Kate Johnson

Children with severe obstructive sleep apnea demonstrate decreased IQ and other neuropsychological deficits, and have metabolic brain abnormalities that can be seen on imaging, indicating possible neuronal injury, according to a new study.

“We speculate that untreated [obstructive sleep apnea] could permanently alter the trajectory of a developing child's ultimate cognitive potential, resulting in a lifetime of health and economic impacts,” wrote Dr. Ann C. Halbower of Johns Hopkins University, Baltimore, and her colleagues in the August 22 issue of the global online journal Public Library of Science Medicine.

The findings do not necessarily indicate a causal relationship between obstructive sleep apnea (OSA) and neuronal abnormalities, they noted. “It remains to be determined if early identification and treatment can reverse the neuronal and performance deficits,” the authors wrote. However, the findings show altered neuronal metabolites in both the hippocampus and right frontal cortex of children with OSA.

“This is truly concerning because we saw changes that suggest brain injury in areas of the brain that house critical cognitive functions, such as attention, learning, and working memory,” Dr. Halbower said in a written statement. The cross-sectional study included 19 children with moderate-severe OSA (defined as an apnea-hypopnea index of 8 or higher as measured by polysomnography) and 12 healthy, nonsnoring children as controls. The groups were matched for age, ethnicity, gender, and socioeconomic status.

Neuropsychological evaluations performed on all subjects revealed that children with OSA had significantly lower scores, compared with controls, on full-scale IQ, and lower performance on measures of executive function, including verbal working memory and word fluency. There were no significant differences between the groups on any other neuropsychological variables, although a trend toward decreased visual-spatial memory and verbal memory in children with OSA might have gained statistical significance with larger numbers, the authors noted. (See box.)

A subset of 26 out of 31 subjects underwent one or two proton magnetic resonance spectroscopy (MRS) studies to detect both steady-state levels and ratios of three brain metabolites: N-acetylaspartate (NAA), choline (Cho), and creatine (Cr).

Single-voxel MRS comparisons of the left hippocampus in six children with OSA and six controls showed that the OSA group had a significant decrease in hippocampal NAA:Cho ratios, and a significant increase in Cho:Cr, “indicating abnormal neuronal metabolism in the static state,” the authors noted. MRS imaging of cortical structures showed a significant decrease in the NAA:Cho ratio in the right frontal cortex of seven children with OSA, compared with six controls.

There were no significant differences in cerebellar Cho:Cr or NAA:Cho ratios in five controls and seven children with OSA–although with larger numbers the latter ratio might have reached significance, the authors suggested.

The OSA subjects were significantly more overweight or obese than controls. “If obesity and [sleep-disordered breathing] interact, these combined problems, as well as lifestyle factors linked with obesity (such as television time), may play an important role in exacerbating neuropsychological impairments associated with sleep apnea,” they wrote.

ELSEVIER GLOBAL MEDICAL NEWS

Children with severe obstructive sleep apnea demonstrate decreased IQ and other neuropsychological deficits, and have metabolic brain abnormalities that can be seen on imaging, indicating possible neuronal injury, according to a new study.

“We speculate that untreated [obstructive sleep apnea] could permanently alter the trajectory of a developing child's ultimate cognitive potential, resulting in a lifetime of health and economic impacts,” wrote Dr. Ann C. Halbower of Johns Hopkins University, Baltimore, and her colleagues in the August 22 issue of the global online journal Public Library of Science Medicine.

The findings do not necessarily indicate a causal relationship between obstructive sleep apnea (OSA) and neuronal abnormalities, they noted. “It remains to be determined if early identification and treatment can reverse the neuronal and performance deficits,” the authors wrote. However, the findings show altered neuronal metabolites in both the hippocampus and right frontal cortex of children with OSA.

“This is truly concerning because we saw changes that suggest brain injury in areas of the brain that house critical cognitive functions, such as attention, learning, and working memory,” Dr. Halbower said in a written statement. The cross-sectional study included 19 children with moderate-severe OSA (defined as an apnea-hypopnea index of 8 or higher as measured by polysomnography) and 12 healthy, nonsnoring children as controls. The groups were matched for age, ethnicity, gender, and socioeconomic status.

Neuropsychological evaluations performed on all subjects revealed that children with OSA had significantly lower scores, compared with controls, on full-scale IQ, and lower performance on measures of executive function, including verbal working memory and word fluency. There were no significant differences between the groups on any other neuropsychological variables, although a trend toward decreased visual-spatial memory and verbal memory in children with OSA might have gained statistical significance with larger numbers, the authors noted. (See box.)

A subset of 26 out of 31 subjects underwent one or two proton magnetic resonance spectroscopy (MRS) studies to detect both steady-state levels and ratios of three brain metabolites: N-acetylaspartate (NAA), choline (Cho), and creatine (Cr).

Single-voxel MRS comparisons of the left hippocampus in six children with OSA and six controls showed that the OSA group had a significant decrease in hippocampal NAA:Cho ratios, and a significant increase in Cho:Cr, “indicating abnormal neuronal metabolism in the static state,” the authors noted. MRS imaging of cortical structures showed a significant decrease in the NAA:Cho ratio in the right frontal cortex of seven children with OSA, compared with six controls.

There were no significant differences in cerebellar Cho:Cr or NAA:Cho ratios in five controls and seven children with OSA–although with larger numbers the latter ratio might have reached significance, the authors suggested.

The OSA subjects were significantly more overweight or obese than controls. “If obesity and [sleep-disordered breathing] interact, these combined problems, as well as lifestyle factors linked with obesity (such as television time), may play an important role in exacerbating neuropsychological impairments associated with sleep apnea,” they wrote.

ELSEVIER GLOBAL MEDICAL NEWS

Children with severe obstructive sleep apnea demonstrate decreased IQ and other neuropsychological deficits, and have metabolic brain abnormalities that can be seen on imaging, indicating possible neuronal injury, according to a new study.

“We speculate that untreated [obstructive sleep apnea] could permanently alter the trajectory of a developing child's ultimate cognitive potential, resulting in a lifetime of health and economic impacts,” wrote Dr. Ann C. Halbower of Johns Hopkins University, Baltimore, and her colleagues in the August 22 issue of the global online journal Public Library of Science Medicine.

The findings do not necessarily indicate a causal relationship between obstructive sleep apnea (OSA) and neuronal abnormalities, they noted. “It remains to be determined if early identification and treatment can reverse the neuronal and performance deficits,” the authors wrote. However, the findings show altered neuronal metabolites in both the hippocampus and right frontal cortex of children with OSA.

“This is truly concerning because we saw changes that suggest brain injury in areas of the brain that house critical cognitive functions, such as attention, learning, and working memory,” Dr. Halbower said in a written statement. The cross-sectional study included 19 children with moderate-severe OSA (defined as an apnea-hypopnea index of 8 or higher as measured by polysomnography) and 12 healthy, nonsnoring children as controls. The groups were matched for age, ethnicity, gender, and socioeconomic status.

Neuropsychological evaluations performed on all subjects revealed that children with OSA had significantly lower scores, compared with controls, on full-scale IQ, and lower performance on measures of executive function, including verbal working memory and word fluency. There were no significant differences between the groups on any other neuropsychological variables, although a trend toward decreased visual-spatial memory and verbal memory in children with OSA might have gained statistical significance with larger numbers, the authors noted. (See box.)

A subset of 26 out of 31 subjects underwent one or two proton magnetic resonance spectroscopy (MRS) studies to detect both steady-state levels and ratios of three brain metabolites: N-acetylaspartate (NAA), choline (Cho), and creatine (Cr).

Single-voxel MRS comparisons of the left hippocampus in six children with OSA and six controls showed that the OSA group had a significant decrease in hippocampal NAA:Cho ratios, and a significant increase in Cho:Cr, “indicating abnormal neuronal metabolism in the static state,” the authors noted. MRS imaging of cortical structures showed a significant decrease in the NAA:Cho ratio in the right frontal cortex of seven children with OSA, compared with six controls.

There were no significant differences in cerebellar Cho:Cr or NAA:Cho ratios in five controls and seven children with OSA–although with larger numbers the latter ratio might have reached significance, the authors suggested.

The OSA subjects were significantly more overweight or obese than controls. “If obesity and [sleep-disordered breathing] interact, these combined problems, as well as lifestyle factors linked with obesity (such as television time), may play an important role in exacerbating neuropsychological impairments associated with sleep apnea,” they wrote.

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Exercise guidelines for children and adolescents should recommend more physical activity than they do currently, according to the authors of a new study.

“To prevent clustering of cardiovascular disease risk factors, physical activity levels should be higher than the current international guidelines of at least 1 hour per day of physical activity of at least moderate intensity,” wrote Lars Bo Andersen, Ph.D., from the Norwegian School of Sport Sciences, Oslo, and colleagues (Lancet 2006;368:299–304). “Achieving 90 minutes of daily activity might be necessary for children to prevent insulin resistance, which seems to be the central feature for clustering of cardiovascular disease risk factors.”

The cross-sectional study included data from 1,732 children aged 9 and 15 years—“on either side of puberty”—from Estonia, Denmark, and Portugal who were enrolled in the European Youth Heart Study. The researchers evaluated a combination of cardiovascular risk factors to calculate a combined risk factor score for each child. Factors that were measured included blood pressure, waist circumference, weight, height, pubertal status, skinfold thickness, cholesterol level, insulin resistance, and aerobic fitness. Each child's physical activity level was monitored with an accelerometer for 4 consecutive days.

The study found that cardiovascular risk decreased with increasing levels of physical activity, such that subjects in the most active quintile of physical activity showed the lowest risk. When compared with the most active quintile of subjects, risk in the third quintile and lower was significantly higher.

Thus, those in the least active quintile had an odds ratio of 3.29 for cardiovascular risk, those in the second quintile had an OR of 3.13, and those in the third quintile had an OR of 2.5, compared with the most active subjects. Subjects in the fourth quintile of physical activity did not have a significantly raised cardiovascular risk compared with the most active quintile. In 9-year-old children, this highest level of activity corresponded to 116 minutes, and in 15-year-olds, it corresponded to 88 minutes of moderate to vigorous intensity activity— the equivalent to a walking speed of 4 km/hour—every day.

“Whether the recommendation should be that all children ought to be as physically active as children in this quintile is a subjective judgment but the present data show consistently raised risk in the three lowest quintiles,” the authors wrote.

In an accompanying commentary, Dr. Ram Weiss and Dr. Itamar Raz from Hadassah Hebrew University Hospital in Jerusalem noted the consistency of the study's findings across all three countries and potentially different dietary habits. They also noted that the association between physical activity and cardiovascular risk “was independent of the degree of adiposity and was similar for lean and overweight children, emphasizing the effect of physical activity as an independent factor and not only as a protective measure against obesity” (Lancet 2006;368:261–2).

The study's authors noted that previous studies on which the current exercise guidelines were based depended on subjective recall of physical activity and often measured only one cardiovascular risk factor. “Clustering of cardiovascular disease risk factors has recently proven a better measure of cardiovascular health in children than single risk factors.”

Exercise guidelines for children and adolescents should recommend more physical activity than they do currently, according to the authors of a new study.

“To prevent clustering of cardiovascular disease risk factors, physical activity levels should be higher than the current international guidelines of at least 1 hour per day of physical activity of at least moderate intensity,” wrote Lars Bo Andersen, Ph.D., from the Norwegian School of Sport Sciences, Oslo, and colleagues (Lancet 2006;368:299–304). “Achieving 90 minutes of daily activity might be necessary for children to prevent insulin resistance, which seems to be the central feature for clustering of cardiovascular disease risk factors.”

The cross-sectional study included data from 1,732 children aged 9 and 15 years—“on either side of puberty”—from Estonia, Denmark, and Portugal who were enrolled in the European Youth Heart Study. The researchers evaluated a combination of cardiovascular risk factors to calculate a combined risk factor score for each child. Factors that were measured included blood pressure, waist circumference, weight, height, pubertal status, skinfold thickness, cholesterol level, insulin resistance, and aerobic fitness. Each child's physical activity level was monitored with an accelerometer for 4 consecutive days.

The study found that cardiovascular risk decreased with increasing levels of physical activity, such that subjects in the most active quintile of physical activity showed the lowest risk. When compared with the most active quintile of subjects, risk in the third quintile and lower was significantly higher.

Thus, those in the least active quintile had an odds ratio of 3.29 for cardiovascular risk, those in the second quintile had an OR of 3.13, and those in the third quintile had an OR of 2.5, compared with the most active subjects. Subjects in the fourth quintile of physical activity did not have a significantly raised cardiovascular risk compared with the most active quintile. In 9-year-old children, this highest level of activity corresponded to 116 minutes, and in 15-year-olds, it corresponded to 88 minutes of moderate to vigorous intensity activity— the equivalent to a walking speed of 4 km/hour—every day.

“Whether the recommendation should be that all children ought to be as physically active as children in this quintile is a subjective judgment but the present data show consistently raised risk in the three lowest quintiles,” the authors wrote.

In an accompanying commentary, Dr. Ram Weiss and Dr. Itamar Raz from Hadassah Hebrew University Hospital in Jerusalem noted the consistency of the study's findings across all three countries and potentially different dietary habits. They also noted that the association between physical activity and cardiovascular risk “was independent of the degree of adiposity and was similar for lean and overweight children, emphasizing the effect of physical activity as an independent factor and not only as a protective measure against obesity” (Lancet 2006;368:261–2).

The study's authors noted that previous studies on which the current exercise guidelines were based depended on subjective recall of physical activity and often measured only one cardiovascular risk factor. “Clustering of cardiovascular disease risk factors has recently proven a better measure of cardiovascular health in children than single risk factors.”

Exercise guidelines for children and adolescents should recommend more physical activity than they do currently, according to the authors of a new study.

“To prevent clustering of cardiovascular disease risk factors, physical activity levels should be higher than the current international guidelines of at least 1 hour per day of physical activity of at least moderate intensity,” wrote Lars Bo Andersen, Ph.D., from the Norwegian School of Sport Sciences, Oslo, and colleagues (Lancet 2006;368:299–304). “Achieving 90 minutes of daily activity might be necessary for children to prevent insulin resistance, which seems to be the central feature for clustering of cardiovascular disease risk factors.”

The cross-sectional study included data from 1,732 children aged 9 and 15 years—“on either side of puberty”—from Estonia, Denmark, and Portugal who were enrolled in the European Youth Heart Study. The researchers evaluated a combination of cardiovascular risk factors to calculate a combined risk factor score for each child. Factors that were measured included blood pressure, waist circumference, weight, height, pubertal status, skinfold thickness, cholesterol level, insulin resistance, and aerobic fitness. Each child's physical activity level was monitored with an accelerometer for 4 consecutive days.

The study found that cardiovascular risk decreased with increasing levels of physical activity, such that subjects in the most active quintile of physical activity showed the lowest risk. When compared with the most active quintile of subjects, risk in the third quintile and lower was significantly higher.

Thus, those in the least active quintile had an odds ratio of 3.29 for cardiovascular risk, those in the second quintile had an OR of 3.13, and those in the third quintile had an OR of 2.5, compared with the most active subjects. Subjects in the fourth quintile of physical activity did not have a significantly raised cardiovascular risk compared with the most active quintile. In 9-year-old children, this highest level of activity corresponded to 116 minutes, and in 15-year-olds, it corresponded to 88 minutes of moderate to vigorous intensity activity— the equivalent to a walking speed of 4 km/hour—every day.

“Whether the recommendation should be that all children ought to be as physically active as children in this quintile is a subjective judgment but the present data show consistently raised risk in the three lowest quintiles,” the authors wrote.

In an accompanying commentary, Dr. Ram Weiss and Dr. Itamar Raz from Hadassah Hebrew University Hospital in Jerusalem noted the consistency of the study's findings across all three countries and potentially different dietary habits. They also noted that the association between physical activity and cardiovascular risk “was independent of the degree of adiposity and was similar for lean and overweight children, emphasizing the effect of physical activity as an independent factor and not only as a protective measure against obesity” (Lancet 2006;368:261–2).

The study's authors noted that previous studies on which the current exercise guidelines were based depended on subjective recall of physical activity and often measured only one cardiovascular risk factor. “Clustering of cardiovascular disease risk factors has recently proven a better measure of cardiovascular health in children than single risk factors.”

COPENHAGEN — Type 1 diabetes, traditionally considered a disease of wasting, is now frequently diagnosed in children who are overweight, according to a new study.

That means that determining which pediatric patient has type 1 diabetes and which has type 2 is getting harder, said Dr. Ingrid M. Libman, assistant professor of pediatric endocrinology at the University of Pittsburgh.

“The problem now is that the lines are blurred between what we thought was clearly defined as type 1 and 2 diabetes,” Dr. Libman said in an interview. “The distinction can no longer be made based on phenotype.”

Data she presented at the annual meeting of the European Association for the Study of Diabetes showed that over 23 years of observation (1979–2002), the overall prevalence of overweight and obesity in children with newly diagnosed insulin-treated diabetes (traditionally considered type 1 disease) has more than tripled—doubling in African American children (from 30% to 62%) and quadrupling in white children (from 6% to 26%).

“In some cases we now have no clear way of distinguishing what kind of diabetes someone has based on how they look,” she said, adding that acanthosis nigricans, traditionally associated with type 2 diabetes, is now commonly found in overweight patients with type 1 disease as well.

Subjects diagnosed in period I (1979–1989) and period II (1990–98) were tested for beta-cell autoimmunity. In those with autoimmune positivity (known as diabetes type 1a), there was a similar increase in the prevalence of obesity between periods I and II: 6% to 21% among whites and 22% to 43% among African Americans. For period III (1999–2002), autoimmune antibodies are still being measured, she said. Autoimmune-negative subjects in the study may have had type 2 diabetes or type 1b—an insulin-dependent, nonautoimmune form of the disorder.

Dr. Libman said physicians might frequently face a new presentation of diabetes in which patients may actually have a confusing combination of characteristics.

“What we argue is that some kids may have characteristics of both type 1 and type 2 disease processes going on. If they are autoimmune positive, they have type 1a diabetes; however, if they are also overweight and have acanthosis nigricans, you could argue that they may also be insulin resistant.”

Although establishing a clear diagnosis may often seem essential to physicians, Dr. Libman said that in the end, it might not be so important.

“If the child is really sick, does it matter if they have type 1 or 2? You will need to treat them with insulin. If they are overweight, not sick, and diagnosed randomly, you can likely control their blood sugars with lifestyle and metformin. If their antibodies come back positive, it doesn't mean you should start insulin—but you may need to monitor them more carefully and you may have a lower threshold for starting it.”

Overweight in children may not only make them more susceptible to developing type 2 disease, but in those who are genetically susceptible, it may also increase their risk or accelerate the development of type 1 disease—the concept of “double diabetes,” she said.

“Genetically, they have the genes to develop diabetes at some point (or not), but if they become overweight, they may have more chance. Weight makes the beta cell work harder and may trigger an increased immune response—this is known as the 'accelerator hypothesis,' “she said, adding that first-degree relatives of patients with type 1 diabetes have a 1 in 20 chance of developing the disorder, making overweight particularly dangerous in this group.

COPENHAGEN — Type 1 diabetes, traditionally considered a disease of wasting, is now frequently diagnosed in children who are overweight, according to a new study.

That means that determining which pediatric patient has type 1 diabetes and which has type 2 is getting harder, said Dr. Ingrid M. Libman, assistant professor of pediatric endocrinology at the University of Pittsburgh.

“The problem now is that the lines are blurred between what we thought was clearly defined as type 1 and 2 diabetes,” Dr. Libman said in an interview. “The distinction can no longer be made based on phenotype.”

Data she presented at the annual meeting of the European Association for the Study of Diabetes showed that over 23 years of observation (1979–2002), the overall prevalence of overweight and obesity in children with newly diagnosed insulin-treated diabetes (traditionally considered type 1 disease) has more than tripled—doubling in African American children (from 30% to 62%) and quadrupling in white children (from 6% to 26%).

“In some cases we now have no clear way of distinguishing what kind of diabetes someone has based on how they look,” she said, adding that acanthosis nigricans, traditionally associated with type 2 diabetes, is now commonly found in overweight patients with type 1 disease as well.

Subjects diagnosed in period I (1979–1989) and period II (1990–98) were tested for beta-cell autoimmunity. In those with autoimmune positivity (known as diabetes type 1a), there was a similar increase in the prevalence of obesity between periods I and II: 6% to 21% among whites and 22% to 43% among African Americans. For period III (1999–2002), autoimmune antibodies are still being measured, she said. Autoimmune-negative subjects in the study may have had type 2 diabetes or type 1b—an insulin-dependent, nonautoimmune form of the disorder.

Dr. Libman said physicians might frequently face a new presentation of diabetes in which patients may actually have a confusing combination of characteristics.

“What we argue is that some kids may have characteristics of both type 1 and type 2 disease processes going on. If they are autoimmune positive, they have type 1a diabetes; however, if they are also overweight and have acanthosis nigricans, you could argue that they may also be insulin resistant.”

Although establishing a clear diagnosis may often seem essential to physicians, Dr. Libman said that in the end, it might not be so important.

“If the child is really sick, does it matter if they have type 1 or 2? You will need to treat them with insulin. If they are overweight, not sick, and diagnosed randomly, you can likely control their blood sugars with lifestyle and metformin. If their antibodies come back positive, it doesn't mean you should start insulin—but you may need to monitor them more carefully and you may have a lower threshold for starting it.”

Overweight in children may not only make them more susceptible to developing type 2 disease, but in those who are genetically susceptible, it may also increase their risk or accelerate the development of type 1 disease—the concept of “double diabetes,” she said.

“Genetically, they have the genes to develop diabetes at some point (or not), but if they become overweight, they may have more chance. Weight makes the beta cell work harder and may trigger an increased immune response—this is known as the 'accelerator hypothesis,' “she said, adding that first-degree relatives of patients with type 1 diabetes have a 1 in 20 chance of developing the disorder, making overweight particularly dangerous in this group.

COPENHAGEN — Type 1 diabetes, traditionally considered a disease of wasting, is now frequently diagnosed in children who are overweight, according to a new study.

That means that determining which pediatric patient has type 1 diabetes and which has type 2 is getting harder, said Dr. Ingrid M. Libman, assistant professor of pediatric endocrinology at the University of Pittsburgh.

“The problem now is that the lines are blurred between what we thought was clearly defined as type 1 and 2 diabetes,” Dr. Libman said in an interview. “The distinction can no longer be made based on phenotype.”

Data she presented at the annual meeting of the European Association for the Study of Diabetes showed that over 23 years of observation (1979–2002), the overall prevalence of overweight and obesity in children with newly diagnosed insulin-treated diabetes (traditionally considered type 1 disease) has more than tripled—doubling in African American children (from 30% to 62%) and quadrupling in white children (from 6% to 26%).

“In some cases we now have no clear way of distinguishing what kind of diabetes someone has based on how they look,” she said, adding that acanthosis nigricans, traditionally associated with type 2 diabetes, is now commonly found in overweight patients with type 1 disease as well.

Subjects diagnosed in period I (1979–1989) and period II (1990–98) were tested for beta-cell autoimmunity. In those with autoimmune positivity (known as diabetes type 1a), there was a similar increase in the prevalence of obesity between periods I and II: 6% to 21% among whites and 22% to 43% among African Americans. For period III (1999–2002), autoimmune antibodies are still being measured, she said. Autoimmune-negative subjects in the study may have had type 2 diabetes or type 1b—an insulin-dependent, nonautoimmune form of the disorder.

Dr. Libman said physicians might frequently face a new presentation of diabetes in which patients may actually have a confusing combination of characteristics.

“What we argue is that some kids may have characteristics of both type 1 and type 2 disease processes going on. If they are autoimmune positive, they have type 1a diabetes; however, if they are also overweight and have acanthosis nigricans, you could argue that they may also be insulin resistant.”

Although establishing a clear diagnosis may often seem essential to physicians, Dr. Libman said that in the end, it might not be so important.

“If the child is really sick, does it matter if they have type 1 or 2? You will need to treat them with insulin. If they are overweight, not sick, and diagnosed randomly, you can likely control their blood sugars with lifestyle and metformin. If their antibodies come back positive, it doesn't mean you should start insulin—but you may need to monitor them more carefully and you may have a lower threshold for starting it.”

Overweight in children may not only make them more susceptible to developing type 2 disease, but in those who are genetically susceptible, it may also increase their risk or accelerate the development of type 1 disease—the concept of “double diabetes,” she said.

“Genetically, they have the genes to develop diabetes at some point (or not), but if they become overweight, they may have more chance. Weight makes the beta cell work harder and may trigger an increased immune response—this is known as the 'accelerator hypothesis,' “she said, adding that first-degree relatives of patients with type 1 diabetes have a 1 in 20 chance of developing the disorder, making overweight particularly dangerous in this group.

COPENHAGEN — Children who are newly diagnosed with type 1 diabetes should be screened annually for celiac disease for at least 3 years and not just at diagnosis, according to Dr. Karin Larsson of Kristianstad (Sweden) Hospital.

Study findings, which were presented at annual meeting of the European Association for the Study of Diabetes, were based on 300 patients under age 20 (mean age 10 years) who were newly diagnosed with type 1 diabetes at six different pediatric diabetes centers in Sweden. Serum IgA-antiendomysium antibody (EMA) testing was done at baseline to screen for celiac disease and, if negative, testing was repeated annually for 5 years. Patients with a positive blood screening test then underwent intestinal biopsy to confirm celiac disease.

At the end of the 5-year study, 29 diabetes patients (10%) had been diagnosed with celiac disease after their diagnosis of diabetes. Two had preexisting celiac disease before their diagnosis of diabetes—one patient 2 years earlier; the other,10 years earlier. Twelve patients had a positive EMA test at the time of their diabetes diagnosis followed by biopsy confirmation of celiac disease. In the first year after the diabetes diagnosis, another 10 patients were diagnosed with celiac disease; another 5 were diagnosed in the second year. One more patient was diagnosed in year 3 and a final one in the fifth year. Of those diagnosed with celiac disease, 59% had no symptoms.

COPENHAGEN — Children who are newly diagnosed with type 1 diabetes should be screened annually for celiac disease for at least 3 years and not just at diagnosis, according to Dr. Karin Larsson of Kristianstad (Sweden) Hospital.

Study findings, which were presented at annual meeting of the European Association for the Study of Diabetes, were based on 300 patients under age 20 (mean age 10 years) who were newly diagnosed with type 1 diabetes at six different pediatric diabetes centers in Sweden. Serum IgA-antiendomysium antibody (EMA) testing was done at baseline to screen for celiac disease and, if negative, testing was repeated annually for 5 years. Patients with a positive blood screening test then underwent intestinal biopsy to confirm celiac disease.

At the end of the 5-year study, 29 diabetes patients (10%) had been diagnosed with celiac disease after their diagnosis of diabetes. Two had preexisting celiac disease before their diagnosis of diabetes—one patient 2 years earlier; the other,10 years earlier. Twelve patients had a positive EMA test at the time of their diabetes diagnosis followed by biopsy confirmation of celiac disease. In the first year after the diabetes diagnosis, another 10 patients were diagnosed with celiac disease; another 5 were diagnosed in the second year. One more patient was diagnosed in year 3 and a final one in the fifth year. Of those diagnosed with celiac disease, 59% had no symptoms.

COPENHAGEN — Children who are newly diagnosed with type 1 diabetes should be screened annually for celiac disease for at least 3 years and not just at diagnosis, according to Dr. Karin Larsson of Kristianstad (Sweden) Hospital.

Study findings, which were presented at annual meeting of the European Association for the Study of Diabetes, were based on 300 patients under age 20 (mean age 10 years) who were newly diagnosed with type 1 diabetes at six different pediatric diabetes centers in Sweden. Serum IgA-antiendomysium antibody (EMA) testing was done at baseline to screen for celiac disease and, if negative, testing was repeated annually for 5 years. Patients with a positive blood screening test then underwent intestinal biopsy to confirm celiac disease.

At the end of the 5-year study, 29 diabetes patients (10%) had been diagnosed with celiac disease after their diagnosis of diabetes. Two had preexisting celiac disease before their diagnosis of diabetes—one patient 2 years earlier; the other,10 years earlier. Twelve patients had a positive EMA test at the time of their diabetes diagnosis followed by biopsy confirmation of celiac disease. In the first year after the diabetes diagnosis, another 10 patients were diagnosed with celiac disease; another 5 were diagnosed in the second year. One more patient was diagnosed in year 3 and a final one in the fifth year. Of those diagnosed with celiac disease, 59% had no symptoms.

COPENHAGEN — Physicians should pay particular attention to prediabetes when considering a patient's cardiovascular health, according to new joint guidelines on diabetes and cardiovascular disease unveiled at the annual meeting of the European Association for the Study of Diabetes.

“The negative impact of dysglycemia is apparent before the onset of diabetes,” said Dr. Eberhard Standl of the International Diabetes Research Unit, Munich, and vice president of the association (EASD). “There are signs of diastolic dysfunction with impaired glucose tolerance before the development of overt diabetes.”

An executive summary of the joint guidelines, “Diabetes, Prediabetes, and Cardiovascular Disease,” drafted by the EASD and the European Society of Cardiology (ESC), is expected to be published simultaneously in the official journals of both organizations—the European Heart Journal and Diabetologia—in November. The full 200-page text, which includes 72 recommendations, will appear in the European Journal of Cardiovascular Prevention and Rehabilitation, as well as on the EASD and ESC Web sites, Dr. Standl said at press briefing during the meeting. Pocket guidelines also are being prepared.

The guidelines reflect a growing recognition within both fields of the common co-occurrence of diabetes and cardiovascular disease.

An algorithm included in the document recommends that physicians assess cardiovascular health in all their patients with known or unknown cardiovascular disease, using electrocardiography, echocardiography, and exercise testing. Patients with positive findings should be referred to a cardiologist.

Cardiologists are advised to assess diabetic status in their patients using the oral glucose tolerance test (OGTT). Although testing is not recommended in all cardiology patients, the decision about who to test can be made using the Finnish Diabetes Risk Score (FINDRISC), Dr. Standl said.

According to the EASD/ESC document, the OGTT is “the best method to diagnose previously unknown diabetes or prediabetes,” compared with fasting glucose measurements.

However, a spokesman for the American Diabetes Association said although the OGTT recommendation will mean greater identification of diabetes cases, it raises the risk of noncompliance.

“The test is somewhat cumbersome and adds to the burden of so many things that need to be done with these patients,” Dr. Vivian Fonseca said in an interview. Dr. Fonseca, professor of medicine at Tulane University, New Orleans, is drafting similar joint guidelines with the American Heart Association.

COPENHAGEN — Physicians should pay particular attention to prediabetes when considering a patient's cardiovascular health, according to new joint guidelines on diabetes and cardiovascular disease unveiled at the annual meeting of the European Association for the Study of Diabetes.

“The negative impact of dysglycemia is apparent before the onset of diabetes,” said Dr. Eberhard Standl of the International Diabetes Research Unit, Munich, and vice president of the association (EASD). “There are signs of diastolic dysfunction with impaired glucose tolerance before the development of overt diabetes.”

An executive summary of the joint guidelines, “Diabetes, Prediabetes, and Cardiovascular Disease,” drafted by the EASD and the European Society of Cardiology (ESC), is expected to be published simultaneously in the official journals of both organizations—the European Heart Journal and Diabetologia—in November. The full 200-page text, which includes 72 recommendations, will appear in the European Journal of Cardiovascular Prevention and Rehabilitation, as well as on the EASD and ESC Web sites, Dr. Standl said at press briefing during the meeting. Pocket guidelines also are being prepared.

The guidelines reflect a growing recognition within both fields of the common co-occurrence of diabetes and cardiovascular disease.

An algorithm included in the document recommends that physicians assess cardiovascular health in all their patients with known or unknown cardiovascular disease, using electrocardiography, echocardiography, and exercise testing. Patients with positive findings should be referred to a cardiologist.

Cardiologists are advised to assess diabetic status in their patients using the oral glucose tolerance test (OGTT). Although testing is not recommended in all cardiology patients, the decision about who to test can be made using the Finnish Diabetes Risk Score (FINDRISC), Dr. Standl said.

According to the EASD/ESC document, the OGTT is “the best method to diagnose previously unknown diabetes or prediabetes,” compared with fasting glucose measurements.

However, a spokesman for the American Diabetes Association said although the OGTT recommendation will mean greater identification of diabetes cases, it raises the risk of noncompliance.

“The test is somewhat cumbersome and adds to the burden of so many things that need to be done with these patients,” Dr. Vivian Fonseca said in an interview. Dr. Fonseca, professor of medicine at Tulane University, New Orleans, is drafting similar joint guidelines with the American Heart Association.

COPENHAGEN — Physicians should pay particular attention to prediabetes when considering a patient's cardiovascular health, according to new joint guidelines on diabetes and cardiovascular disease unveiled at the annual meeting of the European Association for the Study of Diabetes.

“The negative impact of dysglycemia is apparent before the onset of diabetes,” said Dr. Eberhard Standl of the International Diabetes Research Unit, Munich, and vice president of the association (EASD). “There are signs of diastolic dysfunction with impaired glucose tolerance before the development of overt diabetes.”

An executive summary of the joint guidelines, “Diabetes, Prediabetes, and Cardiovascular Disease,” drafted by the EASD and the European Society of Cardiology (ESC), is expected to be published simultaneously in the official journals of both organizations—the European Heart Journal and Diabetologia—in November. The full 200-page text, which includes 72 recommendations, will appear in the European Journal of Cardiovascular Prevention and Rehabilitation, as well as on the EASD and ESC Web sites, Dr. Standl said at press briefing during the meeting. Pocket guidelines also are being prepared.

The guidelines reflect a growing recognition within both fields of the common co-occurrence of diabetes and cardiovascular disease.

An algorithm included in the document recommends that physicians assess cardiovascular health in all their patients with known or unknown cardiovascular disease, using electrocardiography, echocardiography, and exercise testing. Patients with positive findings should be referred to a cardiologist.

Cardiologists are advised to assess diabetic status in their patients using the oral glucose tolerance test (OGTT). Although testing is not recommended in all cardiology patients, the decision about who to test can be made using the Finnish Diabetes Risk Score (FINDRISC), Dr. Standl said.

According to the EASD/ESC document, the OGTT is “the best method to diagnose previously unknown diabetes or prediabetes,” compared with fasting glucose measurements.

However, a spokesman for the American Diabetes Association said although the OGTT recommendation will mean greater identification of diabetes cases, it raises the risk of noncompliance.

“The test is somewhat cumbersome and adds to the burden of so many things that need to be done with these patients,” Dr. Vivian Fonseca said in an interview. Dr. Fonseca, professor of medicine at Tulane University, New Orleans, is drafting similar joint guidelines with the American Heart Association.

COPENHAGEN — Skin autofluorescence is a strong and independent predictor of mortality in patients with well-controlled type 2 diabetes, according to data presented at the annual meeting of the European Association for the Study of Diabetes.

The study was headed by Dr. Andries Smit, head of the vascular unit of the University Medical Center in Groningen, the Netherlands, and medical director and founder of DiagnOptics, which markets a skin autofluorescence (AF) measuring device called the AGE Reader.

Elevated levels of advanced glycation end products (AGEs) have been shown to predict cardiovascular complications better than blood sugar levels in patients with diabetes. Dr. Smit's group previously showed that AGE levels can be measured in diabetic patients using skin AF (Diabetologia 2004;47:1324–30; Ann. N.Y. Acad. Sci. 2005;1043:290–8).

The current study involved 973 patients with type 2 diabetes (median duration 4.2 years) and well-controlled hemoglobin A_1c (HbA_1c). Skin AF levels were measured with the AGE Reader at baseline and a median of 3.2 years later. A total of 86 patients died during the study, 44 from cardiovascular disease, said Dr. Helen Lutgers, of the diabetes outpatient clinic, Isala Clinics, Zwolle, the Netherlands, who presented the study at the meeting.

In a Cox regression analysis, smoking, the presence of peripheral vascular disease, and skin AF predicted mortality, with relative risks of 2.17, 2.15, and 1.69, respectively, she reported, but blood sugar, blood pressure, and lipid parameters were not predictive. “This is a superior measurement to HbA_1c.”

The AGE Reader measures skin AF noninvasively and can give results in 30 seconds, Dr. Smit said in an interview. “[It] gives incremental prognostic information … in type 2 diabetes at a fraction of the burden and cost of [other] tools.”

The device is approved for marketing in Europe (at a cost of about $25,500). The company is waiting for Food and Drug Administration approval in the United States. U.S. physicians can order the equipment and use it as an investigational device, Dr. Smit said.

The AGE Reader noninvasively detects advanced glycation end products. DiagnOptics BV

COPENHAGEN — Skin autofluorescence is a strong and independent predictor of mortality in patients with well-controlled type 2 diabetes, according to data presented at the annual meeting of the European Association for the Study of Diabetes.

The study was headed by Dr. Andries Smit, head of the vascular unit of the University Medical Center in Groningen, the Netherlands, and medical director and founder of DiagnOptics, which markets a skin autofluorescence (AF) measuring device called the AGE Reader.

Elevated levels of advanced glycation end products (AGEs) have been shown to predict cardiovascular complications better than blood sugar levels in patients with diabetes. Dr. Smit's group previously showed that AGE levels can be measured in diabetic patients using skin AF (Diabetologia 2004;47:1324–30; Ann. N.Y. Acad. Sci. 2005;1043:290–8).

The current study involved 973 patients with type 2 diabetes (median duration 4.2 years) and well-controlled hemoglobin A_1c (HbA_1c). Skin AF levels were measured with the AGE Reader at baseline and a median of 3.2 years later. A total of 86 patients died during the study, 44 from cardiovascular disease, said Dr. Helen Lutgers, of the diabetes outpatient clinic, Isala Clinics, Zwolle, the Netherlands, who presented the study at the meeting.

In a Cox regression analysis, smoking, the presence of peripheral vascular disease, and skin AF predicted mortality, with relative risks of 2.17, 2.15, and 1.69, respectively, she reported, but blood sugar, blood pressure, and lipid parameters were not predictive. “This is a superior measurement to HbA_1c.”

The AGE Reader measures skin AF noninvasively and can give results in 30 seconds, Dr. Smit said in an interview. “[It] gives incremental prognostic information … in type 2 diabetes at a fraction of the burden and cost of [other] tools.”

The device is approved for marketing in Europe (at a cost of about $25,500). The company is waiting for Food and Drug Administration approval in the United States. U.S. physicians can order the equipment and use it as an investigational device, Dr. Smit said.

The AGE Reader noninvasively detects advanced glycation end products. DiagnOptics BV

COPENHAGEN — Skin autofluorescence is a strong and independent predictor of mortality in patients with well-controlled type 2 diabetes, according to data presented at the annual meeting of the European Association for the Study of Diabetes.

The study was headed by Dr. Andries Smit, head of the vascular unit of the University Medical Center in Groningen, the Netherlands, and medical director and founder of DiagnOptics, which markets a skin autofluorescence (AF) measuring device called the AGE Reader.

Elevated levels of advanced glycation end products (AGEs) have been shown to predict cardiovascular complications better than blood sugar levels in patients with diabetes. Dr. Smit's group previously showed that AGE levels can be measured in diabetic patients using skin AF (Diabetologia 2004;47:1324–30; Ann. N.Y. Acad. Sci. 2005;1043:290–8).

The current study involved 973 patients with type 2 diabetes (median duration 4.2 years) and well-controlled hemoglobin A_1c (HbA_1c). Skin AF levels were measured with the AGE Reader at baseline and a median of 3.2 years later. A total of 86 patients died during the study, 44 from cardiovascular disease, said Dr. Helen Lutgers, of the diabetes outpatient clinic, Isala Clinics, Zwolle, the Netherlands, who presented the study at the meeting.

In a Cox regression analysis, smoking, the presence of peripheral vascular disease, and skin AF predicted mortality, with relative risks of 2.17, 2.15, and 1.69, respectively, she reported, but blood sugar, blood pressure, and lipid parameters were not predictive. “This is a superior measurement to HbA_1c.”

The AGE Reader measures skin AF noninvasively and can give results in 30 seconds, Dr. Smit said in an interview. “[It] gives incremental prognostic information … in type 2 diabetes at a fraction of the burden and cost of [other] tools.”

The device is approved for marketing in Europe (at a cost of about $25,500). The company is waiting for Food and Drug Administration approval in the United States. U.S. physicians can order the equipment and use it as an investigational device, Dr. Smit said.

The AGE Reader noninvasively detects advanced glycation end products. DiagnOptics BV

COPENHAGEN — Inhaled insulin is less effective in diabetic patients with chronic lung conditions such as asthma and chronic obstructive pulmonary disease, compared with patients who have healthy lungs, according to data from two industry-sponsored studies presented at the annual meeting of the European Association for the Study of Diabetes.

However, in patients with mild asthma, predosing with a bronchodilator can result in inhaled insulin exposures similar to those for patients without asthma.

The asthma study was supported by Pfizer, manufacturer of the only approved inhaled insulin treatment, Exubera. Eli Lilly & Co. supported the other study.

Exubera is not approved for use in diabetic patients with asthma or chronic obstructive pulmonary disease (COPD), said Robert J. Fountaine, Pharm.D., of Pfizer's department of global research and development, who presented the Exubera study. Studies are under way to support long-term safety and efficacy in those patients.

Dr. Fountaine's open-label crossover study included 67 nondiabetic subjects with asthma: 30 with moderate asthma (those with a mean unmedicated forced expiratory volume [FEV1] of between 50% and 80% of predicted values); and 37 with mild asthma (defined as between 80% and 100% of predicted values). Also included were 19 healthy, nonasthmatic subjects.

All nonasthmatic subjects received inhaled insulin (3 mg) alone on days 1 and 3, whereas the asthmatic subjects received one of the following regimens in a randomized sequence on days 1, 3, 5, and 7: inhaled insulin alone, 180 mcg of the bronchodilator albuterol (a short-acting β-agonist) followed by inhaled insulin 30 minutes later, albuterol followed by inhaled insulin 10 minutes later, or the inhaled corticosteroid fluticasone (440 mcg) followed by inhaled insulin 30 minutes later.

Investigators collected blood samples at set times, beginning 30 minutes before insulin dosing until 360 minutes after, from which serum insulin and C-peptide levels were calculated. They also performed spirometry before and 10 minutes after each inhaled insulin dose, and before and 30 minutes after each albuterol dose.

The results showed that in the absence of albuterol, pulmonary absorption of inhaled insulin was reduced in patients with mild to moderate asthma, compared with nonasthmatic patients, said Dr. Fountaine. However, prior dosing with albuterol 30 minutes before insulin inhalation increased insulin absorption by 25%–35% in patients with mild asthma (resulting in absorption rates that approximated those in healthy subjects) and by 45%–50% in those with moderate asthma (resulting in absorption rates that were still lower than those seen in nonasthmatic subjects). The administration of fluticasone before inhaled insulin did not adversely affect insulin pharmacokinetics, and spirometry testing showed that inhaled insulin did not interfere with the efficacy of albuterol, he said.

The Lilly-sponsored study evaluated the company's inhaled insulin system, AIR, which is still under development. It found a reduced metabolic effect of inhaled insulin in nondiabetic patients with COPD, compared with healthy patients and compared with subcutaneous insulin administration, said Dr. Klaus Rave of Profil Institut für Stoffwechselforschung in Neuss, Germany.

The study included 15 subjects with healthy lungs and 27 with COPD, of whom 13 had chronic bronchitis and 14 had emphysema. All received two separate doses of inhaled insulin (5.2 mg each) and one dose of subcutaneous insulin (12 U). A euglycemic glucose clamp was used to assess glucodynamic responses, and serum insulin measurements were used to assess pharmacokinetics. Pulmonary function tests and spirometry were also performed.

The results showed that although total insulin exposure and metabolic effect was similar in all subjects after subcutaneous insulin, it was reduced after inhaled insulin in patients with COPD. Insulin exposure after inhaled insulin was cut by 22% in those with emphysema and by 44% in those with chronic bronchitis, compared with healthy subjects. The metabolic effect of inhaled insulin was reduced by 33% in those with emphysema and by 40% in those with chronic bronchitis.

There was no difference in pulmonary function tests done before and after inhaled insulin, but spirometry results showed an FEV1 decline after inhaled insulin and insulin administered subcutaneously, warranting a long-term safety evaluation of inhaled insulin in COPDpatients.

COPENHAGEN — Inhaled insulin is less effective in diabetic patients with chronic lung conditions such as asthma and chronic obstructive pulmonary disease, compared with patients who have healthy lungs, according to data from two industry-sponsored studies presented at the annual meeting of the European Association for the Study of Diabetes.

However, in patients with mild asthma, predosing with a bronchodilator can result in inhaled insulin exposures similar to those for patients without asthma.

The asthma study was supported by Pfizer, manufacturer of the only approved inhaled insulin treatment, Exubera. Eli Lilly & Co. supported the other study.

Exubera is not approved for use in diabetic patients with asthma or chronic obstructive pulmonary disease (COPD), said Robert J. Fountaine, Pharm.D., of Pfizer's department of global research and development, who presented the Exubera study. Studies are under way to support long-term safety and efficacy in those patients.

Dr. Fountaine's open-label crossover study included 67 nondiabetic subjects with asthma: 30 with moderate asthma (those with a mean unmedicated forced expiratory volume [FEV1] of between 50% and 80% of predicted values); and 37 with mild asthma (defined as between 80% and 100% of predicted values). Also included were 19 healthy, nonasthmatic subjects.

All nonasthmatic subjects received inhaled insulin (3 mg) alone on days 1 and 3, whereas the asthmatic subjects received one of the following regimens in a randomized sequence on days 1, 3, 5, and 7: inhaled insulin alone, 180 mcg of the bronchodilator albuterol (a short-acting β-agonist) followed by inhaled insulin 30 minutes later, albuterol followed by inhaled insulin 10 minutes later, or the inhaled corticosteroid fluticasone (440 mcg) followed by inhaled insulin 30 minutes later.

Investigators collected blood samples at set times, beginning 30 minutes before insulin dosing until 360 minutes after, from which serum insulin and C-peptide levels were calculated. They also performed spirometry before and 10 minutes after each inhaled insulin dose, and before and 30 minutes after each albuterol dose.

The results showed that in the absence of albuterol, pulmonary absorption of inhaled insulin was reduced in patients with mild to moderate asthma, compared with nonasthmatic patients, said Dr. Fountaine. However, prior dosing with albuterol 30 minutes before insulin inhalation increased insulin absorption by 25%–35% in patients with mild asthma (resulting in absorption rates that approximated those in healthy subjects) and by 45%–50% in those with moderate asthma (resulting in absorption rates that were still lower than those seen in nonasthmatic subjects). The administration of fluticasone before inhaled insulin did not adversely affect insulin pharmacokinetics, and spirometry testing showed that inhaled insulin did not interfere with the efficacy of albuterol, he said.

The Lilly-sponsored study evaluated the company's inhaled insulin system, AIR, which is still under development. It found a reduced metabolic effect of inhaled insulin in nondiabetic patients with COPD, compared with healthy patients and compared with subcutaneous insulin administration, said Dr. Klaus Rave of Profil Institut für Stoffwechselforschung in Neuss, Germany.

The study included 15 subjects with healthy lungs and 27 with COPD, of whom 13 had chronic bronchitis and 14 had emphysema. All received two separate doses of inhaled insulin (5.2 mg each) and one dose of subcutaneous insulin (12 U). A euglycemic glucose clamp was used to assess glucodynamic responses, and serum insulin measurements were used to assess pharmacokinetics. Pulmonary function tests and spirometry were also performed.

The results showed that although total insulin exposure and metabolic effect was similar in all subjects after subcutaneous insulin, it was reduced after inhaled insulin in patients with COPD. Insulin exposure after inhaled insulin was cut by 22% in those with emphysema and by 44% in those with chronic bronchitis, compared with healthy subjects. The metabolic effect of inhaled insulin was reduced by 33% in those with emphysema and by 40% in those with chronic bronchitis.

There was no difference in pulmonary function tests done before and after inhaled insulin, but spirometry results showed an FEV1 decline after inhaled insulin and insulin administered subcutaneously, warranting a long-term safety evaluation of inhaled insulin in COPDpatients.

COPENHAGEN — Inhaled insulin is less effective in diabetic patients with chronic lung conditions such as asthma and chronic obstructive pulmonary disease, compared with patients who have healthy lungs, according to data from two industry-sponsored studies presented at the annual meeting of the European Association for the Study of Diabetes.

However, in patients with mild asthma, predosing with a bronchodilator can result in inhaled insulin exposures similar to those for patients without asthma.

The asthma study was supported by Pfizer, manufacturer of the only approved inhaled insulin treatment, Exubera. Eli Lilly & Co. supported the other study.

Exubera is not approved for use in diabetic patients with asthma or chronic obstructive pulmonary disease (COPD), said Robert J. Fountaine, Pharm.D., of Pfizer's department of global research and development, who presented the Exubera study. Studies are under way to support long-term safety and efficacy in those patients.

Dr. Fountaine's open-label crossover study included 67 nondiabetic subjects with asthma: 30 with moderate asthma (those with a mean unmedicated forced expiratory volume [FEV1] of between 50% and 80% of predicted values); and 37 with mild asthma (defined as between 80% and 100% of predicted values). Also included were 19 healthy, nonasthmatic subjects.

All nonasthmatic subjects received inhaled insulin (3 mg) alone on days 1 and 3, whereas the asthmatic subjects received one of the following regimens in a randomized sequence on days 1, 3, 5, and 7: inhaled insulin alone, 180 mcg of the bronchodilator albuterol (a short-acting β-agonist) followed by inhaled insulin 30 minutes later, albuterol followed by inhaled insulin 10 minutes later, or the inhaled corticosteroid fluticasone (440 mcg) followed by inhaled insulin 30 minutes later.

Investigators collected blood samples at set times, beginning 30 minutes before insulin dosing until 360 minutes after, from which serum insulin and C-peptide levels were calculated. They also performed spirometry before and 10 minutes after each inhaled insulin dose, and before and 30 minutes after each albuterol dose.

The results showed that in the absence of albuterol, pulmonary absorption of inhaled insulin was reduced in patients with mild to moderate asthma, compared with nonasthmatic patients, said Dr. Fountaine. However, prior dosing with albuterol 30 minutes before insulin inhalation increased insulin absorption by 25%–35% in patients with mild asthma (resulting in absorption rates that approximated those in healthy subjects) and by 45%–50% in those with moderate asthma (resulting in absorption rates that were still lower than those seen in nonasthmatic subjects). The administration of fluticasone before inhaled insulin did not adversely affect insulin pharmacokinetics, and spirometry testing showed that inhaled insulin did not interfere with the efficacy of albuterol, he said.

The Lilly-sponsored study evaluated the company's inhaled insulin system, AIR, which is still under development. It found a reduced metabolic effect of inhaled insulin in nondiabetic patients with COPD, compared with healthy patients and compared with subcutaneous insulin administration, said Dr. Klaus Rave of Profil Institut für Stoffwechselforschung in Neuss, Germany.

The study included 15 subjects with healthy lungs and 27 with COPD, of whom 13 had chronic bronchitis and 14 had emphysema. All received two separate doses of inhaled insulin (5.2 mg each) and one dose of subcutaneous insulin (12 U). A euglycemic glucose clamp was used to assess glucodynamic responses, and serum insulin measurements were used to assess pharmacokinetics. Pulmonary function tests and spirometry were also performed.

The results showed that although total insulin exposure and metabolic effect was similar in all subjects after subcutaneous insulin, it was reduced after inhaled insulin in patients with COPD. Insulin exposure after inhaled insulin was cut by 22% in those with emphysema and by 44% in those with chronic bronchitis, compared with healthy subjects. The metabolic effect of inhaled insulin was reduced by 33% in those with emphysema and by 40% in those with chronic bronchitis.

There was no difference in pulmonary function tests done before and after inhaled insulin, but spirometry results showed an FEV1 decline after inhaled insulin and insulin administered subcutaneously, warranting a long-term safety evaluation of inhaled insulin in COPDpatients.

COPENHAGEN — Two-year data on the only approved inhaled-insulin treatment show that it has minimal adverse effects on pulmonary function, according to two new studies supported by Pfizer Inc., which manufactures the product (Exubera).

“It's safe, effective, and easy,” said Dr. Jay Skyler, who presented one of the studies at the annual meeting of the European Association for the Study of Diabetes. The findings offer reassuring evidence about possible effects on pulmonary function, which “lots of people have been concerned about,” he said in an interview. Two previous short-term studies (12 and 24 weeks) of inhaled insulin in patients with type 1 diabetes showed similar findings, but a longer-term study was needed, he added.

Dr. Skyler's study involved 580 patients with type 1 diabetes who were 18–65 years of age and had normal lung function. All were treated with basal insulin and were randomized either to subcutaneous prandial insulin (290 patients) or to inhaled prandial insulin (290 patients) three times daily for 2 years. The primary end point of the study was pulmonary function; secondary end points included blood sugar levels (HbA_1c), fasting plasma glucose (FPG), hypoglycemia, and body weight.

The data showed slightly decreased pulmonary function (less than 2% of baseline values) in subjects using inhaled insulin, compared with subcutaneous insulin. “The changes were small, occurred early [by 3 months], and did not progress,” said Dr. Skyler, who is a professor in the division of endocrinology, diabetes, and metabolism at the University of Miami.

The incidence of cough was more common in people using inhaled therapy (38% vs. 13%); however, it was predominantly a mild cough that was rarely productive and rarely occurred at night. “Other studies have shown this small change in pulmonary function reverses when the medication is stopped. We are stopping the medication now and then plan to resume it 6 months later to demonstrate this,” said Dr. Skyler.

HbA_1c levels were maintained in both groups throughout the study, but FPG levels were improved in the inhaled-insulin group, compared with the subcutaneous insulin group (from 170.1 to 156.8 mg/dL, compared with 166.9 to 173.5 mg/dL). The overall rate of hypoglycemic events was similar in both groups; however, there were fewer severe hypoglycemic events in patients using inhaled insulin (2.8 vs. 4.1 events per 100 subject-months, relative risk 0.67). In addition, patients using inhaled insulin experienced less weight gain than did patients using subcutaneous therapy (0.7 kg vs. 2.0 kg), he reported.

A striking difference between the two groups was the level of insulin antibodies, which was markedly elevated in the inhaled-insulin group, said Dr. Skyler. “Antibodies occur in response to any peptide that's given, and there is a greater proclivity to form antibodies anytime something is given across a mucosal surface. What's interesting in this study is that the antibodies went up, and started going down after a year.”

He said the issue is not whether antibodies form, but the fact that they had no adverse effect. “They don't impair the action of the insulin in any way or lead to any other adverse effect, and that's consistent with what we know about injected insulin as well.”

In addition to being the principal investigator for Pfizer on this study, Dr. Skyler has chaired Pfizer's global Exubera advisory board and has also worked with all the other companies that are developing inhaled insulin: Novo Nordisk Inc., MannKind Corp., Eli Lilly and Co., and Kos Pharmaceuticals Inc.

A second Pfizer study presented as a poster was designed identically but included 635 patients with type 2 diabetes, rather than type 1 disease. A total of 319 subjects were randomized to the inhaled-insulin arm, whereas 316 received subcutaneous therapy, reported Dr. William Cefalu, professor and chief of the division of nutrition and chronic diseases at the Pennington Biomedical Research Center in Baton Rouge, La., and colleagues. The center is affiliated with Louisiana State University.

For the same primary and secondary end points, the study's results were similar to those of the Miami study, except that all hypoglycemic events, including severe events, were comparable in both groups.

“These data support previous findings that Exubera is an appropriate treatment for adult patients with [type 2 diabetes]. Availability of Exubera may provide an opportunity to increase the acceptance of insulin therapy, and thus improve glycemic control” in patients with type 2 diabetes who are suboptimally controlled on oral agents, wrote the authors.

Dr. Cefalu has served as research investigator for several inhaled-insulin studies for Pfizer and on Pfizer's inhaled-insulin advisory boards. He has worked with all other companies developing inhaled insulin.

Patients who used inhaled insulin had slight decreases in pulmonary function that occurred early and did not progress. Cough was reported by 38%. Pfizer Inc

COPENHAGEN — Two-year data on the only approved inhaled-insulin treatment show that it has minimal adverse effects on pulmonary function, according to two new studies supported by Pfizer Inc., which manufactures the product (Exubera).

“It's safe, effective, and easy,” said Dr. Jay Skyler, who presented one of the studies at the annual meeting of the European Association for the Study of Diabetes. The findings offer reassuring evidence about possible effects on pulmonary function, which “lots of people have been concerned about,” he said in an interview. Two previous short-term studies (12 and 24 weeks) of inhaled insulin in patients with type 1 diabetes showed similar findings, but a longer-term study was needed, he added.

Dr. Skyler's study involved 580 patients with type 1 diabetes who were 18–65 years of age and had normal lung function. All were treated with basal insulin and were randomized either to subcutaneous prandial insulin (290 patients) or to inhaled prandial insulin (290 patients) three times daily for 2 years. The primary end point of the study was pulmonary function; secondary end points included blood sugar levels (HbA_1c), fasting plasma glucose (FPG), hypoglycemia, and body weight.

The data showed slightly decreased pulmonary function (less than 2% of baseline values) in subjects using inhaled insulin, compared with subcutaneous insulin. “The changes were small, occurred early [by 3 months], and did not progress,” said Dr. Skyler, who is a professor in the division of endocrinology, diabetes, and metabolism at the University of Miami.

The incidence of cough was more common in people using inhaled therapy (38% vs. 13%); however, it was predominantly a mild cough that was rarely productive and rarely occurred at night. “Other studies have shown this small change in pulmonary function reverses when the medication is stopped. We are stopping the medication now and then plan to resume it 6 months later to demonstrate this,” said Dr. Skyler.

HbA_1c levels were maintained in both groups throughout the study, but FPG levels were improved in the inhaled-insulin group, compared with the subcutaneous insulin group (from 170.1 to 156.8 mg/dL, compared with 166.9 to 173.5 mg/dL). The overall rate of hypoglycemic events was similar in both groups; however, there were fewer severe hypoglycemic events in patients using inhaled insulin (2.8 vs. 4.1 events per 100 subject-months, relative risk 0.67). In addition, patients using inhaled insulin experienced less weight gain than did patients using subcutaneous therapy (0.7 kg vs. 2.0 kg), he reported.

A striking difference between the two groups was the level of insulin antibodies, which was markedly elevated in the inhaled-insulin group, said Dr. Skyler. “Antibodies occur in response to any peptide that's given, and there is a greater proclivity to form antibodies anytime something is given across a mucosal surface. What's interesting in this study is that the antibodies went up, and started going down after a year.”

He said the issue is not whether antibodies form, but the fact that they had no adverse effect. “They don't impair the action of the insulin in any way or lead to any other adverse effect, and that's consistent with what we know about injected insulin as well.”

In addition to being the principal investigator for Pfizer on this study, Dr. Skyler has chaired Pfizer's global Exubera advisory board and has also worked with all the other companies that are developing inhaled insulin: Novo Nordisk Inc., MannKind Corp., Eli Lilly and Co., and Kos Pharmaceuticals Inc.

A second Pfizer study presented as a poster was designed identically but included 635 patients with type 2 diabetes, rather than type 1 disease. A total of 319 subjects were randomized to the inhaled-insulin arm, whereas 316 received subcutaneous therapy, reported Dr. William Cefalu, professor and chief of the division of nutrition and chronic diseases at the Pennington Biomedical Research Center in Baton Rouge, La., and colleagues. The center is affiliated with Louisiana State University.

For the same primary and secondary end points, the study's results were similar to those of the Miami study, except that all hypoglycemic events, including severe events, were comparable in both groups.

“These data support previous findings that Exubera is an appropriate treatment for adult patients with [type 2 diabetes]. Availability of Exubera may provide an opportunity to increase the acceptance of insulin therapy, and thus improve glycemic control” in patients with type 2 diabetes who are suboptimally controlled on oral agents, wrote the authors.

Dr. Cefalu has served as research investigator for several inhaled-insulin studies for Pfizer and on Pfizer's inhaled-insulin advisory boards. He has worked with all other companies developing inhaled insulin.

Patients who used inhaled insulin had slight decreases in pulmonary function that occurred early and did not progress. Cough was reported by 38%. Pfizer Inc

COPENHAGEN — Two-year data on the only approved inhaled-insulin treatment show that it has minimal adverse effects on pulmonary function, according to two new studies supported by Pfizer Inc., which manufactures the product (Exubera).

“It's safe, effective, and easy,” said Dr. Jay Skyler, who presented one of the studies at the annual meeting of the European Association for the Study of Diabetes. The findings offer reassuring evidence about possible effects on pulmonary function, which “lots of people have been concerned about,” he said in an interview. Two previous short-term studies (12 and 24 weeks) of inhaled insulin in patients with type 1 diabetes showed similar findings, but a longer-term study was needed, he added.

Dr. Skyler's study involved 580 patients with type 1 diabetes who were 18–65 years of age and had normal lung function. All were treated with basal insulin and were randomized either to subcutaneous prandial insulin (290 patients) or to inhaled prandial insulin (290 patients) three times daily for 2 years. The primary end point of the study was pulmonary function; secondary end points included blood sugar levels (HbA_1c), fasting plasma glucose (FPG), hypoglycemia, and body weight.

The data showed slightly decreased pulmonary function (less than 2% of baseline values) in subjects using inhaled insulin, compared with subcutaneous insulin. “The changes were small, occurred early [by 3 months], and did not progress,” said Dr. Skyler, who is a professor in the division of endocrinology, diabetes, and metabolism at the University of Miami.

The incidence of cough was more common in people using inhaled therapy (38% vs. 13%); however, it was predominantly a mild cough that was rarely productive and rarely occurred at night. “Other studies have shown this small change in pulmonary function reverses when the medication is stopped. We are stopping the medication now and then plan to resume it 6 months later to demonstrate this,” said Dr. Skyler.

HbA_1c levels were maintained in both groups throughout the study, but FPG levels were improved in the inhaled-insulin group, compared with the subcutaneous insulin group (from 170.1 to 156.8 mg/dL, compared with 166.9 to 173.5 mg/dL). The overall rate of hypoglycemic events was similar in both groups; however, there were fewer severe hypoglycemic events in patients using inhaled insulin (2.8 vs. 4.1 events per 100 subject-months, relative risk 0.67). In addition, patients using inhaled insulin experienced less weight gain than did patients using subcutaneous therapy (0.7 kg vs. 2.0 kg), he reported.

A striking difference between the two groups was the level of insulin antibodies, which was markedly elevated in the inhaled-insulin group, said Dr. Skyler. “Antibodies occur in response to any peptide that's given, and there is a greater proclivity to form antibodies anytime something is given across a mucosal surface. What's interesting in this study is that the antibodies went up, and started going down after a year.”

He said the issue is not whether antibodies form, but the fact that they had no adverse effect. “They don't impair the action of the insulin in any way or lead to any other adverse effect, and that's consistent with what we know about injected insulin as well.”

In addition to being the principal investigator for Pfizer on this study, Dr. Skyler has chaired Pfizer's global Exubera advisory board and has also worked with all the other companies that are developing inhaled insulin: Novo Nordisk Inc., MannKind Corp., Eli Lilly and Co., and Kos Pharmaceuticals Inc.

A second Pfizer study presented as a poster was designed identically but included 635 patients with type 2 diabetes, rather than type 1 disease. A total of 319 subjects were randomized to the inhaled-insulin arm, whereas 316 received subcutaneous therapy, reported Dr. William Cefalu, professor and chief of the division of nutrition and chronic diseases at the Pennington Biomedical Research Center in Baton Rouge, La., and colleagues. The center is affiliated with Louisiana State University.

For the same primary and secondary end points, the study's results were similar to those of the Miami study, except that all hypoglycemic events, including severe events, were comparable in both groups.

“These data support previous findings that Exubera is an appropriate treatment for adult patients with [type 2 diabetes]. Availability of Exubera may provide an opportunity to increase the acceptance of insulin therapy, and thus improve glycemic control” in patients with type 2 diabetes who are suboptimally controlled on oral agents, wrote the authors.

Dr. Cefalu has served as research investigator for several inhaled-insulin studies for Pfizer and on Pfizer's inhaled-insulin advisory boards. He has worked with all other companies developing inhaled insulin.

Patients who used inhaled insulin had slight decreases in pulmonary function that occurred early and did not progress. Cough was reported by 38%. Pfizer Inc

Polycystic ovary syndrome is primarily a disorder of hyperandrogenism—either biochemical or clinical, or both, according to a newly released position statement from the Androgen Excess Society.

“Overall, … women with oligomenorrhea and polycystic-appearing ovaries on ultrasonography but no evidence of hyperandrogenism do not have PCOS,” wrote the society's seven-person task force of international experts (J. Clin. Endocrin. Metab. [Epub doi:10.1210/jc.2006–0178]).

The task force also acknowledged a minority opinion that there may possibly be forms of polycystic ovary syndrome (PCOS) “without overt evidence of hyperandrogenism,” although “more data are required before validating this supposition.”

A diagnosis of hyperandrogenism can be made biochemically by the confirmation of elevated circulating androgens or clinically with the observation of hirsutism, according to Dr. Ricardo Azziz, who chaired the Androgen Excess Society (AES) task force.

“People … often rely heavily on biochemical androgen levels, which is a mistake because it can leave out those patients with hirsutism but normal androgen levels. You have to look at the clinical picture as well,” he said in an interview.

The AES position statement, produced after a systematic review of 527 published, peer-reviewed medical articles, is aimed at establishing an evidence-based definition of PCOS, said Dr. Azziz, director of the Center for Androgen-Related Disorders and professor and chair of obstetrics and gynecology at Cedars-Sinai Medical Center at the University of California, Los Angeles.

The position statement stipulates that all three of the following criteria must be present for a diagnosis of PCOS:

▸ Hyperandrogenism—either biochemical or clinical, or both.

▸ Oligo-ovulation or polycystic ovaries, or both.

▸ Exclusion of other androgen excess disorders.

The two definitions that are currently used were established by expert panels—the first at the National Institutes of Health in 1990 and the second, in Rotterdam in 2003. They differ markedly on the necessity of hyperandrogenism for diagnosing PCOS and the relevance of an ultrasound finding of polycystic ovaries. (See box.)

The AES statement is a combination and clarification of the NIH and Rotterdam definitions and the first definition to come out of a review of evidence-based data, Dr. Azziz said. “With this definition, we capture what we think is the majority of patients with PCOS. It is broader than the NIH criteria but doesn't capture as much as the Rotterdam criteria, which were overly broad and resulted in the diagnosis of PCOS in women who simply had irregular ovulation and polycystic-looking ovaries. There may still be a few patients who may not be captured by this definition who in the future may be identified by new tests.”

Another important aspect of the statement is its de-emphasis of ultrasound findings in the diagnosis, said Dr. Neil Goodman, a reproductive endocrinologist in private practice in Miami and professor of medicine at the University of Miami. “Up to 20% of women with regular cycles, no hirsutism, and no evidence of androgen excess can have a polycystic ovary appearance on ultrasound,” said Dr. Goodman, who is chair of the American Association of Clinical Endocrinologists' task force on hyperandrogenic disorders and was not involved with the AES task force. “We need to document hyperandrogenism before we diagnose PCOS.”

ELSEVIER GLOBAL MEDICAL NEWS

Polycystic ovary syndrome is primarily a disorder of hyperandrogenism—either biochemical or clinical, or both, according to a newly released position statement from the Androgen Excess Society.

“Overall, … women with oligomenorrhea and polycystic-appearing ovaries on ultrasonography but no evidence of hyperandrogenism do not have PCOS,” wrote the society's seven-person task force of international experts (J. Clin. Endocrin. Metab. [Epub doi:10.1210/jc.2006–0178]).

The task force also acknowledged a minority opinion that there may possibly be forms of polycystic ovary syndrome (PCOS) “without overt evidence of hyperandrogenism,” although “more data are required before validating this supposition.”

A diagnosis of hyperandrogenism can be made biochemically by the confirmation of elevated circulating androgens or clinically with the observation of hirsutism, according to Dr. Ricardo Azziz, who chaired the Androgen Excess Society (AES) task force.

“People … often rely heavily on biochemical androgen levels, which is a mistake because it can leave out those patients with hirsutism but normal androgen levels. You have to look at the clinical picture as well,” he said in an interview.

The AES position statement, produced after a systematic review of 527 published, peer-reviewed medical articles, is aimed at establishing an evidence-based definition of PCOS, said Dr. Azziz, director of the Center for Androgen-Related Disorders and professor and chair of obstetrics and gynecology at Cedars-Sinai Medical Center at the University of California, Los Angeles.

The position statement stipulates that all three of the following criteria must be present for a diagnosis of PCOS:

▸ Hyperandrogenism—either biochemical or clinical, or both.

▸ Oligo-ovulation or polycystic ovaries, or both.

▸ Exclusion of other androgen excess disorders.

The two definitions that are currently used were established by expert panels—the first at the National Institutes of Health in 1990 and the second, in Rotterdam in 2003. They differ markedly on the necessity of hyperandrogenism for diagnosing PCOS and the relevance of an ultrasound finding of polycystic ovaries. (See box.)

The AES statement is a combination and clarification of the NIH and Rotterdam definitions and the first definition to come out of a review of evidence-based data, Dr. Azziz said. “With this definition, we capture what we think is the majority of patients with PCOS. It is broader than the NIH criteria but doesn't capture as much as the Rotterdam criteria, which were overly broad and resulted in the diagnosis of PCOS in women who simply had irregular ovulation and polycystic-looking ovaries. There may still be a few patients who may not be captured by this definition who in the future may be identified by new tests.”

Another important aspect of the statement is its de-emphasis of ultrasound findings in the diagnosis, said Dr. Neil Goodman, a reproductive endocrinologist in private practice in Miami and professor of medicine at the University of Miami. “Up to 20% of women with regular cycles, no hirsutism, and no evidence of androgen excess can have a polycystic ovary appearance on ultrasound,” said Dr. Goodman, who is chair of the American Association of Clinical Endocrinologists' task force on hyperandrogenic disorders and was not involved with the AES task force. “We need to document hyperandrogenism before we diagnose PCOS.”

ELSEVIER GLOBAL MEDICAL NEWS

Polycystic ovary syndrome is primarily a disorder of hyperandrogenism—either biochemical or clinical, or both, according to a newly released position statement from the Androgen Excess Society.

“Overall, … women with oligomenorrhea and polycystic-appearing ovaries on ultrasonography but no evidence of hyperandrogenism do not have PCOS,” wrote the society's seven-person task force of international experts (J. Clin. Endocrin. Metab. [Epub doi:10.1210/jc.2006–0178]).

The task force also acknowledged a minority opinion that there may possibly be forms of polycystic ovary syndrome (PCOS) “without overt evidence of hyperandrogenism,” although “more data are required before validating this supposition.”

A diagnosis of hyperandrogenism can be made biochemically by the confirmation of elevated circulating androgens or clinically with the observation of hirsutism, according to Dr. Ricardo Azziz, who chaired the Androgen Excess Society (AES) task force.

“People … often rely heavily on biochemical androgen levels, which is a mistake because it can leave out those patients with hirsutism but normal androgen levels. You have to look at the clinical picture as well,” he said in an interview.

The AES position statement, produced after a systematic review of 527 published, peer-reviewed medical articles, is aimed at establishing an evidence-based definition of PCOS, said Dr. Azziz, director of the Center for Androgen-Related Disorders and professor and chair of obstetrics and gynecology at Cedars-Sinai Medical Center at the University of California, Los Angeles.

The position statement stipulates that all three of the following criteria must be present for a diagnosis of PCOS:

▸ Hyperandrogenism—either biochemical or clinical, or both.

▸ Oligo-ovulation or polycystic ovaries, or both.

▸ Exclusion of other androgen excess disorders.

The two definitions that are currently used were established by expert panels—the first at the National Institutes of Health in 1990 and the second, in Rotterdam in 2003. They differ markedly on the necessity of hyperandrogenism for diagnosing PCOS and the relevance of an ultrasound finding of polycystic ovaries. (See box.)

The AES statement is a combination and clarification of the NIH and Rotterdam definitions and the first definition to come out of a review of evidence-based data, Dr. Azziz said. “With this definition, we capture what we think is the majority of patients with PCOS. It is broader than the NIH criteria but doesn't capture as much as the Rotterdam criteria, which were overly broad and resulted in the diagnosis of PCOS in women who simply had irregular ovulation and polycystic-looking ovaries. There may still be a few patients who may not be captured by this definition who in the future may be identified by new tests.”

Another important aspect of the statement is its de-emphasis of ultrasound findings in the diagnosis, said Dr. Neil Goodman, a reproductive endocrinologist in private practice in Miami and professor of medicine at the University of Miami. “Up to 20% of women with regular cycles, no hirsutism, and no evidence of androgen excess can have a polycystic ovary appearance on ultrasound,” said Dr. Goodman, who is chair of the American Association of Clinical Endocrinologists' task force on hyperandrogenic disorders and was not involved with the AES task force. “We need to document hyperandrogenism before we diagnose PCOS.”

ELSEVIER GLOBAL MEDICAL NEWS

COPENHAGEN — Skin autofluorescence is a strong and independent predictor of mortality in patients with well-controlled type 2 diabetes, according to a study presented at the annual meeting of the European Association for the Study of Diabetes.

The study was headed by Dr. Andries Smit, head of the vascular unit of the University Medical Center in Groningen, the Netherlands, and medical director and founder of DiagnOptics, a company that markets a skin autofluorescence (AF) measuring device called the AGE Reader.

Elevated levels of advanced glycation end products (AGEs) have previously been shown to predict cardiovascular complications better than blood sugar levels in patients with diabetes, and Dr. Smit's group has previously shown that AGE levels can be measured in diabetic patients using skin AF (Diabetologia 2004;47:1324–30; Ann. N.Y. Acad. Sci. 2005;1043:290–8).

The current study involved 973 patients with type 2 diabetes (median duration 4.2 years) and well-controlled hemoglobin A_1c (HbA_1c). Baseline skin AF measurements performed with the AGE Reader were compared with follow-up data a median of 3.2 years later. A total of 86 patients died during the study, 44 from cardiovascular disease, said Dr. Helen Lutgers, who presented the study at the meeting. In a Cox regression analysis, smoking, the presence of peripheral vascular disease, and skin AF were the only factors predicting mortality, with relative risks of 2.17, 2.15, and 1.69, she reported. Blood sugar, blood pressure, and lipid parameters were not predictive. “This is a superior measurement to HbA_1c,” said Dr. Lutgers of the diabetes outpatient clinic, Isala Clinics, Zwolle, the Netherlands.

The AGE Reader measures skin AF noninvasively and can give results in 30 seconds, Dr. Smit said in an interview. “[It] gives incremental prognostic information … in type 2 diabetes at a fraction of the burden and cost of [other] tools,” he said. Although the device is approved for marketing in Europe (at a cost of about 20,000 euros, or approximately $25,500), the company is waiting for Food and Drug Administration approval in the United States. However, in the interim, U.S. physicians can order the equipment from the company and use it as an investigational device, said Dr. Smit.

The AGE Reader noninvasively detects advanced glycation end products, which have been shown to predict cardiovascular complications in patients with diabetes. Measurement and display of results can be completed within 30 seconds. DiagnOptics BV

COPENHAGEN — Skin autofluorescence is a strong and independent predictor of mortality in patients with well-controlled type 2 diabetes, according to a study presented at the annual meeting of the European Association for the Study of Diabetes.

The study was headed by Dr. Andries Smit, head of the vascular unit of the University Medical Center in Groningen, the Netherlands, and medical director and founder of DiagnOptics, a company that markets a skin autofluorescence (AF) measuring device called the AGE Reader.

Elevated levels of advanced glycation end products (AGEs) have previously been shown to predict cardiovascular complications better than blood sugar levels in patients with diabetes, and Dr. Smit's group has previously shown that AGE levels can be measured in diabetic patients using skin AF (Diabetologia 2004;47:1324–30; Ann. N.Y. Acad. Sci. 2005;1043:290–8).

The current study involved 973 patients with type 2 diabetes (median duration 4.2 years) and well-controlled hemoglobin A_1c (HbA_1c). Baseline skin AF measurements performed with the AGE Reader were compared with follow-up data a median of 3.2 years later. A total of 86 patients died during the study, 44 from cardiovascular disease, said Dr. Helen Lutgers, who presented the study at the meeting. In a Cox regression analysis, smoking, the presence of peripheral vascular disease, and skin AF were the only factors predicting mortality, with relative risks of 2.17, 2.15, and 1.69, she reported. Blood sugar, blood pressure, and lipid parameters were not predictive. “This is a superior measurement to HbA_1c,” said Dr. Lutgers of the diabetes outpatient clinic, Isala Clinics, Zwolle, the Netherlands.

The AGE Reader measures skin AF noninvasively and can give results in 30 seconds, Dr. Smit said in an interview. “[It] gives incremental prognostic information … in type 2 diabetes at a fraction of the burden and cost of [other] tools,” he said. Although the device is approved for marketing in Europe (at a cost of about 20,000 euros, or approximately $25,500), the company is waiting for Food and Drug Administration approval in the United States. However, in the interim, U.S. physicians can order the equipment from the company and use it as an investigational device, said Dr. Smit.

The AGE Reader noninvasively detects advanced glycation end products, which have been shown to predict cardiovascular complications in patients with diabetes. Measurement and display of results can be completed within 30 seconds. DiagnOptics BV

COPENHAGEN — Skin autofluorescence is a strong and independent predictor of mortality in patients with well-controlled type 2 diabetes, according to a study presented at the annual meeting of the European Association for the Study of Diabetes.

The study was headed by Dr. Andries Smit, head of the vascular unit of the University Medical Center in Groningen, the Netherlands, and medical director and founder of DiagnOptics, a company that markets a skin autofluorescence (AF) measuring device called the AGE Reader.

Elevated levels of advanced glycation end products (AGEs) have previously been shown to predict cardiovascular complications better than blood sugar levels in patients with diabetes, and Dr. Smit's group has previously shown that AGE levels can be measured in diabetic patients using skin AF (Diabetologia 2004;47:1324–30; Ann. N.Y. Acad. Sci. 2005;1043:290–8).

The current study involved 973 patients with type 2 diabetes (median duration 4.2 years) and well-controlled hemoglobin A_1c (HbA_1c). Baseline skin AF measurements performed with the AGE Reader were compared with follow-up data a median of 3.2 years later. A total of 86 patients died during the study, 44 from cardiovascular disease, said Dr. Helen Lutgers, who presented the study at the meeting. In a Cox regression analysis, smoking, the presence of peripheral vascular disease, and skin AF were the only factors predicting mortality, with relative risks of 2.17, 2.15, and 1.69, she reported. Blood sugar, blood pressure, and lipid parameters were not predictive. “This is a superior measurement to HbA_1c,” said Dr. Lutgers of the diabetes outpatient clinic, Isala Clinics, Zwolle, the Netherlands.

The AGE Reader measures skin AF noninvasively and can give results in 30 seconds, Dr. Smit said in an interview. “[It] gives incremental prognostic information … in type 2 diabetes at a fraction of the burden and cost of [other] tools,” he said. Although the device is approved for marketing in Europe (at a cost of about 20,000 euros, or approximately $25,500), the company is waiting for Food and Drug Administration approval in the United States. However, in the interim, U.S. physicians can order the equipment from the company and use it as an investigational device, said Dr. Smit.

The AGE Reader noninvasively detects advanced glycation end products, which have been shown to predict cardiovascular complications in patients with diabetes. Measurement and display of results can be completed within 30 seconds. DiagnOptics BV