Susan London

VANCOUVER, B.C. – Pediatricians and public health professionals can estimate children’s asthma risk based on the density of housing code violations in their neighborhood, according to a retrospective cohort study reported at the annual meeting of the Pediatric Academic Societies.

Investigators led by Dr. Andrew F. Beck, of the pediatrics department at Cincinnati Children’s Hospital Medical Center, calculated the density of asthma-relevant housing code violations – those for cockroaches, rodents, mold, and water damage – for 113 neighborhoods (census tracts) in the Greater Cincinnati area.

Analyses showed that this density was significantly and positively associated with the neighborhood’s rate of pediatric asthma-related emergency department (ED) visits and hospital admissions.

Also, among the subset of patients who were admitted for asthma, the odds of another ED visit or admission in the next year increased with the density of violations. It was elevated by more than 50% for those living in neighborhoods with a medium-high or high density of violations relative to those living in neighborhoods with a low density.

"A measure of housing code violation density ... was found to be significantly correlated with asthma utilization rates at the population level, and significantly and independently associated with reutilization at the patient level," Dr. Beck commented.

"In an era where home visits are rare, local geographic data that highlight the impact of context on health provide a virtual home or neighborhood visit. Such information could help to identify upstream areas where disparity reduction can be targeted within care delivery, a focus especially relevant for diseases like asthma that are heavily impacted by the quality of one’s surroundings," he maintained.

"We expect that local risk-specific data can influence delivery of public health services more proactively. For example, the pairing of housing data with outcome data could facilitate identification of geographic areas likely to benefit from targeted housing assessments and actions," Dr. Beck added. "We also believe that contextual housing data can be integrated into clinical care. Such information could rapidly inform and drive focused interventions for connections to housing experts; for example, patients could be more efficiently connected to social workers, home health providers, and community partners such as legal advocates and community health workers, all of whom may be more suited to handling underlying housing risks than the medical team."

Study results showed that across neighborhoods, the median density of asthma-relevant housing code violations was 11 per 1,000 homes and apartments, with a range from 0 to 120, according to Dr. Beck.

The investigators identified 8,736 asthma-related ED visits and admissions to Cincinnati Children’s Hospital Medical Center by children aged 1-16 years during the study period. As the neighborhood density of housing code violations increased, so did this rate (r = 0.59; P less than .0001).

Moreover, the association remained significant after adjustment for neighborhood poverty level. Overall, the density of violations accounted for 25% of the variation across neighborhoods in such asthma-related health care use.

Among 1,531 pediatric patients with an index hospital admission for asthma, 37% had another ED visit or admission during a year of follow-up.

In a multivariate analysis, the adjusted odds of such repeat use increased with the neighborhood housing code violation density. Relative to peers living in neighborhoods with low density, children living in ones with medium-high density or high density had a significantly elevated risk (odds ratios, 1.54 and 1.84, respectively).

"In our region, housing assessments are complaint-driven; thus, the true breadth of violations is unknown," Dr. Beck noted, addressing study limitations. Also, generalizability is unclear; "we expect that many jurisdictions, however, collect similar data and use that data in similar ways."

Dr. Beck disclosed no relevant conflicts of interest.

VANCOUVER, B.C. – Pediatricians and public health professionals can estimate children’s asthma risk based on the density of housing code violations in their neighborhood, according to a retrospective cohort study reported at the annual meeting of the Pediatric Academic Societies.

Investigators led by Dr. Andrew F. Beck, of the pediatrics department at Cincinnati Children’s Hospital Medical Center, calculated the density of asthma-relevant housing code violations – those for cockroaches, rodents, mold, and water damage – for 113 neighborhoods (census tracts) in the Greater Cincinnati area.

Analyses showed that this density was significantly and positively associated with the neighborhood’s rate of pediatric asthma-related emergency department (ED) visits and hospital admissions.

Also, among the subset of patients who were admitted for asthma, the odds of another ED visit or admission in the next year increased with the density of violations. It was elevated by more than 50% for those living in neighborhoods with a medium-high or high density of violations relative to those living in neighborhoods with a low density.

"A measure of housing code violation density ... was found to be significantly correlated with asthma utilization rates at the population level, and significantly and independently associated with reutilization at the patient level," Dr. Beck commented.

"In an era where home visits are rare, local geographic data that highlight the impact of context on health provide a virtual home or neighborhood visit. Such information could help to identify upstream areas where disparity reduction can be targeted within care delivery, a focus especially relevant for diseases like asthma that are heavily impacted by the quality of one’s surroundings," he maintained.

"We expect that local risk-specific data can influence delivery of public health services more proactively. For example, the pairing of housing data with outcome data could facilitate identification of geographic areas likely to benefit from targeted housing assessments and actions," Dr. Beck added. "We also believe that contextual housing data can be integrated into clinical care. Such information could rapidly inform and drive focused interventions for connections to housing experts; for example, patients could be more efficiently connected to social workers, home health providers, and community partners such as legal advocates and community health workers, all of whom may be more suited to handling underlying housing risks than the medical team."

Study results showed that across neighborhoods, the median density of asthma-relevant housing code violations was 11 per 1,000 homes and apartments, with a range from 0 to 120, according to Dr. Beck.

The investigators identified 8,736 asthma-related ED visits and admissions to Cincinnati Children’s Hospital Medical Center by children aged 1-16 years during the study period. As the neighborhood density of housing code violations increased, so did this rate (r = 0.59; P less than .0001).

Moreover, the association remained significant after adjustment for neighborhood poverty level. Overall, the density of violations accounted for 25% of the variation across neighborhoods in such asthma-related health care use.

Among 1,531 pediatric patients with an index hospital admission for asthma, 37% had another ED visit or admission during a year of follow-up.

In a multivariate analysis, the adjusted odds of such repeat use increased with the neighborhood housing code violation density. Relative to peers living in neighborhoods with low density, children living in ones with medium-high density or high density had a significantly elevated risk (odds ratios, 1.54 and 1.84, respectively).

"In our region, housing assessments are complaint-driven; thus, the true breadth of violations is unknown," Dr. Beck noted, addressing study limitations. Also, generalizability is unclear; "we expect that many jurisdictions, however, collect similar data and use that data in similar ways."

Dr. Beck disclosed no relevant conflicts of interest.

VANCOUVER, B.C. – Pediatricians and public health professionals can estimate children’s asthma risk based on the density of housing code violations in their neighborhood, according to a retrospective cohort study reported at the annual meeting of the Pediatric Academic Societies.

Investigators led by Dr. Andrew F. Beck, of the pediatrics department at Cincinnati Children’s Hospital Medical Center, calculated the density of asthma-relevant housing code violations – those for cockroaches, rodents, mold, and water damage – for 113 neighborhoods (census tracts) in the Greater Cincinnati area.

Analyses showed that this density was significantly and positively associated with the neighborhood’s rate of pediatric asthma-related emergency department (ED) visits and hospital admissions.

Also, among the subset of patients who were admitted for asthma, the odds of another ED visit or admission in the next year increased with the density of violations. It was elevated by more than 50% for those living in neighborhoods with a medium-high or high density of violations relative to those living in neighborhoods with a low density.

"A measure of housing code violation density ... was found to be significantly correlated with asthma utilization rates at the population level, and significantly and independently associated with reutilization at the patient level," Dr. Beck commented.

"In an era where home visits are rare, local geographic data that highlight the impact of context on health provide a virtual home or neighborhood visit. Such information could help to identify upstream areas where disparity reduction can be targeted within care delivery, a focus especially relevant for diseases like asthma that are heavily impacted by the quality of one’s surroundings," he maintained.

"We expect that local risk-specific data can influence delivery of public health services more proactively. For example, the pairing of housing data with outcome data could facilitate identification of geographic areas likely to benefit from targeted housing assessments and actions," Dr. Beck added. "We also believe that contextual housing data can be integrated into clinical care. Such information could rapidly inform and drive focused interventions for connections to housing experts; for example, patients could be more efficiently connected to social workers, home health providers, and community partners such as legal advocates and community health workers, all of whom may be more suited to handling underlying housing risks than the medical team."

Study results showed that across neighborhoods, the median density of asthma-relevant housing code violations was 11 per 1,000 homes and apartments, with a range from 0 to 120, according to Dr. Beck.

The investigators identified 8,736 asthma-related ED visits and admissions to Cincinnati Children’s Hospital Medical Center by children aged 1-16 years during the study period. As the neighborhood density of housing code violations increased, so did this rate (r = 0.59; P less than .0001).

Moreover, the association remained significant after adjustment for neighborhood poverty level. Overall, the density of violations accounted for 25% of the variation across neighborhoods in such asthma-related health care use.

Among 1,531 pediatric patients with an index hospital admission for asthma, 37% had another ED visit or admission during a year of follow-up.

In a multivariate analysis, the adjusted odds of such repeat use increased with the neighborhood housing code violation density. Relative to peers living in neighborhoods with low density, children living in ones with medium-high density or high density had a significantly elevated risk (odds ratios, 1.54 and 1.84, respectively).

"In our region, housing assessments are complaint-driven; thus, the true breadth of violations is unknown," Dr. Beck noted, addressing study limitations. Also, generalizability is unclear; "we expect that many jurisdictions, however, collect similar data and use that data in similar ways."

Dr. Beck disclosed no relevant conflicts of interest.

LAS VEGAS – Anorexia nervosa in men may present in unusual ways, confounding the diagnosis and leading to inappropriate treatment, suggests a case series reported at the annual meeting of the American Association of Clinical Endocrinologists.

The four men, who ranged in age from 21 to 24 years, were seen in the emergency department with abnormal thyroid function test results, hypogonadism, and hypercortisolemia, according to data reported in a poster. Their symptoms included bradycardia (with heart rates in the 20s and 30s), gastroparesis, hypothermia, acute systolic heart failure, and erectile dysfunction.

"Only one of the cases had a prior diagnosis of anorexia, so it was kind of a mystery to everyone when they came in," first author Dr. Aren H. Skolnick said in a press briefing.

Some of the men were transferred to the cardiac care unit. Two were scheduled for cardiac pacemaker implantation, and one was scheduled for gastric pacemaker implantation before endocrinologists delved further into their history and made the correct diagnosis of anorexia.

"When we think of anorexia, we think of young women with eating disorders. No one really thinks about the guy with anorexia," said Dr. Skolnick, an endocrinology fellow at Hofstra North Shore-LIJ School of Medicine, Long Island (New York) Jewish Medical Center. "These patients were going to go for invasive procedures that they didn’t need, so [anorexia] really needs to be on the differential diagnosis, at least for anyone coming in with any of these endocrinopathies who you suspect may have had weight loss or are malnourished."

Most of the patients’ symptoms resolved with improved caloric intake and nutrition, although it hasn’t been smooth sailing in all cases, Dr. Skolnick said. "The best treatment we know of is nutrition – getting these people fed," he maintained. Although studies have looked at treatment with recombinant growth hormone, recombinant insulinlike growth factor-1 (IGF-1), estrogen for women, and thyroid hormone, "hormone therapy isn’t appropriate most of the time."

Some data suggest that men account for only about 10% of patients with anorexia, but they probably make up more like 25% because of underreporting and misdiagnosis, In fact, one of the diagnostic criteria in the DSM-IV is amenorrhea, "but there are no criteria for hypogonadal symptoms for men, so there is a bias even with the diagnostic criteria."

Male anorexia – sometimes termed "manorexia" – and female anorexia share similar risk factors, but their features differ somewhat. "Women tend to strive for thinness; men strive for a more muscular appearance. Women tend to have a little more of the laxative use or purging type; men are the more excessive exercise type," he explained.

There is also a sex disparity in treatment benefit. "Women tend to benefit more from treatment, possibly because they are picked up earlier," Dr. Skolnick elaborated. "There is more social support for them; people know how to treat female anorexia. And people aren’t picking up on the male anorexia, so they are coming to physicians later and their cases are may be more severe, or people don’t feel comfortable dealing with it."

Patients can develop a variety of endocrinopathies that may trigger endocrinology consults. Anorexia can affect the hypothalamic-pituitary axis, including the gonadal axis, leading to hypogonadal symptoms; the pituitary-thyroid axis; growth hormone or IGF-1, leading to impaired growth in children and adolescents; and the adrenal axis.

Dr. Skolnick and his colleagues were asked to consult on the patients because their laboratory findings were inconsistent. "Some of them had a sick euthyroid type of hypothyroidism, where their TSH may be borderline low-normal, with a low T3 or T4, which is why they called us, because they weren’t sure what was going on. In addition, they had symptoms of hypogonadism, low testosterone on labs, and cortisol resistance or increased cortisol because of the stress," he explained.

The endocrinologists’ differential diagnosis consisted of anorexia, depression, and malingering. Detailed histories revealed that the patients had a weight loss of up to 113 pounds over the past few months; therefore, they had severe protein and caloric malnourishment. They also reported depression, not eating, and exercising a lot; one said he had been using a fat-reducing agent.

Dr. Skolnick disclosed no relevant conflicts of interest.

LAS VEGAS – Anorexia nervosa in men may present in unusual ways, confounding the diagnosis and leading to inappropriate treatment, suggests a case series reported at the annual meeting of the American Association of Clinical Endocrinologists.

The four men, who ranged in age from 21 to 24 years, were seen in the emergency department with abnormal thyroid function test results, hypogonadism, and hypercortisolemia, according to data reported in a poster. Their symptoms included bradycardia (with heart rates in the 20s and 30s), gastroparesis, hypothermia, acute systolic heart failure, and erectile dysfunction.

"Only one of the cases had a prior diagnosis of anorexia, so it was kind of a mystery to everyone when they came in," first author Dr. Aren H. Skolnick said in a press briefing.

Some of the men were transferred to the cardiac care unit. Two were scheduled for cardiac pacemaker implantation, and one was scheduled for gastric pacemaker implantation before endocrinologists delved further into their history and made the correct diagnosis of anorexia.

"When we think of anorexia, we think of young women with eating disorders. No one really thinks about the guy with anorexia," said Dr. Skolnick, an endocrinology fellow at Hofstra North Shore-LIJ School of Medicine, Long Island (New York) Jewish Medical Center. "These patients were going to go for invasive procedures that they didn’t need, so [anorexia] really needs to be on the differential diagnosis, at least for anyone coming in with any of these endocrinopathies who you suspect may have had weight loss or are malnourished."

Most of the patients’ symptoms resolved with improved caloric intake and nutrition, although it hasn’t been smooth sailing in all cases, Dr. Skolnick said. "The best treatment we know of is nutrition – getting these people fed," he maintained. Although studies have looked at treatment with recombinant growth hormone, recombinant insulinlike growth factor-1 (IGF-1), estrogen for women, and thyroid hormone, "hormone therapy isn’t appropriate most of the time."

Some data suggest that men account for only about 10% of patients with anorexia, but they probably make up more like 25% because of underreporting and misdiagnosis, In fact, one of the diagnostic criteria in the DSM-IV is amenorrhea, "but there are no criteria for hypogonadal symptoms for men, so there is a bias even with the diagnostic criteria."

Male anorexia – sometimes termed "manorexia" – and female anorexia share similar risk factors, but their features differ somewhat. "Women tend to strive for thinness; men strive for a more muscular appearance. Women tend to have a little more of the laxative use or purging type; men are the more excessive exercise type," he explained.

There is also a sex disparity in treatment benefit. "Women tend to benefit more from treatment, possibly because they are picked up earlier," Dr. Skolnick elaborated. "There is more social support for them; people know how to treat female anorexia. And people aren’t picking up on the male anorexia, so they are coming to physicians later and their cases are may be more severe, or people don’t feel comfortable dealing with it."

Patients can develop a variety of endocrinopathies that may trigger endocrinology consults. Anorexia can affect the hypothalamic-pituitary axis, including the gonadal axis, leading to hypogonadal symptoms; the pituitary-thyroid axis; growth hormone or IGF-1, leading to impaired growth in children and adolescents; and the adrenal axis.

Dr. Skolnick and his colleagues were asked to consult on the patients because their laboratory findings were inconsistent. "Some of them had a sick euthyroid type of hypothyroidism, where their TSH may be borderline low-normal, with a low T3 or T4, which is why they called us, because they weren’t sure what was going on. In addition, they had symptoms of hypogonadism, low testosterone on labs, and cortisol resistance or increased cortisol because of the stress," he explained.

The endocrinologists’ differential diagnosis consisted of anorexia, depression, and malingering. Detailed histories revealed that the patients had a weight loss of up to 113 pounds over the past few months; therefore, they had severe protein and caloric malnourishment. They also reported depression, not eating, and exercising a lot; one said he had been using a fat-reducing agent.

Dr. Skolnick disclosed no relevant conflicts of interest.

LAS VEGAS – Anorexia nervosa in men may present in unusual ways, confounding the diagnosis and leading to inappropriate treatment, suggests a case series reported at the annual meeting of the American Association of Clinical Endocrinologists.

The four men, who ranged in age from 21 to 24 years, were seen in the emergency department with abnormal thyroid function test results, hypogonadism, and hypercortisolemia, according to data reported in a poster. Their symptoms included bradycardia (with heart rates in the 20s and 30s), gastroparesis, hypothermia, acute systolic heart failure, and erectile dysfunction.

"Only one of the cases had a prior diagnosis of anorexia, so it was kind of a mystery to everyone when they came in," first author Dr. Aren H. Skolnick said in a press briefing.

Some of the men were transferred to the cardiac care unit. Two were scheduled for cardiac pacemaker implantation, and one was scheduled for gastric pacemaker implantation before endocrinologists delved further into their history and made the correct diagnosis of anorexia.

"When we think of anorexia, we think of young women with eating disorders. No one really thinks about the guy with anorexia," said Dr. Skolnick, an endocrinology fellow at Hofstra North Shore-LIJ School of Medicine, Long Island (New York) Jewish Medical Center. "These patients were going to go for invasive procedures that they didn’t need, so [anorexia] really needs to be on the differential diagnosis, at least for anyone coming in with any of these endocrinopathies who you suspect may have had weight loss or are malnourished."

Most of the patients’ symptoms resolved with improved caloric intake and nutrition, although it hasn’t been smooth sailing in all cases, Dr. Skolnick said. "The best treatment we know of is nutrition – getting these people fed," he maintained. Although studies have looked at treatment with recombinant growth hormone, recombinant insulinlike growth factor-1 (IGF-1), estrogen for women, and thyroid hormone, "hormone therapy isn’t appropriate most of the time."

Some data suggest that men account for only about 10% of patients with anorexia, but they probably make up more like 25% because of underreporting and misdiagnosis, In fact, one of the diagnostic criteria in the DSM-IV is amenorrhea, "but there are no criteria for hypogonadal symptoms for men, so there is a bias even with the diagnostic criteria."

Male anorexia – sometimes termed "manorexia" – and female anorexia share similar risk factors, but their features differ somewhat. "Women tend to strive for thinness; men strive for a more muscular appearance. Women tend to have a little more of the laxative use or purging type; men are the more excessive exercise type," he explained.

There is also a sex disparity in treatment benefit. "Women tend to benefit more from treatment, possibly because they are picked up earlier," Dr. Skolnick elaborated. "There is more social support for them; people know how to treat female anorexia. And people aren’t picking up on the male anorexia, so they are coming to physicians later and their cases are may be more severe, or people don’t feel comfortable dealing with it."

Patients can develop a variety of endocrinopathies that may trigger endocrinology consults. Anorexia can affect the hypothalamic-pituitary axis, including the gonadal axis, leading to hypogonadal symptoms; the pituitary-thyroid axis; growth hormone or IGF-1, leading to impaired growth in children and adolescents; and the adrenal axis.

Dr. Skolnick and his colleagues were asked to consult on the patients because their laboratory findings were inconsistent. "Some of them had a sick euthyroid type of hypothyroidism, where their TSH may be borderline low-normal, with a low T3 or T4, which is why they called us, because they weren’t sure what was going on. In addition, they had symptoms of hypogonadism, low testosterone on labs, and cortisol resistance or increased cortisol because of the stress," he explained.

The endocrinologists’ differential diagnosis consisted of anorexia, depression, and malingering. Detailed histories revealed that the patients had a weight loss of up to 113 pounds over the past few months; therefore, they had severe protein and caloric malnourishment. They also reported depression, not eating, and exercising a lot; one said he had been using a fat-reducing agent.

Dr. Skolnick disclosed no relevant conflicts of interest.

LAS VEGAS – Nondiabetic patients with nonalcoholic fatty liver disease already have insulin perturbations putting them on track for a variety of more serious health conditions, new data show.

In a study of 98 consecutive nondiabetic patients with NAFLD referred to a metabolic liver clinic, the mean fasting insulin level was 14.3 microIU/mL, according to data reported at the annual meeting of the American Association of Clinical Endocrinologists.

Additionally, mean insulin levels during an oral glucose tolerance test (OGTT) exceeded the upper limit of normal from 60 minutes after glucose administration onward, with the gap increasing out to 120 minutes.

"Hyperinsulinemia and insulin resistance are already present in patients with NAFLD," commented first author Dr. Leah Folb of Weill Cornell Medical College, Houston Methodist Hospital in Texas. Intervention at this early point might help prevent progression to nonalcoholic steatohepatitis (NASH), diabetes, and cardiovascular disease, she said.

This patient population should be further evaluated, according to Dr. Folb. "Consider OGTT in all patients with persistent abnormal liver function tests if you have ruled out other causes, such as alcoholic [etiology] and hepatitis. And consider NASH FibroSure in all the patients with abnormal liver function tests and/or insulin resistance," she recommended.

The investigators are establishing a registry to follow such patients longitudinally and determine the natural history of insulin resistance. "We want to assess the response to interventions such as pioglitazone [Actos] and vitamin E based on the PIVENS study [Pioglitazone or Vitamin E for NASH Study]," she added.

Session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, Boston, said the findings were "not surprising," as previous studies, especially by investigators in Finland, have shown that higher liver fat content is associated with insulin resistance.

This new study "adds to our understanding that NAFLD is associated with insulin resistance and metabolic abnormalities," he commented in an interview. "We should be treating, and probably the best way to treat this is by dietary restriction and weight loss and lifestyle modifications."

Explaining the study’s rationale, Dr. Folb noted that the risk of cardiovascular death increases with simple steatosis and increases further still with the more advanced NASH. "We’re thinking that insulin resistance and maybe hyperinsulinemia may be the link here," she said.

On average, the patients studied had a body mass index of 30 kg/m², triglyceride level of 149 mg/dL, and HDL cholesterol level of 47 mg/dL. Results of NASH FibroSure testing showed that their mean fibroscore was 0.25 and their mean steatosis score was 0.60.

Fully 40% of the patients overall (48% of women and 28% of men) had prediabetes, Dr. Folb reported.

Analyses showed positive correlations of steatosis score with BMI (P less than .0001); of steatosis score with hemoglobin A_1c (P = .003); of beta-cell function, as ascertained from HOMA-B, with BMI (P = .01); and of insulin resistance, as ascertained from HOMA-IR, with BMI (P = .02).

Dr. Folb disclosed no relevant conflicts of interest.

LAS VEGAS – Nondiabetic patients with nonalcoholic fatty liver disease already have insulin perturbations putting them on track for a variety of more serious health conditions, new data show.

In a study of 98 consecutive nondiabetic patients with NAFLD referred to a metabolic liver clinic, the mean fasting insulin level was 14.3 microIU/mL, according to data reported at the annual meeting of the American Association of Clinical Endocrinologists.

Additionally, mean insulin levels during an oral glucose tolerance test (OGTT) exceeded the upper limit of normal from 60 minutes after glucose administration onward, with the gap increasing out to 120 minutes.

"Hyperinsulinemia and insulin resistance are already present in patients with NAFLD," commented first author Dr. Leah Folb of Weill Cornell Medical College, Houston Methodist Hospital in Texas. Intervention at this early point might help prevent progression to nonalcoholic steatohepatitis (NASH), diabetes, and cardiovascular disease, she said.

This patient population should be further evaluated, according to Dr. Folb. "Consider OGTT in all patients with persistent abnormal liver function tests if you have ruled out other causes, such as alcoholic [etiology] and hepatitis. And consider NASH FibroSure in all the patients with abnormal liver function tests and/or insulin resistance," she recommended.

The investigators are establishing a registry to follow such patients longitudinally and determine the natural history of insulin resistance. "We want to assess the response to interventions such as pioglitazone [Actos] and vitamin E based on the PIVENS study [Pioglitazone or Vitamin E for NASH Study]," she added.

Session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, Boston, said the findings were "not surprising," as previous studies, especially by investigators in Finland, have shown that higher liver fat content is associated with insulin resistance.

This new study "adds to our understanding that NAFLD is associated with insulin resistance and metabolic abnormalities," he commented in an interview. "We should be treating, and probably the best way to treat this is by dietary restriction and weight loss and lifestyle modifications."

Explaining the study’s rationale, Dr. Folb noted that the risk of cardiovascular death increases with simple steatosis and increases further still with the more advanced NASH. "We’re thinking that insulin resistance and maybe hyperinsulinemia may be the link here," she said.

On average, the patients studied had a body mass index of 30 kg/m², triglyceride level of 149 mg/dL, and HDL cholesterol level of 47 mg/dL. Results of NASH FibroSure testing showed that their mean fibroscore was 0.25 and their mean steatosis score was 0.60.

Fully 40% of the patients overall (48% of women and 28% of men) had prediabetes, Dr. Folb reported.

Analyses showed positive correlations of steatosis score with BMI (P less than .0001); of steatosis score with hemoglobin A_1c (P = .003); of beta-cell function, as ascertained from HOMA-B, with BMI (P = .01); and of insulin resistance, as ascertained from HOMA-IR, with BMI (P = .02).

Dr. Folb disclosed no relevant conflicts of interest.

LAS VEGAS – Nondiabetic patients with nonalcoholic fatty liver disease already have insulin perturbations putting them on track for a variety of more serious health conditions, new data show.

In a study of 98 consecutive nondiabetic patients with NAFLD referred to a metabolic liver clinic, the mean fasting insulin level was 14.3 microIU/mL, according to data reported at the annual meeting of the American Association of Clinical Endocrinologists.

Additionally, mean insulin levels during an oral glucose tolerance test (OGTT) exceeded the upper limit of normal from 60 minutes after glucose administration onward, with the gap increasing out to 120 minutes.

"Hyperinsulinemia and insulin resistance are already present in patients with NAFLD," commented first author Dr. Leah Folb of Weill Cornell Medical College, Houston Methodist Hospital in Texas. Intervention at this early point might help prevent progression to nonalcoholic steatohepatitis (NASH), diabetes, and cardiovascular disease, she said.

This patient population should be further evaluated, according to Dr. Folb. "Consider OGTT in all patients with persistent abnormal liver function tests if you have ruled out other causes, such as alcoholic [etiology] and hepatitis. And consider NASH FibroSure in all the patients with abnormal liver function tests and/or insulin resistance," she recommended.

The investigators are establishing a registry to follow such patients longitudinally and determine the natural history of insulin resistance. "We want to assess the response to interventions such as pioglitazone [Actos] and vitamin E based on the PIVENS study [Pioglitazone or Vitamin E for NASH Study]," she added.

Session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, Boston, said the findings were "not surprising," as previous studies, especially by investigators in Finland, have shown that higher liver fat content is associated with insulin resistance.

This new study "adds to our understanding that NAFLD is associated with insulin resistance and metabolic abnormalities," he commented in an interview. "We should be treating, and probably the best way to treat this is by dietary restriction and weight loss and lifestyle modifications."

Explaining the study’s rationale, Dr. Folb noted that the risk of cardiovascular death increases with simple steatosis and increases further still with the more advanced NASH. "We’re thinking that insulin resistance and maybe hyperinsulinemia may be the link here," she said.

On average, the patients studied had a body mass index of 30 kg/m², triglyceride level of 149 mg/dL, and HDL cholesterol level of 47 mg/dL. Results of NASH FibroSure testing showed that their mean fibroscore was 0.25 and their mean steatosis score was 0.60.

Fully 40% of the patients overall (48% of women and 28% of men) had prediabetes, Dr. Folb reported.

Analyses showed positive correlations of steatosis score with BMI (P less than .0001); of steatosis score with hemoglobin A_1c (P = .003); of beta-cell function, as ascertained from HOMA-B, with BMI (P = .01); and of insulin resistance, as ascertained from HOMA-IR, with BMI (P = .02).

Dr. Folb disclosed no relevant conflicts of interest.

LAS VEGAS – Nondiabetic patients with nonalcoholic fatty liver disease already have insulin perturbations putting them on track for a variety of more serious health conditions, new data show.

In a study of 98 consecutive nondiabetic patients with NAFLD referred to a metabolic liver clinic, the mean fasting insulin level was 14.3 microIU/mL, according to data reported May 16 at the annual meeting of the American Association of Clinical Endocrinologists.

Additionally, mean insulin levels during an oral glucose tolerance test (OGTT) exceeded the upper limit of normal from 60 minutes after glucose administration onward, with the gap increasing out to 120 minutes.

"Hyperinsulinemia and insulin resistance are already present in patients with NAFLD," commented first author Dr. Leah Folb of Weill Cornell Medical College, Houston Methodist Hospital in Texas. Intervention at this early point might help prevent progression to nonalcoholic steatohepatitis (NASH), diabetes, and cardiovascular disease, she said.

This patient population should be further evaluated, according to Dr. Folb. "Consider OGTT in all patients with persistent abnormal liver function tests if you have ruled out other causes, such as alcoholic [etiology] and hepatitis. And consider NASH FibroSure in all the patients with abnormal liver function tests and/or insulin resistance," she recommended.

The investigators are establishing a registry to follow such patients longitudinally and determine the natural history of insulin resistance. "We want to assess the response to interventions such as pioglitazone [Actos] and vitamin E based on the PIVENS study [Pioglitazone or Vitamin E for NASH Study]," she added.

Session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, Boston, said the findings were "not surprising," as previous studies, especially by investigators in Finland, have shown that higher liver fat content is associated with insulin resistance.

This new study "adds to our understanding that NAFLD is associated with insulin resistance and metabolic abnormalities," he commented in an interview. "We should be treating, and probably the best way to treat this is by dietary restriction and weight loss and lifestyle modifications."

Explaining the study’s rationale, Dr. Folb noted that the risk of cardiovascular death increases with simple steatosis and increases further still with the more advanced NASH. "We’re thinking that insulin resistance and maybe hyperinsulinemia may be the link here," she said.

On average, the patients studied had a body mass index of 30 kg/m², triglyceride level of 149 mg/dL, and HDL cholesterol level of 47 mg/dL. Results of NASH FibroSure testing showed that their mean fibroscore was 0.25 and their mean steatosis score was 0.60.

Fully 40% of the patients overall (48% of women and 28% of men) had prediabetes, Dr. Folb reported.

Analyses showed positive correlations of steatosis score with BMI (P less than .0001); of steatosis score with hemoglobin A_1c (P = .003); of beta-cell function, as ascertained from HOMA-B, with BMI (P = .01); and of insulin resistance, as ascertained from HOMA-IR, with BMI (P = .02).

Dr. Folb disclosed no relevant conflicts of interest.

LAS VEGAS – Nondiabetic patients with nonalcoholic fatty liver disease already have insulin perturbations putting them on track for a variety of more serious health conditions, new data show.

In a study of 98 consecutive nondiabetic patients with NAFLD referred to a metabolic liver clinic, the mean fasting insulin level was 14.3 microIU/mL, according to data reported May 16 at the annual meeting of the American Association of Clinical Endocrinologists.

Additionally, mean insulin levels during an oral glucose tolerance test (OGTT) exceeded the upper limit of normal from 60 minutes after glucose administration onward, with the gap increasing out to 120 minutes.

"Hyperinsulinemia and insulin resistance are already present in patients with NAFLD," commented first author Dr. Leah Folb of Weill Cornell Medical College, Houston Methodist Hospital in Texas. Intervention at this early point might help prevent progression to nonalcoholic steatohepatitis (NASH), diabetes, and cardiovascular disease, she said.

This patient population should be further evaluated, according to Dr. Folb. "Consider OGTT in all patients with persistent abnormal liver function tests if you have ruled out other causes, such as alcoholic [etiology] and hepatitis. And consider NASH FibroSure in all the patients with abnormal liver function tests and/or insulin resistance," she recommended.

The investigators are establishing a registry to follow such patients longitudinally and determine the natural history of insulin resistance. "We want to assess the response to interventions such as pioglitazone [Actos] and vitamin E based on the PIVENS study [Pioglitazone or Vitamin E for NASH Study]," she added.

Session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, Boston, said the findings were "not surprising," as previous studies, especially by investigators in Finland, have shown that higher liver fat content is associated with insulin resistance.

This new study "adds to our understanding that NAFLD is associated with insulin resistance and metabolic abnormalities," he commented in an interview. "We should be treating, and probably the best way to treat this is by dietary restriction and weight loss and lifestyle modifications."

Explaining the study’s rationale, Dr. Folb noted that the risk of cardiovascular death increases with simple steatosis and increases further still with the more advanced NASH. "We’re thinking that insulin resistance and maybe hyperinsulinemia may be the link here," she said.

On average, the patients studied had a body mass index of 30 kg/m², triglyceride level of 149 mg/dL, and HDL cholesterol level of 47 mg/dL. Results of NASH FibroSure testing showed that their mean fibroscore was 0.25 and their mean steatosis score was 0.60.

Fully 40% of the patients overall (48% of women and 28% of men) had prediabetes, Dr. Folb reported.

Analyses showed positive correlations of steatosis score with BMI (P less than .0001); of steatosis score with hemoglobin A_1c (P = .003); of beta-cell function, as ascertained from HOMA-B, with BMI (P = .01); and of insulin resistance, as ascertained from HOMA-IR, with BMI (P = .02).

Dr. Folb disclosed no relevant conflicts of interest.

LAS VEGAS – Nondiabetic patients with nonalcoholic fatty liver disease already have insulin perturbations putting them on track for a variety of more serious health conditions, new data show.

In a study of 98 consecutive nondiabetic patients with NAFLD referred to a metabolic liver clinic, the mean fasting insulin level was 14.3 microIU/mL, according to data reported May 16 at the annual meeting of the American Association of Clinical Endocrinologists.

Additionally, mean insulin levels during an oral glucose tolerance test (OGTT) exceeded the upper limit of normal from 60 minutes after glucose administration onward, with the gap increasing out to 120 minutes.

"Hyperinsulinemia and insulin resistance are already present in patients with NAFLD," commented first author Dr. Leah Folb of Weill Cornell Medical College, Houston Methodist Hospital in Texas. Intervention at this early point might help prevent progression to nonalcoholic steatohepatitis (NASH), diabetes, and cardiovascular disease, she said.

This patient population should be further evaluated, according to Dr. Folb. "Consider OGTT in all patients with persistent abnormal liver function tests if you have ruled out other causes, such as alcoholic [etiology] and hepatitis. And consider NASH FibroSure in all the patients with abnormal liver function tests and/or insulin resistance," she recommended.

The investigators are establishing a registry to follow such patients longitudinally and determine the natural history of insulin resistance. "We want to assess the response to interventions such as pioglitazone [Actos] and vitamin E based on the PIVENS study [Pioglitazone or Vitamin E for NASH Study]," she added.

Session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, Boston, said the findings were "not surprising," as previous studies, especially by investigators in Finland, have shown that higher liver fat content is associated with insulin resistance.

This new study "adds to our understanding that NAFLD is associated with insulin resistance and metabolic abnormalities," he commented in an interview. "We should be treating, and probably the best way to treat this is by dietary restriction and weight loss and lifestyle modifications."

Explaining the study’s rationale, Dr. Folb noted that the risk of cardiovascular death increases with simple steatosis and increases further still with the more advanced NASH. "We’re thinking that insulin resistance and maybe hyperinsulinemia may be the link here," she said.

On average, the patients studied had a body mass index of 30 kg/m², triglyceride level of 149 mg/dL, and HDL cholesterol level of 47 mg/dL. Results of NASH FibroSure testing showed that their mean fibroscore was 0.25 and their mean steatosis score was 0.60.

Fully 40% of the patients overall (48% of women and 28% of men) had prediabetes, Dr. Folb reported.

Analyses showed positive correlations of steatosis score with BMI (P less than .0001); of steatosis score with hemoglobin A_1c (P = .003); of beta-cell function, as ascertained from HOMA-B, with BMI (P = .01); and of insulin resistance, as ascertained from HOMA-IR, with BMI (P = .02).

Dr. Folb disclosed no relevant conflicts of interest.

LAS VEGAS – The antidiabetic drug liraglutide promotes weight loss in overweight and obese individuals who do not have diabetes, according to results from a randomized trial reported on May 16 at the annual meeting of the American Association of Clinical Endocrinologists.

The 3,731 patients enrolled in the SCALE (Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities) trial were randomized 2:1 to treatment with once-daily subcutaneous 3.0 mg liraglutide or placebo, each along with caloric reduction and exercise. All patients were overweight or obese, with no known diabetes. About two-thirds had prediabetes.

At 56 weeks, patients given liraglutide had lost 8.0% of their body weight, compared with their counterparts given placebo, who had lost 2.6% (P less than .0001), reported lead author Dr. F. Xavier Pi-Sunyer, codirector of the New York Obesity Nutrition Research Center at St. Luke’s–Roosevelt Hospital Center, and professor of medicine at the Institute of Human Nutrition, Columbia University, in New York. The drug also had significant positive effects on various metabolic and lipid measures.

Rates of serious adverse events were similar with liraglutide and placebo, with the exception of pancreatitis and gallbladder disorders, which although still rare, were more than twice as common with the drug.

Liraglutide, in formulations of 1.2 mg and 1.8 mg for daily injections, was approved in 2010 for the treatment of type 2 diabetes and is marketed as Victoza. The 3.0-mg formulation used in SCALE is investigational.* 

"Liraglutide 3.0 mg, as an adjunct to diet and exercise, was efficacious and generally well tolerated. It was associated with significant benefits in addition to weight loss, including improvement in hemoglobin A_1c, fasting plasma glucose, blood pressure, and fasting lipids," Dr. Pi-Sunyer commented.

"The imbalance on pancreatitis and gallbladder disorders is undergoing further investigation," he added. "With regard to acute pancreatitis, no consistent mode or latency period was found. The majority of the events were mild according to the revised Atlanta criteria and were quickly reversible with stopping of the drug."

Session attendee Dr. Daniel Hurley, an endocrinologist at the Mayo Clinic in Rochester, Minn., asked, "In the patients with pancreatitis, any clinical idea whether this was gallstone induced or triglyceride induced?"

"Actually, the group that had the best result with regard to triglycerides did have a little more pancreatitis, so I don’t think it’s a triglyceride effect; in other words, the drug did drop triglycerides in these patients," Dr. Pi-Sunyer replied. "Only one patient developed both gallstones and pancreatitis; I don’t believe the two are probably related. We know that with weight loss, you get more gallstones and cholecystitis, and the drug group obviously had much better weight loss than the control group. I think that probably explains the gallbladder effect."

Liraglutide and other long-acting glucagonlike peptide–1 (GLP-1) receptor agonists are well known to decrease appetite and produce satiety, session comoderator Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, noted in an interview.

"So there’s a lot of interest now in using that not just for improving glucose metabolism in the diabetic, but as a weight loss agent. In the diabetes field, it’s really a two-fer – you basically improve glucose metabolism and you get the weight loss. But this is one of the first trials specifically just treating obesity without diabetes, and I’m sure they want to get FDA [Food and Drug Administration] approval for it" for this indication, he said. "It’s coming; we’re going to be using the GLP-1 receptor agonists for obesity," he predicted.

The 3.0-mg dose used in the trial is higher than the dose of 1.8 mg or so typically used in patients with diabetes, Dr. Horton noted. "There has been all the controversy about pancreatitis and so forth, and what was important here was showing that the higher dose didn’t increase the risk for any of these rare complications. But you have to be aware of them, and anybody who’s had pancreatitis, that’s a contraindication of course. But I think the drugs are safe even at the higher dose."

In the trial, patients given liraglutide (manufactured by Novo Nordisk) had significant improvements from baseline in waist circumference (–4.2 cm), body mass index (–2.0 kg/m²), fasting plasma glucose level (–6.9 mg/dL), hemoglobin A_1c level (–0.2%), systolic and diastolic blood pressure (–2.8/–0.9 mm Hg), and fasting lipids.

The rate of serious adverse events was 6.2% with the drug and 5.0% with placebo. The respective rates of events leading to treatment discontinuation were 9.9% and 3.8%.

The leading adverse events were nausea, diarrhea, and constipation. Nausea most commonly appeared in the first 4 weeks of treatment and was generally mild or moderate.

"The safety profile was generally consistent with that of previous clinical trials with liraglutide 3.0 mg and liraglutide 1.8 mg in individuals with type 2 diabetes," Dr. Pi-Sunyer commented.

Patients in the liraglutide group had a higher rate of acute pancreatitis (0.3 vs. 0.1 events per 100 patient-years of exposure) and gallbladder disorders (2.7 vs. 1.0 events per 100 patient-years of exposure). A single patient in each treatment group had both conditions.

Dr. Pi-Sunyer disclosed that he is an adviser to Novo Nordisk, Weight Watchers, Johnson & Johnson, Vivus, Eisai, and Zafgen. Novo Nordisk sponsored the trial and supported preparation of the presentation.

*CORRECTION, 5/22/14: A previous version of this article stated that Victoza was used in the SCALE trial. The liraglutide 3.0-mg formulation used in SCALE is investigational.

LAS VEGAS – The antidiabetic drug liraglutide promotes weight loss in overweight and obese individuals who do not have diabetes, according to results from a randomized trial reported on May 16 at the annual meeting of the American Association of Clinical Endocrinologists.

The 3,731 patients enrolled in the SCALE (Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities) trial were randomized 2:1 to treatment with once-daily subcutaneous 3.0 mg liraglutide or placebo, each along with caloric reduction and exercise. All patients were overweight or obese, with no known diabetes. About two-thirds had prediabetes.

At 56 weeks, patients given liraglutide had lost 8.0% of their body weight, compared with their counterparts given placebo, who had lost 2.6% (P less than .0001), reported lead author Dr. F. Xavier Pi-Sunyer, codirector of the New York Obesity Nutrition Research Center at St. Luke’s–Roosevelt Hospital Center, and professor of medicine at the Institute of Human Nutrition, Columbia University, in New York. The drug also had significant positive effects on various metabolic and lipid measures.

Rates of serious adverse events were similar with liraglutide and placebo, with the exception of pancreatitis and gallbladder disorders, which although still rare, were more than twice as common with the drug.

Liraglutide, in formulations of 1.2 mg and 1.8 mg for daily injections, was approved in 2010 for the treatment of type 2 diabetes and is marketed as Victoza. The 3.0-mg formulation used in SCALE is investigational.* 

"Liraglutide 3.0 mg, as an adjunct to diet and exercise, was efficacious and generally well tolerated. It was associated with significant benefits in addition to weight loss, including improvement in hemoglobin A_1c, fasting plasma glucose, blood pressure, and fasting lipids," Dr. Pi-Sunyer commented.

"The imbalance on pancreatitis and gallbladder disorders is undergoing further investigation," he added. "With regard to acute pancreatitis, no consistent mode or latency period was found. The majority of the events were mild according to the revised Atlanta criteria and were quickly reversible with stopping of the drug."

Session attendee Dr. Daniel Hurley, an endocrinologist at the Mayo Clinic in Rochester, Minn., asked, "In the patients with pancreatitis, any clinical idea whether this was gallstone induced or triglyceride induced?"

"Actually, the group that had the best result with regard to triglycerides did have a little more pancreatitis, so I don’t think it’s a triglyceride effect; in other words, the drug did drop triglycerides in these patients," Dr. Pi-Sunyer replied. "Only one patient developed both gallstones and pancreatitis; I don’t believe the two are probably related. We know that with weight loss, you get more gallstones and cholecystitis, and the drug group obviously had much better weight loss than the control group. I think that probably explains the gallbladder effect."

Liraglutide and other long-acting glucagonlike peptide–1 (GLP-1) receptor agonists are well known to decrease appetite and produce satiety, session comoderator Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, noted in an interview.

"So there’s a lot of interest now in using that not just for improving glucose metabolism in the diabetic, but as a weight loss agent. In the diabetes field, it’s really a two-fer – you basically improve glucose metabolism and you get the weight loss. But this is one of the first trials specifically just treating obesity without diabetes, and I’m sure they want to get FDA [Food and Drug Administration] approval for it" for this indication, he said. "It’s coming; we’re going to be using the GLP-1 receptor agonists for obesity," he predicted.

The 3.0-mg dose used in the trial is higher than the dose of 1.8 mg or so typically used in patients with diabetes, Dr. Horton noted. "There has been all the controversy about pancreatitis and so forth, and what was important here was showing that the higher dose didn’t increase the risk for any of these rare complications. But you have to be aware of them, and anybody who’s had pancreatitis, that’s a contraindication of course. But I think the drugs are safe even at the higher dose."

In the trial, patients given liraglutide (manufactured by Novo Nordisk) had significant improvements from baseline in waist circumference (–4.2 cm), body mass index (–2.0 kg/m²), fasting plasma glucose level (–6.9 mg/dL), hemoglobin A_1c level (–0.2%), systolic and diastolic blood pressure (–2.8/–0.9 mm Hg), and fasting lipids.

The rate of serious adverse events was 6.2% with the drug and 5.0% with placebo. The respective rates of events leading to treatment discontinuation were 9.9% and 3.8%.

The leading adverse events were nausea, diarrhea, and constipation. Nausea most commonly appeared in the first 4 weeks of treatment and was generally mild or moderate.

"The safety profile was generally consistent with that of previous clinical trials with liraglutide 3.0 mg and liraglutide 1.8 mg in individuals with type 2 diabetes," Dr. Pi-Sunyer commented.

Patients in the liraglutide group had a higher rate of acute pancreatitis (0.3 vs. 0.1 events per 100 patient-years of exposure) and gallbladder disorders (2.7 vs. 1.0 events per 100 patient-years of exposure). A single patient in each treatment group had both conditions.

Dr. Pi-Sunyer disclosed that he is an adviser to Novo Nordisk, Weight Watchers, Johnson & Johnson, Vivus, Eisai, and Zafgen. Novo Nordisk sponsored the trial and supported preparation of the presentation.

*CORRECTION, 5/22/14: A previous version of this article stated that Victoza was used in the SCALE trial. The liraglutide 3.0-mg formulation used in SCALE is investigational.

LAS VEGAS – The antidiabetic drug liraglutide promotes weight loss in overweight and obese individuals who do not have diabetes, according to results from a randomized trial reported on May 16 at the annual meeting of the American Association of Clinical Endocrinologists.

The 3,731 patients enrolled in the SCALE (Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities) trial were randomized 2:1 to treatment with once-daily subcutaneous 3.0 mg liraglutide or placebo, each along with caloric reduction and exercise. All patients were overweight or obese, with no known diabetes. About two-thirds had prediabetes.

At 56 weeks, patients given liraglutide had lost 8.0% of their body weight, compared with their counterparts given placebo, who had lost 2.6% (P less than .0001), reported lead author Dr. F. Xavier Pi-Sunyer, codirector of the New York Obesity Nutrition Research Center at St. Luke’s–Roosevelt Hospital Center, and professor of medicine at the Institute of Human Nutrition, Columbia University, in New York. The drug also had significant positive effects on various metabolic and lipid measures.

Rates of serious adverse events were similar with liraglutide and placebo, with the exception of pancreatitis and gallbladder disorders, which although still rare, were more than twice as common with the drug.

Liraglutide, in formulations of 1.2 mg and 1.8 mg for daily injections, was approved in 2010 for the treatment of type 2 diabetes and is marketed as Victoza. The 3.0-mg formulation used in SCALE is investigational.* 

"Liraglutide 3.0 mg, as an adjunct to diet and exercise, was efficacious and generally well tolerated. It was associated with significant benefits in addition to weight loss, including improvement in hemoglobin A_1c, fasting plasma glucose, blood pressure, and fasting lipids," Dr. Pi-Sunyer commented.

"The imbalance on pancreatitis and gallbladder disorders is undergoing further investigation," he added. "With regard to acute pancreatitis, no consistent mode or latency period was found. The majority of the events were mild according to the revised Atlanta criteria and were quickly reversible with stopping of the drug."

Session attendee Dr. Daniel Hurley, an endocrinologist at the Mayo Clinic in Rochester, Minn., asked, "In the patients with pancreatitis, any clinical idea whether this was gallstone induced or triglyceride induced?"

"Actually, the group that had the best result with regard to triglycerides did have a little more pancreatitis, so I don’t think it’s a triglyceride effect; in other words, the drug did drop triglycerides in these patients," Dr. Pi-Sunyer replied. "Only one patient developed both gallstones and pancreatitis; I don’t believe the two are probably related. We know that with weight loss, you get more gallstones and cholecystitis, and the drug group obviously had much better weight loss than the control group. I think that probably explains the gallbladder effect."

Liraglutide and other long-acting glucagonlike peptide–1 (GLP-1) receptor agonists are well known to decrease appetite and produce satiety, session comoderator Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, noted in an interview.

"So there’s a lot of interest now in using that not just for improving glucose metabolism in the diabetic, but as a weight loss agent. In the diabetes field, it’s really a two-fer – you basically improve glucose metabolism and you get the weight loss. But this is one of the first trials specifically just treating obesity without diabetes, and I’m sure they want to get FDA [Food and Drug Administration] approval for it" for this indication, he said. "It’s coming; we’re going to be using the GLP-1 receptor agonists for obesity," he predicted.

The 3.0-mg dose used in the trial is higher than the dose of 1.8 mg or so typically used in patients with diabetes, Dr. Horton noted. "There has been all the controversy about pancreatitis and so forth, and what was important here was showing that the higher dose didn’t increase the risk for any of these rare complications. But you have to be aware of them, and anybody who’s had pancreatitis, that’s a contraindication of course. But I think the drugs are safe even at the higher dose."

In the trial, patients given liraglutide (manufactured by Novo Nordisk) had significant improvements from baseline in waist circumference (–4.2 cm), body mass index (–2.0 kg/m²), fasting plasma glucose level (–6.9 mg/dL), hemoglobin A_1c level (–0.2%), systolic and diastolic blood pressure (–2.8/–0.9 mm Hg), and fasting lipids.

The rate of serious adverse events was 6.2% with the drug and 5.0% with placebo. The respective rates of events leading to treatment discontinuation were 9.9% and 3.8%.

The leading adverse events were nausea, diarrhea, and constipation. Nausea most commonly appeared in the first 4 weeks of treatment and was generally mild or moderate.

"The safety profile was generally consistent with that of previous clinical trials with liraglutide 3.0 mg and liraglutide 1.8 mg in individuals with type 2 diabetes," Dr. Pi-Sunyer commented.

Patients in the liraglutide group had a higher rate of acute pancreatitis (0.3 vs. 0.1 events per 100 patient-years of exposure) and gallbladder disorders (2.7 vs. 1.0 events per 100 patient-years of exposure). A single patient in each treatment group had both conditions.

Dr. Pi-Sunyer disclosed that he is an adviser to Novo Nordisk, Weight Watchers, Johnson & Johnson, Vivus, Eisai, and Zafgen. Novo Nordisk sponsored the trial and supported preparation of the presentation.

*CORRECTION, 5/22/14: A previous version of this article stated that Victoza was used in the SCALE trial. The liraglutide 3.0-mg formulation used in SCALE is investigational.

LAS VEGAS – Testosterone improves insulin sensitivity and insulin signaling in diabetic men who are deficient in this hormone, finds a randomized trial reported at the annual meeting of the American Association of Clinical Endocrinologists.

Investigators led by Dr. Manav Batra of the University at Buffalo, State University of New York, assigned 41 men with hypogonadotropic hypogonadism evenly to receive intramuscular testosterone (250 mg) or placebo every 2 weeks for 24 weeks. The testosterone dose was adjusted to achieve free testosterone levels in the mid-normal range for healthy young men.

Main results of the trial showed that men in the testosterone group had a statistically significant 32% improvement in insulin sensitivity from baseline, but their counterparts in the placebo group had essentially no change in this measure.

Testosterone treatment also was associated with increased expression in adipose tissue of genes that mediate insulin signaling and decreased expression in mononuclear cells of genes that mediate insulin resistance. Placebo treatment was not associated with any changes.

The findings are important, as roughly one-third of men with type 2 diabetes have hypogonadotropic hypogonadism and testosterone deficiency is linked to unfavorable metabolic, lipid, and anthropometric changes that may increase cardiovascular risk, according to Dr. Batra.

"Testosterone replacement reverses these changes, and there is decline in fat mass, increase in lean mass, decline in inflammatory markers, and improved insulin signaling and hence insulin sensitivity, which may potentially reduce cardiovascular risk," he said in an interview.

"As these changes may have a bearing on future cardiovascular outcomes in people with hypogonadotropic hypogonadism in type 2 diabetes, the results of this study will lay the foundations for future longer-term studies investigating the effects of testosterone replacement on atherosclerosis and cardiovascular disease in hypogonadal type 2 diabetic and obese subjects," he added.

The study is consistent with earlier research linking both low and high testosterone levels with insulin resistance, Dr. Edward S. Horton, comoderator of the session in which the data were reported, said in an interview.

"The idea that testosterone deficiency is associated with insulin resistance has been around for 30 years. I look at this study as basically showing by modern methods that some of these old ideas are really holding up – that that’s true," he said.

"The data are very interesting and good data showing that, for people who are hypogonadal, we should be treating them to improve insulin sensitivity and getting the beneficial effects of testosterone beyond just the androgenic effects," maintained Dr. Horton, director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston.

In the study, the investigators first compared the 41 hypogonadal diabetic men participating in the trial with 50 eugonadal diabetic men, showing that the former did indeed have a host of adverse cardiometabolic measures when compared with the latter.

Among other favorable changes seen with testosterone treatment, men in that group had improvements from baseline in levels of insulin, homeostatic model assessment of insulin resistance (HOMA-IR), leptin, and C-reactive protein, Dr. Batra reported. Meanwhile, these measures remained unchanged in the placebo group.

Testosterone therapy was not associated with any significant improvements in levels of glucose or glycated hemoglobin, or in lipid profiles.

Dr. Batra disclosed no relevant conflicts of interest.

LAS VEGAS – Testosterone improves insulin sensitivity and insulin signaling in diabetic men who are deficient in this hormone, finds a randomized trial reported at the annual meeting of the American Association of Clinical Endocrinologists.

Investigators led by Dr. Manav Batra of the University at Buffalo, State University of New York, assigned 41 men with hypogonadotropic hypogonadism evenly to receive intramuscular testosterone (250 mg) or placebo every 2 weeks for 24 weeks. The testosterone dose was adjusted to achieve free testosterone levels in the mid-normal range for healthy young men.

Main results of the trial showed that men in the testosterone group had a statistically significant 32% improvement in insulin sensitivity from baseline, but their counterparts in the placebo group had essentially no change in this measure.

Testosterone treatment also was associated with increased expression in adipose tissue of genes that mediate insulin signaling and decreased expression in mononuclear cells of genes that mediate insulin resistance. Placebo treatment was not associated with any changes.

The findings are important, as roughly one-third of men with type 2 diabetes have hypogonadotropic hypogonadism and testosterone deficiency is linked to unfavorable metabolic, lipid, and anthropometric changes that may increase cardiovascular risk, according to Dr. Batra.

"Testosterone replacement reverses these changes, and there is decline in fat mass, increase in lean mass, decline in inflammatory markers, and improved insulin signaling and hence insulin sensitivity, which may potentially reduce cardiovascular risk," he said in an interview.

"As these changes may have a bearing on future cardiovascular outcomes in people with hypogonadotropic hypogonadism in type 2 diabetes, the results of this study will lay the foundations for future longer-term studies investigating the effects of testosterone replacement on atherosclerosis and cardiovascular disease in hypogonadal type 2 diabetic and obese subjects," he added.

The study is consistent with earlier research linking both low and high testosterone levels with insulin resistance, Dr. Edward S. Horton, comoderator of the session in which the data were reported, said in an interview.

"The idea that testosterone deficiency is associated with insulin resistance has been around for 30 years. I look at this study as basically showing by modern methods that some of these old ideas are really holding up – that that’s true," he said.

"The data are very interesting and good data showing that, for people who are hypogonadal, we should be treating them to improve insulin sensitivity and getting the beneficial effects of testosterone beyond just the androgenic effects," maintained Dr. Horton, director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston.

In the study, the investigators first compared the 41 hypogonadal diabetic men participating in the trial with 50 eugonadal diabetic men, showing that the former did indeed have a host of adverse cardiometabolic measures when compared with the latter.

Among other favorable changes seen with testosterone treatment, men in that group had improvements from baseline in levels of insulin, homeostatic model assessment of insulin resistance (HOMA-IR), leptin, and C-reactive protein, Dr. Batra reported. Meanwhile, these measures remained unchanged in the placebo group.

Testosterone therapy was not associated with any significant improvements in levels of glucose or glycated hemoglobin, or in lipid profiles.

Dr. Batra disclosed no relevant conflicts of interest.

LAS VEGAS – Testosterone improves insulin sensitivity and insulin signaling in diabetic men who are deficient in this hormone, finds a randomized trial reported at the annual meeting of the American Association of Clinical Endocrinologists.

Investigators led by Dr. Manav Batra of the University at Buffalo, State University of New York, assigned 41 men with hypogonadotropic hypogonadism evenly to receive intramuscular testosterone (250 mg) or placebo every 2 weeks for 24 weeks. The testosterone dose was adjusted to achieve free testosterone levels in the mid-normal range for healthy young men.

Main results of the trial showed that men in the testosterone group had a statistically significant 32% improvement in insulin sensitivity from baseline, but their counterparts in the placebo group had essentially no change in this measure.

Testosterone treatment also was associated with increased expression in adipose tissue of genes that mediate insulin signaling and decreased expression in mononuclear cells of genes that mediate insulin resistance. Placebo treatment was not associated with any changes.

The findings are important, as roughly one-third of men with type 2 diabetes have hypogonadotropic hypogonadism and testosterone deficiency is linked to unfavorable metabolic, lipid, and anthropometric changes that may increase cardiovascular risk, according to Dr. Batra.

"Testosterone replacement reverses these changes, and there is decline in fat mass, increase in lean mass, decline in inflammatory markers, and improved insulin signaling and hence insulin sensitivity, which may potentially reduce cardiovascular risk," he said in an interview.

"As these changes may have a bearing on future cardiovascular outcomes in people with hypogonadotropic hypogonadism in type 2 diabetes, the results of this study will lay the foundations for future longer-term studies investigating the effects of testosterone replacement on atherosclerosis and cardiovascular disease in hypogonadal type 2 diabetic and obese subjects," he added.

The study is consistent with earlier research linking both low and high testosterone levels with insulin resistance, Dr. Edward S. Horton, comoderator of the session in which the data were reported, said in an interview.

"The idea that testosterone deficiency is associated with insulin resistance has been around for 30 years. I look at this study as basically showing by modern methods that some of these old ideas are really holding up – that that’s true," he said.

"The data are very interesting and good data showing that, for people who are hypogonadal, we should be treating them to improve insulin sensitivity and getting the beneficial effects of testosterone beyond just the androgenic effects," maintained Dr. Horton, director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston.

In the study, the investigators first compared the 41 hypogonadal diabetic men participating in the trial with 50 eugonadal diabetic men, showing that the former did indeed have a host of adverse cardiometabolic measures when compared with the latter.

Among other favorable changes seen with testosterone treatment, men in that group had improvements from baseline in levels of insulin, homeostatic model assessment of insulin resistance (HOMA-IR), leptin, and C-reactive protein, Dr. Batra reported. Meanwhile, these measures remained unchanged in the placebo group.

Testosterone therapy was not associated with any significant improvements in levels of glucose or glycated hemoglobin, or in lipid profiles.

Dr. Batra disclosed no relevant conflicts of interest.

LAS VEGAS – Evolocumab, an investigational antibody that inhibits PCSK9, reduces levels of low-density lipoprotein cholesterol in hypercholesterolemic patients who have dysglycemia or metabolic syndrome – without worsening glucose metabolism, in contrast to what has been seen with high-intensity statin therapy, a new analysis shows.

"LDL-C reduction is an important intervention for patients with dysglycemia or metabolic syndrome. This analysis suggests evolocumab can safely reduce LDL-C in these patients and could become a valuable tool in their care," lead investigator Dr. Robert R. Henry said in an interview prior to presenting the results at the annual meeting of the American Association of Clinical Endocrinologists.

"PCSK9 inhibitors are evolving as a novel and exciting class of medications that significantly reduce LDL-C. Patients with conditions like diabetes may greatly benefit from these treatments, particularly many of them [who] are unable to achieve their LDL targets or have difficulty with statin-associated side effects," he added.

But before this new class of drugs becomes available to clinicians, "I think there are still lots of studies to be done with evolocumab," said Dr. Henry, who is with the division of endocrinology and metabolism at the University of California, San Diego.

"The efficacy is quite striking. Of course, it’s currently being evaluated in cardiovascular outcome trials whether evolocumab translates to reduced cardiovascular events. And there is a large study ongoing of about 22,500 high-risk cardiovascular patients who are being studied for cardiovascular outcomes. So in the future, assuming these studies are positive, there is, I guess, a good chance this will be available."

In an interview, session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston, commented, "That’s very impressive data, a 50% reduction in LDL cholesterol with this drug. I think those data are very exciting. The drug has to go through the whole development process, but if it holds up in longer, more detailed studies, I think it looks very promising."

"Right now, the other options are basically statins," Dr. Horton noted. "Statins are very, very effective, but a lot of people get side effects from the statins, particularly the myositis can be a major problem. So this may be a very good alternative for the people who don’t tolerate statins. The fact that it’s an injection once a month I think is not a big deal, rather than just an oral agent. Statins are easy to take – you just take your statin orally, but a lot of people have trouble with the statins. So I think it’s going to have a role."

The patients studied were participants in the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER), an extension trial in which patients from four phase II studies of evolocumab were randomized 2:1 to open-label monthly subcutaneous evolocumab plus standard of care or to standard of care alone for 1 year.

Results for the entire trial population, reported previously, showed that evolocumab was safe, well tolerated, and efficacious (Circulation 2014;129:234-43).

The new analysis, which additionally looked at impact on glucose metabolism in the subset with metabolic perturbations, was based on 109 patients with type 2 diabetes, 134 with impaired fasting glucose, and 425 with metabolic syndrome, some of whom had more than one condition.

Evolocumab was associated with an LDL-C reduction of 47% in patients with type 2 diabetes, 51% in those with impaired fasting glucose, and 52% in those with metabolic syndrome – this compared with no change in their counterparts given standard of care alone. (It was 53% with evolocumab in trial patients who did not have any of metabolic perturbations.)

"Reductions were comparable to those observed in OSLER patients without these conditions," pointed out Dr. Henry.

The drug was also associated with improvement relative to standard care in levels of HDL cholesterol, triglycerides, and lipoprotein(a) that were again similar to those seen in trial patients who did not have these conditions.

Importantly, evolocumab was not associated with any significant changes in fasting plasma glucose or glycated hemoglobin levels relative to standard of care.

The combined evolocumab group and standard of care group had essentially the same rates of adverse events (78% and 72%) and serious adverse events (8% and 6%). Rates of serious laboratory abnormalities such as marked elevation of creatine kinase were low and similar as well.

The trial was sponsored by Amgen. Dr. Henry disclosed that he has affiliations with Amgen and Sanofi.

LAS VEGAS – Evolocumab, an investigational antibody that inhibits PCSK9, reduces levels of low-density lipoprotein cholesterol in hypercholesterolemic patients who have dysglycemia or metabolic syndrome – without worsening glucose metabolism, in contrast to what has been seen with high-intensity statin therapy, a new analysis shows.

"LDL-C reduction is an important intervention for patients with dysglycemia or metabolic syndrome. This analysis suggests evolocumab can safely reduce LDL-C in these patients and could become a valuable tool in their care," lead investigator Dr. Robert R. Henry said in an interview prior to presenting the results at the annual meeting of the American Association of Clinical Endocrinologists.

"PCSK9 inhibitors are evolving as a novel and exciting class of medications that significantly reduce LDL-C. Patients with conditions like diabetes may greatly benefit from these treatments, particularly many of them [who] are unable to achieve their LDL targets or have difficulty with statin-associated side effects," he added.

But before this new class of drugs becomes available to clinicians, "I think there are still lots of studies to be done with evolocumab," said Dr. Henry, who is with the division of endocrinology and metabolism at the University of California, San Diego.

"The efficacy is quite striking. Of course, it’s currently being evaluated in cardiovascular outcome trials whether evolocumab translates to reduced cardiovascular events. And there is a large study ongoing of about 22,500 high-risk cardiovascular patients who are being studied for cardiovascular outcomes. So in the future, assuming these studies are positive, there is, I guess, a good chance this will be available."

In an interview, session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston, commented, "That’s very impressive data, a 50% reduction in LDL cholesterol with this drug. I think those data are very exciting. The drug has to go through the whole development process, but if it holds up in longer, more detailed studies, I think it looks very promising."

"Right now, the other options are basically statins," Dr. Horton noted. "Statins are very, very effective, but a lot of people get side effects from the statins, particularly the myositis can be a major problem. So this may be a very good alternative for the people who don’t tolerate statins. The fact that it’s an injection once a month I think is not a big deal, rather than just an oral agent. Statins are easy to take – you just take your statin orally, but a lot of people have trouble with the statins. So I think it’s going to have a role."

The patients studied were participants in the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER), an extension trial in which patients from four phase II studies of evolocumab were randomized 2:1 to open-label monthly subcutaneous evolocumab plus standard of care or to standard of care alone for 1 year.

Results for the entire trial population, reported previously, showed that evolocumab was safe, well tolerated, and efficacious (Circulation 2014;129:234-43).

The new analysis, which additionally looked at impact on glucose metabolism in the subset with metabolic perturbations, was based on 109 patients with type 2 diabetes, 134 with impaired fasting glucose, and 425 with metabolic syndrome, some of whom had more than one condition.

Evolocumab was associated with an LDL-C reduction of 47% in patients with type 2 diabetes, 51% in those with impaired fasting glucose, and 52% in those with metabolic syndrome – this compared with no change in their counterparts given standard of care alone. (It was 53% with evolocumab in trial patients who did not have any of metabolic perturbations.)

"Reductions were comparable to those observed in OSLER patients without these conditions," pointed out Dr. Henry.

The drug was also associated with improvement relative to standard care in levels of HDL cholesterol, triglycerides, and lipoprotein(a) that were again similar to those seen in trial patients who did not have these conditions.

Importantly, evolocumab was not associated with any significant changes in fasting plasma glucose or glycated hemoglobin levels relative to standard of care.

The combined evolocumab group and standard of care group had essentially the same rates of adverse events (78% and 72%) and serious adverse events (8% and 6%). Rates of serious laboratory abnormalities such as marked elevation of creatine kinase were low and similar as well.

The trial was sponsored by Amgen. Dr. Henry disclosed that he has affiliations with Amgen and Sanofi.

LAS VEGAS – Evolocumab, an investigational antibody that inhibits PCSK9, reduces levels of low-density lipoprotein cholesterol in hypercholesterolemic patients who have dysglycemia or metabolic syndrome – without worsening glucose metabolism, in contrast to what has been seen with high-intensity statin therapy, a new analysis shows.

"LDL-C reduction is an important intervention for patients with dysglycemia or metabolic syndrome. This analysis suggests evolocumab can safely reduce LDL-C in these patients and could become a valuable tool in their care," lead investigator Dr. Robert R. Henry said in an interview prior to presenting the results at the annual meeting of the American Association of Clinical Endocrinologists.

"PCSK9 inhibitors are evolving as a novel and exciting class of medications that significantly reduce LDL-C. Patients with conditions like diabetes may greatly benefit from these treatments, particularly many of them [who] are unable to achieve their LDL targets or have difficulty with statin-associated side effects," he added.

But before this new class of drugs becomes available to clinicians, "I think there are still lots of studies to be done with evolocumab," said Dr. Henry, who is with the division of endocrinology and metabolism at the University of California, San Diego.

"The efficacy is quite striking. Of course, it’s currently being evaluated in cardiovascular outcome trials whether evolocumab translates to reduced cardiovascular events. And there is a large study ongoing of about 22,500 high-risk cardiovascular patients who are being studied for cardiovascular outcomes. So in the future, assuming these studies are positive, there is, I guess, a good chance this will be available."

In an interview, session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston, commented, "That’s very impressive data, a 50% reduction in LDL cholesterol with this drug. I think those data are very exciting. The drug has to go through the whole development process, but if it holds up in longer, more detailed studies, I think it looks very promising."

"Right now, the other options are basically statins," Dr. Horton noted. "Statins are very, very effective, but a lot of people get side effects from the statins, particularly the myositis can be a major problem. So this may be a very good alternative for the people who don’t tolerate statins. The fact that it’s an injection once a month I think is not a big deal, rather than just an oral agent. Statins are easy to take – you just take your statin orally, but a lot of people have trouble with the statins. So I think it’s going to have a role."

The patients studied were participants in the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER), an extension trial in which patients from four phase II studies of evolocumab were randomized 2:1 to open-label monthly subcutaneous evolocumab plus standard of care or to standard of care alone for 1 year.

Results for the entire trial population, reported previously, showed that evolocumab was safe, well tolerated, and efficacious (Circulation 2014;129:234-43).

The new analysis, which additionally looked at impact on glucose metabolism in the subset with metabolic perturbations, was based on 109 patients with type 2 diabetes, 134 with impaired fasting glucose, and 425 with metabolic syndrome, some of whom had more than one condition.

Evolocumab was associated with an LDL-C reduction of 47% in patients with type 2 diabetes, 51% in those with impaired fasting glucose, and 52% in those with metabolic syndrome – this compared with no change in their counterparts given standard of care alone. (It was 53% with evolocumab in trial patients who did not have any of metabolic perturbations.)

"Reductions were comparable to those observed in OSLER patients without these conditions," pointed out Dr. Henry.

The drug was also associated with improvement relative to standard care in levels of HDL cholesterol, triglycerides, and lipoprotein(a) that were again similar to those seen in trial patients who did not have these conditions.

Importantly, evolocumab was not associated with any significant changes in fasting plasma glucose or glycated hemoglobin levels relative to standard of care.

The combined evolocumab group and standard of care group had essentially the same rates of adverse events (78% and 72%) and serious adverse events (8% and 6%). Rates of serious laboratory abnormalities such as marked elevation of creatine kinase were low and similar as well.

The trial was sponsored by Amgen. Dr. Henry disclosed that he has affiliations with Amgen and Sanofi.

LAS VEGAS – Evolocumab, an investigational antibody that inhibits PCSK9, reduces levels of low-density lipoprotein cholesterol in hypercholesterolemic patients who have dysglycemia or metabolic syndrome – without worsening glucose metabolism, in contrast to what has been seen with high-intensity statin therapy, a new analysis shows.

"LDL-C reduction is an important intervention for patients with dysglycemia or metabolic syndrome. This analysis suggests evolocumab can safely reduce LDL-C in these patients and could become a valuable tool in their care," lead investigator Dr. Robert R. Henry said in an interview prior to presenting the results at the annual meeting of the American Association of Clinical Endocrinologists.

"PCSK9 inhibitors are evolving as a novel and exciting class of medications that significantly reduce LDL-C. Patients with conditions like diabetes may greatly benefit from these treatments, particularly many of them [who] are unable to achieve their LDL targets or have difficulty with statin-associated side effects," he added.

But before this new class of drugs becomes available to clinicians, "I think there are still lots of studies to be done with evolocumab," said Dr. Henry, who is with the division of endocrinology and metabolism at the University of California, San Diego.

"The efficacy is quite striking. Of course, it’s currently being evaluated in cardiovascular outcome trials whether evolocumab translates to reduced cardiovascular events. And there is a large study ongoing of about 22,500 high-risk cardiovascular patients who are being studied for cardiovascular outcomes. So in the future, assuming these studies are positive, there is, I guess, a good chance this will be available."

In an interview, session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston, commented, "That’s very impressive data, a 50% reduction in LDL cholesterol with this drug. I think those data are very exciting. The drug has to go through the whole development process, but if it holds up in longer, more detailed studies, I think it looks very promising."

"Right now, the other options are basically statins," Dr. Horton noted. "Statins are very, very effective, but a lot of people get side effects from the statins, particularly the myositis can be a major problem. So this may be a very good alternative for the people who don’t tolerate statins. The fact that it’s an injection once a month I think is not a big deal, rather than just an oral agent. Statins are easy to take – you just take your statin orally, but a lot of people have trouble with the statins. So I think it’s going to have a role."

The patients studied were participants in the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER), an extension trial in which patients from four phase II studies of evolocumab were randomized 2:1 to open-label monthly subcutaneous evolocumab plus standard of care or to standard of care alone for 1 year.

Results for the entire trial population, reported previously, showed that evolocumab was safe, well tolerated, and efficacious (Circulation 2014;129:234-43).

The new analysis, which additionally looked at impact on glucose metabolism in the subset with metabolic perturbations, was based on 109 patients with type 2 diabetes, 134 with impaired fasting glucose, and 425 with metabolic syndrome, some of whom had more than one condition.

Evolocumab was associated with an LDL-C reduction of 47% in patients with type 2 diabetes, 51% in those with impaired fasting glucose, and 52% in those with metabolic syndrome – this compared with no change in their counterparts given standard of care alone. (It was 53% with evolocumab in trial patients who did not have any of metabolic perturbations.)

"Reductions were comparable to those observed in OSLER patients without these conditions," pointed out Dr. Henry.

The drug was also associated with improvement relative to standard care in levels of HDL cholesterol, triglycerides, and lipoprotein(a) that were again similar to those seen in trial patients who did not have these conditions.

Importantly, evolocumab was not associated with any significant changes in fasting plasma glucose or glycated hemoglobin levels relative to standard of care.

The combined evolocumab group and standard of care group had essentially the same rates of adverse events (78% and 72%) and serious adverse events (8% and 6%). Rates of serious laboratory abnormalities such as marked elevation of creatine kinase were low and similar as well.

The trial was sponsored by Amgen. Dr. Henry disclosed that he has affiliations with Amgen and Sanofi.

LAS VEGAS – Evolocumab, an investigational antibody that inhibits PCSK9, reduces levels of low-density lipoprotein cholesterol in hypercholesterolemic patients who have dysglycemia or metabolic syndrome – without worsening glucose metabolism, in contrast to what has been seen with high-intensity statin therapy, a new analysis shows.

"LDL-C reduction is an important intervention for patients with dysglycemia or metabolic syndrome. This analysis suggests evolocumab can safely reduce LDL-C in these patients and could become a valuable tool in their care," lead investigator Dr. Robert R. Henry said in an interview prior to presenting the results at the annual meeting of the American Association of Clinical Endocrinologists.

"PCSK9 inhibitors are evolving as a novel and exciting class of medications that significantly reduce LDL-C. Patients with conditions like diabetes may greatly benefit from these treatments, particularly many of them [who] are unable to achieve their LDL targets or have difficulty with statin-associated side effects," he added.

But before this new class of drugs becomes available to clinicians, "I think there are still lots of studies to be done with evolocumab," said Dr. Henry, who is with the division of endocrinology and metabolism at the University of California, San Diego.

"The efficacy is quite striking. Of course, it’s currently being evaluated in cardiovascular outcome trials whether evolocumab translates to reduced cardiovascular events. And there is a large study ongoing of about 22,500 high-risk cardiovascular patients who are being studied for cardiovascular outcomes. So in the future, assuming these studies are positive, there is, I guess, a good chance this will be available."

In an interview, session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston, commented, "That’s very impressive data, a 50% reduction in LDL cholesterol with this drug. I think those data are very exciting. The drug has to go through the whole development process, but if it holds up in longer, more detailed studies, I think it looks very promising."

"Right now, the other options are basically statins," Dr. Horton noted. "Statins are very, very effective, but a lot of people get side effects from the statins, particularly the myositis can be a major problem. So this may be a very good alternative for the people who don’t tolerate statins. The fact that it’s an injection once a month I think is not a big deal, rather than just an oral agent. Statins are easy to take – you just take your statin orally, but a lot of people have trouble with the statins. So I think it’s going to have a role."

The patients studied were participants in the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER), an extension trial in which patients from four phase II studies of evolocumab were randomized 2:1 to open-label monthly subcutaneous evolocumab plus standard of care or to standard of care alone for 1 year.

Results for the entire trial population, reported previously, showed that evolocumab was safe, well tolerated, and efficacious (Circulation 2014;129:234-43).

The new analysis, which additionally looked at impact on glucose metabolism in the subset with metabolic perturbations, was based on 109 patients with type 2 diabetes, 134 with impaired fasting glucose, and 425 with metabolic syndrome, some of whom had more than one condition.

Evolocumab was associated with an LDL-C reduction of 47% in patients with type 2 diabetes, 51% in those with impaired fasting glucose, and 52% in those with metabolic syndrome – this compared with no change in their counterparts given standard of care alone. (It was 53% with evolocumab in trial patients who did not have any of metabolic perturbations.)

"Reductions were comparable to those observed in OSLER patients without these conditions," pointed out Dr. Henry.

The drug was also associated with improvement relative to standard care in levels of HDL cholesterol, triglycerides, and lipoprotein(a) that were again similar to those seen in trial patients who did not have these conditions.

Importantly, evolocumab was not associated with any significant changes in fasting plasma glucose or glycated hemoglobin levels relative to standard of care.

The combined evolocumab group and standard of care group had essentially the same rates of adverse events (78% and 72%) and serious adverse events (8% and 6%). Rates of serious laboratory abnormalities such as marked elevation of creatine kinase were low and similar as well.

The trial was sponsored by Amgen. Dr. Henry disclosed that he has affiliations with Amgen and Sanofi.

LAS VEGAS – Evolocumab, an investigational antibody that inhibits PCSK9, reduces levels of low-density lipoprotein cholesterol in hypercholesterolemic patients who have dysglycemia or metabolic syndrome – without worsening glucose metabolism, in contrast to what has been seen with high-intensity statin therapy, a new analysis shows.

"LDL-C reduction is an important intervention for patients with dysglycemia or metabolic syndrome. This analysis suggests evolocumab can safely reduce LDL-C in these patients and could become a valuable tool in their care," lead investigator Dr. Robert R. Henry said in an interview prior to presenting the results at the annual meeting of the American Association of Clinical Endocrinologists.

"PCSK9 inhibitors are evolving as a novel and exciting class of medications that significantly reduce LDL-C. Patients with conditions like diabetes may greatly benefit from these treatments, particularly many of them [who] are unable to achieve their LDL targets or have difficulty with statin-associated side effects," he added.

But before this new class of drugs becomes available to clinicians, "I think there are still lots of studies to be done with evolocumab," said Dr. Henry, who is with the division of endocrinology and metabolism at the University of California, San Diego.

"The efficacy is quite striking. Of course, it’s currently being evaluated in cardiovascular outcome trials whether evolocumab translates to reduced cardiovascular events. And there is a large study ongoing of about 22,500 high-risk cardiovascular patients who are being studied for cardiovascular outcomes. So in the future, assuming these studies are positive, there is, I guess, a good chance this will be available."

In an interview, session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston, commented, "That’s very impressive data, a 50% reduction in LDL cholesterol with this drug. I think those data are very exciting. The drug has to go through the whole development process, but if it holds up in longer, more detailed studies, I think it looks very promising."

"Right now, the other options are basically statins," Dr. Horton noted. "Statins are very, very effective, but a lot of people get side effects from the statins, particularly the myositis can be a major problem. So this may be a very good alternative for the people who don’t tolerate statins. The fact that it’s an injection once a month I think is not a big deal, rather than just an oral agent. Statins are easy to take – you just take your statin orally, but a lot of people have trouble with the statins. So I think it’s going to have a role."

The patients studied were participants in the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER), an extension trial in which patients from four phase II studies of evolocumab were randomized 2:1 to open-label monthly subcutaneous evolocumab plus standard of care or to standard of care alone for 1 year.

Results for the entire trial population, reported previously, showed that evolocumab was safe, well tolerated, and efficacious (Circulation 2014;129:234-43).

The new analysis, which additionally looked at impact on glucose metabolism in the subset with metabolic perturbations, was based on 109 patients with type 2 diabetes, 134 with impaired fasting glucose, and 425 with metabolic syndrome, some of whom had more than one condition.

Evolocumab was associated with an LDL-C reduction of 47% in patients with type 2 diabetes, 51% in those with impaired fasting glucose, and 52% in those with metabolic syndrome – this compared with no change in their counterparts given standard of care alone. (It was 53% with evolocumab in trial patients who did not have any of metabolic perturbations.)

"Reductions were comparable to those observed in OSLER patients without these conditions," pointed out Dr. Henry.

The drug was also associated with improvement relative to standard care in levels of HDL cholesterol, triglycerides, and lipoprotein(a) that were again similar to those seen in trial patients who did not have these conditions.

Importantly, evolocumab was not associated with any significant changes in fasting plasma glucose or glycated hemoglobin levels relative to standard of care.

The combined evolocumab group and standard of care group had essentially the same rates of adverse events (78% and 72%) and serious adverse events (8% and 6%). Rates of serious laboratory abnormalities such as marked elevation of creatine kinase were low and similar as well.

The trial was sponsored by Amgen. Dr. Henry disclosed that he has affiliations with Amgen and Sanofi.

LAS VEGAS – Hispanic adults have high prevalences of diabetes and related disorders overall, the largest ongoing U.S. health study of this population showed, but there are noteworthy differences by sex and ancestry that argue against a one-size-fits-all approach to care for this population.

Participants in the Hispanic Community Health Study/Study of Latinos are 16,415 individuals aged 18-74 years from four cities (San Diego, Chicago, Miami, and New York) who self identified as Hispanic/Latino. Seventy-nine percent were foreign born.

Among key findings of the study’s 2008-2011 baseline examination, about 35% of participants had metabolic syndrome, 36% had prediabetes, and 17% had diabetes, lead investigator Dr. Larissa Avilés-Santa reported at the annual meeting of the American Association of Clinical Endocrinologists.

Subgroup analyses showed that women were more likely than men to have the abdominal obesity component of metabolic syndrome but less likely to have elevated triglycerides. And individuals of Cuban ancestry were the most likely to have high blood pressure.

There were similar variations for prediabetes (most common in participants of Mexican ancestry and least common in those of Dominican ancestry) and diabetes (most common in those of Dominican, Puerto Rican, and Mexican ancestry and least common in those of South American ancestry).

"One of the main messages is that Hispanics are not a monolith. It has been assumed for a long time that Hispanics are a very homogenous group ... and that is not the case. Although we have cultural, historical, religious similarities, we also have differences," she commented in a press briefing. "Assuming homogeneity is not the way to address clinical care with Hispanics. It’s better to ask questions, to get to know the patient – where the patient is coming from – and then go from there."

The observed differences may stem from factors related to both country of origin and current living environment, proposed Dr. Avilés-Santa, who is a medical officer with the division of cardiovascular sciences of the National Heart, Lung, and Blood Institute in Bethesda, Md. Those factors could range from the more easily measured (genetics, diet, and language barriers) to the harder to pin down (health policy, discrimination, health-related beliefs, and religion).

"All of that, taken into consideration, is important because all of it may be playing a big role in the differences that we are observing among Hispanic groups," she maintained.

Additional study data showed the age-adjusted prevalence of hypertension was about 25% among participants overall (Am. J. Hypertens. 2014;27:793-800). It was lowest for those of Mexican and South American ancestry and highest for those of Puerto Rican and Dominican ancestry.

The proportion of participants aged 18-64 years who lacked health insurance ranged from 29% in New York to 71% in Miami. Among older participants, it ranged from 4% in New York to 26% in San Diego. "This is ... a question about policy because the majority who are insured are insured through Medicare. So what is happening with the Hispanic elders? And what is happening with their health if they are not having appropriate insurance coverage?" Dr. Avilés-Santa asked.

The data raise the question as to whether current screening practices for the general population are appropriate for Hispanics, she said. Also, they suggest there are as yet unidentified risk and protective factors at work when it comes to the development of diabetes.

In the study’s longitudinal component, the investigators are following the participants by telephone annually and will reexamine them later this year. Follow-up will continue through at least 2019.

In addition to disseminating the findings to the various communities, the investigators have collected DNA samples and are exploring associations of genetic variants with health measures and outcomes through the Omics in Latinos (OLa) project.

Dr. Avilés-Santa had no relevant conflicts of interest.

LAS VEGAS – Hispanic adults have high prevalences of diabetes and related disorders overall, the largest ongoing U.S. health study of this population showed, but there are noteworthy differences by sex and ancestry that argue against a one-size-fits-all approach to care for this population.

Participants in the Hispanic Community Health Study/Study of Latinos are 16,415 individuals aged 18-74 years from four cities (San Diego, Chicago, Miami, and New York) who self identified as Hispanic/Latino. Seventy-nine percent were foreign born.

Among key findings of the study’s 2008-2011 baseline examination, about 35% of participants had metabolic syndrome, 36% had prediabetes, and 17% had diabetes, lead investigator Dr. Larissa Avilés-Santa reported at the annual meeting of the American Association of Clinical Endocrinologists.

Subgroup analyses showed that women were more likely than men to have the abdominal obesity component of metabolic syndrome but less likely to have elevated triglycerides. And individuals of Cuban ancestry were the most likely to have high blood pressure.

There were similar variations for prediabetes (most common in participants of Mexican ancestry and least common in those of Dominican ancestry) and diabetes (most common in those of Dominican, Puerto Rican, and Mexican ancestry and least common in those of South American ancestry).

"One of the main messages is that Hispanics are not a monolith. It has been assumed for a long time that Hispanics are a very homogenous group ... and that is not the case. Although we have cultural, historical, religious similarities, we also have differences," she commented in a press briefing. "Assuming homogeneity is not the way to address clinical care with Hispanics. It’s better to ask questions, to get to know the patient – where the patient is coming from – and then go from there."

The observed differences may stem from factors related to both country of origin and current living environment, proposed Dr. Avilés-Santa, who is a medical officer with the division of cardiovascular sciences of the National Heart, Lung, and Blood Institute in Bethesda, Md. Those factors could range from the more easily measured (genetics, diet, and language barriers) to the harder to pin down (health policy, discrimination, health-related beliefs, and religion).

"All of that, taken into consideration, is important because all of it may be playing a big role in the differences that we are observing among Hispanic groups," she maintained.

Additional study data showed the age-adjusted prevalence of hypertension was about 25% among participants overall (Am. J. Hypertens. 2014;27:793-800). It was lowest for those of Mexican and South American ancestry and highest for those of Puerto Rican and Dominican ancestry.

The proportion of participants aged 18-64 years who lacked health insurance ranged from 29% in New York to 71% in Miami. Among older participants, it ranged from 4% in New York to 26% in San Diego. "This is ... a question about policy because the majority who are insured are insured through Medicare. So what is happening with the Hispanic elders? And what is happening with their health if they are not having appropriate insurance coverage?" Dr. Avilés-Santa asked.

The data raise the question as to whether current screening practices for the general population are appropriate for Hispanics, she said. Also, they suggest there are as yet unidentified risk and protective factors at work when it comes to the development of diabetes.

In the study’s longitudinal component, the investigators are following the participants by telephone annually and will reexamine them later this year. Follow-up will continue through at least 2019.

In addition to disseminating the findings to the various communities, the investigators have collected DNA samples and are exploring associations of genetic variants with health measures and outcomes through the Omics in Latinos (OLa) project.

Dr. Avilés-Santa had no relevant conflicts of interest.

LAS VEGAS – Hispanic adults have high prevalences of diabetes and related disorders overall, the largest ongoing U.S. health study of this population showed, but there are noteworthy differences by sex and ancestry that argue against a one-size-fits-all approach to care for this population.

Participants in the Hispanic Community Health Study/Study of Latinos are 16,415 individuals aged 18-74 years from four cities (San Diego, Chicago, Miami, and New York) who self identified as Hispanic/Latino. Seventy-nine percent were foreign born.

Among key findings of the study’s 2008-2011 baseline examination, about 35% of participants had metabolic syndrome, 36% had prediabetes, and 17% had diabetes, lead investigator Dr. Larissa Avilés-Santa reported at the annual meeting of the American Association of Clinical Endocrinologists.

Subgroup analyses showed that women were more likely than men to have the abdominal obesity component of metabolic syndrome but less likely to have elevated triglycerides. And individuals of Cuban ancestry were the most likely to have high blood pressure.

There were similar variations for prediabetes (most common in participants of Mexican ancestry and least common in those of Dominican ancestry) and diabetes (most common in those of Dominican, Puerto Rican, and Mexican ancestry and least common in those of South American ancestry).

"One of the main messages is that Hispanics are not a monolith. It has been assumed for a long time that Hispanics are a very homogenous group ... and that is not the case. Although we have cultural, historical, religious similarities, we also have differences," she commented in a press briefing. "Assuming homogeneity is not the way to address clinical care with Hispanics. It’s better to ask questions, to get to know the patient – where the patient is coming from – and then go from there."

The observed differences may stem from factors related to both country of origin and current living environment, proposed Dr. Avilés-Santa, who is a medical officer with the division of cardiovascular sciences of the National Heart, Lung, and Blood Institute in Bethesda, Md. Those factors could range from the more easily measured (genetics, diet, and language barriers) to the harder to pin down (health policy, discrimination, health-related beliefs, and religion).

"All of that, taken into consideration, is important because all of it may be playing a big role in the differences that we are observing among Hispanic groups," she maintained.

Additional study data showed the age-adjusted prevalence of hypertension was about 25% among participants overall (Am. J. Hypertens. 2014;27:793-800). It was lowest for those of Mexican and South American ancestry and highest for those of Puerto Rican and Dominican ancestry.

The proportion of participants aged 18-64 years who lacked health insurance ranged from 29% in New York to 71% in Miami. Among older participants, it ranged from 4% in New York to 26% in San Diego. "This is ... a question about policy because the majority who are insured are insured through Medicare. So what is happening with the Hispanic elders? And what is happening with their health if they are not having appropriate insurance coverage?" Dr. Avilés-Santa asked.

The data raise the question as to whether current screening practices for the general population are appropriate for Hispanics, she said. Also, they suggest there are as yet unidentified risk and protective factors at work when it comes to the development of diabetes.

In the study’s longitudinal component, the investigators are following the participants by telephone annually and will reexamine them later this year. Follow-up will continue through at least 2019.

In addition to disseminating the findings to the various communities, the investigators have collected DNA samples and are exploring associations of genetic variants with health measures and outcomes through the Omics in Latinos (OLa) project.

Dr. Avilés-Santa had no relevant conflicts of interest.

SCOTTSDALE, ARIZ. – Rates of perioperative complications among women undergoing hysterectomy for benign indications vary according to the route, an ancillary analysis of a retrospective cohort study found.

Analyses were based on 1,440 women who underwent hysterectomy at four teaching hospitals, with procedures about evenly split between the eras before and after introduction of robotic surgery, lead author Dr. Salma Rahimi of Mount Sinai Hospital, New York, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.

In the prerobot era, the rate of intraoperative complications – injury of the ureter, bladder, or bowel, or transfusion – was lowest at 3.7% for laparoscopic hysterectomy, about half that for abdominal procedures, and roughly the same as that for vaginal ones. The rate of postoperative complications – infection requiring antibiotics, transfusion, small bowel obstruction, or ileus – was 1.8% with laparoscopic hysterectomy, roughly a third of that seen with the other approaches.

In the postrobot era, the rate of intraoperative complications was 2.8% with vaginal hysterectomy, the lowest value for any approach, including the robotic one. The rate of postoperative complications was 3.0% for robotic hysterectomy, about a quarter of that for abdominal procedures and roughly on a par with that for vaginal and laparoscopic ones.

"Our data demonstrate that a vaginal hysterectomy is associated with fewer intraoperative complications in both the pre- and postrobot period," Dr. Rahimi commented. However, "vaginal hysterectomy was associated with more postoperative infections in the prerobot period."

"The highest complications were noted in the abdominal group, mostly due to transfusions, infections, small bowel obstructions, and ileus," she added.

Introducing the study, she noted that the American College of Obstetricians and Gynecologists recommends vaginal hysterectomy as a first choice over other routes given its relatively better outcomes and lower rates of complications (Obstet. Gynecol. 2009;114:1156-8). "Despite this, most are performed by laparotomy, and there is an increasing trend toward the use of minimally invasive abdominal approaches. Only about 20% are performed by the vaginal approach," she said.

The investigators studied women undergoing hysterectomy identified through the Fellows’ Pelvic Research Network. All of the operations were performed at hospitals with an obstetrics and gynecology residency and had a fellow belonging to the network. Women were excluded if their hysterectomy was performed by a gynecologic oncologist, was for a suspected malignancy, or was done emergently (including cesarean hysterectomies).

Analyses were based on 732 women in the prerobot era (the year before introduction of robotics at each hospital) and 708 in the postrobot era (2011). Characteristics of the women from the two eras were essentially the same, Dr. Rahimi reported at the meeting, jointly sponsored by the American College of Surgeons.

In the prerobot era, the rate of intraoperative complications was 3.9% for vaginal hysterectomy, compared with 7.4% for abdominal hysterectomy (P less than .05) and 3.7% for laparoscopic hysterectomy (P not significant).

The rate of postoperative complications was 8.3% for vaginal hysterectomy, compared with 7.4% for abdominal hysterectomy (P not significant) and 1.8% for laparoscopic hysterectomy (P = .001). These differences were mainly driven by higher rates of infection with the vaginal and abdominal approaches, and a higher rate of small bowel obstruction and ileus with the abdominal approach.

In the postrobot era, the rate of intraoperative complications was 2.8% for vaginal hysterectomy, compared with 10.8% for abdominal hysterectomy (P = .003), 4.6% for laparoscopic hysterectomy (P not significant), and 3.0% for robotic hysterectomy (P not significant). The differences were mainly due to a higher rate of transfusion with the abdominal approach.

The rate of postoperative complications was 5.1% for vaginal hysterectomy, compared with 13.9% for abdominal hysterectomy (P = .008), 3.6% for laparoscopic hysterectomy (P not significant), and 3.0% for robotic hysterectomy (P not significant). The differences again were mainly due to a higher rate of transfusion when surgery was done abdominally.

Dr. Rahimi disclosed no relevant conflicts of interest.

SCOTTSDALE, ARIZ. – Rates of perioperative complications among women undergoing hysterectomy for benign indications vary according to the route, an ancillary analysis of a retrospective cohort study found.

Analyses were based on 1,440 women who underwent hysterectomy at four teaching hospitals, with procedures about evenly split between the eras before and after introduction of robotic surgery, lead author Dr. Salma Rahimi of Mount Sinai Hospital, New York, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.

In the prerobot era, the rate of intraoperative complications – injury of the ureter, bladder, or bowel, or transfusion – was lowest at 3.7% for laparoscopic hysterectomy, about half that for abdominal procedures, and roughly the same as that for vaginal ones. The rate of postoperative complications – infection requiring antibiotics, transfusion, small bowel obstruction, or ileus – was 1.8% with laparoscopic hysterectomy, roughly a third of that seen with the other approaches.

In the postrobot era, the rate of intraoperative complications was 2.8% with vaginal hysterectomy, the lowest value for any approach, including the robotic one. The rate of postoperative complications was 3.0% for robotic hysterectomy, about a quarter of that for abdominal procedures and roughly on a par with that for vaginal and laparoscopic ones.

"Our data demonstrate that a vaginal hysterectomy is associated with fewer intraoperative complications in both the pre- and postrobot period," Dr. Rahimi commented. However, "vaginal hysterectomy was associated with more postoperative infections in the prerobot period."

"The highest complications were noted in the abdominal group, mostly due to transfusions, infections, small bowel obstructions, and ileus," she added.

Introducing the study, she noted that the American College of Obstetricians and Gynecologists recommends vaginal hysterectomy as a first choice over other routes given its relatively better outcomes and lower rates of complications (Obstet. Gynecol. 2009;114:1156-8). "Despite this, most are performed by laparotomy, and there is an increasing trend toward the use of minimally invasive abdominal approaches. Only about 20% are performed by the vaginal approach," she said.

The investigators studied women undergoing hysterectomy identified through the Fellows’ Pelvic Research Network. All of the operations were performed at hospitals with an obstetrics and gynecology residency and had a fellow belonging to the network. Women were excluded if their hysterectomy was performed by a gynecologic oncologist, was for a suspected malignancy, or was done emergently (including cesarean hysterectomies).

Analyses were based on 732 women in the prerobot era (the year before introduction of robotics at each hospital) and 708 in the postrobot era (2011). Characteristics of the women from the two eras were essentially the same, Dr. Rahimi reported at the meeting, jointly sponsored by the American College of Surgeons.

In the prerobot era, the rate of intraoperative complications was 3.9% for vaginal hysterectomy, compared with 7.4% for abdominal hysterectomy (P less than .05) and 3.7% for laparoscopic hysterectomy (P not significant).

The rate of postoperative complications was 8.3% for vaginal hysterectomy, compared with 7.4% for abdominal hysterectomy (P not significant) and 1.8% for laparoscopic hysterectomy (P = .001). These differences were mainly driven by higher rates of infection with the vaginal and abdominal approaches, and a higher rate of small bowel obstruction and ileus with the abdominal approach.

In the postrobot era, the rate of intraoperative complications was 2.8% for vaginal hysterectomy, compared with 10.8% for abdominal hysterectomy (P = .003), 4.6% for laparoscopic hysterectomy (P not significant), and 3.0% for robotic hysterectomy (P not significant). The differences were mainly due to a higher rate of transfusion with the abdominal approach.

The rate of postoperative complications was 5.1% for vaginal hysterectomy, compared with 13.9% for abdominal hysterectomy (P = .008), 3.6% for laparoscopic hysterectomy (P not significant), and 3.0% for robotic hysterectomy (P not significant). The differences again were mainly due to a higher rate of transfusion when surgery was done abdominally.

Dr. Rahimi disclosed no relevant conflicts of interest.

SCOTTSDALE, ARIZ. – Rates of perioperative complications among women undergoing hysterectomy for benign indications vary according to the route, an ancillary analysis of a retrospective cohort study found.

Analyses were based on 1,440 women who underwent hysterectomy at four teaching hospitals, with procedures about evenly split between the eras before and after introduction of robotic surgery, lead author Dr. Salma Rahimi of Mount Sinai Hospital, New York, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.

In the prerobot era, the rate of intraoperative complications – injury of the ureter, bladder, or bowel, or transfusion – was lowest at 3.7% for laparoscopic hysterectomy, about half that for abdominal procedures, and roughly the same as that for vaginal ones. The rate of postoperative complications – infection requiring antibiotics, transfusion, small bowel obstruction, or ileus – was 1.8% with laparoscopic hysterectomy, roughly a third of that seen with the other approaches.

In the postrobot era, the rate of intraoperative complications was 2.8% with vaginal hysterectomy, the lowest value for any approach, including the robotic one. The rate of postoperative complications was 3.0% for robotic hysterectomy, about a quarter of that for abdominal procedures and roughly on a par with that for vaginal and laparoscopic ones.

"Our data demonstrate that a vaginal hysterectomy is associated with fewer intraoperative complications in both the pre- and postrobot period," Dr. Rahimi commented. However, "vaginal hysterectomy was associated with more postoperative infections in the prerobot period."

"The highest complications were noted in the abdominal group, mostly due to transfusions, infections, small bowel obstructions, and ileus," she added.

Introducing the study, she noted that the American College of Obstetricians and Gynecologists recommends vaginal hysterectomy as a first choice over other routes given its relatively better outcomes and lower rates of complications (Obstet. Gynecol. 2009;114:1156-8). "Despite this, most are performed by laparotomy, and there is an increasing trend toward the use of minimally invasive abdominal approaches. Only about 20% are performed by the vaginal approach," she said.

The investigators studied women undergoing hysterectomy identified through the Fellows’ Pelvic Research Network. All of the operations were performed at hospitals with an obstetrics and gynecology residency and had a fellow belonging to the network. Women were excluded if their hysterectomy was performed by a gynecologic oncologist, was for a suspected malignancy, or was done emergently (including cesarean hysterectomies).

Analyses were based on 732 women in the prerobot era (the year before introduction of robotics at each hospital) and 708 in the postrobot era (2011). Characteristics of the women from the two eras were essentially the same, Dr. Rahimi reported at the meeting, jointly sponsored by the American College of Surgeons.

In the prerobot era, the rate of intraoperative complications was 3.9% for vaginal hysterectomy, compared with 7.4% for abdominal hysterectomy (P less than .05) and 3.7% for laparoscopic hysterectomy (P not significant).

The rate of postoperative complications was 8.3% for vaginal hysterectomy, compared with 7.4% for abdominal hysterectomy (P not significant) and 1.8% for laparoscopic hysterectomy (P = .001). These differences were mainly driven by higher rates of infection with the vaginal and abdominal approaches, and a higher rate of small bowel obstruction and ileus with the abdominal approach.

In the postrobot era, the rate of intraoperative complications was 2.8% for vaginal hysterectomy, compared with 10.8% for abdominal hysterectomy (P = .003), 4.6% for laparoscopic hysterectomy (P not significant), and 3.0% for robotic hysterectomy (P not significant). The differences were mainly due to a higher rate of transfusion with the abdominal approach.

The rate of postoperative complications was 5.1% for vaginal hysterectomy, compared with 13.9% for abdominal hysterectomy (P = .008), 3.6% for laparoscopic hysterectomy (P not significant), and 3.0% for robotic hysterectomy (P not significant). The differences again were mainly due to a higher rate of transfusion when surgery was done abdominally.

Dr. Rahimi disclosed no relevant conflicts of interest.