Kate Johnson

MONTREAL — A diet rich in pulses and nuts can improve glycemic control in type 2 diabetes patients to within ranges seen with pharmaceutical intervention, researchers reported at the World Diabetes Congress.

A meta-analysis of 41 trials of pulses, either alone or combined with low-glycemic or high-fiber diets, noted improved markers of long-term glycemic control (Diabetologia 2009;52:1479-95), reported Dr. John Sievenpiper of the risk factor modification center of St. Michael's Hospital, Toronto.

Another study, also conducted by his group, found that 75 g of mixed nuts daily for 3 months improved blood lipids and glycemic control in patients with type 2 diabetes, compared with a mixture of nuts and muffins, or muffins alone. “Whatever your favorite nut or form of nut, it's good to get it into your diet,” said Dr. Cyril Kendall of the University of Toronto's department of nutritional sciences.

Both researchers acknowledged long lists of industry relationships: serving on advisory boards for a number of food companies, as well as the International Nut Council, and the Canola and Flax Councils of Canada, and receiving consultant fees from Pulse Canada.

“These are very nice, confirmatory studies,” commented Dr. Jim Mann, an endocrinologist who was not connected to the analyses, but performed some of the first studies in the 1980s showing similar results.

“I believe implicitly that patients do respond to dietary advice. In fact, the degree of response for type 2 diabetes is quite often as great as it is for some of the medications, if people comply,” the professor of human nutrition and medicine at Edgar National Center for Diabetes Research in Dunedin, New Zealand, said in an interview. “Most physicians don't believe that people will adhere sufficiently to dietary advice to make a significant difference, and because physicians are not convinced, neither are their patients. It takes an enthusiastic physician to get an enthusiastic patient.”

Dietary pulses such as chickpeas, beans, lentils, and peas are characterized by a low glycemic index, high fiber content, high levels of amylose and resistant starches, and vegetable protein and various other antinutrients “which may act as enzyme inhibitors,” Dr. Sievenpiper said. “The effect is to decrease starch digestion and absorption and therefore postprandial glycemia.”

In his meta-analysis, “modest improvement in medium to long-term glycemic control was seen when [pulses] were given alone or in combination with dietary maneuvers to reduce the glycemic index in the diet.”

The analysis included 11 trials that examined consumption of pulses alone, which noted an overall decrease in standardized mean difference (SMD) of 0.71 in fasting blood glucose (FBG) and 0.62 in serum insulin. Similarly, 19 trials looking at consumption of pulses in low glycemic index diets noted an SMD decrease of 0.28 in glycosylated blood proteins—either hemoglobin A_1c or fructosamine. And in 11 trials examining pulses in high-fiber diets, there were SMD reductions in fasting blood glucose of 0.32 and in glycosylated blood protein of 0.27.

Based on these results, “we would expect about a 0.48% reduction in HbA_1c, and this level of benefit approaches that seen with acarbose, exceeds the [Food and Drug Administration] proposed clinically meaningful threshold of 0.3%, and lies at the lower limit of efficacy of what you might expect for oral agents,” Dr. Sievenpiper said.

The nut study randomized 117 patients with type 2 diabetes to consume either 75 g nuts, 38 g nuts and 1.5 bran muffins (150 kcal per muffin), or three muffins daily for 3 months. Nut portions included a mix of almonds, cashews, macadamias, pecans, pistachios, walnuts, and peanuts. All treatment portions were equivalent to 475 kcal/day and were designed to maintain rather than decrease body weight. The primary outcome of the study was change in HbA_1c and serum lipids.

The patients' baseline characteristics were similar across the groups. They ranged in age from 61 to 63 years, 75% were men, ethnic backgrounds were diverse, and body mass indexes ranged from 28.8 to 30.3 kg/m

All patients were being treated with oral hypoglycemic medication, and their mean HbA_1c level was 7.1%. Baseline lipid profiles were balanced across the groups, and the mean duration of diabetes was 7-8 years.

A total of 100 patients completed the study, with a similar dropout rate in each group.

An intention-to-treat analysis revealed that HbA_1c levels were significantly lower in the nuts-only group, compared with the nut-muffin combination group (6.88% versus 7.02%), although the latter was not significantly lower than the muffin-only group (7.06%), Dr. Kendall said. There was a significant dose response seen in LDL cholesterol level, which fell by 0.19 mmol/L in the full-nut group, compared with full-muffin group.

Weight change from baseline was not significant, although there was a trend toward more weight loss in the nuts-only group. This was particularly interesting, given that more daily calories were consumed in this group (2,072 kcal), compared with the muffin-only group (1,932 kcal), Dr. Kendall said.

Previous studies by Dr. Kendall and his colleagues, as well as other studies, have shown this same effect, he said. “What we've found is that nuts are not entirely digested and there's an excretion of about 15%-20% that are simply not absorbed and pass through the gastrointestinal tract.”

Previous unpublished work by his group has shown that nuts have favorable effects on postprandial glucose response to common carbohydrates such as white bread, potatoes, rice, and pasta. “You get a graded reduction in glycemic response depending on the dose of nuts,” Dr. Kendall said.

Dietary intake of pulses—such as chickpeas, beans, lentils, and peas—can help diabetic patients reduce postprandial glycemia.

Source © Tinka/Fotolia.com

MONTREAL — A diet rich in pulses and nuts can improve glycemic control in type 2 diabetes patients to within ranges seen with pharmaceutical intervention, researchers reported at the World Diabetes Congress.

A meta-analysis of 41 trials of pulses, either alone or combined with low-glycemic or high-fiber diets, noted improved markers of long-term glycemic control (Diabetologia 2009;52:1479-95), reported Dr. John Sievenpiper of the risk factor modification center of St. Michael's Hospital, Toronto.

Another study, also conducted by his group, found that 75 g of mixed nuts daily for 3 months improved blood lipids and glycemic control in patients with type 2 diabetes, compared with a mixture of nuts and muffins, or muffins alone. “Whatever your favorite nut or form of nut, it's good to get it into your diet,” said Dr. Cyril Kendall of the University of Toronto's department of nutritional sciences.

Both researchers acknowledged long lists of industry relationships: serving on advisory boards for a number of food companies, as well as the International Nut Council, and the Canola and Flax Councils of Canada, and receiving consultant fees from Pulse Canada.

“These are very nice, confirmatory studies,” commented Dr. Jim Mann, an endocrinologist who was not connected to the analyses, but performed some of the first studies in the 1980s showing similar results.

“I believe implicitly that patients do respond to dietary advice. In fact, the degree of response for type 2 diabetes is quite often as great as it is for some of the medications, if people comply,” the professor of human nutrition and medicine at Edgar National Center for Diabetes Research in Dunedin, New Zealand, said in an interview. “Most physicians don't believe that people will adhere sufficiently to dietary advice to make a significant difference, and because physicians are not convinced, neither are their patients. It takes an enthusiastic physician to get an enthusiastic patient.”

Dietary pulses such as chickpeas, beans, lentils, and peas are characterized by a low glycemic index, high fiber content, high levels of amylose and resistant starches, and vegetable protein and various other antinutrients “which may act as enzyme inhibitors,” Dr. Sievenpiper said. “The effect is to decrease starch digestion and absorption and therefore postprandial glycemia.”

In his meta-analysis, “modest improvement in medium to long-term glycemic control was seen when [pulses] were given alone or in combination with dietary maneuvers to reduce the glycemic index in the diet.”

The analysis included 11 trials that examined consumption of pulses alone, which noted an overall decrease in standardized mean difference (SMD) of 0.71 in fasting blood glucose (FBG) and 0.62 in serum insulin. Similarly, 19 trials looking at consumption of pulses in low glycemic index diets noted an SMD decrease of 0.28 in glycosylated blood proteins—either hemoglobin A_1c or fructosamine. And in 11 trials examining pulses in high-fiber diets, there were SMD reductions in fasting blood glucose of 0.32 and in glycosylated blood protein of 0.27.

Based on these results, “we would expect about a 0.48% reduction in HbA_1c, and this level of benefit approaches that seen with acarbose, exceeds the [Food and Drug Administration] proposed clinically meaningful threshold of 0.3%, and lies at the lower limit of efficacy of what you might expect for oral agents,” Dr. Sievenpiper said.

The nut study randomized 117 patients with type 2 diabetes to consume either 75 g nuts, 38 g nuts and 1.5 bran muffins (150 kcal per muffin), or three muffins daily for 3 months. Nut portions included a mix of almonds, cashews, macadamias, pecans, pistachios, walnuts, and peanuts. All treatment portions were equivalent to 475 kcal/day and were designed to maintain rather than decrease body weight. The primary outcome of the study was change in HbA_1c and serum lipids.

The patients' baseline characteristics were similar across the groups. They ranged in age from 61 to 63 years, 75% were men, ethnic backgrounds were diverse, and body mass indexes ranged from 28.8 to 30.3 kg/m

All patients were being treated with oral hypoglycemic medication, and their mean HbA_1c level was 7.1%. Baseline lipid profiles were balanced across the groups, and the mean duration of diabetes was 7-8 years.

A total of 100 patients completed the study, with a similar dropout rate in each group.

An intention-to-treat analysis revealed that HbA_1c levels were significantly lower in the nuts-only group, compared with the nut-muffin combination group (6.88% versus 7.02%), although the latter was not significantly lower than the muffin-only group (7.06%), Dr. Kendall said. There was a significant dose response seen in LDL cholesterol level, which fell by 0.19 mmol/L in the full-nut group, compared with full-muffin group.

Weight change from baseline was not significant, although there was a trend toward more weight loss in the nuts-only group. This was particularly interesting, given that more daily calories were consumed in this group (2,072 kcal), compared with the muffin-only group (1,932 kcal), Dr. Kendall said.

Previous studies by Dr. Kendall and his colleagues, as well as other studies, have shown this same effect, he said. “What we've found is that nuts are not entirely digested and there's an excretion of about 15%-20% that are simply not absorbed and pass through the gastrointestinal tract.”

Previous unpublished work by his group has shown that nuts have favorable effects on postprandial glucose response to common carbohydrates such as white bread, potatoes, rice, and pasta. “You get a graded reduction in glycemic response depending on the dose of nuts,” Dr. Kendall said.

Dietary intake of pulses—such as chickpeas, beans, lentils, and peas—can help diabetic patients reduce postprandial glycemia.

Source © Tinka/Fotolia.com

MONTREAL — A diet rich in pulses and nuts can improve glycemic control in type 2 diabetes patients to within ranges seen with pharmaceutical intervention, researchers reported at the World Diabetes Congress.

A meta-analysis of 41 trials of pulses, either alone or combined with low-glycemic or high-fiber diets, noted improved markers of long-term glycemic control (Diabetologia 2009;52:1479-95), reported Dr. John Sievenpiper of the risk factor modification center of St. Michael's Hospital, Toronto.

Another study, also conducted by his group, found that 75 g of mixed nuts daily for 3 months improved blood lipids and glycemic control in patients with type 2 diabetes, compared with a mixture of nuts and muffins, or muffins alone. “Whatever your favorite nut or form of nut, it's good to get it into your diet,” said Dr. Cyril Kendall of the University of Toronto's department of nutritional sciences.

Both researchers acknowledged long lists of industry relationships: serving on advisory boards for a number of food companies, as well as the International Nut Council, and the Canola and Flax Councils of Canada, and receiving consultant fees from Pulse Canada.

“These are very nice, confirmatory studies,” commented Dr. Jim Mann, an endocrinologist who was not connected to the analyses, but performed some of the first studies in the 1980s showing similar results.

“I believe implicitly that patients do respond to dietary advice. In fact, the degree of response for type 2 diabetes is quite often as great as it is for some of the medications, if people comply,” the professor of human nutrition and medicine at Edgar National Center for Diabetes Research in Dunedin, New Zealand, said in an interview. “Most physicians don't believe that people will adhere sufficiently to dietary advice to make a significant difference, and because physicians are not convinced, neither are their patients. It takes an enthusiastic physician to get an enthusiastic patient.”

Dietary pulses such as chickpeas, beans, lentils, and peas are characterized by a low glycemic index, high fiber content, high levels of amylose and resistant starches, and vegetable protein and various other antinutrients “which may act as enzyme inhibitors,” Dr. Sievenpiper said. “The effect is to decrease starch digestion and absorption and therefore postprandial glycemia.”

In his meta-analysis, “modest improvement in medium to long-term glycemic control was seen when [pulses] were given alone or in combination with dietary maneuvers to reduce the glycemic index in the diet.”

The analysis included 11 trials that examined consumption of pulses alone, which noted an overall decrease in standardized mean difference (SMD) of 0.71 in fasting blood glucose (FBG) and 0.62 in serum insulin. Similarly, 19 trials looking at consumption of pulses in low glycemic index diets noted an SMD decrease of 0.28 in glycosylated blood proteins—either hemoglobin A_1c or fructosamine. And in 11 trials examining pulses in high-fiber diets, there were SMD reductions in fasting blood glucose of 0.32 and in glycosylated blood protein of 0.27.

Based on these results, “we would expect about a 0.48% reduction in HbA_1c, and this level of benefit approaches that seen with acarbose, exceeds the [Food and Drug Administration] proposed clinically meaningful threshold of 0.3%, and lies at the lower limit of efficacy of what you might expect for oral agents,” Dr. Sievenpiper said.

The nut study randomized 117 patients with type 2 diabetes to consume either 75 g nuts, 38 g nuts and 1.5 bran muffins (150 kcal per muffin), or three muffins daily for 3 months. Nut portions included a mix of almonds, cashews, macadamias, pecans, pistachios, walnuts, and peanuts. All treatment portions were equivalent to 475 kcal/day and were designed to maintain rather than decrease body weight. The primary outcome of the study was change in HbA_1c and serum lipids.

The patients' baseline characteristics were similar across the groups. They ranged in age from 61 to 63 years, 75% were men, ethnic backgrounds were diverse, and body mass indexes ranged from 28.8 to 30.3 kg/m

All patients were being treated with oral hypoglycemic medication, and their mean HbA_1c level was 7.1%. Baseline lipid profiles were balanced across the groups, and the mean duration of diabetes was 7-8 years.

A total of 100 patients completed the study, with a similar dropout rate in each group.

An intention-to-treat analysis revealed that HbA_1c levels were significantly lower in the nuts-only group, compared with the nut-muffin combination group (6.88% versus 7.02%), although the latter was not significantly lower than the muffin-only group (7.06%), Dr. Kendall said. There was a significant dose response seen in LDL cholesterol level, which fell by 0.19 mmol/L in the full-nut group, compared with full-muffin group.

Weight change from baseline was not significant, although there was a trend toward more weight loss in the nuts-only group. This was particularly interesting, given that more daily calories were consumed in this group (2,072 kcal), compared with the muffin-only group (1,932 kcal), Dr. Kendall said.

Previous studies by Dr. Kendall and his colleagues, as well as other studies, have shown this same effect, he said. “What we've found is that nuts are not entirely digested and there's an excretion of about 15%-20% that are simply not absorbed and pass through the gastrointestinal tract.”

Previous unpublished work by his group has shown that nuts have favorable effects on postprandial glucose response to common carbohydrates such as white bread, potatoes, rice, and pasta. “You get a graded reduction in glycemic response depending on the dose of nuts,” Dr. Kendall said.

Dietary intake of pulses—such as chickpeas, beans, lentils, and peas—can help diabetic patients reduce postprandial glycemia.

Source © Tinka/Fotolia.com

MONTREAL — Better identification of risk, but lack of explanation for it, continues to frustrate investigators as they search for reasons for the excess mortality associated with intensive glycemic control in the ACCORD trial.

However, complex interactions between baseline characteristics, postrandomization characteristics, and treatment strategy are still being explored.

In the latest set of analyses, “neither rapid reduction of blood glucose nor the achievement of near normal hemoglobin A_1c levels led to an excess risk of all-cause or CV death with the intensive strategy,” said Dr. Matthew Riddle, who presented an update on the Action to Control Cardiovascular Risk in Diabetes trial at the World Diabetes Congress.

“We haven't been able to find either baseline characteristics or obvious events during the course of treatment that strongly predicted which group was at risk for cardiovascular death,” he said in an interview.

ACCORD compared intensive versus standard glycemic control in 10,251 adults from 77 sites. The hypothesis was that lowering HbA_1c levels below 6% would reduce cardiovascular events compared with levels of 7.0%-7.9%. However, the intensive arm of the trial was stopped early when it showed a 22% increase in all-cause mortality compared with standard treatment. There were 257 deaths in the intensive treatment arm, compared with 203 in the standard treatment arm.

Several previous analyses of the data have revealed baseline characteristics such as high HbA_1c (8.5% or more), self-reported neuropathy, and aspirin use as predictors for increased mortality risk with intensive treatment, said Dr. Riddle, professor of medicine at Oregon Health and Science University in Portland.

It could be hypothesized that a high HbA_1c is a surrogate for relative severity of metabolic control, neuropathy is a surrogate for established and significant microvascular disease, and aspirin use may be a surrogate for cardiovascular disease, he suggested.

However, this still does not explain the excess risk seen with intensive versus standard treatment. “We still do not know the mechanisms involved in this unfavorable finding,” he said.

An epidemiologic analysis of the whole study population showed every 1% increase in average HbA_1c above normal was associated with a 20% increased risk of all-cause mortality, CV mortality, MI, and stroke. Further investigation into the interaction between this finding and treatment strategy suggests patients who were unable to lower HbA_1c levels with intensive treatment were at greatest risk for all-cause and cardiovascular mortality. “This supports a lot of people's intuitive idea that the further along in the course of diabetes patients are, the higher their risks from any kind of intensive intervention, and thus the more cautious the approach should be,” he said in an interview.

“When should we stop being aggressive?” Dr. Rury Holman of the Diabetes Trials Unit at the University of Oxford (England) asked during the question period. “What is it that tells us that we're not winning, and if we continue to be aggressive the patient will fall into this high-risk category?”

“I can't speak for ACCORD as a whole,” answered Dr. Riddle, “but my own opinion is that I think we know within the first 6 months of attempting an intervention whether that person is going to succeed. If they are struggling with it for any reason, whether it's a physiologic reason, a medication-adherence reason, or any recurrent illness reason, I believe that would be a reason to back off.”

The investigators are still working on several other hypotheses for the excess risk seen with intensive treatment, including hypoglycemia, “although we've been unable to find a direct relationship,” he said. In addition, “weight gain remains on the table as a serious possibility, and certainly, possible unfavorable effects of high doses of the medications,”

Dr. Riddle has received lecture fees or research grants from Sanofi-Aventis, Amylin, Eli Lilly & Co., and GlaxoSmithKline; and has done advisory board work with Amylin, Eli Lilly, Sanofi-Aventis, and Valeritas Inc.

MONTREAL — Better identification of risk, but lack of explanation for it, continues to frustrate investigators as they search for reasons for the excess mortality associated with intensive glycemic control in the ACCORD trial.

However, complex interactions between baseline characteristics, postrandomization characteristics, and treatment strategy are still being explored.

In the latest set of analyses, “neither rapid reduction of blood glucose nor the achievement of near normal hemoglobin A_1c levels led to an excess risk of all-cause or CV death with the intensive strategy,” said Dr. Matthew Riddle, who presented an update on the Action to Control Cardiovascular Risk in Diabetes trial at the World Diabetes Congress.

“We haven't been able to find either baseline characteristics or obvious events during the course of treatment that strongly predicted which group was at risk for cardiovascular death,” he said in an interview.

ACCORD compared intensive versus standard glycemic control in 10,251 adults from 77 sites. The hypothesis was that lowering HbA_1c levels below 6% would reduce cardiovascular events compared with levels of 7.0%-7.9%. However, the intensive arm of the trial was stopped early when it showed a 22% increase in all-cause mortality compared with standard treatment. There were 257 deaths in the intensive treatment arm, compared with 203 in the standard treatment arm.

Several previous analyses of the data have revealed baseline characteristics such as high HbA_1c (8.5% or more), self-reported neuropathy, and aspirin use as predictors for increased mortality risk with intensive treatment, said Dr. Riddle, professor of medicine at Oregon Health and Science University in Portland.

It could be hypothesized that a high HbA_1c is a surrogate for relative severity of metabolic control, neuropathy is a surrogate for established and significant microvascular disease, and aspirin use may be a surrogate for cardiovascular disease, he suggested.

However, this still does not explain the excess risk seen with intensive versus standard treatment. “We still do not know the mechanisms involved in this unfavorable finding,” he said.

An epidemiologic analysis of the whole study population showed every 1% increase in average HbA_1c above normal was associated with a 20% increased risk of all-cause mortality, CV mortality, MI, and stroke. Further investigation into the interaction between this finding and treatment strategy suggests patients who were unable to lower HbA_1c levels with intensive treatment were at greatest risk for all-cause and cardiovascular mortality. “This supports a lot of people's intuitive idea that the further along in the course of diabetes patients are, the higher their risks from any kind of intensive intervention, and thus the more cautious the approach should be,” he said in an interview.

“When should we stop being aggressive?” Dr. Rury Holman of the Diabetes Trials Unit at the University of Oxford (England) asked during the question period. “What is it that tells us that we're not winning, and if we continue to be aggressive the patient will fall into this high-risk category?”

“I can't speak for ACCORD as a whole,” answered Dr. Riddle, “but my own opinion is that I think we know within the first 6 months of attempting an intervention whether that person is going to succeed. If they are struggling with it for any reason, whether it's a physiologic reason, a medication-adherence reason, or any recurrent illness reason, I believe that would be a reason to back off.”

The investigators are still working on several other hypotheses for the excess risk seen with intensive treatment, including hypoglycemia, “although we've been unable to find a direct relationship,” he said. In addition, “weight gain remains on the table as a serious possibility, and certainly, possible unfavorable effects of high doses of the medications,”

Dr. Riddle has received lecture fees or research grants from Sanofi-Aventis, Amylin, Eli Lilly & Co., and GlaxoSmithKline; and has done advisory board work with Amylin, Eli Lilly, Sanofi-Aventis, and Valeritas Inc.

MONTREAL — Better identification of risk, but lack of explanation for it, continues to frustrate investigators as they search for reasons for the excess mortality associated with intensive glycemic control in the ACCORD trial.

However, complex interactions between baseline characteristics, postrandomization characteristics, and treatment strategy are still being explored.

In the latest set of analyses, “neither rapid reduction of blood glucose nor the achievement of near normal hemoglobin A_1c levels led to an excess risk of all-cause or CV death with the intensive strategy,” said Dr. Matthew Riddle, who presented an update on the Action to Control Cardiovascular Risk in Diabetes trial at the World Diabetes Congress.

“We haven't been able to find either baseline characteristics or obvious events during the course of treatment that strongly predicted which group was at risk for cardiovascular death,” he said in an interview.

ACCORD compared intensive versus standard glycemic control in 10,251 adults from 77 sites. The hypothesis was that lowering HbA_1c levels below 6% would reduce cardiovascular events compared with levels of 7.0%-7.9%. However, the intensive arm of the trial was stopped early when it showed a 22% increase in all-cause mortality compared with standard treatment. There were 257 deaths in the intensive treatment arm, compared with 203 in the standard treatment arm.

Several previous analyses of the data have revealed baseline characteristics such as high HbA_1c (8.5% or more), self-reported neuropathy, and aspirin use as predictors for increased mortality risk with intensive treatment, said Dr. Riddle, professor of medicine at Oregon Health and Science University in Portland.

It could be hypothesized that a high HbA_1c is a surrogate for relative severity of metabolic control, neuropathy is a surrogate for established and significant microvascular disease, and aspirin use may be a surrogate for cardiovascular disease, he suggested.

However, this still does not explain the excess risk seen with intensive versus standard treatment. “We still do not know the mechanisms involved in this unfavorable finding,” he said.

An epidemiologic analysis of the whole study population showed every 1% increase in average HbA_1c above normal was associated with a 20% increased risk of all-cause mortality, CV mortality, MI, and stroke. Further investigation into the interaction between this finding and treatment strategy suggests patients who were unable to lower HbA_1c levels with intensive treatment were at greatest risk for all-cause and cardiovascular mortality. “This supports a lot of people's intuitive idea that the further along in the course of diabetes patients are, the higher their risks from any kind of intensive intervention, and thus the more cautious the approach should be,” he said in an interview.

“When should we stop being aggressive?” Dr. Rury Holman of the Diabetes Trials Unit at the University of Oxford (England) asked during the question period. “What is it that tells us that we're not winning, and if we continue to be aggressive the patient will fall into this high-risk category?”

“I can't speak for ACCORD as a whole,” answered Dr. Riddle, “but my own opinion is that I think we know within the first 6 months of attempting an intervention whether that person is going to succeed. If they are struggling with it for any reason, whether it's a physiologic reason, a medication-adherence reason, or any recurrent illness reason, I believe that would be a reason to back off.”

The investigators are still working on several other hypotheses for the excess risk seen with intensive treatment, including hypoglycemia, “although we've been unable to find a direct relationship,” he said. In addition, “weight gain remains on the table as a serious possibility, and certainly, possible unfavorable effects of high doses of the medications,”

Dr. Riddle has received lecture fees or research grants from Sanofi-Aventis, Amylin, Eli Lilly & Co., and GlaxoSmithKline; and has done advisory board work with Amylin, Eli Lilly, Sanofi-Aventis, and Valeritas Inc.

Women with metabolic syndrome have an increased risk of developing symptomatic peripheral artery disease, compared with healthy women, according to a new analysis of the Women's Health Study.

“In this generally low-risk population of women, the excess risk associated with [metabolic syndrome] may be mediated through heightened inflammation and/or endothelial activation,” reported Dr. Aruna Pradhan of Brigham and Women's Hospital, Boston, and colleagues.

The prospective cohort study included a subgroup of 27,111 women, aged at least 45 years, who were enrolled in the Women's Health Study and followed for a median of 13 years (Circulation 2009 Sept. 8 [doi:10.1161/circulationaha.109.863092]).

About one-quarter of the study population (6,920) had metabolic syndrome, defined according to the ATP (Adult Treatment Panel) III guidelines as the presence of three or more of the following traits: a waist circumference of 88 cm or more; a triglyceride level of 150 mg/dL or greater; HDL cholesterol levels lower than 50 mg/dL; a blood pressure of at least 130/85 mm Hg; and abnormal glucose metabolism as identified by a fasting blood glucose level of at least 100 mg/dL.

Incident symptomatic peripheral artery disease (PAD), defined as intermittent claudication and/or peripheral artery surgery inclusive of catheter-based interventions, occurred in 114 women, 70 of them with metabolic syndrome and 44 without.

The hazard ratio for PAD with metabolic syndrome, compared with PAD without metabolic syndrome, was 1.62 on univariate analysis, and 1.48 after adjustment for patient age and smoking status.

Even among women who did not have metabolic syndrome, the risk for PAD increased with the number of metabolic syndrome traits. Compared with women who did not have any traits, those who had one or two traits had a 2.5-fold increased risk of PAD.

The hazard ratios for PAD were 0.98 with elevated body mass index, 1.39 for elevated triglycerides, 1.50 for hypertension, 1.60 for low HDL cholesterol, and 2.05 for dysglycemia, reported the authors.

By comparison, the hazard ratio associated with current smoking was 12.7.

“Smoking was by far the strongest risk in this population,” the researchers wrote. “This study underscores the importance of abstinence from smoking for the prevention of PAD.”

Women with metabolic syndrome have an increased risk of developing symptomatic peripheral artery disease, compared with healthy women, according to a new analysis of the Women's Health Study.

“In this generally low-risk population of women, the excess risk associated with [metabolic syndrome] may be mediated through heightened inflammation and/or endothelial activation,” reported Dr. Aruna Pradhan of Brigham and Women's Hospital, Boston, and colleagues.

The prospective cohort study included a subgroup of 27,111 women, aged at least 45 years, who were enrolled in the Women's Health Study and followed for a median of 13 years (Circulation 2009 Sept. 8 [doi:10.1161/circulationaha.109.863092]).

About one-quarter of the study population (6,920) had metabolic syndrome, defined according to the ATP (Adult Treatment Panel) III guidelines as the presence of three or more of the following traits: a waist circumference of 88 cm or more; a triglyceride level of 150 mg/dL or greater; HDL cholesterol levels lower than 50 mg/dL; a blood pressure of at least 130/85 mm Hg; and abnormal glucose metabolism as identified by a fasting blood glucose level of at least 100 mg/dL.

Incident symptomatic peripheral artery disease (PAD), defined as intermittent claudication and/or peripheral artery surgery inclusive of catheter-based interventions, occurred in 114 women, 70 of them with metabolic syndrome and 44 without.

The hazard ratio for PAD with metabolic syndrome, compared with PAD without metabolic syndrome, was 1.62 on univariate analysis, and 1.48 after adjustment for patient age and smoking status.

Even among women who did not have metabolic syndrome, the risk for PAD increased with the number of metabolic syndrome traits. Compared with women who did not have any traits, those who had one or two traits had a 2.5-fold increased risk of PAD.

The hazard ratios for PAD were 0.98 with elevated body mass index, 1.39 for elevated triglycerides, 1.50 for hypertension, 1.60 for low HDL cholesterol, and 2.05 for dysglycemia, reported the authors.

By comparison, the hazard ratio associated with current smoking was 12.7.

“Smoking was by far the strongest risk in this population,” the researchers wrote. “This study underscores the importance of abstinence from smoking for the prevention of PAD.”

Women with metabolic syndrome have an increased risk of developing symptomatic peripheral artery disease, compared with healthy women, according to a new analysis of the Women's Health Study.

“In this generally low-risk population of women, the excess risk associated with [metabolic syndrome] may be mediated through heightened inflammation and/or endothelial activation,” reported Dr. Aruna Pradhan of Brigham and Women's Hospital, Boston, and colleagues.

The prospective cohort study included a subgroup of 27,111 women, aged at least 45 years, who were enrolled in the Women's Health Study and followed for a median of 13 years (Circulation 2009 Sept. 8 [doi:10.1161/circulationaha.109.863092]).

About one-quarter of the study population (6,920) had metabolic syndrome, defined according to the ATP (Adult Treatment Panel) III guidelines as the presence of three or more of the following traits: a waist circumference of 88 cm or more; a triglyceride level of 150 mg/dL or greater; HDL cholesterol levels lower than 50 mg/dL; a blood pressure of at least 130/85 mm Hg; and abnormal glucose metabolism as identified by a fasting blood glucose level of at least 100 mg/dL.

Incident symptomatic peripheral artery disease (PAD), defined as intermittent claudication and/or peripheral artery surgery inclusive of catheter-based interventions, occurred in 114 women, 70 of them with metabolic syndrome and 44 without.

The hazard ratio for PAD with metabolic syndrome, compared with PAD without metabolic syndrome, was 1.62 on univariate analysis, and 1.48 after adjustment for patient age and smoking status.

Even among women who did not have metabolic syndrome, the risk for PAD increased with the number of metabolic syndrome traits. Compared with women who did not have any traits, those who had one or two traits had a 2.5-fold increased risk of PAD.

The hazard ratios for PAD were 0.98 with elevated body mass index, 1.39 for elevated triglycerides, 1.50 for hypertension, 1.60 for low HDL cholesterol, and 2.05 for dysglycemia, reported the authors.

By comparison, the hazard ratio associated with current smoking was 12.7.

“Smoking was by far the strongest risk in this population,” the researchers wrote. “This study underscores the importance of abstinence from smoking for the prevention of PAD.”

MONTREAL — A diet rich in pulses and nuts can improve glycemic control in type 2 diabetes patients to within ranges seen with pharmaceutical intervention, researchers reported at the World Diabetes Congress.

A meta-analysis of 41 trials of pulses, either alone or combined with low glycemic or high fiber diets, noted improved markers of long-term glycemic control (Diabetologia 2009;52:1479–95), reported Dr. John Sievenpiper of St. Michael's Hospital's risk factor modification center, Toronto.

Another study, also conducted by his group, found that 75 g of mixed nuts daily for 3 months improved blood lipids and glycemic control in patients with type 2 diabetes, compared with a mixture of nuts and muffins, or muffins alone. “Whatever your favorite nut or form of nut, it's good to get it into your diet,” said Dr. Cyril Kendall of the University of Toronto's department of nutritional sciences.

Both researchers acknowledged long lists of industry relationships: serving on advisory boards for a number of food companies, as well as the International Nut Council, and the Canola and Flax Councils of Canada, and receiving consultant fees from Pulse Canada.

Dietary pulses such as chickpeas, beans, lentils, and peas are characterized by a low glycemic index, high fiber content, high levels of amylose and resistant starches, and vegetable protein, and various other antinutrients “which may act as enzyme inhibitors,” said Dr. Sievenpiper. “The effect is to decrease starch digestion and absorption and therefore postprandial glycemia.”

His meta-analysis included 11 trials that examined consumption of pulses alone, which noted an overall decrease in standardized mean difference (SMD) of 0.71 in fasting blood glucose (FBG) and 0.62 in serum insulin. Similarly, 19 trials looking at consumption of pulses in low glycemic index (GI) diets noted an SMD decrease of 0.28 in glycosylated blood proteins (GP)—either hemoglobin A_1c or fructosamine. And in 11 trials examining pulses in high-fiber diets, there were SMD reductions in fasting blood glucose of 0.32 and in GP of 0.27.

Based on these results, “We would expect about a 0.48% reduction in HbA_1c, and this level of benefit approaches that seen with acarbose, exceeds the [Food and Drug Administration] proposed clinically meaningful threshold of 0.3%, and lies at the lower limit of efficacy of what you might expect for oral agents,” Dr. Sievenpiper said.

The nut study randomized 117 patients with type 2 diabetes to consume either 75 g nuts, 38 g nuts and 1.5 bran muffins (150 kcal per muffin), or three muffins daily for 3 months. Nut portions included a mix of almonds, cashews, macadamias, pecans, pistachios, walnuts, and peanuts. All treatment portions were equivalent to 475 kcal/day and were designed to maintain rather than decrease body weight.

The primary outcome of the study was change in HbA_1c and serum lipids.

The patients' baseline characteristics were similar across the groups. They ranged in age from 61 to 63 years, 75% were male, ethnic backgrounds were diverse, and body mass index ranged from 28.8 to 30.3.

All patients were being treated with oral hypoglycemic medication, and their mean HbA_1c level was 7.1%. The mean duration of diabetes was 7–8 years. One hundred patients completed the study, with a similar dropout rate in each group.

An intention-to-treat analysis revealed that HbA_1c levels were significantly lower in the nuts-only group, compared with the nut-muffin combination group (6.88% versus 7.02%), although the latter was not significantly lower than the muffin-only group (7.06%), said Dr. Kendall.

There was a significant dose response seen in LDL cholesterol, which fell by 0.19 mmol/L in the full-nut group, compared with full-muffin group.

Previous studies have shown that “nuts are not entirely digested and there's an excretion of about 15%–20% that are simply not absorbed and pass through the gastrointestinal tract,” Dr. Kendall said.

MONTREAL — A diet rich in pulses and nuts can improve glycemic control in type 2 diabetes patients to within ranges seen with pharmaceutical intervention, researchers reported at the World Diabetes Congress.

A meta-analysis of 41 trials of pulses, either alone or combined with low glycemic or high fiber diets, noted improved markers of long-term glycemic control (Diabetologia 2009;52:1479–95), reported Dr. John Sievenpiper of St. Michael's Hospital's risk factor modification center, Toronto.

Another study, also conducted by his group, found that 75 g of mixed nuts daily for 3 months improved blood lipids and glycemic control in patients with type 2 diabetes, compared with a mixture of nuts and muffins, or muffins alone. “Whatever your favorite nut or form of nut, it's good to get it into your diet,” said Dr. Cyril Kendall of the University of Toronto's department of nutritional sciences.

Both researchers acknowledged long lists of industry relationships: serving on advisory boards for a number of food companies, as well as the International Nut Council, and the Canola and Flax Councils of Canada, and receiving consultant fees from Pulse Canada.

Dietary pulses such as chickpeas, beans, lentils, and peas are characterized by a low glycemic index, high fiber content, high levels of amylose and resistant starches, and vegetable protein, and various other antinutrients “which may act as enzyme inhibitors,” said Dr. Sievenpiper. “The effect is to decrease starch digestion and absorption and therefore postprandial glycemia.”

His meta-analysis included 11 trials that examined consumption of pulses alone, which noted an overall decrease in standardized mean difference (SMD) of 0.71 in fasting blood glucose (FBG) and 0.62 in serum insulin. Similarly, 19 trials looking at consumption of pulses in low glycemic index (GI) diets noted an SMD decrease of 0.28 in glycosylated blood proteins (GP)—either hemoglobin A_1c or fructosamine. And in 11 trials examining pulses in high-fiber diets, there were SMD reductions in fasting blood glucose of 0.32 and in GP of 0.27.

Based on these results, “We would expect about a 0.48% reduction in HbA_1c, and this level of benefit approaches that seen with acarbose, exceeds the [Food and Drug Administration] proposed clinically meaningful threshold of 0.3%, and lies at the lower limit of efficacy of what you might expect for oral agents,” Dr. Sievenpiper said.

The nut study randomized 117 patients with type 2 diabetes to consume either 75 g nuts, 38 g nuts and 1.5 bran muffins (150 kcal per muffin), or three muffins daily for 3 months. Nut portions included a mix of almonds, cashews, macadamias, pecans, pistachios, walnuts, and peanuts. All treatment portions were equivalent to 475 kcal/day and were designed to maintain rather than decrease body weight.

The primary outcome of the study was change in HbA_1c and serum lipids.

The patients' baseline characteristics were similar across the groups. They ranged in age from 61 to 63 years, 75% were male, ethnic backgrounds were diverse, and body mass index ranged from 28.8 to 30.3.

All patients were being treated with oral hypoglycemic medication, and their mean HbA_1c level was 7.1%. The mean duration of diabetes was 7–8 years. One hundred patients completed the study, with a similar dropout rate in each group.

An intention-to-treat analysis revealed that HbA_1c levels were significantly lower in the nuts-only group, compared with the nut-muffin combination group (6.88% versus 7.02%), although the latter was not significantly lower than the muffin-only group (7.06%), said Dr. Kendall.

There was a significant dose response seen in LDL cholesterol, which fell by 0.19 mmol/L in the full-nut group, compared with full-muffin group.

Previous studies have shown that “nuts are not entirely digested and there's an excretion of about 15%–20% that are simply not absorbed and pass through the gastrointestinal tract,” Dr. Kendall said.

MONTREAL — A diet rich in pulses and nuts can improve glycemic control in type 2 diabetes patients to within ranges seen with pharmaceutical intervention, researchers reported at the World Diabetes Congress.

A meta-analysis of 41 trials of pulses, either alone or combined with low glycemic or high fiber diets, noted improved markers of long-term glycemic control (Diabetologia 2009;52:1479–95), reported Dr. John Sievenpiper of St. Michael's Hospital's risk factor modification center, Toronto.

Another study, also conducted by his group, found that 75 g of mixed nuts daily for 3 months improved blood lipids and glycemic control in patients with type 2 diabetes, compared with a mixture of nuts and muffins, or muffins alone. “Whatever your favorite nut or form of nut, it's good to get it into your diet,” said Dr. Cyril Kendall of the University of Toronto's department of nutritional sciences.

Both researchers acknowledged long lists of industry relationships: serving on advisory boards for a number of food companies, as well as the International Nut Council, and the Canola and Flax Councils of Canada, and receiving consultant fees from Pulse Canada.

Dietary pulses such as chickpeas, beans, lentils, and peas are characterized by a low glycemic index, high fiber content, high levels of amylose and resistant starches, and vegetable protein, and various other antinutrients “which may act as enzyme inhibitors,” said Dr. Sievenpiper. “The effect is to decrease starch digestion and absorption and therefore postprandial glycemia.”

His meta-analysis included 11 trials that examined consumption of pulses alone, which noted an overall decrease in standardized mean difference (SMD) of 0.71 in fasting blood glucose (FBG) and 0.62 in serum insulin. Similarly, 19 trials looking at consumption of pulses in low glycemic index (GI) diets noted an SMD decrease of 0.28 in glycosylated blood proteins (GP)—either hemoglobin A_1c or fructosamine. And in 11 trials examining pulses in high-fiber diets, there were SMD reductions in fasting blood glucose of 0.32 and in GP of 0.27.

Based on these results, “We would expect about a 0.48% reduction in HbA_1c, and this level of benefit approaches that seen with acarbose, exceeds the [Food and Drug Administration] proposed clinically meaningful threshold of 0.3%, and lies at the lower limit of efficacy of what you might expect for oral agents,” Dr. Sievenpiper said.

The nut study randomized 117 patients with type 2 diabetes to consume either 75 g nuts, 38 g nuts and 1.5 bran muffins (150 kcal per muffin), or three muffins daily for 3 months. Nut portions included a mix of almonds, cashews, macadamias, pecans, pistachios, walnuts, and peanuts. All treatment portions were equivalent to 475 kcal/day and were designed to maintain rather than decrease body weight.

The primary outcome of the study was change in HbA_1c and serum lipids.

The patients' baseline characteristics were similar across the groups. They ranged in age from 61 to 63 years, 75% were male, ethnic backgrounds were diverse, and body mass index ranged from 28.8 to 30.3.

All patients were being treated with oral hypoglycemic medication, and their mean HbA_1c level was 7.1%. The mean duration of diabetes was 7–8 years. One hundred patients completed the study, with a similar dropout rate in each group.

An intention-to-treat analysis revealed that HbA_1c levels were significantly lower in the nuts-only group, compared with the nut-muffin combination group (6.88% versus 7.02%), although the latter was not significantly lower than the muffin-only group (7.06%), said Dr. Kendall.

There was a significant dose response seen in LDL cholesterol, which fell by 0.19 mmol/L in the full-nut group, compared with full-muffin group.

Previous studies have shown that “nuts are not entirely digested and there's an excretion of about 15%–20% that are simply not absorbed and pass through the gastrointestinal tract,” Dr. Kendall said.

MONTREAL — The presence of bone marrow lesions in pain-free knees may be a marker for an increased risk of future osteoarthritis among people who participate in vigorous activity. However, it's not known whether a modified exercise program could reduce this risk, said Dr. Anita Wluka at the World Congress on Osteoarthritis.

“It's possible that we should be changing our recommendations from weight-bearing to non–weight-bearing physical activity in this group, but this warrants further investigation,” said Dr. Wluka of Monash University in Clayton, Victoria, Australia.

Dr. Wluka's findings were based on a subgroup analysis of people participating in the longitudinal Melbourne Collaborative Cohort (MCC) study, established in 1990 to assess the role of diet and lifestyle in the risk for cancer and diabetes. The original cohort included 41,500 people (aged 40-69 years). In 2002, the investigators expanded the outcomes of interest to include cardiovascular disease and metabolic syndrome.

In a subanalysis, her group identified 271 individuals (aged 50-79 years) who had no knee disease or pain at baseline and results from two magnetic resonance imaging scans taken 2 years apart. Both cartilage volume and defects, as well as the presence of bone marrow lesions (BMLs), were assessed on MRI.

Degree of participation in vigorous physical activity was recorded when subjects first entered the larger MCC study (1990-1994), and again around the time of the first MRI (2004).

Overall, the worsening of cartilage loss and defects was similar among all subjects from the first to the second MRI, regardless of their level of exercise, she said.

“These were not people who ran marathons. These were people who jogged, or danced, or played tennis for more than 20 minutes—enough to raise a sweat or become short of breath.”

However, when the cohort was divided according to the presence (37 subjects) or absence (234 subjects) of BMLs on MRI, the risk of medical knee cartilage defects and volume loss was much more pronounced among exercisers, compared with nonexercisers (odds ratio, 3.4).

“This study identifies a subgroup—those with BML—who are more likely to have adverse outcomes with exercise,” she concluded. “It may be that the biomechanical properties of bones with BML are altered, and this alters the ability of cartilage to withstand normal or abnormal loading related to physical activity.”

Dr. Wluka said her group chose to look at BMLs because they have been associated with pain and progression in patients with symptomatic OA. Even in clinically asymptomatic populations, BMLs have been associated with an increased prevalence of cartilage defects and loss, she said.

“I'm not suggesting everyone go out and get an MRI to see if they have BMLs, but looking at why people have BMLs might be helpful, and there might be noninvasive ways of identifying them,” she said in an interview.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Wluka said she had no conflicts of interest.

Patients with bone marrow lesions, as shown above on MRI, had adverse outcomes with exercise.

Source Courtesy Dr. Anita Wluka

MONTREAL — The presence of bone marrow lesions in pain-free knees may be a marker for an increased risk of future osteoarthritis among people who participate in vigorous activity. However, it's not known whether a modified exercise program could reduce this risk, said Dr. Anita Wluka at the World Congress on Osteoarthritis.

“It's possible that we should be changing our recommendations from weight-bearing to non–weight-bearing physical activity in this group, but this warrants further investigation,” said Dr. Wluka of Monash University in Clayton, Victoria, Australia.

Dr. Wluka's findings were based on a subgroup analysis of people participating in the longitudinal Melbourne Collaborative Cohort (MCC) study, established in 1990 to assess the role of diet and lifestyle in the risk for cancer and diabetes. The original cohort included 41,500 people (aged 40-69 years). In 2002, the investigators expanded the outcomes of interest to include cardiovascular disease and metabolic syndrome.

In a subanalysis, her group identified 271 individuals (aged 50-79 years) who had no knee disease or pain at baseline and results from two magnetic resonance imaging scans taken 2 years apart. Both cartilage volume and defects, as well as the presence of bone marrow lesions (BMLs), were assessed on MRI.

Degree of participation in vigorous physical activity was recorded when subjects first entered the larger MCC study (1990-1994), and again around the time of the first MRI (2004).

Overall, the worsening of cartilage loss and defects was similar among all subjects from the first to the second MRI, regardless of their level of exercise, she said.

“These were not people who ran marathons. These were people who jogged, or danced, or played tennis for more than 20 minutes—enough to raise a sweat or become short of breath.”

However, when the cohort was divided according to the presence (37 subjects) or absence (234 subjects) of BMLs on MRI, the risk of medical knee cartilage defects and volume loss was much more pronounced among exercisers, compared with nonexercisers (odds ratio, 3.4).

“This study identifies a subgroup—those with BML—who are more likely to have adverse outcomes with exercise,” she concluded. “It may be that the biomechanical properties of bones with BML are altered, and this alters the ability of cartilage to withstand normal or abnormal loading related to physical activity.”

Dr. Wluka said her group chose to look at BMLs because they have been associated with pain and progression in patients with symptomatic OA. Even in clinically asymptomatic populations, BMLs have been associated with an increased prevalence of cartilage defects and loss, she said.

“I'm not suggesting everyone go out and get an MRI to see if they have BMLs, but looking at why people have BMLs might be helpful, and there might be noninvasive ways of identifying them,” she said in an interview.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Wluka said she had no conflicts of interest.

Patients with bone marrow lesions, as shown above on MRI, had adverse outcomes with exercise.

Source Courtesy Dr. Anita Wluka

MONTREAL — The presence of bone marrow lesions in pain-free knees may be a marker for an increased risk of future osteoarthritis among people who participate in vigorous activity. However, it's not known whether a modified exercise program could reduce this risk, said Dr. Anita Wluka at the World Congress on Osteoarthritis.

“It's possible that we should be changing our recommendations from weight-bearing to non–weight-bearing physical activity in this group, but this warrants further investigation,” said Dr. Wluka of Monash University in Clayton, Victoria, Australia.

Dr. Wluka's findings were based on a subgroup analysis of people participating in the longitudinal Melbourne Collaborative Cohort (MCC) study, established in 1990 to assess the role of diet and lifestyle in the risk for cancer and diabetes. The original cohort included 41,500 people (aged 40-69 years). In 2002, the investigators expanded the outcomes of interest to include cardiovascular disease and metabolic syndrome.

In a subanalysis, her group identified 271 individuals (aged 50-79 years) who had no knee disease or pain at baseline and results from two magnetic resonance imaging scans taken 2 years apart. Both cartilage volume and defects, as well as the presence of bone marrow lesions (BMLs), were assessed on MRI.

Degree of participation in vigorous physical activity was recorded when subjects first entered the larger MCC study (1990-1994), and again around the time of the first MRI (2004).

Overall, the worsening of cartilage loss and defects was similar among all subjects from the first to the second MRI, regardless of their level of exercise, she said.

“These were not people who ran marathons. These were people who jogged, or danced, or played tennis for more than 20 minutes—enough to raise a sweat or become short of breath.”

However, when the cohort was divided according to the presence (37 subjects) or absence (234 subjects) of BMLs on MRI, the risk of medical knee cartilage defects and volume loss was much more pronounced among exercisers, compared with nonexercisers (odds ratio, 3.4).

“This study identifies a subgroup—those with BML—who are more likely to have adverse outcomes with exercise,” she concluded. “It may be that the biomechanical properties of bones with BML are altered, and this alters the ability of cartilage to withstand normal or abnormal loading related to physical activity.”

Dr. Wluka said her group chose to look at BMLs because they have been associated with pain and progression in patients with symptomatic OA. Even in clinically asymptomatic populations, BMLs have been associated with an increased prevalence of cartilage defects and loss, she said.

“I'm not suggesting everyone go out and get an MRI to see if they have BMLs, but looking at why people have BMLs might be helpful, and there might be noninvasive ways of identifying them,” she said in an interview.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Wluka said she had no conflicts of interest.

Patients with bone marrow lesions, as shown above on MRI, had adverse outcomes with exercise.

Source Courtesy Dr. Anita Wluka

MONTREAL – Despite postmarketing concerns about the psychiatric side effects of varenicline for smoking cessation, the medication appears to be safe in patients who are depressed or at risk for depression, Jennifer B. McClure, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

In a subanalysis of the Chronicle Offers Management to Patients With Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, 661 smokers with a baseline history of depression, or a risk of depression, were monitored for mood changes and compared with 516 nondepressed smokers during their 12-week course of varenicline (Chantix) combined with behavioral smoking-cessation counseling (J. Gen. Intern. Med. 2009;24:563-9).

“We think that physicians should continue to closely monitor patients who are using varenicline, particularly if they have a psychiatric history,” she said. Although people with a history of depression were more likely than nondepressed people to report side effects with the medication, “we didn't find an overall difference in their qualitative symptom experience, or treatment outcomes,” said Dr. McClure, who is affiliated with Group Health Center for Health Studies, Seattle.

The study, funded by the National Cancer Institute, was a collaborative effort between Group Health; Free & Clear Inc., Seattle; and SRI International, an independent, nonprofit, research and development organization in Menlo Park, Calif. Medication was provided by Pfizer Inc., maker of varenicline.

Varenicline was approved by the Food and Drug Administration about 3 years ago. It works by blocking nicotinic receptors and thus the rewarding effects of nicotine, while stimulating some dopamine release to provide relief from craving and withdrawal, Dr. McClure said.

Shortly after its release to market, the FDA raised concerns that varenicline might be associated with increased neuropsychiatric symptoms, including depressed mood, agitation, suicidal ideation, and behavior–particularly in people with a psychiatric history, she said.

“Unfortunately, due to the nature of the reports to the FDA, we are not able to determine if varenicline itself was the cause of the symptoms reported–it's possible they were due to nicotine withdrawal, substance use, the psychiatric conditions themselves, or some other factors. Unfortunately, subjects with a psychiatric history were excluded from the original efficacy trials.”

Research shows that between one- and two-thirds of smokers have a history of depression, and that smokers with a history of depression report more symptoms of nicotine withdrawal, have more negative affect after they quit, and have higher relapse rates, compared with nondepressed smokers, she added.

“But because varenicline does stimulate some release of dopamine, it's possible that it might ameliorate some of this negative effect and other side effects, and so prevent relapse.”

At baseline, the subjects in the study were screened for symptoms of depression. “We didn't do an in-depth clinical interview; we just looked for the hallmark symptoms by asking: 'Have you ever, for a 2-week period or more, felt down, depressed, or hopeless, or had little interest or pleasure in doing things?'” she said.

Depressed and nondepressed subjects had similar nonsmoking rates at 21 days (49% vs. 47%, respectively), and 3 months (45% vs. 43%, respectively). However, depressed patients were more likely to endorse depression, anxiety, tension, agitation, difficulty concentrating and sleeping, and confusion. Depressed patients also were more likely to report other known side effects of the medication. However, despite this, negative affect actually declined in both groups, Dr. McClure said. One case of suicidal ideation was reported in a subject with undisclosed, untreated bipolar disorder.

Additional research is necessary to tease out the safety and effectiveness of varenicline among psychologically vulnerable populations, she concluded.

Dr. McClure said she had no conflicts to disclose in connection with this study.

MONTREAL – Despite postmarketing concerns about the psychiatric side effects of varenicline for smoking cessation, the medication appears to be safe in patients who are depressed or at risk for depression, Jennifer B. McClure, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

In a subanalysis of the Chronicle Offers Management to Patients With Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, 661 smokers with a baseline history of depression, or a risk of depression, were monitored for mood changes and compared with 516 nondepressed smokers during their 12-week course of varenicline (Chantix) combined with behavioral smoking-cessation counseling (J. Gen. Intern. Med. 2009;24:563-9).

“We think that physicians should continue to closely monitor patients who are using varenicline, particularly if they have a psychiatric history,” she said. Although people with a history of depression were more likely than nondepressed people to report side effects with the medication, “we didn't find an overall difference in their qualitative symptom experience, or treatment outcomes,” said Dr. McClure, who is affiliated with Group Health Center for Health Studies, Seattle.

The study, funded by the National Cancer Institute, was a collaborative effort between Group Health; Free & Clear Inc., Seattle; and SRI International, an independent, nonprofit, research and development organization in Menlo Park, Calif. Medication was provided by Pfizer Inc., maker of varenicline.

Varenicline was approved by the Food and Drug Administration about 3 years ago. It works by blocking nicotinic receptors and thus the rewarding effects of nicotine, while stimulating some dopamine release to provide relief from craving and withdrawal, Dr. McClure said.

Shortly after its release to market, the FDA raised concerns that varenicline might be associated with increased neuropsychiatric symptoms, including depressed mood, agitation, suicidal ideation, and behavior–particularly in people with a psychiatric history, she said.

“Unfortunately, due to the nature of the reports to the FDA, we are not able to determine if varenicline itself was the cause of the symptoms reported–it's possible they were due to nicotine withdrawal, substance use, the psychiatric conditions themselves, or some other factors. Unfortunately, subjects with a psychiatric history were excluded from the original efficacy trials.”

Research shows that between one- and two-thirds of smokers have a history of depression, and that smokers with a history of depression report more symptoms of nicotine withdrawal, have more negative affect after they quit, and have higher relapse rates, compared with nondepressed smokers, she added.

“But because varenicline does stimulate some release of dopamine, it's possible that it might ameliorate some of this negative effect and other side effects, and so prevent relapse.”

At baseline, the subjects in the study were screened for symptoms of depression. “We didn't do an in-depth clinical interview; we just looked for the hallmark symptoms by asking: 'Have you ever, for a 2-week period or more, felt down, depressed, or hopeless, or had little interest or pleasure in doing things?'” she said.

Depressed and nondepressed subjects had similar nonsmoking rates at 21 days (49% vs. 47%, respectively), and 3 months (45% vs. 43%, respectively). However, depressed patients were more likely to endorse depression, anxiety, tension, agitation, difficulty concentrating and sleeping, and confusion. Depressed patients also were more likely to report other known side effects of the medication. However, despite this, negative affect actually declined in both groups, Dr. McClure said. One case of suicidal ideation was reported in a subject with undisclosed, untreated bipolar disorder.

Additional research is necessary to tease out the safety and effectiveness of varenicline among psychologically vulnerable populations, she concluded.

Dr. McClure said she had no conflicts to disclose in connection with this study.

MONTREAL – Despite postmarketing concerns about the psychiatric side effects of varenicline for smoking cessation, the medication appears to be safe in patients who are depressed or at risk for depression, Jennifer B. McClure, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

In a subanalysis of the Chronicle Offers Management to Patients With Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, 661 smokers with a baseline history of depression, or a risk of depression, were monitored for mood changes and compared with 516 nondepressed smokers during their 12-week course of varenicline (Chantix) combined with behavioral smoking-cessation counseling (J. Gen. Intern. Med. 2009;24:563-9).

“We think that physicians should continue to closely monitor patients who are using varenicline, particularly if they have a psychiatric history,” she said. Although people with a history of depression were more likely than nondepressed people to report side effects with the medication, “we didn't find an overall difference in their qualitative symptom experience, or treatment outcomes,” said Dr. McClure, who is affiliated with Group Health Center for Health Studies, Seattle.

The study, funded by the National Cancer Institute, was a collaborative effort between Group Health; Free & Clear Inc., Seattle; and SRI International, an independent, nonprofit, research and development organization in Menlo Park, Calif. Medication was provided by Pfizer Inc., maker of varenicline.

Varenicline was approved by the Food and Drug Administration about 3 years ago. It works by blocking nicotinic receptors and thus the rewarding effects of nicotine, while stimulating some dopamine release to provide relief from craving and withdrawal, Dr. McClure said.

Shortly after its release to market, the FDA raised concerns that varenicline might be associated with increased neuropsychiatric symptoms, including depressed mood, agitation, suicidal ideation, and behavior–particularly in people with a psychiatric history, she said.

“Unfortunately, due to the nature of the reports to the FDA, we are not able to determine if varenicline itself was the cause of the symptoms reported–it's possible they were due to nicotine withdrawal, substance use, the psychiatric conditions themselves, or some other factors. Unfortunately, subjects with a psychiatric history were excluded from the original efficacy trials.”

Research shows that between one- and two-thirds of smokers have a history of depression, and that smokers with a history of depression report more symptoms of nicotine withdrawal, have more negative affect after they quit, and have higher relapse rates, compared with nondepressed smokers, she added.

“But because varenicline does stimulate some release of dopamine, it's possible that it might ameliorate some of this negative effect and other side effects, and so prevent relapse.”

At baseline, the subjects in the study were screened for symptoms of depression. “We didn't do an in-depth clinical interview; we just looked for the hallmark symptoms by asking: 'Have you ever, for a 2-week period or more, felt down, depressed, or hopeless, or had little interest or pleasure in doing things?'” she said.

Depressed and nondepressed subjects had similar nonsmoking rates at 21 days (49% vs. 47%, respectively), and 3 months (45% vs. 43%, respectively). However, depressed patients were more likely to endorse depression, anxiety, tension, agitation, difficulty concentrating and sleeping, and confusion. Depressed patients also were more likely to report other known side effects of the medication. However, despite this, negative affect actually declined in both groups, Dr. McClure said. One case of suicidal ideation was reported in a subject with undisclosed, untreated bipolar disorder.

Additional research is necessary to tease out the safety and effectiveness of varenicline among psychologically vulnerable populations, she concluded.

Dr. McClure said she had no conflicts to disclose in connection with this study.

MONTREAL — Patients with hypoglycemia at the time of hospitalization for community-acquired pneumonia have an increased risk of death, compared with patients with normoglycemia, according to a study reported at the World Diabetes Congress.

“Hypoglycemia is an easy-to-measure variable on admission, and should be a red flag to alert physicians to possible high-risk pneumonia patients,” said John-Michael Gamble, of the University of Alberta (Edmonton).

Because an influx of community-acquired pneumonia (CAP) cases resulting from pandemic influenza A(H1N1) is expected in hospital intensive care units, quick recognition of high-risk factors is particularly important, Mr. Gamble said in an interview.

His prospective study included 956 CAP patients admitted to six Edmonton hospitals between 2000 and 2002, for whom random venous blood glucose tests measured 6.1 mmol/L or lower.

Hypoglycemia was defined as a measurement less than 4.0 mmol/L, and normoglycemia was defined as a measurement between 4.0 mmol/L and 6.1 mmol/L.

The primary outcome of the study was in-hospital mortality. Secondary outcomes included 30-day and 1-year mortality. The mean age of the patients was 65 years, and 15% resided in nursing homes.

Hypoglycemia was present at hospital admission in 54 patients (6%); among those patients, fewer than half (46%) were previously diagnosed diabetes patients.

The mortality rate was significantly greater at all time points among patients with hypoglycemia at admission, compared with normoglycemic patients, Mr. Gamble reported.

The in-hospital and 30-day mortality rates were both 20% for patients with hypoglycemia at admission, compared with 9% and 10%, respectively, in those with normoglycemia.

Similarly, at 1 year, patients with hypoglycemia at admission had a 35% mortality rate, compared with 25% in those patients with normoglycemia.

In addition to adjusting for age, sex, comorbidities, medication, and nursing home residence, the study adjusted for pneumonia severity index (PSI), smoking status, presence of advance directives, previous pneumococcal vaccine, and direct admission to the ICU. Several additional sensitivity analyses included clinical markers of physiologic stress, exclusion of patients admitted to the ICU, and exclusion of patients with diabetes.

Whether high or low, blood glucose abnormalities in general “may serve as a marker for sicker patients,” commented Dr. Silvio Inzucchi, professor of medicine and clinical director of the section of endocrinology at Yale University, New Haven, Conn. Among nondiabetic patients, blood glucose abnormalities may be “particularly dangerous,” Dr. Inzucchi explained in a separate presentation at the meeting.

Endocrinologists and intensivists are facing a “pendulum swing” regarding inpatient glucose control, Dr. Inzucchi noted, in light of a recent publication suggesting “very surprisingly” that intensive versus conventional control of hyperglycemia is associated with a 15-fold increase in hypoglycemia and significantly higher mortality (27.5% versus 24.9%) (N. Engl. J. Med. 2009;360:1283–97).

As a result, Dr. Inzucchi helped draft the recent American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control, which recognizes the potential hypoglycemic risks of intensive control and recommends relaxing target blood glucose levels (Diabetes Care 2009;32:1344–5; Endocr. Pract. 2009;15:353–69).

“Specifically in the case of CAP, we need to look at the risks and benefits of treating admission hypoglycemia,” Mr. Gamble commented.

Mr. Gamble said he had no conflicts of interest. Dr. Inzucchi declared paid lecturing with Novo Nordisk, an advisory board agreement with Medtronic Inc., research sponsored by Eli Lilly Co., and CME program participation in which Sanofi-Aventis was a funding source.

MONTREAL — Patients with hypoglycemia at the time of hospitalization for community-acquired pneumonia have an increased risk of death, compared with patients with normoglycemia, according to a study reported at the World Diabetes Congress.

“Hypoglycemia is an easy-to-measure variable on admission, and should be a red flag to alert physicians to possible high-risk pneumonia patients,” said John-Michael Gamble, of the University of Alberta (Edmonton).

Because an influx of community-acquired pneumonia (CAP) cases resulting from pandemic influenza A(H1N1) is expected in hospital intensive care units, quick recognition of high-risk factors is particularly important, Mr. Gamble said in an interview.

His prospective study included 956 CAP patients admitted to six Edmonton hospitals between 2000 and 2002, for whom random venous blood glucose tests measured 6.1 mmol/L or lower.

Hypoglycemia was defined as a measurement less than 4.0 mmol/L, and normoglycemia was defined as a measurement between 4.0 mmol/L and 6.1 mmol/L.

The primary outcome of the study was in-hospital mortality. Secondary outcomes included 30-day and 1-year mortality. The mean age of the patients was 65 years, and 15% resided in nursing homes.

Hypoglycemia was present at hospital admission in 54 patients (6%); among those patients, fewer than half (46%) were previously diagnosed diabetes patients.

The mortality rate was significantly greater at all time points among patients with hypoglycemia at admission, compared with normoglycemic patients, Mr. Gamble reported.

The in-hospital and 30-day mortality rates were both 20% for patients with hypoglycemia at admission, compared with 9% and 10%, respectively, in those with normoglycemia.

Similarly, at 1 year, patients with hypoglycemia at admission had a 35% mortality rate, compared with 25% in those patients with normoglycemia.

In addition to adjusting for age, sex, comorbidities, medication, and nursing home residence, the study adjusted for pneumonia severity index (PSI), smoking status, presence of advance directives, previous pneumococcal vaccine, and direct admission to the ICU. Several additional sensitivity analyses included clinical markers of physiologic stress, exclusion of patients admitted to the ICU, and exclusion of patients with diabetes.

Whether high or low, blood glucose abnormalities in general “may serve as a marker for sicker patients,” commented Dr. Silvio Inzucchi, professor of medicine and clinical director of the section of endocrinology at Yale University, New Haven, Conn. Among nondiabetic patients, blood glucose abnormalities may be “particularly dangerous,” Dr. Inzucchi explained in a separate presentation at the meeting.

Endocrinologists and intensivists are facing a “pendulum swing” regarding inpatient glucose control, Dr. Inzucchi noted, in light of a recent publication suggesting “very surprisingly” that intensive versus conventional control of hyperglycemia is associated with a 15-fold increase in hypoglycemia and significantly higher mortality (27.5% versus 24.9%) (N. Engl. J. Med. 2009;360:1283–97).

As a result, Dr. Inzucchi helped draft the recent American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control, which recognizes the potential hypoglycemic risks of intensive control and recommends relaxing target blood glucose levels (Diabetes Care 2009;32:1344–5; Endocr. Pract. 2009;15:353–69).

“Specifically in the case of CAP, we need to look at the risks and benefits of treating admission hypoglycemia,” Mr. Gamble commented.

Mr. Gamble said he had no conflicts of interest. Dr. Inzucchi declared paid lecturing with Novo Nordisk, an advisory board agreement with Medtronic Inc., research sponsored by Eli Lilly Co., and CME program participation in which Sanofi-Aventis was a funding source.

MONTREAL — Patients with hypoglycemia at the time of hospitalization for community-acquired pneumonia have an increased risk of death, compared with patients with normoglycemia, according to a study reported at the World Diabetes Congress.

“Hypoglycemia is an easy-to-measure variable on admission, and should be a red flag to alert physicians to possible high-risk pneumonia patients,” said John-Michael Gamble, of the University of Alberta (Edmonton).

Because an influx of community-acquired pneumonia (CAP) cases resulting from pandemic influenza A(H1N1) is expected in hospital intensive care units, quick recognition of high-risk factors is particularly important, Mr. Gamble said in an interview.

His prospective study included 956 CAP patients admitted to six Edmonton hospitals between 2000 and 2002, for whom random venous blood glucose tests measured 6.1 mmol/L or lower.

Hypoglycemia was defined as a measurement less than 4.0 mmol/L, and normoglycemia was defined as a measurement between 4.0 mmol/L and 6.1 mmol/L.

The primary outcome of the study was in-hospital mortality. Secondary outcomes included 30-day and 1-year mortality. The mean age of the patients was 65 years, and 15% resided in nursing homes.

Hypoglycemia was present at hospital admission in 54 patients (6%); among those patients, fewer than half (46%) were previously diagnosed diabetes patients.

The mortality rate was significantly greater at all time points among patients with hypoglycemia at admission, compared with normoglycemic patients, Mr. Gamble reported.

The in-hospital and 30-day mortality rates were both 20% for patients with hypoglycemia at admission, compared with 9% and 10%, respectively, in those with normoglycemia.

Similarly, at 1 year, patients with hypoglycemia at admission had a 35% mortality rate, compared with 25% in those patients with normoglycemia.

In addition to adjusting for age, sex, comorbidities, medication, and nursing home residence, the study adjusted for pneumonia severity index (PSI), smoking status, presence of advance directives, previous pneumococcal vaccine, and direct admission to the ICU. Several additional sensitivity analyses included clinical markers of physiologic stress, exclusion of patients admitted to the ICU, and exclusion of patients with diabetes.

Whether high or low, blood glucose abnormalities in general “may serve as a marker for sicker patients,” commented Dr. Silvio Inzucchi, professor of medicine and clinical director of the section of endocrinology at Yale University, New Haven, Conn. Among nondiabetic patients, blood glucose abnormalities may be “particularly dangerous,” Dr. Inzucchi explained in a separate presentation at the meeting.

Endocrinologists and intensivists are facing a “pendulum swing” regarding inpatient glucose control, Dr. Inzucchi noted, in light of a recent publication suggesting “very surprisingly” that intensive versus conventional control of hyperglycemia is associated with a 15-fold increase in hypoglycemia and significantly higher mortality (27.5% versus 24.9%) (N. Engl. J. Med. 2009;360:1283–97).

As a result, Dr. Inzucchi helped draft the recent American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control, which recognizes the potential hypoglycemic risks of intensive control and recommends relaxing target blood glucose levels (Diabetes Care 2009;32:1344–5; Endocr. Pract. 2009;15:353–69).

“Specifically in the case of CAP, we need to look at the risks and benefits of treating admission hypoglycemia,” Mr. Gamble commented.

Mr. Gamble said he had no conflicts of interest. Dr. Inzucchi declared paid lecturing with Novo Nordisk, an advisory board agreement with Medtronic Inc., research sponsored by Eli Lilly Co., and CME program participation in which Sanofi-Aventis was a funding source.

MONTREAL — Rheumatologists and general practitioners report significant variations in the way they manage patients with knee osteoarthritis, and in addition, their patient populations are also quite different, according to a French study sponsored by Wyeth Pharmaceuticals.

“This study identified variability in key aspects of management of knee OA as a function of medical specialty,” reported Dr. Pascal Richette of Hôpital Lariboisière, Paris, and colleagues in a poster at the World Congress on Osteoarthritis.

The study used a cross-sectional survey of 808 general practitioners and 134 rheumatologists, representing 1,570 and 251 patients respectively. Each physician completed a medical questionnaire for their two most recent patients who fulfilled criteria for knee OA as defined by the American College of Rheumatology.

The clinical profiles of patients varied considerably between the specialties, with patients in the care of general practitioners experiencing more pain than did patients under the care of a rheumatologist (49.8 vs. 46.2 on a 0-100 Visual Analog Scale). In addition, general practitioners reported that their patients' pain had been of longer duration than that of patients reported by the rheumatologists (7.9 vs. 6.8 years). Patients of general practitioners were also more likely to have a second joint affected by OA (71.2% vs. 63.7%).

In terms of prescribing practices, general practitioners prescribed symptomatic slow-acting drugs in OA significantly less frequently than did rheumatologists (39% vs. 45% of the time), the authors reported. Instead, general practitioners prescribed more low-dose, oral, and topical NSAIDs. The use of symptomatic slow-acting drugs in OA has been controversial because of conflicting data on the efficacy of these agents. This category of drugs includes nutritional supplements and medications designed to reduce the symptoms of OA over the long term.

In addition, intra-articular injection of steroids or hyaluronic acid was performed significantly less often by general practitioners (7.6% and 2.5% of the time, respectively) than by rheumatologists (31.5% and 46.2% of the time). Rheumatologists performed joint puncture significantly more frequently (18% vs. 4% of the time).

Rehabilitation and weight loss were prescribed more often by general practitioners (in 34% and 65% of cases, respectively) than by rheumatologists (in 22% and 51% of cases, respectively), whereas exercise was prescribed by 47% of rheumatologists vs. 34% of general practitioners.

General practitioners prescribed NSAIDs significantly more frequently and symptomatic slow-acting drugs in OA significantly less frequently than did rheumatologists.

The congress was sponsored by the Osteoarthritis Research Society International. There was no conflict of interest disclosure.

MONTREAL — Rheumatologists and general practitioners report significant variations in the way they manage patients with knee osteoarthritis, and in addition, their patient populations are also quite different, according to a French study sponsored by Wyeth Pharmaceuticals.

“This study identified variability in key aspects of management of knee OA as a function of medical specialty,” reported Dr. Pascal Richette of Hôpital Lariboisière, Paris, and colleagues in a poster at the World Congress on Osteoarthritis.

The study used a cross-sectional survey of 808 general practitioners and 134 rheumatologists, representing 1,570 and 251 patients respectively. Each physician completed a medical questionnaire for their two most recent patients who fulfilled criteria for knee OA as defined by the American College of Rheumatology.

The clinical profiles of patients varied considerably between the specialties, with patients in the care of general practitioners experiencing more pain than did patients under the care of a rheumatologist (49.8 vs. 46.2 on a 0-100 Visual Analog Scale). In addition, general practitioners reported that their patients' pain had been of longer duration than that of patients reported by the rheumatologists (7.9 vs. 6.8 years). Patients of general practitioners were also more likely to have a second joint affected by OA (71.2% vs. 63.7%).

In terms of prescribing practices, general practitioners prescribed symptomatic slow-acting drugs in OA significantly less frequently than did rheumatologists (39% vs. 45% of the time), the authors reported. Instead, general practitioners prescribed more low-dose, oral, and topical NSAIDs. The use of symptomatic slow-acting drugs in OA has been controversial because of conflicting data on the efficacy of these agents. This category of drugs includes nutritional supplements and medications designed to reduce the symptoms of OA over the long term.

In addition, intra-articular injection of steroids or hyaluronic acid was performed significantly less often by general practitioners (7.6% and 2.5% of the time, respectively) than by rheumatologists (31.5% and 46.2% of the time). Rheumatologists performed joint puncture significantly more frequently (18% vs. 4% of the time).

Rehabilitation and weight loss were prescribed more often by general practitioners (in 34% and 65% of cases, respectively) than by rheumatologists (in 22% and 51% of cases, respectively), whereas exercise was prescribed by 47% of rheumatologists vs. 34% of general practitioners.

General practitioners prescribed NSAIDs significantly more frequently and symptomatic slow-acting drugs in OA significantly less frequently than did rheumatologists.

The congress was sponsored by the Osteoarthritis Research Society International. There was no conflict of interest disclosure.

MONTREAL — Rheumatologists and general practitioners report significant variations in the way they manage patients with knee osteoarthritis, and in addition, their patient populations are also quite different, according to a French study sponsored by Wyeth Pharmaceuticals.

“This study identified variability in key aspects of management of knee OA as a function of medical specialty,” reported Dr. Pascal Richette of Hôpital Lariboisière, Paris, and colleagues in a poster at the World Congress on Osteoarthritis.

The study used a cross-sectional survey of 808 general practitioners and 134 rheumatologists, representing 1,570 and 251 patients respectively. Each physician completed a medical questionnaire for their two most recent patients who fulfilled criteria for knee OA as defined by the American College of Rheumatology.

The clinical profiles of patients varied considerably between the specialties, with patients in the care of general practitioners experiencing more pain than did patients under the care of a rheumatologist (49.8 vs. 46.2 on a 0-100 Visual Analog Scale). In addition, general practitioners reported that their patients' pain had been of longer duration than that of patients reported by the rheumatologists (7.9 vs. 6.8 years). Patients of general practitioners were also more likely to have a second joint affected by OA (71.2% vs. 63.7%).

In terms of prescribing practices, general practitioners prescribed symptomatic slow-acting drugs in OA significantly less frequently than did rheumatologists (39% vs. 45% of the time), the authors reported. Instead, general practitioners prescribed more low-dose, oral, and topical NSAIDs. The use of symptomatic slow-acting drugs in OA has been controversial because of conflicting data on the efficacy of these agents. This category of drugs includes nutritional supplements and medications designed to reduce the symptoms of OA over the long term.

In addition, intra-articular injection of steroids or hyaluronic acid was performed significantly less often by general practitioners (7.6% and 2.5% of the time, respectively) than by rheumatologists (31.5% and 46.2% of the time). Rheumatologists performed joint puncture significantly more frequently (18% vs. 4% of the time).

Rehabilitation and weight loss were prescribed more often by general practitioners (in 34% and 65% of cases, respectively) than by rheumatologists (in 22% and 51% of cases, respectively), whereas exercise was prescribed by 47% of rheumatologists vs. 34% of general practitioners.

General practitioners prescribed NSAIDs significantly more frequently and symptomatic slow-acting drugs in OA significantly less frequently than did rheumatologists.

The congress was sponsored by the Osteoarthritis Research Society International. There was no conflict of interest disclosure.

MONTREAL — The presence of bone marrow lesions in pain-free knees may be a marker for an increased risk of future osteoarthritis among people who participate in vigorous activity. However, it's not known whether a modified exercise program could reduce this risk, Dr. Anita Wluka said at the World Congress on Osteoarthritis.

“It's possible that we should be changing our recommendations from weight-bearing to non–weight-bearing physical activity in this group, but this warrants further investigation,” said Dr. Wluka of Monash University in Clayton, Victoria, Australia.

Dr. Wluka's findings were based on a subgroup analysis of people participating in the longitudinal Melbourne Collaborative Cohort (MCC) study, established in 1990 to assess the role of diet and lifestyle in the risk for cancer and diabetes. The original cohort included 41,500 people (aged 40-69 years). In 2002, the investigators expanded the outcomes of interest to include cardiovascular disease and metabolic syndrome.

In a subanalysis, her group identified 271 individuals (aged 50-79 years) who had no knee disease or pain at baseline and results from two magnetic resonance imaging scans taken 2 years apart. Cartilage volume and defects, as well as the presence of bone marrow lesions (BMLs), were assessed on MRI.

The degree of participation in vigorous physical activity was recorded when subjects first entered the larger MCC study (1990-94), and again around the time of the first MRI (2004).

Overall, the worsening of cartilage loss and defects was similar among all of the individuals from the first to the second MRI, regardless of their level of exercise, she said.

“These were not people who ran marathons. These were people who jogged, or danced, or played tennis for more than 20 minutes—enough to raise a sweat or become short of breath.”

The cohort was divided according to the presence (37 subjects) or absence (234 subjects) of BMLs on MRI. Among those with BMLs, the risk of medical knee cartilage defects and volume loss was much more pronounced among exercisers, compared with nonexercisers (odds ratio 3.4).

“This study identifies a subgroup—those with BML—who are more likely to have adverse outcomes with exercise,” she concluded. “It may be that the biomechanical properties of bones with BML are altered, and this alters the ability of cartilage to withstand normal or abnormal loading related to physical activity,” Dr. Wluka said.

Dr. Wluka said that her group chose to look at BMLs because they have been associated with pain and progression in patients with symptomatic OA. Even in clinically asymptomatic populations, BMLs have been associated with an increased prevalence of cartilage defects and loss, she said at the congress, which was sponsored by the Osteoarthritis Research Society International.

“I'm not suggesting everyone go out and get an MRI to see if they have BMLs, but looking at why people have BMLs might be helpful, and there might be noninvasive ways of identifying them,” she said in an interview.

Dr. Wluka said she had no conflicts of interest.

A bone marrow lesion, seen on MRI in this patient's knee, may signal an increased risk of OA with exercise.

Source Courtesy Dr. Anita Wluka

MONTREAL — The presence of bone marrow lesions in pain-free knees may be a marker for an increased risk of future osteoarthritis among people who participate in vigorous activity. However, it's not known whether a modified exercise program could reduce this risk, Dr. Anita Wluka said at the World Congress on Osteoarthritis.

“It's possible that we should be changing our recommendations from weight-bearing to non–weight-bearing physical activity in this group, but this warrants further investigation,” said Dr. Wluka of Monash University in Clayton, Victoria, Australia.

Dr. Wluka's findings were based on a subgroup analysis of people participating in the longitudinal Melbourne Collaborative Cohort (MCC) study, established in 1990 to assess the role of diet and lifestyle in the risk for cancer and diabetes. The original cohort included 41,500 people (aged 40-69 years). In 2002, the investigators expanded the outcomes of interest to include cardiovascular disease and metabolic syndrome.

In a subanalysis, her group identified 271 individuals (aged 50-79 years) who had no knee disease or pain at baseline and results from two magnetic resonance imaging scans taken 2 years apart. Cartilage volume and defects, as well as the presence of bone marrow lesions (BMLs), were assessed on MRI.

The degree of participation in vigorous physical activity was recorded when subjects first entered the larger MCC study (1990-94), and again around the time of the first MRI (2004).

Overall, the worsening of cartilage loss and defects was similar among all of the individuals from the first to the second MRI, regardless of their level of exercise, she said.

“These were not people who ran marathons. These were people who jogged, or danced, or played tennis for more than 20 minutes—enough to raise a sweat or become short of breath.”

The cohort was divided according to the presence (37 subjects) or absence (234 subjects) of BMLs on MRI. Among those with BMLs, the risk of medical knee cartilage defects and volume loss was much more pronounced among exercisers, compared with nonexercisers (odds ratio 3.4).

“This study identifies a subgroup—those with BML—who are more likely to have adverse outcomes with exercise,” she concluded. “It may be that the biomechanical properties of bones with BML are altered, and this alters the ability of cartilage to withstand normal or abnormal loading related to physical activity,” Dr. Wluka said.

Dr. Wluka said that her group chose to look at BMLs because they have been associated with pain and progression in patients with symptomatic OA. Even in clinically asymptomatic populations, BMLs have been associated with an increased prevalence of cartilage defects and loss, she said at the congress, which was sponsored by the Osteoarthritis Research Society International.

“I'm not suggesting everyone go out and get an MRI to see if they have BMLs, but looking at why people have BMLs might be helpful, and there might be noninvasive ways of identifying them,” she said in an interview.

Dr. Wluka said she had no conflicts of interest.

A bone marrow lesion, seen on MRI in this patient's knee, may signal an increased risk of OA with exercise.

Source Courtesy Dr. Anita Wluka

MONTREAL — The presence of bone marrow lesions in pain-free knees may be a marker for an increased risk of future osteoarthritis among people who participate in vigorous activity. However, it's not known whether a modified exercise program could reduce this risk, Dr. Anita Wluka said at the World Congress on Osteoarthritis.

“It's possible that we should be changing our recommendations from weight-bearing to non–weight-bearing physical activity in this group, but this warrants further investigation,” said Dr. Wluka of Monash University in Clayton, Victoria, Australia.

Dr. Wluka's findings were based on a subgroup analysis of people participating in the longitudinal Melbourne Collaborative Cohort (MCC) study, established in 1990 to assess the role of diet and lifestyle in the risk for cancer and diabetes. The original cohort included 41,500 people (aged 40-69 years). In 2002, the investigators expanded the outcomes of interest to include cardiovascular disease and metabolic syndrome.

In a subanalysis, her group identified 271 individuals (aged 50-79 years) who had no knee disease or pain at baseline and results from two magnetic resonance imaging scans taken 2 years apart. Cartilage volume and defects, as well as the presence of bone marrow lesions (BMLs), were assessed on MRI.

The degree of participation in vigorous physical activity was recorded when subjects first entered the larger MCC study (1990-94), and again around the time of the first MRI (2004).

Overall, the worsening of cartilage loss and defects was similar among all of the individuals from the first to the second MRI, regardless of their level of exercise, she said.

“These were not people who ran marathons. These were people who jogged, or danced, or played tennis for more than 20 minutes—enough to raise a sweat or become short of breath.”

The cohort was divided according to the presence (37 subjects) or absence (234 subjects) of BMLs on MRI. Among those with BMLs, the risk of medical knee cartilage defects and volume loss was much more pronounced among exercisers, compared with nonexercisers (odds ratio 3.4).

“This study identifies a subgroup—those with BML—who are more likely to have adverse outcomes with exercise,” she concluded. “It may be that the biomechanical properties of bones with BML are altered, and this alters the ability of cartilage to withstand normal or abnormal loading related to physical activity,” Dr. Wluka said.

Dr. Wluka said that her group chose to look at BMLs because they have been associated with pain and progression in patients with symptomatic OA. Even in clinically asymptomatic populations, BMLs have been associated with an increased prevalence of cartilage defects and loss, she said at the congress, which was sponsored by the Osteoarthritis Research Society International.

“I'm not suggesting everyone go out and get an MRI to see if they have BMLs, but looking at why people have BMLs might be helpful, and there might be noninvasive ways of identifying them,” she said in an interview.

Dr. Wluka said she had no conflicts of interest.

A bone marrow lesion, seen on MRI in this patient's knee, may signal an increased risk of OA with exercise.

Source Courtesy Dr. Anita Wluka

MONTREAL — Almost one-fifth of patients with chronic knee osteoarthritis may have symptoms of neuropathic pain, requiring consideration of an alternative approach to their pain management, reported Dr. Jacqueline Hochman at the World Congress on Osteoarthritis.

“In clinical practice, neuropathic pain is generally not considered a feature of osteoarthritis, and among osteoarthritis researchers it is a novel concept,” she said in an interview. “But a growing body of literature suggests that one reason for treatment failure in osteoarthritis might be a mismatch between the current medications we're using and the underlying mechanisms of pain.”

Dr. Hochman, a rheumatologist at Women's College Hospital in Toronto, explained that current theories about pain point to the possible development of neuropathic pain as a result of the chronic, nociceptive stimulation associated with osteoarthritis.

“Most likely, central sensitization in osteoarthritis arises from chronic or recurrent stimulation of peripheral nociceptors, leading to modifications in the central nervous system that cause hyperexcitability in the spinal cord and, perhaps, supraspinal centers involved in the central transmission of pain,” Dr. Hochman said.

The diagnosis of neuropathic pain is a clinical one that is “based on a characteristic symptom profile that includes spontaneous sensations such as burning pain, numbness, and tingling, and evoked sensations such as sensitivity to light touch,” she said. In the presence of these symptoms, sensory abnormalities on physical examination, such as pinprick hyperalgesia and allodynia, can aid the diagnosis.

However, there is a paucity of data on symptoms of neuropathic pain in OA, Dr. Hochman said. Because symptoms “are going to lead our patients to seek medical care and alert their physicians to the possibility of underlying neuropathic mechanisms, it's important to know whether people with OA have symptoms of neuropathic pain.”

Therefore, in a group of 171 patients (median age, 76 years) with chronic, symptomatic knee osteoarthritis, she administered a modification of the painDETECT questionnaire (mPD-Q) that is designed to distinguish neuropathic from nociceptive pain.

Other study measures included biopsychosocial factors, such as depression, anxiety, pain catastrophizing, and sleepiness; sociodemographics; osteoarthritis severity; comorbid conditions; and medication use.

After the exclusion of the patients who had neurologic conditions (neuropathy, sciatica, shingles, postherpetic neuralgia, multiple sclerosis, stroke, and Parkinson's disease), the study identified 19% of the patients who had symptoms suggestive of neuropathic pain, Dr. Hochman reported.

On multivariate analysis, greater pain intensity and chronic hip or back pain with radiation down either leg (but not below the knee) were correlated with higher scores for neuropathic pain (odds ratio, 3.6).

“The subgroup of patients with neuropathic pain symptoms may benefit from further evaluation and possibly treatment for neuropathic pain,” she said.

Neuropathic pain medications include anticonvulsants such as gabapentin and pregabalin, and tricyclic antidepressants such as amitriptyline and nortriptyline, which are believed to “disrupt the central pain pathway and impact central reorganization at the higher spinal centers,” Dr. Hochman said. Antidepressants may also alleviate the depression, anxiety, and sleep disturbances that often accompany—and can also amplify—pain.

Dr. Roy Altman noted that Dr. Hochman is documenting something that many clinicians have long suspected, namely that neuropathic pain plays a role as a part of the pain syndrome in osteoarthritis as a consequence of central pain sensitization.

This information is useful in supporting the use of medications that are not typically considered for osteoarthritis. Since older studies have not documented the value of gabapentin and pregabolin in unselected patients with osteoarthritis, it appears that some benefit could be achieved in selected patients with symptoms compatible with neuropathic pain, according to Dr. Altman, professor of rheumatology at the University of California, Los Angeles.

Additional study of this selected population seems to be in order. Also, more recent research has suggested that in a more general population, serotonin norepinephrine reuptake inhibitors are of value in osteoarthritis, he added.

Dr. Hochman said that further research is needed to determine whether people with painful osteoarthritis who have symptoms of neuropathic pain respond better to neuropathic treatments vs. standard medications such as NSAIDs and acetaminophen. She said that there is little research to date to guide clinicians on whether to treat both nociceptive and neuropathic pain concomitantly, or whether treatment for neuropathic pain can be stopped if pain improves.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Hochman said she had no conflicts of interest.

Many clinicians have long suspected that neuropathic pain plays a role as a part of the pain syndrome in OA.

Source DR. ALTMAN

MONTREAL — Almost one-fifth of patients with chronic knee osteoarthritis may have symptoms of neuropathic pain, requiring consideration of an alternative approach to their pain management, reported Dr. Jacqueline Hochman at the World Congress on Osteoarthritis.

“In clinical practice, neuropathic pain is generally not considered a feature of osteoarthritis, and among osteoarthritis researchers it is a novel concept,” she said in an interview. “But a growing body of literature suggests that one reason for treatment failure in osteoarthritis might be a mismatch between the current medications we're using and the underlying mechanisms of pain.”

Dr. Hochman, a rheumatologist at Women's College Hospital in Toronto, explained that current theories about pain point to the possible development of neuropathic pain as a result of the chronic, nociceptive stimulation associated with osteoarthritis.

“Most likely, central sensitization in osteoarthritis arises from chronic or recurrent stimulation of peripheral nociceptors, leading to modifications in the central nervous system that cause hyperexcitability in the spinal cord and, perhaps, supraspinal centers involved in the central transmission of pain,” Dr. Hochman said.

The diagnosis of neuropathic pain is a clinical one that is “based on a characteristic symptom profile that includes spontaneous sensations such as burning pain, numbness, and tingling, and evoked sensations such as sensitivity to light touch,” she said. In the presence of these symptoms, sensory abnormalities on physical examination, such as pinprick hyperalgesia and allodynia, can aid the diagnosis.

However, there is a paucity of data on symptoms of neuropathic pain in OA, Dr. Hochman said. Because symptoms “are going to lead our patients to seek medical care and alert their physicians to the possibility of underlying neuropathic mechanisms, it's important to know whether people with OA have symptoms of neuropathic pain.”

Therefore, in a group of 171 patients (median age, 76 years) with chronic, symptomatic knee osteoarthritis, she administered a modification of the painDETECT questionnaire (mPD-Q) that is designed to distinguish neuropathic from nociceptive pain.

Other study measures included biopsychosocial factors, such as depression, anxiety, pain catastrophizing, and sleepiness; sociodemographics; osteoarthritis severity; comorbid conditions; and medication use.

After the exclusion of the patients who had neurologic conditions (neuropathy, sciatica, shingles, postherpetic neuralgia, multiple sclerosis, stroke, and Parkinson's disease), the study identified 19% of the patients who had symptoms suggestive of neuropathic pain, Dr. Hochman reported.

On multivariate analysis, greater pain intensity and chronic hip or back pain with radiation down either leg (but not below the knee) were correlated with higher scores for neuropathic pain (odds ratio, 3.6).

“The subgroup of patients with neuropathic pain symptoms may benefit from further evaluation and possibly treatment for neuropathic pain,” she said.

Neuropathic pain medications include anticonvulsants such as gabapentin and pregabalin, and tricyclic antidepressants such as amitriptyline and nortriptyline, which are believed to “disrupt the central pain pathway and impact central reorganization at the higher spinal centers,” Dr. Hochman said. Antidepressants may also alleviate the depression, anxiety, and sleep disturbances that often accompany—and can also amplify—pain.

Dr. Roy Altman noted that Dr. Hochman is documenting something that many clinicians have long suspected, namely that neuropathic pain plays a role as a part of the pain syndrome in osteoarthritis as a consequence of central pain sensitization.

This information is useful in supporting the use of medications that are not typically considered for osteoarthritis. Since older studies have not documented the value of gabapentin and pregabolin in unselected patients with osteoarthritis, it appears that some benefit could be achieved in selected patients with symptoms compatible with neuropathic pain, according to Dr. Altman, professor of rheumatology at the University of California, Los Angeles.

Additional study of this selected population seems to be in order. Also, more recent research has suggested that in a more general population, serotonin norepinephrine reuptake inhibitors are of value in osteoarthritis, he added.

Dr. Hochman said that further research is needed to determine whether people with painful osteoarthritis who have symptoms of neuropathic pain respond better to neuropathic treatments vs. standard medications such as NSAIDs and acetaminophen. She said that there is little research to date to guide clinicians on whether to treat both nociceptive and neuropathic pain concomitantly, or whether treatment for neuropathic pain can be stopped if pain improves.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Hochman said she had no conflicts of interest.

Many clinicians have long suspected that neuropathic pain plays a role as a part of the pain syndrome in OA.

Source DR. ALTMAN

MONTREAL — Almost one-fifth of patients with chronic knee osteoarthritis may have symptoms of neuropathic pain, requiring consideration of an alternative approach to their pain management, reported Dr. Jacqueline Hochman at the World Congress on Osteoarthritis.

“In clinical practice, neuropathic pain is generally not considered a feature of osteoarthritis, and among osteoarthritis researchers it is a novel concept,” she said in an interview. “But a growing body of literature suggests that one reason for treatment failure in osteoarthritis might be a mismatch between the current medications we're using and the underlying mechanisms of pain.”

Dr. Hochman, a rheumatologist at Women's College Hospital in Toronto, explained that current theories about pain point to the possible development of neuropathic pain as a result of the chronic, nociceptive stimulation associated with osteoarthritis.

“Most likely, central sensitization in osteoarthritis arises from chronic or recurrent stimulation of peripheral nociceptors, leading to modifications in the central nervous system that cause hyperexcitability in the spinal cord and, perhaps, supraspinal centers involved in the central transmission of pain,” Dr. Hochman said.

The diagnosis of neuropathic pain is a clinical one that is “based on a characteristic symptom profile that includes spontaneous sensations such as burning pain, numbness, and tingling, and evoked sensations such as sensitivity to light touch,” she said. In the presence of these symptoms, sensory abnormalities on physical examination, such as pinprick hyperalgesia and allodynia, can aid the diagnosis.

However, there is a paucity of data on symptoms of neuropathic pain in OA, Dr. Hochman said. Because symptoms “are going to lead our patients to seek medical care and alert their physicians to the possibility of underlying neuropathic mechanisms, it's important to know whether people with OA have symptoms of neuropathic pain.”

Therefore, in a group of 171 patients (median age, 76 years) with chronic, symptomatic knee osteoarthritis, she administered a modification of the painDETECT questionnaire (mPD-Q) that is designed to distinguish neuropathic from nociceptive pain.

Other study measures included biopsychosocial factors, such as depression, anxiety, pain catastrophizing, and sleepiness; sociodemographics; osteoarthritis severity; comorbid conditions; and medication use.

After the exclusion of the patients who had neurologic conditions (neuropathy, sciatica, shingles, postherpetic neuralgia, multiple sclerosis, stroke, and Parkinson's disease), the study identified 19% of the patients who had symptoms suggestive of neuropathic pain, Dr. Hochman reported.

On multivariate analysis, greater pain intensity and chronic hip or back pain with radiation down either leg (but not below the knee) were correlated with higher scores for neuropathic pain (odds ratio, 3.6).

“The subgroup of patients with neuropathic pain symptoms may benefit from further evaluation and possibly treatment for neuropathic pain,” she said.

Neuropathic pain medications include anticonvulsants such as gabapentin and pregabalin, and tricyclic antidepressants such as amitriptyline and nortriptyline, which are believed to “disrupt the central pain pathway and impact central reorganization at the higher spinal centers,” Dr. Hochman said. Antidepressants may also alleviate the depression, anxiety, and sleep disturbances that often accompany—and can also amplify—pain.

Dr. Roy Altman noted that Dr. Hochman is documenting something that many clinicians have long suspected, namely that neuropathic pain plays a role as a part of the pain syndrome in osteoarthritis as a consequence of central pain sensitization.

This information is useful in supporting the use of medications that are not typically considered for osteoarthritis. Since older studies have not documented the value of gabapentin and pregabolin in unselected patients with osteoarthritis, it appears that some benefit could be achieved in selected patients with symptoms compatible with neuropathic pain, according to Dr. Altman, professor of rheumatology at the University of California, Los Angeles.

Additional study of this selected population seems to be in order. Also, more recent research has suggested that in a more general population, serotonin norepinephrine reuptake inhibitors are of value in osteoarthritis, he added.

Dr. Hochman said that further research is needed to determine whether people with painful osteoarthritis who have symptoms of neuropathic pain respond better to neuropathic treatments vs. standard medications such as NSAIDs and acetaminophen. She said that there is little research to date to guide clinicians on whether to treat both nociceptive and neuropathic pain concomitantly, or whether treatment for neuropathic pain can be stopped if pain improves.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Hochman said she had no conflicts of interest.

Many clinicians have long suspected that neuropathic pain plays a role as a part of the pain syndrome in OA.

Source DR. ALTMAN