Prediabetes — even at lower levels of impaired fasting glucose (IFG) as defined by the American Diabetes Association (ADA) — is associated with a significant increase in cancer risk that is independent of the effects of obesity, according to the results of a large new meta-analysis.
Yuli Huang, MD, PhD, from First People's Hospital of Shunde, Foshan, China, and colleagues found that prediabetes was associated with a 15% increased risk for cancer overall, based on data derived from 16 prospective cohort studies, with differing risks depending on the type of cancer. The risk was particularly increased for liver cancer and stomach or colorectal cancer.
"Epidemiological studies have shown that diabetes increases the incidence of cancer and mortality from it, but we thought that maybe not only diabetes but prediabetes may be associated with an elevated cancer risk," Dr. Huang said.
"And considering the high prevalence of prediabetes as well as the robust and significant association between prediabetes and cancer we demonstrated in our study, a successful lifestyle intervention could have a major public-health impact on cancer prevention," he added.
"This information is important to health professionals and those engaged in the prevention of cancer," Dr. Huang and colleagues stress.
The study was published online September 8 in Diabetologia.
Screen for Prediabetes Using ADA Criteria for Cancer Prevention
A total of 891,426 participants from the 16 studies, 4 of which were from Asia, 11 from the United States and Europe, and 1 from Africa, were included in the meta-analysis. Prediabetes included individuals with impaired glucose tolerance (IGT), IFG, or a combination of the 2.
Over 10 years ago, the ADA lowered its definition of prediabetes to that of a fasting plasma glucose concentration ranging from 5.6 to 6.9 mmol/L, but other organizations have maintained their definition at a higher level, as a fasting plasma glucose concentration between 6.1 and 6.9 mmol/L.
The risks of site-specific cancer among individuals with prediabetes was highest for liver cancer (relative risk [RR], 2.01), followed by colorectal and stomach cancer (RR, 1.55 for both), endometrial cancer (RR, 1.60), and breast as well as pancreatic cancer (RR, 1.19 for both).
But prediabetes was not associated with cancer of the bronchus, lung, prostate, ovary, kidney, or bladder.
The risks were increased even when a lower fasting plasma glucose value of 5.6 to 6.9 mmol/L was used, as well as in participants with IGT — "an interesting finding," investigators note, "and one that reaffirms the importance of screening for prediabetes using the ADA criteria with a view to cancer prevention."
As the authors point out, obesity — in itself a key risk factor for diabetes — has also been linked to cancer.
To rule out obesity as a potential confounder, the authors did a sensitivity analysis that included only studies that adjusted for body mass index (BMI).
After controlling for BMI, "we found that...the presence of prediabetes remained associated with an increased risk of cancer by 22%," they state. "So we believe that the increased risk of cancer in individuals with prediabetes is independent of obesity."
"Our study indicates that, on the basis of a snapshot blood glucose measurement, prediabetes is associated with an increased risk of cancer," they state.
Need for Trials of Metformin to Prevent Cancer
Speculating on the reasons for the association between prediabetes and increased cancer risk, Dr. Huang and colleagues suggest that chronic hyperglycemia and resulting states, including chronic oxidative stress and the accumulation of advanced glycated end products, may serve as carcinogens.
Alternatively, increased insulin resistance characteristic of prediabetes increases insulin secretion, and increased insulin levels may promote the growth of cancer cells.
Certain genetic mutations may also predispose individuals with prediabetes to an elevated cancer risk, they suggest.
As the authors point out, it is noteworthy that metformin is associated with an approximately 30% reduction in the lifetime risk of cancer in diabetic patients.
"Considering the protective anticancer properties of metformin in patients with diabetes, as well as its ability to delay progress to diabetes in patients with prediabetes, we feel studies are urgently needed to explore the effects of metformin on cancer risk in people with prediabetes, and [if shown to be protective], metformin might be recommended in select high-risk individuals, especially those with IGT or a combination of IGT and IFG," they conclude.
Welcome to my collection of health articles. Most of them contain little nuggets of health wisdom that we can easily apply to our daily lives. As you can gather, I've been consuming all sorts of supplements over the years, most of them from iherb. They deliver on time (DHL), and prices are good. If you're a first-time buyer, use my code 'pot089' to enjoy up to $10 off.
Thursday, 11 September 2014
Wednesday, 12 March 2014
How Selenium, Vitamin E Increase Prostate Cancer Risk
New data from the much publicized Selenium and Vitamin E Cancer Prevention Trial (SELECT), which sought to determine whether these supplements could protect against the development of prostate cancer, confirm that both antioxidants can be risky business for men.
As previously reported, men receive no preventive benefit from either selenium or vitamin E supplements; in fact, for certain men, these supplements actually increased the risk for prostate cancer.
The new study, published online February 22 in the Journal of the National Cancer Institute, explored which men who take these supplements are most at risk for prostate cancer, and why.
However, the ongoing public health message from the trial remains the same, said a trial investigator.
"Men using these supplements should stop, period. Neither selenium nor vitamin E supplementation confer any known [health] benefits — only risks," said lead author Alan Kristal, DrPH, from the Fred Hutchinson Cancer Research Center in Seattle, in a press statement.
"Many people think that dietary supplements are helpful or at the least innocuous. This is not true," he added.
The cohort of 4856 men was culled from SELECT, the larger phase 3 placebo-controlled trial in which more than 35,000 men were randomized to high-dose vitamin E (400 IU/day) and/or selenium (200 µg/day) supplements.
SELECT began in 2001 and was expected to run for 12 years, but it was stopped early, in 2008, after participants had been on the supplements for an average of 5 years. The results demonstrated that there was no protective effect from selenium and suggested that vitamin E increased prostate cancer risk.
Although the use of the supplements stopped, the study actually continued. After 2 years of follow-up, the men who took vitamin E had a statistically significant 17% increased risk for prostate cancer, as previously reported.
Notably, the rate of prostate cancer detection was higher in the groups that received either supplement alone or a combination of the 2 than in the placebo group (but the difference was significant only in the vitamin E group).
Selenium is a nonmetallic trace element found in plant in foods such as rice, wheat, and Brazil nuts, and in seafood and meat. In a previous large skin cancer prevention trial, it was associated with a reduced risk for prostate cancer. According to the National Cancer Institute, it is an antioxidant that might help control cell damage that can lead to cancer.
Vitamin E is found in a wide range of foods, especially vegetables, vegetable oils, nuts, and egg yolks. Like selenium, vitamin E is considered an antioxidant.
Key: Increased Risk Depends on Baseline Selenium
In this new case–cohort study, 1739 men diagnosed with prostate cancer during SELECT were compared with 3117 men who were not.
Dr. Kristal and colleagues found that baseline selenium status alone, in the absence of supplementation, was not associated with prostate cancer risk.
However, they also found that the effects of the supplements differed substantially between men with low levels at baseline and those with high levels.
Specifically, selenium supplementation increased the risk for prostate cancer in men who already had high selenium levels at baseline.
Before SELECT even began, there was evidence that selenium supplementation would not benefit men who already had an adequate intake of the nutrient.
For this reason, at baseline, the investigators measured the concentration of selenium in the toenails of participants. The plan was to test whether supplementation would benefit only the subset of men with low selenium levels at baseline, they explain.
Instead, they found that men with high selenium levels at baseline who took selenium supplements increased their risk for high-grade cancer by 91% (P = .007). In other words, the levels of selenium in these men became toxic.
The investigators also report that vitamin E increased prostate cancer risk in men, but only in those with low selenium levels at baseline.
Specifically, in the men with low levels of selenium randomized to receive vitamin E alone, the total risk for prostate cancer increased by 63% (P = .02) and the risk for high-grade cancer increased by 111% (P = .01).
This might explain why, in the 2008 SELECT results, only the men randomized to receive vitamin E alone, not those who received both vitamin E and selenium, had an increased risk for prostate cancer.
There is some evidence from basic science to support the idea of a meaningful dynamic. "An interaction between vitamin E and selenium has long been hypothesized because of their activities in preventing lipid peroxidation," Dr. Kristal and colleagues write.
Selenium, whether from dietary sources or supplements, might protect men from the harmful effects of vitamin E, they suggest. So selenium, at low levels, is not necessarily harmful to men.
Nevertheless, these new results are consistent with the medical literature on supplements and cancer, the investigators report. The message is that nothing good is gained in healthy people.
The literature "suggests that effects of supplementation are dependent upon the nutrient status of the target population, such that supplementation of populations with adequate nutrient status, leading to supraphysiological exposure, has either no effect or increases cancer risk," they write.
As previously reported, men receive no preventive benefit from either selenium or vitamin E supplements; in fact, for certain men, these supplements actually increased the risk for prostate cancer.
The new study, published online February 22 in the Journal of the National Cancer Institute, explored which men who take these supplements are most at risk for prostate cancer, and why.
However, the ongoing public health message from the trial remains the same, said a trial investigator.
"Men using these supplements should stop, period. Neither selenium nor vitamin E supplementation confer any known [health] benefits — only risks," said lead author Alan Kristal, DrPH, from the Fred Hutchinson Cancer Research Center in Seattle, in a press statement.
"Many people think that dietary supplements are helpful or at the least innocuous. This is not true," he added.
The cohort of 4856 men was culled from SELECT, the larger phase 3 placebo-controlled trial in which more than 35,000 men were randomized to high-dose vitamin E (400 IU/day) and/or selenium (200 µg/day) supplements.
SELECT began in 2001 and was expected to run for 12 years, but it was stopped early, in 2008, after participants had been on the supplements for an average of 5 years. The results demonstrated that there was no protective effect from selenium and suggested that vitamin E increased prostate cancer risk.
Although the use of the supplements stopped, the study actually continued. After 2 years of follow-up, the men who took vitamin E had a statistically significant 17% increased risk for prostate cancer, as previously reported.
Notably, the rate of prostate cancer detection was higher in the groups that received either supplement alone or a combination of the 2 than in the placebo group (but the difference was significant only in the vitamin E group).
Selenium is a nonmetallic trace element found in plant in foods such as rice, wheat, and Brazil nuts, and in seafood and meat. In a previous large skin cancer prevention trial, it was associated with a reduced risk for prostate cancer. According to the National Cancer Institute, it is an antioxidant that might help control cell damage that can lead to cancer.
Vitamin E is found in a wide range of foods, especially vegetables, vegetable oils, nuts, and egg yolks. Like selenium, vitamin E is considered an antioxidant.
Key: Increased Risk Depends on Baseline Selenium
In this new case–cohort study, 1739 men diagnosed with prostate cancer during SELECT were compared with 3117 men who were not.
Dr. Kristal and colleagues found that baseline selenium status alone, in the absence of supplementation, was not associated with prostate cancer risk.
However, they also found that the effects of the supplements differed substantially between men with low levels at baseline and those with high levels.
Specifically, selenium supplementation increased the risk for prostate cancer in men who already had high selenium levels at baseline.
Before SELECT even began, there was evidence that selenium supplementation would not benefit men who already had an adequate intake of the nutrient.
For this reason, at baseline, the investigators measured the concentration of selenium in the toenails of participants. The plan was to test whether supplementation would benefit only the subset of men with low selenium levels at baseline, they explain.
Instead, they found that men with high selenium levels at baseline who took selenium supplements increased their risk for high-grade cancer by 91% (P = .007). In other words, the levels of selenium in these men became toxic.
The investigators also report that vitamin E increased prostate cancer risk in men, but only in those with low selenium levels at baseline.
Specifically, in the men with low levels of selenium randomized to receive vitamin E alone, the total risk for prostate cancer increased by 63% (P = .02) and the risk for high-grade cancer increased by 111% (P = .01).
This might explain why, in the 2008 SELECT results, only the men randomized to receive vitamin E alone, not those who received both vitamin E and selenium, had an increased risk for prostate cancer.
There is some evidence from basic science to support the idea of a meaningful dynamic. "An interaction between vitamin E and selenium has long been hypothesized because of their activities in preventing lipid peroxidation," Dr. Kristal and colleagues write.
Selenium, whether from dietary sources or supplements, might protect men from the harmful effects of vitamin E, they suggest. So selenium, at low levels, is not necessarily harmful to men.
Nevertheless, these new results are consistent with the medical literature on supplements and cancer, the investigators report. The message is that nothing good is gained in healthy people.
The literature "suggests that effects of supplementation are dependent upon the nutrient status of the target population, such that supplementation of populations with adequate nutrient status, leading to supraphysiological exposure, has either no effect or increases cancer risk," they write.
Adding Flavanols to Dark Chocolate Doesn't Improve Health Benefits
Excuses for regularly indulging in dark chocolate keep accumulating, with the added possibility that its ingredients, thought to promote relaxed arteries, also have biochemical effects that may discourage atherosclerosis. But special flavanol-enriched formulations of dark chocolate may do little to enhance its vascular benefits, suggests a report published in the March 2014 issue of the FASEB Journal.
In a randomized, double-blind study, eating dark chocolate—acutely and over weeks—not only improved objective measures of endovascular function, it also improved biochemical markers that reflect leukocyte activation, inflammation, and other signs of atherogenesis.
The study further compared normal- vs high-flavanol dark-chocolate consumption by its participants, a few dozen overweight and mildly obese middle-aged male volunteers. It saw few important differences in vascular functional or biochemical effects following ingestion of either formulation of chocolate.
Changes in endothelial function were reflected in improved flow-mediated dilation (FMD), blood pressure, and augmentation index (AIX), while "changes in leukocyte-cell counts, plasma cytokines, and leukocyte adherence markers after chocolate consumption point toward a less-activated state of cellular adherence and, hence, a less atherogenic milieu," according to the authors, led by Dr Diederik Esser (Top Institute Food and Nutrition and Wageningen University, the Netherlands).
"Extra flavanols did not augment these effects," they write, "but did affect taste and had a negative effect on the motivation to eat chocolate."
Beneficial vascular changes and even improved clinical outcomes have long been attributed to consumption of flavanol- and polyphenol-rich foods like chocolate, red wine, cinnamon, and tea in both observational and interventional studies. Chocolate itself has been associated with improved blood pressure and cerebral perfusion and a reduction in stroke, heart failure, and other cardiovascular-event outcomes.
Acute Chocolate Effects
In a double-blind crossover randomization, 29 men consumed 70 g of chocolate on each of two days separated by at least one week. On one occasion, the chocolate contained normal levels of flavanols, and on the other it was supplemented with extra flavanols.
Ingestion of both types of chocolate decreased AIX (indicating decreased central aortic pressure) but didn't affect FMD (reflecting endothelial function). Similarly, hematocrit and counts of thrombocytes, lymphocytes, monocytes, and neutrophils went up within two hours. Plasma soluble intercellular adhesion molecule (sICAM) 3, interleukin (IL)-1β, and von Willebrand factor levels went up, and plasma IL-6 levels fell two hours after ingestion of both kinds of chocolate. Insulin also went up after both chocolates, but more so after the high-flavanol kind.
The Four-Week Crossover Trial
The same 29 subjects plus an additional 15 participated in a second double-blind experiment in which four weeks of 70 g per day of either high- or low-flavanol chocolate was followed by a four-week washout period and then crossover to four weeks of the other kind of chocolate. They followed certain dietary restrictions to minimize background flavanol intake.
Four weeks of consuming chocolate of either kind elevated fasting FMD by a percentage point and dropped AIX to a similar extent; both measures reverted to baseline after the washout period. The literature suggests a significant 13% reduction in cardiovascular-event risk for every 1% rise in FMD after chocolate consumption, according to the authors.
In a novel finding, four weeks of chocolate consumption significantly lowered counts of circulating leukocytes, suggesting decreased inflammation; also, "leukocytes can transmigrate through the endothelium and therefore play a crucial role in the formation of atherosclerosis."
Chocolate also lowered protein expression of lymphocytes CD62L and CD11b, monocyte CD62L, and neutrophils CD66b and CD11c. "These cell-surface molecules are involved in leukocyte recruitment and adherence to the endothelium during the initial steps of atherosclerosis," the group writes.
"A minor but significant" 0.1-mL rise in fasting plasma glucose and 0.3-mL increase in plasma free fatty acids was evident after four weeks of chocolate of either kind.
Taking the High-Fat Challenge
"High-fat-challenge" tests conducted after each four-week period of chocolate intake required drinking a 95 fat-gram shake of yogurt, canola oil, and other ingredients followed by endothelial-function and metabolic marker tests at 1.5 and 3.0 hours to assess postprandial responses.
Consumption of the high-fat shake was followed by average declines in FMD by 1.8 percentage points, in AIX by four percentage points, and in diastolic blood pressure by 2 mm Hg, regardless of whether the background chocolate contained normal or high flavanol levels. Also seen at postprandial testing were rises in hematocrit; counts of thrombocytes, lymphocytes, monocytes, and neutrophils; plasma concentrations of sICAM1, soluble vascular cell adhesion molecule (sVCAM) 1, sICAM3, P-selectin, IL-8, and tumor necrosis factor-alpha (TNF-α); and expression of lymphocytes CD11c and CD11b, monocyte CD11c and CD11b, and neutrophils CD62l and CD11b adhesion molecules. At the same time, monocyte CD62l expression and IL-6 plasma levels fell.
"Our results indicate that flavanol-enriched chocolate was not healthier than regular dark chocolate with respect to vascular health markers," according to Esser et al.
Limits on flavanol absorption didn't account for the similar effects, they determined, based on plasma and urine measures of flavanol intake; normal-flavanol–level chocolate may simply attain maximal flavanol effects on vascular health, the group writes.
In a randomized, double-blind study, eating dark chocolate—acutely and over weeks—not only improved objective measures of endovascular function, it also improved biochemical markers that reflect leukocyte activation, inflammation, and other signs of atherogenesis.
The study further compared normal- vs high-flavanol dark-chocolate consumption by its participants, a few dozen overweight and mildly obese middle-aged male volunteers. It saw few important differences in vascular functional or biochemical effects following ingestion of either formulation of chocolate.
Changes in endothelial function were reflected in improved flow-mediated dilation (FMD), blood pressure, and augmentation index (AIX), while "changes in leukocyte-cell counts, plasma cytokines, and leukocyte adherence markers after chocolate consumption point toward a less-activated state of cellular adherence and, hence, a less atherogenic milieu," according to the authors, led by Dr Diederik Esser (Top Institute Food and Nutrition and Wageningen University, the Netherlands).
"Extra flavanols did not augment these effects," they write, "but did affect taste and had a negative effect on the motivation to eat chocolate."
Beneficial vascular changes and even improved clinical outcomes have long been attributed to consumption of flavanol- and polyphenol-rich foods like chocolate, red wine, cinnamon, and tea in both observational and interventional studies. Chocolate itself has been associated with improved blood pressure and cerebral perfusion and a reduction in stroke, heart failure, and other cardiovascular-event outcomes.
Acute Chocolate Effects
In a double-blind crossover randomization, 29 men consumed 70 g of chocolate on each of two days separated by at least one week. On one occasion, the chocolate contained normal levels of flavanols, and on the other it was supplemented with extra flavanols.
Ingestion of both types of chocolate decreased AIX (indicating decreased central aortic pressure) but didn't affect FMD (reflecting endothelial function). Similarly, hematocrit and counts of thrombocytes, lymphocytes, monocytes, and neutrophils went up within two hours. Plasma soluble intercellular adhesion molecule (sICAM) 3, interleukin (IL)-1β, and von Willebrand factor levels went up, and plasma IL-6 levels fell two hours after ingestion of both kinds of chocolate. Insulin also went up after both chocolates, but more so after the high-flavanol kind.
The Four-Week Crossover Trial
The same 29 subjects plus an additional 15 participated in a second double-blind experiment in which four weeks of 70 g per day of either high- or low-flavanol chocolate was followed by a four-week washout period and then crossover to four weeks of the other kind of chocolate. They followed certain dietary restrictions to minimize background flavanol intake.
Four weeks of consuming chocolate of either kind elevated fasting FMD by a percentage point and dropped AIX to a similar extent; both measures reverted to baseline after the washout period. The literature suggests a significant 13% reduction in cardiovascular-event risk for every 1% rise in FMD after chocolate consumption, according to the authors.
In a novel finding, four weeks of chocolate consumption significantly lowered counts of circulating leukocytes, suggesting decreased inflammation; also, "leukocytes can transmigrate through the endothelium and therefore play a crucial role in the formation of atherosclerosis."
Chocolate also lowered protein expression of lymphocytes CD62L and CD11b, monocyte CD62L, and neutrophils CD66b and CD11c. "These cell-surface molecules are involved in leukocyte recruitment and adherence to the endothelium during the initial steps of atherosclerosis," the group writes.
"A minor but significant" 0.1-mL rise in fasting plasma glucose and 0.3-mL increase in plasma free fatty acids was evident after four weeks of chocolate of either kind.
Taking the High-Fat Challenge
"High-fat-challenge" tests conducted after each four-week period of chocolate intake required drinking a 95 fat-gram shake of yogurt, canola oil, and other ingredients followed by endothelial-function and metabolic marker tests at 1.5 and 3.0 hours to assess postprandial responses.
Consumption of the high-fat shake was followed by average declines in FMD by 1.8 percentage points, in AIX by four percentage points, and in diastolic blood pressure by 2 mm Hg, regardless of whether the background chocolate contained normal or high flavanol levels. Also seen at postprandial testing were rises in hematocrit; counts of thrombocytes, lymphocytes, monocytes, and neutrophils; plasma concentrations of sICAM1, soluble vascular cell adhesion molecule (sVCAM) 1, sICAM3, P-selectin, IL-8, and tumor necrosis factor-alpha (TNF-α); and expression of lymphocytes CD11c and CD11b, monocyte CD11c and CD11b, and neutrophils CD62l and CD11b adhesion molecules. At the same time, monocyte CD62l expression and IL-6 plasma levels fell.
"Our results indicate that flavanol-enriched chocolate was not healthier than regular dark chocolate with respect to vascular health markers," according to Esser et al.
Limits on flavanol absorption didn't account for the similar effects, they determined, based on plasma and urine measures of flavanol intake; normal-flavanol–level chocolate may simply attain maximal flavanol effects on vascular health, the group writes.
Wednesday, 12 February 2014
Low-Dose Aspirin Ups Survival in Heart Failure
Daily low-dose aspirin, defined as 75 mg/day, was followed by a 42% mortality reduction over several years in a cohort of patients participating in a heart-failure disease-management program [1] . Aspirin prolonged survival regardless of whether patients had a standard aspirin indication, such as ischemic heart disease, peripheral vascular disease, or stroke, reported investigators in their study, published online February 3, 2014 in Circulation: Heart Failure. There was no such survival benefit, however, at dosages higher than 75 mg/day, although both low- and higher-dose aspirin improved heart-failure hospitalizations.
The findings contrast with and go beyond prior studies of narrower heart-failure populations treated with aspirin, observe its authors, led by Dr Margaret Bermingham (St Vincent's University Hospital, Dublin, Ireland). Of those randomized trials, they note,WARCEF saw more bleeding and otherwise no clinical advantage for warfarin over aspirin; and in WASH and WATCH , neither aspirin nor warfarin seemed to protect against events.
But the group notes that aspirin in those trials was given at two to four times the low dose of the current analysis, which suggests "that low-dose aspirin may have a continuing role in secondary prevention once patients are diagnosed with HF" and points to a need for "more, preferably prospective, trials of low-dose aspirin use in HF."
Of the 1476 patients in the retrospective analysis, who were followed for a median of 2.15 years (range one day to 12 years), 892 (about 60%) were prescribed aspirin at baseline. Of those, 91% received aspirin at 75 mg/day and the remainder received aspirin at higher dosages.
Another antiplatelet, such as clopidogrel, was also given to 18.4% of the aspirin group, while 27.8% of them took added warfarin, and 2.1% received dual antiplatelets and warfarin.
The findings "add to the controversy on aspirin use in HF by presenting reassuring results on low-dose aspirin use in a clinical-practice population," the group writes. "They challenge the belief that aspirin should be avoided in secondary-prevention patients who go on to develop HF and suggest that patients on higher antiplatelet doses may benefit from dose reduction."
The findings contrast with and go beyond prior studies of narrower heart-failure populations treated with aspirin, observe its authors, led by Dr Margaret Bermingham (St Vincent's University Hospital, Dublin, Ireland). Of those randomized trials, they note,WARCEF saw more bleeding and otherwise no clinical advantage for warfarin over aspirin; and in WASH and WATCH , neither aspirin nor warfarin seemed to protect against events.
But the group notes that aspirin in those trials was given at two to four times the low dose of the current analysis, which suggests "that low-dose aspirin may have a continuing role in secondary prevention once patients are diagnosed with HF" and points to a need for "more, preferably prospective, trials of low-dose aspirin use in HF."
Of the 1476 patients in the retrospective analysis, who were followed for a median of 2.15 years (range one day to 12 years), 892 (about 60%) were prescribed aspirin at baseline. Of those, 91% received aspirin at 75 mg/day and the remainder received aspirin at higher dosages.
Another antiplatelet, such as clopidogrel, was also given to 18.4% of the aspirin group, while 27.8% of them took added warfarin, and 2.1% received dual antiplatelets and warfarin.
The findings "add to the controversy on aspirin use in HF by presenting reassuring results on low-dose aspirin use in a clinical-practice population," the group writes. "They challenge the belief that aspirin should be avoided in secondary-prevention patients who go on to develop HF and suggest that patients on higher antiplatelet doses may benefit from dose reduction."
Low fat yoghurt cuts risk of type 2 diabetes
Swapping snacks — such as potato chips — for low-fat yogurt can cut the risk of developing type 2 diabetes by almost half, according to the results of a new observational study.
The findings, involving a randomly selected subgroup from the larger EPIC-Norfolk study, were published online February 5 inDiabetologia by Nita G. Forouhi, MBB, PhD, from the Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, United Kingdom, and colleagues.
"A good place to include yogurt in your diet to reap the benefits against onset of diabetes would be instead of a packet of crisps [potato chips].We found that swapping crisps for yogurt offered protection against onset of diabetes. This may form a practical dietary change suggestion for patients at risk of diabetes as well as among the general population," Dr. Forouhi revealed in an email.
In the study — the first to examine the relationship of dairy consumption with incident type 2 diabetes using prospective 7-day food diaries — subjects with the highest low-fat yogurt consumption had a 28% lower risk of developing type 2 diabetes over 11 years of follow-up compared with those who ate very little or no yogurt, after adjustment for a variety of possible confounders.
"Current US dietary guidelines recommend increasing intake of fat-free or low-fat milk and milk products such as milk, yogurt, and cheese… Recommending yogurt intake is therefore in keeping with dietary guidelines for all patients," Dr. Forouhi said.
And, she noted, "At a time when other research has shown that certain foods raise health risks, such as consuming high amounts of added sugar, it is reassuring to have messages about other foods, like yogurt and low-fat fermented dairy products, that could be good for our health."
Dietary Dairy Examined
The study compared a detailed daily record of all the food and drink consumed over a week at the time of study entry among 753 people who developed new-onset type 2 diabetes over 11 years of follow-up, with 3502 randomly selected study participants from EPIC-Norfolk, which comprised more than 25,000 men and women.
At baseline, subjects had a mean age of 59 years and body mass index (BMI) of 26 kg/m 2; they filled in detailed diary questionnaires that asked about all foods containing dairy as the main ingredient and the type of dairy product (yogurt, cheese, or milk). These were divided into high-fat and low-fat based on a 3.9% cutoff for total fat content. Fermented dairy products (all yogurt, all cheese, sour cream, and crème fraiche) were also categorized separately into high- and low-fat.
Milk was the most-consumed dairy product, accounting for 82%, followed by cheese (9%) and yogurt (8%). Total average dairy consumption was 269 g/day, of which 65% was low-fat.
Total overall dairy consumption was not associated with the development of diabetes, but low-fat dairy intake was, after adjustment for age and sex. Yet even this became nonsignificant after further adjustment for other confounders including BMI, smoking, alcohol consumption, social class, physical activity, and other dietary components.
Similarly, total fermented dairy-product consumption was associated with a 19% lower risk, but this also became nonsignificant after adjustment for possible confounders.
Low-Fat Fermented Dairy Products Linked to Lower Risk
But after full adjustment, a significant relationship remained between intake of low-fat fermented dairy products and the development of type 2 diabetes, with a hazard ratio of 0.76 for the highest vs lowest tertiles (P for trend = .049).
"In public-health terms this equates to 4.5 standard-size portions (125 g) per week of low-fat fermented dairy products, largely composed of yogurt (all types) and including low-fat unripened cheese such as low-fat cottage cheese and fromage frais," the researchers say.
Low-fat yogurt in particular was associated with a 35% reduced risk after adjustment for age and sex ( P for trend < .001), and this relationship remained significant even after adjustment for other potential confounders (HR 0.72, P for trend = .017).
In a separate analysis, the effect of substituting dairy products for snacks — such as cake, pudding, biscuits, or chips — was examined. Eating yogurt instead of such snacks resulted in a 47% lower risk for diabetes, but none of the other substitutions resulted in a significant reduction in diabetes risk.
Several possible mechanisms could explain the relationship between fermented dairy and diabetes, including promotion of the synthesis of menaquinone (vitamin K 2), which has been linked to reduced rates of type 2 diabetes, or the actions of probiotic bacteria, which have been found to improve lipid profiles and antioxidant status in patients with type 2 diabetes, the researchers suggest.
Moreover, low-fat fermented dairy products are "naturally low in fat and high in water content and are, therefore, low energy-dense foods. Studies have shown an independent association of low energy-dense foods with lower fasting insulin levels and the metabolic syndrome and a lower risk of type 2 diabetes," they say.
Dr. Forouhi said that the use of 7-day food diaries allows for a much more careful analysis of dairy intake than has been done in prior studies.
"This work gives us important…and more detailed information than our own past research and that of others. We were able to estimate people's diets in much more detail and in real time with all food and drink that was consumed being recorded with a 7-day food diary.
"This gets around an important limitation of the past research, which has relied on participants' recall of foods they have eaten in the past. This gives us greater confidence that low-fat fermented dairy and yogurt specifically within that group can be important for the prevention of diabetes as part of an overall healthy lifestyle," she concluded.
The findings, involving a randomly selected subgroup from the larger EPIC-Norfolk study, were published online February 5 inDiabetologia by Nita G. Forouhi, MBB, PhD, from the Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, United Kingdom, and colleagues.
"A good place to include yogurt in your diet to reap the benefits against onset of diabetes would be instead of a packet of crisps [potato chips].We found that swapping crisps for yogurt offered protection against onset of diabetes. This may form a practical dietary change suggestion for patients at risk of diabetes as well as among the general population," Dr. Forouhi revealed in an email.
In the study — the first to examine the relationship of dairy consumption with incident type 2 diabetes using prospective 7-day food diaries — subjects with the highest low-fat yogurt consumption had a 28% lower risk of developing type 2 diabetes over 11 years of follow-up compared with those who ate very little or no yogurt, after adjustment for a variety of possible confounders.
"Current US dietary guidelines recommend increasing intake of fat-free or low-fat milk and milk products such as milk, yogurt, and cheese… Recommending yogurt intake is therefore in keeping with dietary guidelines for all patients," Dr. Forouhi said.
And, she noted, "At a time when other research has shown that certain foods raise health risks, such as consuming high amounts of added sugar, it is reassuring to have messages about other foods, like yogurt and low-fat fermented dairy products, that could be good for our health."
Dietary Dairy Examined
The study compared a detailed daily record of all the food and drink consumed over a week at the time of study entry among 753 people who developed new-onset type 2 diabetes over 11 years of follow-up, with 3502 randomly selected study participants from EPIC-Norfolk, which comprised more than 25,000 men and women.
At baseline, subjects had a mean age of 59 years and body mass index (BMI) of 26 kg/m 2; they filled in detailed diary questionnaires that asked about all foods containing dairy as the main ingredient and the type of dairy product (yogurt, cheese, or milk). These were divided into high-fat and low-fat based on a 3.9% cutoff for total fat content. Fermented dairy products (all yogurt, all cheese, sour cream, and crème fraiche) were also categorized separately into high- and low-fat.
Milk was the most-consumed dairy product, accounting for 82%, followed by cheese (9%) and yogurt (8%). Total average dairy consumption was 269 g/day, of which 65% was low-fat.
Total overall dairy consumption was not associated with the development of diabetes, but low-fat dairy intake was, after adjustment for age and sex. Yet even this became nonsignificant after further adjustment for other confounders including BMI, smoking, alcohol consumption, social class, physical activity, and other dietary components.
Similarly, total fermented dairy-product consumption was associated with a 19% lower risk, but this also became nonsignificant after adjustment for possible confounders.
Low-Fat Fermented Dairy Products Linked to Lower Risk
But after full adjustment, a significant relationship remained between intake of low-fat fermented dairy products and the development of type 2 diabetes, with a hazard ratio of 0.76 for the highest vs lowest tertiles (P for trend = .049).
"In public-health terms this equates to 4.5 standard-size portions (125 g) per week of low-fat fermented dairy products, largely composed of yogurt (all types) and including low-fat unripened cheese such as low-fat cottage cheese and fromage frais," the researchers say.
Low-fat yogurt in particular was associated with a 35% reduced risk after adjustment for age and sex ( P for trend < .001), and this relationship remained significant even after adjustment for other potential confounders (HR 0.72, P for trend = .017).
In a separate analysis, the effect of substituting dairy products for snacks — such as cake, pudding, biscuits, or chips — was examined. Eating yogurt instead of such snacks resulted in a 47% lower risk for diabetes, but none of the other substitutions resulted in a significant reduction in diabetes risk.
Several possible mechanisms could explain the relationship between fermented dairy and diabetes, including promotion of the synthesis of menaquinone (vitamin K 2), which has been linked to reduced rates of type 2 diabetes, or the actions of probiotic bacteria, which have been found to improve lipid profiles and antioxidant status in patients with type 2 diabetes, the researchers suggest.
Moreover, low-fat fermented dairy products are "naturally low in fat and high in water content and are, therefore, low energy-dense foods. Studies have shown an independent association of low energy-dense foods with lower fasting insulin levels and the metabolic syndrome and a lower risk of type 2 diabetes," they say.
Dr. Forouhi said that the use of 7-day food diaries allows for a much more careful analysis of dairy intake than has been done in prior studies.
"This work gives us important…and more detailed information than our own past research and that of others. We were able to estimate people's diets in much more detail and in real time with all food and drink that was consumed being recorded with a 7-day food diary.
"This gets around an important limitation of the past research, which has relied on participants' recall of foods they have eaten in the past. This gives us greater confidence that low-fat fermented dairy and yogurt specifically within that group can be important for the prevention of diabetes as part of an overall healthy lifestyle," she concluded.
Thursday, 6 February 2014
Coffee Linked to Lower Type 2 Diabetes Risk
Coffee consumption is strongly associated with a reduced risk for type 2 diabetes, regardless of whether the coffee is caffeinated or not, according to a new meta-analysis of 28 prospective studies, published in the February issue of Diabetes Care.
"Compared with no coffee consumption…6 cups/day of coffee was associated with a 33% lower risk of type 2 diabetes," the authors write, adding, "Caffeinated coffee and decaffeinated coffee consumption were both associated with a lower risk of type 2 diabetes."
Drinking coffee has been well-established in previous meta-analyses as being associated with a reduced risk for type 2 diabetes; however, the new review was needed to account for more recent trials evaluating the benefits of caffeinated vs decaffeinated coffee, the authors explain.
"We found that a 1-cup/day increment of regular coffee was associated with a 9% reduction in diabetes, and 1 cup/day of decaf was associated with 6% reduction in diabetes, but the difference in risk reduction between the 2 types of coffee was not statistically different," said senior author Frank B. Hu, MD, PhD, a professor of nutrition and epidemiology with the Harvard School of Public Health in Boston, Massachusetts.
"This study provides strong evidence that regular consumption of coffee is beneficial for prevention of diabetes," Dr. Hu said. "For individuals who already drink coffee, they may enjoy this and other potential health benefits, and for those who are sensitive to the effects of caffeine, decaf may confer similar benefits."
Robust Findings
The 28 studies in the analysis included 1,109,272 participants, and all had the outcome of risk for type 2 diabetes; there were 45,335 cases of diabetes, with follow-up ranging from 10 months to 20 years.
The relative risk for type 2 diabetes with coffee consumption, compared with no or rare consumption, ranged from 0.92 for 1 cup per day, 0.85 for 2 cups, 0.79 for 3 cups, 0.75 for 4 cups, 0.71 for 5 cups, and 0.67 for 6 cups.
Meanwhile, the relative risk for diabetes associated with 1 cup of caffeinated coffee per day (compared to no or rare coffee consumption) was 0.91 compared with 0.94 for 1 cup of decaffeinated coffee per day ( P = .17).
The findings were consistent for men as well as women, and while coffee-brewing methods were not assessed in the studies, the inclusion of diverse populations likely covered a wide array of methods, the authors note.
"Most coffee is likely to be filtered coffee, and the results from studies conducted in various populations, including US, European, and Asian, were similar, indicating consistency of the results despite potentially different preparation and processing methods," they observe.
And while none of the studies assessed levels of sugar and dairy added to coffee, the amounts are "likely to be small compared with other food sources," they add.
While this meta-analysis does provide "strong evidence" that higher consumption of coffee is associated with a significantly lower risk for diabetes," longer-term randomised controlled trials are needed to establish causality and to elucidate the underlying mechanisms," they conclude.
Coffee Just a Small Part of the Diabetes Equation
One possible explanation for the reduced risk for diabetes with coffee consumption could be the role of chlorogenic acid, a phenolic compound and a major component of coffee, Dr. Hu said.
"Chlorogenic acid has been shown to improve insulin sensitivity and reduce blood sugar absorption," he said.
"Compounds in coffee also include antioxidant polyphenols, minerals such as magnesium and chromium, [and] vitamins; however, it is impossible to tease out the effects of individual compounds, because they don't exist in isolation in coffee and they may have synergistic effects."
He stressed also that coffee consumption remains a small piece of the picture.
"Coffee is only one of many dietary and lifestyle factors that can contribute to diabetes prevention. Clearly, maintaining a healthy weight through diet and exercise is the most important way to reduce risk of diabetes. For those who drink coffee regularly, they should enjoy it, but they still need to watch their weight and be physically active."
"Compared with no coffee consumption…6 cups/day of coffee was associated with a 33% lower risk of type 2 diabetes," the authors write, adding, "Caffeinated coffee and decaffeinated coffee consumption were both associated with a lower risk of type 2 diabetes."
Drinking coffee has been well-established in previous meta-analyses as being associated with a reduced risk for type 2 diabetes; however, the new review was needed to account for more recent trials evaluating the benefits of caffeinated vs decaffeinated coffee, the authors explain.
"We found that a 1-cup/day increment of regular coffee was associated with a 9% reduction in diabetes, and 1 cup/day of decaf was associated with 6% reduction in diabetes, but the difference in risk reduction between the 2 types of coffee was not statistically different," said senior author Frank B. Hu, MD, PhD, a professor of nutrition and epidemiology with the Harvard School of Public Health in Boston, Massachusetts.
"This study provides strong evidence that regular consumption of coffee is beneficial for prevention of diabetes," Dr. Hu said. "For individuals who already drink coffee, they may enjoy this and other potential health benefits, and for those who are sensitive to the effects of caffeine, decaf may confer similar benefits."
Robust Findings
The 28 studies in the analysis included 1,109,272 participants, and all had the outcome of risk for type 2 diabetes; there were 45,335 cases of diabetes, with follow-up ranging from 10 months to 20 years.
The relative risk for type 2 diabetes with coffee consumption, compared with no or rare consumption, ranged from 0.92 for 1 cup per day, 0.85 for 2 cups, 0.79 for 3 cups, 0.75 for 4 cups, 0.71 for 5 cups, and 0.67 for 6 cups.
Meanwhile, the relative risk for diabetes associated with 1 cup of caffeinated coffee per day (compared to no or rare coffee consumption) was 0.91 compared with 0.94 for 1 cup of decaffeinated coffee per day ( P = .17).
The findings were consistent for men as well as women, and while coffee-brewing methods were not assessed in the studies, the inclusion of diverse populations likely covered a wide array of methods, the authors note.
"Most coffee is likely to be filtered coffee, and the results from studies conducted in various populations, including US, European, and Asian, were similar, indicating consistency of the results despite potentially different preparation and processing methods," they observe.
And while none of the studies assessed levels of sugar and dairy added to coffee, the amounts are "likely to be small compared with other food sources," they add.
While this meta-analysis does provide "strong evidence" that higher consumption of coffee is associated with a significantly lower risk for diabetes," longer-term randomised controlled trials are needed to establish causality and to elucidate the underlying mechanisms," they conclude.
Coffee Just a Small Part of the Diabetes Equation
One possible explanation for the reduced risk for diabetes with coffee consumption could be the role of chlorogenic acid, a phenolic compound and a major component of coffee, Dr. Hu said.
"Chlorogenic acid has been shown to improve insulin sensitivity and reduce blood sugar absorption," he said.
"Compounds in coffee also include antioxidant polyphenols, minerals such as magnesium and chromium, [and] vitamins; however, it is impossible to tease out the effects of individual compounds, because they don't exist in isolation in coffee and they may have synergistic effects."
He stressed also that coffee consumption remains a small piece of the picture.
"Coffee is only one of many dietary and lifestyle factors that can contribute to diabetes prevention. Clearly, maintaining a healthy weight through diet and exercise is the most important way to reduce risk of diabetes. For those who drink coffee regularly, they should enjoy it, but they still need to watch their weight and be physically active."
Resistance training boosts testosterone in older men
Resistance training can increase the production of sex steroids in the muscles of older men, a new study shows.
If borne out by further research, the findings could have important implications for a wide range of conditions experienced by many aging individuals and linked to a decline in sex steroid hormones, say Koji Sato, PhD, and colleagues from Ritsumeikan University in Kyoto, Japan in their report in the Journal of the Federation of American Societies for Experimental Biology published online January 17.
"Resistance-training–induced increased muscular sex steroid hormone may positively affect age-related concerns such as accidental falls, diabetes, sarcopenia, and osteoporosis and may improve the quality of life for older individuals," they note.
More and more men are using testosterone supplements in the hope of improving their strength, energy, and sexual performance. But this use has become increasingly controversial, because many experts believe such supplementation is not necessary and there is also mounting evidence of concerning side effects associated with the use of testosterone, particularly in older individuals.
Just last week, the US Food and Drug Administration (FDA) announced it is investigating the potential that FDA-approved testosterone products increase the risk for serious adverse cardiovascular outcomes. The agency cited two studies, the most recent of which shows that men treated with testosterone were significantly more likely to have a myocardial infarction (MI) in the first 90 days after starting the medication.
The second study, of Veterans Affairs (VA) patients, published last year, also found that testosterone therapy in men was linked with an increased risk of death, MI, or ischemic stroke.
Sex Hormones in Skeletal Muscles Boosted by Training
In their new paper, Dr. Sato and colleagues explain that while the testes, ovaries, and adrenal cortex produce most steroid sex hormones in humans, recent animal work has shown that skeletal muscle can also synthesize testosterone, estradiol, dehyroepiandrosterone (DHEA), and dihydrotestosterone (DHT). However, a previous study in men and women in their 20s showed no immediate sign of an increase in these hormones in the quadriceps muscle following training ( J Appl Phys. 2008;105: 1754-1760).
To see what effect resistance training might have on older men over a longer period of training, the Japanese researchers recruited 13 men with a mean age of 67.2 years and 6 men with a mean age of 24.3.
The subjects were moderately active, but none regularly performed resistance exercises.
The older men performed knee extensions and flexions 3 times a week on alternate days, using starting weights that were 70% of each subject's single-repetition maximum strength. Trainers retested this measurement and adjusted weights for each of these men every 4 weeks. The study lasted 12 weeks.
Levels of sex steroid hormones and precursors in each man's vastus lateralis (the largest muscle in the quadriceps) were measured by biopsy before the weight training. The same measurement was taken again in the older men after the weight training.
The researchers also sampled the hormones in the men's blood and measured the size of their quadriceps before and after the training.
The older men had much lower levels of steroidogenic enzymes as well as sex steroid hormones and insulinlike growth factor (IGF-1) than the younger men in both their blood and their muscles. The older men were also weaker and had smaller quadriceps.
Nevertheless, the levels of sex steroid hormones increased significantly in the older men's muscles after the weight training. The older men's isokinetic extension strength and quadriceps sizes also increased significantly.
Serum Testosterone Not Significantly Increased
In the blood, however, although the older men had significantly increased serum DHEA and DHT levels after training ( P < .01), their serum free testosterone did not rise significantly ( P = .052), nor did serum IGF-1 ( P= .055).
Levels of steroidogenic enzymes, as well as their androgen-receptor protein expression, did significantly increase, however.
The muscular steroid hormone levels significantly correlated with muscle strength and size, leading the investigators to conclude that "progressive resistance training seems to restore muscle sex steroid hormone levels via enhancement of steroidogenesis-related enzyme expressions in the skeletal muscle and may partly contribute to the increase in muscle strength and [size]."
Asked to comment on the findings, Jakob Vingren, PhD, an associate professor of kinesiology at the University of North Texas Denton, said that the results reinforce the importance of resistance training. "There are definitely benefits to aerobic exercises and there are definitely benefits to resistance training, and they combine, but there are unique benefits to both," he said.
Dr. Vingren added that men who are on androgen-deprivation therapy, for example, for prostate and other cancers, might particularly benefit from resistance training, since these findings indicate it could help strengthen them without increasing their serum testosterone.
If borne out by further research, the findings could have important implications for a wide range of conditions experienced by many aging individuals and linked to a decline in sex steroid hormones, say Koji Sato, PhD, and colleagues from Ritsumeikan University in Kyoto, Japan in their report in the Journal of the Federation of American Societies for Experimental Biology published online January 17.
"Resistance-training–induced increased muscular sex steroid hormone may positively affect age-related concerns such as accidental falls, diabetes, sarcopenia, and osteoporosis and may improve the quality of life for older individuals," they note.
More and more men are using testosterone supplements in the hope of improving their strength, energy, and sexual performance. But this use has become increasingly controversial, because many experts believe such supplementation is not necessary and there is also mounting evidence of concerning side effects associated with the use of testosterone, particularly in older individuals.
Just last week, the US Food and Drug Administration (FDA) announced it is investigating the potential that FDA-approved testosterone products increase the risk for serious adverse cardiovascular outcomes. The agency cited two studies, the most recent of which shows that men treated with testosterone were significantly more likely to have a myocardial infarction (MI) in the first 90 days after starting the medication.
The second study, of Veterans Affairs (VA) patients, published last year, also found that testosterone therapy in men was linked with an increased risk of death, MI, or ischemic stroke.
Sex Hormones in Skeletal Muscles Boosted by Training
In their new paper, Dr. Sato and colleagues explain that while the testes, ovaries, and adrenal cortex produce most steroid sex hormones in humans, recent animal work has shown that skeletal muscle can also synthesize testosterone, estradiol, dehyroepiandrosterone (DHEA), and dihydrotestosterone (DHT). However, a previous study in men and women in their 20s showed no immediate sign of an increase in these hormones in the quadriceps muscle following training ( J Appl Phys. 2008;105: 1754-1760).
To see what effect resistance training might have on older men over a longer period of training, the Japanese researchers recruited 13 men with a mean age of 67.2 years and 6 men with a mean age of 24.3.
The subjects were moderately active, but none regularly performed resistance exercises.
The older men performed knee extensions and flexions 3 times a week on alternate days, using starting weights that were 70% of each subject's single-repetition maximum strength. Trainers retested this measurement and adjusted weights for each of these men every 4 weeks. The study lasted 12 weeks.
Levels of sex steroid hormones and precursors in each man's vastus lateralis (the largest muscle in the quadriceps) were measured by biopsy before the weight training. The same measurement was taken again in the older men after the weight training.
The researchers also sampled the hormones in the men's blood and measured the size of their quadriceps before and after the training.
The older men had much lower levels of steroidogenic enzymes as well as sex steroid hormones and insulinlike growth factor (IGF-1) than the younger men in both their blood and their muscles. The older men were also weaker and had smaller quadriceps.
Nevertheless, the levels of sex steroid hormones increased significantly in the older men's muscles after the weight training. The older men's isokinetic extension strength and quadriceps sizes also increased significantly.
Serum Testosterone Not Significantly Increased
In the blood, however, although the older men had significantly increased serum DHEA and DHT levels after training ( P < .01), their serum free testosterone did not rise significantly ( P = .052), nor did serum IGF-1 ( P= .055).
Levels of steroidogenic enzymes, as well as their androgen-receptor protein expression, did significantly increase, however.
The muscular steroid hormone levels significantly correlated with muscle strength and size, leading the investigators to conclude that "progressive resistance training seems to restore muscle sex steroid hormone levels via enhancement of steroidogenesis-related enzyme expressions in the skeletal muscle and may partly contribute to the increase in muscle strength and [size]."
Asked to comment on the findings, Jakob Vingren, PhD, an associate professor of kinesiology at the University of North Texas Denton, said that the results reinforce the importance of resistance training. "There are definitely benefits to aerobic exercises and there are definitely benefits to resistance training, and they combine, but there are unique benefits to both," he said.
Dr. Vingren added that men who are on androgen-deprivation therapy, for example, for prostate and other cancers, might particularly benefit from resistance training, since these findings indicate it could help strengthen them without increasing their serum testosterone.
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