Miriam E. Tucker

MONTREAL — The largest-ever clinical trial in patients with type 2 diabetes continues to yield data that are expected to lead to improved prediction of cardiovascular risk as well as a better understanding of the relationship between intensive metabolic control and cardiovascular outcomes.

In a symposium lecture at the World Diabetes Congress, Dr. John P. Chalmers summarized data from published and unpublished substudies of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) study, a randomized, placebo-controlled trial that examined the effect of both intensive blood glucose and blood pressure control on micro- and macrovascular complications. The trial involved a multiethnic cohort of 11,140 patients with type 2 diabetes from 215 centers in 20 countries.

The glucose-lowering arm of ADVANCE, funded by grants from the French pharmaceutical company Servier and the National Health and Medical Research Council of Australia, used modified-release gliclazide along with other glucose-lowering drugs to target a hemoglobin A_1c of 6.5%.

The intensive-treatment group achieved a mean HbA_1c of 6.5%, vs. 7.3% in the standard-treatment group. At a median of 5 years, the intensive group had a 10% relative reduction in the combined outcome of major macro- and microvascular events vs. standard care, primarily as a consequence of a 21% relative reduction in nephropathy. There was a positive trend toward reduction of major cardiovascular (CV) events (N. Engl. J. Med. 2008;358:2560-72). There was no excess mortality, weight gain, or severe hypoglycemic episodes in the intensive group, said Dr. Chalmers, coprincipal investigator for ADVANCE.

In the blood pressure control arm, routine administration of a fixed combination of perindopril and indapamide was associated with a 9% reduction in the relative risk of a major macro- or microvascular event (Lancet 2007;370:829-40).

In a new, not-yet published subgroup analysis of the glucose-lowering arm, the results held true regardless of age, duration of diabetes, sex, body mass index, HbA_1c at study entry, urinary albumin excretion, glomerular filtration rate, or initial glucose-lowering treatment, said Dr. Chalmers, senior director of the George Institute for International Health, Sydney.

Cognitive function, however, was an independent predictor of cardiovascular risk. Mild and severe cognitive dysfunction increased the risk for major CV events. with hazard ratios of 1.27 and 1.42, respectively. Cardiovascular death was increased by hazard ratios of 1.41 and 1.56 for mild and severe cognitive dysfunction, respectively, and all-cause death by 1.33 and 1.50 (Diabetologia 2009;52:2328-36).

Another new and unpublished analysis showed that the risk for microvascular complications had a strong linear relationship with HbA_1c values down to 6.0%. Each percentage point reduction reduced the risk by 22%. For macrovascular events, CV death, and all-cause death, the risk reduction was linear down to an HbA_1c of 7.0%, then leveled off between 7% and 6%.

A substudy of 647 participants showed no significant associations between CV risk and body mass index, but there was a relationship with waist-hip ratio, a better index of visceral fat. Urinary albumin excretion also predicted risk: For every tenfold increase, there was a twofold increase in macrovascular events. Similarly, a halving of glomerular filtration rate was associated with a twofold increased risk for CV events, Dr. Chalmers said.

With ADVANCE data on CV risk predictors, the investigators are developing a risk engine specific for people with diabetes. Data from two other studies presented at the congress showed that neither Framingham score nor the risk engine derived from the 1998 United Kingdom Prospective Diabetes Study (UKPDS) is an accurate risk predictor for patients receiving modern treatments for glucose, blood pressure, and lipid levels.

Dr. Andre Pascal Kengne, also of the George Institute, presented one of these studies, which found that major cardiovascular risk among 7,502 ADVANCE participants was overestimated by 170% and 202% with use of two different Framingham equations.

Disclosures: Dr. Chalmers is on the advisory board for Servier. Dr. Kengne stated that he had no conflicts of interest.

MONTREAL — The largest-ever clinical trial in patients with type 2 diabetes continues to yield data that are expected to lead to improved prediction of cardiovascular risk as well as a better understanding of the relationship between intensive metabolic control and cardiovascular outcomes.

In a symposium lecture at the World Diabetes Congress, Dr. John P. Chalmers summarized data from published and unpublished substudies of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) study, a randomized, placebo-controlled trial that examined the effect of both intensive blood glucose and blood pressure control on micro- and macrovascular complications. The trial involved a multiethnic cohort of 11,140 patients with type 2 diabetes from 215 centers in 20 countries.

The glucose-lowering arm of ADVANCE, funded by grants from the French pharmaceutical company Servier and the National Health and Medical Research Council of Australia, used modified-release gliclazide along with other glucose-lowering drugs to target a hemoglobin A_1c of 6.5%.

The intensive-treatment group achieved a mean HbA_1c of 6.5%, vs. 7.3% in the standard-treatment group. At a median of 5 years, the intensive group had a 10% relative reduction in the combined outcome of major macro- and microvascular events vs. standard care, primarily as a consequence of a 21% relative reduction in nephropathy. There was a positive trend toward reduction of major cardiovascular (CV) events (N. Engl. J. Med. 2008;358:2560-72). There was no excess mortality, weight gain, or severe hypoglycemic episodes in the intensive group, said Dr. Chalmers, coprincipal investigator for ADVANCE.

In the blood pressure control arm, routine administration of a fixed combination of perindopril and indapamide was associated with a 9% reduction in the relative risk of a major macro- or microvascular event (Lancet 2007;370:829-40).

In a new, not-yet published subgroup analysis of the glucose-lowering arm, the results held true regardless of age, duration of diabetes, sex, body mass index, HbA_1c at study entry, urinary albumin excretion, glomerular filtration rate, or initial glucose-lowering treatment, said Dr. Chalmers, senior director of the George Institute for International Health, Sydney.

Cognitive function, however, was an independent predictor of cardiovascular risk. Mild and severe cognitive dysfunction increased the risk for major CV events. with hazard ratios of 1.27 and 1.42, respectively. Cardiovascular death was increased by hazard ratios of 1.41 and 1.56 for mild and severe cognitive dysfunction, respectively, and all-cause death by 1.33 and 1.50 (Diabetologia 2009;52:2328-36).

Another new and unpublished analysis showed that the risk for microvascular complications had a strong linear relationship with HbA_1c values down to 6.0%. Each percentage point reduction reduced the risk by 22%. For macrovascular events, CV death, and all-cause death, the risk reduction was linear down to an HbA_1c of 7.0%, then leveled off between 7% and 6%.

A substudy of 647 participants showed no significant associations between CV risk and body mass index, but there was a relationship with waist-hip ratio, a better index of visceral fat. Urinary albumin excretion also predicted risk: For every tenfold increase, there was a twofold increase in macrovascular events. Similarly, a halving of glomerular filtration rate was associated with a twofold increased risk for CV events, Dr. Chalmers said.

With ADVANCE data on CV risk predictors, the investigators are developing a risk engine specific for people with diabetes. Data from two other studies presented at the congress showed that neither Framingham score nor the risk engine derived from the 1998 United Kingdom Prospective Diabetes Study (UKPDS) is an accurate risk predictor for patients receiving modern treatments for glucose, blood pressure, and lipid levels.

Dr. Andre Pascal Kengne, also of the George Institute, presented one of these studies, which found that major cardiovascular risk among 7,502 ADVANCE participants was overestimated by 170% and 202% with use of two different Framingham equations.

Disclosures: Dr. Chalmers is on the advisory board for Servier. Dr. Kengne stated that he had no conflicts of interest.

MONTREAL — The largest-ever clinical trial in patients with type 2 diabetes continues to yield data that are expected to lead to improved prediction of cardiovascular risk as well as a better understanding of the relationship between intensive metabolic control and cardiovascular outcomes.

In a symposium lecture at the World Diabetes Congress, Dr. John P. Chalmers summarized data from published and unpublished substudies of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) study, a randomized, placebo-controlled trial that examined the effect of both intensive blood glucose and blood pressure control on micro- and macrovascular complications. The trial involved a multiethnic cohort of 11,140 patients with type 2 diabetes from 215 centers in 20 countries.

The glucose-lowering arm of ADVANCE, funded by grants from the French pharmaceutical company Servier and the National Health and Medical Research Council of Australia, used modified-release gliclazide along with other glucose-lowering drugs to target a hemoglobin A_1c of 6.5%.

The intensive-treatment group achieved a mean HbA_1c of 6.5%, vs. 7.3% in the standard-treatment group. At a median of 5 years, the intensive group had a 10% relative reduction in the combined outcome of major macro- and microvascular events vs. standard care, primarily as a consequence of a 21% relative reduction in nephropathy. There was a positive trend toward reduction of major cardiovascular (CV) events (N. Engl. J. Med. 2008;358:2560-72). There was no excess mortality, weight gain, or severe hypoglycemic episodes in the intensive group, said Dr. Chalmers, coprincipal investigator for ADVANCE.

In the blood pressure control arm, routine administration of a fixed combination of perindopril and indapamide was associated with a 9% reduction in the relative risk of a major macro- or microvascular event (Lancet 2007;370:829-40).

In a new, not-yet published subgroup analysis of the glucose-lowering arm, the results held true regardless of age, duration of diabetes, sex, body mass index, HbA_1c at study entry, urinary albumin excretion, glomerular filtration rate, or initial glucose-lowering treatment, said Dr. Chalmers, senior director of the George Institute for International Health, Sydney.

Cognitive function, however, was an independent predictor of cardiovascular risk. Mild and severe cognitive dysfunction increased the risk for major CV events. with hazard ratios of 1.27 and 1.42, respectively. Cardiovascular death was increased by hazard ratios of 1.41 and 1.56 for mild and severe cognitive dysfunction, respectively, and all-cause death by 1.33 and 1.50 (Diabetologia 2009;52:2328-36).

Another new and unpublished analysis showed that the risk for microvascular complications had a strong linear relationship with HbA_1c values down to 6.0%. Each percentage point reduction reduced the risk by 22%. For macrovascular events, CV death, and all-cause death, the risk reduction was linear down to an HbA_1c of 7.0%, then leveled off between 7% and 6%.

A substudy of 647 participants showed no significant associations between CV risk and body mass index, but there was a relationship with waist-hip ratio, a better index of visceral fat. Urinary albumin excretion also predicted risk: For every tenfold increase, there was a twofold increase in macrovascular events. Similarly, a halving of glomerular filtration rate was associated with a twofold increased risk for CV events, Dr. Chalmers said.

With ADVANCE data on CV risk predictors, the investigators are developing a risk engine specific for people with diabetes. Data from two other studies presented at the congress showed that neither Framingham score nor the risk engine derived from the 1998 United Kingdom Prospective Diabetes Study (UKPDS) is an accurate risk predictor for patients receiving modern treatments for glucose, blood pressure, and lipid levels.

Dr. Andre Pascal Kengne, also of the George Institute, presented one of these studies, which found that major cardiovascular risk among 7,502 ADVANCE participants was overestimated by 170% and 202% with use of two different Framingham equations.

Disclosures: Dr. Chalmers is on the advisory board for Servier. Dr. Kengne stated that he had no conflicts of interest.

NEW YORK — Early diabetes complications were seen in a significant proportion of 821 adolescents with type 1 diabetes for just 2-5 years.

Up to 1 in 5 of the adolescents had early indicators of eye, kidney, and/or nerve complications. The findings support early screening for diabetes complications as recommended by some—but not all—published consensus guidelines, Dr. Yoon Hi Cho said at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

The 821 patients were all seen at the Children's Hospital at Westmead, Sydney, between 1990 and 2006. They were aged 11-17 years, with a type 1 diabetes duration of 2-5 years (median 3.8) and a median hemoglobin A_1c level of 8.9%.

Early retinopathy, defined as one microaneurysm or hemorrhage on seven-field stereoscopic fundus photography, was detected in 9% of the patients. Albumin excretion rate (AER) was measured for overnight urine collections. Early nephropathy, defined as a borderline elevation of AER of 7.5 to less than 20 mcg/min, was seen in 22% of the adolescents. Microalbuminuria, defined as an AER of 20 mcg/min or greater, was identified in 3%. Peripheral nerve abnormalities on thermal and vibration thresholds at the feet—measured by thermal threshold tester and biothesiometer—were found in 22% of the patients, said Dr. Cho, a clinical endocrinology fellow at the hospital.

The proportions with borderline AER elevation rose from 16% of those aged 11-13 years to 23% of 13- to 15-year-olds to 25% of those aged 15-17 years. There was no significant effect of age for retinopathy (seen in 6%, 10%, and 11% of the three groups) or for peripheral nerve abnormalities (seen in 27%, 19%, and 22%). The rates of microalbuminuria remained low (4% or below). There was no significant difference in hemoglobin A_1c level between the three age groups (8.2%, 8.5%, and 8.6%), Dr. Cho said.

Retinopathy was significantly related to an elevated diastolic blood pressure level. A mean AER of 7.5 mcg/min or greater was associated with increased age, diabetes duration, and systolic BP. Peripheral nerve abnormalities were correlated with a higher BMI. There was no significant relationship between any of the complications and hemoglobin A_1c level, cholesterol level, sex, insulin dose, or insulin regimen, she said.

Guidelines from the International Society for Pediatric and Adolescent Diabetes and from the Australian Pediatric Endocrinology Group both advise screening children for diabetes complications after a diabetes duration of 5 years in prepubertal children and after 2 years in adolescents. The American Diabetes Association recommends retinopathy screening within 5 years of the onset of diabetes and nephropathy screening after a diabetes duration of 5 years in children aged 10 years and older.

“Longitudinal analysis will help define predictors of early complications and the potential for modifying [their] natural history,” said Dr. Cho, who had no relevant financial disclosures.

NEW YORK — Early diabetes complications were seen in a significant proportion of 821 adolescents with type 1 diabetes for just 2-5 years.

Up to 1 in 5 of the adolescents had early indicators of eye, kidney, and/or nerve complications. The findings support early screening for diabetes complications as recommended by some—but not all—published consensus guidelines, Dr. Yoon Hi Cho said at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

The 821 patients were all seen at the Children's Hospital at Westmead, Sydney, between 1990 and 2006. They were aged 11-17 years, with a type 1 diabetes duration of 2-5 years (median 3.8) and a median hemoglobin A_1c level of 8.9%.

Early retinopathy, defined as one microaneurysm or hemorrhage on seven-field stereoscopic fundus photography, was detected in 9% of the patients. Albumin excretion rate (AER) was measured for overnight urine collections. Early nephropathy, defined as a borderline elevation of AER of 7.5 to less than 20 mcg/min, was seen in 22% of the adolescents. Microalbuminuria, defined as an AER of 20 mcg/min or greater, was identified in 3%. Peripheral nerve abnormalities on thermal and vibration thresholds at the feet—measured by thermal threshold tester and biothesiometer—were found in 22% of the patients, said Dr. Cho, a clinical endocrinology fellow at the hospital.

The proportions with borderline AER elevation rose from 16% of those aged 11-13 years to 23% of 13- to 15-year-olds to 25% of those aged 15-17 years. There was no significant effect of age for retinopathy (seen in 6%, 10%, and 11% of the three groups) or for peripheral nerve abnormalities (seen in 27%, 19%, and 22%). The rates of microalbuminuria remained low (4% or below). There was no significant difference in hemoglobin A_1c level between the three age groups (8.2%, 8.5%, and 8.6%), Dr. Cho said.

Retinopathy was significantly related to an elevated diastolic blood pressure level. A mean AER of 7.5 mcg/min or greater was associated with increased age, diabetes duration, and systolic BP. Peripheral nerve abnormalities were correlated with a higher BMI. There was no significant relationship between any of the complications and hemoglobin A_1c level, cholesterol level, sex, insulin dose, or insulin regimen, she said.

Guidelines from the International Society for Pediatric and Adolescent Diabetes and from the Australian Pediatric Endocrinology Group both advise screening children for diabetes complications after a diabetes duration of 5 years in prepubertal children and after 2 years in adolescents. The American Diabetes Association recommends retinopathy screening within 5 years of the onset of diabetes and nephropathy screening after a diabetes duration of 5 years in children aged 10 years and older.

“Longitudinal analysis will help define predictors of early complications and the potential for modifying [their] natural history,” said Dr. Cho, who had no relevant financial disclosures.

NEW YORK — Early diabetes complications were seen in a significant proportion of 821 adolescents with type 1 diabetes for just 2-5 years.

Up to 1 in 5 of the adolescents had early indicators of eye, kidney, and/or nerve complications. The findings support early screening for diabetes complications as recommended by some—but not all—published consensus guidelines, Dr. Yoon Hi Cho said at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

The 821 patients were all seen at the Children's Hospital at Westmead, Sydney, between 1990 and 2006. They were aged 11-17 years, with a type 1 diabetes duration of 2-5 years (median 3.8) and a median hemoglobin A_1c level of 8.9%.

Early retinopathy, defined as one microaneurysm or hemorrhage on seven-field stereoscopic fundus photography, was detected in 9% of the patients. Albumin excretion rate (AER) was measured for overnight urine collections. Early nephropathy, defined as a borderline elevation of AER of 7.5 to less than 20 mcg/min, was seen in 22% of the adolescents. Microalbuminuria, defined as an AER of 20 mcg/min or greater, was identified in 3%. Peripheral nerve abnormalities on thermal and vibration thresholds at the feet—measured by thermal threshold tester and biothesiometer—were found in 22% of the patients, said Dr. Cho, a clinical endocrinology fellow at the hospital.

The proportions with borderline AER elevation rose from 16% of those aged 11-13 years to 23% of 13- to 15-year-olds to 25% of those aged 15-17 years. There was no significant effect of age for retinopathy (seen in 6%, 10%, and 11% of the three groups) or for peripheral nerve abnormalities (seen in 27%, 19%, and 22%). The rates of microalbuminuria remained low (4% or below). There was no significant difference in hemoglobin A_1c level between the three age groups (8.2%, 8.5%, and 8.6%), Dr. Cho said.

Retinopathy was significantly related to an elevated diastolic blood pressure level. A mean AER of 7.5 mcg/min or greater was associated with increased age, diabetes duration, and systolic BP. Peripheral nerve abnormalities were correlated with a higher BMI. There was no significant relationship between any of the complications and hemoglobin A_1c level, cholesterol level, sex, insulin dose, or insulin regimen, she said.

Guidelines from the International Society for Pediatric and Adolescent Diabetes and from the Australian Pediatric Endocrinology Group both advise screening children for diabetes complications after a diabetes duration of 5 years in prepubertal children and after 2 years in adolescents. The American Diabetes Association recommends retinopathy screening within 5 years of the onset of diabetes and nephropathy screening after a diabetes duration of 5 years in children aged 10 years and older.

“Longitudinal analysis will help define predictors of early complications and the potential for modifying [their] natural history,” said Dr. Cho, who had no relevant financial disclosures.

NEW YORK — Transient elastography correlated with aminotransferase levels in a cross-sectional study of 22 adolescent and young women with Turner's syndrome.

Transient elastography (TE), a novel technique for measuring liver stiffness, has been widely validated as a noninvasive alternative to liver biopsy for evaluating hepatic fibrosis in patients with chronic hepatitis C. It has not been used in Turner's syndrome (TS) patients, in whom liver involvement is common.

Although liver biopsy is the standard method for assessing liver fibrosis, it is an invasive and very expensive procedure that can incur life-threatening complications, and therefore can't be used as a tool to screen or monitor liver function in all TS patients.

TE is a painless procedure in which an ultrasound transducer probe mounted on a vibrator issues a wave through underlying tissues. Pulse-echo ultrasound acquisition is used to follow the propagation of the shear wave and to measure its velocity, which is directly related to tissue stiffness. The stiffer the tissue, the faster the shear wave propagates (J. Hepatol. 2008;48:835-47).

The findings from this small study—which will require replication in a larger number of patients—suggest that TE could be used to identify patients with elevated aminotransferase levels who might qualify for more invasive tests and possibly liver biopsy to better stage the etiology of liver involvement, Dr. Maria Francesca Messina said at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

The procedure could be used to monitor the progression of liver dysfunction in TS patients without exposing them to the significant clinical risks of more invasive procedures, Dr. Messina said.

The 22 TS patients had a mean age of 20.9 years and full pubertal development (spontaneous or pharmacologic). All fasted and underwent TE along with biochemical testing. Six patients were found to have elevated aminotransferase levels.

The mean liver stiffness for the entire group was 4.5 kilopascal (less than 7 kPa is generally considered mild or normal), and was significantly higher among those with elevated transaminase levels compared with those who had normal liver function (6 vs. 4 kPa), said Dr. Messina of the department of pediatrics at the University of Messina (Italy).

The TE device, called FibroScan, is marketed by France-based Echosens International (www.echosens.com

Dr. Messina stated that she has no relevant financial disclosures.

NEW YORK — Transient elastography correlated with aminotransferase levels in a cross-sectional study of 22 adolescent and young women with Turner's syndrome.

Transient elastography (TE), a novel technique for measuring liver stiffness, has been widely validated as a noninvasive alternative to liver biopsy for evaluating hepatic fibrosis in patients with chronic hepatitis C. It has not been used in Turner's syndrome (TS) patients, in whom liver involvement is common.

Although liver biopsy is the standard method for assessing liver fibrosis, it is an invasive and very expensive procedure that can incur life-threatening complications, and therefore can't be used as a tool to screen or monitor liver function in all TS patients.

TE is a painless procedure in which an ultrasound transducer probe mounted on a vibrator issues a wave through underlying tissues. Pulse-echo ultrasound acquisition is used to follow the propagation of the shear wave and to measure its velocity, which is directly related to tissue stiffness. The stiffer the tissue, the faster the shear wave propagates (J. Hepatol. 2008;48:835-47).

The findings from this small study—which will require replication in a larger number of patients—suggest that TE could be used to identify patients with elevated aminotransferase levels who might qualify for more invasive tests and possibly liver biopsy to better stage the etiology of liver involvement, Dr. Maria Francesca Messina said at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

The procedure could be used to monitor the progression of liver dysfunction in TS patients without exposing them to the significant clinical risks of more invasive procedures, Dr. Messina said.

The 22 TS patients had a mean age of 20.9 years and full pubertal development (spontaneous or pharmacologic). All fasted and underwent TE along with biochemical testing. Six patients were found to have elevated aminotransferase levels.

The mean liver stiffness for the entire group was 4.5 kilopascal (less than 7 kPa is generally considered mild or normal), and was significantly higher among those with elevated transaminase levels compared with those who had normal liver function (6 vs. 4 kPa), said Dr. Messina of the department of pediatrics at the University of Messina (Italy).

The TE device, called FibroScan, is marketed by France-based Echosens International (www.echosens.com

Dr. Messina stated that she has no relevant financial disclosures.

NEW YORK — Transient elastography correlated with aminotransferase levels in a cross-sectional study of 22 adolescent and young women with Turner's syndrome.

Transient elastography (TE), a novel technique for measuring liver stiffness, has been widely validated as a noninvasive alternative to liver biopsy for evaluating hepatic fibrosis in patients with chronic hepatitis C. It has not been used in Turner's syndrome (TS) patients, in whom liver involvement is common.

Although liver biopsy is the standard method for assessing liver fibrosis, it is an invasive and very expensive procedure that can incur life-threatening complications, and therefore can't be used as a tool to screen or monitor liver function in all TS patients.

TE is a painless procedure in which an ultrasound transducer probe mounted on a vibrator issues a wave through underlying tissues. Pulse-echo ultrasound acquisition is used to follow the propagation of the shear wave and to measure its velocity, which is directly related to tissue stiffness. The stiffer the tissue, the faster the shear wave propagates (J. Hepatol. 2008;48:835-47).

The findings from this small study—which will require replication in a larger number of patients—suggest that TE could be used to identify patients with elevated aminotransferase levels who might qualify for more invasive tests and possibly liver biopsy to better stage the etiology of liver involvement, Dr. Maria Francesca Messina said at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

The procedure could be used to monitor the progression of liver dysfunction in TS patients without exposing them to the significant clinical risks of more invasive procedures, Dr. Messina said.

The 22 TS patients had a mean age of 20.9 years and full pubertal development (spontaneous or pharmacologic). All fasted and underwent TE along with biochemical testing. Six patients were found to have elevated aminotransferase levels.

The mean liver stiffness for the entire group was 4.5 kilopascal (less than 7 kPa is generally considered mild or normal), and was significantly higher among those with elevated transaminase levels compared with those who had normal liver function (6 vs. 4 kPa), said Dr. Messina of the department of pediatrics at the University of Messina (Italy).

The TE device, called FibroScan, is marketed by France-based Echosens International (www.echosens.com

Dr. Messina stated that she has no relevant financial disclosures.

NATIONAL HARBOR, MD. — Lubiprostone significantly improved spontaneous bowel movement frequency and associated symptoms in a multicenter, open-label study of 109 children with functional constipation.

Lubiprostone, which stimulates intestinal fluid secretion via chloride channel activation, is approved for the treatment of chronic idiopathic constipation in adults. This phase IV study assessed the safety and efficacy of oral lubiprostone in children and adolescents with functional constipation.

Lubiprostone offers the option of taking a small pill, as an alternative to drinking 240 mL or more of polyethylene glycol, Dr. Paul E. Hyman said at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

To qualify for the study, which was sponsored by Sucampo Pharmaceuticals Inc., potential participants had to be less than 18 years of age, at least 12 kg in weight, and capable of swallowing capsules without chewing. The children had to have fewer than three spontaneous bowel movements (SBMs) per week and meet at least one of the following criteria: at least half of the SBMs were hard or with at least moderate pain, or they had large-diameter stools once weekly or less.

A total of 124 children received lubiprostone, with the dosage based on weight: 27 received 12 mcg/day, 65 received 12 mcg twice a day, and 32 received 24 mcg twice a day. A total of 109 children completed the 4-week study. Each child served as his or her own control during a 2-week baseline period prior to the 4-week treatment.

In the intent-to-treat analysis, improvements in SBM frequency were significant in all dosage groups. Overall, there was a doubling, from 1.5 SBMs/week at baseline to approximately 3/week at weeks 1, 2, 3, and 4 of the study. There also were statistically significant reductions in straining and pain during SBMs beginning at week 1 and maintained through week 4, and significant improvement in consistency at all four time points, compared with baseline, said Dr. Hyman, professor of pediatrics and head of the division of gastroenterology in the department of pediatrics at Louisiana State University, New Orleans.

The percentage of patients using rescue medications—such as oral laxatives, suppositories, or enemas—after 3 days without defecation decreased from 29% during the 2-week baseline period to 10% during week 1, 22% during week 2, and 14% at weeks 3 and 4.

About half of the patients were full or moderate responders. The most common treatment-related adverse events were nausea (14.5%), vomiting (9%), and headache (3%), which diminished after the patients were advised to take lubiprostone with food.

Dr. Hyman is a consultant to Sucampo.

NATIONAL HARBOR, MD. — Lubiprostone significantly improved spontaneous bowel movement frequency and associated symptoms in a multicenter, open-label study of 109 children with functional constipation.

Lubiprostone, which stimulates intestinal fluid secretion via chloride channel activation, is approved for the treatment of chronic idiopathic constipation in adults. This phase IV study assessed the safety and efficacy of oral lubiprostone in children and adolescents with functional constipation.

Lubiprostone offers the option of taking a small pill, as an alternative to drinking 240 mL or more of polyethylene glycol, Dr. Paul E. Hyman said at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

To qualify for the study, which was sponsored by Sucampo Pharmaceuticals Inc., potential participants had to be less than 18 years of age, at least 12 kg in weight, and capable of swallowing capsules without chewing. The children had to have fewer than three spontaneous bowel movements (SBMs) per week and meet at least one of the following criteria: at least half of the SBMs were hard or with at least moderate pain, or they had large-diameter stools once weekly or less.

A total of 124 children received lubiprostone, with the dosage based on weight: 27 received 12 mcg/day, 65 received 12 mcg twice a day, and 32 received 24 mcg twice a day. A total of 109 children completed the 4-week study. Each child served as his or her own control during a 2-week baseline period prior to the 4-week treatment.

In the intent-to-treat analysis, improvements in SBM frequency were significant in all dosage groups. Overall, there was a doubling, from 1.5 SBMs/week at baseline to approximately 3/week at weeks 1, 2, 3, and 4 of the study. There also were statistically significant reductions in straining and pain during SBMs beginning at week 1 and maintained through week 4, and significant improvement in consistency at all four time points, compared with baseline, said Dr. Hyman, professor of pediatrics and head of the division of gastroenterology in the department of pediatrics at Louisiana State University, New Orleans.

The percentage of patients using rescue medications—such as oral laxatives, suppositories, or enemas—after 3 days without defecation decreased from 29% during the 2-week baseline period to 10% during week 1, 22% during week 2, and 14% at weeks 3 and 4.

About half of the patients were full or moderate responders. The most common treatment-related adverse events were nausea (14.5%), vomiting (9%), and headache (3%), which diminished after the patients were advised to take lubiprostone with food.

Dr. Hyman is a consultant to Sucampo.

NATIONAL HARBOR, MD. — Lubiprostone significantly improved spontaneous bowel movement frequency and associated symptoms in a multicenter, open-label study of 109 children with functional constipation.

Lubiprostone, which stimulates intestinal fluid secretion via chloride channel activation, is approved for the treatment of chronic idiopathic constipation in adults. This phase IV study assessed the safety and efficacy of oral lubiprostone in children and adolescents with functional constipation.

Lubiprostone offers the option of taking a small pill, as an alternative to drinking 240 mL or more of polyethylene glycol, Dr. Paul E. Hyman said at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

To qualify for the study, which was sponsored by Sucampo Pharmaceuticals Inc., potential participants had to be less than 18 years of age, at least 12 kg in weight, and capable of swallowing capsules without chewing. The children had to have fewer than three spontaneous bowel movements (SBMs) per week and meet at least one of the following criteria: at least half of the SBMs were hard or with at least moderate pain, or they had large-diameter stools once weekly or less.

A total of 124 children received lubiprostone, with the dosage based on weight: 27 received 12 mcg/day, 65 received 12 mcg twice a day, and 32 received 24 mcg twice a day. A total of 109 children completed the 4-week study. Each child served as his or her own control during a 2-week baseline period prior to the 4-week treatment.

In the intent-to-treat analysis, improvements in SBM frequency were significant in all dosage groups. Overall, there was a doubling, from 1.5 SBMs/week at baseline to approximately 3/week at weeks 1, 2, 3, and 4 of the study. There also were statistically significant reductions in straining and pain during SBMs beginning at week 1 and maintained through week 4, and significant improvement in consistency at all four time points, compared with baseline, said Dr. Hyman, professor of pediatrics and head of the division of gastroenterology in the department of pediatrics at Louisiana State University, New Orleans.

The percentage of patients using rescue medications—such as oral laxatives, suppositories, or enemas—after 3 days without defecation decreased from 29% during the 2-week baseline period to 10% during week 1, 22% during week 2, and 14% at weeks 3 and 4.

About half of the patients were full or moderate responders. The most common treatment-related adverse events were nausea (14.5%), vomiting (9%), and headache (3%), which diminished after the patients were advised to take lubiprostone with food.

Dr. Hyman is a consultant to Sucampo.

Thirteen lots of the nasal spray pandemic influenza A(H1N1) vaccine have been recalled because of slightly decreased potency.

The recall of the affected batches of MedImmune's Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal is not safety related, but a result of routine, ongoing stability testing. Last month, the company notified the Centers for Disease Control and Prevention and the Food and Drug Administration that the potency of the 13 lots of nasal spray vaccine had decreased below a prespecified limit or was at risk of falling below that limit.

MedImmune sent providers directions for returning any unused vaccine from the following lots: 500754P, 500751P, 500756P, 500757P, 500758P, 500759P, 500760P, 500761P, 500762P, 500763P, 500764P, 500765P, 500776P. Approximately 4.7 million doses in these lots were distributed in the United States.

Much of the vaccine had already been administered while fully potent. All the vaccine in the affected lots is still expected to be effective in stimulating a protective response, and there is no need to readminister a dose to those who already received vaccine from these lots.

Thirteen lots of the nasal spray pandemic influenza A(H1N1) vaccine have been recalled because of slightly decreased potency.

The recall of the affected batches of MedImmune's Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal is not safety related, but a result of routine, ongoing stability testing. Last month, the company notified the Centers for Disease Control and Prevention and the Food and Drug Administration that the potency of the 13 lots of nasal spray vaccine had decreased below a prespecified limit or was at risk of falling below that limit.

MedImmune sent providers directions for returning any unused vaccine from the following lots: 500754P, 500751P, 500756P, 500757P, 500758P, 500759P, 500760P, 500761P, 500762P, 500763P, 500764P, 500765P, 500776P. Approximately 4.7 million doses in these lots were distributed in the United States.

Much of the vaccine had already been administered while fully potent. All the vaccine in the affected lots is still expected to be effective in stimulating a protective response, and there is no need to readminister a dose to those who already received vaccine from these lots.

Thirteen lots of the nasal spray pandemic influenza A(H1N1) vaccine have been recalled because of slightly decreased potency.

The recall of the affected batches of MedImmune's Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal is not safety related, but a result of routine, ongoing stability testing. Last month, the company notified the Centers for Disease Control and Prevention and the Food and Drug Administration that the potency of the 13 lots of nasal spray vaccine had decreased below a prespecified limit or was at risk of falling below that limit.

MedImmune sent providers directions for returning any unused vaccine from the following lots: 500754P, 500751P, 500756P, 500757P, 500758P, 500759P, 500760P, 500761P, 500762P, 500763P, 500764P, 500765P, 500776P. Approximately 4.7 million doses in these lots were distributed in the United States.

Much of the vaccine had already been administered while fully potent. All the vaccine in the affected lots is still expected to be effective in stimulating a protective response, and there is no need to readminister a dose to those who already received vaccine from these lots.

The National Vaccine Plan should prioritize limited resources to meet unmet health needs and to increase funds for safety research and communication, the Institute of Medicine said in a new report.

The Institute of Medicine, an independent advisory body, launched its new report “Priorities for the National Vaccine Plan” at a press briefing in December.

The National Vaccine Plan, first released in 1994, was mandated by the National Childhood Vaccine Injury Act of 1986. A draft update was issued in 2008. Given current budgetary constraints, the National Vaccine Program Office, part of the Department of Health and Human Services, requested guidance from the IOM on prioritization of activities. The plan is expected to be finalized this year.

Dr. Claire Broome, who chaired the 18-member multidisciplinary committee that wrote the report, said the new plan will be broader in scope than was the 1994 document. That one was intended to be used primarily by the NVPO, which coordinates all vaccine-related activities of multiple federal agencies. In contrast, the new plan will also be aimed at other public and private vaccine stakeholders, including public health offices, health care providers, pharmaceutical companies, health care organizations, and the general public.

“Changes in society, medicine, science, and communication were important considerations for our committee as we looked at the plan for the future of vaccines and immunization,” said Dr. Broome of the Rollins School of Public Health, Emory University, Atlanta.

The document identifies 18 “priority actions” distributed among five main goals, as well as two additional recommendations regarding the role of the plan as the primary tool to be used for all agencies with roles in the NVPO, and for allocation of resources to ensure implementation of vaccine-related activities within the plan.

Under the heading of Vaccine Development, the report advises that the plan incorporate improvements in the vaccine regulatory process that reflect current science and “encourage innovation without compromising safety and efficacy.” Evidence-based approaches should be used to prioritize new and improved vaccine candidates and to develop specifications for high-priority vaccines. Acceleration of high-priority vaccine development should involve the National Institutes of Health and the Department of Defense, as well as private sector partners.

With regard to Vaccine Safety, the committee said that the plan should establish a process to identify potential vaccine safety hypotheses for future basic, clinical, or epidemiologic research through review of data from existing surveillance systems. A framework should be developed to prioritize the national vaccine safety research agenda, and the plan should establish a permanent vaccine safety subcommittee within the National Vaccine Advisory Committee.

The IOM report includes recommendations for development of a national communication strategy on vaccines and immunization targeting both the public and health care professionals. There should be a process for identifying research needs to inform the national communication strategy, the report advises.

Recommendations regarding Vaccine Use and Supply include the development of strategies to eliminate financial barriers to immunization, the application of research and best practices to improve patient access, the exploration of nontraditional approaches to surveillance of disease, vaccine safety, and vaccine coverage.

Global Vaccine Issues within the new National Vaccine Plan should include engagement of U.S. federal agencies and partners in building immunization capacity in low- to middle-income countries through the provision of both expertise and financial resources, and also the endorsement of global policy frameworks to further global adherence to differential pricing in order to ensure access to needed vaccines in all countries.

Dr. Broome and the rest of the committee members do not have any conflicts of interest, according to an IOM spokeswoman.

The National Vaccine Plan should prioritize limited resources to meet unmet health needs and to increase funds for safety research and communication, the Institute of Medicine said in a new report.

The Institute of Medicine, an independent advisory body, launched its new report “Priorities for the National Vaccine Plan” at a press briefing in December.

The National Vaccine Plan, first released in 1994, was mandated by the National Childhood Vaccine Injury Act of 1986. A draft update was issued in 2008. Given current budgetary constraints, the National Vaccine Program Office, part of the Department of Health and Human Services, requested guidance from the IOM on prioritization of activities. The plan is expected to be finalized this year.

Dr. Claire Broome, who chaired the 18-member multidisciplinary committee that wrote the report, said the new plan will be broader in scope than was the 1994 document. That one was intended to be used primarily by the NVPO, which coordinates all vaccine-related activities of multiple federal agencies. In contrast, the new plan will also be aimed at other public and private vaccine stakeholders, including public health offices, health care providers, pharmaceutical companies, health care organizations, and the general public.

“Changes in society, medicine, science, and communication were important considerations for our committee as we looked at the plan for the future of vaccines and immunization,” said Dr. Broome of the Rollins School of Public Health, Emory University, Atlanta.

The document identifies 18 “priority actions” distributed among five main goals, as well as two additional recommendations regarding the role of the plan as the primary tool to be used for all agencies with roles in the NVPO, and for allocation of resources to ensure implementation of vaccine-related activities within the plan.

Under the heading of Vaccine Development, the report advises that the plan incorporate improvements in the vaccine regulatory process that reflect current science and “encourage innovation without compromising safety and efficacy.” Evidence-based approaches should be used to prioritize new and improved vaccine candidates and to develop specifications for high-priority vaccines. Acceleration of high-priority vaccine development should involve the National Institutes of Health and the Department of Defense, as well as private sector partners.

With regard to Vaccine Safety, the committee said that the plan should establish a process to identify potential vaccine safety hypotheses for future basic, clinical, or epidemiologic research through review of data from existing surveillance systems. A framework should be developed to prioritize the national vaccine safety research agenda, and the plan should establish a permanent vaccine safety subcommittee within the National Vaccine Advisory Committee.

The IOM report includes recommendations for development of a national communication strategy on vaccines and immunization targeting both the public and health care professionals. There should be a process for identifying research needs to inform the national communication strategy, the report advises.

Recommendations regarding Vaccine Use and Supply include the development of strategies to eliminate financial barriers to immunization, the application of research and best practices to improve patient access, the exploration of nontraditional approaches to surveillance of disease, vaccine safety, and vaccine coverage.

Global Vaccine Issues within the new National Vaccine Plan should include engagement of U.S. federal agencies and partners in building immunization capacity in low- to middle-income countries through the provision of both expertise and financial resources, and also the endorsement of global policy frameworks to further global adherence to differential pricing in order to ensure access to needed vaccines in all countries.

Dr. Broome and the rest of the committee members do not have any conflicts of interest, according to an IOM spokeswoman.

The National Vaccine Plan should prioritize limited resources to meet unmet health needs and to increase funds for safety research and communication, the Institute of Medicine said in a new report.

The Institute of Medicine, an independent advisory body, launched its new report “Priorities for the National Vaccine Plan” at a press briefing in December.

The National Vaccine Plan, first released in 1994, was mandated by the National Childhood Vaccine Injury Act of 1986. A draft update was issued in 2008. Given current budgetary constraints, the National Vaccine Program Office, part of the Department of Health and Human Services, requested guidance from the IOM on prioritization of activities. The plan is expected to be finalized this year.

Dr. Claire Broome, who chaired the 18-member multidisciplinary committee that wrote the report, said the new plan will be broader in scope than was the 1994 document. That one was intended to be used primarily by the NVPO, which coordinates all vaccine-related activities of multiple federal agencies. In contrast, the new plan will also be aimed at other public and private vaccine stakeholders, including public health offices, health care providers, pharmaceutical companies, health care organizations, and the general public.

“Changes in society, medicine, science, and communication were important considerations for our committee as we looked at the plan for the future of vaccines and immunization,” said Dr. Broome of the Rollins School of Public Health, Emory University, Atlanta.

The document identifies 18 “priority actions” distributed among five main goals, as well as two additional recommendations regarding the role of the plan as the primary tool to be used for all agencies with roles in the NVPO, and for allocation of resources to ensure implementation of vaccine-related activities within the plan.

Under the heading of Vaccine Development, the report advises that the plan incorporate improvements in the vaccine regulatory process that reflect current science and “encourage innovation without compromising safety and efficacy.” Evidence-based approaches should be used to prioritize new and improved vaccine candidates and to develop specifications for high-priority vaccines. Acceleration of high-priority vaccine development should involve the National Institutes of Health and the Department of Defense, as well as private sector partners.

With regard to Vaccine Safety, the committee said that the plan should establish a process to identify potential vaccine safety hypotheses for future basic, clinical, or epidemiologic research through review of data from existing surveillance systems. A framework should be developed to prioritize the national vaccine safety research agenda, and the plan should establish a permanent vaccine safety subcommittee within the National Vaccine Advisory Committee.

The IOM report includes recommendations for development of a national communication strategy on vaccines and immunization targeting both the public and health care professionals. There should be a process for identifying research needs to inform the national communication strategy, the report advises.

Recommendations regarding Vaccine Use and Supply include the development of strategies to eliminate financial barriers to immunization, the application of research and best practices to improve patient access, the exploration of nontraditional approaches to surveillance of disease, vaccine safety, and vaccine coverage.

Global Vaccine Issues within the new National Vaccine Plan should include engagement of U.S. federal agencies and partners in building immunization capacity in low- to middle-income countries through the provision of both expertise and financial resources, and also the endorsement of global policy frameworks to further global adherence to differential pricing in order to ensure access to needed vaccines in all countries.

Dr. Broome and the rest of the committee members do not have any conflicts of interest, according to an IOM spokeswoman.

Major finding: With use of four criteria to help determine whether to monitor infants with congenital hypothyroidism, monthly monitoring was deemed required in 75% of children in the first 6 months of life and in 35% during the second 6 months.

Source of data: A retrospective chart review of 70 infants seen at a single institution.

Disclosures: Dr. Balhara stated that she had no relevant financial disclosures

NEW YORK — Monthly monitoring of thyroid status was justified in 75% of 70 infants with congenital hypothyroidism in the first 6 months of life and for 35% of those infants in the next 6 months, in a retrospective chart analysis.

The findings suggest that monthly monitoring should continue for a year in all infants with congenital hypothyroidism, in contrast to current guidelines stating that serum T₄ and TSH measurements should be performed every 1–2 months during the first 6 months of life, followed by 3- to 4-month intervals from 6 to 36 months of age.

The 2006 guidelines, issued jointly by the American Academy of Pediatrics, the American Thyroid Association, and the Lawson Wilkins Pediatric Endocrine Society, also advise a repeat test at 4 weeks after any change in levothyroxine dosage, and “more frequent intervals” when compliance is questioned, abnormal values are obtained, or the dose or source of medication has been changed (Pediatrics 2006;117:2290–303).

“There is a paucity of literature behind the AAP recommendation. We monitor more frequently in the second 6 months of life. Based on our results, we think [infants with congenital hypothyroidism] need monthly monitoring for the entire first year,” Dr. Bharti Balhara said in an interview during her poster presentation at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

The 70 patients were among 98 who were seen at the pediatric endocrine unit of Massachusetts General Hospital for Children, Boston, where Dr. Balhara works. She and her associates developed the following four criteria to indicate the need for monthly monitoring:

▸ Dose change within a month of previous visit.

▸ Total/free T₄ levels not in the upper half of normal within a month of previous visit.

▸ TSH more than twice the upper limit of normal 2 months after a visit (if monitoring was done every other month) associated with total/free T₄ not in the upper half of normal range.

▸ Any TSH below 0.1 microIU/mL.

Based on those criteria, monthly monitoring was required in 75% of children in the first 6 months of life and in 35% during the second 6 months. Children who required monthly monitoring in the second 6 months of life had higher baseline TSH (326 vs. 192 microIU/mL) and lower baseline total T₄ (5.6 vs. 7.8 mcg/dL), compared with those who did not require it.

Variables found not to predict the need for monthly monitoring included baseline levothyroxine dose, ethnicity, sex, birth weight, or prematurity. Also not significant was thyroid dysgenesis, Dr. Balhara reported.

Major finding: With use of four criteria to help determine whether to monitor infants with congenital hypothyroidism, monthly monitoring was deemed required in 75% of children in the first 6 months of life and in 35% during the second 6 months.

Source of data: A retrospective chart review of 70 infants seen at a single institution.

Disclosures: Dr. Balhara stated that she had no relevant financial disclosures

NEW YORK — Monthly monitoring of thyroid status was justified in 75% of 70 infants with congenital hypothyroidism in the first 6 months of life and for 35% of those infants in the next 6 months, in a retrospective chart analysis.

The findings suggest that monthly monitoring should continue for a year in all infants with congenital hypothyroidism, in contrast to current guidelines stating that serum T₄ and TSH measurements should be performed every 1–2 months during the first 6 months of life, followed by 3- to 4-month intervals from 6 to 36 months of age.

The 2006 guidelines, issued jointly by the American Academy of Pediatrics, the American Thyroid Association, and the Lawson Wilkins Pediatric Endocrine Society, also advise a repeat test at 4 weeks after any change in levothyroxine dosage, and “more frequent intervals” when compliance is questioned, abnormal values are obtained, or the dose or source of medication has been changed (Pediatrics 2006;117:2290–303).

“There is a paucity of literature behind the AAP recommendation. We monitor more frequently in the second 6 months of life. Based on our results, we think [infants with congenital hypothyroidism] need monthly monitoring for the entire first year,” Dr. Bharti Balhara said in an interview during her poster presentation at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

The 70 patients were among 98 who were seen at the pediatric endocrine unit of Massachusetts General Hospital for Children, Boston, where Dr. Balhara works. She and her associates developed the following four criteria to indicate the need for monthly monitoring:

▸ Dose change within a month of previous visit.

▸ Total/free T₄ levels not in the upper half of normal within a month of previous visit.

▸ TSH more than twice the upper limit of normal 2 months after a visit (if monitoring was done every other month) associated with total/free T₄ not in the upper half of normal range.

▸ Any TSH below 0.1 microIU/mL.

Based on those criteria, monthly monitoring was required in 75% of children in the first 6 months of life and in 35% during the second 6 months. Children who required monthly monitoring in the second 6 months of life had higher baseline TSH (326 vs. 192 microIU/mL) and lower baseline total T₄ (5.6 vs. 7.8 mcg/dL), compared with those who did not require it.

Variables found not to predict the need for monthly monitoring included baseline levothyroxine dose, ethnicity, sex, birth weight, or prematurity. Also not significant was thyroid dysgenesis, Dr. Balhara reported.

Major finding: With use of four criteria to help determine whether to monitor infants with congenital hypothyroidism, monthly monitoring was deemed required in 75% of children in the first 6 months of life and in 35% during the second 6 months.

Source of data: A retrospective chart review of 70 infants seen at a single institution.

Disclosures: Dr. Balhara stated that she had no relevant financial disclosures

NEW YORK — Monthly monitoring of thyroid status was justified in 75% of 70 infants with congenital hypothyroidism in the first 6 months of life and for 35% of those infants in the next 6 months, in a retrospective chart analysis.

The findings suggest that monthly monitoring should continue for a year in all infants with congenital hypothyroidism, in contrast to current guidelines stating that serum T₄ and TSH measurements should be performed every 1–2 months during the first 6 months of life, followed by 3- to 4-month intervals from 6 to 36 months of age.

The 2006 guidelines, issued jointly by the American Academy of Pediatrics, the American Thyroid Association, and the Lawson Wilkins Pediatric Endocrine Society, also advise a repeat test at 4 weeks after any change in levothyroxine dosage, and “more frequent intervals” when compliance is questioned, abnormal values are obtained, or the dose or source of medication has been changed (Pediatrics 2006;117:2290–303).

“There is a paucity of literature behind the AAP recommendation. We monitor more frequently in the second 6 months of life. Based on our results, we think [infants with congenital hypothyroidism] need monthly monitoring for the entire first year,” Dr. Bharti Balhara said in an interview during her poster presentation at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

The 70 patients were among 98 who were seen at the pediatric endocrine unit of Massachusetts General Hospital for Children, Boston, where Dr. Balhara works. She and her associates developed the following four criteria to indicate the need for monthly monitoring:

▸ Dose change within a month of previous visit.

▸ Total/free T₄ levels not in the upper half of normal within a month of previous visit.

▸ TSH more than twice the upper limit of normal 2 months after a visit (if monitoring was done every other month) associated with total/free T₄ not in the upper half of normal range.

▸ Any TSH below 0.1 microIU/mL.

Based on those criteria, monthly monitoring was required in 75% of children in the first 6 months of life and in 35% during the second 6 months. Children who required monthly monitoring in the second 6 months of life had higher baseline TSH (326 vs. 192 microIU/mL) and lower baseline total T₄ (5.6 vs. 7.8 mcg/dL), compared with those who did not require it.

Variables found not to predict the need for monthly monitoring included baseline levothyroxine dose, ethnicity, sex, birth weight, or prematurity. Also not significant was thyroid dysgenesis, Dr. Balhara reported.

The National Vaccine Plan should prioritize limited resources to meet unmet health needs and to increase funds for safety research and communication, the Institute of Medicine said in a new report.

The IOM, an independent advisory body, launched its report “Priorities for the National Vaccine Plan” at a press briefing.

The National Vaccine Plan, first released in 1994, was mandated by the National Childhood Vaccine Injury Act of 1986. A draft update was issued in November 2008. Given current budgetary constraints, the National Vaccine Program Office, part of the Department of Health and Human Services, requested guidance from the IOM on prioritization of activities. The plan is expected to be finalized in 2010.

Dr. Claire Broome, who chaired the 18-member multidisciplinary committee that wrote the report, said the new plan will be broader in scope than was the 1994 document. That one was intended to be used primarily by the NVPO, which coordinates all vaccine-related activities of multiple federal agencies. In contrast, the new plan will also be aimed at other public and private vaccine stakeholders, including public health offices, health care providers, pharmaceutical companies, health care organizations, and the general public.

“Changes in society, medicine, science, and communication were important considerations for our committee as we looked at the plan for the future of vaccines and immunization,” said Dr. Broome, an adjunct professor at Emory University, Atlanta.

The document identifies 18 “priority actions” distributed among five main goals, as well as two additional recommendations regarding the role of the plan as the primary tool to be used for all agencies with roles in the NVPO, and for allocation of resources to ensure implementation of vaccine-related activities within the plan.

Under the heading of Vaccine Development, the report advises that the plan incorporate improvements in the vaccine regulatory process that reflect current science and “encourage innovation without compromising safety and efficacy.” Evidence-based approaches should be used to prioritize new and improved vaccine candidates and to develop specifications for high-priority vaccines. Acceleration of high-priority vaccine development should involve the National Institutes of Health and the Department of Defense, as well as private sector partners.

With regard to Vaccine Safety, the committee said that the plan should establish a process to identify potential vaccine safety hypotheses for future basic, clinical, or epidemiologic research through review of data from existing surveillance systems. A framework should be developed to prioritize the national vaccine safety research agenda, and the plan should establish a permanent vaccine safety subcommittee within the National Vaccine Advisory Committee. Funding should be increased for vaccine safety research activities within the various federal agencies.

The IOM report includes recommendations for the development of a national communication strategy on vaccines and immunization targeting both the public and health care professionals.

Recommendations regarding Vaccine Use and Supply include the development of strategies to eliminate financial barriers to immunization, the application of research and best practices to improve patient access, the exploration of nontraditional approaches to surveillance of disease, vaccine safety, and vaccine coverage. The plan should ensure that the NVPO is actively involved in the development of national health information initiatives including electronic medical records, strengthening of the public health infrastructure to support vaccine programs, and assessment of the outcome of national health reform for its impact on immunization priorities.

Global Vaccine Issues within the new National Vaccine Plan should include engagement of U.S. federal agencies and partners in building immunization capacity in low- to middle-income countries through the provision of both expertise and financial resources, and also the endorsement of global policy frameworks to further global adherence to differential pricing in order to ensure access to needed vaccines in all countries.

Dr. Broome and the rest of the committee members do not have any conflicts of interest, according to an IOM spokesperson.

The National Vaccine Plan should prioritize limited resources to meet unmet health needs and to increase funds for safety research and communication, the Institute of Medicine said in a new report.

The IOM, an independent advisory body, launched its report “Priorities for the National Vaccine Plan” at a press briefing.

The National Vaccine Plan, first released in 1994, was mandated by the National Childhood Vaccine Injury Act of 1986. A draft update was issued in November 2008. Given current budgetary constraints, the National Vaccine Program Office, part of the Department of Health and Human Services, requested guidance from the IOM on prioritization of activities. The plan is expected to be finalized in 2010.

Dr. Claire Broome, who chaired the 18-member multidisciplinary committee that wrote the report, said the new plan will be broader in scope than was the 1994 document. That one was intended to be used primarily by the NVPO, which coordinates all vaccine-related activities of multiple federal agencies. In contrast, the new plan will also be aimed at other public and private vaccine stakeholders, including public health offices, health care providers, pharmaceutical companies, health care organizations, and the general public.

“Changes in society, medicine, science, and communication were important considerations for our committee as we looked at the plan for the future of vaccines and immunization,” said Dr. Broome, an adjunct professor at Emory University, Atlanta.

The document identifies 18 “priority actions” distributed among five main goals, as well as two additional recommendations regarding the role of the plan as the primary tool to be used for all agencies with roles in the NVPO, and for allocation of resources to ensure implementation of vaccine-related activities within the plan.

Under the heading of Vaccine Development, the report advises that the plan incorporate improvements in the vaccine regulatory process that reflect current science and “encourage innovation without compromising safety and efficacy.” Evidence-based approaches should be used to prioritize new and improved vaccine candidates and to develop specifications for high-priority vaccines. Acceleration of high-priority vaccine development should involve the National Institutes of Health and the Department of Defense, as well as private sector partners.

With regard to Vaccine Safety, the committee said that the plan should establish a process to identify potential vaccine safety hypotheses for future basic, clinical, or epidemiologic research through review of data from existing surveillance systems. A framework should be developed to prioritize the national vaccine safety research agenda, and the plan should establish a permanent vaccine safety subcommittee within the National Vaccine Advisory Committee. Funding should be increased for vaccine safety research activities within the various federal agencies.

The IOM report includes recommendations for the development of a national communication strategy on vaccines and immunization targeting both the public and health care professionals.

Recommendations regarding Vaccine Use and Supply include the development of strategies to eliminate financial barriers to immunization, the application of research and best practices to improve patient access, the exploration of nontraditional approaches to surveillance of disease, vaccine safety, and vaccine coverage. The plan should ensure that the NVPO is actively involved in the development of national health information initiatives including electronic medical records, strengthening of the public health infrastructure to support vaccine programs, and assessment of the outcome of national health reform for its impact on immunization priorities.

Global Vaccine Issues within the new National Vaccine Plan should include engagement of U.S. federal agencies and partners in building immunization capacity in low- to middle-income countries through the provision of both expertise and financial resources, and also the endorsement of global policy frameworks to further global adherence to differential pricing in order to ensure access to needed vaccines in all countries.

Dr. Broome and the rest of the committee members do not have any conflicts of interest, according to an IOM spokesperson.

The National Vaccine Plan should prioritize limited resources to meet unmet health needs and to increase funds for safety research and communication, the Institute of Medicine said in a new report.

The IOM, an independent advisory body, launched its report “Priorities for the National Vaccine Plan” at a press briefing.

The National Vaccine Plan, first released in 1994, was mandated by the National Childhood Vaccine Injury Act of 1986. A draft update was issued in November 2008. Given current budgetary constraints, the National Vaccine Program Office, part of the Department of Health and Human Services, requested guidance from the IOM on prioritization of activities. The plan is expected to be finalized in 2010.

Dr. Claire Broome, who chaired the 18-member multidisciplinary committee that wrote the report, said the new plan will be broader in scope than was the 1994 document. That one was intended to be used primarily by the NVPO, which coordinates all vaccine-related activities of multiple federal agencies. In contrast, the new plan will also be aimed at other public and private vaccine stakeholders, including public health offices, health care providers, pharmaceutical companies, health care organizations, and the general public.

“Changes in society, medicine, science, and communication were important considerations for our committee as we looked at the plan for the future of vaccines and immunization,” said Dr. Broome, an adjunct professor at Emory University, Atlanta.

The document identifies 18 “priority actions” distributed among five main goals, as well as two additional recommendations regarding the role of the plan as the primary tool to be used for all agencies with roles in the NVPO, and for allocation of resources to ensure implementation of vaccine-related activities within the plan.

Under the heading of Vaccine Development, the report advises that the plan incorporate improvements in the vaccine regulatory process that reflect current science and “encourage innovation without compromising safety and efficacy.” Evidence-based approaches should be used to prioritize new and improved vaccine candidates and to develop specifications for high-priority vaccines. Acceleration of high-priority vaccine development should involve the National Institutes of Health and the Department of Defense, as well as private sector partners.

With regard to Vaccine Safety, the committee said that the plan should establish a process to identify potential vaccine safety hypotheses for future basic, clinical, or epidemiologic research through review of data from existing surveillance systems. A framework should be developed to prioritize the national vaccine safety research agenda, and the plan should establish a permanent vaccine safety subcommittee within the National Vaccine Advisory Committee. Funding should be increased for vaccine safety research activities within the various federal agencies.

The IOM report includes recommendations for the development of a national communication strategy on vaccines and immunization targeting both the public and health care professionals.

Recommendations regarding Vaccine Use and Supply include the development of strategies to eliminate financial barriers to immunization, the application of research and best practices to improve patient access, the exploration of nontraditional approaches to surveillance of disease, vaccine safety, and vaccine coverage. The plan should ensure that the NVPO is actively involved in the development of national health information initiatives including electronic medical records, strengthening of the public health infrastructure to support vaccine programs, and assessment of the outcome of national health reform for its impact on immunization priorities.

Global Vaccine Issues within the new National Vaccine Plan should include engagement of U.S. federal agencies and partners in building immunization capacity in low- to middle-income countries through the provision of both expertise and financial resources, and also the endorsement of global policy frameworks to further global adherence to differential pricing in order to ensure access to needed vaccines in all countries.

Dr. Broome and the rest of the committee members do not have any conflicts of interest, according to an IOM spokesperson.

MONTREAL — No difference in mortality was found at 4 years between baseline hemoglobin A_1c levels of less than 6.5% and levels of 6.5%–7.0% in a prospective observational study of nearly 3,000 unselected patients with type 2 diabetes.

However, the Diabetes in Germany (DIG) study also found a dramatically increased risk of mortality for those with baseline HbA_1c levels greater than 8%, compared with those who began the study with lower HbA_1c values. Other baseline predictors of mortality included age, smoking, cardiovascular disease, and systolic blood pressure, Dr. Markolf Hanefeld reported at the World Diabetes Congress.

“In a diabetes population rather well controlled for hemoglobin A_1c, smoking status and good blood pressure control are of utmost importance for survival. However, at a level greater than 8%, [the degree of] glucose control becomes a serious risk factor for all-cause mortality,” said Dr. Hanefeld of the Center for Clinical Studies, Technical University, Dresden, Germany.

Of an initial 4,020 unselected patients aged 35–80 years with type 2 diabetes from 238 sites in Germany, 2,784 completed the study at a median of 3.7 years and 175 died during that time. Most (86%) had no history of a major adverse cardiovascular event (MACE) at baseline, while 251 (8.5%) reported a first MACE during follow-up.

The average baseline HbA_1c for the entire group was 7.0%. Thirty-seven percent met the International Diabetes Federation's and American Association of Clinical Endocrinologists' target HbA_1c of less than 6.5%, whereas 57% met the American Diabetes Association's target of less than 7.0%. However, 29% had HbA_1c values above 7.5%. The average HbA_1c level for the entire group did not change over the 4-year period, Dr. Hanefeld said.

Among those who died during the study period, 6% had baseline HbA_1c values of less than 6.5%; 5.3% had values of 6.5%–6.9%; 5.1% had values of 7.0%–7.9%; and 7.6% had values of 8% or higher. The same trend was seen in MACE.

In a multivariate analysis, the most significant factor predicting mortality was MACE at baseline, conferring a twofold greater risk. Also significant were smoking, age, and systolic blood pressure. Female gender cut the risk by half. HbA_1c did not contribute significantly to mortality, he said.

A comparison of these DIG findings with the standard care arms of the recent randomized, controlled glucose-lowering trials ADVANCE (Action in Diabetes and Vascular Disease), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and VADT (Veterans Affairs Diabetes Trial) shows no link between HbA_1c and mortality. In fact, the standard care arm of the ADVANCE study had the highest annual death rate (1.92%) but the second-lowest average HbA_1c (7.5%). The 7.0% average HbA_1c in DIG was the lowest of the four trials, but its annual mortality rate was 1.59% (for the entire group, since all were in “standard” care), higher than the 1.14 annual death rate in the standard care arm of ACCORD. That death rate in ACCORD's standard care arm was the lowest of the four studies, while the mean HbA_1cwas the second highest (8.3%, vs. 9.4% in VADT).

Dr. Hanefeld said he had no conflicts of interest.

MONTREAL — No difference in mortality was found at 4 years between baseline hemoglobin A_1c levels of less than 6.5% and levels of 6.5%–7.0% in a prospective observational study of nearly 3,000 unselected patients with type 2 diabetes.

However, the Diabetes in Germany (DIG) study also found a dramatically increased risk of mortality for those with baseline HbA_1c levels greater than 8%, compared with those who began the study with lower HbA_1c values. Other baseline predictors of mortality included age, smoking, cardiovascular disease, and systolic blood pressure, Dr. Markolf Hanefeld reported at the World Diabetes Congress.

“In a diabetes population rather well controlled for hemoglobin A_1c, smoking status and good blood pressure control are of utmost importance for survival. However, at a level greater than 8%, [the degree of] glucose control becomes a serious risk factor for all-cause mortality,” said Dr. Hanefeld of the Center for Clinical Studies, Technical University, Dresden, Germany.

Of an initial 4,020 unselected patients aged 35–80 years with type 2 diabetes from 238 sites in Germany, 2,784 completed the study at a median of 3.7 years and 175 died during that time. Most (86%) had no history of a major adverse cardiovascular event (MACE) at baseline, while 251 (8.5%) reported a first MACE during follow-up.

The average baseline HbA_1c for the entire group was 7.0%. Thirty-seven percent met the International Diabetes Federation's and American Association of Clinical Endocrinologists' target HbA_1c of less than 6.5%, whereas 57% met the American Diabetes Association's target of less than 7.0%. However, 29% had HbA_1c values above 7.5%. The average HbA_1c level for the entire group did not change over the 4-year period, Dr. Hanefeld said.

Among those who died during the study period, 6% had baseline HbA_1c values of less than 6.5%; 5.3% had values of 6.5%–6.9%; 5.1% had values of 7.0%–7.9%; and 7.6% had values of 8% or higher. The same trend was seen in MACE.

In a multivariate analysis, the most significant factor predicting mortality was MACE at baseline, conferring a twofold greater risk. Also significant were smoking, age, and systolic blood pressure. Female gender cut the risk by half. HbA_1c did not contribute significantly to mortality, he said.

A comparison of these DIG findings with the standard care arms of the recent randomized, controlled glucose-lowering trials ADVANCE (Action in Diabetes and Vascular Disease), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and VADT (Veterans Affairs Diabetes Trial) shows no link between HbA_1c and mortality. In fact, the standard care arm of the ADVANCE study had the highest annual death rate (1.92%) but the second-lowest average HbA_1c (7.5%). The 7.0% average HbA_1c in DIG was the lowest of the four trials, but its annual mortality rate was 1.59% (for the entire group, since all were in “standard” care), higher than the 1.14 annual death rate in the standard care arm of ACCORD. That death rate in ACCORD's standard care arm was the lowest of the four studies, while the mean HbA_1cwas the second highest (8.3%, vs. 9.4% in VADT).

Dr. Hanefeld said he had no conflicts of interest.

MONTREAL — No difference in mortality was found at 4 years between baseline hemoglobin A_1c levels of less than 6.5% and levels of 6.5%–7.0% in a prospective observational study of nearly 3,000 unselected patients with type 2 diabetes.

However, the Diabetes in Germany (DIG) study also found a dramatically increased risk of mortality for those with baseline HbA_1c levels greater than 8%, compared with those who began the study with lower HbA_1c values. Other baseline predictors of mortality included age, smoking, cardiovascular disease, and systolic blood pressure, Dr. Markolf Hanefeld reported at the World Diabetes Congress.

“In a diabetes population rather well controlled for hemoglobin A_1c, smoking status and good blood pressure control are of utmost importance for survival. However, at a level greater than 8%, [the degree of] glucose control becomes a serious risk factor for all-cause mortality,” said Dr. Hanefeld of the Center for Clinical Studies, Technical University, Dresden, Germany.

Of an initial 4,020 unselected patients aged 35–80 years with type 2 diabetes from 238 sites in Germany, 2,784 completed the study at a median of 3.7 years and 175 died during that time. Most (86%) had no history of a major adverse cardiovascular event (MACE) at baseline, while 251 (8.5%) reported a first MACE during follow-up.

The average baseline HbA_1c for the entire group was 7.0%. Thirty-seven percent met the International Diabetes Federation's and American Association of Clinical Endocrinologists' target HbA_1c of less than 6.5%, whereas 57% met the American Diabetes Association's target of less than 7.0%. However, 29% had HbA_1c values above 7.5%. The average HbA_1c level for the entire group did not change over the 4-year period, Dr. Hanefeld said.

Among those who died during the study period, 6% had baseline HbA_1c values of less than 6.5%; 5.3% had values of 6.5%–6.9%; 5.1% had values of 7.0%–7.9%; and 7.6% had values of 8% or higher. The same trend was seen in MACE.

In a multivariate analysis, the most significant factor predicting mortality was MACE at baseline, conferring a twofold greater risk. Also significant were smoking, age, and systolic blood pressure. Female gender cut the risk by half. HbA_1c did not contribute significantly to mortality, he said.

A comparison of these DIG findings with the standard care arms of the recent randomized, controlled glucose-lowering trials ADVANCE (Action in Diabetes and Vascular Disease), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and VADT (Veterans Affairs Diabetes Trial) shows no link between HbA_1c and mortality. In fact, the standard care arm of the ADVANCE study had the highest annual death rate (1.92%) but the second-lowest average HbA_1c (7.5%). The 7.0% average HbA_1c in DIG was the lowest of the four trials, but its annual mortality rate was 1.59% (for the entire group, since all were in “standard” care), higher than the 1.14 annual death rate in the standard care arm of ACCORD. That death rate in ACCORD's standard care arm was the lowest of the four studies, while the mean HbA_1cwas the second highest (8.3%, vs. 9.4% in VADT).

Dr. Hanefeld said he had no conflicts of interest.

The American Diabetes Association has officially endorsed the use of hemoglobin A_1c as an option for diagnosing diabetes.

In its Standards of Medical Care in Diabetes, updated annually, the ADA for the first time is officially endorsing the use of HbA_1c as one of four options for diagnosing diabetes, with a cut-point of 6.5% or greater. Recommendations for use of the three previous diagnostic criteria remain unchanged, including a fasting plasma glucose (FPG) of 126 mg/dL or above, a 2-hour plasma glucose of 200 mg/dL or greater following a 75-g oral glucose tolerance test, or a random plasma glucose of 200 mg/dL or greater in an individual with classic symptoms of hyperglycemia (Diabetes Care 2010; doi: 10.2337/dc10-S011

In June 2009, the use of HbA_1c for diabetes diagnosis was endorsed in a consensus statement by an expert panel comprising members of the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation (

The new ADA endorsement is based in part on the fact that HbA_1c assays are now highly standardized, and “their results can be uniformly applied both temporally and across populations.” In addition, epidemiologic data show a relation between HbA_1c and the risk of retinopathy similar to that shown for corresponding FPG and 2-hour postprandial glucose thresholds. The HbA_1c is also more convenient because fasting is not required, and is likely to be more stable than glucose measurements, the statement said.

The ADA acknowledged the greater cost of HbA_1c testing, and the incomplete correlation between HbA_1c and mean glucose levels in some individuals. Also, the HbA_1c can be misleading in patients with certain forms of anemia and hemoglobinopathies. Indeed, unpublished data suggest that an HbA_1c of 6.5% or higher identifies one-third fewer cases of undiagnosed diabetes than does a FPG of 126 mg/dL or greater.

However, the ADA said, “in practice, a large portion of the diabetic population remains unaware of their condition. Thus, the lower sensitivity of A_1c at the designated cut-point may well be offset by the test's greater practicality, and wider application of a more convenient test (A_1c) may actually increase the number of diagnoses made.”

Not everyone agrees. Dr. Zachary T. Bloomgarden of Mount Sinai School of Medicine, New York, said in an interview that although it may be appropriate to use HbA_1c as a screening tool to determine who would be asked to return for an oral glucose tolerance test, he believes that using it for diagnosis is not appropriate because it could lead to overdiagnosis among people with high hemoglobin glycation, or “high glycators,” and underdiagnosis of “low glycators.”

For example, he said, older individuals have higher HbA_1c levels than do younger people, and blacks have higher HbA_1c levels than do whites for a given level of glucose tolerance, so these individuals might be systematically overdiagnosed. On the other hand, many ill persons seeing a physician for chronic kidney disease or other conditions associated with anemia might be low glycators, leading to underdiagnosis. “These are rather common, each certainly affecting 10% of the population,” said Dr. Bloomgarden, editor of the Journal of Diabetes.

The ADA's decision to endorse the HbA_1c as a diagnostic tool is “overall, not to my mind satisfactory,” he added.

But Dr. Mayer Davidson, who was part of the expert panel that endorsed HbA_1c for diagnosing diabetes last summer, is on the opposite end of the spectrum. He said the recommendation to use HbA_1c for diabetes diagnosis is long overdue, and that the ADA erred in not removing glucose criteria as diagnostic options. The International Expert Committee had recommended use of the glucose criteria only if a standardized HbA_1c assay was not available, he noted in an interview.

“Unfortunately, the ADA kept the glucose criteria, which will lead to the confusing situation of people who have diabetes by one criterion but not by the other when both are measured, which is likely to occur frequently,” said Dr. Davidson, professor of medicine, Charles Drew University and University of California, Los Angeles.

Based on the expert committee's deliberations, it's likely that the ADA and the other organizations will ultimately transition to the use of HbA_1c alone for diagnosis, but it may take time. Until then, he advises physicians who want to use repeat testing for diagnosis to stick to the a single test to avoid confusion. Bottom line: “One should not intermingle the glucose and A_1ccriteria.”

Along with the 6.5% cutoff for diabetes diagnosis, the ADA now categorizes patients with HbA_1c levels of 5.7%–6.4% under the new heading “Categories of Increased Risk for Diabetes,” replacing “Diagnosis of Pre-Diabetes.” The 5.7% threshold was derived from unpublished data suggesting that it has the best combination of sensitivity (39%) and specificity (91%) to identify cases of impaired fasting glucose.

Dr. Bloomgarden and Dr. Davidson reported having no financial disclosures.

The American Diabetes Association has officially endorsed the use of hemoglobin A_1c as an option for diagnosing diabetes.

In its Standards of Medical Care in Diabetes, updated annually, the ADA for the first time is officially endorsing the use of HbA_1c as one of four options for diagnosing diabetes, with a cut-point of 6.5% or greater. Recommendations for use of the three previous diagnostic criteria remain unchanged, including a fasting plasma glucose (FPG) of 126 mg/dL or above, a 2-hour plasma glucose of 200 mg/dL or greater following a 75-g oral glucose tolerance test, or a random plasma glucose of 200 mg/dL or greater in an individual with classic symptoms of hyperglycemia (Diabetes Care 2010; doi: 10.2337/dc10-S011

In June 2009, the use of HbA_1c for diabetes diagnosis was endorsed in a consensus statement by an expert panel comprising members of the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation (

The new ADA endorsement is based in part on the fact that HbA_1c assays are now highly standardized, and “their results can be uniformly applied both temporally and across populations.” In addition, epidemiologic data show a relation between HbA_1c and the risk of retinopathy similar to that shown for corresponding FPG and 2-hour postprandial glucose thresholds. The HbA_1c is also more convenient because fasting is not required, and is likely to be more stable than glucose measurements, the statement said.

The ADA acknowledged the greater cost of HbA_1c testing, and the incomplete correlation between HbA_1c and mean glucose levels in some individuals. Also, the HbA_1c can be misleading in patients with certain forms of anemia and hemoglobinopathies. Indeed, unpublished data suggest that an HbA_1c of 6.5% or higher identifies one-third fewer cases of undiagnosed diabetes than does a FPG of 126 mg/dL or greater.

However, the ADA said, “in practice, a large portion of the diabetic population remains unaware of their condition. Thus, the lower sensitivity of A_1c at the designated cut-point may well be offset by the test's greater practicality, and wider application of a more convenient test (A_1c) may actually increase the number of diagnoses made.”

Not everyone agrees. Dr. Zachary T. Bloomgarden of Mount Sinai School of Medicine, New York, said in an interview that although it may be appropriate to use HbA_1c as a screening tool to determine who would be asked to return for an oral glucose tolerance test, he believes that using it for diagnosis is not appropriate because it could lead to overdiagnosis among people with high hemoglobin glycation, or “high glycators,” and underdiagnosis of “low glycators.”

For example, he said, older individuals have higher HbA_1c levels than do younger people, and blacks have higher HbA_1c levels than do whites for a given level of glucose tolerance, so these individuals might be systematically overdiagnosed. On the other hand, many ill persons seeing a physician for chronic kidney disease or other conditions associated with anemia might be low glycators, leading to underdiagnosis. “These are rather common, each certainly affecting 10% of the population,” said Dr. Bloomgarden, editor of the Journal of Diabetes.

The ADA's decision to endorse the HbA_1c as a diagnostic tool is “overall, not to my mind satisfactory,” he added.

But Dr. Mayer Davidson, who was part of the expert panel that endorsed HbA_1c for diagnosing diabetes last summer, is on the opposite end of the spectrum. He said the recommendation to use HbA_1c for diabetes diagnosis is long overdue, and that the ADA erred in not removing glucose criteria as diagnostic options. The International Expert Committee had recommended use of the glucose criteria only if a standardized HbA_1c assay was not available, he noted in an interview.

“Unfortunately, the ADA kept the glucose criteria, which will lead to the confusing situation of people who have diabetes by one criterion but not by the other when both are measured, which is likely to occur frequently,” said Dr. Davidson, professor of medicine, Charles Drew University and University of California, Los Angeles.

Based on the expert committee's deliberations, it's likely that the ADA and the other organizations will ultimately transition to the use of HbA_1c alone for diagnosis, but it may take time. Until then, he advises physicians who want to use repeat testing for diagnosis to stick to the a single test to avoid confusion. Bottom line: “One should not intermingle the glucose and A_1ccriteria.”

Along with the 6.5% cutoff for diabetes diagnosis, the ADA now categorizes patients with HbA_1c levels of 5.7%–6.4% under the new heading “Categories of Increased Risk for Diabetes,” replacing “Diagnosis of Pre-Diabetes.” The 5.7% threshold was derived from unpublished data suggesting that it has the best combination of sensitivity (39%) and specificity (91%) to identify cases of impaired fasting glucose.

Dr. Bloomgarden and Dr. Davidson reported having no financial disclosures.

The American Diabetes Association has officially endorsed the use of hemoglobin A_1c as an option for diagnosing diabetes.

In its Standards of Medical Care in Diabetes, updated annually, the ADA for the first time is officially endorsing the use of HbA_1c as one of four options for diagnosing diabetes, with a cut-point of 6.5% or greater. Recommendations for use of the three previous diagnostic criteria remain unchanged, including a fasting plasma glucose (FPG) of 126 mg/dL or above, a 2-hour plasma glucose of 200 mg/dL or greater following a 75-g oral glucose tolerance test, or a random plasma glucose of 200 mg/dL or greater in an individual with classic symptoms of hyperglycemia (Diabetes Care 2010; doi: 10.2337/dc10-S011

In June 2009, the use of HbA_1c for diabetes diagnosis was endorsed in a consensus statement by an expert panel comprising members of the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation (

The new ADA endorsement is based in part on the fact that HbA_1c assays are now highly standardized, and “their results can be uniformly applied both temporally and across populations.” In addition, epidemiologic data show a relation between HbA_1c and the risk of retinopathy similar to that shown for corresponding FPG and 2-hour postprandial glucose thresholds. The HbA_1c is also more convenient because fasting is not required, and is likely to be more stable than glucose measurements, the statement said.

The ADA acknowledged the greater cost of HbA_1c testing, and the incomplete correlation between HbA_1c and mean glucose levels in some individuals. Also, the HbA_1c can be misleading in patients with certain forms of anemia and hemoglobinopathies. Indeed, unpublished data suggest that an HbA_1c of 6.5% or higher identifies one-third fewer cases of undiagnosed diabetes than does a FPG of 126 mg/dL or greater.

However, the ADA said, “in practice, a large portion of the diabetic population remains unaware of their condition. Thus, the lower sensitivity of A_1c at the designated cut-point may well be offset by the test's greater practicality, and wider application of a more convenient test (A_1c) may actually increase the number of diagnoses made.”

Not everyone agrees. Dr. Zachary T. Bloomgarden of Mount Sinai School of Medicine, New York, said in an interview that although it may be appropriate to use HbA_1c as a screening tool to determine who would be asked to return for an oral glucose tolerance test, he believes that using it for diagnosis is not appropriate because it could lead to overdiagnosis among people with high hemoglobin glycation, or “high glycators,” and underdiagnosis of “low glycators.”

For example, he said, older individuals have higher HbA_1c levels than do younger people, and blacks have higher HbA_1c levels than do whites for a given level of glucose tolerance, so these individuals might be systematically overdiagnosed. On the other hand, many ill persons seeing a physician for chronic kidney disease or other conditions associated with anemia might be low glycators, leading to underdiagnosis. “These are rather common, each certainly affecting 10% of the population,” said Dr. Bloomgarden, editor of the Journal of Diabetes.

The ADA's decision to endorse the HbA_1c as a diagnostic tool is “overall, not to my mind satisfactory,” he added.

But Dr. Mayer Davidson, who was part of the expert panel that endorsed HbA_1c for diagnosing diabetes last summer, is on the opposite end of the spectrum. He said the recommendation to use HbA_1c for diabetes diagnosis is long overdue, and that the ADA erred in not removing glucose criteria as diagnostic options. The International Expert Committee had recommended use of the glucose criteria only if a standardized HbA_1c assay was not available, he noted in an interview.

“Unfortunately, the ADA kept the glucose criteria, which will lead to the confusing situation of people who have diabetes by one criterion but not by the other when both are measured, which is likely to occur frequently,” said Dr. Davidson, professor of medicine, Charles Drew University and University of California, Los Angeles.

Based on the expert committee's deliberations, it's likely that the ADA and the other organizations will ultimately transition to the use of HbA_1c alone for diagnosis, but it may take time. Until then, he advises physicians who want to use repeat testing for diagnosis to stick to the a single test to avoid confusion. Bottom line: “One should not intermingle the glucose and A_1ccriteria.”

Along with the 6.5% cutoff for diabetes diagnosis, the ADA now categorizes patients with HbA_1c levels of 5.7%–6.4% under the new heading “Categories of Increased Risk for Diabetes,” replacing “Diagnosis of Pre-Diabetes.” The 5.7% threshold was derived from unpublished data suggesting that it has the best combination of sensitivity (39%) and specificity (91%) to identify cases of impaired fasting glucose.

Dr. Bloomgarden and Dr. Davidson reported having no financial disclosures.