Sunday, July 1, 2012
Modest Amounts Of Daily Walking May Reduce Diabetes Risk In Obese, Inactive People.
MedWire 
(6/28, Robertson) reports, "Modest amounts of daily walking can
significantly reduce the risk for incident diabetes in obese and
relatively inactive individuals," according to a study
published online June 20 in the journal Diabetes Care. In a five-year
study of some 1,826 native Americans, those "who took at least 3500
steps (approximately 1.75 miles) a day were 29% less likely to develop
diabetes compared with more sedentary participants."
(6/28, Robertson) reports, "Modest amounts of daily walking can
significantly reduce the risk for incident diabetes in obese and
relatively inactive individuals," according to a study
published online June 20 in the journal Diabetes Care. In a five-year
study of some 1,826 native Americans, those "who took at least 3500
steps (approximately 1.75 miles) a day were 29% less likely to develop
diabetes compared with more sedentary participants."
No Weight Gain with Linagliptin in Diabetes
MedPage Link
The DPP-4 inhibitor linagliptin (Tradjenta) may control type 2 diabetes with less hypoglycemia or weight gain than glimepiride (Amaryl) when used as second-line treatment with metformin, a trial showed.
Hemoglobin A1c came down modestly when either drug was added to metformin, with noninferiority between the gliptin and the sulfonylurea, Baptist Gallwitz, MD, of Eberhard-Karls University of Tubingen in Germany, and colleagues found.
Hypoglycemia rates were substantially lower with linagliptin (7% versus 36% with glimepiride, P<0.0001), and patients lost weight, on average, with linagliptin compared with gaining weight with glimepiride, the group reported online in The Lancet.
Cardiovascular event risk appeared 54% lower with linagliptin than with glimepiride; however, the study was not powered or designed to assess cardiovascular outcomes.
"Although glycemic control remains the central feature of type 2 diabetes management for all oral anti-diabetic drugs, their side-effect profiles (including cardiovascular safety) are increasingly important to consider," the investigators wrote.
Their randomized trial findings matched the initial report out of the American Diabetes Association meeting last year.
The association and its European counterpart recommend the gliptin drugs as options for second-line treatment once metformin no longer adequately controls diabetes alone, though noting they lower glycosylated hemoglobin levels somewhat less than sulfonylureas.
In the trial, hemoglobin A1c levels -- starting at a baseline 7.69% average -- fell by 0.16 percentage points with linagliptin versus 0.36 percentage points with glimepiride.
The difference, though falling within the noninferiority threshold of 0.35 percentage points, supported the interpretation of slightly lower efficacy for the gliptin versus sulfonylurea, André J. Scheen, MD, PhD, and Nicolas Paquot, MD, PhD, both of the University of Liège, Belgium, noted in an accompanying commentary.
"However, several advantages are recognized for DPP-4 inhibitors such as no weight gain, a low risk of hypoglycemia, and no need for titration, but at higher cost," they wrote.
The much lower hypoglycemia risk and almost no severe hypoglycemia with linagliptin in the trial (one case versus 12, less than 1% versus 2%) might be a major advantage for some patient groups "and could affect the choice of drug to be added as second-line treatment to metformin," the editorial added.
Another advantage was that weight dropped by 3.1 lbs. (1.4 kg) with linagliptin, whereas it rose by 2.9 lbs. (1.3 kg) with glimepiride over the 2-year trial (P<0.0001).
"Most patients with type 2 diabetes are overweight or obese and so weight management is also an integral part of treatment," the researchers noted.
The study randomized 1,552 patients with type 2 diabetes to double-blind treatment with linagliptin (5 mg) or glimepiride (1 to 4 mg) orally once daily, primarily looking for efficacy but also prospectively assessing cardiovascular safety.
It showed fewer adjudicated major cardiovascular events with the gliptin drug -- 2% versus 3% with glimepiride -- for a relative risk of 0.46 (95% CI 0.23 to 0.91, P=0.0213).
The difference was mainly attributable to fewer nonfatal strokes on linagliptin (RR 0.27, 95% CI 0.08 to 0.97, P=0.0315), not related to hypoglycemic events.
While a cardiovascular risk reduction would be important if confirmed in further study, the finding was based on events in just 12 patients versus 26 with glimepiride over 2 years in a trial underpowered to detect a difference, the editorialists cautioned.
An ongoing large prospective trial known as CAROLINA, looking specifically at cardiovascular outcomes with linagliptin versus glimepiride, should provide the answer.
Add Your Knowledge ™
The DPP-4 inhibitor linagliptin (Tradjenta) may control type 2 diabetes with less hypoglycemia or weight gain than glimepiride (Amaryl) when used as second-line treatment with metformin, a trial showed.
Hemoglobin A1c came down modestly when either drug was added to metformin, with noninferiority between the gliptin and the sulfonylurea, Baptist Gallwitz, MD, of Eberhard-Karls University of Tubingen in Germany, and colleagues found.
Hypoglycemia rates were substantially lower with linagliptin (7% versus 36% with glimepiride, P<0.0001), and patients lost weight, on average, with linagliptin compared with gaining weight with glimepiride, the group reported online in The Lancet.
Cardiovascular event risk appeared 54% lower with linagliptin than with glimepiride; however, the study was not powered or designed to assess cardiovascular outcomes.
"Although glycemic control remains the central feature of type 2 diabetes management for all oral anti-diabetic drugs, their side-effect profiles (including cardiovascular safety) are increasingly important to consider," the investigators wrote.
Their randomized trial findings matched the initial report out of the American Diabetes Association meeting last year.
The association and its European counterpart recommend the gliptin drugs as options for second-line treatment once metformin no longer adequately controls diabetes alone, though noting they lower glycosylated hemoglobin levels somewhat less than sulfonylureas.
In the trial, hemoglobin A1c levels -- starting at a baseline 7.69% average -- fell by 0.16 percentage points with linagliptin versus 0.36 percentage points with glimepiride.
The difference, though falling within the noninferiority threshold of 0.35 percentage points, supported the interpretation of slightly lower efficacy for the gliptin versus sulfonylurea, André J. Scheen, MD, PhD, and Nicolas Paquot, MD, PhD, both of the University of Liège, Belgium, noted in an accompanying commentary.
"However, several advantages are recognized for DPP-4 inhibitors such as no weight gain, a low risk of hypoglycemia, and no need for titration, but at higher cost," they wrote.
The much lower hypoglycemia risk and almost no severe hypoglycemia with linagliptin in the trial (one case versus 12, less than 1% versus 2%) might be a major advantage for some patient groups "and could affect the choice of drug to be added as second-line treatment to metformin," the editorial added.
Another advantage was that weight dropped by 3.1 lbs. (1.4 kg) with linagliptin, whereas it rose by 2.9 lbs. (1.3 kg) with glimepiride over the 2-year trial (P<0.0001).
"Most patients with type 2 diabetes are overweight or obese and so weight management is also an integral part of treatment," the researchers noted.
The study randomized 1,552 patients with type 2 diabetes to double-blind treatment with linagliptin (5 mg) or glimepiride (1 to 4 mg) orally once daily, primarily looking for efficacy but also prospectively assessing cardiovascular safety.
It showed fewer adjudicated major cardiovascular events with the gliptin drug -- 2% versus 3% with glimepiride -- for a relative risk of 0.46 (95% CI 0.23 to 0.91, P=0.0213).
The difference was mainly attributable to fewer nonfatal strokes on linagliptin (RR 0.27, 95% CI 0.08 to 0.97, P=0.0315), not related to hypoglycemic events.
While a cardiovascular risk reduction would be important if confirmed in further study, the finding was based on events in just 12 patients versus 26 with glimepiride over 2 years in a trial underpowered to detect a difference, the editorialists cautioned.
An ongoing large prospective trial known as CAROLINA, looking specifically at cardiovascular outcomes with linagliptin versus glimepiride, should provide the answer.
The study was funded by Boehringer Ingelheim.
Gallwitz reported financial links with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, Merck, Roche, Sanofi, and Takeda.
Scheen reported financial links with AstraZeneca/Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Novo Nordisk, and sanofi-aventis.
Paquot reported financial links with Eli Lilly, Merck Sharp & Dohme, and Novo Nordisk.
Gallwitz reported financial links with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, Merck, Roche, Sanofi, and Takeda.
Scheen reported financial links with AstraZeneca/Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Novo Nordisk, and sanofi-aventis.
Paquot reported financial links with Eli Lilly, Merck Sharp & Dohme, and Novo Nordisk.
Primary source: The Lancet
Source reference:
Gallwitz B, et al "2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial" Lancet 2012; DOI: 10.1016/S0140-6736(12)60859-9.
Additional source: The Lancet
Source reference:
Scheen AJ, Paquot N "Gliptin versus a sulphonylurea as add-on to metformin" Lancet 2012; DOI: 10.1016/S0140-6736(12)60691-6.
Source reference:
Gallwitz B, et al "2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial" Lancet 2012; DOI: 10.1016/S0140-6736(12)60859-9.
Additional source: The Lancet
Source reference:
Scheen AJ, Paquot N "Gliptin versus a sulphonylurea as add-on to metformin" Lancet 2012; DOI: 10.1016/S0140-6736(12)60691-6.
Add Your Knowledge ™
Crystal Phend
Staff Writer
Crystal Phend joined MedPage Today in 2006 after roaming conference halls for publications including The Medical Post, Oncology Times, Doctor’s Guide, and the journal IDrugs. When not covering medical meetings, she writes from Silicon Valley, just south of the San Francisco fog.
Staff Writer
Crystal Phend joined MedPage Today in 2006 after roaming conference halls for publications including The Medical Post, Oncology Times, Doctor’s Guide, and the journal IDrugs. When not covering medical meetings, she writes from Silicon Valley, just south of the San Francisco fog.
Review: Trials (all at high risk for bias), mostly found no evidence of benefit for nutritional support in patients with liver disease.
Koretz RL, Avenell A, Lipman TO. Nutritional support for liver disease. Cochrane Database Syst Rev. 2012 May 16;5:CD008344. (Review)
Cochrane Database Syst Rev. 2012 May 16;5:CD008344.
Nutritional support for liver disease.
Source
Granada Hills, CA, USA. rkoretz@msn.com.Abstract
BACKGROUND:
Weight loss and muscle wasting are commonly found in patients with end-stage liver disease. Since there is an association between malnutrition and poor clinical outcome, such patients (or those at risk of becoming malnourished) are often given parenteral nutrition, enteral nutrition, or oral nutritional supplements. These interventions have costs and adverse effects, so it is important to prove that their use results in improved morbidity or mortality, or both.OBJECTIVES:
To assess the beneficial and harmful effects of parenteral nutrition, enteral nutrition, and oral nutritional supplements on the mortality and morbidity of patients with underlying liver disease.SEARCH METHODS:
The following computerised databases were searched: the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, and Science Citation Index Expanded (January 2012). In addition, reference lists of identified trials and review articles and Clinicaltrials.gov were searched. Trials identified in a previous systematic handsearch of Index Medicus were also considered. Handsearches of a number of medical journals, including abstracts from annual meetings, were done. Experts in the field and manufacturers of nutrient formulations were contacted for potential references.SELECTION CRITERIA:
Randomised clinical trials (parallel or cross-over design) comparing groups of patients with any underlying liver disease who received, or did not receive, enteral or parenteral nutrition or oral nutritional supplements were identified without restriction on date, language, or publication status. Six categories of trials were separately considered: medical or surgical patients receiving parenteral nutrition, enteral nutrition, or supplements.DATA COLLECTION AND ANALYSIS:
The following data were sought in each report: date of publication; geographical location; inclusion and exclusion criteria; the type of nutritional support and constitution of the nutrient formulation; duration of treatment; any nutrition provided to the controls; other interventions provided to the patients; number, sex, age of the study participants; hospital or outpatient status; underlying liver disease; risks of bias (sequence generation, allocation concealment, blinding, incomplete outcome reporting, intention-to-treat analysis, selective outcome reporting, others (vested interests, baseline imbalance, early stopping)); mortality; hepatic morbidity (development or resolution of ascites or hepatic encephalopathy, occurrence of gastrointestinal bleeding); quality of life scores; adverse events; infections; lengths of stay in the hospital or intensive care unit; costs; serum bilirubin; postoperative complications (surgical trials only); and nutritional outcomes (nitrogen balance, anthropometric measurements, body weight). The primary outcomes of this review were mortality, hepatic morbidity, quality of life, and adverse events. Data were extracted in duplicate; differences were resolved by consensus.Data for each outcome were combined in a meta-analysis (RevMan 5.1). Estimates were reported using risk ratios or mean differences, along with the 95% confidence intervals (CI). Both fixed-effect and random-effects models were employed; fixed-effect models were reported unless one model, but not the other, found a significant difference (in which case both were reported). Heterogeneity was assessed by the Chi(2) test and I(2) statistic. Subgroup analyses were planned to assess specific liver diseases (alcoholic hepatitis, cirrhosis, hepatocellular carcinoma), acute or chronic liver diseases, and trials employing standard or branched-chain amino acid formulations (for the hepatic encephalopathy outcomes). Sensitivity analyses were planned to compare trials at low and high risk of bias and trials reported as full papers. The following exploratory analyses were undertaken: 1) medical and surgical trials were combined for each nutritional intervention; 2) intention-to-treat analyses in which missing dichotomous data were imputed as best- and worst-case scenarios; 3) all trials were combined to assess mortality; 4) effects were estimated by absolute risk reductions.MAIN RESULTS:
Thirty-seven trials were identified; only one was at low risk of bias. Most of the analyses failed to find any significant differences. The significant findings that were found were the following: 1) icteric medical patients receiving parenteral nutrition had a reduced serum bilirubin (mean difference (MD) -2.86 mg%, 95% CI -3.82 mg% to -1.89 mg%, 3 trials) and better nitrogen balance (MD 3.60 g/day, 95% CI 0.86 g/day to 6.34 g/day, 1 trial); 2) surgical patients receiving parenteral nutrition had a reduced incidence of postoperative ascites only in the fixed-effect model (RR 0.65, 95% CI 0.48 to 0.87, 2 trials, I(2) = 70%) and one trial demonstrated a reduction in postoperative complications, especially infections (pneumonia in particular); 3) enteral nutrition may have improved nitrogen balance in medical patients (although a combination of the three trials was not possible); 4) one surgical trial of enteral nutrition found a reduction in postoperative complications; and 5) oral nutritional supplements had several effects in medical patients (reduced occurrence of ascites (RR 0.57, 95% CI 0.37 to 0.88, 3 trials), possibly (significant differences only seen in the fixed-effect model) reduced rates of infection (RR 0.49, 95% CI 0.24 to 0.99, 3 trials, I(2) = 14%), and improved resolution of hepatic encephalopathy (RR 3.75, 95% CI 1.15 to 12.18, 2 trials, I(2) = 79%). While there was no overall effect of the supplements on mortality in medical patients, the one low risk of bias trial found an increased risk of death in the recipients of the supplements. Three trials of supplements in surgical patients failed to show any significant differences. No new information was derived from the various subgroup or sensitivity analyses. The exploratory analyses were also unrevealing except for a logical conundrum. There was no difference in mortality when all of the trials were combined, but the trials of parenteral nutrition found that those recipients had better survival (RR 0.53, 95% CI 0.29 to 0.98, 10 trials). Either the former observation represents a type II error or the latter one a type I error.AUTHORS' CONCLUSIONS:
The data do not compellingly justify the routine use of parenteral nutrition, enteral nutrition, or oral nutritional supplements in patients with liver disease. The fact that all but one of these trials were at high risks of bias even casts doubt on the few benefits that were demonstrated. Data from well-designed and executed randomised trials that include an untreated control group are needed before any such recommendation can be made. Future trials have to be powered adequately to see small, but clinically important, differences.- PMID:
- 22592729
- [PubMed - in process]
Watchdog group warns of heart valve risk related to diet pill.
Reuters
(6/26, Kelly) reports that as regulators prepare to rule on whether to
approve Arena Pharmaceuticals' diet pill lorcaserin on Wednesday,
watchdog group Public Citizen has asked the US Food and Drug
Administration to reject the experimental drug, citing concerns that it
could pose a risk to heart valves. The group noted that doctors at an
FDA advisory meeting last month said evidence from clinical trials
showed an
increased heart valve disease risk in patients who used lorcaserin. The
panel still voted to recommend the drug for approval by a vote of 18 to
4.
U-T San Diego
(6/27) reports the FDA "could delay its decision and require Arena to
file more information about Lorcaserin, which could become the first new
weight loss drug of its kind approved in the US in more than a decade.
The agency is expected to review a possible competing drug -- Vivus'
Anexa, on July 17."
Low-carb diet may be better than low-fat diet for maintaining weight loss.
A story on how different diets may affect weight loss received heavy
coverage both in print and online, and was featured on one of last
night's national news broadcasts.
ABC World News (6/26, story 7, 1:45, Stephanopoulos) reported, "A surprising study
out of Harvard today that could change the way we think about dieting.
When it comes to counting calories, what kind we take in may matter as
how many we take in."
The Wall Street Journal
(6/27, A3, Dooren, Subscription Publication) reports that the research
was published in the Journal of the American Medical Association and
received funding from the National Institutes of Health.
USA Today
(6/27, Hellmich) reports that researchers found that "dieters who were
trying to maintain their weight loss burned significantly more calories
eating a low-carb diet than they did eating a low-fat diet." For the
study, investigators "had 21 obese participants, ages 18 to 40, lose 10%
to 15% of their initial body weight (about 30 pounds)."
The Los Angeles Times
(6/27, Brown) reports, "After that, each subject was fed three
different diets for four weeks at a time: a traditional low-fat diet
(60% carbohydrates, 20% fat and 20% protein), a low glycemic index diet
(with 40% carbs, 40% fat and 20% protein) and a very low-carbohydrate
diet a la Atkins (with 10% carbohydrates, 60% fat and 30% protein)."
Bloomberg News
(6/27, Ostrow) reports that the investigators "found that those on the
low-glycemic diet burned calories the equivalent of an hour of light
exercise compared with those eating foods low in fat, while those on a
low-carbohydrate diet burned calories equal to an hour of moderate
exercise without actually engaging in physical activity...said" the
study's senior author, David Ludwig.
The New York Times
(6/27, Bittman) "Opinionator" blog reports, however, that the low-carb
diet "also had marked problems. It raised levels of CRP (c-reactive
protein), which is a measure of chronic inflammation, and cortisol, a
hormone that mediates stress."
MSNBC
/MyHealthNewsDaily (6/27, Cox) reports that participants "on the
low-fat diet experienced the most negative consequences regarding
insulin resistance, lipid levels and HDL (or good) cholesterol."
The Huffington Post
(6/27, Pearson) reports, "Ludwig cautioned that any diet plan that
drastically reduces a major class of nutrients like fat or carbs might
be difficult to stick to because it is so restrictive, thereby
undermining long-term maintenance of a lower weight."
HeartWire
(6/27, Nainggolan) reports that according to Ludwig, "Most of the
professional nutritional associations continue to feature, expressively
or implicitly, targets on fat reduction. Our work -- and really many
other studies -- now suggest that there is absolutely no benefit by
selectively targeting fat for reduction."
HealthDay
(6/27, Gordon) reports, "Dr. George Bray, professor of medicine at the
Pennington Biomedical Research Center at Louisiana State University in
Baton Rouge, expressed caution about the study conclusions." Bray, who
co-authored an accompanying editorial, said, "There are some interesting
physiological responses in this study, but translating this information
for possible long-term results is difficult to do." Also
covering the story are the Boston Globe (6/27, Shen) "Daily Dose" blog, MedPage Today (6/27, Smith), and WebMD (6/27, Boyles).
STEP diet program may be nearly as effective, cheaper than standard program.
Reuters (6/27, Pittman) reports that, according to a study
published in the Journal of the American Medical Association, a
stepped-care program may be nearly as effective as a standard
weight-loss intervention for helping people lose weight, and is cheaper
as well.
MedPage Today
(6/27, Gever) reports, "Patients in a stepped-care weight-loss program
(STEP) lost a mean of 6.9% of their baseline weight after 18 months,
compared with 8.1% for those randomized to a fixed program of diet,
exercise, and group counseling." However, "the STEP program cost only
$785 per participant, compared with $1,357 for the standard program."
MedPage Today adds, "A STEP approach starts with a low-intensity
intervention, which is increased if weight-loss milestones are not
achieved at fixed time points, the authors explained."
Low Carb-High Protein Diets May Put Heart at Risk
MedPage Direct Link
Consuming a low carbohydrate-high protein diet -- like the Atkins diet -- may be associated with a greater risk of cardiovascular disease in women, researchers found.
Decreases in carbohydrate intake and increases in protein intake, as well as in a score combining carbohydrate and protein intake, were all associated with significantly greater risks of incident cardiovascular disease events in young Swedish women, according to Pagona Lagiou, MD, PhD, of the University of Athens in Greece, and colleagues.
The findings, which were reported online in BMJ, "do not answer questions concerning possible beneficial short-term effects of low carbohydrate or high protein diets in the control of body weight or insulin resistance," the authors wrote.
"Instead, they draw attention to the potential for considerable adverse effects on cardiovascular health of these diets when they are used on a regular basis, without consideration of the nature of carbohydrates (complex versus refined) or the source of proteins (plant versus animal)," they wrote.
Low carb-high protein diets have become popular because of the short-term effects on weight control, but concerns have been raised about the potential cardiovascular effects over the long term. Studies exploring the issue have given mixed results, with a U.S. study showing no relationship between such a diet and rates of ischemic heart disease.
But three European studies showed a greater risk of cardiovascular mortality with such a diet.
Lagiou and colleagues examined data from the Swedish Women's Lifestyle and Health Cohort, a prospective study conducted among women living in the healthcare region of Uppsala. The current analysis included 43,396 women, ages 30 to 49 at baseline, who completed a comprehensive questionnaire on lifestyle and dietary factors, as well as medical history. They were followed for an average of 15.7 years.
The researchers scored each participant according to their carbohydrate and protein consumption. Carbohydrate intake was scored from 1 (very high) to 10 (very low). Protein intake was scored from 1 (very low) to 10 (very high). A combined carbohydrate-protein score ranged from 2 (very high consumption of carbs and very low consumption of protein) to 20 (very low consumption of carbs and very high consumption of protein).
During follow-up, there were 1,270 incident cardiovascular events, which included ischemic heart disease, ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage, and peripheral arterial disease.
After adjustment for energy intake, saturated and unsaturated fat intake, and numerous cardiovascular risk factors, each one-point decrease in carb intake was associated with a relative 4% increase in cardiovascular events (95% CI 0% to 8%). A one-point increase in protein intake also was associated with a relative 4% increase in events (95% CI 2% to 6%).
Each two-point increase in the low carbohydrate-high protein score -- equivalent to a 20-gram decrease in daily carb intake and 5-gram increase in daily protein intake -- was associated with a relative 5% increase in cardiovascular events (95% CI 2% to 8%).
There was a suggestion that the associations were stronger for women whose protein came mostly from animal sources, but the test for interaction did not reach statistical significance for nearly all of the individual outcomes.
"Although these results are based on an observational study, their biological plausibility seems self evident," according to Anna Floegel, MPH, of the German Institute of Human Nutrition Potsdam-Rehbruecke, and Tobias Pischon, MD, MPH, of the Max Delbrück Center for Molecular Medicine Berlin-Buch.
"A low carbohydrate diet implies low consumption of whole-grain foods, fruits, and starchy vegetables and consequently reduced intake of fiber, vitamins, and minerals. A high protein diet may indicate higher intake of red and processed meat and thus higher intake of iron, cholesterol, and saturated fat," they explained in an accompanying editorial.
"These single factors have previously been linked to a higher risk of major chronic diseases, including cardiovascular disease, in observational studies, so it is not surprising that this combination of risk factors is linked to a higher incidence of disease and mortality," they said.
Lagiou and colleagues acknowledged that their study was limited by the possible misclassification of diet based on participant self-report only at the beginning of the study, the lack of information on cardiovascular medication use and blood cholesterol levels, and the possibility of residual confounding.
Consuming a low carbohydrate-high protein diet -- like the Atkins diet -- may be associated with a greater risk of cardiovascular disease in women, researchers found.
Decreases in carbohydrate intake and increases in protein intake, as well as in a score combining carbohydrate and protein intake, were all associated with significantly greater risks of incident cardiovascular disease events in young Swedish women, according to Pagona Lagiou, MD, PhD, of the University of Athens in Greece, and colleagues.
The findings, which were reported online in BMJ, "do not answer questions concerning possible beneficial short-term effects of low carbohydrate or high protein diets in the control of body weight or insulin resistance," the authors wrote.
"Instead, they draw attention to the potential for considerable adverse effects on cardiovascular health of these diets when they are used on a regular basis, without consideration of the nature of carbohydrates (complex versus refined) or the source of proteins (plant versus animal)," they wrote.
Low carb-high protein diets have become popular because of the short-term effects on weight control, but concerns have been raised about the potential cardiovascular effects over the long term. Studies exploring the issue have given mixed results, with a U.S. study showing no relationship between such a diet and rates of ischemic heart disease.
But three European studies showed a greater risk of cardiovascular mortality with such a diet.
Lagiou and colleagues examined data from the Swedish Women's Lifestyle and Health Cohort, a prospective study conducted among women living in the healthcare region of Uppsala. The current analysis included 43,396 women, ages 30 to 49 at baseline, who completed a comprehensive questionnaire on lifestyle and dietary factors, as well as medical history. They were followed for an average of 15.7 years.
The researchers scored each participant according to their carbohydrate and protein consumption. Carbohydrate intake was scored from 1 (very high) to 10 (very low). Protein intake was scored from 1 (very low) to 10 (very high). A combined carbohydrate-protein score ranged from 2 (very high consumption of carbs and very low consumption of protein) to 20 (very low consumption of carbs and very high consumption of protein).
During follow-up, there were 1,270 incident cardiovascular events, which included ischemic heart disease, ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage, and peripheral arterial disease.
After adjustment for energy intake, saturated and unsaturated fat intake, and numerous cardiovascular risk factors, each one-point decrease in carb intake was associated with a relative 4% increase in cardiovascular events (95% CI 0% to 8%). A one-point increase in protein intake also was associated with a relative 4% increase in events (95% CI 2% to 6%).
Each two-point increase in the low carbohydrate-high protein score -- equivalent to a 20-gram decrease in daily carb intake and 5-gram increase in daily protein intake -- was associated with a relative 5% increase in cardiovascular events (95% CI 2% to 8%).
There was a suggestion that the associations were stronger for women whose protein came mostly from animal sources, but the test for interaction did not reach statistical significance for nearly all of the individual outcomes.
"Although these results are based on an observational study, their biological plausibility seems self evident," according to Anna Floegel, MPH, of the German Institute of Human Nutrition Potsdam-Rehbruecke, and Tobias Pischon, MD, MPH, of the Max Delbrück Center for Molecular Medicine Berlin-Buch.
"A low carbohydrate diet implies low consumption of whole-grain foods, fruits, and starchy vegetables and consequently reduced intake of fiber, vitamins, and minerals. A high protein diet may indicate higher intake of red and processed meat and thus higher intake of iron, cholesterol, and saturated fat," they explained in an accompanying editorial.
"These single factors have previously been linked to a higher risk of major chronic diseases, including cardiovascular disease, in observational studies, so it is not surprising that this combination of risk factors is linked to a higher incidence of disease and mortality," they said.
Lagiou and colleagues acknowledged that their study was limited by the possible misclassification of diet based on participant self-report only at the beginning of the study, the lack of information on cardiovascular medication use and blood cholesterol levels, and the possibility of residual confounding.
The study was supported by grants from the Swedish Cancer Society and the Swedish Research Council.
The study authors and the editorialists reported no conflicts of interest.
From the American Heart Association:The study authors and the editorialists reported no conflicts of interest.
- 2011 Guidelines for CVD Prevention in Women
- AHA Diet and Lifestyle Recommendations Revision 2006
- Interventions to Promote Physical Activity and Dietary Lifestyle Changes for Cardiovascular Risk Factor Reduction in Adults
Primary source: BMJ
Source reference:
Lagiou P, et al "Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study" BMJ 2012; DOI:10.1136/bmj.e4026.
Additional source: BMJ
Source reference:
Floegel A, Pischon T "Low carbohydrate-high protein diets" BMJ 2012; DOI:10.1136/bmj.e3801
Source reference:
Lagiou P, et al "Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study" BMJ 2012; DOI:10.1136/bmj.e4026.
Additional source: BMJ
Source reference:
Floegel A, Pischon T "Low carbohydrate-high protein diets" BMJ 2012; DOI:10.1136/bmj.e3801
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