Miriam E. Tucker

Women who are diagnosed with gestational diabetes during pregnancy may be at greater risk for cardiovascular events later in life, reported Dr. Darcy B. Carr and her associates, of the University of Washington, Seattle.

Previous studies have demonstrated that women with a history of gestational diabetes mellitus (GDM) are at increased risk for a wide array of cardiovascular risk factors, including central adiposity, insulin resistance, dyslipidemia, and hypertension. Now, data from the Genetics of Non-Insulin-Dependent Diabetes (GENNID) study suggest that among women with a family history of type 2 diabetes, these risk factors actually translate into a significantly higher prevalence of cardiovascular disease events in those with prior GDM.

“Interventions have been shown to reduce the progression to type 2 diabetes in subjects at risk for the disease, including women with a history of GDM, and offer primary prevention of cardiovascular disease (CVD) events in established type 2 diabetes. We believe our findings provide a strong rationale to further consider efforts to target women who have a history of GDM with interventions in order to improve both their metabolic and cardiovascular health,” Dr. Carr and her associates wrote (Diabetes Care 2006;29:2078–83).

In GENNID, genetic and phenotypic information was collected at multiple U.S. sites between 1993 and 2001 from families with type 2 diabetes. Among parous women in the study who had a first-degree relative with type 2 diabetes but who did not have pregestational diabetes themselves, a total of 332 reported having had GDM during at least one previous pregnancy, compared with 662 who did not.

At a mean follow-up of 30 years after the index pregnancy, the women with prior GDM were younger (49 vs. 52 years) and more likely to be African American (40% vs. 29%) than were those without GDM.

Although both groups were obese, women in the prior GDM group had a more atherogenic lipid profile and higher fasting plasma glucose and insulin levels, suggesting increased insulin resistance. Among the risk factors that were reported by significantly more women in the GDM group were history of hypertension (47% vs. 37%), dyslipidemia (34% vs. 26%), and type 2 diabetes (93% vs. 63%). Among women who had these risk factors, those with GDM were diagnosed with them at younger ages.

Women with GDM were more than three times as likely as those without to meet all the criteria for metabolic syndrome, even after adjusting for age, menopausal status, and race/ethnicity, Dr. Carr and her associates reported.

Self-reported history of cardiovascular disease (coronary artery disease [CAD] and/or stroke) was significantly more common in women with prior GDM and remained significant after adjustment for race/ethnicity, age, and menopausal status. Overall cardiovascular disease was reported by 15.5% with GDM, compared with 12% without, CAD by 12% vs. 11%, and stroke by 6% vs. 5%. The CVD and CAD differences were statistically significant, but stroke was not, due to small numbers of patients, they said.

Among the 890 women for whom complete data for metabolic syndrome criteria were available, a history of GDM was associated with an independent risk for CVD after adjustment for metabolic syndrome (OR 1.74) and for type 2 diabetes (OR 1.56).

Women who are diagnosed with gestational diabetes during pregnancy may be at greater risk for cardiovascular events later in life, reported Dr. Darcy B. Carr and her associates, of the University of Washington, Seattle.

Previous studies have demonstrated that women with a history of gestational diabetes mellitus (GDM) are at increased risk for a wide array of cardiovascular risk factors, including central adiposity, insulin resistance, dyslipidemia, and hypertension. Now, data from the Genetics of Non-Insulin-Dependent Diabetes (GENNID) study suggest that among women with a family history of type 2 diabetes, these risk factors actually translate into a significantly higher prevalence of cardiovascular disease events in those with prior GDM.

“Interventions have been shown to reduce the progression to type 2 diabetes in subjects at risk for the disease, including women with a history of GDM, and offer primary prevention of cardiovascular disease (CVD) events in established type 2 diabetes. We believe our findings provide a strong rationale to further consider efforts to target women who have a history of GDM with interventions in order to improve both their metabolic and cardiovascular health,” Dr. Carr and her associates wrote (Diabetes Care 2006;29:2078–83).

In GENNID, genetic and phenotypic information was collected at multiple U.S. sites between 1993 and 2001 from families with type 2 diabetes. Among parous women in the study who had a first-degree relative with type 2 diabetes but who did not have pregestational diabetes themselves, a total of 332 reported having had GDM during at least one previous pregnancy, compared with 662 who did not.

At a mean follow-up of 30 years after the index pregnancy, the women with prior GDM were younger (49 vs. 52 years) and more likely to be African American (40% vs. 29%) than were those without GDM.

Although both groups were obese, women in the prior GDM group had a more atherogenic lipid profile and higher fasting plasma glucose and insulin levels, suggesting increased insulin resistance. Among the risk factors that were reported by significantly more women in the GDM group were history of hypertension (47% vs. 37%), dyslipidemia (34% vs. 26%), and type 2 diabetes (93% vs. 63%). Among women who had these risk factors, those with GDM were diagnosed with them at younger ages.

Women with GDM were more than three times as likely as those without to meet all the criteria for metabolic syndrome, even after adjusting for age, menopausal status, and race/ethnicity, Dr. Carr and her associates reported.

Self-reported history of cardiovascular disease (coronary artery disease [CAD] and/or stroke) was significantly more common in women with prior GDM and remained significant after adjustment for race/ethnicity, age, and menopausal status. Overall cardiovascular disease was reported by 15.5% with GDM, compared with 12% without, CAD by 12% vs. 11%, and stroke by 6% vs. 5%. The CVD and CAD differences were statistically significant, but stroke was not, due to small numbers of patients, they said.

Among the 890 women for whom complete data for metabolic syndrome criteria were available, a history of GDM was associated with an independent risk for CVD after adjustment for metabolic syndrome (OR 1.74) and for type 2 diabetes (OR 1.56).

Women who are diagnosed with gestational diabetes during pregnancy may be at greater risk for cardiovascular events later in life, reported Dr. Darcy B. Carr and her associates, of the University of Washington, Seattle.

Previous studies have demonstrated that women with a history of gestational diabetes mellitus (GDM) are at increased risk for a wide array of cardiovascular risk factors, including central adiposity, insulin resistance, dyslipidemia, and hypertension. Now, data from the Genetics of Non-Insulin-Dependent Diabetes (GENNID) study suggest that among women with a family history of type 2 diabetes, these risk factors actually translate into a significantly higher prevalence of cardiovascular disease events in those with prior GDM.

“Interventions have been shown to reduce the progression to type 2 diabetes in subjects at risk for the disease, including women with a history of GDM, and offer primary prevention of cardiovascular disease (CVD) events in established type 2 diabetes. We believe our findings provide a strong rationale to further consider efforts to target women who have a history of GDM with interventions in order to improve both their metabolic and cardiovascular health,” Dr. Carr and her associates wrote (Diabetes Care 2006;29:2078–83).

In GENNID, genetic and phenotypic information was collected at multiple U.S. sites between 1993 and 2001 from families with type 2 diabetes. Among parous women in the study who had a first-degree relative with type 2 diabetes but who did not have pregestational diabetes themselves, a total of 332 reported having had GDM during at least one previous pregnancy, compared with 662 who did not.

At a mean follow-up of 30 years after the index pregnancy, the women with prior GDM were younger (49 vs. 52 years) and more likely to be African American (40% vs. 29%) than were those without GDM.

Although both groups were obese, women in the prior GDM group had a more atherogenic lipid profile and higher fasting plasma glucose and insulin levels, suggesting increased insulin resistance. Among the risk factors that were reported by significantly more women in the GDM group were history of hypertension (47% vs. 37%), dyslipidemia (34% vs. 26%), and type 2 diabetes (93% vs. 63%). Among women who had these risk factors, those with GDM were diagnosed with them at younger ages.

Women with GDM were more than three times as likely as those without to meet all the criteria for metabolic syndrome, even after adjusting for age, menopausal status, and race/ethnicity, Dr. Carr and her associates reported.

Self-reported history of cardiovascular disease (coronary artery disease [CAD] and/or stroke) was significantly more common in women with prior GDM and remained significant after adjustment for race/ethnicity, age, and menopausal status. Overall cardiovascular disease was reported by 15.5% with GDM, compared with 12% without, CAD by 12% vs. 11%, and stroke by 6% vs. 5%. The CVD and CAD differences were statistically significant, but stroke was not, due to small numbers of patients, they said.

Among the 890 women for whom complete data for metabolic syndrome criteria were available, a history of GDM was associated with an independent risk for CVD after adjustment for metabolic syndrome (OR 1.74) and for type 2 diabetes (OR 1.56).

COPENHAGEN — Self-treatment with a biofeedback device that guides breathing can significantly lower blood pressure among patients with type 2 diabetes, Dr. Moshe H. Schein reported at the annual meeting of the European Association for the Study of Diabetes.

The device, called RESPeRATE, is made by InterCure Ltd., Lod, Israel. It was approved for use by the Food and Drug Administration in 2002 for use in stress reduction and as adjunctive treatment for hypertension, together with other pharmacologic and nonpharmacologic interventions. It works by using melodic tones to guide the patient through progressively slower inhalation and exhalation.

Previous data have shown that the device-guided technique results in significant blood pressure reductions among hypertensive patients who use it at home on a daily basis (J. Hum. Hypertens. 2001;15:271–8).

In the new study, a total of 60 patients with type 2 diabetes who had blood pressures greater than 130/80 mm Hg were randomized to the use of the device for 15 minutes a day along with usual treatment, or to usual treatment alone for 8 weeks. The group was 60% male, with a mean age of 64 years and a mean body mass index of 30 kg/m

At baseline, mean blood pressure was 149/82 mm Hg in the treatment group and 146/81 mm Hg in the control group, even though the majority—78% of the treatment group and 89% of the controls—were taking blood pressure medication, said Dr. Schein, director of the Family Medicine Unit, Hadassah University Hospital, Jerusalem.

Systolic blood pressure dropped by 9.5 mm Hg in the group using the device, compared with an increase of 2.1 mm Hg among the controls, a significant difference between the two groups. The change in pulse pressure also was significantly different at 2 months; it dropped by 5.9 mm Hg from a mean of 67 mm Hg at baseline in the guided-breathing group, and increased by 3.6 mm Hg from a mean of 66 mm Hg in the controls.

Diastolic blood pressure dropped slightly in both groups, by 3.5 mm Hg in the guided-breathing patients and by 1.5 mm Hg among the controls, an insignificant difference.

There was a dose-response relationship between use of the device and systolic blood pressure reduction: The longer the patient spent in the slow breathing exercise, the greater the drop. (Although patients had been told to perform the device-guided breathing exercise daily, they actually did it for a mean of 5.6 sessions per week. However, each session lasted 15.9 minutes, slightly longer than the instructed 15 minutes.)

Blood pressure control—defined as 130/80 mm Hg or below—was achieved by 8 of 30 (27%) in the device group, compared with just 2 of the 30 (7%) of the controls, Dr. Schein reported.

COPENHAGEN — Self-treatment with a biofeedback device that guides breathing can significantly lower blood pressure among patients with type 2 diabetes, Dr. Moshe H. Schein reported at the annual meeting of the European Association for the Study of Diabetes.

The device, called RESPeRATE, is made by InterCure Ltd., Lod, Israel. It was approved for use by the Food and Drug Administration in 2002 for use in stress reduction and as adjunctive treatment for hypertension, together with other pharmacologic and nonpharmacologic interventions. It works by using melodic tones to guide the patient through progressively slower inhalation and exhalation.

Previous data have shown that the device-guided technique results in significant blood pressure reductions among hypertensive patients who use it at home on a daily basis (J. Hum. Hypertens. 2001;15:271–8).

In the new study, a total of 60 patients with type 2 diabetes who had blood pressures greater than 130/80 mm Hg were randomized to the use of the device for 15 minutes a day along with usual treatment, or to usual treatment alone for 8 weeks. The group was 60% male, with a mean age of 64 years and a mean body mass index of 30 kg/m

At baseline, mean blood pressure was 149/82 mm Hg in the treatment group and 146/81 mm Hg in the control group, even though the majority—78% of the treatment group and 89% of the controls—were taking blood pressure medication, said Dr. Schein, director of the Family Medicine Unit, Hadassah University Hospital, Jerusalem.

Systolic blood pressure dropped by 9.5 mm Hg in the group using the device, compared with an increase of 2.1 mm Hg among the controls, a significant difference between the two groups. The change in pulse pressure also was significantly different at 2 months; it dropped by 5.9 mm Hg from a mean of 67 mm Hg at baseline in the guided-breathing group, and increased by 3.6 mm Hg from a mean of 66 mm Hg in the controls.

Diastolic blood pressure dropped slightly in both groups, by 3.5 mm Hg in the guided-breathing patients and by 1.5 mm Hg among the controls, an insignificant difference.

There was a dose-response relationship between use of the device and systolic blood pressure reduction: The longer the patient spent in the slow breathing exercise, the greater the drop. (Although patients had been told to perform the device-guided breathing exercise daily, they actually did it for a mean of 5.6 sessions per week. However, each session lasted 15.9 minutes, slightly longer than the instructed 15 minutes.)

Blood pressure control—defined as 130/80 mm Hg or below—was achieved by 8 of 30 (27%) in the device group, compared with just 2 of the 30 (7%) of the controls, Dr. Schein reported.

COPENHAGEN — Self-treatment with a biofeedback device that guides breathing can significantly lower blood pressure among patients with type 2 diabetes, Dr. Moshe H. Schein reported at the annual meeting of the European Association for the Study of Diabetes.

The device, called RESPeRATE, is made by InterCure Ltd., Lod, Israel. It was approved for use by the Food and Drug Administration in 2002 for use in stress reduction and as adjunctive treatment for hypertension, together with other pharmacologic and nonpharmacologic interventions. It works by using melodic tones to guide the patient through progressively slower inhalation and exhalation.

Previous data have shown that the device-guided technique results in significant blood pressure reductions among hypertensive patients who use it at home on a daily basis (J. Hum. Hypertens. 2001;15:271–8).

In the new study, a total of 60 patients with type 2 diabetes who had blood pressures greater than 130/80 mm Hg were randomized to the use of the device for 15 minutes a day along with usual treatment, or to usual treatment alone for 8 weeks. The group was 60% male, with a mean age of 64 years and a mean body mass index of 30 kg/m

At baseline, mean blood pressure was 149/82 mm Hg in the treatment group and 146/81 mm Hg in the control group, even though the majority—78% of the treatment group and 89% of the controls—were taking blood pressure medication, said Dr. Schein, director of the Family Medicine Unit, Hadassah University Hospital, Jerusalem.

Systolic blood pressure dropped by 9.5 mm Hg in the group using the device, compared with an increase of 2.1 mm Hg among the controls, a significant difference between the two groups. The change in pulse pressure also was significantly different at 2 months; it dropped by 5.9 mm Hg from a mean of 67 mm Hg at baseline in the guided-breathing group, and increased by 3.6 mm Hg from a mean of 66 mm Hg in the controls.

Diastolic blood pressure dropped slightly in both groups, by 3.5 mm Hg in the guided-breathing patients and by 1.5 mm Hg among the controls, an insignificant difference.

There was a dose-response relationship between use of the device and systolic blood pressure reduction: The longer the patient spent in the slow breathing exercise, the greater the drop. (Although patients had been told to perform the device-guided breathing exercise daily, they actually did it for a mean of 5.6 sessions per week. However, each session lasted 15.9 minutes, slightly longer than the instructed 15 minutes.)

Blood pressure control—defined as 130/80 mm Hg or below—was achieved by 8 of 30 (27%) in the device group, compared with just 2 of the 30 (7%) of the controls, Dr. Schein reported.

Women who are diagnosed with gestational diabetes during pregnancy may be at greater risk for cardiovascular events later in life, reported Dr. Darcy B. Carr and her associates, of the University of Washington, Seattle.

Previous studies have demonstrated that women with a history of gestational diabetes mellitus (GDM) are at increased risk for a wide array of cardiovascular risk factors, including central adiposity, insulin resistance, dyslipidemia, and hypertension. Now, data from the Genetics of Non-Insulin-Dependent Diabetes (GENNID) study suggest that among women with a family history of type 2 diabetes, these risk factors actually translate into a significantly higher prevalence of cardiovascular disease events in those with prior GDM.

“Interventions have been shown to reduce the progression to type 2 diabetes in subjects at risk for the disease, including women with a history of GDM, and offer primary prevention of cardiovascular disease (CVD) events in established type 2 diabetes. We believe our findings provide a strong rationale to further consider efforts to target women who have a history of GDM with interventions in order to improve both their metabolic and cardiovascular health,” Dr. Carr and her associates wrote (Diabetes Care 2006;29:2078–83).

In GENNID, genetic and phenotypic information was collected at multiple U.S. sites between 1993 and 2001 from families with type 2 diabetes. Among parous women in the study who had a first-degree relative with type 2 diabetes but who did not have pregestational diabetes themselves, a total of 332 reported having had GDM during at least one previous pregnancy, while 662 did not report a history of GDM.

At a mean follow-up of 30 years after the index pregnancy, the women with prior GDM were younger (49 vs. 52 years), more likely to be African American (40% vs. 29%), and less likely to be postmenopausal (48% vs. 58%) than were those without GDM.

Although both groups were obese, women in the prior GDM group had a more atherogenic lipid profile and higher fasting plasma glucose and insulin levels, suggesting increased insulin resistance. Among the risk factors that were reported by significantly more women in the GDM group were history of hypertension (47% vs. 37%), dyslipidemia (34% vs. 26%), and type 2 diabetes (93% vs. 63%). Among women who had these risk factors, those with GDM were diagnosed with them at younger ages: 40 vs. 48 years for hypertension, 48 vs. 52 for dyslipidemia, and 37 vs. 47 for type 2 diabetes.

Women with GDM were more than three times as likely as those without GDMto meet all the criteria for metabolic syndrome, even after adjusting for age, menopausal status, and race/ethnicity, Dr. Carr and her associates reported.

Self-reported history of cardiovascular disease (coronary artery disease [CAD] and/or stroke) was significantly more common in women with prior GDM (odds ratio 1.85) and remained significant after adjustment for race/ethnicity, age, and menopausal status (OR 1.66). Overall, cardiovascular disease was reported by 15.5% with GDM compared with 12% without, CAD by 12% vs. 11%, and stroke by 6% vs. 5%.

The CVD and CAD differences were statistically significant, but stroke was not, due to small numbers of patients, the investigators said.

Among the 890 women for whom complete data for metabolic syndrome criteria were available, a history of GDM was associated with an independent risk for CVD after adjustment for metabolic syndrome (OR 1.74) and for type 2 diabetes (OR 1.56).

Women who are diagnosed with gestational diabetes during pregnancy may be at greater risk for cardiovascular events later in life, reported Dr. Darcy B. Carr and her associates, of the University of Washington, Seattle.

Previous studies have demonstrated that women with a history of gestational diabetes mellitus (GDM) are at increased risk for a wide array of cardiovascular risk factors, including central adiposity, insulin resistance, dyslipidemia, and hypertension. Now, data from the Genetics of Non-Insulin-Dependent Diabetes (GENNID) study suggest that among women with a family history of type 2 diabetes, these risk factors actually translate into a significantly higher prevalence of cardiovascular disease events in those with prior GDM.

“Interventions have been shown to reduce the progression to type 2 diabetes in subjects at risk for the disease, including women with a history of GDM, and offer primary prevention of cardiovascular disease (CVD) events in established type 2 diabetes. We believe our findings provide a strong rationale to further consider efforts to target women who have a history of GDM with interventions in order to improve both their metabolic and cardiovascular health,” Dr. Carr and her associates wrote (Diabetes Care 2006;29:2078–83).

In GENNID, genetic and phenotypic information was collected at multiple U.S. sites between 1993 and 2001 from families with type 2 diabetes. Among parous women in the study who had a first-degree relative with type 2 diabetes but who did not have pregestational diabetes themselves, a total of 332 reported having had GDM during at least one previous pregnancy, while 662 did not report a history of GDM.

At a mean follow-up of 30 years after the index pregnancy, the women with prior GDM were younger (49 vs. 52 years), more likely to be African American (40% vs. 29%), and less likely to be postmenopausal (48% vs. 58%) than were those without GDM.

Although both groups were obese, women in the prior GDM group had a more atherogenic lipid profile and higher fasting plasma glucose and insulin levels, suggesting increased insulin resistance. Among the risk factors that were reported by significantly more women in the GDM group were history of hypertension (47% vs. 37%), dyslipidemia (34% vs. 26%), and type 2 diabetes (93% vs. 63%). Among women who had these risk factors, those with GDM were diagnosed with them at younger ages: 40 vs. 48 years for hypertension, 48 vs. 52 for dyslipidemia, and 37 vs. 47 for type 2 diabetes.

Women with GDM were more than three times as likely as those without GDMto meet all the criteria for metabolic syndrome, even after adjusting for age, menopausal status, and race/ethnicity, Dr. Carr and her associates reported.

Self-reported history of cardiovascular disease (coronary artery disease [CAD] and/or stroke) was significantly more common in women with prior GDM (odds ratio 1.85) and remained significant after adjustment for race/ethnicity, age, and menopausal status (OR 1.66). Overall, cardiovascular disease was reported by 15.5% with GDM compared with 12% without, CAD by 12% vs. 11%, and stroke by 6% vs. 5%.

The CVD and CAD differences were statistically significant, but stroke was not, due to small numbers of patients, the investigators said.

Among the 890 women for whom complete data for metabolic syndrome criteria were available, a history of GDM was associated with an independent risk for CVD after adjustment for metabolic syndrome (OR 1.74) and for type 2 diabetes (OR 1.56).

Women who are diagnosed with gestational diabetes during pregnancy may be at greater risk for cardiovascular events later in life, reported Dr. Darcy B. Carr and her associates, of the University of Washington, Seattle.

Previous studies have demonstrated that women with a history of gestational diabetes mellitus (GDM) are at increased risk for a wide array of cardiovascular risk factors, including central adiposity, insulin resistance, dyslipidemia, and hypertension. Now, data from the Genetics of Non-Insulin-Dependent Diabetes (GENNID) study suggest that among women with a family history of type 2 diabetes, these risk factors actually translate into a significantly higher prevalence of cardiovascular disease events in those with prior GDM.

“Interventions have been shown to reduce the progression to type 2 diabetes in subjects at risk for the disease, including women with a history of GDM, and offer primary prevention of cardiovascular disease (CVD) events in established type 2 diabetes. We believe our findings provide a strong rationale to further consider efforts to target women who have a history of GDM with interventions in order to improve both their metabolic and cardiovascular health,” Dr. Carr and her associates wrote (Diabetes Care 2006;29:2078–83).

In GENNID, genetic and phenotypic information was collected at multiple U.S. sites between 1993 and 2001 from families with type 2 diabetes. Among parous women in the study who had a first-degree relative with type 2 diabetes but who did not have pregestational diabetes themselves, a total of 332 reported having had GDM during at least one previous pregnancy, while 662 did not report a history of GDM.

At a mean follow-up of 30 years after the index pregnancy, the women with prior GDM were younger (49 vs. 52 years), more likely to be African American (40% vs. 29%), and less likely to be postmenopausal (48% vs. 58%) than were those without GDM.

Although both groups were obese, women in the prior GDM group had a more atherogenic lipid profile and higher fasting plasma glucose and insulin levels, suggesting increased insulin resistance. Among the risk factors that were reported by significantly more women in the GDM group were history of hypertension (47% vs. 37%), dyslipidemia (34% vs. 26%), and type 2 diabetes (93% vs. 63%). Among women who had these risk factors, those with GDM were diagnosed with them at younger ages: 40 vs. 48 years for hypertension, 48 vs. 52 for dyslipidemia, and 37 vs. 47 for type 2 diabetes.

Women with GDM were more than three times as likely as those without GDMto meet all the criteria for metabolic syndrome, even after adjusting for age, menopausal status, and race/ethnicity, Dr. Carr and her associates reported.

Self-reported history of cardiovascular disease (coronary artery disease [CAD] and/or stroke) was significantly more common in women with prior GDM (odds ratio 1.85) and remained significant after adjustment for race/ethnicity, age, and menopausal status (OR 1.66). Overall, cardiovascular disease was reported by 15.5% with GDM compared with 12% without, CAD by 12% vs. 11%, and stroke by 6% vs. 5%.

The CVD and CAD differences were statistically significant, but stroke was not, due to small numbers of patients, the investigators said.

Among the 890 women for whom complete data for metabolic syndrome criteria were available, a history of GDM was associated with an independent risk for CVD after adjustment for metabolic syndrome (OR 1.74) and for type 2 diabetes (OR 1.56).

TORONTO — Postpartum testing in women who had gestational diabetes during pregnancy should include both an oral glucose-tolerance test and a lipid profile, Genevieve Dubé and her colleagues advised in a poster presented at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

Data from a retrospective analysis of 223 women who had gestational diabetes mellitus (GDM) during pregnancy revealed that postpartum glucose-tolerance abnormalities were common, affecting one-fourth of all women. Moreover, “Isolated fasting glucose testing would have failed to identify most cases of postpartum dysglycemia,” noted Ms. Dubé and her colleagues at the Centre Régional du Diabète de Laval (Que.).

The data also suggested that a lipid profile should be part of the assessment, because many of the women with previous GDM—including those with normal postpartum oral glucose-tolerance test (OGTT) results—have altered lipids suggestive of features of the cardiometabolic syndrome, they said.

The 223 women had received prenatal care between June 2004 and April 2005 at Laval's diabetic pregnancy clinic, which has had a program of routine postnatal GDM follow-up since 2002. The group had a mean age of 31 years and a mean body mass index (kg/m2) of 28.3. Two-thirds of the women were white. Insulin treatment was used by 34% during pregnancy.

All were told to return at 2 months—whether or not they were still breast-feeding—for postpartum lab testing, which included a 12-hour fasting glucose, a 75-g OGTT, a lipid profile, and a thyroid-stimulating hormone test. A total of 74% (165 patients) showed up, at a mean of 3 months following delivery.

Of the 164 who underwent the OGTT, some form of impaired glucose tolerance was detected in 25% (41 patients), including frank type 2 diabetes in 4% (7 patients), isolated impaired glucose tolerance in 16% (26 patients), isolated impaired fasting glucose in 2% (3 patients), and both impaired glucose tolerance and impaired fasting glucose in 3% (5 patients).

No matter what fasting blood glucose (FBG) cutoff was used, more than half of all dysglycemic women would have been missed if postpartum lab screening included only FBG instead of OGTT. Among the 41 women with abnormal 2-hour OGTT results, 49% had FBG values at or above 5.6 mmol/L, 41.5% had FBG levels at or above 5.8 mmol/L, and 32% had FBG levels at or above 6.1 mmol/L.

The need for insulin therapy and a first-trimester FBG above 6.1 mmol/L were the only risk factors analyzed that significantly predicted postpartum abnormal OGTT, with odds ratios of 1.89 and 3.41, respectively. Maternal age, BMI, parity, macrosomia, and nonwhite race were not predictive of postpartum glucose status, they said.

Among the 165 women who had postpartum lipid tests, 70% had at least one abnormality, defined as a triglyceride level of 1.7 mmol/L or higher, HDL cholesterol level at or lower than 1.3 mmol/L, or a total cholesterol/HDL cholesterol ratio of 5.0 or greater.

Cardiometabolic risk factors were not limited to women with abnormal OGTT results and diabetes. Indeed, two-thirds of the 123 women with normal postpartum glucose tolerance had at least one lipid abnormality; 23% had triglyceride levels of 1.7 mmol/L or higher, and 23% had HDL cholesterol of 1.3 mmol/L or lower. In fact, only when those two abnormalities were combined was there a significant correlation with OGTT results: The proportion of women with normal glucose tolerance who had both high triglycerides and low HDL cholesterol was 13%, compared with 24% of those with abnormal OGTT.

Among 129 of the women whose breast-feeding status was known, 63% were breast-feeding at the time of the postpartum visit. Breast-feeding was associated with significantly lower triglyceride level, higher HDL cholesterol, lower total cholesterol/HDL ratio, lower mean fasting glucose at the OGTT, and lower prevalence of any postpartum abnormality of glucose tolerance, including diabetes. Although these differences did not seem to be attributable to different maternal characteristics, there was a trend toward a lower prevalence of obesity (defined as a BMI of 27 or higher) among the breast-feeding women (49% vs. 62.5%).

TORONTO — Postpartum testing in women who had gestational diabetes during pregnancy should include both an oral glucose-tolerance test and a lipid profile, Genevieve Dubé and her colleagues advised in a poster presented at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

Data from a retrospective analysis of 223 women who had gestational diabetes mellitus (GDM) during pregnancy revealed that postpartum glucose-tolerance abnormalities were common, affecting one-fourth of all women. Moreover, “Isolated fasting glucose testing would have failed to identify most cases of postpartum dysglycemia,” noted Ms. Dubé and her colleagues at the Centre Régional du Diabète de Laval (Que.).

The data also suggested that a lipid profile should be part of the assessment, because many of the women with previous GDM—including those with normal postpartum oral glucose-tolerance test (OGTT) results—have altered lipids suggestive of features of the cardiometabolic syndrome, they said.

The 223 women had received prenatal care between June 2004 and April 2005 at Laval's diabetic pregnancy clinic, which has had a program of routine postnatal GDM follow-up since 2002. The group had a mean age of 31 years and a mean body mass index (kg/m2) of 28.3. Two-thirds of the women were white. Insulin treatment was used by 34% during pregnancy.

All were told to return at 2 months—whether or not they were still breast-feeding—for postpartum lab testing, which included a 12-hour fasting glucose, a 75-g OGTT, a lipid profile, and a thyroid-stimulating hormone test. A total of 74% (165 patients) showed up, at a mean of 3 months following delivery.

Of the 164 who underwent the OGTT, some form of impaired glucose tolerance was detected in 25% (41 patients), including frank type 2 diabetes in 4% (7 patients), isolated impaired glucose tolerance in 16% (26 patients), isolated impaired fasting glucose in 2% (3 patients), and both impaired glucose tolerance and impaired fasting glucose in 3% (5 patients).

No matter what fasting blood glucose (FBG) cutoff was used, more than half of all dysglycemic women would have been missed if postpartum lab screening included only FBG instead of OGTT. Among the 41 women with abnormal 2-hour OGTT results, 49% had FBG values at or above 5.6 mmol/L, 41.5% had FBG levels at or above 5.8 mmol/L, and 32% had FBG levels at or above 6.1 mmol/L.

The need for insulin therapy and a first-trimester FBG above 6.1 mmol/L were the only risk factors analyzed that significantly predicted postpartum abnormal OGTT, with odds ratios of 1.89 and 3.41, respectively. Maternal age, BMI, parity, macrosomia, and nonwhite race were not predictive of postpartum glucose status, they said.

Among the 165 women who had postpartum lipid tests, 70% had at least one abnormality, defined as a triglyceride level of 1.7 mmol/L or higher, HDL cholesterol level at or lower than 1.3 mmol/L, or a total cholesterol/HDL cholesterol ratio of 5.0 or greater.

Cardiometabolic risk factors were not limited to women with abnormal OGTT results and diabetes. Indeed, two-thirds of the 123 women with normal postpartum glucose tolerance had at least one lipid abnormality; 23% had triglyceride levels of 1.7 mmol/L or higher, and 23% had HDL cholesterol of 1.3 mmol/L or lower. In fact, only when those two abnormalities were combined was there a significant correlation with OGTT results: The proportion of women with normal glucose tolerance who had both high triglycerides and low HDL cholesterol was 13%, compared with 24% of those with abnormal OGTT.

Among 129 of the women whose breast-feeding status was known, 63% were breast-feeding at the time of the postpartum visit. Breast-feeding was associated with significantly lower triglyceride level, higher HDL cholesterol, lower total cholesterol/HDL ratio, lower mean fasting glucose at the OGTT, and lower prevalence of any postpartum abnormality of glucose tolerance, including diabetes. Although these differences did not seem to be attributable to different maternal characteristics, there was a trend toward a lower prevalence of obesity (defined as a BMI of 27 or higher) among the breast-feeding women (49% vs. 62.5%).

TORONTO — Postpartum testing in women who had gestational diabetes during pregnancy should include both an oral glucose-tolerance test and a lipid profile, Genevieve Dubé and her colleagues advised in a poster presented at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

Data from a retrospective analysis of 223 women who had gestational diabetes mellitus (GDM) during pregnancy revealed that postpartum glucose-tolerance abnormalities were common, affecting one-fourth of all women. Moreover, “Isolated fasting glucose testing would have failed to identify most cases of postpartum dysglycemia,” noted Ms. Dubé and her colleagues at the Centre Régional du Diabète de Laval (Que.).

The data also suggested that a lipid profile should be part of the assessment, because many of the women with previous GDM—including those with normal postpartum oral glucose-tolerance test (OGTT) results—have altered lipids suggestive of features of the cardiometabolic syndrome, they said.

The 223 women had received prenatal care between June 2004 and April 2005 at Laval's diabetic pregnancy clinic, which has had a program of routine postnatal GDM follow-up since 2002. The group had a mean age of 31 years and a mean body mass index (kg/m2) of 28.3. Two-thirds of the women were white. Insulin treatment was used by 34% during pregnancy.

All were told to return at 2 months—whether or not they were still breast-feeding—for postpartum lab testing, which included a 12-hour fasting glucose, a 75-g OGTT, a lipid profile, and a thyroid-stimulating hormone test. A total of 74% (165 patients) showed up, at a mean of 3 months following delivery.

Of the 164 who underwent the OGTT, some form of impaired glucose tolerance was detected in 25% (41 patients), including frank type 2 diabetes in 4% (7 patients), isolated impaired glucose tolerance in 16% (26 patients), isolated impaired fasting glucose in 2% (3 patients), and both impaired glucose tolerance and impaired fasting glucose in 3% (5 patients).

No matter what fasting blood glucose (FBG) cutoff was used, more than half of all dysglycemic women would have been missed if postpartum lab screening included only FBG instead of OGTT. Among the 41 women with abnormal 2-hour OGTT results, 49% had FBG values at or above 5.6 mmol/L, 41.5% had FBG levels at or above 5.8 mmol/L, and 32% had FBG levels at or above 6.1 mmol/L.

The need for insulin therapy and a first-trimester FBG above 6.1 mmol/L were the only risk factors analyzed that significantly predicted postpartum abnormal OGTT, with odds ratios of 1.89 and 3.41, respectively. Maternal age, BMI, parity, macrosomia, and nonwhite race were not predictive of postpartum glucose status, they said.

Among the 165 women who had postpartum lipid tests, 70% had at least one abnormality, defined as a triglyceride level of 1.7 mmol/L or higher, HDL cholesterol level at or lower than 1.3 mmol/L, or a total cholesterol/HDL cholesterol ratio of 5.0 or greater.

Cardiometabolic risk factors were not limited to women with abnormal OGTT results and diabetes. Indeed, two-thirds of the 123 women with normal postpartum glucose tolerance had at least one lipid abnormality; 23% had triglyceride levels of 1.7 mmol/L or higher, and 23% had HDL cholesterol of 1.3 mmol/L or lower. In fact, only when those two abnormalities were combined was there a significant correlation with OGTT results: The proportion of women with normal glucose tolerance who had both high triglycerides and low HDL cholesterol was 13%, compared with 24% of those with abnormal OGTT.

Among 129 of the women whose breast-feeding status was known, 63% were breast-feeding at the time of the postpartum visit. Breast-feeding was associated with significantly lower triglyceride level, higher HDL cholesterol, lower total cholesterol/HDL ratio, lower mean fasting glucose at the OGTT, and lower prevalence of any postpartum abnormality of glucose tolerance, including diabetes. Although these differences did not seem to be attributable to different maternal characteristics, there was a trend toward a lower prevalence of obesity (defined as a BMI of 27 or higher) among the breast-feeding women (49% vs. 62.5%).

ATLANTA — No major safety issues have arisen thus far with the new rotavirus vaccine, Penina Haber said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

In fact, rates of intussusception—the complication that resulted in the 1999 withdrawal from the market of the old rotavirus vaccine (Wyeth-Ayerst's RotaShield)—are actually lower with Merck's Rotateq than would be expected in the general population, said Ms. Haber, an epidemiologist with the CDC's Immunization Safety Office.

The CDC is monitoring Rotateq for gastrointestinal-related adverse events as well as any other unexpected problems via the passive Vaccine Adverse Event Reporting System (VAERS). Should any safety “signals” arise, the active surveillance system known as the Vaccine Safety Datalink (VSD), comprising eight large HMOs (covering 3% of the U.S. population), will be utilized to investigate further.

The CDC is now using VAERS and VSD to monitor safety for all new vaccines, with researchers from the CDC and the Food and Drug Administration reviewing all reports sent to VAERS on a daily basis, Robert L. Davis, director of the CDC's Immunization Safety Office, said during a joint presentation with Ms. Haber on vaccine safety.

From March 1, 2006, through Oct. 23, 2006, VAERS received a total of 189 adverse event reports following receipt of Rotateq, from a background of 1,786,476 doses distributed as of Sept. 30, 2006. Of the 189 reports, 48% were associated with receipt of Rotateq alone, and the rest were in combination with other vaccines. Children aged 2–3 months accounted for 57% of the reports, while 5% were for children under 2 months of age. (The vaccine is recommended at ages 2, 4, and 6 months.) Fifty-five percent of reports were of events occurring within 2 days of vaccination, while another 5% occurred within 7 days.

Among the most frequent adverse events following receipt of Rotateq in children up to 12 months of age were diarrhea (24% vs. 3% following all other vaccines), vomiting (22% vs. 5%), GI hemorrhage (7% vs. 0%), and melena (6% vs. 1%). A total of 30 (16%) of the reports were of serious events, including 6 cases of intussusception. Four occurred after dose 1 and two after the second dose, at an interval of 2–32 days following vaccination.

Calculated from the VSD background intussusception rate of 2.98 per 10,000 person-years, the expected number of cases within a 21-day period would be 30.7. In contrast, just four cases were observed within 21 days of Rotateq receipt. If an underreporting rate of 47% is assumed (Am. J. Epidemiol. 2001;154:1006–12), the number of intussusceptions associated with Rotateq would still be significantly lower than expected, Ms. Haber said.

Excluding the intussusception cases, there were 19 reports of hematochezia following Rotateq. During the same time period, hematochezia was reported in 4 children receiving other vaccines in 2,248 VAERS reports. Most of the hematochezia cases occurred within 3 days of vaccination, and none was serious. In addition to the approximately 96,000 infants born each year who are surveilled in VSD and will be followed for adverse events after administration of Rotateq, about 45,000 infants will provide additional data to Merck in a phase 4 study, she noted.

ATLANTA — No major safety issues have arisen thus far with the new rotavirus vaccine, Penina Haber said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

In fact, rates of intussusception—the complication that resulted in the 1999 withdrawal from the market of the old rotavirus vaccine (Wyeth-Ayerst's RotaShield)—are actually lower with Merck's Rotateq than would be expected in the general population, said Ms. Haber, an epidemiologist with the CDC's Immunization Safety Office.

The CDC is monitoring Rotateq for gastrointestinal-related adverse events as well as any other unexpected problems via the passive Vaccine Adverse Event Reporting System (VAERS). Should any safety “signals” arise, the active surveillance system known as the Vaccine Safety Datalink (VSD), comprising eight large HMOs (covering 3% of the U.S. population), will be utilized to investigate further.

The CDC is now using VAERS and VSD to monitor safety for all new vaccines, with researchers from the CDC and the Food and Drug Administration reviewing all reports sent to VAERS on a daily basis, Robert L. Davis, director of the CDC's Immunization Safety Office, said during a joint presentation with Ms. Haber on vaccine safety.

From March 1, 2006, through Oct. 23, 2006, VAERS received a total of 189 adverse event reports following receipt of Rotateq, from a background of 1,786,476 doses distributed as of Sept. 30, 2006. Of the 189 reports, 48% were associated with receipt of Rotateq alone, and the rest were in combination with other vaccines. Children aged 2–3 months accounted for 57% of the reports, while 5% were for children under 2 months of age. (The vaccine is recommended at ages 2, 4, and 6 months.) Fifty-five percent of reports were of events occurring within 2 days of vaccination, while another 5% occurred within 7 days.

Among the most frequent adverse events following receipt of Rotateq in children up to 12 months of age were diarrhea (24% vs. 3% following all other vaccines), vomiting (22% vs. 5%), GI hemorrhage (7% vs. 0%), and melena (6% vs. 1%). A total of 30 (16%) of the reports were of serious events, including 6 cases of intussusception. Four occurred after dose 1 and two after the second dose, at an interval of 2–32 days following vaccination.

Calculated from the VSD background intussusception rate of 2.98 per 10,000 person-years, the expected number of cases within a 21-day period would be 30.7. In contrast, just four cases were observed within 21 days of Rotateq receipt. If an underreporting rate of 47% is assumed (Am. J. Epidemiol. 2001;154:1006–12), the number of intussusceptions associated with Rotateq would still be significantly lower than expected, Ms. Haber said.

Excluding the intussusception cases, there were 19 reports of hematochezia following Rotateq. During the same time period, hematochezia was reported in 4 children receiving other vaccines in 2,248 VAERS reports. Most of the hematochezia cases occurred within 3 days of vaccination, and none was serious. In addition to the approximately 96,000 infants born each year who are surveilled in VSD and will be followed for adverse events after administration of Rotateq, about 45,000 infants will provide additional data to Merck in a phase 4 study, she noted.

ATLANTA — No major safety issues have arisen thus far with the new rotavirus vaccine, Penina Haber said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

In fact, rates of intussusception—the complication that resulted in the 1999 withdrawal from the market of the old rotavirus vaccine (Wyeth-Ayerst's RotaShield)—are actually lower with Merck's Rotateq than would be expected in the general population, said Ms. Haber, an epidemiologist with the CDC's Immunization Safety Office.

The CDC is monitoring Rotateq for gastrointestinal-related adverse events as well as any other unexpected problems via the passive Vaccine Adverse Event Reporting System (VAERS). Should any safety “signals” arise, the active surveillance system known as the Vaccine Safety Datalink (VSD), comprising eight large HMOs (covering 3% of the U.S. population), will be utilized to investigate further.

The CDC is now using VAERS and VSD to monitor safety for all new vaccines, with researchers from the CDC and the Food and Drug Administration reviewing all reports sent to VAERS on a daily basis, Robert L. Davis, director of the CDC's Immunization Safety Office, said during a joint presentation with Ms. Haber on vaccine safety.

From March 1, 2006, through Oct. 23, 2006, VAERS received a total of 189 adverse event reports following receipt of Rotateq, from a background of 1,786,476 doses distributed as of Sept. 30, 2006. Of the 189 reports, 48% were associated with receipt of Rotateq alone, and the rest were in combination with other vaccines. Children aged 2–3 months accounted for 57% of the reports, while 5% were for children under 2 months of age. (The vaccine is recommended at ages 2, 4, and 6 months.) Fifty-five percent of reports were of events occurring within 2 days of vaccination, while another 5% occurred within 7 days.

Among the most frequent adverse events following receipt of Rotateq in children up to 12 months of age were diarrhea (24% vs. 3% following all other vaccines), vomiting (22% vs. 5%), GI hemorrhage (7% vs. 0%), and melena (6% vs. 1%). A total of 30 (16%) of the reports were of serious events, including 6 cases of intussusception. Four occurred after dose 1 and two after the second dose, at an interval of 2–32 days following vaccination.

Calculated from the VSD background intussusception rate of 2.98 per 10,000 person-years, the expected number of cases within a 21-day period would be 30.7. In contrast, just four cases were observed within 21 days of Rotateq receipt. If an underreporting rate of 47% is assumed (Am. J. Epidemiol. 2001;154:1006–12), the number of intussusceptions associated with Rotateq would still be significantly lower than expected, Ms. Haber said.

Excluding the intussusception cases, there were 19 reports of hematochezia following Rotateq. During the same time period, hematochezia was reported in 4 children receiving other vaccines in 2,248 VAERS reports. Most of the hematochezia cases occurred within 3 days of vaccination, and none was serious. In addition to the approximately 96,000 infants born each year who are surveilled in VSD and will be followed for adverse events after administration of Rotateq, about 45,000 infants will provide additional data to Merck in a phase 4 study, she noted.

ATLANTA — Guillain-Barré syndrome has been reported in 17 recipients of the tetravalent meningococcal conjugate vaccine, but it's unclear whether the association is causal, Dr. Robert L. Davis said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The data, also reported the week prior to the meeting in the Oct. 20 issue of CDC's Morbidity and Mortality Weekly Report, suggest an excess risk for Guillain-Barré syndrome (GBS) of about 1.25 cases per million doses of the vaccine. But the limitations of the data collection methods and uncertainty about background rates of GBS prevent any firm conclusions about causation. The additional cases do not affect current CDC recommendations for vaccination, said Dr. Davis, director of the CDC's Immunization Safety Office.

Indeed, a “decision analysis” presented by Dr. Bo-Hyun Cho of the CDC's National Center for Immunization and Respiratory Diseases, suggests that even if the association is real, it is outweighed by the risk of contracting meningococcal disease without the vaccine.

The CDC and the Food and Drug Administration had previously alerted health care providers about a possible association between GBS and the tetravalent meningococcal conjugate vaccine (MCV4), which is marketed as Menactra by Sanofi Pasteur Inc. Five cases were reported in an October 2005 alert, and three cases in an April 2006 notice. Since then, an additional nine cases have been reported to the Vaccine Adverse Event Reporting System (VAERS), bringing to 17 the total number of reported cases since the MCV4 vaccine became available in March 2005.

The onset interval for the 17 cases ranged from 2 to 33 days after vaccination, with a mean of 15.7 days, Dr. Davis said.

Further analysis was restricted to the 15 patients aged 11–19 years, because 94% of MCV4 recipients are in that age range (the other 2 patients were aged 30 and 43 years). A total of 5.9 million doses of MCV4 have been distributed to individuals in that age group.

Compared with the observed GBS rate of 0.2 cases per 100,000 person-months for those vaccinated, data from two separate databases (the Healthcare Cost and Utilization Project and the Vaccine Safety Datalink) both yielded an expected background relative risk for GBS of 0.11 per 100,000 person-months.

“There is evidence for a small increased risk of GBS after MCV4. The timing of neurologic symptoms within 1–5 weeks of vaccination among reported cases is of concern,” Dr. Davis said.

He added, “Substantial uncertainty exists regarding the risk estimate, using either the HCUS or VSD background incidence rate.” Underreporting is assumed with the VAERS, a passive reporting system, but no surges in GBS reports occurred following either of the previous MMWR notices, he said.

The increased risk appears confined to older adolescents, with a relative risk of 0.27 per 100,000 person-months among those aged 11–14 years (based on 1 case out of 2.5 million doses distributed), compared with 2.55 per 100,000 person-months in the 15- to 19-year-old group (14 cases among 3.5 million doses).

Dr. Ban Mishu Allos, an ACIP member from the department of infectious diseases at Vanderbilt University, Nashville, Tenn., noted that many of the older adolescents would likely have received the vaccine before the start of college classes during the summer, which happens to be the season for Campylobacter jejuni infection, a frequent antecedent to GBS. The younger teens would be more likely to receive the vaccine at other times of the year as well.

No patient had reported diarrheal prodromes, and none of the four individuals tested for campylobacter were positive. However, the infection is often asymptomatic, and the organism would not be detected in stool by the time GBS symptoms appeared, Dr. Allos remarked.

Dr. Cho's analysis compared the health outcomes of vaccination versus no vaccination in the birth cohort of 11-year-olds, which includes 4,076,600 individuals. Among the assumptions were that the risk for GBS lasts 6 weeks after vaccination, and that an 11-year-old has a life expectancy of 67.7 more years. Parameters included a 5% morbidity rate among adolescents with GBS, which overall carries a favorable prognosis (Lancet 1998;352:635–41).

Meningococcal disease, on the other hand, has a case-fatality rate of 10%. Incidence of disease caused by one of the vaccine's serogroups (A, C, Y, and W-135) is 0.77 per 100,000 unvaccinated individuals, of which the vaccine prevents 93%. With those and other published and unpublished data, Dr. Cho calculated that the vaccine prevents 163 cases of meningococcal disease and 16 deaths due to a vaccine strain for every 3 additional cases of GBS.

These data are subject to many limitations and should be considered preliminary. But they do suggest that “the period of risk of vaccine-attributable GBS is small and short [compared with] the prolonged benefit of meningococcal disease prevention,” Dr. Cho said.

Dr. Michael D. Decker, vice president of Scientific Affairs at Sanofi-Pasteur, said his company is supporting a study to further investigate the issue over a 2-year period in the 11- to 17-year-old population in an HMO database of over 100 million covered lives. “We believe there is enough power to clarify the association,” he said in an interview.

The CDC also is continuing to evaluate the issue.

Clinicians are requested to report adverse events related to the MCV4 vaccine by going to www.vaers.hhs.gov

A Vaccine Information Statement and fact sheet with information on the vaccine and reported GBS cases are available at www.cdc.gov/nip/publications/vis/default.htmwww.cdc.gov/nip/vacsafe/concerns/gbs/menactra.htm

Christine Kilgore contributed to this report.

ATLANTA — Guillain-Barré syndrome has been reported in 17 recipients of the tetravalent meningococcal conjugate vaccine, but it's unclear whether the association is causal, Dr. Robert L. Davis said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The data, also reported the week prior to the meeting in the Oct. 20 issue of CDC's Morbidity and Mortality Weekly Report, suggest an excess risk for Guillain-Barré syndrome (GBS) of about 1.25 cases per million doses of the vaccine. But the limitations of the data collection methods and uncertainty about background rates of GBS prevent any firm conclusions about causation. The additional cases do not affect current CDC recommendations for vaccination, said Dr. Davis, director of the CDC's Immunization Safety Office.

Indeed, a “decision analysis” presented by Dr. Bo-Hyun Cho of the CDC's National Center for Immunization and Respiratory Diseases, suggests that even if the association is real, it is outweighed by the risk of contracting meningococcal disease without the vaccine.

The CDC and the Food and Drug Administration had previously alerted health care providers about a possible association between GBS and the tetravalent meningococcal conjugate vaccine (MCV4), which is marketed as Menactra by Sanofi Pasteur Inc. Five cases were reported in an October 2005 alert, and three cases in an April 2006 notice. Since then, an additional nine cases have been reported to the Vaccine Adverse Event Reporting System (VAERS), bringing to 17 the total number of reported cases since the MCV4 vaccine became available in March 2005.

The onset interval for the 17 cases ranged from 2 to 33 days after vaccination, with a mean of 15.7 days, Dr. Davis said.

Further analysis was restricted to the 15 patients aged 11–19 years, because 94% of MCV4 recipients are in that age range (the other 2 patients were aged 30 and 43 years). A total of 5.9 million doses of MCV4 have been distributed to individuals in that age group.

Compared with the observed GBS rate of 0.2 cases per 100,000 person-months for those vaccinated, data from two separate databases (the Healthcare Cost and Utilization Project and the Vaccine Safety Datalink) both yielded an expected background relative risk for GBS of 0.11 per 100,000 person-months.

“There is evidence for a small increased risk of GBS after MCV4. The timing of neurologic symptoms within 1–5 weeks of vaccination among reported cases is of concern,” Dr. Davis said.

He added, “Substantial uncertainty exists regarding the risk estimate, using either the HCUS or VSD background incidence rate.” Underreporting is assumed with the VAERS, a passive reporting system, but no surges in GBS reports occurred following either of the previous MMWR notices, he said.

The increased risk appears confined to older adolescents, with a relative risk of 0.27 per 100,000 person-months among those aged 11–14 years (based on 1 case out of 2.5 million doses distributed), compared with 2.55 per 100,000 person-months in the 15- to 19-year-old group (14 cases among 3.5 million doses).

Dr. Ban Mishu Allos, an ACIP member from the department of infectious diseases at Vanderbilt University, Nashville, Tenn., noted that many of the older adolescents would likely have received the vaccine before the start of college classes during the summer, which happens to be the season for Campylobacter jejuni infection, a frequent antecedent to GBS. The younger teens would be more likely to receive the vaccine at other times of the year as well.

No patient had reported diarrheal prodromes, and none of the four individuals tested for campylobacter were positive. However, the infection is often asymptomatic, and the organism would not be detected in stool by the time GBS symptoms appeared, Dr. Allos remarked.

Dr. Cho's analysis compared the health outcomes of vaccination versus no vaccination in the birth cohort of 11-year-olds, which includes 4,076,600 individuals. Among the assumptions were that the risk for GBS lasts 6 weeks after vaccination, and that an 11-year-old has a life expectancy of 67.7 more years. Parameters included a 5% morbidity rate among adolescents with GBS, which overall carries a favorable prognosis (Lancet 1998;352:635–41).

Meningococcal disease, on the other hand, has a case-fatality rate of 10%. Incidence of disease caused by one of the vaccine's serogroups (A, C, Y, and W-135) is 0.77 per 100,000 unvaccinated individuals, of which the vaccine prevents 93%. With those and other published and unpublished data, Dr. Cho calculated that the vaccine prevents 163 cases of meningococcal disease and 16 deaths due to a vaccine strain for every 3 additional cases of GBS.

These data are subject to many limitations and should be considered preliminary. But they do suggest that “the period of risk of vaccine-attributable GBS is small and short [compared with] the prolonged benefit of meningococcal disease prevention,” Dr. Cho said.

Dr. Michael D. Decker, vice president of Scientific Affairs at Sanofi-Pasteur, said his company is supporting a study to further investigate the issue over a 2-year period in the 11- to 17-year-old population in an HMO database of over 100 million covered lives. “We believe there is enough power to clarify the association,” he said in an interview.

The CDC also is continuing to evaluate the issue.

Clinicians are requested to report adverse events related to the MCV4 vaccine by going to www.vaers.hhs.gov

A Vaccine Information Statement and fact sheet with information on the vaccine and reported GBS cases are available at www.cdc.gov/nip/publications/vis/default.htmwww.cdc.gov/nip/vacsafe/concerns/gbs/menactra.htm

Christine Kilgore contributed to this report.

ATLANTA — Guillain-Barré syndrome has been reported in 17 recipients of the tetravalent meningococcal conjugate vaccine, but it's unclear whether the association is causal, Dr. Robert L. Davis said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The data, also reported the week prior to the meeting in the Oct. 20 issue of CDC's Morbidity and Mortality Weekly Report, suggest an excess risk for Guillain-Barré syndrome (GBS) of about 1.25 cases per million doses of the vaccine. But the limitations of the data collection methods and uncertainty about background rates of GBS prevent any firm conclusions about causation. The additional cases do not affect current CDC recommendations for vaccination, said Dr. Davis, director of the CDC's Immunization Safety Office.

Indeed, a “decision analysis” presented by Dr. Bo-Hyun Cho of the CDC's National Center for Immunization and Respiratory Diseases, suggests that even if the association is real, it is outweighed by the risk of contracting meningococcal disease without the vaccine.

The CDC and the Food and Drug Administration had previously alerted health care providers about a possible association between GBS and the tetravalent meningococcal conjugate vaccine (MCV4), which is marketed as Menactra by Sanofi Pasteur Inc. Five cases were reported in an October 2005 alert, and three cases in an April 2006 notice. Since then, an additional nine cases have been reported to the Vaccine Adverse Event Reporting System (VAERS), bringing to 17 the total number of reported cases since the MCV4 vaccine became available in March 2005.

The onset interval for the 17 cases ranged from 2 to 33 days after vaccination, with a mean of 15.7 days, Dr. Davis said.

Further analysis was restricted to the 15 patients aged 11–19 years, because 94% of MCV4 recipients are in that age range (the other 2 patients were aged 30 and 43 years). A total of 5.9 million doses of MCV4 have been distributed to individuals in that age group.

Compared with the observed GBS rate of 0.2 cases per 100,000 person-months for those vaccinated, data from two separate databases (the Healthcare Cost and Utilization Project and the Vaccine Safety Datalink) both yielded an expected background relative risk for GBS of 0.11 per 100,000 person-months.

“There is evidence for a small increased risk of GBS after MCV4. The timing of neurologic symptoms within 1–5 weeks of vaccination among reported cases is of concern,” Dr. Davis said.

He added, “Substantial uncertainty exists regarding the risk estimate, using either the HCUS or VSD background incidence rate.” Underreporting is assumed with the VAERS, a passive reporting system, but no surges in GBS reports occurred following either of the previous MMWR notices, he said.

The increased risk appears confined to older adolescents, with a relative risk of 0.27 per 100,000 person-months among those aged 11–14 years (based on 1 case out of 2.5 million doses distributed), compared with 2.55 per 100,000 person-months in the 15- to 19-year-old group (14 cases among 3.5 million doses).

Dr. Ban Mishu Allos, an ACIP member from the department of infectious diseases at Vanderbilt University, Nashville, Tenn., noted that many of the older adolescents would likely have received the vaccine before the start of college classes during the summer, which happens to be the season for Campylobacter jejuni infection, a frequent antecedent to GBS. The younger teens would be more likely to receive the vaccine at other times of the year as well.

No patient had reported diarrheal prodromes, and none of the four individuals tested for campylobacter were positive. However, the infection is often asymptomatic, and the organism would not be detected in stool by the time GBS symptoms appeared, Dr. Allos remarked.

Dr. Cho's analysis compared the health outcomes of vaccination versus no vaccination in the birth cohort of 11-year-olds, which includes 4,076,600 individuals. Among the assumptions were that the risk for GBS lasts 6 weeks after vaccination, and that an 11-year-old has a life expectancy of 67.7 more years. Parameters included a 5% morbidity rate among adolescents with GBS, which overall carries a favorable prognosis (Lancet 1998;352:635–41).

Meningococcal disease, on the other hand, has a case-fatality rate of 10%. Incidence of disease caused by one of the vaccine's serogroups (A, C, Y, and W-135) is 0.77 per 100,000 unvaccinated individuals, of which the vaccine prevents 93%. With those and other published and unpublished data, Dr. Cho calculated that the vaccine prevents 163 cases of meningococcal disease and 16 deaths due to a vaccine strain for every 3 additional cases of GBS.

These data are subject to many limitations and should be considered preliminary. But they do suggest that “the period of risk of vaccine-attributable GBS is small and short [compared with] the prolonged benefit of meningococcal disease prevention,” Dr. Cho said.

Dr. Michael D. Decker, vice president of Scientific Affairs at Sanofi-Pasteur, said his company is supporting a study to further investigate the issue over a 2-year period in the 11- to 17-year-old population in an HMO database of over 100 million covered lives. “We believe there is enough power to clarify the association,” he said in an interview.

The CDC also is continuing to evaluate the issue.

Clinicians are requested to report adverse events related to the MCV4 vaccine by going to www.vaers.hhs.gov

A Vaccine Information Statement and fact sheet with information on the vaccine and reported GBS cases are available at www.cdc.gov/nip/publications/vis/default.htmwww.cdc.gov/nip/vacsafe/concerns/gbs/menactra.htm

Christine Kilgore contributed to this report.

ATLANTA — Medimmune's investigational cold-adapted trivalent influenza vaccine appears to have a highly favorable risk-benefit profile in children aged 12–59 months without a history of wheezing, Dr. Robert Walker said at the fall meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

The cold-adapted influenza vaccine, trivalent (CAIV-T) is Medimmune's next-generation intranasal influenza vaccine. Unlike its currently licensed live-virus intranasal influenza vaccine, Flumist, CAIV-T does not need to be kept frozen and may be stored at 2°–8° Celsius in a refrigerator, said Dr. Walker, vice president of clinical development at Medimmune.

The company has submitted a biologics licensing application to switch formulations from Flumist, currently approved for healthy individuals aged 5–49 years, to CAIV-T for the same population. It also is seeking an expanded label for CAIV-T in children aged between 12 and 59 months without a history of wheezing. A Food and Drug Administration response is expected in the second quarter of 2007. Pending a positive outcome, Medimmune plans to commercially provide CAIV-T for the 2007–2008 influenza season, according to a company statement.

At the ACIP meeting, Dr. Walker presented pivotal data from a double-blind, multinational study in which 8,475 children aged 6–59 months were randomized to receive two doses of either CAIV-T or the injected trivalent influenza vaccine (TIV). All first doses were given by Oct. 29, 2004.

From Nov. 1, 2004, through June 1, 2005, the overall attack rate of all influenza strains was 3.9% among the CAIV-T recipients, compared with 8.6% among the children who received TIV, a significant 54.7% improvement in efficacy. Attack rates also were significantly lower with CAIV-T for the H1N1 strain (0.1% vs. 0.7%) and for H3N2 (0.9% vs. 4.5%), while the difference in attack rates of influenza B was not significant (2.9% vs. 3.5%).

Runny and/or stuffy noses were reported more often with CAIV-T, while injection site reactions were more common with TIV. Among children younger than 2 years, medically significant wheezing was significantly more common within 42 days after the first dose among the CAIV-T group, occurring in 3.2%, compared with 2.0% of the TIV recipients at weeks 2, 3, and 4 after immunization. Those rates were not different after 42 days or after the second dose, he said.

Hospitalization associated with medically significant wheezing occurred in 0.3% with CAIV-T and 0.2% with TIV, with mean durations of 4.5 days and 4.0 days, respectively. There were no deaths, and no patient required intensive care or a ventilator. Recurrences of medically significant wheezing occurred in 32% of CAIV-T recipients and in 28% with TIV.

All-cause hospitalization was significantly greater with CAIV-T only in children aged 6–11 months (6.1% of 684 patients, compared with 2.8% of 683 who received TIV). The most common reasons for hospitalization were lower respiratory tract infections and gastrointestinal problems (frequently rotavirus), Dr. Walker noted.

In children with a history of wheezing, those aged 12–47 months in the CAIV-T group had significantly higher hospitalization rates than did those in the TIV group. In the 12- to 23-month age group with a history of wheezing, for example, 5.1% of the CAIV-T recipients compared with 2.6% of TIV patients were hospitalized.

However, among the children aged 12–59 months who did not have a history of wheezing, there were no differences in hospitalization rates between the CAIV-T and the TIV recipients. Similar reductions in influenza rates were seen with CAIV-T compared to TIV in the groups with and without wheezing, Dr. Walker reported. About 80% of children aged 12–59 months have no history of wheezing. Using CAIV-T in that population instead of TIV would result in about 1.5 million fewer cases of symptomatic influenza annually, he said.

ATLANTA — Medimmune's investigational cold-adapted trivalent influenza vaccine appears to have a highly favorable risk-benefit profile in children aged 12–59 months without a history of wheezing, Dr. Robert Walker said at the fall meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

The cold-adapted influenza vaccine, trivalent (CAIV-T) is Medimmune's next-generation intranasal influenza vaccine. Unlike its currently licensed live-virus intranasal influenza vaccine, Flumist, CAIV-T does not need to be kept frozen and may be stored at 2°–8° Celsius in a refrigerator, said Dr. Walker, vice president of clinical development at Medimmune.

The company has submitted a biologics licensing application to switch formulations from Flumist, currently approved for healthy individuals aged 5–49 years, to CAIV-T for the same population. It also is seeking an expanded label for CAIV-T in children aged between 12 and 59 months without a history of wheezing. A Food and Drug Administration response is expected in the second quarter of 2007. Pending a positive outcome, Medimmune plans to commercially provide CAIV-T for the 2007–2008 influenza season, according to a company statement.

At the ACIP meeting, Dr. Walker presented pivotal data from a double-blind, multinational study in which 8,475 children aged 6–59 months were randomized to receive two doses of either CAIV-T or the injected trivalent influenza vaccine (TIV). All first doses were given by Oct. 29, 2004.

From Nov. 1, 2004, through June 1, 2005, the overall attack rate of all influenza strains was 3.9% among the CAIV-T recipients, compared with 8.6% among the children who received TIV, a significant 54.7% improvement in efficacy. Attack rates also were significantly lower with CAIV-T for the H1N1 strain (0.1% vs. 0.7%) and for H3N2 (0.9% vs. 4.5%), while the difference in attack rates of influenza B was not significant (2.9% vs. 3.5%).

Runny and/or stuffy noses were reported more often with CAIV-T, while injection site reactions were more common with TIV. Among children younger than 2 years, medically significant wheezing was significantly more common within 42 days after the first dose among the CAIV-T group, occurring in 3.2%, compared with 2.0% of the TIV recipients at weeks 2, 3, and 4 after immunization. Those rates were not different after 42 days or after the second dose, he said.

Hospitalization associated with medically significant wheezing occurred in 0.3% with CAIV-T and 0.2% with TIV, with mean durations of 4.5 days and 4.0 days, respectively. There were no deaths, and no patient required intensive care or a ventilator. Recurrences of medically significant wheezing occurred in 32% of CAIV-T recipients and in 28% with TIV.

All-cause hospitalization was significantly greater with CAIV-T only in children aged 6–11 months (6.1% of 684 patients, compared with 2.8% of 683 who received TIV). The most common reasons for hospitalization were lower respiratory tract infections and gastrointestinal problems (frequently rotavirus), Dr. Walker noted.

In children with a history of wheezing, those aged 12–47 months in the CAIV-T group had significantly higher hospitalization rates than did those in the TIV group. In the 12- to 23-month age group with a history of wheezing, for example, 5.1% of the CAIV-T recipients compared with 2.6% of TIV patients were hospitalized.

However, among the children aged 12–59 months who did not have a history of wheezing, there were no differences in hospitalization rates between the CAIV-T and the TIV recipients. Similar reductions in influenza rates were seen with CAIV-T compared to TIV in the groups with and without wheezing, Dr. Walker reported. About 80% of children aged 12–59 months have no history of wheezing. Using CAIV-T in that population instead of TIV would result in about 1.5 million fewer cases of symptomatic influenza annually, he said.

ATLANTA — Medimmune's investigational cold-adapted trivalent influenza vaccine appears to have a highly favorable risk-benefit profile in children aged 12–59 months without a history of wheezing, Dr. Robert Walker said at the fall meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

The cold-adapted influenza vaccine, trivalent (CAIV-T) is Medimmune's next-generation intranasal influenza vaccine. Unlike its currently licensed live-virus intranasal influenza vaccine, Flumist, CAIV-T does not need to be kept frozen and may be stored at 2°–8° Celsius in a refrigerator, said Dr. Walker, vice president of clinical development at Medimmune.

The company has submitted a biologics licensing application to switch formulations from Flumist, currently approved for healthy individuals aged 5–49 years, to CAIV-T for the same population. It also is seeking an expanded label for CAIV-T in children aged between 12 and 59 months without a history of wheezing. A Food and Drug Administration response is expected in the second quarter of 2007. Pending a positive outcome, Medimmune plans to commercially provide CAIV-T for the 2007–2008 influenza season, according to a company statement.

At the ACIP meeting, Dr. Walker presented pivotal data from a double-blind, multinational study in which 8,475 children aged 6–59 months were randomized to receive two doses of either CAIV-T or the injected trivalent influenza vaccine (TIV). All first doses were given by Oct. 29, 2004.

From Nov. 1, 2004, through June 1, 2005, the overall attack rate of all influenza strains was 3.9% among the CAIV-T recipients, compared with 8.6% among the children who received TIV, a significant 54.7% improvement in efficacy. Attack rates also were significantly lower with CAIV-T for the H1N1 strain (0.1% vs. 0.7%) and for H3N2 (0.9% vs. 4.5%), while the difference in attack rates of influenza B was not significant (2.9% vs. 3.5%).

Runny and/or stuffy noses were reported more often with CAIV-T, while injection site reactions were more common with TIV. Among children younger than 2 years, medically significant wheezing was significantly more common within 42 days after the first dose among the CAIV-T group, occurring in 3.2%, compared with 2.0% of the TIV recipients at weeks 2, 3, and 4 after immunization. Those rates were not different after 42 days or after the second dose, he said.

Hospitalization associated with medically significant wheezing occurred in 0.3% with CAIV-T and 0.2% with TIV, with mean durations of 4.5 days and 4.0 days, respectively. There were no deaths, and no patient required intensive care or a ventilator. Recurrences of medically significant wheezing occurred in 32% of CAIV-T recipients and in 28% with TIV.

All-cause hospitalization was significantly greater with CAIV-T only in children aged 6–11 months (6.1% of 684 patients, compared with 2.8% of 683 who received TIV). The most common reasons for hospitalization were lower respiratory tract infections and gastrointestinal problems (frequently rotavirus), Dr. Walker noted.

In children with a history of wheezing, those aged 12–47 months in the CAIV-T group had significantly higher hospitalization rates than did those in the TIV group. In the 12- to 23-month age group with a history of wheezing, for example, 5.1% of the CAIV-T recipients compared with 2.6% of TIV patients were hospitalized.

However, among the children aged 12–59 months who did not have a history of wheezing, there were no differences in hospitalization rates between the CAIV-T and the TIV recipients. Similar reductions in influenza rates were seen with CAIV-T compared to TIV in the groups with and without wheezing, Dr. Walker reported. About 80% of children aged 12–59 months have no history of wheezing. Using CAIV-T in that population instead of TIV would result in about 1.5 million fewer cases of symptomatic influenza annually, he said.

TORONTO — A formulation of insulin that is sprayed in the mouth and absorbed buccally seems to control glucose as well as injected insulin when used before a meal, Dr. Gerald Bernstein reported at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

The product, Generex Oral-lyn, is manufacturered by the Toronto-based company Generex Biotechnology.

When sprayed into the mouth using the company's RapidMist device, the insulin is absorbed into the buccal epithelium and is dispersed directly into the vascular system, thereby avoiding the problem of digestion that would occur if insulin were swallowed.

Dr. Bernstein, the company's vice president for medical affairs, presented a 3-month interim analysis of a 6-month study by Dr. Jaime Guevara-Aguirre and his associates at the Institute of Endocrinology IEMYR in Quito, Ecuador, where the product has been approved for use for patients with type 1 and type 2 diabetes.

First, 24 adolescents (mean age 15 years) and 5 young adults (21 years) with type 1 diabetes were stabilized for 6 weeks with basal twice-daily glargine and premeal injections of regular insulin.

For the next 6 weeks, they took Ora-lyn immediately before and after lunch rather than the injected regular insulin, while still injecting the glargine twice daily and the regular insulin before breakfast and dinner.

At baseline, the group had a mean hemoglobin A_1c of 9.9% and mean glucose of 236.6 mg/dL. After stabilization, their mean A_1c level had dropped to 8.4% and mean glucose (measured by the patients six times a day) to 140.4 mg/dL. After 3 weeks of substituting Ora-lyn for regular insulin at lunch, the mean A_1c was 8.5%, and mean glucose 143.3 mg/dL. Three weeks later (study week 12), the mean A_1c was 8.0%.

Doses of the glargine and the prelunch Oral-lyn were split in this study because previous data on each had shown that doing so improves efficacy. But in practice, piatients could take the entire dose of Ora-lyn before the meal, because the timing of its action is similar to that of available short-acting analogues: It begins working within 5 minutes, peaks at 30 minutes, and is cleared from the bloodstream by 2 hours. A larger study is underway to compare glargine plus either regular insulin or Ora-lyn given before each meal.

Generex Biotechnology plans to file a submission for approval in Canada and Europe concurrently in the next 12–15 months. Submission to the U.S. Food and Drug Administration is expected to follow and may fall within an 18-month time frame, according to a company spokesperson.

TORONTO — A formulation of insulin that is sprayed in the mouth and absorbed buccally seems to control glucose as well as injected insulin when used before a meal, Dr. Gerald Bernstein reported at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

The product, Generex Oral-lyn, is manufacturered by the Toronto-based company Generex Biotechnology.

When sprayed into the mouth using the company's RapidMist device, the insulin is absorbed into the buccal epithelium and is dispersed directly into the vascular system, thereby avoiding the problem of digestion that would occur if insulin were swallowed.

Dr. Bernstein, the company's vice president for medical affairs, presented a 3-month interim analysis of a 6-month study by Dr. Jaime Guevara-Aguirre and his associates at the Institute of Endocrinology IEMYR in Quito, Ecuador, where the product has been approved for use for patients with type 1 and type 2 diabetes.

First, 24 adolescents (mean age 15 years) and 5 young adults (21 years) with type 1 diabetes were stabilized for 6 weeks with basal twice-daily glargine and premeal injections of regular insulin.

For the next 6 weeks, they took Ora-lyn immediately before and after lunch rather than the injected regular insulin, while still injecting the glargine twice daily and the regular insulin before breakfast and dinner.

At baseline, the group had a mean hemoglobin A_1c of 9.9% and mean glucose of 236.6 mg/dL. After stabilization, their mean A_1c level had dropped to 8.4% and mean glucose (measured by the patients six times a day) to 140.4 mg/dL. After 3 weeks of substituting Ora-lyn for regular insulin at lunch, the mean A_1c was 8.5%, and mean glucose 143.3 mg/dL. Three weeks later (study week 12), the mean A_1c was 8.0%.

Doses of the glargine and the prelunch Oral-lyn were split in this study because previous data on each had shown that doing so improves efficacy. But in practice, piatients could take the entire dose of Ora-lyn before the meal, because the timing of its action is similar to that of available short-acting analogues: It begins working within 5 minutes, peaks at 30 minutes, and is cleared from the bloodstream by 2 hours. A larger study is underway to compare glargine plus either regular insulin or Ora-lyn given before each meal.

Generex Biotechnology plans to file a submission for approval in Canada and Europe concurrently in the next 12–15 months. Submission to the U.S. Food and Drug Administration is expected to follow and may fall within an 18-month time frame, according to a company spokesperson.

TORONTO — A formulation of insulin that is sprayed in the mouth and absorbed buccally seems to control glucose as well as injected insulin when used before a meal, Dr. Gerald Bernstein reported at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

The product, Generex Oral-lyn, is manufacturered by the Toronto-based company Generex Biotechnology.

When sprayed into the mouth using the company's RapidMist device, the insulin is absorbed into the buccal epithelium and is dispersed directly into the vascular system, thereby avoiding the problem of digestion that would occur if insulin were swallowed.

Dr. Bernstein, the company's vice president for medical affairs, presented a 3-month interim analysis of a 6-month study by Dr. Jaime Guevara-Aguirre and his associates at the Institute of Endocrinology IEMYR in Quito, Ecuador, where the product has been approved for use for patients with type 1 and type 2 diabetes.

First, 24 adolescents (mean age 15 years) and 5 young adults (21 years) with type 1 diabetes were stabilized for 6 weeks with basal twice-daily glargine and premeal injections of regular insulin.

For the next 6 weeks, they took Ora-lyn immediately before and after lunch rather than the injected regular insulin, while still injecting the glargine twice daily and the regular insulin before breakfast and dinner.

At baseline, the group had a mean hemoglobin A_1c of 9.9% and mean glucose of 236.6 mg/dL. After stabilization, their mean A_1c level had dropped to 8.4% and mean glucose (measured by the patients six times a day) to 140.4 mg/dL. After 3 weeks of substituting Ora-lyn for regular insulin at lunch, the mean A_1c was 8.5%, and mean glucose 143.3 mg/dL. Three weeks later (study week 12), the mean A_1c was 8.0%.

Doses of the glargine and the prelunch Oral-lyn were split in this study because previous data on each had shown that doing so improves efficacy. But in practice, piatients could take the entire dose of Ora-lyn before the meal, because the timing of its action is similar to that of available short-acting analogues: It begins working within 5 minutes, peaks at 30 minutes, and is cleared from the bloodstream by 2 hours. A larger study is underway to compare glargine plus either regular insulin or Ora-lyn given before each meal.

Generex Biotechnology plans to file a submission for approval in Canada and Europe concurrently in the next 12–15 months. Submission to the U.S. Food and Drug Administration is expected to follow and may fall within an 18-month time frame, according to a company spokesperson.

TORONTO — The risk for hip fractures appears to be elevated in elderly men and women with diabetes, Dr. Lorraine L. Lipscome reported in a poster at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

In a retrospective cohort study using population-based Ontario health care databases from 1994 to 2003, researchers compared the risk of hip fractures between individuals older than 65 years of age with and without diabetes. The study population comprised 207,252 diabetics and 414,504 nondiabetics, with a mean age of 71.7 years for the entire group, said Dr. Lipscome, of the University of Toronto.

After a mean of 6.1 years, the risk for hip fractures was significantly higher in those with diabetes, at 7.21 per 1,000 person-years, compared with 6.15 per 1,000 person-years among those without diabetes.

Those with diabetes had more comorbidity, were less likely to have had a bone mineral density test, and were more likely to be taking drugs that affected fall risk and bone density.

Women had a significantly higher risk for fracture than did men, but diabetes increased the risk in both genders, with hazard ratios of 1.22 for men and 1.19 for women. The increased risk remained significant (1.18 in men and 1.11 in women) after adjustment for age, comorbidity, and other factors, Dr. Lipscome reported.

Insulin use among the patients with diabetes increased the fracture risk, with hazard ratios of 1.34 in women and 1.64 in men compared with those not using insulin.

Until the phenomenon is better understood, bone fracture risk assessment and enhanced prevention strategies are warranted in all patients with diabetes, she said.

TORONTO — The risk for hip fractures appears to be elevated in elderly men and women with diabetes, Dr. Lorraine L. Lipscome reported in a poster at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

In a retrospective cohort study using population-based Ontario health care databases from 1994 to 2003, researchers compared the risk of hip fractures between individuals older than 65 years of age with and without diabetes. The study population comprised 207,252 diabetics and 414,504 nondiabetics, with a mean age of 71.7 years for the entire group, said Dr. Lipscome, of the University of Toronto.

After a mean of 6.1 years, the risk for hip fractures was significantly higher in those with diabetes, at 7.21 per 1,000 person-years, compared with 6.15 per 1,000 person-years among those without diabetes.

Those with diabetes had more comorbidity, were less likely to have had a bone mineral density test, and were more likely to be taking drugs that affected fall risk and bone density.

Women had a significantly higher risk for fracture than did men, but diabetes increased the risk in both genders, with hazard ratios of 1.22 for men and 1.19 for women. The increased risk remained significant (1.18 in men and 1.11 in women) after adjustment for age, comorbidity, and other factors, Dr. Lipscome reported.

Insulin use among the patients with diabetes increased the fracture risk, with hazard ratios of 1.34 in women and 1.64 in men compared with those not using insulin.

Until the phenomenon is better understood, bone fracture risk assessment and enhanced prevention strategies are warranted in all patients with diabetes, she said.

TORONTO — The risk for hip fractures appears to be elevated in elderly men and women with diabetes, Dr. Lorraine L. Lipscome reported in a poster at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

In a retrospective cohort study using population-based Ontario health care databases from 1994 to 2003, researchers compared the risk of hip fractures between individuals older than 65 years of age with and without diabetes. The study population comprised 207,252 diabetics and 414,504 nondiabetics, with a mean age of 71.7 years for the entire group, said Dr. Lipscome, of the University of Toronto.

After a mean of 6.1 years, the risk for hip fractures was significantly higher in those with diabetes, at 7.21 per 1,000 person-years, compared with 6.15 per 1,000 person-years among those without diabetes.

Those with diabetes had more comorbidity, were less likely to have had a bone mineral density test, and were more likely to be taking drugs that affected fall risk and bone density.

Women had a significantly higher risk for fracture than did men, but diabetes increased the risk in both genders, with hazard ratios of 1.22 for men and 1.19 for women. The increased risk remained significant (1.18 in men and 1.11 in women) after adjustment for age, comorbidity, and other factors, Dr. Lipscome reported.

Insulin use among the patients with diabetes increased the fracture risk, with hazard ratios of 1.34 in women and 1.64 in men compared with those not using insulin.

Until the phenomenon is better understood, bone fracture risk assessment and enhanced prevention strategies are warranted in all patients with diabetes, she said.

ATLANTA — Supply problems with the tetravalent meningococcal conjugate vaccine have been resolved, and routine vaccination of 11- to 12-year-olds should be resumed.

That recommendation from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices was discussed at the committee's fall meeting.

The supply problem was announced in May of 2006, with Sanofi Pasteur's estimation that demand for Menactra would outpace the supply at least through the summer. At that time, the CDC recommended deferral of routine use of the vaccine in 11- to 12-year-olds (MMWR 2006;55:567–8). Vaccination with MCV4 was to continue in high-risk groups.

More than 6 million doses of Menactra had been distributed by the end of September. Now, an additional 3.5–4.5 million doses are projected to be distributed through March of 2007, enough to allow a return to routine immunization of 11- to 12-year-olds and continuation in all the other recommended groups, said Dr. Gregory S. Wallace, chief of the CDC's Vaccine Supply and Assurance Branch.

ATLANTA — Supply problems with the tetravalent meningococcal conjugate vaccine have been resolved, and routine vaccination of 11- to 12-year-olds should be resumed.

That recommendation from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices was discussed at the committee's fall meeting.

The supply problem was announced in May of 2006, with Sanofi Pasteur's estimation that demand for Menactra would outpace the supply at least through the summer. At that time, the CDC recommended deferral of routine use of the vaccine in 11- to 12-year-olds (MMWR 2006;55:567–8). Vaccination with MCV4 was to continue in high-risk groups.

More than 6 million doses of Menactra had been distributed by the end of September. Now, an additional 3.5–4.5 million doses are projected to be distributed through March of 2007, enough to allow a return to routine immunization of 11- to 12-year-olds and continuation in all the other recommended groups, said Dr. Gregory S. Wallace, chief of the CDC's Vaccine Supply and Assurance Branch.

ATLANTA — Supply problems with the tetravalent meningococcal conjugate vaccine have been resolved, and routine vaccination of 11- to 12-year-olds should be resumed.

That recommendation from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices was discussed at the committee's fall meeting.

The supply problem was announced in May of 2006, with Sanofi Pasteur's estimation that demand for Menactra would outpace the supply at least through the summer. At that time, the CDC recommended deferral of routine use of the vaccine in 11- to 12-year-olds (MMWR 2006;55:567–8). Vaccination with MCV4 was to continue in high-risk groups.

More than 6 million doses of Menactra had been distributed by the end of September. Now, an additional 3.5–4.5 million doses are projected to be distributed through March of 2007, enough to allow a return to routine immunization of 11- to 12-year-olds and continuation in all the other recommended groups, said Dr. Gregory S. Wallace, chief of the CDC's Vaccine Supply and Assurance Branch.