Miriam E. Tucker

VIENNA — The glucose-lowering drug metformin is increasingly showing an anticancer effect.

The data come from studies conducted in both the diabetes and oncology research communities, according to experts at the annual meeting of the European Association for the Study of Diabetes.

The subject first caught the medical community's attention this summer, with the publication of a series of articles on the putative association between insulin glargine and cancer in EASD's journal Diabetologia (I

The question has been whether glargine or other insulin analogues could accelerate the growth of cancers in patients predisposed to the disease. At the meeting, representatives from Sanofi-Aventis, maker of insulin glargine (Lantus), and Novo Nordisk, maker of detemir (Levemir), presented data showing no statistically significant relationship between their products and cancer.

But evidence for a protective effect of metformin did appear in one of the Diabetologia studies that caused the furor. Craig J. Currie, Ph.D., of Cardiff (Wales) University and his associates found the lowest risk for cancer among users of metformin, compared with other diabetes treatments; adding metformin to insulin reduced the progression to cancer, compared with insulin treatment alone, with a hazard ratio of 0.54 in a retrospective cohort study of more than 62,809 diabetes patients.

Several lines of investigation are now looking at metformin as a potential anticancer treatment outside of diabetes, said Dr. Edwin Gale, of the University of Bristol (England) and editor-in-chief of Diabetologia.

The Cardiff study showed that diabetes patients on insulin or insulin secretagogues were more likely to develop solid cancers than were those on metformin, while the combination with metformin abolished most of this excess risk. Metformin use was associated with lower risks of colon or pancreatic cancer, but did not affect the risk of breast or prostate cancer. Use of insulin analogues was not associated with increased cancer risk, compared with human insulin (Diabetologia 2009;52:1766–77).

Dr. Ulf Smith, president of the EASD, said that two just-published studies further support the notion that metformin may have a protective effect against cancer. One showed a better response rate to chemotherapy among diabetic patients with breast cancer who were taking metformin (J. Clin. Oncol. 2009;27:3297–302).

The other study, published online, supports the so-called “cancer stem cell” hypothesis, which suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Drugs that selectively target cancer stem cells offer promise for cancer treatment, particularly in combination with chemotherapy. In this study on mice, metformin inhibited cellular transformation and selectively killed cancer stem cells in four genetically different types of breast cancer, and the combination of metformin and doxorubicin killed both cancer stem cells and non-stem cancer cells in culture (Cancer Res. 2009 Sept. 14 [doi:10.1158/0008-5472.CAN-09-2994]).

“The story with metformin is extremely exciting,” said Dr. Smith of the Sahlgrenska Center for Cardiovascular and Metabolic Research, Göteborg, Sweden.

The lowest cancer risk was in patients who used metformin, compared with other diabetes treatments.

Source Dr. Currie

VIENNA — The glucose-lowering drug metformin is increasingly showing an anticancer effect.

The data come from studies conducted in both the diabetes and oncology research communities, according to experts at the annual meeting of the European Association for the Study of Diabetes.

The subject first caught the medical community's attention this summer, with the publication of a series of articles on the putative association between insulin glargine and cancer in EASD's journal Diabetologia (I

The question has been whether glargine or other insulin analogues could accelerate the growth of cancers in patients predisposed to the disease. At the meeting, representatives from Sanofi-Aventis, maker of insulin glargine (Lantus), and Novo Nordisk, maker of detemir (Levemir), presented data showing no statistically significant relationship between their products and cancer.

But evidence for a protective effect of metformin did appear in one of the Diabetologia studies that caused the furor. Craig J. Currie, Ph.D., of Cardiff (Wales) University and his associates found the lowest risk for cancer among users of metformin, compared with other diabetes treatments; adding metformin to insulin reduced the progression to cancer, compared with insulin treatment alone, with a hazard ratio of 0.54 in a retrospective cohort study of more than 62,809 diabetes patients.

Several lines of investigation are now looking at metformin as a potential anticancer treatment outside of diabetes, said Dr. Edwin Gale, of the University of Bristol (England) and editor-in-chief of Diabetologia.

The Cardiff study showed that diabetes patients on insulin or insulin secretagogues were more likely to develop solid cancers than were those on metformin, while the combination with metformin abolished most of this excess risk. Metformin use was associated with lower risks of colon or pancreatic cancer, but did not affect the risk of breast or prostate cancer. Use of insulin analogues was not associated with increased cancer risk, compared with human insulin (Diabetologia 2009;52:1766–77).

Dr. Ulf Smith, president of the EASD, said that two just-published studies further support the notion that metformin may have a protective effect against cancer. One showed a better response rate to chemotherapy among diabetic patients with breast cancer who were taking metformin (J. Clin. Oncol. 2009;27:3297–302).

The other study, published online, supports the so-called “cancer stem cell” hypothesis, which suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Drugs that selectively target cancer stem cells offer promise for cancer treatment, particularly in combination with chemotherapy. In this study on mice, metformin inhibited cellular transformation and selectively killed cancer stem cells in four genetically different types of breast cancer, and the combination of metformin and doxorubicin killed both cancer stem cells and non-stem cancer cells in culture (Cancer Res. 2009 Sept. 14 [doi:10.1158/0008-5472.CAN-09-2994]).

“The story with metformin is extremely exciting,” said Dr. Smith of the Sahlgrenska Center for Cardiovascular and Metabolic Research, Göteborg, Sweden.

The lowest cancer risk was in patients who used metformin, compared with other diabetes treatments.

Source Dr. Currie

VIENNA — The glucose-lowering drug metformin is increasingly showing an anticancer effect.

The data come from studies conducted in both the diabetes and oncology research communities, according to experts at the annual meeting of the European Association for the Study of Diabetes.

The subject first caught the medical community's attention this summer, with the publication of a series of articles on the putative association between insulin glargine and cancer in EASD's journal Diabetologia (I

The question has been whether glargine or other insulin analogues could accelerate the growth of cancers in patients predisposed to the disease. At the meeting, representatives from Sanofi-Aventis, maker of insulin glargine (Lantus), and Novo Nordisk, maker of detemir (Levemir), presented data showing no statistically significant relationship between their products and cancer.

But evidence for a protective effect of metformin did appear in one of the Diabetologia studies that caused the furor. Craig J. Currie, Ph.D., of Cardiff (Wales) University and his associates found the lowest risk for cancer among users of metformin, compared with other diabetes treatments; adding metformin to insulin reduced the progression to cancer, compared with insulin treatment alone, with a hazard ratio of 0.54 in a retrospective cohort study of more than 62,809 diabetes patients.

Several lines of investigation are now looking at metformin as a potential anticancer treatment outside of diabetes, said Dr. Edwin Gale, of the University of Bristol (England) and editor-in-chief of Diabetologia.

The Cardiff study showed that diabetes patients on insulin or insulin secretagogues were more likely to develop solid cancers than were those on metformin, while the combination with metformin abolished most of this excess risk. Metformin use was associated with lower risks of colon or pancreatic cancer, but did not affect the risk of breast or prostate cancer. Use of insulin analogues was not associated with increased cancer risk, compared with human insulin (Diabetologia 2009;52:1766–77).

Dr. Ulf Smith, president of the EASD, said that two just-published studies further support the notion that metformin may have a protective effect against cancer. One showed a better response rate to chemotherapy among diabetic patients with breast cancer who were taking metformin (J. Clin. Oncol. 2009;27:3297–302).

The other study, published online, supports the so-called “cancer stem cell” hypothesis, which suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Drugs that selectively target cancer stem cells offer promise for cancer treatment, particularly in combination with chemotherapy. In this study on mice, metformin inhibited cellular transformation and selectively killed cancer stem cells in four genetically different types of breast cancer, and the combination of metformin and doxorubicin killed both cancer stem cells and non-stem cancer cells in culture (Cancer Res. 2009 Sept. 14 [doi:10.1158/0008-5472.CAN-09-2994]).

“The story with metformin is extremely exciting,” said Dr. Smith of the Sahlgrenska Center for Cardiovascular and Metabolic Research, Göteborg, Sweden.

The lowest cancer risk was in patients who used metformin, compared with other diabetes treatments.

Source Dr. Currie

VIENNA — Both diabetes itself and insulin therapy are associated with an increased risk for cancer, but the question of whether insulin glargine—or insulin analogues in general—is associated with a further increased risk remains open, five speakers said at a special symposium during the annual meeting of the European Association for the Study of Diabetes.

A series of studies in EASD's journal Diabetologia suggested that the insulin analogue glargine may be associated with an increased risk for cancer (www.diabetologia-journal.org/cancer.html

“We're talking about what I think is one of the most interesting, challenging, and important issues to confront us since I came into the field of diabetes: the relationship between diabetes and cancer. Two areas of expertise have suddenly come together,” said Dr. Edwin Gale of the University of Bristol (England) and Diabetologia editor-in-chief.

Dr. Jeffrey A. Johnson of the University of Alberta, Edmonton, said that strong associations have been found between diabetes and obesity and a variety of cancers (relative risk, 1.52 for all cancers in one large study), with a likely role for insulin resistance and hyperinsulinemia. Evidence also suggests that glucose-lowering medications that modulate these factors could have modifying effects with regard to cancer, he said.

Craig J. Currie, Ph.D., of Cardiff (Wales) University presented new data from an extension study of the one published online in July (Diabetologia 2009;52:1766–77). They examined 31,421 type 2 diabetes patients on metformin monotherapy, 5,035 on insulin plus metformin, and 4,829 on insulin only. There was a strong dose-response relationship between insulin exposure and first diagnosis of a solid cancer tumor. Compared with the crude rate of 10 cancers per 1,000 person-years for those taking metformin alone, the rates for those on insulin plus metformin increased from 9 for those using fewer than 7 insulin prescriptions per year to 11–12 for 8–14 prescriptions per year to 34 for more than 15 prescriptions per year, Dr. Currie reported.

Patients on insulin monotherapy showed an even greater dose response: Those using fewer than 7 prescriptions per year had a rate of 15 per 1,000 person-years, those with 7–15 prescriptions had 19, and those with more than 15 prescriptions had three times that rate, at 60 cancers per 1,000 person-years.

After adjustment for age, sex, and smoking status, hazard ratios in the insulin plus metformin groups were 0.87 per 1,000 person-years for metformin alone, 1.0 for 8–14 prescriptions a year, and 3.2 for those with more than 15 prescriptions a year. For those on insulin alone, hazard ratios were 1.05 for metformin alone, up to 5.73 for those with more than 15 prescriptions per year. The same pattern of association persisted after adjustment for other covariates such as weight, insulin exposure, and hemoglobin A_1c, he said. Some of the risk is attenuated in those using metformin with insulin, because metformin appears to have a protective effect, he noted.

Dr. Ulf Smith, president of the EASD, noted that insulin is not oncogenic, but may promote growth of cells that have already undergone oncogenic transformation. “I don't think anyone has suggested that insulin causes cancer, but it is a growth-promoting hormone.” The mechanism is likely to relate to insulin's binding of insulinlike growth factor receptors on tumors, said Dr. Smith of the Sahlgrenska Center for Cardiovascular and Metabolic Research, Göteborg, Sweden.

Dr. Jay Skyler of the University of Miami spoke on behalf of glargine (Lantus) manufacturer Sanofi-Aventis. He noted that even in the original four Diabetologia studies, only one—the original German database analysis—showed any statistically significant increase in cancer risk with glargine, but that was only after adjustment for insulin dose, and that method has been called invalid by many experts.

The other three studies show no statistically significant overall increased risk for glargine, nor did a subsequent analysis conducted by Sanofi-Aventis of its data from 31 clinical trials involving a combined population of 10,880 people with 5,657 on glargine. For all cancers, the rates were no different from those in the general population. A further analysis from 26 uncontrolled trails also showed no indication of increased risk, Dr. Skyler said.

In the ongoing ORIGIN (Outcome Reduction With an Initial Glargine Intervention) study of more than 12,612 randomized subjects, no increased cancer risk has been found in more than 50,000 patient-years of exposure, he added. “The totality of the available evidence suggests that the headlines which suggested that 'Glargine Causes Cancer' are unsubstantiated, unwarranted, and unproven,” Dr. Skyler commented.

Dr. David Russell-Jones gave an overview of a new meta-analysis of safety data conducted by Novo Nordisk for its long-acting insulin analogue, detemir. In studies lasting about 24 weeks, the risk for cancers of all types among 3,983 patients with either type 1 or type 2 diabetes on detemir was 0.36 per 1,000 person-years of exposure, compared with 0.92 for 2,661 similar patients using NPH insulin.

Those rates yielded an identical odds ratio of 2.53 when two different methods of statistical calculation were used, said Dr. Russell-Jones of the University of Surrey, Guildford, England.

Dr. Gale, in his closing remarks, referred to Diabetologia as the “epicenter of the storm.” As a result, “many members of the medical community and the public have been confused, and in some cases angry. I think this has been one of the most difficult, confusing, emotive, and controversial issues I have ever had to deal with.”

Acknowledging that he had received some criticism for publishing the articles in the first place, Dr. Gale said he has no regrets, noting, “The answer to the question may well be negative, but the question has to be asked.”

Dr. Johnson declared he had participated as a speaker for Eli Lilly & Co. Dr. Gale, Dr. Smith, and Dr. Currie stated they had no conflicts of interest. Both Dr. Skyler and Dr. Russell-Jones declared financial relationships with other diabetes-related companies in addition to the ones they were representing at the symposium.

On Sept. 29, Sanofi-Aventis announced the launch of a research program to investigate whether there is a relationship between cancer and insulin use, including the analogues (http://en.sanofi-aventis.com/binaries/20090929_easd_lantus_en_tcm28-26400.pdf

Headlines suggesting that glargine causes cancer are 'unsubstantiated, unwarranted, and unproven.'

Source Dr. Skyler

VIENNA — Both diabetes itself and insulin therapy are associated with an increased risk for cancer, but the question of whether insulin glargine—or insulin analogues in general—is associated with a further increased risk remains open, five speakers said at a special symposium during the annual meeting of the European Association for the Study of Diabetes.

A series of studies in EASD's journal Diabetologia suggested that the insulin analogue glargine may be associated with an increased risk for cancer (www.diabetologia-journal.org/cancer.html

“We're talking about what I think is one of the most interesting, challenging, and important issues to confront us since I came into the field of diabetes: the relationship between diabetes and cancer. Two areas of expertise have suddenly come together,” said Dr. Edwin Gale of the University of Bristol (England) and Diabetologia editor-in-chief.

Dr. Jeffrey A. Johnson of the University of Alberta, Edmonton, said that strong associations have been found between diabetes and obesity and a variety of cancers (relative risk, 1.52 for all cancers in one large study), with a likely role for insulin resistance and hyperinsulinemia. Evidence also suggests that glucose-lowering medications that modulate these factors could have modifying effects with regard to cancer, he said.

Craig J. Currie, Ph.D., of Cardiff (Wales) University presented new data from an extension study of the one published online in July (Diabetologia 2009;52:1766–77). They examined 31,421 type 2 diabetes patients on metformin monotherapy, 5,035 on insulin plus metformin, and 4,829 on insulin only. There was a strong dose-response relationship between insulin exposure and first diagnosis of a solid cancer tumor. Compared with the crude rate of 10 cancers per 1,000 person-years for those taking metformin alone, the rates for those on insulin plus metformin increased from 9 for those using fewer than 7 insulin prescriptions per year to 11–12 for 8–14 prescriptions per year to 34 for more than 15 prescriptions per year, Dr. Currie reported.

Patients on insulin monotherapy showed an even greater dose response: Those using fewer than 7 prescriptions per year had a rate of 15 per 1,000 person-years, those with 7–15 prescriptions had 19, and those with more than 15 prescriptions had three times that rate, at 60 cancers per 1,000 person-years.

After adjustment for age, sex, and smoking status, hazard ratios in the insulin plus metformin groups were 0.87 per 1,000 person-years for metformin alone, 1.0 for 8–14 prescriptions a year, and 3.2 for those with more than 15 prescriptions a year. For those on insulin alone, hazard ratios were 1.05 for metformin alone, up to 5.73 for those with more than 15 prescriptions per year. The same pattern of association persisted after adjustment for other covariates such as weight, insulin exposure, and hemoglobin A_1c, he said. Some of the risk is attenuated in those using metformin with insulin, because metformin appears to have a protective effect, he noted.

Dr. Ulf Smith, president of the EASD, noted that insulin is not oncogenic, but may promote growth of cells that have already undergone oncogenic transformation. “I don't think anyone has suggested that insulin causes cancer, but it is a growth-promoting hormone.” The mechanism is likely to relate to insulin's binding of insulinlike growth factor receptors on tumors, said Dr. Smith of the Sahlgrenska Center for Cardiovascular and Metabolic Research, Göteborg, Sweden.

Dr. Jay Skyler of the University of Miami spoke on behalf of glargine (Lantus) manufacturer Sanofi-Aventis. He noted that even in the original four Diabetologia studies, only one—the original German database analysis—showed any statistically significant increase in cancer risk with glargine, but that was only after adjustment for insulin dose, and that method has been called invalid by many experts.

The other three studies show no statistically significant overall increased risk for glargine, nor did a subsequent analysis conducted by Sanofi-Aventis of its data from 31 clinical trials involving a combined population of 10,880 people with 5,657 on glargine. For all cancers, the rates were no different from those in the general population. A further analysis from 26 uncontrolled trails also showed no indication of increased risk, Dr. Skyler said.

In the ongoing ORIGIN (Outcome Reduction With an Initial Glargine Intervention) study of more than 12,612 randomized subjects, no increased cancer risk has been found in more than 50,000 patient-years of exposure, he added. “The totality of the available evidence suggests that the headlines which suggested that 'Glargine Causes Cancer' are unsubstantiated, unwarranted, and unproven,” Dr. Skyler commented.

Dr. David Russell-Jones gave an overview of a new meta-analysis of safety data conducted by Novo Nordisk for its long-acting insulin analogue, detemir. In studies lasting about 24 weeks, the risk for cancers of all types among 3,983 patients with either type 1 or type 2 diabetes on detemir was 0.36 per 1,000 person-years of exposure, compared with 0.92 for 2,661 similar patients using NPH insulin.

Those rates yielded an identical odds ratio of 2.53 when two different methods of statistical calculation were used, said Dr. Russell-Jones of the University of Surrey, Guildford, England.

Dr. Gale, in his closing remarks, referred to Diabetologia as the “epicenter of the storm.” As a result, “many members of the medical community and the public have been confused, and in some cases angry. I think this has been one of the most difficult, confusing, emotive, and controversial issues I have ever had to deal with.”

Acknowledging that he had received some criticism for publishing the articles in the first place, Dr. Gale said he has no regrets, noting, “The answer to the question may well be negative, but the question has to be asked.”

Dr. Johnson declared he had participated as a speaker for Eli Lilly & Co. Dr. Gale, Dr. Smith, and Dr. Currie stated they had no conflicts of interest. Both Dr. Skyler and Dr. Russell-Jones declared financial relationships with other diabetes-related companies in addition to the ones they were representing at the symposium.

On Sept. 29, Sanofi-Aventis announced the launch of a research program to investigate whether there is a relationship between cancer and insulin use, including the analogues (http://en.sanofi-aventis.com/binaries/20090929_easd_lantus_en_tcm28-26400.pdf

Headlines suggesting that glargine causes cancer are 'unsubstantiated, unwarranted, and unproven.'

Source Dr. Skyler

VIENNA — Both diabetes itself and insulin therapy are associated with an increased risk for cancer, but the question of whether insulin glargine—or insulin analogues in general—is associated with a further increased risk remains open, five speakers said at a special symposium during the annual meeting of the European Association for the Study of Diabetes.

A series of studies in EASD's journal Diabetologia suggested that the insulin analogue glargine may be associated with an increased risk for cancer (www.diabetologia-journal.org/cancer.html

“We're talking about what I think is one of the most interesting, challenging, and important issues to confront us since I came into the field of diabetes: the relationship between diabetes and cancer. Two areas of expertise have suddenly come together,” said Dr. Edwin Gale of the University of Bristol (England) and Diabetologia editor-in-chief.

Dr. Jeffrey A. Johnson of the University of Alberta, Edmonton, said that strong associations have been found between diabetes and obesity and a variety of cancers (relative risk, 1.52 for all cancers in one large study), with a likely role for insulin resistance and hyperinsulinemia. Evidence also suggests that glucose-lowering medications that modulate these factors could have modifying effects with regard to cancer, he said.

Craig J. Currie, Ph.D., of Cardiff (Wales) University presented new data from an extension study of the one published online in July (Diabetologia 2009;52:1766–77). They examined 31,421 type 2 diabetes patients on metformin monotherapy, 5,035 on insulin plus metformin, and 4,829 on insulin only. There was a strong dose-response relationship between insulin exposure and first diagnosis of a solid cancer tumor. Compared with the crude rate of 10 cancers per 1,000 person-years for those taking metformin alone, the rates for those on insulin plus metformin increased from 9 for those using fewer than 7 insulin prescriptions per year to 11–12 for 8–14 prescriptions per year to 34 for more than 15 prescriptions per year, Dr. Currie reported.

Patients on insulin monotherapy showed an even greater dose response: Those using fewer than 7 prescriptions per year had a rate of 15 per 1,000 person-years, those with 7–15 prescriptions had 19, and those with more than 15 prescriptions had three times that rate, at 60 cancers per 1,000 person-years.

After adjustment for age, sex, and smoking status, hazard ratios in the insulin plus metformin groups were 0.87 per 1,000 person-years for metformin alone, 1.0 for 8–14 prescriptions a year, and 3.2 for those with more than 15 prescriptions a year. For those on insulin alone, hazard ratios were 1.05 for metformin alone, up to 5.73 for those with more than 15 prescriptions per year. The same pattern of association persisted after adjustment for other covariates such as weight, insulin exposure, and hemoglobin A_1c, he said. Some of the risk is attenuated in those using metformin with insulin, because metformin appears to have a protective effect, he noted.

Dr. Ulf Smith, president of the EASD, noted that insulin is not oncogenic, but may promote growth of cells that have already undergone oncogenic transformation. “I don't think anyone has suggested that insulin causes cancer, but it is a growth-promoting hormone.” The mechanism is likely to relate to insulin's binding of insulinlike growth factor receptors on tumors, said Dr. Smith of the Sahlgrenska Center for Cardiovascular and Metabolic Research, Göteborg, Sweden.

Dr. Jay Skyler of the University of Miami spoke on behalf of glargine (Lantus) manufacturer Sanofi-Aventis. He noted that even in the original four Diabetologia studies, only one—the original German database analysis—showed any statistically significant increase in cancer risk with glargine, but that was only after adjustment for insulin dose, and that method has been called invalid by many experts.

The other three studies show no statistically significant overall increased risk for glargine, nor did a subsequent analysis conducted by Sanofi-Aventis of its data from 31 clinical trials involving a combined population of 10,880 people with 5,657 on glargine. For all cancers, the rates were no different from those in the general population. A further analysis from 26 uncontrolled trails also showed no indication of increased risk, Dr. Skyler said.

In the ongoing ORIGIN (Outcome Reduction With an Initial Glargine Intervention) study of more than 12,612 randomized subjects, no increased cancer risk has been found in more than 50,000 patient-years of exposure, he added. “The totality of the available evidence suggests that the headlines which suggested that 'Glargine Causes Cancer' are unsubstantiated, unwarranted, and unproven,” Dr. Skyler commented.

Dr. David Russell-Jones gave an overview of a new meta-analysis of safety data conducted by Novo Nordisk for its long-acting insulin analogue, detemir. In studies lasting about 24 weeks, the risk for cancers of all types among 3,983 patients with either type 1 or type 2 diabetes on detemir was 0.36 per 1,000 person-years of exposure, compared with 0.92 for 2,661 similar patients using NPH insulin.

Those rates yielded an identical odds ratio of 2.53 when two different methods of statistical calculation were used, said Dr. Russell-Jones of the University of Surrey, Guildford, England.

Dr. Gale, in his closing remarks, referred to Diabetologia as the “epicenter of the storm.” As a result, “many members of the medical community and the public have been confused, and in some cases angry. I think this has been one of the most difficult, confusing, emotive, and controversial issues I have ever had to deal with.”

Acknowledging that he had received some criticism for publishing the articles in the first place, Dr. Gale said he has no regrets, noting, “The answer to the question may well be negative, but the question has to be asked.”

Dr. Johnson declared he had participated as a speaker for Eli Lilly & Co. Dr. Gale, Dr. Smith, and Dr. Currie stated they had no conflicts of interest. Both Dr. Skyler and Dr. Russell-Jones declared financial relationships with other diabetes-related companies in addition to the ones they were representing at the symposium.

On Sept. 29, Sanofi-Aventis announced the launch of a research program to investigate whether there is a relationship between cancer and insulin use, including the analogues (http://en.sanofi-aventis.com/binaries/20090929_easd_lantus_en_tcm28-26400.pdf

Headlines suggesting that glargine causes cancer are 'unsubstantiated, unwarranted, and unproven.'

Source Dr. Skyler

NEW YORK — Ovarian volume assessed by transabdominal ultrasound correlated strongly with serum testosterone levels in a study of 39 adolescent girls undergoing evaluation for polycystic ovary syndrome.

While magnetic resonance imaging and transrectal or transvaginal ultrasound (TVUS) may better visualize ovarian follicles, transabdominal ultrasound (TAUS) is a less invasive, cheaper, and more readily available imaging modality to diagnose polycystic ovary syndrome (PCOS), Dr. Clare A. Flannery said in a poster presented at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

With TAUS, the ovarian volume—the sum of the stromal volume and multiple follicles—can be easily calculated from the three dimensions of the ovary. Elevation of serum testosterone, a well-validated diagnostic criterion for PCOS, has been shown to correlate with typical PCOS using TVUS but little is known about how accurately it relates to increased ovarian volume in TAUS, said Dr. Flannery of the department of endocrinology-internal medicine at Yale University, New Haven, Conn.

The 39 adolescents had a mean age of 15.3 years, a mean body mass index of 31.5 kg/m

They underwent TAUS that was read by a radiologist blinded to all clinical information. Ovarian volume was calculated with three diameter measurements, and total ovarian volume was obtained by adding the volume of both ovaries. They had a mean total ovarian volume of 23.2 cm

Total testosterone levels correlated with both single largest ovary volume and total ovarian volume, as did free testosterone. When ovarian volume was analyzed on a continuum, adolescents whose ovaries were less than 10 cm

Differences were seen between the 18 obese (BMI greater than 30), 12 overweight (BMI of 25-29.9), and 9 lean (BMI less than 25) patients. The overweight and obese groups had lower sex hormone–binding globulin than did the lean group (37 nmol/L and 27 nmol/L, respectively, compared with 66 nmol/L in the lean group). They also had greater insulin resistance, as measured by the homeostasis assessment model (5.1 and 3.3, compared with 2.0 in the lean group).

Total testosterone levels were not statistically different between the three BMI groups, although they trended higher in the obese group (mean total testosterone, 56 mg/dL). Everyone in the lean group had at least one enlarged ovary, as did slightly over half of the overweight and obese groups. Bilateral ovarian enlargement was present in 33%-44% of the girls in each group.

In an interview, Dr. Flannery said that the majority of the adolescent girls referred to their specialty clinic are obese with symptoms that may be consistent with signs of puberty, namely irregular periods and acne. It is a challenge to differentiate between girls with early or established PCOS versus girls with just obesity and insulin resistance. Examination of ovarian morphology provides another tool for diagnosis, she said.

Dr. Flannery stated that neither she nor Dr. Burgert had any financial disclosures.

NEW YORK — Ovarian volume assessed by transabdominal ultrasound correlated strongly with serum testosterone levels in a study of 39 adolescent girls undergoing evaluation for polycystic ovary syndrome.

While magnetic resonance imaging and transrectal or transvaginal ultrasound (TVUS) may better visualize ovarian follicles, transabdominal ultrasound (TAUS) is a less invasive, cheaper, and more readily available imaging modality to diagnose polycystic ovary syndrome (PCOS), Dr. Clare A. Flannery said in a poster presented at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

With TAUS, the ovarian volume—the sum of the stromal volume and multiple follicles—can be easily calculated from the three dimensions of the ovary. Elevation of serum testosterone, a well-validated diagnostic criterion for PCOS, has been shown to correlate with typical PCOS using TVUS but little is known about how accurately it relates to increased ovarian volume in TAUS, said Dr. Flannery of the department of endocrinology-internal medicine at Yale University, New Haven, Conn.

The 39 adolescents had a mean age of 15.3 years, a mean body mass index of 31.5 kg/m

They underwent TAUS that was read by a radiologist blinded to all clinical information. Ovarian volume was calculated with three diameter measurements, and total ovarian volume was obtained by adding the volume of both ovaries. They had a mean total ovarian volume of 23.2 cm

Total testosterone levels correlated with both single largest ovary volume and total ovarian volume, as did free testosterone. When ovarian volume was analyzed on a continuum, adolescents whose ovaries were less than 10 cm

Differences were seen between the 18 obese (BMI greater than 30), 12 overweight (BMI of 25-29.9), and 9 lean (BMI less than 25) patients. The overweight and obese groups had lower sex hormone–binding globulin than did the lean group (37 nmol/L and 27 nmol/L, respectively, compared with 66 nmol/L in the lean group). They also had greater insulin resistance, as measured by the homeostasis assessment model (5.1 and 3.3, compared with 2.0 in the lean group).

Total testosterone levels were not statistically different between the three BMI groups, although they trended higher in the obese group (mean total testosterone, 56 mg/dL). Everyone in the lean group had at least one enlarged ovary, as did slightly over half of the overweight and obese groups. Bilateral ovarian enlargement was present in 33%-44% of the girls in each group.

In an interview, Dr. Flannery said that the majority of the adolescent girls referred to their specialty clinic are obese with symptoms that may be consistent with signs of puberty, namely irregular periods and acne. It is a challenge to differentiate between girls with early or established PCOS versus girls with just obesity and insulin resistance. Examination of ovarian morphology provides another tool for diagnosis, she said.

Dr. Flannery stated that neither she nor Dr. Burgert had any financial disclosures.

NEW YORK — Ovarian volume assessed by transabdominal ultrasound correlated strongly with serum testosterone levels in a study of 39 adolescent girls undergoing evaluation for polycystic ovary syndrome.

While magnetic resonance imaging and transrectal or transvaginal ultrasound (TVUS) may better visualize ovarian follicles, transabdominal ultrasound (TAUS) is a less invasive, cheaper, and more readily available imaging modality to diagnose polycystic ovary syndrome (PCOS), Dr. Clare A. Flannery said in a poster presented at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

With TAUS, the ovarian volume—the sum of the stromal volume and multiple follicles—can be easily calculated from the three dimensions of the ovary. Elevation of serum testosterone, a well-validated diagnostic criterion for PCOS, has been shown to correlate with typical PCOS using TVUS but little is known about how accurately it relates to increased ovarian volume in TAUS, said Dr. Flannery of the department of endocrinology-internal medicine at Yale University, New Haven, Conn.

The 39 adolescents had a mean age of 15.3 years, a mean body mass index of 31.5 kg/m

They underwent TAUS that was read by a radiologist blinded to all clinical information. Ovarian volume was calculated with three diameter measurements, and total ovarian volume was obtained by adding the volume of both ovaries. They had a mean total ovarian volume of 23.2 cm

Total testosterone levels correlated with both single largest ovary volume and total ovarian volume, as did free testosterone. When ovarian volume was analyzed on a continuum, adolescents whose ovaries were less than 10 cm

Differences were seen between the 18 obese (BMI greater than 30), 12 overweight (BMI of 25-29.9), and 9 lean (BMI less than 25) patients. The overweight and obese groups had lower sex hormone–binding globulin than did the lean group (37 nmol/L and 27 nmol/L, respectively, compared with 66 nmol/L in the lean group). They also had greater insulin resistance, as measured by the homeostasis assessment model (5.1 and 3.3, compared with 2.0 in the lean group).

Total testosterone levels were not statistically different between the three BMI groups, although they trended higher in the obese group (mean total testosterone, 56 mg/dL). Everyone in the lean group had at least one enlarged ovary, as did slightly over half of the overweight and obese groups. Bilateral ovarian enlargement was present in 33%-44% of the girls in each group.

In an interview, Dr. Flannery said that the majority of the adolescent girls referred to their specialty clinic are obese with symptoms that may be consistent with signs of puberty, namely irregular periods and acne. It is a challenge to differentiate between girls with early or established PCOS versus girls with just obesity and insulin resistance. Examination of ovarian morphology provides another tool for diagnosis, she said.

Dr. Flannery stated that neither she nor Dr. Burgert had any financial disclosures.

VIENNA — Diabetes was a significant risk factor for atrial fibrillation among women but not men in an analysis of electronic medical records from a large HMO database.

The study also found that both the prevalence and the incidence of atrial fibrillation (AF) were more than 40% higher among patients with diabetes than in those without. After accounting for other risk factors, diabetes increased the risk for AF by 16%, Gregory A. Nichols, Ph.D., said in an interview held prior to his scheduled presentation of the findings at the annual meeting of the European Association for the Study of Diabetes.

The results were published in Diabetes Care (2009;32:1851-6).

Although diabetes was previously known to be a risk factor for AF, this analysis is the first to assess its independent contribution by controlling for factors common to both conditions, and also the first to identify a strong sex difference in the relationship between the two conditions, said Dr. Nichols, a researcher at Kaiser Permanente Center for Health Research, Portland, Ore.

“Clinicians may be disincentivized to look for atrial fibrillation in women because it is such a male-dominated condition, but when diabetes is present in women the risk for atrial fibrillation is the same as it is for a man,” Dr. Nichols said in the interview.

Data were analyzed for 10,213 individuals who were members of the Kaiser Permanente Northwest diabetes registry as of Jan. 1, 1999, and another 7,159 patients who entered the registry by Dec. 31, 2004, for a total of 17,372.

The subjects had a mean age of 58 years, and 51% were male. Those with diabetes were heavier and had higher blood pressures and were significantly more likely to have a history of stroke, hypertension, and heart failure. At baseline, the prevalence of AF was 3.6% among those with diabetes versus 2.5% among age and sex-matched controls without diabetes, a significant 44% difference. The difference was most significant in the 55- to 64-year age group, with 3.0% of the diabetics versus 1.6% of the nondiabetics found to have AF, an 87% difference. The difference in AF prevalence between the diabetic and nondiabetic groups became smaller in the older age groups, he said.

Men had an overall greater prevalence of AF than did women, but the difference between the diabetic and nondiabetic groups was far greater in the women. In the 55- to 64-year age group, 2.2% of the nondiabetic versus 3.3% diabetic men had AF, a 50% difference. For the women, 1.0% vs. 2.7% had AF, a 170% difference, said Dr. Nichols.

The incidence analysis compared 16,057 diabetes patients who did not have AF at baseline with 16,471 without diabetes or AF at baseline. Over a mean follow-up of 7.2 years, the diabetic patients developed AF at an age/sex–adjusted incidence rate of 9.1/1,000 person-years, compared with 6.6 in the nondiabetic patients.

For men, AF incidence per 1,000 person-years was 10.8 for diabetics and 8.3 for nondiabetics, a 31% difference. For the woman, those figures were 7.6 vs. 5.0, a difference of 46%.

After controlling for age, sex, race, body mass index, systolic blood pressure, cigarette smoking, and comorbidities including ischemic heart disease, stroke, valvular disease, hypertension, and heart failure, diabetes still increased the AF risk by 16% overall.

But in men the increase was a nonsignificant 9%, compared with a highly significant 26% in women. The risk from female sex was larger than the overall increased risk conferred by either body mass index greater than 30 kg/m

Dr. Nichols stated that he had no relevant financial disclosures.

VIENNA — Diabetes was a significant risk factor for atrial fibrillation among women but not men in an analysis of electronic medical records from a large HMO database.

The study also found that both the prevalence and the incidence of atrial fibrillation (AF) were more than 40% higher among patients with diabetes than in those without. After accounting for other risk factors, diabetes increased the risk for AF by 16%, Gregory A. Nichols, Ph.D., said in an interview held prior to his scheduled presentation of the findings at the annual meeting of the European Association for the Study of Diabetes.

The results were published in Diabetes Care (2009;32:1851-6).

Although diabetes was previously known to be a risk factor for AF, this analysis is the first to assess its independent contribution by controlling for factors common to both conditions, and also the first to identify a strong sex difference in the relationship between the two conditions, said Dr. Nichols, a researcher at Kaiser Permanente Center for Health Research, Portland, Ore.

“Clinicians may be disincentivized to look for atrial fibrillation in women because it is such a male-dominated condition, but when diabetes is present in women the risk for atrial fibrillation is the same as it is for a man,” Dr. Nichols said in the interview.

Data were analyzed for 10,213 individuals who were members of the Kaiser Permanente Northwest diabetes registry as of Jan. 1, 1999, and another 7,159 patients who entered the registry by Dec. 31, 2004, for a total of 17,372.

The subjects had a mean age of 58 years, and 51% were male. Those with diabetes were heavier and had higher blood pressures and were significantly more likely to have a history of stroke, hypertension, and heart failure. At baseline, the prevalence of AF was 3.6% among those with diabetes versus 2.5% among age and sex-matched controls without diabetes, a significant 44% difference. The difference was most significant in the 55- to 64-year age group, with 3.0% of the diabetics versus 1.6% of the nondiabetics found to have AF, an 87% difference. The difference in AF prevalence between the diabetic and nondiabetic groups became smaller in the older age groups, he said.

Men had an overall greater prevalence of AF than did women, but the difference between the diabetic and nondiabetic groups was far greater in the women. In the 55- to 64-year age group, 2.2% of the nondiabetic versus 3.3% diabetic men had AF, a 50% difference. For the women, 1.0% vs. 2.7% had AF, a 170% difference, said Dr. Nichols.

The incidence analysis compared 16,057 diabetes patients who did not have AF at baseline with 16,471 without diabetes or AF at baseline. Over a mean follow-up of 7.2 years, the diabetic patients developed AF at an age/sex–adjusted incidence rate of 9.1/1,000 person-years, compared with 6.6 in the nondiabetic patients.

For men, AF incidence per 1,000 person-years was 10.8 for diabetics and 8.3 for nondiabetics, a 31% difference. For the woman, those figures were 7.6 vs. 5.0, a difference of 46%.

After controlling for age, sex, race, body mass index, systolic blood pressure, cigarette smoking, and comorbidities including ischemic heart disease, stroke, valvular disease, hypertension, and heart failure, diabetes still increased the AF risk by 16% overall.

But in men the increase was a nonsignificant 9%, compared with a highly significant 26% in women. The risk from female sex was larger than the overall increased risk conferred by either body mass index greater than 30 kg/m

Dr. Nichols stated that he had no relevant financial disclosures.

VIENNA — Diabetes was a significant risk factor for atrial fibrillation among women but not men in an analysis of electronic medical records from a large HMO database.

The study also found that both the prevalence and the incidence of atrial fibrillation (AF) were more than 40% higher among patients with diabetes than in those without. After accounting for other risk factors, diabetes increased the risk for AF by 16%, Gregory A. Nichols, Ph.D., said in an interview held prior to his scheduled presentation of the findings at the annual meeting of the European Association for the Study of Diabetes.

The results were published in Diabetes Care (2009;32:1851-6).

Although diabetes was previously known to be a risk factor for AF, this analysis is the first to assess its independent contribution by controlling for factors common to both conditions, and also the first to identify a strong sex difference in the relationship between the two conditions, said Dr. Nichols, a researcher at Kaiser Permanente Center for Health Research, Portland, Ore.

“Clinicians may be disincentivized to look for atrial fibrillation in women because it is such a male-dominated condition, but when diabetes is present in women the risk for atrial fibrillation is the same as it is for a man,” Dr. Nichols said in the interview.

Data were analyzed for 10,213 individuals who were members of the Kaiser Permanente Northwest diabetes registry as of Jan. 1, 1999, and another 7,159 patients who entered the registry by Dec. 31, 2004, for a total of 17,372.

The subjects had a mean age of 58 years, and 51% were male. Those with diabetes were heavier and had higher blood pressures and were significantly more likely to have a history of stroke, hypertension, and heart failure. At baseline, the prevalence of AF was 3.6% among those with diabetes versus 2.5% among age and sex-matched controls without diabetes, a significant 44% difference. The difference was most significant in the 55- to 64-year age group, with 3.0% of the diabetics versus 1.6% of the nondiabetics found to have AF, an 87% difference. The difference in AF prevalence between the diabetic and nondiabetic groups became smaller in the older age groups, he said.

Men had an overall greater prevalence of AF than did women, but the difference between the diabetic and nondiabetic groups was far greater in the women. In the 55- to 64-year age group, 2.2% of the nondiabetic versus 3.3% diabetic men had AF, a 50% difference. For the women, 1.0% vs. 2.7% had AF, a 170% difference, said Dr. Nichols.

The incidence analysis compared 16,057 diabetes patients who did not have AF at baseline with 16,471 without diabetes or AF at baseline. Over a mean follow-up of 7.2 years, the diabetic patients developed AF at an age/sex–adjusted incidence rate of 9.1/1,000 person-years, compared with 6.6 in the nondiabetic patients.

For men, AF incidence per 1,000 person-years was 10.8 for diabetics and 8.3 for nondiabetics, a 31% difference. For the woman, those figures were 7.6 vs. 5.0, a difference of 46%.

After controlling for age, sex, race, body mass index, systolic blood pressure, cigarette smoking, and comorbidities including ischemic heart disease, stroke, valvular disease, hypertension, and heart failure, diabetes still increased the AF risk by 16% overall.

But in men the increase was a nonsignificant 9%, compared with a highly significant 26% in women. The risk from female sex was larger than the overall increased risk conferred by either body mass index greater than 30 kg/m

Dr. Nichols stated that he had no relevant financial disclosures.

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

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

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

Early retinopathy, defined as one microaneurysm or hemorrhage on seven-field stereoscopic fundus photography, was detected in 9% of the patients.

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

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

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

The American Diabetes Association recommends retinopathy screening within 5 years of the onset of diabetes and nephropathy screening after a diabetes duration of 5 years in children aged 10 years and older.

“Longitudinal analysis will help define predictors of early complications and the potential for modifying [their] natural history,” Dr. Cho said.

She stated that she had no relevant financial disclosures.

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

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

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

Early retinopathy, defined as one microaneurysm or hemorrhage on seven-field stereoscopic fundus photography, was detected in 9% of the patients.

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

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

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

The American Diabetes Association recommends retinopathy screening within 5 years of the onset of diabetes and nephropathy screening after a diabetes duration of 5 years in children aged 10 years and older.

“Longitudinal analysis will help define predictors of early complications and the potential for modifying [their] natural history,” Dr. Cho said.

She stated that she had no relevant financial disclosures.

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

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

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

Early retinopathy, defined as one microaneurysm or hemorrhage on seven-field stereoscopic fundus photography, was detected in 9% of the patients.

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

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

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

The American Diabetes Association recommends retinopathy screening within 5 years of the onset of diabetes and nephropathy screening after a diabetes duration of 5 years in children aged 10 years and older.

“Longitudinal analysis will help define predictors of early complications and the potential for modifying [their] natural history,” Dr. Cho said.

She stated that she had no relevant financial disclosures.

ATLANTA — Using a weight-based method for calculating insulin correction dosing resulted in superior blood glucose control, compared with a traditional sliding-scale method in a pilot study of hyperglycemic inpatients.

In recent years, it has become clear that nonindividualized sliding-scale regimens often result in out-of-target blood glucose levels. “Sliding scales look backwards to correct the past, and fail to anticipate the future,” Diane M. Thompson, R.N., said at the annual meeting of the American Association of Diabetes Educators.

In cooperation with a local endocrinologist and critical care physician, Ms. Thompson and Heatherann Cundiff, R.N., who both work for Nashville, Tenn.–based Diabetes Healthways, which contracts with the hospital for diabetes management, developed a method for using a patient's weight to calculate the insulin dose needed to correct an elevated blood sugar. In a 2006 pilot study at Monroe Regional Medical Center, Ocala, Fla., the weight-based method resulted in 70% of 681 blood sugar values being less than 180 mg/dL in 54 patients, versus 46% of 719 values in 64 patients treated based on the sliding-scale method.

The weight-based method uses this formula to derive a sensitivity factor (SF): 3,000/kg body weight. The SF expresses how many mg/dL the blood glucose is lowered by 1 U of fast-acting insulin. The SF is calculated on admission, and documented on the patient's order sheet after verification by two nurses.

The correction dose is designed to bring the blood glucose to a target of 110 mg/dL, assuming that basal and prandial needs are met, either with medication or naturally by the body. This formula is used to calculate the required number of units of insulin: subtract 110 from the blood glucose in mg/dL, divide the result by the SF, then round the result to the nearest whole number.

For example, a 124-kg patient would have a SF of 24 (3,000/124). If her blood glucose was 250 mg/dL before breakfast, her correction dose would be 5.83 (250 − 110 = 140; 140/24 = 5.83), which would be rounded up to 6 U.

In the pilot study, the weight-based method was used in 64 patients during 1 month, yielding 31 different SFs (range 19–86). The number of blood glucose readings greater than 300 mg/dL dropped from 85 to 38 in those 64 patients, and the number of readings between 180 mg/dL and 300 mg/dL dropped from 270 to 168. The average blood glucose was 186 mg/dL with the sliding-scale method and 149 with the weight-based method, Ms. Cundiff reported.

'Sliding scales look backwards to correct the past, and fail to anticipate the future.'

Source MS. THOMPSON

ATLANTA — Using a weight-based method for calculating insulin correction dosing resulted in superior blood glucose control, compared with a traditional sliding-scale method in a pilot study of hyperglycemic inpatients.

In recent years, it has become clear that nonindividualized sliding-scale regimens often result in out-of-target blood glucose levels. “Sliding scales look backwards to correct the past, and fail to anticipate the future,” Diane M. Thompson, R.N., said at the annual meeting of the American Association of Diabetes Educators.

In cooperation with a local endocrinologist and critical care physician, Ms. Thompson and Heatherann Cundiff, R.N., who both work for Nashville, Tenn.–based Diabetes Healthways, which contracts with the hospital for diabetes management, developed a method for using a patient's weight to calculate the insulin dose needed to correct an elevated blood sugar. In a 2006 pilot study at Monroe Regional Medical Center, Ocala, Fla., the weight-based method resulted in 70% of 681 blood sugar values being less than 180 mg/dL in 54 patients, versus 46% of 719 values in 64 patients treated based on the sliding-scale method.

The weight-based method uses this formula to derive a sensitivity factor (SF): 3,000/kg body weight. The SF expresses how many mg/dL the blood glucose is lowered by 1 U of fast-acting insulin. The SF is calculated on admission, and documented on the patient's order sheet after verification by two nurses.

The correction dose is designed to bring the blood glucose to a target of 110 mg/dL, assuming that basal and prandial needs are met, either with medication or naturally by the body. This formula is used to calculate the required number of units of insulin: subtract 110 from the blood glucose in mg/dL, divide the result by the SF, then round the result to the nearest whole number.

For example, a 124-kg patient would have a SF of 24 (3,000/124). If her blood glucose was 250 mg/dL before breakfast, her correction dose would be 5.83 (250 − 110 = 140; 140/24 = 5.83), which would be rounded up to 6 U.

In the pilot study, the weight-based method was used in 64 patients during 1 month, yielding 31 different SFs (range 19–86). The number of blood glucose readings greater than 300 mg/dL dropped from 85 to 38 in those 64 patients, and the number of readings between 180 mg/dL and 300 mg/dL dropped from 270 to 168. The average blood glucose was 186 mg/dL with the sliding-scale method and 149 with the weight-based method, Ms. Cundiff reported.

'Sliding scales look backwards to correct the past, and fail to anticipate the future.'

Source MS. THOMPSON

ATLANTA — Using a weight-based method for calculating insulin correction dosing resulted in superior blood glucose control, compared with a traditional sliding-scale method in a pilot study of hyperglycemic inpatients.

In recent years, it has become clear that nonindividualized sliding-scale regimens often result in out-of-target blood glucose levels. “Sliding scales look backwards to correct the past, and fail to anticipate the future,” Diane M. Thompson, R.N., said at the annual meeting of the American Association of Diabetes Educators.

In cooperation with a local endocrinologist and critical care physician, Ms. Thompson and Heatherann Cundiff, R.N., who both work for Nashville, Tenn.–based Diabetes Healthways, which contracts with the hospital for diabetes management, developed a method for using a patient's weight to calculate the insulin dose needed to correct an elevated blood sugar. In a 2006 pilot study at Monroe Regional Medical Center, Ocala, Fla., the weight-based method resulted in 70% of 681 blood sugar values being less than 180 mg/dL in 54 patients, versus 46% of 719 values in 64 patients treated based on the sliding-scale method.

The weight-based method uses this formula to derive a sensitivity factor (SF): 3,000/kg body weight. The SF expresses how many mg/dL the blood glucose is lowered by 1 U of fast-acting insulin. The SF is calculated on admission, and documented on the patient's order sheet after verification by two nurses.

The correction dose is designed to bring the blood glucose to a target of 110 mg/dL, assuming that basal and prandial needs are met, either with medication or naturally by the body. This formula is used to calculate the required number of units of insulin: subtract 110 from the blood glucose in mg/dL, divide the result by the SF, then round the result to the nearest whole number.

For example, a 124-kg patient would have a SF of 24 (3,000/124). If her blood glucose was 250 mg/dL before breakfast, her correction dose would be 5.83 (250 − 110 = 140; 140/24 = 5.83), which would be rounded up to 6 U.

In the pilot study, the weight-based method was used in 64 patients during 1 month, yielding 31 different SFs (range 19–86). The number of blood glucose readings greater than 300 mg/dL dropped from 85 to 38 in those 64 patients, and the number of readings between 180 mg/dL and 300 mg/dL dropped from 270 to 168. The average blood glucose was 186 mg/dL with the sliding-scale method and 149 with the weight-based method, Ms. Cundiff reported.

'Sliding scales look backwards to correct the past, and fail to anticipate the future.'

Source MS. THOMPSON

ATLANTA — Hemoglobin A_1c levels and glycemic excursions among children attending a residential diabetes camp did not change significantly over a 12-year period, despite increased use of insulin pumps, designer insulins, and glucose self-monitoring, study results showed.

Data were collected from children and adolescents who attended one of two week-long camping sessions at Camp Seale Harris in Jackson's Gap, Ala., during 1996, 2002, and 2008. The research hypothesis was that children attending diabetes camp in 2008 would be able to achieve better overall control and have fewer hypoglycemic and hyperglycemic excursions while at camp than in either of the earlier study years because they now have access to improved diabetes management, education, and technology.

“Compared to 1996, in 2008 we had better insulin analogues, better insulin pumps, more children using pumps, better glucose monitors, and more children receiving HbA_1c analyses from their primary caregiver before coming to camp. All of these factors should contribute to better glycemic control and fewer severe glycemic excursions,” Dennis J. Pillion, Ph.D., said at the annual meeting of the American Association of Diabetes Educators.

What was actually observed was “unexpected, and points out the fact that diabetes care in 2008 remains imperfect,” said Dr. Pillion, professor of pharmacology and toxicology at the comprehensive diabetes center of the University of Alabama at Birmingham.

The children were aged 8–17, and all had type 1 diabetes. Hemoglobin A_1c levels were recorded from the medical charts in 2002 and 2008, while in 1996 they were actually measured at camp. Blood glucose levels during camp were measured four to six times daily—including twice during the night—and the daily activity regimen was held constant. About 150–300 campers attended each of the week-long sessions, one of which was for teenagers, the other for younger children.

The proportions of children using insulin pumps rose from about 40% in 2002 to 60% in 2008, with the relative proportions using injections falling as a consequence. Data on pump use weren't available for 1996, although it was estimated that no more than 5%-10% were using the pump back then. Among those using injections, the proportion using basal-bolus regimens and insulin analogues rose, while the use of split-mix regimens and of regular and other human insulins declined.

The mean HbA_1c value dropped from 9.4% (for 119 children) in 1996 to 8.5% (for 184 children) in 2008. The difference was not statistically different, because of the wide range in HbA_1c values. In 1996, just 7% of campers had an HbA_1c value below 7%. By 2008, that number had risen to only 11% among the campers who used pumps, while remaining at just 7% among those taking injections, despite the increased use of multiple daily injections and bolus dose adjustments. The drop from 7% to 11% represented a trend but was not statistically significant, Dr. Pillion noted.

The number of moderate or severe hypoglycemic events (defined as blood glucose levels of 50–70 mg/dL or below 50 mg/dL) also did not differ between 2002 and 2008, with campers experiencing an average of 1.5–2.0 moderate hypoglycemic events and 0.5 severe events during their week at camp. Campers using insulin pumps were no less likely to experience low blood sugar than were those taking injections. (Those data were not available for 1996.)

Hyperglycemic excursions also were not significantly less common in 2008 than in 2002, with campers experiencing about four to five moderately high (200–300 mg/dL) levels and one to two extremely high (greater than 300 mg/dL) levels during the camping week. Moreover, “the insulin pump did not provide a significant advantage over subcutaneous injections in terms of the number of severe or moderate glucose excursions that occurred at camp,” Dr. Pillion said.

Dr. Pillion stated that he had no financial relationships relevant to this program.

The mean HbA_1c value dropped from 9.4% in 1996 to 8.5% in 2008, a nonsignificant difference.

Source DR. PILLION

ATLANTA — Hemoglobin A_1c levels and glycemic excursions among children attending a residential diabetes camp did not change significantly over a 12-year period, despite increased use of insulin pumps, designer insulins, and glucose self-monitoring, study results showed.

Data were collected from children and adolescents who attended one of two week-long camping sessions at Camp Seale Harris in Jackson's Gap, Ala., during 1996, 2002, and 2008. The research hypothesis was that children attending diabetes camp in 2008 would be able to achieve better overall control and have fewer hypoglycemic and hyperglycemic excursions while at camp than in either of the earlier study years because they now have access to improved diabetes management, education, and technology.

“Compared to 1996, in 2008 we had better insulin analogues, better insulin pumps, more children using pumps, better glucose monitors, and more children receiving HbA_1c analyses from their primary caregiver before coming to camp. All of these factors should contribute to better glycemic control and fewer severe glycemic excursions,” Dennis J. Pillion, Ph.D., said at the annual meeting of the American Association of Diabetes Educators.

What was actually observed was “unexpected, and points out the fact that diabetes care in 2008 remains imperfect,” said Dr. Pillion, professor of pharmacology and toxicology at the comprehensive diabetes center of the University of Alabama at Birmingham.

The children were aged 8–17, and all had type 1 diabetes. Hemoglobin A_1c levels were recorded from the medical charts in 2002 and 2008, while in 1996 they were actually measured at camp. Blood glucose levels during camp were measured four to six times daily—including twice during the night—and the daily activity regimen was held constant. About 150–300 campers attended each of the week-long sessions, one of which was for teenagers, the other for younger children.

The proportions of children using insulin pumps rose from about 40% in 2002 to 60% in 2008, with the relative proportions using injections falling as a consequence. Data on pump use weren't available for 1996, although it was estimated that no more than 5%-10% were using the pump back then. Among those using injections, the proportion using basal-bolus regimens and insulin analogues rose, while the use of split-mix regimens and of regular and other human insulins declined.

The mean HbA_1c value dropped from 9.4% (for 119 children) in 1996 to 8.5% (for 184 children) in 2008. The difference was not statistically different, because of the wide range in HbA_1c values. In 1996, just 7% of campers had an HbA_1c value below 7%. By 2008, that number had risen to only 11% among the campers who used pumps, while remaining at just 7% among those taking injections, despite the increased use of multiple daily injections and bolus dose adjustments. The drop from 7% to 11% represented a trend but was not statistically significant, Dr. Pillion noted.

The number of moderate or severe hypoglycemic events (defined as blood glucose levels of 50–70 mg/dL or below 50 mg/dL) also did not differ between 2002 and 2008, with campers experiencing an average of 1.5–2.0 moderate hypoglycemic events and 0.5 severe events during their week at camp. Campers using insulin pumps were no less likely to experience low blood sugar than were those taking injections. (Those data were not available for 1996.)

Hyperglycemic excursions also were not significantly less common in 2008 than in 2002, with campers experiencing about four to five moderately high (200–300 mg/dL) levels and one to two extremely high (greater than 300 mg/dL) levels during the camping week. Moreover, “the insulin pump did not provide a significant advantage over subcutaneous injections in terms of the number of severe or moderate glucose excursions that occurred at camp,” Dr. Pillion said.

Dr. Pillion stated that he had no financial relationships relevant to this program.

The mean HbA_1c value dropped from 9.4% in 1996 to 8.5% in 2008, a nonsignificant difference.

Source DR. PILLION

ATLANTA — Hemoglobin A_1c levels and glycemic excursions among children attending a residential diabetes camp did not change significantly over a 12-year period, despite increased use of insulin pumps, designer insulins, and glucose self-monitoring, study results showed.

Data were collected from children and adolescents who attended one of two week-long camping sessions at Camp Seale Harris in Jackson's Gap, Ala., during 1996, 2002, and 2008. The research hypothesis was that children attending diabetes camp in 2008 would be able to achieve better overall control and have fewer hypoglycemic and hyperglycemic excursions while at camp than in either of the earlier study years because they now have access to improved diabetes management, education, and technology.

“Compared to 1996, in 2008 we had better insulin analogues, better insulin pumps, more children using pumps, better glucose monitors, and more children receiving HbA_1c analyses from their primary caregiver before coming to camp. All of these factors should contribute to better glycemic control and fewer severe glycemic excursions,” Dennis J. Pillion, Ph.D., said at the annual meeting of the American Association of Diabetes Educators.

What was actually observed was “unexpected, and points out the fact that diabetes care in 2008 remains imperfect,” said Dr. Pillion, professor of pharmacology and toxicology at the comprehensive diabetes center of the University of Alabama at Birmingham.

The children were aged 8–17, and all had type 1 diabetes. Hemoglobin A_1c levels were recorded from the medical charts in 2002 and 2008, while in 1996 they were actually measured at camp. Blood glucose levels during camp were measured four to six times daily—including twice during the night—and the daily activity regimen was held constant. About 150–300 campers attended each of the week-long sessions, one of which was for teenagers, the other for younger children.

The proportions of children using insulin pumps rose from about 40% in 2002 to 60% in 2008, with the relative proportions using injections falling as a consequence. Data on pump use weren't available for 1996, although it was estimated that no more than 5%-10% were using the pump back then. Among those using injections, the proportion using basal-bolus regimens and insulin analogues rose, while the use of split-mix regimens and of regular and other human insulins declined.

The mean HbA_1c value dropped from 9.4% (for 119 children) in 1996 to 8.5% (for 184 children) in 2008. The difference was not statistically different, because of the wide range in HbA_1c values. In 1996, just 7% of campers had an HbA_1c value below 7%. By 2008, that number had risen to only 11% among the campers who used pumps, while remaining at just 7% among those taking injections, despite the increased use of multiple daily injections and bolus dose adjustments. The drop from 7% to 11% represented a trend but was not statistically significant, Dr. Pillion noted.

The number of moderate or severe hypoglycemic events (defined as blood glucose levels of 50–70 mg/dL or below 50 mg/dL) also did not differ between 2002 and 2008, with campers experiencing an average of 1.5–2.0 moderate hypoglycemic events and 0.5 severe events during their week at camp. Campers using insulin pumps were no less likely to experience low blood sugar than were those taking injections. (Those data were not available for 1996.)

Hyperglycemic excursions also were not significantly less common in 2008 than in 2002, with campers experiencing about four to five moderately high (200–300 mg/dL) levels and one to two extremely high (greater than 300 mg/dL) levels during the camping week. Moreover, “the insulin pump did not provide a significant advantage over subcutaneous injections in terms of the number of severe or moderate glucose excursions that occurred at camp,” Dr. Pillion said.

Dr. Pillion stated that he had no financial relationships relevant to this program.

The mean HbA_1c value dropped from 9.4% in 1996 to 8.5% in 2008, a nonsignificant difference.

Source DR. PILLION

NEW YORK — Partial anomalous pulmonary venous return was detected by cardiac magnetic resonance imaging in 7 of 39 adolescent and young adult women with Turner's syndrome whose charts were retrospectively evaluated.

The finding suggests that careful screening for the partial anomalous pulmonary venous return (PAPVR) heart defect is indicated in the Turner's syndrome population, along with appropriate cardiac referral and management, Dr. Iris Gutmark-Little said at the joint meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Pediatric Endocrinology.

Results from the study also suggest that cardiac magnetic resonance (CMR) imaging is a more sensitive modality than echocardiography for the detection of PAPVR in patients with Turner's syndrome, said Dr. Gutmark-Little of Cincinnati Children's Hospital Medical Center.

The 39 patients were the first to be screened with CMR after Cincinnati Children's began using the modality routinely in all Turner's syndrome patients during the early teen years. The patients also underwent echocardiographic evaluation.

A total of seven patients (18%) were found to have PAPVR by cardiac magnetic resonance imaging, six of them following a normal echocardiogram. Aberrant drainage of the right upper pulmonary veins was seen in five patients, of whom three also had involvement of at least a portion of the right middle lobe vein. The other two had the defect in the left upper pulmonary vein.

The 18% PAPVR prevalence seen here is similar to the 13% found in a previous study of adult Turner's syndrome patients (Circulation 2004;110:1694–700), she noted.

In one patient, PAPVR was associated with clinically significant enlargement of the right ventricle, with a pulmonary-to-systemic blood flow ratio (Qp:Qs) of 1.9:1. She required surgical repair. The other six patients had Qp:Qs ratios ranging from 1.24:1 to 1.62:1 (mean, 1.5:1), and did not require intervention.

There were no differences in age, height, karyotype, or right ventricular ejection fraction between the 7 patients with PAPVR and the 32 without, nor did the two groups differ in peripheral lymphedema, neck webbing, renal malformations, coarctation, or bicuspid aortic valve. This finding differs from previous studies that have linked some of these features to PAPVR in Turner's syndrome patients. It's possible that the small sample size may have missed the associations, Dr. Gutmark-Little commented.

After her presentation, an audience member asked Dr. Gutmark-Little if she would recommend cardiac magnetic resonance imaging in asymptomatic Turner's syndrome patients. She replied, “Not necessarily primarily for detecting PAPVR, but I think it's important to use CMR during the teen years in order to look at aortic size and function.”

Dr. Gutmark-Little stated that she had no financial disclosures.

A four-chamber MRI shows a dilated right ventricle as a result of a right-sided PAPVR lesion in an adolescent female Turner's syndrome patient.

A three-dimensional MRI shows a right-sided PAPVR lesion in an adolescent female Turner's syndrome patient. The right middle– and right upper–lobe anomalous pulmonary veins are seen draining into the superior vena cava. This patient had a nearly 2:1 left-to-right shunt, resulting in right ventricular dilatation. This necessitated surgical repair of her PAPVR.

Source Images courtesy Cincinnati Children's Hospital

NEW YORK — Partial anomalous pulmonary venous return was detected by cardiac magnetic resonance imaging in 7 of 39 adolescent and young adult women with Turner's syndrome whose charts were retrospectively evaluated.

The finding suggests that careful screening for the partial anomalous pulmonary venous return (PAPVR) heart defect is indicated in the Turner's syndrome population, along with appropriate cardiac referral and management, Dr. Iris Gutmark-Little said at the joint meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Pediatric Endocrinology.

Results from the study also suggest that cardiac magnetic resonance (CMR) imaging is a more sensitive modality than echocardiography for the detection of PAPVR in patients with Turner's syndrome, said Dr. Gutmark-Little of Cincinnati Children's Hospital Medical Center.

The 39 patients were the first to be screened with CMR after Cincinnati Children's began using the modality routinely in all Turner's syndrome patients during the early teen years. The patients also underwent echocardiographic evaluation.

A total of seven patients (18%) were found to have PAPVR by cardiac magnetic resonance imaging, six of them following a normal echocardiogram. Aberrant drainage of the right upper pulmonary veins was seen in five patients, of whom three also had involvement of at least a portion of the right middle lobe vein. The other two had the defect in the left upper pulmonary vein.

The 18% PAPVR prevalence seen here is similar to the 13% found in a previous study of adult Turner's syndrome patients (Circulation 2004;110:1694–700), she noted.

In one patient, PAPVR was associated with clinically significant enlargement of the right ventricle, with a pulmonary-to-systemic blood flow ratio (Qp:Qs) of 1.9:1. She required surgical repair. The other six patients had Qp:Qs ratios ranging from 1.24:1 to 1.62:1 (mean, 1.5:1), and did not require intervention.

There were no differences in age, height, karyotype, or right ventricular ejection fraction between the 7 patients with PAPVR and the 32 without, nor did the two groups differ in peripheral lymphedema, neck webbing, renal malformations, coarctation, or bicuspid aortic valve. This finding differs from previous studies that have linked some of these features to PAPVR in Turner's syndrome patients. It's possible that the small sample size may have missed the associations, Dr. Gutmark-Little commented.

After her presentation, an audience member asked Dr. Gutmark-Little if she would recommend cardiac magnetic resonance imaging in asymptomatic Turner's syndrome patients. She replied, “Not necessarily primarily for detecting PAPVR, but I think it's important to use CMR during the teen years in order to look at aortic size and function.”

Dr. Gutmark-Little stated that she had no financial disclosures.

A four-chamber MRI shows a dilated right ventricle as a result of a right-sided PAPVR lesion in an adolescent female Turner's syndrome patient.

A three-dimensional MRI shows a right-sided PAPVR lesion in an adolescent female Turner's syndrome patient. The right middle– and right upper–lobe anomalous pulmonary veins are seen draining into the superior vena cava. This patient had a nearly 2:1 left-to-right shunt, resulting in right ventricular dilatation. This necessitated surgical repair of her PAPVR.

Source Images courtesy Cincinnati Children's Hospital

NEW YORK — Partial anomalous pulmonary venous return was detected by cardiac magnetic resonance imaging in 7 of 39 adolescent and young adult women with Turner's syndrome whose charts were retrospectively evaluated.

The finding suggests that careful screening for the partial anomalous pulmonary venous return (PAPVR) heart defect is indicated in the Turner's syndrome population, along with appropriate cardiac referral and management, Dr. Iris Gutmark-Little said at the joint meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Pediatric Endocrinology.

Results from the study also suggest that cardiac magnetic resonance (CMR) imaging is a more sensitive modality than echocardiography for the detection of PAPVR in patients with Turner's syndrome, said Dr. Gutmark-Little of Cincinnati Children's Hospital Medical Center.

The 39 patients were the first to be screened with CMR after Cincinnati Children's began using the modality routinely in all Turner's syndrome patients during the early teen years. The patients also underwent echocardiographic evaluation.

A total of seven patients (18%) were found to have PAPVR by cardiac magnetic resonance imaging, six of them following a normal echocardiogram. Aberrant drainage of the right upper pulmonary veins was seen in five patients, of whom three also had involvement of at least a portion of the right middle lobe vein. The other two had the defect in the left upper pulmonary vein.

The 18% PAPVR prevalence seen here is similar to the 13% found in a previous study of adult Turner's syndrome patients (Circulation 2004;110:1694–700), she noted.

In one patient, PAPVR was associated with clinically significant enlargement of the right ventricle, with a pulmonary-to-systemic blood flow ratio (Qp:Qs) of 1.9:1. She required surgical repair. The other six patients had Qp:Qs ratios ranging from 1.24:1 to 1.62:1 (mean, 1.5:1), and did not require intervention.

There were no differences in age, height, karyotype, or right ventricular ejection fraction between the 7 patients with PAPVR and the 32 without, nor did the two groups differ in peripheral lymphedema, neck webbing, renal malformations, coarctation, or bicuspid aortic valve. This finding differs from previous studies that have linked some of these features to PAPVR in Turner's syndrome patients. It's possible that the small sample size may have missed the associations, Dr. Gutmark-Little commented.

After her presentation, an audience member asked Dr. Gutmark-Little if she would recommend cardiac magnetic resonance imaging in asymptomatic Turner's syndrome patients. She replied, “Not necessarily primarily for detecting PAPVR, but I think it's important to use CMR during the teen years in order to look at aortic size and function.”

Dr. Gutmark-Little stated that she had no financial disclosures.

A four-chamber MRI shows a dilated right ventricle as a result of a right-sided PAPVR lesion in an adolescent female Turner's syndrome patient.

A three-dimensional MRI shows a right-sided PAPVR lesion in an adolescent female Turner's syndrome patient. The right middle– and right upper–lobe anomalous pulmonary veins are seen draining into the superior vena cava. This patient had a nearly 2:1 left-to-right shunt, resulting in right ventricular dilatation. This necessitated surgical repair of her PAPVR.

Source Images courtesy Cincinnati Children's Hospital

NEW YORK — The investigational bone-targeting enzyme replacement therapy ENB-0040 was associated with significant bone mineralization and clinical improvements at 6 months in five infants with life-threatening hypophosphatasia who were given the compound in a phase II open-label trial.

The 24-week study initially enrolled six patients (five girls) aged 6–36 months at baseline who were all symptomatic early in life, with severe rickets, respiratory insufficiency, hypercalcemia, and nephrocalcinosis. All had a high likelihood of death or significant morbidity. Dosing was 2 mg/kg given once intravenously, followed by subcutaneous doses of 1 mg/kg thrice weekly for 23 months, with the possibility of dose adjustment depending on clinical response.

Marked improvements were seen in the radiographic appearance of rickets in three infants, with increased mineralization, resolution of radiolucencies, physeal narrowing, and less flaring. There were no new fractures. Another infant showed substantial improvement that was not quite as dramatic as the other three. The fifth infant, with profound hypomineralization, had no radiographic improvement, Dr. Michael P. Whyte said at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Pediatric Endocrinology.

Radiographic evidence of skeletal mineralization was associated with reduced plasma levels of pyridoxal 5′-phosphate and increased levels of parathyroid hormone, which was initially suppressed in all patients. There was a concurrent decline in the calcium to creatinine ratio, “as though bone and mineral were moving into the skeleton, a sign of hungry bones,” accompanied by a need to increase dietary calcium, said Dr. Whyte, medical/scientific director of the center for metabolic bone disease and molecular research at Shriners Hospitals for Children, St. Louis.

Evidence of improved growth, including linear growth, head circumference, and growth catch-up appearing in later assessments, was seen in all five patients. Respiratory problems, present in four of the five infants at baseline, improved in three infants after 6 months of therapy. One patient, who had been on continuous positive airway pressure and bilevel positive airway pressure and was on the verge of endotracheal intubation, was able to be treated with just nighttime nasal oxygen after 6 months of ENB-0040. Motor function, assessed by Bayley scores, also improved in all five patients.

There were no drug-related serious adverse events and the subcutaneous doses were well tolerated, with only mild redness and swelling seen at the injection site. There were no clinical signs or symptoms of hypocalcemia or of increased intracranial pressure. No anti–ENB-0040 antibodies developed. One infant was withdrawn after showing signs of distress during treatment, leaving five for subsequent analysis.

There is currently no established treatment for hypophosphatasia (HPP), an inborn error of metabolism resulting from a mutation within a gene that codes for tissue-nonspecific alkaline phosphatase (TNSALP). Mortality among infants less than 6 months of age with the perinatal form of the disease is around 50%, he said.

Manufactured by Montreal-based Enobia Pharma Inc., ENB-0040 is a subcutaneously administered recombinant compound of TNSALP fused to a patented bone-targeting peptide, designed to replace the missing enzyme in HPP patients. It was given an orphan drug designation in the United States and the European Union in 2008 and was granted fast-track status for HPP treatment by the Food and Drug Administration in May 2009, according to the company Web site. Dr. Whyte is a consultant for Enobia Pharma and received grant support for this study.

X-rays above show response to treatment using a recombinant compound of TNSALP fused to a bone-targeting peptide.

Source Courtesy Enobia Pharma Inc.

NEW YORK — The investigational bone-targeting enzyme replacement therapy ENB-0040 was associated with significant bone mineralization and clinical improvements at 6 months in five infants with life-threatening hypophosphatasia who were given the compound in a phase II open-label trial.

The 24-week study initially enrolled six patients (five girls) aged 6–36 months at baseline who were all symptomatic early in life, with severe rickets, respiratory insufficiency, hypercalcemia, and nephrocalcinosis. All had a high likelihood of death or significant morbidity. Dosing was 2 mg/kg given once intravenously, followed by subcutaneous doses of 1 mg/kg thrice weekly for 23 months, with the possibility of dose adjustment depending on clinical response.

Marked improvements were seen in the radiographic appearance of rickets in three infants, with increased mineralization, resolution of radiolucencies, physeal narrowing, and less flaring. There were no new fractures. Another infant showed substantial improvement that was not quite as dramatic as the other three. The fifth infant, with profound hypomineralization, had no radiographic improvement, Dr. Michael P. Whyte said at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Pediatric Endocrinology.

Radiographic evidence of skeletal mineralization was associated with reduced plasma levels of pyridoxal 5′-phosphate and increased levels of parathyroid hormone, which was initially suppressed in all patients. There was a concurrent decline in the calcium to creatinine ratio, “as though bone and mineral were moving into the skeleton, a sign of hungry bones,” accompanied by a need to increase dietary calcium, said Dr. Whyte, medical/scientific director of the center for metabolic bone disease and molecular research at Shriners Hospitals for Children, St. Louis.

Evidence of improved growth, including linear growth, head circumference, and growth catch-up appearing in later assessments, was seen in all five patients. Respiratory problems, present in four of the five infants at baseline, improved in three infants after 6 months of therapy. One patient, who had been on continuous positive airway pressure and bilevel positive airway pressure and was on the verge of endotracheal intubation, was able to be treated with just nighttime nasal oxygen after 6 months of ENB-0040. Motor function, assessed by Bayley scores, also improved in all five patients.

There were no drug-related serious adverse events and the subcutaneous doses were well tolerated, with only mild redness and swelling seen at the injection site. There were no clinical signs or symptoms of hypocalcemia or of increased intracranial pressure. No anti–ENB-0040 antibodies developed. One infant was withdrawn after showing signs of distress during treatment, leaving five for subsequent analysis.

There is currently no established treatment for hypophosphatasia (HPP), an inborn error of metabolism resulting from a mutation within a gene that codes for tissue-nonspecific alkaline phosphatase (TNSALP). Mortality among infants less than 6 months of age with the perinatal form of the disease is around 50%, he said.

Manufactured by Montreal-based Enobia Pharma Inc., ENB-0040 is a subcutaneously administered recombinant compound of TNSALP fused to a patented bone-targeting peptide, designed to replace the missing enzyme in HPP patients. It was given an orphan drug designation in the United States and the European Union in 2008 and was granted fast-track status for HPP treatment by the Food and Drug Administration in May 2009, according to the company Web site. Dr. Whyte is a consultant for Enobia Pharma and received grant support for this study.

X-rays above show response to treatment using a recombinant compound of TNSALP fused to a bone-targeting peptide.

Source Courtesy Enobia Pharma Inc.

NEW YORK — The investigational bone-targeting enzyme replacement therapy ENB-0040 was associated with significant bone mineralization and clinical improvements at 6 months in five infants with life-threatening hypophosphatasia who were given the compound in a phase II open-label trial.

The 24-week study initially enrolled six patients (five girls) aged 6–36 months at baseline who were all symptomatic early in life, with severe rickets, respiratory insufficiency, hypercalcemia, and nephrocalcinosis. All had a high likelihood of death or significant morbidity. Dosing was 2 mg/kg given once intravenously, followed by subcutaneous doses of 1 mg/kg thrice weekly for 23 months, with the possibility of dose adjustment depending on clinical response.

Marked improvements were seen in the radiographic appearance of rickets in three infants, with increased mineralization, resolution of radiolucencies, physeal narrowing, and less flaring. There were no new fractures. Another infant showed substantial improvement that was not quite as dramatic as the other three. The fifth infant, with profound hypomineralization, had no radiographic improvement, Dr. Michael P. Whyte said at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Pediatric Endocrinology.

Radiographic evidence of skeletal mineralization was associated with reduced plasma levels of pyridoxal 5′-phosphate and increased levels of parathyroid hormone, which was initially suppressed in all patients. There was a concurrent decline in the calcium to creatinine ratio, “as though bone and mineral were moving into the skeleton, a sign of hungry bones,” accompanied by a need to increase dietary calcium, said Dr. Whyte, medical/scientific director of the center for metabolic bone disease and molecular research at Shriners Hospitals for Children, St. Louis.

Evidence of improved growth, including linear growth, head circumference, and growth catch-up appearing in later assessments, was seen in all five patients. Respiratory problems, present in four of the five infants at baseline, improved in three infants after 6 months of therapy. One patient, who had been on continuous positive airway pressure and bilevel positive airway pressure and was on the verge of endotracheal intubation, was able to be treated with just nighttime nasal oxygen after 6 months of ENB-0040. Motor function, assessed by Bayley scores, also improved in all five patients.

There were no drug-related serious adverse events and the subcutaneous doses were well tolerated, with only mild redness and swelling seen at the injection site. There were no clinical signs or symptoms of hypocalcemia or of increased intracranial pressure. No anti–ENB-0040 antibodies developed. One infant was withdrawn after showing signs of distress during treatment, leaving five for subsequent analysis.

There is currently no established treatment for hypophosphatasia (HPP), an inborn error of metabolism resulting from a mutation within a gene that codes for tissue-nonspecific alkaline phosphatase (TNSALP). Mortality among infants less than 6 months of age with the perinatal form of the disease is around 50%, he said.

Manufactured by Montreal-based Enobia Pharma Inc., ENB-0040 is a subcutaneously administered recombinant compound of TNSALP fused to a patented bone-targeting peptide, designed to replace the missing enzyme in HPP patients. It was given an orphan drug designation in the United States and the European Union in 2008 and was granted fast-track status for HPP treatment by the Food and Drug Administration in May 2009, according to the company Web site. Dr. Whyte is a consultant for Enobia Pharma and received grant support for this study.

X-rays above show response to treatment using a recombinant compound of TNSALP fused to a bone-targeting peptide.

Source Courtesy Enobia Pharma Inc.

NEW YORK — An investigational combination of recombinant human growth hormone and recombinant human insulin-like growth factor-1 produced significant increases in height velocity and favorable changes in height relative to bone age, according to preliminary study data.

The findings are from an early assessment from an ongoing, 3-year study of prepubertal children with short stature associated with low insulin-like growth factor-1 (IGF-1). The data were presented at the 8th Joint Meeting of the Lawson Wilkins Pediatric Endocrine Society and European Society for Pediatric Endocrinology.

The research was funded by Tercica, Inc., a subsidiary of the Ipsen Group, which developed the human growth hormone and recombinant human insulin-like growth factor-1 (rhGH/rhIGF-1) combination, according to Dr. George M. Bright, Tercica's vice president and medical director, endocrinology.

A total of 106 children have been randomized thus far to one of four arms: 45 mcg/kg of rhGH alone given subcutaneously, or in combination with 50, 100, or 150 mcg/kg of rhIGF-1 (given as a separate injection). The children were all treatment-naive, with otherwise unexplained short stature (height standard deviation score of −2 or less), an IGF-1 SD score of −1 or less and a maximum stimulated GH level of 10 ng/mL or greater. All were prepubertal at the start of the study.

Safety data were available for all 106 children and efficacy data for 36 who completed the first year of the study. For the primary end point, first-year height velocity, the mean values were 9.2 cm/year for the rhGH monotherapy group (n=11), and 10.4, 10.7, and 12.1 cm/year, respectively, for the combinations of rhGH plus 50 (n=7), 100 (n=9), and 150 (n=9) mcg/kg of rhIGF-1.

First-year increases in height SD scores were 0.72, 0.88, 0.91, and 1.1, respectively, Dr. Bright reported at the meeting.

The study protocol specified reducing the rhIGF-1 dose if a subject had an IGF-1 score measurement above plus-4. This occurred in seven subjects, three from the 100-mcg/kg rhIGF-1 dose group and four from the 150 mcg/kg dose group. It's not clear that this level actually poses a danger, but it was done as a safeguard, he noted. Most of the children appeared to show greater change in height age than in bone age, he added.

Four serious adverse events have occurred thus far in 2 of the 106 children. A 10-year-old male experienced thrombocytopenia, hematuria, and viral infection and was diagnosed with Evans syndrome. This was considered not drug related, but he did discontinue the study. An 11-year-old male in the 150-mcg/kg rhIGF-1 group had transient papilledema with probable intracranial hypertension, which was considered probably drug related. Treatment was stopped and re-started without recurrence.

Five patients withdrew early from the study, four of them due to adverse events. In addition to the Evans syndrome patient, two had generalized urticaria that was considered drug-related. One had alopecia that was considered possibly/probably drug-related. The fifth withdrew due to noncompliance.

Headache was reported by a fourth of the rhGH monotherapy group and by half of the highest dose combo group, with the two middle groups falling in between. Vomiting occurred in 12%-15% of all four groups. However, only eight patients reported both headache and vomiting. Two children are thought to have had intracranial hypertension, Dr. Bright said.

Transient elevations in transaminases were seen during weeks 0–13 in some of the patients, he said but most were less than 2.5 times the upper limit of normal, and resolved by 13 weeks.

NEW YORK — An investigational combination of recombinant human growth hormone and recombinant human insulin-like growth factor-1 produced significant increases in height velocity and favorable changes in height relative to bone age, according to preliminary study data.

The findings are from an early assessment from an ongoing, 3-year study of prepubertal children with short stature associated with low insulin-like growth factor-1 (IGF-1). The data were presented at the 8th Joint Meeting of the Lawson Wilkins Pediatric Endocrine Society and European Society for Pediatric Endocrinology.

The research was funded by Tercica, Inc., a subsidiary of the Ipsen Group, which developed the human growth hormone and recombinant human insulin-like growth factor-1 (rhGH/rhIGF-1) combination, according to Dr. George M. Bright, Tercica's vice president and medical director, endocrinology.

A total of 106 children have been randomized thus far to one of four arms: 45 mcg/kg of rhGH alone given subcutaneously, or in combination with 50, 100, or 150 mcg/kg of rhIGF-1 (given as a separate injection). The children were all treatment-naive, with otherwise unexplained short stature (height standard deviation score of −2 or less), an IGF-1 SD score of −1 or less and a maximum stimulated GH level of 10 ng/mL or greater. All were prepubertal at the start of the study.

Safety data were available for all 106 children and efficacy data for 36 who completed the first year of the study. For the primary end point, first-year height velocity, the mean values were 9.2 cm/year for the rhGH monotherapy group (n=11), and 10.4, 10.7, and 12.1 cm/year, respectively, for the combinations of rhGH plus 50 (n=7), 100 (n=9), and 150 (n=9) mcg/kg of rhIGF-1.

First-year increases in height SD scores were 0.72, 0.88, 0.91, and 1.1, respectively, Dr. Bright reported at the meeting.

The study protocol specified reducing the rhIGF-1 dose if a subject had an IGF-1 score measurement above plus-4. This occurred in seven subjects, three from the 100-mcg/kg rhIGF-1 dose group and four from the 150 mcg/kg dose group. It's not clear that this level actually poses a danger, but it was done as a safeguard, he noted. Most of the children appeared to show greater change in height age than in bone age, he added.

Four serious adverse events have occurred thus far in 2 of the 106 children. A 10-year-old male experienced thrombocytopenia, hematuria, and viral infection and was diagnosed with Evans syndrome. This was considered not drug related, but he did discontinue the study. An 11-year-old male in the 150-mcg/kg rhIGF-1 group had transient papilledema with probable intracranial hypertension, which was considered probably drug related. Treatment was stopped and re-started without recurrence.

Five patients withdrew early from the study, four of them due to adverse events. In addition to the Evans syndrome patient, two had generalized urticaria that was considered drug-related. One had alopecia that was considered possibly/probably drug-related. The fifth withdrew due to noncompliance.

Headache was reported by a fourth of the rhGH monotherapy group and by half of the highest dose combo group, with the two middle groups falling in between. Vomiting occurred in 12%-15% of all four groups. However, only eight patients reported both headache and vomiting. Two children are thought to have had intracranial hypertension, Dr. Bright said.

Transient elevations in transaminases were seen during weeks 0–13 in some of the patients, he said but most were less than 2.5 times the upper limit of normal, and resolved by 13 weeks.

NEW YORK — An investigational combination of recombinant human growth hormone and recombinant human insulin-like growth factor-1 produced significant increases in height velocity and favorable changes in height relative to bone age, according to preliminary study data.

The findings are from an early assessment from an ongoing, 3-year study of prepubertal children with short stature associated with low insulin-like growth factor-1 (IGF-1). The data were presented at the 8th Joint Meeting of the Lawson Wilkins Pediatric Endocrine Society and European Society for Pediatric Endocrinology.

The research was funded by Tercica, Inc., a subsidiary of the Ipsen Group, which developed the human growth hormone and recombinant human insulin-like growth factor-1 (rhGH/rhIGF-1) combination, according to Dr. George M. Bright, Tercica's vice president and medical director, endocrinology.

A total of 106 children have been randomized thus far to one of four arms: 45 mcg/kg of rhGH alone given subcutaneously, or in combination with 50, 100, or 150 mcg/kg of rhIGF-1 (given as a separate injection). The children were all treatment-naive, with otherwise unexplained short stature (height standard deviation score of −2 or less), an IGF-1 SD score of −1 or less and a maximum stimulated GH level of 10 ng/mL or greater. All were prepubertal at the start of the study.

Safety data were available for all 106 children and efficacy data for 36 who completed the first year of the study. For the primary end point, first-year height velocity, the mean values were 9.2 cm/year for the rhGH monotherapy group (n=11), and 10.4, 10.7, and 12.1 cm/year, respectively, for the combinations of rhGH plus 50 (n=7), 100 (n=9), and 150 (n=9) mcg/kg of rhIGF-1.

First-year increases in height SD scores were 0.72, 0.88, 0.91, and 1.1, respectively, Dr. Bright reported at the meeting.

The study protocol specified reducing the rhIGF-1 dose if a subject had an IGF-1 score measurement above plus-4. This occurred in seven subjects, three from the 100-mcg/kg rhIGF-1 dose group and four from the 150 mcg/kg dose group. It's not clear that this level actually poses a danger, but it was done as a safeguard, he noted. Most of the children appeared to show greater change in height age than in bone age, he added.

Four serious adverse events have occurred thus far in 2 of the 106 children. A 10-year-old male experienced thrombocytopenia, hematuria, and viral infection and was diagnosed with Evans syndrome. This was considered not drug related, but he did discontinue the study. An 11-year-old male in the 150-mcg/kg rhIGF-1 group had transient papilledema with probable intracranial hypertension, which was considered probably drug related. Treatment was stopped and re-started without recurrence.

Five patients withdrew early from the study, four of them due to adverse events. In addition to the Evans syndrome patient, two had generalized urticaria that was considered drug-related. One had alopecia that was considered possibly/probably drug-related. The fifth withdrew due to noncompliance.

Headache was reported by a fourth of the rhGH monotherapy group and by half of the highest dose combo group, with the two middle groups falling in between. Vomiting occurred in 12%-15% of all four groups. However, only eight patients reported both headache and vomiting. Two children are thought to have had intracranial hypertension, Dr. Bright said.

Transient elevations in transaminases were seen during weeks 0–13 in some of the patients, he said but most were less than 2.5 times the upper limit of normal, and resolved by 13 weeks.