pooled safety analyses showed an increased rate of death from any cause in patients treated with the Respimat inhaler at a dose of 5 μg of tiotropium, as compared with placebo, an effect that was particularly evident in patients with a history of cardiac arrhythmias.1 All of a sudden, the previous hints at the possibility of cardiovascular risk for ipratropium and tiotropium held more water and needed to be addressed, especially given the widespread use of this drug, the increasing global prevalence of COPD, the guideline recommendations for tiotropium as a first-line COPD treatment, and the high burden of coexisting cardiac conditions and deaths in the COPD population.

Multiple meta-analyses and observational database studies did not resolve the issue, and regulators issued warnings.2 In a systematic review of pooled data from 17 trials (enrolling a total of 13,645 participants), patients with COPD who received inhaled anticholinergic medications had higher rates of myocardial infarction, stroke, and death from cardiovascular causes or a composite of all three outcomes than those receiving placebo or an active control, with a relative risk of 1.60 (95% confidence interval [CI], 1.22 to 2.10; P<0.001) for cardiovascular events and 1.29 (95% CI, 1.00 to 1.65; P=0.05) for death from any cause.3 However, several other meta-analyses showed no evidence of increased rates of cardiovascular events or death.4,5 Most important, data from the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial6 were consistent with a reduction in all-cause mortality in patients with COPD who were receiving tiotropium, as compared with those receiving placebo, during a 4-year period, with a protective effect for cardiac mortality. A subsequent meta-analysis of 30 trials including UPLIFT (enrolling a total of 19,545 participants) showed that tiotropium was associated with reduced rates of death from any cause and from cardiac causes and of cardiovascular events.5However, the soft-mist Respimat inhaler remained under a cloud, with a systematic review reporting a 50% increased risk of death in 2011.1 Although a Cochrane review of 22 studies (enrolling a total of 23,309 participants) did not show an increased risk of death from any cause associated with dry-powder tiotropium HandiHaler, it showed significantly more deaths associated with the soft-mist Respimat inhaler (Peto odds ratio, 1.47; 95% CI, 1.04 to 2.08), with placebo used as the control in the two comparisons.7

Large randomized, controlled trials are usually designed and powered to meet statistical certainty for efficacy end points that have clinical significance for clinicians, patients, or regulators. But when efficacy has been established and safety is then questioned, it is sadly not the rule that rigorous, well-powered studies are conducted to address these concerns. Most studies are grossly underpowered for safety outcomes, and adverse events are listed with small numbers to which only an eyeball test can be applied. The reporting of “no difference” between adverse events in an intervention group and those in a control group is hardly ever questioned, even though it rarely has statistical validity.

In the Tiotropium Safety and Performance in Respimat (TIOSPIR) study,8 Wise et al. turn this tradition on its head by seriously addressing the widely expressed concern about the safety of tiotropium Respimat. In this large clinical trial, now reported in the Journal, involving 17,135 patients with COPD for a median duration of 835 days, the investigators compared the safety and efficacy of once-daily tiotropium doses of 2.5 μg and 5 μg delivered by Respimat with a once-daily dose of 18 μg of tiotropium delivered by HandiHaler. Primary end points were the rate of death (noninferiority study for both doses of Respimat vs. HandiHaler) and the rate of the first COPD exacerbation (superiority study for Respimat 5 μg vs. HandiHaler). There was no significant difference among the three study groups with respect to death (hazard ratio for Respimat 5 μg vs. Handihaler, 0.96; 95% CI, 0.84 to 1.09; hazard ratio for Respimat 2.5 μg vs. Handihaler, 1.0; 95% CI, 0.87 to 1.14) or the first exacerbation (hazard ratio for Respimat 5 μg vs. HandiHaler, 0.98; 95% CI, 0.93 to 1.03). Patients with stable cardiac disease were included in the study, and there was no significant difference in mortality for those with a history of arrhythmia. The incidences of major cardiovascular adverse events were similar in the three study groups.

These results address several previous criticisms leveled against randomized, controlled trials and meta-analyses that did not identify an increased risk of death (or that showed a risk reduction) associated with tiotropium. A major concern was the possibility that the failure to identify a risk of death in some meta-analyses was due to the exclusion of patients with a cardiac history, especially arrhythmia or recent myocardial infarction, or those with other serious coexisting illnesses who might be at risk because of participation in the trial. In the TIOSPIR study, the clinical characteristics, coexisting illnesses, and coprescribed medications of the recruited patients suggest they do represent typical patients with symptomatic COPD, and the rate of follow-up was 99.7%. However, it is important to note that the absence of a placebo group in this study has implications for its interpretation and that it cannot be concluded from these results that tiotropium reduces mortality in patients with COPD.

The rigor, careful conduct, scrupulous follow-up of patients, and use of clinically appropriate entry criteria in this study will reassure many clinicians who may have had concerns about the narrow focus of some COPD trials. The global recruitment, fast completion, and clear outcomes of the trial should also encourage all those who fear that real-world studies enrolling patients who truly reflect typically heterogeneous populations and phenotypes will produce messy, uninterpretable results. This study clears the air regarding the safety of tiotropium delivered by Respimat and at the same time establishes a high standard for clinical trials involving patients with COPD, particularly studies that focus on patient safety.


Source: NEJM



Researcher Files Lawsuit vs. FDA After His Petition Calling for Ban on Artificial Trans Fats Was Ignored.

Story at-a-glance

  • Dr. Fred Kummerow filed a petition to ban synthetic trans fats with the US Food and Drug Administration (FDA) in 2009
  • The FDA did not issue a final response, so Dr. Kummerow has filed a lawsuit against them for failing to ban synthetic trans fats as well as their delay in responding to the original petition
  • Research has shown that heart disease is often the result of synthetic trans fat deposited in the veins and arteries, which can cause sudden death due to blockage
  • Many processed foods on the market still contain trans fats; to avoid them, skip processed foods or check the ingredients and look for partially hydrogenated oil. If the product lists this ingredient, it contains trans fat.
  • trans-fat

In 2009, Dr. Fred Kummerow, who has studied heart disease for more than 60 years, filed a citizen petition with the US Food and Drug Administration (FDA) calling for a ban on synthetic trans fats.1

In the petition, he noted that heart disease is often the result of trans fat deposited in veins and arteries, which can cause sudden death due to blockage. He stated:

“Trans fat calcifies both the arteries and veins and causes blood clots. Trans fat leads to the reduction of pro stacyclin that is needed to prevent blood clots in the arteries. A blood clot in any of the coronary arteries can result in sudden death.”

The FDA is required to respond to such petitions within 180 days, but Dr. Kummerow has yet to receive a final response even four years later. So, he’s taking matters a step further …

FDA Slammed with Lawsuit for Ignoring Petition to Ban Artificial Trans Fats

Dr. Kummerow, now 98, has filed a lawsuit against the FDA, which alleges that the agency’s failure to ban partially hydrogenated oils (which contain synthetic trans fats) along with their unreasonable delay in responding to his 2009 petition, violate the Administrative Procedure Act and the Food, Drug, and Cosmetic Act.

The Food, Drug, and Cosmetic Act prohibits the sale of foods containing poisonous or deleterious substances, and an extensive body of research has linked synthetic trans fats to heart disease, diabetes, cancer, Alzheimer’s disease and even violent behavior.

The FDA has not commented on the pending lawsuit, although Dr. Kummerow pointed out that it would be simple for the FDA to ban synthetic trans fats while leaving natural trans fats, which may actually have health benefits, unregulated.

The FDA has a history of siding with industry, however, and so far has caved to industry pressure in allowing synthetic trans fats to remain on the market — despite their proven, and significant, risks to public health.

Why Are Trans Fats so Deadly?

Trans fats are formed when hydrogen is added to vegetable oil during food processing in order to make it solidify. This process, known as hydrogenation, makes fats less likely to spoil, so foods appear to remain fresh longer, have a longer shelf life and also have a less greasy feel.

Trans fats are common in fried foods like French fries, fried chicken, and doughnuts — as well as cookies, pastries and crackers. Food manufacturers love them because they’re cheap and they significantly reduce perishability and remain stable even at room temperature. But these completely unnatural man-made fats cause dysfunction and chaos in your body on a cellular level. Studies have linked trans fats to:

Cancer: They interfere with enzymes your body uses to fight cancer Diabetes: They interfere with the insulin receptors in your cell membranes
Decreased immune function: They reduce your immune response Problems with reproduction: They interfere with enzymes needed to produce sex hormones
Trans fats interfere with your body’s use of beneficial omega-3 fats Heart disease: Trans fats can cause major clogging of your arteries. (Among women with underlying coronary heart disease, eating trans fats increased the risk of sudden cardiac arrest three-fold)
Obesity Asthma
Alzheimer’s disease Aggressive and violent behavior

Progress Is Slowing in the Removal of Trans Fats from Foods

After it became widespread knowledge that trans fats are dangerous, the industry responded by reformulating many products. It’s estimated that 66 percent of foods that formerly contained trans fats have been reformulated, although one study suggested that many synthetic trans-fat–laden foods still remain on the market.2 The researchers concluded:

“Some US products and food manufacturers have made progress in reducing TFA [trans fatty acids], but substantial variation exists by food type and by parent company, and overall progress has significantly slowed over time.  Because TFA consumption is harmful even at low levels, our results emphasize the need for continued efforts toward reformulating or discontinuing foods to eliminate PHVO [partially hydrogenated vegetable oils].”

Even if a product claims to be free from trans fats, it may actually contain up to 0.5 grams per serving. If you eat a few servings, you’re quickly ingesting a physiologically significant amount of this deadly fat. So to truly avoid trans fats, you need to read the label and look for more than just 0 grams of trans fat. Check the ingredients and look for partially hydrogenated oil. If the product lists this ingredient, it contains trans fat. It’s important to keep your intake of trans fat as low as possible, if you eat it at all, as very small amounts pose health risks. In fact, increasing your daily consumption of trans fats from 2 grams to 4.67 grams increases your risk of heart disease by 30 percent!3

Trans Fats’ Replacement May Also Be Harmful

It’s worth noting that many processed food manufacturers are swapping out trans fats for what’s known as interesterified fats. The interesterification process hardens fat, similar to the hydrogenation process, but without producing oils that contain trans fats. The end product, like trans fat, is less likely to go rancid and is stable enough to use to fry foods. However, while the highly industrialized process of interesterification may result in a product that is trans fat-free, that product will still contain chemical residues, hexanes (crude oil derivatives), and other hazardous waste products full of free radicals that cause cell damage.

Studies show that interesterified fat raises your blood glucose and depresses insulin production.4 These conditions are common precursors to diabetes, and can present an even more immediate danger if you already have the disease. Interesterified fats are in virtually all the foods that trans fats are, so by avoiding trans fat, and processed foods in general, you will also avoid interesterified fats. If a processed food product is labeled “0 grams trans-fats” or “no trans-fats” but is made from vegetable oils, you can be certain it probably contains either interesterified fats or fully hydrogenated vegetable oils, both of which you’ll want to avoid in addition to the partially hydrogenated oils that contain trans fats.

Examples of Healthy Fats to Eat More Of

There’s no telling how long it will be before the FDA wisens up and bans synthetic trans fats from the market… if they ever do. So when it comes to fats, remember the simple ground rule, that natural, not man-made, is best. This includes saturated fats found in animal products as well as natural trans fats like trans vaccenic acid (VA) — a natural animal omega-7 fat found in dairy and beef products – which can actually reduce risk factors associated with heart disease, diabetes and obesity.5 The tips that follow can help ensure you’re eating the right fats for your health. You can also use the chart at the end of the article to help you select healthy fats.

  • Use organic butter preferably made from raw milk) instead of margarines and vegetable oil spreads. Butter is a healthy whole food that has received an unwarranted bad rap.
  • Use coconut oil for cooking. It is far superior to any other cooking oil and is loaded with health benefits. (Remember that olive oil should be used COLD, drizzled over salad or fish, for example, not to cook with.)
  • Following my nutrition plan will automatically reduce your modified fat intake, as it will teach you to focus on healthy whole foods instead of processed junk food.
  • To round out your healthy fat intake, be sure to eat raw fats, such as those from avocados, raw nuts, raw dairy products, and olive oil, and also take a high-quality source of animal-based omega-3 fat, such as krill oil.

Examples of healthy natural fats include:

Olives and Olive oil Coconuts and coconut oil Butter made from raw grass-fed organic milk
Raw nuts, such as almonds or pecans Organic pastured egg yolks Avocados
Grass-fed meats Unprocessed palm oil Unheated organic nut oils





SAVOR-TIMI 53 raises bar for CV outcome trials in diabetes.

When added to standard care in patients with type 2 diabetes at high CV risk, saxagliptin neither reduced nor increased risk for ischemic events, according to results from the SAVOR-TIMI 53 trial.

Saxagliptin (Onglyza, AstraZeneca and Bristol-Myers Squibb) was also shown to improve glycemic control, but was associated with a small increase in the rate of hospitalization for HF.

The multicenter, randomized, double blind, placebo-controlled, phase 4 trial was designed to determine whether saxagliptin was noninferior to placebo when added to background therapy, for the composite endpoint of CV death, nonfatal MI or nonfatal ischemic stroke, Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School and Chief Medical Editor of Cardiology Today’s Intervention, said at an ESC Congress 2013 press conference.

During a mean follow-up of 2.1 years, the primary endpointoccurred in 7.3% of patients assigned saxagliptin compared with 7.2% assigned placebo (HR=1.00; 95% CI, 0.89-1.12;P=.99 for superiority; P<.001 for noninferiority). An on-treatment analysis yielded similar results (HR=1.03; 95% CI, 0.91-1.17).

The major secondary endpoint, a composite of CV death, MI, stroke and hospitalization for unstable angina, coronary revascularization or HF, occurred in 12.8% of patients assigned saxagliptin compared with 12.4% assigned placebo (HR=1.02; 95% CI, 0.94-1.11). Of note, the saxagliptin group had more hospitalizations for HF (3.5% vs. 2.8%; HR=1.27; 95% CI, 1.07-1.51). In addition, a prespecified secondary endpoint of all-cause mortality occurred in 4.9% of patients assigned saxagliptin compared with 4.2% assigned placebo (HR=1.11; 95% CI, 0.96-1.27).

“The high risk of hospitalization for HF was unexpected, but it was a predefined adjudicated endpoint. Therefore, it does merit further evaluation given the history of other diabetic agents and HF,” Bhatt said. “Additional analyses are ongoing and preliminary data suggest that the risk is highest in those with elevated baseline clinical risk for HF, such as a history of prior HF and/or elevated BNP levels at baseline.”

Fewer patients assigned saxagliptin required the addition or increase of any new antidiabetic medications (23.7% vs. 29.3%; HR=0.77; 95% CI, 0.73-0.82) or the initiation of insulin therapy for more than 3 months (5.5% vs. 7.8%; HR=0.7; 95% CI, 0.62-0.79). Reductions in blood glucose were also greater with saxagliptin, with mean reductions in HbA1c of 0.5% at 2 years in the saxagliptin group compared with 0.2% in the placebo group (P<.001). More patients assigned saxagliptin achieved or maintained goal HbA1c <7% (40% vs. 30.3%; P<.001). About 15% of patients in the saxagliptin group reported at least one hypoglycemic event compared with 13.4% of patients in the placebo group (P<.001). Hospitalization for hypoglycemia was infrequent and similar between groups (0.6% vs. 0.5%; P=.33).

Additionally, saxagliptin was associated with reduced development and progession of microalbuminuria.

“It is very encouraging that within such a short time, 2 years of follow-up, that saxagliptin has demonstrated a beneficial effect on the kidney,” researcherItamar Raz, MD, head of the diabetes unit, department of medicine, Haddassah University Medical Center, Jerusalem, told Cardiology Today.

Rates of pancreatitis were similar with saxagliptin and placebo (0.3% for both; P=.77). Five cases of pancreatic cancer were reported in the saxagliptin group compared with 12 in the placebo group. The incidence of other prespecified safety endpoints were balanced, Bhatt said.

Premature discontinuation of the study drug occurred more in the placebo group (20.8% vs. 18.4%; P<.001).

“There is still a great need to bring patients to HbA1c target and we know today that we only have 50% to 60% of diabetes patients at target. [Saxagliptin] is a safe drug that was not shown to do CV harm, as was shown in the primary and secondary endpoint results,” Raz said.

In The New England Journal of Medicine study, the researchers acknowledged “there remains a strong clinical need to identify antihyperglycemic agents that are, at a minimum, safe and that can potentially reduce cardiovascular complications.”

Saxagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. – by Katie Kalvaitis

Source: Endocrine Today.



Calcium, vitamin D failed to halt BMD loss in breast cancer.

Calcium plus vitamin D supplements are often suggested for patients at risk for osteoporosis and in women undergoing breast cancer treatment, but a recent analysis published in Critical Reviews in Oncology/Hematologyhighlights the insignificant data behind this methodology.

“We evaluated clinical trial evidence for calcium and vitamin D supplementation in maintaining skeletal health of women with breast cancer,” Gary G. Schwartz, PhD, a cancer epidemiologist at Wake Forest Baptist Medical Center in Winston-Salem, N.C., said in a press release. “At the doses recommended, the data show that these supplements are inadequate to prevent loss of [bone mineral density].”

Of 16 trials, researchers found that none of them evaluated calcium plus vitamin D supplements vs. no supplements in preventing BMD loss in women with breast cancer. Additionally, researchers reported inadequacies in the prevention of BMD loss when doses of 500 mg to 1,500 mg calcium and 200 IU to 1,000 IU vitamin D per day were administered among pre- and postmenopausal women with breast cancer.

However, exercise or pharmacologic interventions could prevent BMD loss in this patient population when such supplementation is not effective, researchers wrote. The researchers added that controversial literature exists regarding the risk for cardiovascular disease with the use ofcalcium supplements.

“The take-home message is that this very common practice of supplementation doesn’t really seem to be working,” Schwartz said. “Future trials are needed to evaluate the safety and efficacy of calcium and vitamin D supplementation in women undergoing breast cancer therapy.”

Source: Endocrine Today.


Diabetes prevalence continues to climb in China.

Data from a survey of over 98,000 Chinese adults indicate that the prevalence of diabetes affects approximately 50% of the Chinese population, and only 25.8% of diagnosed patients are being treated.

“These data suggest that diabetes may have reached an alert level in the Chinese general population with the potential for a major epidemic of diabetes-related complications, including cardiovascular disease, stroke and chronic kidney disease in China in the near future without an effective national intervention,” the researchers wrote.

Researchers from the 2010 China Noncommunicable Disease Surveillance Group collected data from 162 study sites in the Chinese Center for Disease Control and Prevention’s (CDC’s) National Disease Surveillance Point System. According to researchers, measurements of HbA1c, fasting plasma glucose and 2-hour plasma glucose were collected from a nationally representative sample of 98,658 adults aged 18 years or older in 2010.

They found that the overall prevalence of diabetes was about 11.6% (95% CI, 11.3% to 11.8%) among the adult Chinese population (12.1% in men vs. 11% in women).

Further data indicate the prevalence of previously diagnosed diabetes was estimated to be 3.5% (95% CI, 3.4% to 3.6%) in the Chinese population (3.6% in men vs. 3.4% in women). Undiagnosed diabetes was estimated at 8.1% (95% CI, 7.9% to 8.3%) in the overall population (8.5% in men vs. 7.7% in women), according to data.

Moreover, the prevalence of prediabetes was estimated to be 50.1% (95% CI, 49.7% to 50.6%) in Chinese adults (52.1% in men vs. 48.1% in women).

The prevalence for prediabetes was greater among patients in older age groups (P<.001), urban residents, patients living in economically-developed regions and those who were overweight or obese, researchers wrote.

Data also demonstrate only 25.8% of patients with diabetes received treatment. Of those treated, only 39.7% had HbA1c levels less than 7% (40.7% in men vs. 38.6% in women), researchers wrote.

In an accompanying editorial, Juliana C. N. Chan, MD, FRCP, from the department of medicine and therapeutics at the Hong Kong Institute of Diabetes and Obesity, the Chinese University of Hong Kong Prince of Wales Hospital International Diabetes Federation Centre of Education, Shatin, Hong Kong, SAR, China, wrote that diabetes is a societal and health care challenge.

“To this end, government leaderships, partnerships, and community empowerment will be needed to create a health-promoting environment, encourage self-management, and strengthen the health care system to make health a reality,” Chan wrote.

Source: Endocrine Today.



Antidepressants did not increase risk for bone loss in middle-aged women.

Although previous studies have suggested selective serotonin reuptake inhibitors and tricyclic antidepressants have adverse effects on bone mineral density, a recent prospective study at five clinical centers in the United States demonstrates there is no increased risk for bone loss at the spine, total hip or femoral neck.

According to Susan J. Diem, MD, MPH,from the department of medicine and division of epidemiology and community health at the University of Minnesota in Minneapolis, and colleagues, these findings did not vary by level of depressive symptoms.

“Our findings should provide reassurance for women in midlife regarding the effects of selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) on bone loss during the menopausal transition,” researchers wrote.

The study compared the annual BMD changes among community-dwelling women (aged 42 years and older) categorized as: nonusers (n=1,590), those taking SSRIs (n=311) or TCAs (n=71). All of the patients were enrolled in the Study of Women’s Health Across the Nation (SWAN), researchers wrote.

According to data, mean lumbar spine BMD decreased 0.68% per year in nonusers, 0.63% in SSRI users and 0.40% per year in TCA users, signaling no statistically significant increased rate of bone loss. Similarly, patients on SSRIs or TCAs displayed no significant bone loss at the total hip and femoral neck, researchers wrote.

In a secondary stratified analysis of depressive symptoms, Diem and colleagues reported no increase in the rate of bone loss among SSRI users or TCA users.

Source: Endocrine Today.


Joint guideline contains new recommendations for diabetes, CVD.

New guidelines on diabetes, prediabetes and CVD unveiled at the ESC Congress 2013 recommend diagnosis using HbA1c, less-strict BP targets and optimal use of revascularization.

The guidelines were developed as a collaboration between the ESC and the European Association for the Study of Diabetes (EASD).

“The growing awareness of the strong biological relationship between diabetes and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007,” the statement reads.

Among the notable updates is the recommendation to use HbA1c for the diagnosis of diabetes. If HbA1c is elevated, the patient is diagnosed with diabetes; if not elevated, patients with CVD should receive an oral glucose tolerance test.

“We have simplified diagnosis because many patients may be disclosed with HbA1c, limiting the numbers who need the lengthier test. But a normal HbA1c does not rule out diabetes in high-risk patients, who need to have an oral glucose tolerance test,” ESC chairperson Lars Rydén, MD, PhD, of the cardiology unit at Karolinska Institute, Sweden, stated in a press release.

The guidelines also simplify CV risk assessment and no longer advocate the use of risk engines. “Risk engines which accumulate risk factors and produce a low-, medium- or high-risk score are less useful for patients with diabetes,” EASD chairperson Peter J. Grant, MD, from the division of cardiovascular and diabetes research at University of Leeds, U.K., stated in the release.

Patients with diabetes are considered at high CV risk. Patients with diabetes and CVD, including MI, angina or peripheral vascular disease, are considered at very high risk for recurrent CVD, according to the release.

Recommendations on revascularization have also changed since the previous guidelines. Medical therapy is now recommended before intervention for patients with stable CAD and no complex coronary lesions. “In former days, we were quick to do coronary interventions, but based on new trial data we now do not advocate bypass surgery and coronaryangioplasty until medical therapy has been tried,” Rydén stated.

Another addition is the recommendation that patients with several or complex coronary artery stenoses should be offered bypass surgery before percutaneous coronary dilatation. This change was based on new trial data that show superior morbidity and mortality with bypass surgery as compared with coronary dilatation, according to the release.

The guidelines also individualize targets for BP and glycemic control. The general BP target for patients with diabetes is <140/85 mm Hg; in the 2007 version, the target was 130/80 mm Hg. In patients with diabetes and kidney disease, the target is <130/85 mm Hg. Stricter BP control is also urged for patients at risk for stroke. Younger patients with a recent diagnosis of diabetes and no CVD history have lower recommended glycemic control targets, while those who are older and have longstanding diabetes and CVD have more modest targets.

Other changes in the new guidelines include the prioritization of weight stabilization over reduction, recommendations against drugs to increase HDL levels and aspirin use in patients with diabetes and no CVD, and a new chapter on patient-centered care with emphasis on shared decision-making.

Source: Endocrine Today.