Hannah Brown

BIRMINGHAM, ENGLAND — A direct relationship between gadodiamide—a chelate used regularly to identify renal artery stenosis in patients who are potential transplant recipients—and the activation of fibroblasts in nephrogenic systemic fibrosis has been identified, Dr. Susie Mukherjee reported at the annual meeting of the British Association of Dermatologists.

The origin of nephrogenic systemic fibrosis (NSF) has long intrigued the radiologic, renal, and dermatologic worlds because of the paucity of cases, said Dr. Mukherjee. Although NSF was initially thought to be a cutaneous condition, two recent case reports have indicated that it is in fact systemic.

Dr. Mukherjee, a dermatologist at Glasgow University, and her colleagues examined the levels of hyaluronan and collagen—both key components of the extracellular matrix—of six female patients with end-stage renal failure and biopsy proven NSF. Their median duration of dialysis was 4.8 years and the mean time to developing NSF symptoms after receiving gadodiamide was 1 month.

The investigators obtained 20 mL of blood from the patients and compared the blood with that of controls. Punch biopsies were used to establish fibroblast activity.

Serum samples from the NSF patients stimulated up to a 7-fold increase in hyaluronan synthesis and a 3.3-fold increase in collagen; both increases were statistically significant when compared with control patient samples, she said. Histology samples showed thickened collagen bundles signified by strong alcian blue staining on slides, she said.

Dr. Mukherjee also found that it only takes tiny concentrations of gadolinium to stimulate hyaluronan synthesis by fibroblasts. Both 10-mmol/L and 1-mmol/L concentrations of gadolinium caused a 2.3-fold increase in hyaluronan synthesis, "which is still quite a small level compared to what patients are exposed to," she said. "So really from these simple in vitro experiments we can suggest that NSF lesional fibroblasts synthesize excess hyaluronan and collagen, which increases after prolonged exposure to gadodiamide," explained Dr. Mukherjee. "These are the first experiments to demonstrate a direct relation between gadodiamide and activation of fibroblasts."

Evidence for a link between NSF and gadolinium was first described in a case series of 13 patients, all of whom developed NSF after being exposed to gadolinium (J. Am. Soc. Nephrol. 2006;17:2359-62).

Early symptoms of NSF include swelling, pruritus, and muscle pain of the limbs. Later changes include flexion contractures and grossly thickened indurated skin.

Further work should assess the effect of gadolinium on circulating fibrocytes and their ability to migrate into skin, according to Dr. Mukherjee.

BIRMINGHAM, ENGLAND — A direct relationship between gadodiamide—a chelate used regularly to identify renal artery stenosis in patients who are potential transplant recipients—and the activation of fibroblasts in nephrogenic systemic fibrosis has been identified, Dr. Susie Mukherjee reported at the annual meeting of the British Association of Dermatologists.

The origin of nephrogenic systemic fibrosis (NSF) has long intrigued the radiologic, renal, and dermatologic worlds because of the paucity of cases, said Dr. Mukherjee. Although NSF was initially thought to be a cutaneous condition, two recent case reports have indicated that it is in fact systemic.

Dr. Mukherjee, a dermatologist at Glasgow University, and her colleagues examined the levels of hyaluronan and collagen—both key components of the extracellular matrix—of six female patients with end-stage renal failure and biopsy proven NSF. Their median duration of dialysis was 4.8 years and the mean time to developing NSF symptoms after receiving gadodiamide was 1 month.

The investigators obtained 20 mL of blood from the patients and compared the blood with that of controls. Punch biopsies were used to establish fibroblast activity.

Serum samples from the NSF patients stimulated up to a 7-fold increase in hyaluronan synthesis and a 3.3-fold increase in collagen; both increases were statistically significant when compared with control patient samples, she said. Histology samples showed thickened collagen bundles signified by strong alcian blue staining on slides, she said.

Dr. Mukherjee also found that it only takes tiny concentrations of gadolinium to stimulate hyaluronan synthesis by fibroblasts. Both 10-mmol/L and 1-mmol/L concentrations of gadolinium caused a 2.3-fold increase in hyaluronan synthesis, "which is still quite a small level compared to what patients are exposed to," she said. "So really from these simple in vitro experiments we can suggest that NSF lesional fibroblasts synthesize excess hyaluronan and collagen, which increases after prolonged exposure to gadodiamide," explained Dr. Mukherjee. "These are the first experiments to demonstrate a direct relation between gadodiamide and activation of fibroblasts."

Evidence for a link between NSF and gadolinium was first described in a case series of 13 patients, all of whom developed NSF after being exposed to gadolinium (J. Am. Soc. Nephrol. 2006;17:2359-62).

Early symptoms of NSF include swelling, pruritus, and muscle pain of the limbs. Later changes include flexion contractures and grossly thickened indurated skin.

Further work should assess the effect of gadolinium on circulating fibrocytes and their ability to migrate into skin, according to Dr. Mukherjee.

BIRMINGHAM, ENGLAND — A direct relationship between gadodiamide—a chelate used regularly to identify renal artery stenosis in patients who are potential transplant recipients—and the activation of fibroblasts in nephrogenic systemic fibrosis has been identified, Dr. Susie Mukherjee reported at the annual meeting of the British Association of Dermatologists.

The origin of nephrogenic systemic fibrosis (NSF) has long intrigued the radiologic, renal, and dermatologic worlds because of the paucity of cases, said Dr. Mukherjee. Although NSF was initially thought to be a cutaneous condition, two recent case reports have indicated that it is in fact systemic.

Dr. Mukherjee, a dermatologist at Glasgow University, and her colleagues examined the levels of hyaluronan and collagen—both key components of the extracellular matrix—of six female patients with end-stage renal failure and biopsy proven NSF. Their median duration of dialysis was 4.8 years and the mean time to developing NSF symptoms after receiving gadodiamide was 1 month.

The investigators obtained 20 mL of blood from the patients and compared the blood with that of controls. Punch biopsies were used to establish fibroblast activity.

Serum samples from the NSF patients stimulated up to a 7-fold increase in hyaluronan synthesis and a 3.3-fold increase in collagen; both increases were statistically significant when compared with control patient samples, she said. Histology samples showed thickened collagen bundles signified by strong alcian blue staining on slides, she said.

Dr. Mukherjee also found that it only takes tiny concentrations of gadolinium to stimulate hyaluronan synthesis by fibroblasts. Both 10-mmol/L and 1-mmol/L concentrations of gadolinium caused a 2.3-fold increase in hyaluronan synthesis, "which is still quite a small level compared to what patients are exposed to," she said. "So really from these simple in vitro experiments we can suggest that NSF lesional fibroblasts synthesize excess hyaluronan and collagen, which increases after prolonged exposure to gadodiamide," explained Dr. Mukherjee. "These are the first experiments to demonstrate a direct relation between gadodiamide and activation of fibroblasts."

Evidence for a link between NSF and gadolinium was first described in a case series of 13 patients, all of whom developed NSF after being exposed to gadolinium (J. Am. Soc. Nephrol. 2006;17:2359-62).

Early symptoms of NSF include swelling, pruritus, and muscle pain of the limbs. Later changes include flexion contractures and grossly thickened indurated skin.

Further work should assess the effect of gadolinium on circulating fibrocytes and their ability to migrate into skin, according to Dr. Mukherjee.

BARCELONA — Patients with HIV who receive antiretroviral therapy are more likely to have metabolic syndrome than are their untreated counterparts, Dr. Julian Falutz said at an international congress on prediabetes and the metabolic syndrome.

Dr. Falutz and colleague Dr. Leonard Rosenthall compared several metabolic, HIV-related, and body-composition variables in two groups of HIV-positive men, one treated (172 patients) and one untreated (32 patients). Specific measurements included body mass index, waist circumference, blood pressure, trunk fat mass, fasting lipids, and glucose homeostasis markers. Metabolic syndrome among the men in both groups was assessed according to the five most commonly used sets of diagnostic criteria: NCEP (National Cholesterol Education Program), WHO (World Health Organization), IDF (International Diabetes Federation), EGIR (European Group for the Study of Insulin Resistance), and ACE (American College of Endocrinology).

The researchers found a statistically significant difference in the rate of metabolic syndrome as assessed by at least one of the classification schemes between the two groups. Overall, 20% of untreated individuals had at least one classification of metabolic syndrome, compared with almost 40% of treated men. However, there were substantial discrepancies between the rates of diagnosis of metabolic syndrome of the five classification schemes among the treated group, said Dr. Falutz, director of the HIV Metabolic Clinic at McGill University, Montreal.

With the NCEP criteria, metabolic syndrome prevalence in the treated group was 24%; under the WHO classification, it was 15%. The IDF criteria pegged the prevalence at 18%, under the EGIR criteria it was 24%, and ACE identified only 4% of the men as having metabolic syndrome.

These rates are similar to those in the general population, showing that “basically our patients are at similar risk for developing metabolic syndrome,” said Dr. Falutz. However, he added, “because the different published classification schemes do not identify the same people, there is a lack of consensus on how to diagnose metabolic syndrome.”

Dr. Falutz said he believes that more work needs to be done to sort out which classification scheme is best for predicting risk of cardiovascular events by linking diagnoses of metabolic syndrome to outcomes. “You need a very large group to be able to find out if the risk of myocardial infarction is increased, compared with other classifications,” he said. “We are going to see if we can use a combination of two classification schemes to see if people actually develop a myocardial infarction.”

Although Dr. Falutz's work is focused on patients with HIV, he said the problems he had encountered with narrowing down a definition of metabolic syndrome are applicable to other patient groups, too. “We looked at metabolic syndrome in our population because it is becoming an increasing problem,” he explained. “There are some people at higher risk, but you have to be careful when identifying them because no one classification scheme is the best, and we have to be aware of the controversy in the HIV-negative world. We may miss some people by using one [particular] scheme,” he warned.

BARCELONA — Patients with HIV who receive antiretroviral therapy are more likely to have metabolic syndrome than are their untreated counterparts, Dr. Julian Falutz said at an international congress on prediabetes and the metabolic syndrome.

Dr. Falutz and colleague Dr. Leonard Rosenthall compared several metabolic, HIV-related, and body-composition variables in two groups of HIV-positive men, one treated (172 patients) and one untreated (32 patients). Specific measurements included body mass index, waist circumference, blood pressure, trunk fat mass, fasting lipids, and glucose homeostasis markers. Metabolic syndrome among the men in both groups was assessed according to the five most commonly used sets of diagnostic criteria: NCEP (National Cholesterol Education Program), WHO (World Health Organization), IDF (International Diabetes Federation), EGIR (European Group for the Study of Insulin Resistance), and ACE (American College of Endocrinology).

The researchers found a statistically significant difference in the rate of metabolic syndrome as assessed by at least one of the classification schemes between the two groups. Overall, 20% of untreated individuals had at least one classification of metabolic syndrome, compared with almost 40% of treated men. However, there were substantial discrepancies between the rates of diagnosis of metabolic syndrome of the five classification schemes among the treated group, said Dr. Falutz, director of the HIV Metabolic Clinic at McGill University, Montreal.

With the NCEP criteria, metabolic syndrome prevalence in the treated group was 24%; under the WHO classification, it was 15%. The IDF criteria pegged the prevalence at 18%, under the EGIR criteria it was 24%, and ACE identified only 4% of the men as having metabolic syndrome.

These rates are similar to those in the general population, showing that “basically our patients are at similar risk for developing metabolic syndrome,” said Dr. Falutz. However, he added, “because the different published classification schemes do not identify the same people, there is a lack of consensus on how to diagnose metabolic syndrome.”

Dr. Falutz said he believes that more work needs to be done to sort out which classification scheme is best for predicting risk of cardiovascular events by linking diagnoses of metabolic syndrome to outcomes. “You need a very large group to be able to find out if the risk of myocardial infarction is increased, compared with other classifications,” he said. “We are going to see if we can use a combination of two classification schemes to see if people actually develop a myocardial infarction.”

Although Dr. Falutz's work is focused on patients with HIV, he said the problems he had encountered with narrowing down a definition of metabolic syndrome are applicable to other patient groups, too. “We looked at metabolic syndrome in our population because it is becoming an increasing problem,” he explained. “There are some people at higher risk, but you have to be careful when identifying them because no one classification scheme is the best, and we have to be aware of the controversy in the HIV-negative world. We may miss some people by using one [particular] scheme,” he warned.

BARCELONA — Patients with HIV who receive antiretroviral therapy are more likely to have metabolic syndrome than are their untreated counterparts, Dr. Julian Falutz said at an international congress on prediabetes and the metabolic syndrome.

Dr. Falutz and colleague Dr. Leonard Rosenthall compared several metabolic, HIV-related, and body-composition variables in two groups of HIV-positive men, one treated (172 patients) and one untreated (32 patients). Specific measurements included body mass index, waist circumference, blood pressure, trunk fat mass, fasting lipids, and glucose homeostasis markers. Metabolic syndrome among the men in both groups was assessed according to the five most commonly used sets of diagnostic criteria: NCEP (National Cholesterol Education Program), WHO (World Health Organization), IDF (International Diabetes Federation), EGIR (European Group for the Study of Insulin Resistance), and ACE (American College of Endocrinology).

The researchers found a statistically significant difference in the rate of metabolic syndrome as assessed by at least one of the classification schemes between the two groups. Overall, 20% of untreated individuals had at least one classification of metabolic syndrome, compared with almost 40% of treated men. However, there were substantial discrepancies between the rates of diagnosis of metabolic syndrome of the five classification schemes among the treated group, said Dr. Falutz, director of the HIV Metabolic Clinic at McGill University, Montreal.

With the NCEP criteria, metabolic syndrome prevalence in the treated group was 24%; under the WHO classification, it was 15%. The IDF criteria pegged the prevalence at 18%, under the EGIR criteria it was 24%, and ACE identified only 4% of the men as having metabolic syndrome.

These rates are similar to those in the general population, showing that “basically our patients are at similar risk for developing metabolic syndrome,” said Dr. Falutz. However, he added, “because the different published classification schemes do not identify the same people, there is a lack of consensus on how to diagnose metabolic syndrome.”

Dr. Falutz said he believes that more work needs to be done to sort out which classification scheme is best for predicting risk of cardiovascular events by linking diagnoses of metabolic syndrome to outcomes. “You need a very large group to be able to find out if the risk of myocardial infarction is increased, compared with other classifications,” he said. “We are going to see if we can use a combination of two classification schemes to see if people actually develop a myocardial infarction.”

Although Dr. Falutz's work is focused on patients with HIV, he said the problems he had encountered with narrowing down a definition of metabolic syndrome are applicable to other patient groups, too. “We looked at metabolic syndrome in our population because it is becoming an increasing problem,” he explained. “There are some people at higher risk, but you have to be careful when identifying them because no one classification scheme is the best, and we have to be aware of the controversy in the HIV-negative world. We may miss some people by using one [particular] scheme,” he warned.

BARCELONA — Although body mass index is a poor predictor of mortality from myocardial infarction in patients with diabetes, this measure should not be discounted altogether, Dr. Jonathan Shaw said at an international congress on prediabetes and metabolic syndrome.

“Within every tertile of BMI there is increasing risk with increasing waist-to-hip ratio, and with every tertile of waist-to-hip ratio there is increasing risk with [increasing] BMI, so both parameters give different information,” said Dr. Shaw, who is director of clinical research at Australia's Monash University, Clayton, Victoria. However, he added, BMI, waist-to-hip ratio, and waist circumference “are just proxy measures for the real problem: visceral obesity.”

Analyses of epidemiologic data looking at how BMI and waist-hip ratio predict cardiac dysfunction, such as those presented in the Heart Outcomes Prevention Evaluation study (N. Engl. J. Med. 2000;342:145–53), suggest that although BMI has little relation to mortality, there is a stronger association for waist circumference and waist-to-hip ratio. “Two individuals with the same BMI and waist circumference can have different depositions of visceral fat, so measurements of central obesity might be better at predicting MI than BMI,” Dr. Shaw said.

So how good is waist circumference at predicting risk? According to Dr. Shaw, Japanese data from 2002 (Circ. J. 2002;66:987–92) show a correlation between waist circumference and visceral fat, although the volume of this fat can vary between 40 cm

“Waist circumference was a significant predictor of changes in each of the other parameters, whereas none of the others predicted changes. Therefore, waist circumference seems to come before [the other parameters] and might be close to the core [driver of risk],” Dr. Shaw said.

In addition, cross-sectional associations between waist circumference and other risk factors or components of metabolic syndrome show that with increasing waist circumference, there is increasing prevalence of other risk factors. Dr. Shaw added that although there is little doubt that central obesity predicts cardiovascular disease risk, whether or not waist circumference and waist-to-hip ratio are independent of other risk factors is not yet confirmed.

Data from the AusDiab study reported by Dr. Shaw show that the greatest increases in waist circumference are occurring in younger people, and changes are 50% greater in women than in men. “If there is a target for public health campaigns to modify behavior, it is young women who need to be targeted,” Dr. Shaw said.

BARCELONA — Although body mass index is a poor predictor of mortality from myocardial infarction in patients with diabetes, this measure should not be discounted altogether, Dr. Jonathan Shaw said at an international congress on prediabetes and metabolic syndrome.

“Within every tertile of BMI there is increasing risk with increasing waist-to-hip ratio, and with every tertile of waist-to-hip ratio there is increasing risk with [increasing] BMI, so both parameters give different information,” said Dr. Shaw, who is director of clinical research at Australia's Monash University, Clayton, Victoria. However, he added, BMI, waist-to-hip ratio, and waist circumference “are just proxy measures for the real problem: visceral obesity.”

Analyses of epidemiologic data looking at how BMI and waist-hip ratio predict cardiac dysfunction, such as those presented in the Heart Outcomes Prevention Evaluation study (N. Engl. J. Med. 2000;342:145–53), suggest that although BMI has little relation to mortality, there is a stronger association for waist circumference and waist-to-hip ratio. “Two individuals with the same BMI and waist circumference can have different depositions of visceral fat, so measurements of central obesity might be better at predicting MI than BMI,” Dr. Shaw said.

So how good is waist circumference at predicting risk? According to Dr. Shaw, Japanese data from 2002 (Circ. J. 2002;66:987–92) show a correlation between waist circumference and visceral fat, although the volume of this fat can vary between 40 cm

“Waist circumference was a significant predictor of changes in each of the other parameters, whereas none of the others predicted changes. Therefore, waist circumference seems to come before [the other parameters] and might be close to the core [driver of risk],” Dr. Shaw said.

In addition, cross-sectional associations between waist circumference and other risk factors or components of metabolic syndrome show that with increasing waist circumference, there is increasing prevalence of other risk factors. Dr. Shaw added that although there is little doubt that central obesity predicts cardiovascular disease risk, whether or not waist circumference and waist-to-hip ratio are independent of other risk factors is not yet confirmed.

Data from the AusDiab study reported by Dr. Shaw show that the greatest increases in waist circumference are occurring in younger people, and changes are 50% greater in women than in men. “If there is a target for public health campaigns to modify behavior, it is young women who need to be targeted,” Dr. Shaw said.

BARCELONA — Although body mass index is a poor predictor of mortality from myocardial infarction in patients with diabetes, this measure should not be discounted altogether, Dr. Jonathan Shaw said at an international congress on prediabetes and metabolic syndrome.

“Within every tertile of BMI there is increasing risk with increasing waist-to-hip ratio, and with every tertile of waist-to-hip ratio there is increasing risk with [increasing] BMI, so both parameters give different information,” said Dr. Shaw, who is director of clinical research at Australia's Monash University, Clayton, Victoria. However, he added, BMI, waist-to-hip ratio, and waist circumference “are just proxy measures for the real problem: visceral obesity.”

Analyses of epidemiologic data looking at how BMI and waist-hip ratio predict cardiac dysfunction, such as those presented in the Heart Outcomes Prevention Evaluation study (N. Engl. J. Med. 2000;342:145–53), suggest that although BMI has little relation to mortality, there is a stronger association for waist circumference and waist-to-hip ratio. “Two individuals with the same BMI and waist circumference can have different depositions of visceral fat, so measurements of central obesity might be better at predicting MI than BMI,” Dr. Shaw said.

So how good is waist circumference at predicting risk? According to Dr. Shaw, Japanese data from 2002 (Circ. J. 2002;66:987–92) show a correlation between waist circumference and visceral fat, although the volume of this fat can vary between 40 cm

“Waist circumference was a significant predictor of changes in each of the other parameters, whereas none of the others predicted changes. Therefore, waist circumference seems to come before [the other parameters] and might be close to the core [driver of risk],” Dr. Shaw said.

In addition, cross-sectional associations between waist circumference and other risk factors or components of metabolic syndrome show that with increasing waist circumference, there is increasing prevalence of other risk factors. Dr. Shaw added that although there is little doubt that central obesity predicts cardiovascular disease risk, whether or not waist circumference and waist-to-hip ratio are independent of other risk factors is not yet confirmed.

Data from the AusDiab study reported by Dr. Shaw show that the greatest increases in waist circumference are occurring in younger people, and changes are 50% greater in women than in men. “If there is a target for public health campaigns to modify behavior, it is young women who need to be targeted,” Dr. Shaw said.

BARCELONA — Additional supplementation of olive oil in the diets of patients with type 2 diabetes may reduce their risk of cardiac problems, according to research presented at an international congress on prediabetes and metabolic syndrome.

In a preliminary study to identify a potential mechanism through which the Mediterranean diet protects against cardiovascular disease, Dr. Mohammed Hammami, head of the biochemistry laboratory, faculty of medicine, Monastir, Tunisia, and colleagues analyzed the relationship between homocysteine and other modifiable cardiovascular risk factors, including diet, in type 2 diabetes patients.

Previous work has linked high levels of homocysteine to a high prevalence of macroangiopathy, coronary heart disease, and renal insufficiency in patients with type 2 diabetes. In addition, clinical trials testing vitamin supplementation in these patients have resulted in decreased homocysteine levels in patients with diabetic dyslipidemia, suggesting that lowering homocysteine levels could reverse the lipid problems.

The researchers recruited 70 patients with type 2 diabetes and evaluated their nutritional habits based on a validated food frequency questionnaire. On average, those with diabetes consumed foods high in fat. Dr. Hammami and his colleagues measured mean homocysteine levels, which were 13.6 plus or minus 6.06 micromol/L for the group; 27.5% of participants had levels of plasma homocysteine assessed as high (greater than 15 micromol/L). Further studies showed an inverse correlation between homocysteine levels and dietary saturated fatty acids or daily cholesterol intake.

According to Dr. Hammami, plasma homocysteine levels were lower in patients with diabetes who consumed extra virgin olive oil than in those who consumed little or none (10 micromol/L vs. 14 micromol/L, respectively). “Our study supports other studies showing the beneficial effects of the Mediterranean diet on the cardiovascular risk factors, essentially on homocysteine levels,” he said.

“We have revealed a potential mechanism by which a Mediterranean type of diet may affect coronary risk,” Dr. Hammami continued. “The consumption of olive oil, the major fat in this diet type, may lead to decreased levels of homocysteine.”

He suggested that his study “should be followed up by investigations on the effects of the different components of olive oil”—not only oleic acid but also minor components such as vitamins and polyphenols—”on the reduction of homocysteine levels.” Dr. Hammami said he plans to do more extensive patient recruitment and supplementary analysis on such things as thiolactonase activity measurement.

BARCELONA — Additional supplementation of olive oil in the diets of patients with type 2 diabetes may reduce their risk of cardiac problems, according to research presented at an international congress on prediabetes and metabolic syndrome.

In a preliminary study to identify a potential mechanism through which the Mediterranean diet protects against cardiovascular disease, Dr. Mohammed Hammami, head of the biochemistry laboratory, faculty of medicine, Monastir, Tunisia, and colleagues analyzed the relationship between homocysteine and other modifiable cardiovascular risk factors, including diet, in type 2 diabetes patients.

Previous work has linked high levels of homocysteine to a high prevalence of macroangiopathy, coronary heart disease, and renal insufficiency in patients with type 2 diabetes. In addition, clinical trials testing vitamin supplementation in these patients have resulted in decreased homocysteine levels in patients with diabetic dyslipidemia, suggesting that lowering homocysteine levels could reverse the lipid problems.

The researchers recruited 70 patients with type 2 diabetes and evaluated their nutritional habits based on a validated food frequency questionnaire. On average, those with diabetes consumed foods high in fat. Dr. Hammami and his colleagues measured mean homocysteine levels, which were 13.6 plus or minus 6.06 micromol/L for the group; 27.5% of participants had levels of plasma homocysteine assessed as high (greater than 15 micromol/L). Further studies showed an inverse correlation between homocysteine levels and dietary saturated fatty acids or daily cholesterol intake.

According to Dr. Hammami, plasma homocysteine levels were lower in patients with diabetes who consumed extra virgin olive oil than in those who consumed little or none (10 micromol/L vs. 14 micromol/L, respectively). “Our study supports other studies showing the beneficial effects of the Mediterranean diet on the cardiovascular risk factors, essentially on homocysteine levels,” he said.

“We have revealed a potential mechanism by which a Mediterranean type of diet may affect coronary risk,” Dr. Hammami continued. “The consumption of olive oil, the major fat in this diet type, may lead to decreased levels of homocysteine.”

He suggested that his study “should be followed up by investigations on the effects of the different components of olive oil”—not only oleic acid but also minor components such as vitamins and polyphenols—”on the reduction of homocysteine levels.” Dr. Hammami said he plans to do more extensive patient recruitment and supplementary analysis on such things as thiolactonase activity measurement.

BARCELONA — Additional supplementation of olive oil in the diets of patients with type 2 diabetes may reduce their risk of cardiac problems, according to research presented at an international congress on prediabetes and metabolic syndrome.

In a preliminary study to identify a potential mechanism through which the Mediterranean diet protects against cardiovascular disease, Dr. Mohammed Hammami, head of the biochemistry laboratory, faculty of medicine, Monastir, Tunisia, and colleagues analyzed the relationship between homocysteine and other modifiable cardiovascular risk factors, including diet, in type 2 diabetes patients.

Previous work has linked high levels of homocysteine to a high prevalence of macroangiopathy, coronary heart disease, and renal insufficiency in patients with type 2 diabetes. In addition, clinical trials testing vitamin supplementation in these patients have resulted in decreased homocysteine levels in patients with diabetic dyslipidemia, suggesting that lowering homocysteine levels could reverse the lipid problems.

The researchers recruited 70 patients with type 2 diabetes and evaluated their nutritional habits based on a validated food frequency questionnaire. On average, those with diabetes consumed foods high in fat. Dr. Hammami and his colleagues measured mean homocysteine levels, which were 13.6 plus or minus 6.06 micromol/L for the group; 27.5% of participants had levels of plasma homocysteine assessed as high (greater than 15 micromol/L). Further studies showed an inverse correlation between homocysteine levels and dietary saturated fatty acids or daily cholesterol intake.

According to Dr. Hammami, plasma homocysteine levels were lower in patients with diabetes who consumed extra virgin olive oil than in those who consumed little or none (10 micromol/L vs. 14 micromol/L, respectively). “Our study supports other studies showing the beneficial effects of the Mediterranean diet on the cardiovascular risk factors, essentially on homocysteine levels,” he said.

“We have revealed a potential mechanism by which a Mediterranean type of diet may affect coronary risk,” Dr. Hammami continued. “The consumption of olive oil, the major fat in this diet type, may lead to decreased levels of homocysteine.”

He suggested that his study “should be followed up by investigations on the effects of the different components of olive oil”—not only oleic acid but also minor components such as vitamins and polyphenols—”on the reduction of homocysteine levels.” Dr. Hammami said he plans to do more extensive patient recruitment and supplementary analysis on such things as thiolactonase activity measurement.

BARCELONA — Patients with type 2 diabetes who have detectable coronary artery disease at diagnosis are at higher risk for cardiac events than are their counterparts in whom there is no evidence of atherosclerosis, Dr. Christoph Säly said at an international congress on prediabetes and the metabolic syndrome.

Current guidelines consider all patients with type 2 diabetes to have equivalent risk for developing a cardiac event. However, existing epidemiologic studies on the risk conferred by type 2 diabetes do not include data on the state of coronary arteries at baseline.

Dr. Säly and his colleagues from the Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria, reasoned that because “type 2 diabetes often represents a state of evolving coronary atherosclerosis,” coronary artery disease may be present in many patients but may not yet have caused clinical symptoms, and that this damage may underlie the increased cardiac risk of some patients.

“Previously undiagnosed CAD among patients with diabetes therefore may account largely for their increased cardiovascular risk, which thus is erroneously attributed to diabetes per se,” Dr. Säly said.

To test the effect of CAD on cardiovascular risk in patients with type 2 diabetes, the researchers studied 756 patients who were undergoing coronary angiography for the evaluation of CAD between October 1999 and October 2000. Of the sample, 244 had neither CAD nor type 2 diabetes at baseline, 50 had diabetes with no CAD, 342 had CAD with no diabetes, and 114 had both conditions. Six patients were excluded because they had type 1 diabetes. All study participants were followed for an average of 3.9 years, and cardiovascular events were identified through interviews and patient records.

Event-free survival was significantly lower in patients with both type 2 diabetes and CAD than in all other groups, but patients with type 2 diabetes in whom there was no coronary artery stenoses at baseline survived longer than patients who had CAD but no diabetes. Furthermore, patients with both diabetes and CAD had an event rate of 43%, which was significantly higher than all other groups, and patients with diabetes but no CAD had a significantly lower event rate than did patients with no diabetes but with detectable CAD.

“Type 2 diabetes in the absence of significant coronary stenoses carries a much better prognosis than previously assumed,” said Dr. Säly, adding that as long as the development of significant CAD can be prevented, patients with type 2 diabetes could have much better outcomes.

However, he cautioned, “patients with diabetes who at the baseline angiography of our study did not have significant coronary stenoses of course may develop such stenoses over time and then be at a high risk of vascular events. We therefore intend to perform follow-up examinations over a longer time period.”

The conclusion Dr. Säly and colleagues drew from their work is that “a combination of an angiographic and prospective study thus appears necessary to discern between the risk inherent to diabetes per se and that of evolving atherosclerosis.

“With this approach, the question should be answered whether an increased prevalence of CAD at baseline accounts for the high risk of diabetic patients or, alternatively, whether diabetes per se determines the risk.”

BARCELONA — Patients with type 2 diabetes who have detectable coronary artery disease at diagnosis are at higher risk for cardiac events than are their counterparts in whom there is no evidence of atherosclerosis, Dr. Christoph Säly said at an international congress on prediabetes and the metabolic syndrome.

Current guidelines consider all patients with type 2 diabetes to have equivalent risk for developing a cardiac event. However, existing epidemiologic studies on the risk conferred by type 2 diabetes do not include data on the state of coronary arteries at baseline.

Dr. Säly and his colleagues from the Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria, reasoned that because “type 2 diabetes often represents a state of evolving coronary atherosclerosis,” coronary artery disease may be present in many patients but may not yet have caused clinical symptoms, and that this damage may underlie the increased cardiac risk of some patients.

“Previously undiagnosed CAD among patients with diabetes therefore may account largely for their increased cardiovascular risk, which thus is erroneously attributed to diabetes per se,” Dr. Säly said.

To test the effect of CAD on cardiovascular risk in patients with type 2 diabetes, the researchers studied 756 patients who were undergoing coronary angiography for the evaluation of CAD between October 1999 and October 2000. Of the sample, 244 had neither CAD nor type 2 diabetes at baseline, 50 had diabetes with no CAD, 342 had CAD with no diabetes, and 114 had both conditions. Six patients were excluded because they had type 1 diabetes. All study participants were followed for an average of 3.9 years, and cardiovascular events were identified through interviews and patient records.

Event-free survival was significantly lower in patients with both type 2 diabetes and CAD than in all other groups, but patients with type 2 diabetes in whom there was no coronary artery stenoses at baseline survived longer than patients who had CAD but no diabetes. Furthermore, patients with both diabetes and CAD had an event rate of 43%, which was significantly higher than all other groups, and patients with diabetes but no CAD had a significantly lower event rate than did patients with no diabetes but with detectable CAD.

“Type 2 diabetes in the absence of significant coronary stenoses carries a much better prognosis than previously assumed,” said Dr. Säly, adding that as long as the development of significant CAD can be prevented, patients with type 2 diabetes could have much better outcomes.

However, he cautioned, “patients with diabetes who at the baseline angiography of our study did not have significant coronary stenoses of course may develop such stenoses over time and then be at a high risk of vascular events. We therefore intend to perform follow-up examinations over a longer time period.”

The conclusion Dr. Säly and colleagues drew from their work is that “a combination of an angiographic and prospective study thus appears necessary to discern between the risk inherent to diabetes per se and that of evolving atherosclerosis.

“With this approach, the question should be answered whether an increased prevalence of CAD at baseline accounts for the high risk of diabetic patients or, alternatively, whether diabetes per se determines the risk.”

BARCELONA — Patients with type 2 diabetes who have detectable coronary artery disease at diagnosis are at higher risk for cardiac events than are their counterparts in whom there is no evidence of atherosclerosis, Dr. Christoph Säly said at an international congress on prediabetes and the metabolic syndrome.

Current guidelines consider all patients with type 2 diabetes to have equivalent risk for developing a cardiac event. However, existing epidemiologic studies on the risk conferred by type 2 diabetes do not include data on the state of coronary arteries at baseline.

Dr. Säly and his colleagues from the Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria, reasoned that because “type 2 diabetes often represents a state of evolving coronary atherosclerosis,” coronary artery disease may be present in many patients but may not yet have caused clinical symptoms, and that this damage may underlie the increased cardiac risk of some patients.

“Previously undiagnosed CAD among patients with diabetes therefore may account largely for their increased cardiovascular risk, which thus is erroneously attributed to diabetes per se,” Dr. Säly said.

To test the effect of CAD on cardiovascular risk in patients with type 2 diabetes, the researchers studied 756 patients who were undergoing coronary angiography for the evaluation of CAD between October 1999 and October 2000. Of the sample, 244 had neither CAD nor type 2 diabetes at baseline, 50 had diabetes with no CAD, 342 had CAD with no diabetes, and 114 had both conditions. Six patients were excluded because they had type 1 diabetes. All study participants were followed for an average of 3.9 years, and cardiovascular events were identified through interviews and patient records.

Event-free survival was significantly lower in patients with both type 2 diabetes and CAD than in all other groups, but patients with type 2 diabetes in whom there was no coronary artery stenoses at baseline survived longer than patients who had CAD but no diabetes. Furthermore, patients with both diabetes and CAD had an event rate of 43%, which was significantly higher than all other groups, and patients with diabetes but no CAD had a significantly lower event rate than did patients with no diabetes but with detectable CAD.

“Type 2 diabetes in the absence of significant coronary stenoses carries a much better prognosis than previously assumed,” said Dr. Säly, adding that as long as the development of significant CAD can be prevented, patients with type 2 diabetes could have much better outcomes.

However, he cautioned, “patients with diabetes who at the baseline angiography of our study did not have significant coronary stenoses of course may develop such stenoses over time and then be at a high risk of vascular events. We therefore intend to perform follow-up examinations over a longer time period.”

The conclusion Dr. Säly and colleagues drew from their work is that “a combination of an angiographic and prospective study thus appears necessary to discern between the risk inherent to diabetes per se and that of evolving atherosclerosis.

“With this approach, the question should be answered whether an increased prevalence of CAD at baseline accounts for the high risk of diabetic patients or, alternatively, whether diabetes per se determines the risk.”

BARCELONA — It remains unclear whether people with psychiatric problems taking atypical antipsychotic medicines develop diabetes more frequently than do other people, according to the results of a systematic evidence review presented at an international congress on prediabetes and the metabolic syndrome.

Several previously published case reports and cross-sectional studies have suggested that there is an association between atypical antipsychotic agents and type 2 diabetes, said Jeffrey Johnson, Ph.D., of the Institute of Health Economics at the University of Alberta, Edmonton. So Dr. Johnson and a colleague, Lauren Brown, set out to do a systematic review of available evidence on this issue to examine whether the risk of type 2 diabetes in people with psychotic illnesses who are taking atypical antipsychotic agents is actually raised compared with individuals not taking these medications.

Dr. Johnson and Ms. Brown searched several electronic literature databases, including the Cochrane Library and Medline, to collect evidence for their study. The researchers identified 228 studies relating to this issue, of which 22 matched the inclusion criteria. The studies included those looking at populations of individuals diagnosed with schizophrenia or schizoaffective disorder who had been treated with clozapine, olanzapine, quetiapine, or risperidone, with type 2 diabetes diagnosis as an outcome. Selected studies were restricted to case-control trials or those with randomized controlled or cohort design.

Of the 22 studies selected for evaluation in the systematic review, 17 were retrospective cohort design and 5 were case-control studies. According to the researchers, the resulting group of investigations included a heterogeneous mix of psychotic illnesses, drugs, dosages, and comparison treatments, making the analysis of underlying effects difficult to ascertain. Heterogeneity between studies was related to study design, length of study, the stage at which the illness was diagnosed, medication dose, age of study population, and study quality.

By pooling the results of the studies with all treatments, Dr. Johnson and Ms. Brown calculated that the odds ratio for a diagnosis of diabetes in people taking any atypical antipsychotic agent compared with controls was 1.16 (95% confidence interval 1.01–1.33) in favor of the treatment, suggesting that the treatment slightly increased the risk of type 2 diabetes. But when Dr. Johnson and Ms. Brown did a separate analysis looking at diagnoses of type 2 diabetes in people taking just two drugs—risperidone or olanzapine—the odds ratio was 1.10 (95% CI 0.96–1.27), with the effect slightly bigger with olanzapine.

“Based on inconsistent results of the available observational studies, it is unclear whether atypical antipsychotic agents increase risk of diabetes compared with controls,” Dr. Johnson said. He also cautioned that the overall effect sizes must be interpreted with care “due to a significant heterogeneity between studies, and because the overall effect sizes were calculated based on unadjusted odds ratios.”

Dr. Johnson added that “Until more information regarding the relationship between atypical antipsychotic agents and diabetes is available, individuals taking atypical antipsychotics should have baseline and follow-up metabolic evaluations.”

BARCELONA — It remains unclear whether people with psychiatric problems taking atypical antipsychotic medicines develop diabetes more frequently than do other people, according to the results of a systematic evidence review presented at an international congress on prediabetes and the metabolic syndrome.

Several previously published case reports and cross-sectional studies have suggested that there is an association between atypical antipsychotic agents and type 2 diabetes, said Jeffrey Johnson, Ph.D., of the Institute of Health Economics at the University of Alberta, Edmonton. So Dr. Johnson and a colleague, Lauren Brown, set out to do a systematic review of available evidence on this issue to examine whether the risk of type 2 diabetes in people with psychotic illnesses who are taking atypical antipsychotic agents is actually raised compared with individuals not taking these medications.

Dr. Johnson and Ms. Brown searched several electronic literature databases, including the Cochrane Library and Medline, to collect evidence for their study. The researchers identified 228 studies relating to this issue, of which 22 matched the inclusion criteria. The studies included those looking at populations of individuals diagnosed with schizophrenia or schizoaffective disorder who had been treated with clozapine, olanzapine, quetiapine, or risperidone, with type 2 diabetes diagnosis as an outcome. Selected studies were restricted to case-control trials or those with randomized controlled or cohort design.

Of the 22 studies selected for evaluation in the systematic review, 17 were retrospective cohort design and 5 were case-control studies. According to the researchers, the resulting group of investigations included a heterogeneous mix of psychotic illnesses, drugs, dosages, and comparison treatments, making the analysis of underlying effects difficult to ascertain. Heterogeneity between studies was related to study design, length of study, the stage at which the illness was diagnosed, medication dose, age of study population, and study quality.

By pooling the results of the studies with all treatments, Dr. Johnson and Ms. Brown calculated that the odds ratio for a diagnosis of diabetes in people taking any atypical antipsychotic agent compared with controls was 1.16 (95% confidence interval 1.01–1.33) in favor of the treatment, suggesting that the treatment slightly increased the risk of type 2 diabetes. But when Dr. Johnson and Ms. Brown did a separate analysis looking at diagnoses of type 2 diabetes in people taking just two drugs—risperidone or olanzapine—the odds ratio was 1.10 (95% CI 0.96–1.27), with the effect slightly bigger with olanzapine.

“Based on inconsistent results of the available observational studies, it is unclear whether atypical antipsychotic agents increase risk of diabetes compared with controls,” Dr. Johnson said. He also cautioned that the overall effect sizes must be interpreted with care “due to a significant heterogeneity between studies, and because the overall effect sizes were calculated based on unadjusted odds ratios.”

Dr. Johnson added that “Until more information regarding the relationship between atypical antipsychotic agents and diabetes is available, individuals taking atypical antipsychotics should have baseline and follow-up metabolic evaluations.”

BARCELONA — It remains unclear whether people with psychiatric problems taking atypical antipsychotic medicines develop diabetes more frequently than do other people, according to the results of a systematic evidence review presented at an international congress on prediabetes and the metabolic syndrome.

Several previously published case reports and cross-sectional studies have suggested that there is an association between atypical antipsychotic agents and type 2 diabetes, said Jeffrey Johnson, Ph.D., of the Institute of Health Economics at the University of Alberta, Edmonton. So Dr. Johnson and a colleague, Lauren Brown, set out to do a systematic review of available evidence on this issue to examine whether the risk of type 2 diabetes in people with psychotic illnesses who are taking atypical antipsychotic agents is actually raised compared with individuals not taking these medications.

Dr. Johnson and Ms. Brown searched several electronic literature databases, including the Cochrane Library and Medline, to collect evidence for their study. The researchers identified 228 studies relating to this issue, of which 22 matched the inclusion criteria. The studies included those looking at populations of individuals diagnosed with schizophrenia or schizoaffective disorder who had been treated with clozapine, olanzapine, quetiapine, or risperidone, with type 2 diabetes diagnosis as an outcome. Selected studies were restricted to case-control trials or those with randomized controlled or cohort design.

Of the 22 studies selected for evaluation in the systematic review, 17 were retrospective cohort design and 5 were case-control studies. According to the researchers, the resulting group of investigations included a heterogeneous mix of psychotic illnesses, drugs, dosages, and comparison treatments, making the analysis of underlying effects difficult to ascertain. Heterogeneity between studies was related to study design, length of study, the stage at which the illness was diagnosed, medication dose, age of study population, and study quality.

By pooling the results of the studies with all treatments, Dr. Johnson and Ms. Brown calculated that the odds ratio for a diagnosis of diabetes in people taking any atypical antipsychotic agent compared with controls was 1.16 (95% confidence interval 1.01–1.33) in favor of the treatment, suggesting that the treatment slightly increased the risk of type 2 diabetes. But when Dr. Johnson and Ms. Brown did a separate analysis looking at diagnoses of type 2 diabetes in people taking just two drugs—risperidone or olanzapine—the odds ratio was 1.10 (95% CI 0.96–1.27), with the effect slightly bigger with olanzapine.

“Based on inconsistent results of the available observational studies, it is unclear whether atypical antipsychotic agents increase risk of diabetes compared with controls,” Dr. Johnson said. He also cautioned that the overall effect sizes must be interpreted with care “due to a significant heterogeneity between studies, and because the overall effect sizes were calculated based on unadjusted odds ratios.”

Dr. Johnson added that “Until more information regarding the relationship between atypical antipsychotic agents and diabetes is available, individuals taking atypical antipsychotics should have baseline and follow-up metabolic evaluations.”

BARCELONA — Additional supplementation of olive oil in the diets of patients with type 2 diabetes may reduce their risk of cardiac problems, according to research presented at an international congress on prediabetes and metabolic syndrome.

In a preliminary study to identify a potential mechanism through which the Mediterranean diet protects against cardiovascular disease, Dr. Mohammed Hammami, head of the biochemistry laboratory, Universeté du Centre, Monastir, Tunisia, and colleagues analyzed the relationship between homocysteine and other modifiable cardiovascular risk factors, including diet, in type 2 diabetes patients.

Previous work has linked high levels of homocysteine to a high prevalence of macroangiopathy, coronary heart disease, and renal insufficiency in patients with type 2 diabetes. In addition, clinical trials testing vitamin supplementation in these patients have resulted in decreased homocysteine levels in patients with diabetic dyslipidemia, suggesting that lowering homocysteine levels could reverse the lipid problems.

The researchers recruited 70 patients with type 2 diabetes and evaluated their nutritional habits based on a validated food frequency questionnaire. On average, those with diabetes consumed foods high in fat. Dr. Hammami and his colleagues measured mean homocysteine levels, which were 13.6 plus or minus 6.06 micromol/L for the group; 27.5% of participants had levels of plasma homocysteine assessed as high (greater than 15 micromol/L). Further studies showed an inverse correlation between homocysteine levels and dietary saturated fatty acids or daily cholesterol intake.

According to Dr. Hammami, plasma homocysteine levels were lower in patients with diabetes who consumed extra virgin olive oil than in those who consumed little or none (10 micromol/L vs. 14 micromol/L, respectively). “Our study supports other studies showing the beneficial effects of the Mediterranean diet on the cardiovascular risk factors, essentially on homocysteine levels,” he said.

“We have revealed a potential mechanism by which a Mediterranean type of diet may affect coronary risk,” Dr. Hammami continued. “The consumption of olive oil, the major fat in this diet type, may lead to decreased levels of homocysteine.”

He suggested that his study “should be followed up by investigations on the effects of the different components of olive oil”—not only oleic acid but also minor components such as vitamins and polyphenols—”on the reduction of homocysteine levels.” Dr. Hammami said he plans to do more extensive patient recruitment and supplementary analysis on such things as thiolactonase activity measurement.

BARCELONA — Additional supplementation of olive oil in the diets of patients with type 2 diabetes may reduce their risk of cardiac problems, according to research presented at an international congress on prediabetes and metabolic syndrome.

In a preliminary study to identify a potential mechanism through which the Mediterranean diet protects against cardiovascular disease, Dr. Mohammed Hammami, head of the biochemistry laboratory, Universeté du Centre, Monastir, Tunisia, and colleagues analyzed the relationship between homocysteine and other modifiable cardiovascular risk factors, including diet, in type 2 diabetes patients.

Previous work has linked high levels of homocysteine to a high prevalence of macroangiopathy, coronary heart disease, and renal insufficiency in patients with type 2 diabetes. In addition, clinical trials testing vitamin supplementation in these patients have resulted in decreased homocysteine levels in patients with diabetic dyslipidemia, suggesting that lowering homocysteine levels could reverse the lipid problems.

The researchers recruited 70 patients with type 2 diabetes and evaluated their nutritional habits based on a validated food frequency questionnaire. On average, those with diabetes consumed foods high in fat. Dr. Hammami and his colleagues measured mean homocysteine levels, which were 13.6 plus or minus 6.06 micromol/L for the group; 27.5% of participants had levels of plasma homocysteine assessed as high (greater than 15 micromol/L). Further studies showed an inverse correlation between homocysteine levels and dietary saturated fatty acids or daily cholesterol intake.

According to Dr. Hammami, plasma homocysteine levels were lower in patients with diabetes who consumed extra virgin olive oil than in those who consumed little or none (10 micromol/L vs. 14 micromol/L, respectively). “Our study supports other studies showing the beneficial effects of the Mediterranean diet on the cardiovascular risk factors, essentially on homocysteine levels,” he said.

“We have revealed a potential mechanism by which a Mediterranean type of diet may affect coronary risk,” Dr. Hammami continued. “The consumption of olive oil, the major fat in this diet type, may lead to decreased levels of homocysteine.”

He suggested that his study “should be followed up by investigations on the effects of the different components of olive oil”—not only oleic acid but also minor components such as vitamins and polyphenols—”on the reduction of homocysteine levels.” Dr. Hammami said he plans to do more extensive patient recruitment and supplementary analysis on such things as thiolactonase activity measurement.

BARCELONA — Additional supplementation of olive oil in the diets of patients with type 2 diabetes may reduce their risk of cardiac problems, according to research presented at an international congress on prediabetes and metabolic syndrome.

In a preliminary study to identify a potential mechanism through which the Mediterranean diet protects against cardiovascular disease, Dr. Mohammed Hammami, head of the biochemistry laboratory, Universeté du Centre, Monastir, Tunisia, and colleagues analyzed the relationship between homocysteine and other modifiable cardiovascular risk factors, including diet, in type 2 diabetes patients.

Previous work has linked high levels of homocysteine to a high prevalence of macroangiopathy, coronary heart disease, and renal insufficiency in patients with type 2 diabetes. In addition, clinical trials testing vitamin supplementation in these patients have resulted in decreased homocysteine levels in patients with diabetic dyslipidemia, suggesting that lowering homocysteine levels could reverse the lipid problems.

The researchers recruited 70 patients with type 2 diabetes and evaluated their nutritional habits based on a validated food frequency questionnaire. On average, those with diabetes consumed foods high in fat. Dr. Hammami and his colleagues measured mean homocysteine levels, which were 13.6 plus or minus 6.06 micromol/L for the group; 27.5% of participants had levels of plasma homocysteine assessed as high (greater than 15 micromol/L). Further studies showed an inverse correlation between homocysteine levels and dietary saturated fatty acids or daily cholesterol intake.

According to Dr. Hammami, plasma homocysteine levels were lower in patients with diabetes who consumed extra virgin olive oil than in those who consumed little or none (10 micromol/L vs. 14 micromol/L, respectively). “Our study supports other studies showing the beneficial effects of the Mediterranean diet on the cardiovascular risk factors, essentially on homocysteine levels,” he said.

“We have revealed a potential mechanism by which a Mediterranean type of diet may affect coronary risk,” Dr. Hammami continued. “The consumption of olive oil, the major fat in this diet type, may lead to decreased levels of homocysteine.”

He suggested that his study “should be followed up by investigations on the effects of the different components of olive oil”—not only oleic acid but also minor components such as vitamins and polyphenols—”on the reduction of homocysteine levels.” Dr. Hammami said he plans to do more extensive patient recruitment and supplementary analysis on such things as thiolactonase activity measurement.

BARCELONA — Patients with HIV who are treated with antiretrovirals are more likely to have metabolic syndrome than are their untreated counterparts, Dr. Julian Falutz said at an international congress on prediabetes and the metabolic syndrome.

Dr Falutz and colleague Dr. Leonard Rosenthall compared several metabolic, HIV-related, and body-composition variables in two groups of HIV-positive men, one treated (172 patients) and one untreated (32 patients). Specific measurements included body mass index, waist circumference, blood pressure, trunk fat mass, fasting lipids, and glucose homeostasis markers.

Metabolic syndrome among the men in both of the groups was assessed according to the five most commonly used sets of diagnostic criteria: NCEP (National Cholesterol Education Program), WHO (World Health Organization), IDF (International Diabetes Federation), EGIR (European Group for the Study of Insulin Resistance), and ACE (American College of Endocrinology).

The researchers found a statistically significant difference in the rate of metabolic syndrome as assessed by at least one of the classification schemes between the two groups. Overall, 20% of untreated individuals had at least one classification of metabolic syndrome, compared with almost 40% of treated men. However, there were substantial discrepancies between the rates of diagnosis of metabolic syndrome of the five classification schemes among the treated group, said Dr. Falutz, director of the HIV Metabolic Clinic at McGill University, Montreal.

With the NCEP criteria, metabolic syndrome prevalence in the treated group was 24%; under the WHO classification, it was 15%. The IDF criteria pegged the prevalence at 18%, under the EGIR criteria it was 24%, and ACE identified only 4% of the men as having metabolic syndrome. These rates are similar to those in the general population, showing that “basically our patients are at similar risk for developing metabolic syndrome,” said Dr. Falutz.

However, he added, “because the different published classification schemes do not identify the same people, there is a lack of consensus on how to diagnose metabolic syndrome.”

Dr. Falutz said he believes that more work needs to be done to sort out which classification scheme is best for predicting risk of cardiovascular events by linking diagnoses of metabolic syndrome to outcomes. “You need a very large group to be able to find out if the risk of myocardial infarction is increased, compared with other classifications,” he said. “We are going to see if we can use a combination of two classification schemes to see if people actually develop a myocardial infarction.”

Although Dr. Falutz's work is focused on patients with HIV, he said the problems he had encountered with narrowing down a definition of metabolic syndrome are applicable to other patient groups, too. “We looked at metabolic syndrome in our population because it is becoming an increasing problem,” he explained.

“There are some people at higher risk, but you have to be careful when identifying them because no one classification scheme is the best, and we have to be aware of the controversy in the HIV-negative world. We may miss some people by using one [particular] scheme,” he warned.

BARCELONA — Patients with HIV who are treated with antiretrovirals are more likely to have metabolic syndrome than are their untreated counterparts, Dr. Julian Falutz said at an international congress on prediabetes and the metabolic syndrome.

Dr Falutz and colleague Dr. Leonard Rosenthall compared several metabolic, HIV-related, and body-composition variables in two groups of HIV-positive men, one treated (172 patients) and one untreated (32 patients). Specific measurements included body mass index, waist circumference, blood pressure, trunk fat mass, fasting lipids, and glucose homeostasis markers.

Metabolic syndrome among the men in both of the groups was assessed according to the five most commonly used sets of diagnostic criteria: NCEP (National Cholesterol Education Program), WHO (World Health Organization), IDF (International Diabetes Federation), EGIR (European Group for the Study of Insulin Resistance), and ACE (American College of Endocrinology).

The researchers found a statistically significant difference in the rate of metabolic syndrome as assessed by at least one of the classification schemes between the two groups. Overall, 20% of untreated individuals had at least one classification of metabolic syndrome, compared with almost 40% of treated men. However, there were substantial discrepancies between the rates of diagnosis of metabolic syndrome of the five classification schemes among the treated group, said Dr. Falutz, director of the HIV Metabolic Clinic at McGill University, Montreal.

With the NCEP criteria, metabolic syndrome prevalence in the treated group was 24%; under the WHO classification, it was 15%. The IDF criteria pegged the prevalence at 18%, under the EGIR criteria it was 24%, and ACE identified only 4% of the men as having metabolic syndrome. These rates are similar to those in the general population, showing that “basically our patients are at similar risk for developing metabolic syndrome,” said Dr. Falutz.

However, he added, “because the different published classification schemes do not identify the same people, there is a lack of consensus on how to diagnose metabolic syndrome.”

Dr. Falutz said he believes that more work needs to be done to sort out which classification scheme is best for predicting risk of cardiovascular events by linking diagnoses of metabolic syndrome to outcomes. “You need a very large group to be able to find out if the risk of myocardial infarction is increased, compared with other classifications,” he said. “We are going to see if we can use a combination of two classification schemes to see if people actually develop a myocardial infarction.”

Although Dr. Falutz's work is focused on patients with HIV, he said the problems he had encountered with narrowing down a definition of metabolic syndrome are applicable to other patient groups, too. “We looked at metabolic syndrome in our population because it is becoming an increasing problem,” he explained.

“There are some people at higher risk, but you have to be careful when identifying them because no one classification scheme is the best, and we have to be aware of the controversy in the HIV-negative world. We may miss some people by using one [particular] scheme,” he warned.

BARCELONA — Patients with HIV who are treated with antiretrovirals are more likely to have metabolic syndrome than are their untreated counterparts, Dr. Julian Falutz said at an international congress on prediabetes and the metabolic syndrome.

Dr Falutz and colleague Dr. Leonard Rosenthall compared several metabolic, HIV-related, and body-composition variables in two groups of HIV-positive men, one treated (172 patients) and one untreated (32 patients). Specific measurements included body mass index, waist circumference, blood pressure, trunk fat mass, fasting lipids, and glucose homeostasis markers.

Metabolic syndrome among the men in both of the groups was assessed according to the five most commonly used sets of diagnostic criteria: NCEP (National Cholesterol Education Program), WHO (World Health Organization), IDF (International Diabetes Federation), EGIR (European Group for the Study of Insulin Resistance), and ACE (American College of Endocrinology).

The researchers found a statistically significant difference in the rate of metabolic syndrome as assessed by at least one of the classification schemes between the two groups. Overall, 20% of untreated individuals had at least one classification of metabolic syndrome, compared with almost 40% of treated men. However, there were substantial discrepancies between the rates of diagnosis of metabolic syndrome of the five classification schemes among the treated group, said Dr. Falutz, director of the HIV Metabolic Clinic at McGill University, Montreal.

With the NCEP criteria, metabolic syndrome prevalence in the treated group was 24%; under the WHO classification, it was 15%. The IDF criteria pegged the prevalence at 18%, under the EGIR criteria it was 24%, and ACE identified only 4% of the men as having metabolic syndrome. These rates are similar to those in the general population, showing that “basically our patients are at similar risk for developing metabolic syndrome,” said Dr. Falutz.

However, he added, “because the different published classification schemes do not identify the same people, there is a lack of consensus on how to diagnose metabolic syndrome.”

Dr. Falutz said he believes that more work needs to be done to sort out which classification scheme is best for predicting risk of cardiovascular events by linking diagnoses of metabolic syndrome to outcomes. “You need a very large group to be able to find out if the risk of myocardial infarction is increased, compared with other classifications,” he said. “We are going to see if we can use a combination of two classification schemes to see if people actually develop a myocardial infarction.”

Although Dr. Falutz's work is focused on patients with HIV, he said the problems he had encountered with narrowing down a definition of metabolic syndrome are applicable to other patient groups, too. “We looked at metabolic syndrome in our population because it is becoming an increasing problem,” he explained.

“There are some people at higher risk, but you have to be careful when identifying them because no one classification scheme is the best, and we have to be aware of the controversy in the HIV-negative world. We may miss some people by using one [particular] scheme,” he warned.

GLASGOW, SCOTLAND — Serum fibrosis markers—currently used as a research tool—have high sensitivity and specificity for diagnosing more severe forms of nonalcoholic fatty liver disease, according to a presentation at the Diabetes U.K. Annual Professional Conference.

Diagnosis of the most severe forms of nonalcoholic fatty liver disease (NAFLD), which include the onset of steatohepatitis and subsequent fibrosis and cirrhosis, requires measurement of the extent of inflammation and the presence of fibrosis. Currently, only liver biopsy can identify patients with these symptoms; such patients must be managed more aggressively than patients with less severe forms of the disease, particularly with respect to cardiovascular risk factors. However, biopsy is an expensive diagnostic procedure and is dangerous for the patient.

Dr. Christopher Byrne, head of the endocrinology and metabolism unit at the University of Southampton (England), said he believes that “in future, noninvasive serum markers might be better. Research is beginning to suggest that within NAFLD, a scoring system such as that using ELF [enhanced liver fibrosis assay, which looks at several serum biomarkers of fibrosis] might prove useful.” When combined with age as a risk factor, the three markers assessed by the ELF blood test—hyaluronic acid, procollagen III amino terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1)—have around 85% specificity and sensitivity for moderate to severe NAFLD, he noted.

Alanine aminotransferase (ALT) and GammaGT, plasma markers currently used to help guide diagnosis for NAFLD, are not very accurate, according to Dr. Byrne. “ALT is an extraordinarily poor proxy. Both GammaGT and ALT are in the normal range in patients who have quite extensive NAFLD when they get to biopsy,” he said.

NAFLD is one of the most common forms of chronic liver disease in developed countries, affecting 10%–24% of the general population, and it is especially common in people with type 2 diabetes. Liver damage in this condition is caused by accumulation of lipids, oxidative stress, and inflammation caused by release of proinflammatory cytokines. The associated marked insulin resistance in NAFLD has led some scientists to propose that it might be a malignant form of metabolic syndrome.

“Even adjusting for obesity, patients with NAFLD have marked increases in nonesterified fatty acid accumulation,” Dr. Byrne said. “So release of these from adipocyte depots into circulation is abnormal in these patients. But we don't know why [it is] associated with marked insulin resistance.”

He presented research showing that a group of 1,974 type 2 diabetes patients with NAFLD had a significantly higher prevalence of coronary, cerebral, and peripheral cardiovascular disease than a group of 418 type 2 diabetics without fatty livers. “NAFLD is associated with increased mortality, especially at the more severe end,” Dr. Byrne said. “In these patients, even adjusting for all conventional cardiovascular risk factors and features of the metabolic syndrome, NAFLD is an independent cardiovascular risk factor. If you find NAFLD, think accelerated cardiovascular risk and treat aggressively.”

Treatment recommendations include initial weight loss in obese patients; limited evidence suggests that therapy with glitazones also can be used to increase insulin sensitivity and decrease liver fat content. “Glitazones show promise,” Dr. Byrne said. “A new indication for glitazone therapy may prove to be NAFLD.”

GLASGOW, SCOTLAND — Serum fibrosis markers—currently used as a research tool—have high sensitivity and specificity for diagnosing more severe forms of nonalcoholic fatty liver disease, according to a presentation at the Diabetes U.K. Annual Professional Conference.

Diagnosis of the most severe forms of nonalcoholic fatty liver disease (NAFLD), which include the onset of steatohepatitis and subsequent fibrosis and cirrhosis, requires measurement of the extent of inflammation and the presence of fibrosis. Currently, only liver biopsy can identify patients with these symptoms; such patients must be managed more aggressively than patients with less severe forms of the disease, particularly with respect to cardiovascular risk factors. However, biopsy is an expensive diagnostic procedure and is dangerous for the patient.

Dr. Christopher Byrne, head of the endocrinology and metabolism unit at the University of Southampton (England), said he believes that “in future, noninvasive serum markers might be better. Research is beginning to suggest that within NAFLD, a scoring system such as that using ELF [enhanced liver fibrosis assay, which looks at several serum biomarkers of fibrosis] might prove useful.” When combined with age as a risk factor, the three markers assessed by the ELF blood test—hyaluronic acid, procollagen III amino terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1)—have around 85% specificity and sensitivity for moderate to severe NAFLD, he noted.

Alanine aminotransferase (ALT) and GammaGT, plasma markers currently used to help guide diagnosis for NAFLD, are not very accurate, according to Dr. Byrne. “ALT is an extraordinarily poor proxy. Both GammaGT and ALT are in the normal range in patients who have quite extensive NAFLD when they get to biopsy,” he said.

NAFLD is one of the most common forms of chronic liver disease in developed countries, affecting 10%–24% of the general population, and it is especially common in people with type 2 diabetes. Liver damage in this condition is caused by accumulation of lipids, oxidative stress, and inflammation caused by release of proinflammatory cytokines. The associated marked insulin resistance in NAFLD has led some scientists to propose that it might be a malignant form of metabolic syndrome.

“Even adjusting for obesity, patients with NAFLD have marked increases in nonesterified fatty acid accumulation,” Dr. Byrne said. “So release of these from adipocyte depots into circulation is abnormal in these patients. But we don't know why [it is] associated with marked insulin resistance.”

He presented research showing that a group of 1,974 type 2 diabetes patients with NAFLD had a significantly higher prevalence of coronary, cerebral, and peripheral cardiovascular disease than a group of 418 type 2 diabetics without fatty livers. “NAFLD is associated with increased mortality, especially at the more severe end,” Dr. Byrne said. “In these patients, even adjusting for all conventional cardiovascular risk factors and features of the metabolic syndrome, NAFLD is an independent cardiovascular risk factor. If you find NAFLD, think accelerated cardiovascular risk and treat aggressively.”

Treatment recommendations include initial weight loss in obese patients; limited evidence suggests that therapy with glitazones also can be used to increase insulin sensitivity and decrease liver fat content. “Glitazones show promise,” Dr. Byrne said. “A new indication for glitazone therapy may prove to be NAFLD.”

GLASGOW, SCOTLAND — Serum fibrosis markers—currently used as a research tool—have high sensitivity and specificity for diagnosing more severe forms of nonalcoholic fatty liver disease, according to a presentation at the Diabetes U.K. Annual Professional Conference.

Diagnosis of the most severe forms of nonalcoholic fatty liver disease (NAFLD), which include the onset of steatohepatitis and subsequent fibrosis and cirrhosis, requires measurement of the extent of inflammation and the presence of fibrosis. Currently, only liver biopsy can identify patients with these symptoms; such patients must be managed more aggressively than patients with less severe forms of the disease, particularly with respect to cardiovascular risk factors. However, biopsy is an expensive diagnostic procedure and is dangerous for the patient.

Dr. Christopher Byrne, head of the endocrinology and metabolism unit at the University of Southampton (England), said he believes that “in future, noninvasive serum markers might be better. Research is beginning to suggest that within NAFLD, a scoring system such as that using ELF [enhanced liver fibrosis assay, which looks at several serum biomarkers of fibrosis] might prove useful.” When combined with age as a risk factor, the three markers assessed by the ELF blood test—hyaluronic acid, procollagen III amino terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1)—have around 85% specificity and sensitivity for moderate to severe NAFLD, he noted.

Alanine aminotransferase (ALT) and GammaGT, plasma markers currently used to help guide diagnosis for NAFLD, are not very accurate, according to Dr. Byrne. “ALT is an extraordinarily poor proxy. Both GammaGT and ALT are in the normal range in patients who have quite extensive NAFLD when they get to biopsy,” he said.

NAFLD is one of the most common forms of chronic liver disease in developed countries, affecting 10%–24% of the general population, and it is especially common in people with type 2 diabetes. Liver damage in this condition is caused by accumulation of lipids, oxidative stress, and inflammation caused by release of proinflammatory cytokines. The associated marked insulin resistance in NAFLD has led some scientists to propose that it might be a malignant form of metabolic syndrome.

“Even adjusting for obesity, patients with NAFLD have marked increases in nonesterified fatty acid accumulation,” Dr. Byrne said. “So release of these from adipocyte depots into circulation is abnormal in these patients. But we don't know why [it is] associated with marked insulin resistance.”

He presented research showing that a group of 1,974 type 2 diabetes patients with NAFLD had a significantly higher prevalence of coronary, cerebral, and peripheral cardiovascular disease than a group of 418 type 2 diabetics without fatty livers. “NAFLD is associated with increased mortality, especially at the more severe end,” Dr. Byrne said. “In these patients, even adjusting for all conventional cardiovascular risk factors and features of the metabolic syndrome, NAFLD is an independent cardiovascular risk factor. If you find NAFLD, think accelerated cardiovascular risk and treat aggressively.”

Treatment recommendations include initial weight loss in obese patients; limited evidence suggests that therapy with glitazones also can be used to increase insulin sensitivity and decrease liver fat content. “Glitazones show promise,” Dr. Byrne said. “A new indication for glitazone therapy may prove to be NAFLD.”

BARCELONA — Changes in body fat may underlie the higher risk of metabolic complications observed in HIV-positive people, Dr. Esteban Martinez said at an international congress on prediabetes and the metabolic syndrome.

Antiretroviral therapy (ART) has changed HIV infection from a rapidly fatal disease into a chronic condition, but this has resulted in an aging population of HIV-positive individuals that seems to be at higher-than-expected risk of diabetes and cardiovascular disease, said Dr. Martinez of the Hospital Clinic at the University of Barcelona. Over time, this problem will become more significant as a larger number of people live with the infection.

One of the observations to result from studies of long-living individuals with HIV is the development of body fat changes, including the thinning of extremities, loss of subcutaneous fat, potential for accumulating fat in the abdomen, and a risk of accumulating fat in the “buffalo hump” at the top of the shoulders. “These abnormalities might be associated with metabolic problems,” Dr. Martinez said.

HIV is known to decrease plasma concentrations of cholesterol—both low- and high-density lipoproteins—and induce fat loss. However, the initiation of ART induces fat gain followed by limb fat loss. “After a certain time point, some patients will experience a small loss of central abdominal fat, which then becomes stable, but the limb fat goes right down, which can change the way people look,” Dr. Martinez said. Lipid values go up, in some cases above prestudy values, he added. “For any ART that is going to be initiated in a patient, you can expect lipids to increase.” But the magnitude of the increase depends on the type of therapy used.

Insulin resistance also is common in patients with lipodystrophy and is associated with limb fat loss. Dr. Martinez reported a small study (J. Acquir. Immune Defic. Syndr. 2000;25:312–21) of 15 patients with HIV-associated lipodystrophy, 14 HIV-infected people without fat changes, and 12 non-HIV-infected controls. Low insulin sensitivity was closely associated with the loss of peripheral fat in the HIV and lipodystrophy group, Dr. Martinez said.

BARCELONA — Changes in body fat may underlie the higher risk of metabolic complications observed in HIV-positive people, Dr. Esteban Martinez said at an international congress on prediabetes and the metabolic syndrome.

Antiretroviral therapy (ART) has changed HIV infection from a rapidly fatal disease into a chronic condition, but this has resulted in an aging population of HIV-positive individuals that seems to be at higher-than-expected risk of diabetes and cardiovascular disease, said Dr. Martinez of the Hospital Clinic at the University of Barcelona. Over time, this problem will become more significant as a larger number of people live with the infection.

One of the observations to result from studies of long-living individuals with HIV is the development of body fat changes, including the thinning of extremities, loss of subcutaneous fat, potential for accumulating fat in the abdomen, and a risk of accumulating fat in the “buffalo hump” at the top of the shoulders. “These abnormalities might be associated with metabolic problems,” Dr. Martinez said.

HIV is known to decrease plasma concentrations of cholesterol—both low- and high-density lipoproteins—and induce fat loss. However, the initiation of ART induces fat gain followed by limb fat loss. “After a certain time point, some patients will experience a small loss of central abdominal fat, which then becomes stable, but the limb fat goes right down, which can change the way people look,” Dr. Martinez said. Lipid values go up, in some cases above prestudy values, he added. “For any ART that is going to be initiated in a patient, you can expect lipids to increase.” But the magnitude of the increase depends on the type of therapy used.

Insulin resistance also is common in patients with lipodystrophy and is associated with limb fat loss. Dr. Martinez reported a small study (J. Acquir. Immune Defic. Syndr. 2000;25:312–21) of 15 patients with HIV-associated lipodystrophy, 14 HIV-infected people without fat changes, and 12 non-HIV-infected controls. Low insulin sensitivity was closely associated with the loss of peripheral fat in the HIV and lipodystrophy group, Dr. Martinez said.

BARCELONA — Changes in body fat may underlie the higher risk of metabolic complications observed in HIV-positive people, Dr. Esteban Martinez said at an international congress on prediabetes and the metabolic syndrome.

Antiretroviral therapy (ART) has changed HIV infection from a rapidly fatal disease into a chronic condition, but this has resulted in an aging population of HIV-positive individuals that seems to be at higher-than-expected risk of diabetes and cardiovascular disease, said Dr. Martinez of the Hospital Clinic at the University of Barcelona. Over time, this problem will become more significant as a larger number of people live with the infection.

One of the observations to result from studies of long-living individuals with HIV is the development of body fat changes, including the thinning of extremities, loss of subcutaneous fat, potential for accumulating fat in the abdomen, and a risk of accumulating fat in the “buffalo hump” at the top of the shoulders. “These abnormalities might be associated with metabolic problems,” Dr. Martinez said.

HIV is known to decrease plasma concentrations of cholesterol—both low- and high-density lipoproteins—and induce fat loss. However, the initiation of ART induces fat gain followed by limb fat loss. “After a certain time point, some patients will experience a small loss of central abdominal fat, which then becomes stable, but the limb fat goes right down, which can change the way people look,” Dr. Martinez said. Lipid values go up, in some cases above prestudy values, he added. “For any ART that is going to be initiated in a patient, you can expect lipids to increase.” But the magnitude of the increase depends on the type of therapy used.

Insulin resistance also is common in patients with lipodystrophy and is associated with limb fat loss. Dr. Martinez reported a small study (J. Acquir. Immune Defic. Syndr. 2000;25:312–21) of 15 patients with HIV-associated lipodystrophy, 14 HIV-infected people without fat changes, and 12 non-HIV-infected controls. Low insulin sensitivity was closely associated with the loss of peripheral fat in the HIV and lipodystrophy group, Dr. Martinez said.