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Jeff Evans has been editor of Rheumatology News/MDedge Rheumatology and the EULAR Congress News since 2013. He started at Frontline Medical Communications in 2001 and was a reporter for 8 years before serving as editor of Clinical Neurology News and World Neurology, and briefly as editor of GI & Hepatology News. He graduated cum laude from Cornell University (New York) with a BA in biological sciences, concentrating in neurobiology and behavior.
Child Immunization Rates Show Growth
Immunization coverage in 2006 for children aged 1935 months held steady for most recommended vaccines and grew for several types, but more recent recommendations in coverage for adolescents aged 1317 years have not yet reached the same levels of success, according to results from the most recent National Immunization Survey.
The Centers for Disease Control and Prevention estimated that the percentage of children aged 1935 months who have received the recommended series of childhood vaccines grew from 76% in 2005 to 77% in 2006 (MMWR 2007;56:8805).
"While we're very pleased with how high the complete series coverage is, we know we still have a way to go to reach the 80% goal for [the Healthy People 2010 target] and the 90% coverage for individual vaccines," Dr. Melinda Wharton, deputy director for the National Center for Immunization and Respiratory Diseases at the CDC, said during a teleconference.
Adolescents aged 1317 yearswho were included in the survey for the first timefulfilled the recommended immunizations at high percentages for measles, mumps, and rubella vaccine (87% for 1315 years of age) and hepatitis B vaccine (82%). But recommendations made in 2005 for vaccination with tetanus-diphtheria or tetanus, reduced diphtheria, and acellular pertussis vaccines (Tdap) and meningococcal conjugate vaccine (MCV4) reached levels of only 60% (after age 10 years) and 12%, respectively (MMWR 2007;56:8858).
Any new vaccine recommended by the Advisory Committee on Immunization Practices has a target coverage of 90% or higher within 5 years of the recommendation, according to the CDC.
The survey did not report on human papillomavirus (HPV) vaccination because it was conducted before HPV vaccination recommendations were published.
The survey estimated immunization coverage through a quarterly, random-digit-dialed sample of telephone numbers in each of the 50 states, plus 30 local areas (counties and cities). The household responses are then corroborated with vaccination records from their health care providers. The household response rates for the child and adolescent surveys were 65% and 56%, respectively. The 21,044 children with provider-reported vaccination records represented 70% of all children with completed household interviews, whereas the 2,882 adolescents with provider-reported vaccination records represented 53% of adolescents with completed household interviews.
For children aged 1935 months, the levels of coverage rose significantly from 2005 levels for pneumococcal conjugate vaccine (from 83% to 87%, for three or more doses), varicella vaccine (from 88% to 89%), and poliovirus vaccine (from 92% to 93%).
Across the states, the percentage of children who received the recommended series of childhood vaccines ranged from 84% in Massachusetts to 60% in Nevada. These rates also varied across local areas, ranging from 81% in Boston to 65% in Detroit.
Coverage for the recommended series of childhood vaccines was significantly lower for black children than white children (74% vs. 78%), but after adjustment for income the difference in coverage was no longer significant.
"Vaccination funding through the federal Vaccines for Children program has contributed to record coverage levels among children who are uninsured or underinsured, but additional measures are needed to deliver vaccines to children who live below the poverty level," according to the CDC.
"Clearly we need to do more to get information to parents and health care providers, and to make sure that everyone has a good understanding of the recommendations and the health benefits that the vaccines provide," Dr. Wharton said.
Dr. Wharton suggested that physicians can use immunization registries or electronic medical records to track the immunization status of individual children. Such systems "can really be part of the solution because many children may move from provider to provider or community to community," and may have already received vaccines even though it has not been recorded.
Immunization coverage in 2006 for children aged 1935 months held steady for most recommended vaccines and grew for several types, but more recent recommendations in coverage for adolescents aged 1317 years have not yet reached the same levels of success, according to results from the most recent National Immunization Survey.
The Centers for Disease Control and Prevention estimated that the percentage of children aged 1935 months who have received the recommended series of childhood vaccines grew from 76% in 2005 to 77% in 2006 (MMWR 2007;56:8805).
"While we're very pleased with how high the complete series coverage is, we know we still have a way to go to reach the 80% goal for [the Healthy People 2010 target] and the 90% coverage for individual vaccines," Dr. Melinda Wharton, deputy director for the National Center for Immunization and Respiratory Diseases at the CDC, said during a teleconference.
Adolescents aged 1317 yearswho were included in the survey for the first timefulfilled the recommended immunizations at high percentages for measles, mumps, and rubella vaccine (87% for 1315 years of age) and hepatitis B vaccine (82%). But recommendations made in 2005 for vaccination with tetanus-diphtheria or tetanus, reduced diphtheria, and acellular pertussis vaccines (Tdap) and meningococcal conjugate vaccine (MCV4) reached levels of only 60% (after age 10 years) and 12%, respectively (MMWR 2007;56:8858).
Any new vaccine recommended by the Advisory Committee on Immunization Practices has a target coverage of 90% or higher within 5 years of the recommendation, according to the CDC.
The survey did not report on human papillomavirus (HPV) vaccination because it was conducted before HPV vaccination recommendations were published.
The survey estimated immunization coverage through a quarterly, random-digit-dialed sample of telephone numbers in each of the 50 states, plus 30 local areas (counties and cities). The household responses are then corroborated with vaccination records from their health care providers. The household response rates for the child and adolescent surveys were 65% and 56%, respectively. The 21,044 children with provider-reported vaccination records represented 70% of all children with completed household interviews, whereas the 2,882 adolescents with provider-reported vaccination records represented 53% of adolescents with completed household interviews.
For children aged 1935 months, the levels of coverage rose significantly from 2005 levels for pneumococcal conjugate vaccine (from 83% to 87%, for three or more doses), varicella vaccine (from 88% to 89%), and poliovirus vaccine (from 92% to 93%).
Across the states, the percentage of children who received the recommended series of childhood vaccines ranged from 84% in Massachusetts to 60% in Nevada. These rates also varied across local areas, ranging from 81% in Boston to 65% in Detroit.
Coverage for the recommended series of childhood vaccines was significantly lower for black children than white children (74% vs. 78%), but after adjustment for income the difference in coverage was no longer significant.
"Vaccination funding through the federal Vaccines for Children program has contributed to record coverage levels among children who are uninsured or underinsured, but additional measures are needed to deliver vaccines to children who live below the poverty level," according to the CDC.
"Clearly we need to do more to get information to parents and health care providers, and to make sure that everyone has a good understanding of the recommendations and the health benefits that the vaccines provide," Dr. Wharton said.
Dr. Wharton suggested that physicians can use immunization registries or electronic medical records to track the immunization status of individual children. Such systems "can really be part of the solution because many children may move from provider to provider or community to community," and may have already received vaccines even though it has not been recorded.
Immunization coverage in 2006 for children aged 1935 months held steady for most recommended vaccines and grew for several types, but more recent recommendations in coverage for adolescents aged 1317 years have not yet reached the same levels of success, according to results from the most recent National Immunization Survey.
The Centers for Disease Control and Prevention estimated that the percentage of children aged 1935 months who have received the recommended series of childhood vaccines grew from 76% in 2005 to 77% in 2006 (MMWR 2007;56:8805).
"While we're very pleased with how high the complete series coverage is, we know we still have a way to go to reach the 80% goal for [the Healthy People 2010 target] and the 90% coverage for individual vaccines," Dr. Melinda Wharton, deputy director for the National Center for Immunization and Respiratory Diseases at the CDC, said during a teleconference.
Adolescents aged 1317 yearswho were included in the survey for the first timefulfilled the recommended immunizations at high percentages for measles, mumps, and rubella vaccine (87% for 1315 years of age) and hepatitis B vaccine (82%). But recommendations made in 2005 for vaccination with tetanus-diphtheria or tetanus, reduced diphtheria, and acellular pertussis vaccines (Tdap) and meningococcal conjugate vaccine (MCV4) reached levels of only 60% (after age 10 years) and 12%, respectively (MMWR 2007;56:8858).
Any new vaccine recommended by the Advisory Committee on Immunization Practices has a target coverage of 90% or higher within 5 years of the recommendation, according to the CDC.
The survey did not report on human papillomavirus (HPV) vaccination because it was conducted before HPV vaccination recommendations were published.
The survey estimated immunization coverage through a quarterly, random-digit-dialed sample of telephone numbers in each of the 50 states, plus 30 local areas (counties and cities). The household responses are then corroborated with vaccination records from their health care providers. The household response rates for the child and adolescent surveys were 65% and 56%, respectively. The 21,044 children with provider-reported vaccination records represented 70% of all children with completed household interviews, whereas the 2,882 adolescents with provider-reported vaccination records represented 53% of adolescents with completed household interviews.
For children aged 1935 months, the levels of coverage rose significantly from 2005 levels for pneumococcal conjugate vaccine (from 83% to 87%, for three or more doses), varicella vaccine (from 88% to 89%), and poliovirus vaccine (from 92% to 93%).
Across the states, the percentage of children who received the recommended series of childhood vaccines ranged from 84% in Massachusetts to 60% in Nevada. These rates also varied across local areas, ranging from 81% in Boston to 65% in Detroit.
Coverage for the recommended series of childhood vaccines was significantly lower for black children than white children (74% vs. 78%), but after adjustment for income the difference in coverage was no longer significant.
"Vaccination funding through the federal Vaccines for Children program has contributed to record coverage levels among children who are uninsured or underinsured, but additional measures are needed to deliver vaccines to children who live below the poverty level," according to the CDC.
"Clearly we need to do more to get information to parents and health care providers, and to make sure that everyone has a good understanding of the recommendations and the health benefits that the vaccines provide," Dr. Wharton said.
Dr. Wharton suggested that physicians can use immunization registries or electronic medical records to track the immunization status of individual children. Such systems "can really be part of the solution because many children may move from provider to provider or community to community," and may have already received vaccines even though it has not been recorded.
Merck Updates Vaccine Stocking Delays, Shortages
Merck & Co. Inc. issued an update on the status of its vaccine delays and shortages in a letter to physicians.
The company announced that ProQuad (measles, mumps, rubella, and varicella virus vaccine live) will be unavailable for ordering through the rest of 2007, although existing back orders were filled through August. It said it was too early to decide if ProQuad will be available in 2008.
Merck had earlier requested that customers transition from ProQuad to M-M-R II and Varivax (varicella vaccine). The Centers for Disease Control and Prevention continues to report that current projections forecast an adequate supply to implement the recommended immunization schedule fully for varicella vaccine for all age groups and for the recommended use of Zostavax, the herpes zoster vaccine.
Varivax is currently available in adequate supply, according to Merck, but customers should expect shipping delays of up to 15–20 business days. The company expects to return to normal delivery schedules in late September or early October, but in the meantime two additional shipping days have been added and at least one order per office is being shipped—instead of the normal first-in, first-out model—to minimize the impact on customers with no supply of Varivax.
Production delays also have plagued Merck in manufacturing its pediatric and adult hepatitis A vaccine (Pediatric and Adult Vaqta). It said orders that it received early- to mid-September will continue to be filled on a 6- to 7-week back order, but orders that are received after mid-September will not be available for shipment until near the end of the first quarter of 2008.
Merck & Co. Inc. issued an update on the status of its vaccine delays and shortages in a letter to physicians.
The company announced that ProQuad (measles, mumps, rubella, and varicella virus vaccine live) will be unavailable for ordering through the rest of 2007, although existing back orders were filled through August. It said it was too early to decide if ProQuad will be available in 2008.
Merck had earlier requested that customers transition from ProQuad to M-M-R II and Varivax (varicella vaccine). The Centers for Disease Control and Prevention continues to report that current projections forecast an adequate supply to implement the recommended immunization schedule fully for varicella vaccine for all age groups and for the recommended use of Zostavax, the herpes zoster vaccine.
Varivax is currently available in adequate supply, according to Merck, but customers should expect shipping delays of up to 15–20 business days. The company expects to return to normal delivery schedules in late September or early October, but in the meantime two additional shipping days have been added and at least one order per office is being shipped—instead of the normal first-in, first-out model—to minimize the impact on customers with no supply of Varivax.
Production delays also have plagued Merck in manufacturing its pediatric and adult hepatitis A vaccine (Pediatric and Adult Vaqta). It said orders that it received early- to mid-September will continue to be filled on a 6- to 7-week back order, but orders that are received after mid-September will not be available for shipment until near the end of the first quarter of 2008.
Merck & Co. Inc. issued an update on the status of its vaccine delays and shortages in a letter to physicians.
The company announced that ProQuad (measles, mumps, rubella, and varicella virus vaccine live) will be unavailable for ordering through the rest of 2007, although existing back orders were filled through August. It said it was too early to decide if ProQuad will be available in 2008.
Merck had earlier requested that customers transition from ProQuad to M-M-R II and Varivax (varicella vaccine). The Centers for Disease Control and Prevention continues to report that current projections forecast an adequate supply to implement the recommended immunization schedule fully for varicella vaccine for all age groups and for the recommended use of Zostavax, the herpes zoster vaccine.
Varivax is currently available in adequate supply, according to Merck, but customers should expect shipping delays of up to 15–20 business days. The company expects to return to normal delivery schedules in late September or early October, but in the meantime two additional shipping days have been added and at least one order per office is being shipped—instead of the normal first-in, first-out model—to minimize the impact on customers with no supply of Varivax.
Production delays also have plagued Merck in manufacturing its pediatric and adult hepatitis A vaccine (Pediatric and Adult Vaqta). It said orders that it received early- to mid-September will continue to be filled on a 6- to 7-week back order, but orders that are received after mid-September will not be available for shipment until near the end of the first quarter of 2008.
Obesity Plus Hypertension Ups Renal Cancer Risk
Obesity and hypertension may interact to increase the risk of renal cell carcinoma to a greater degree than does either factor alone, according to results of a case-control study.
The findings “suggest synergistic action between obesity and elevated blood pressure, implying that control of either could be effective in lowering RCC risk,” wrote Kaye E. Brock, Ph.D., of the University of Sydney and her associates (Obesity Res. Clin. Pract. 2007;1:147–53).
Of the many case-control studies that have investigated the relationship among RCC, obesity, and hypertension, only two have reported synergism between hypertension and body mass index (BMI).
Lipid peroxidation in hypertensive and overweight patients has been proposed to explain the associations of obesity and hypertension with RCC because of its occurrence in clinical findings, animal models, and human renal cell tissue. Renal DNA is known to react with by-products of lipid peroxidation to form adducts, which, without proper DNA repair, may lead to carcinogenesis, the investigators said.
Dr. Brock and her colleagues compared 373 patients, who had histologically confirmed RCCs identified by the State Health Registry of Iowa during 1985–1987, with 2,250 population-based controls, who were matched to the cases by gender and 5-year age groupings. Overall, 99% of the patients were white and had an age range of 40–85 years.
The researchers found that hypertension was associated with significantly higher odds (odds ratio 1.74) of developing RCC after adjustment for BMI, whereas BMI also was associated with significantly higher odds (OR 1.82) of developing RCC after adjusting for hypertension.
Risk of RCC steadily rose as BMI (kg/m
But there was little increase in the risk of RCC as the severity of obesity rose in patients with normal blood pressure.
Each analysis was adjusted for age, gender, and pack-years of smoking. A proxy respondent filled out a questionnaire on behalf of some patients because of death or illness, so the investigators also adjusted each analysis for proxy status.
Obesity and hypertension may interact to increase the risk of renal cell carcinoma to a greater degree than does either factor alone, according to results of a case-control study.
The findings “suggest synergistic action between obesity and elevated blood pressure, implying that control of either could be effective in lowering RCC risk,” wrote Kaye E. Brock, Ph.D., of the University of Sydney and her associates (Obesity Res. Clin. Pract. 2007;1:147–53).
Of the many case-control studies that have investigated the relationship among RCC, obesity, and hypertension, only two have reported synergism between hypertension and body mass index (BMI).
Lipid peroxidation in hypertensive and overweight patients has been proposed to explain the associations of obesity and hypertension with RCC because of its occurrence in clinical findings, animal models, and human renal cell tissue. Renal DNA is known to react with by-products of lipid peroxidation to form adducts, which, without proper DNA repair, may lead to carcinogenesis, the investigators said.
Dr. Brock and her colleagues compared 373 patients, who had histologically confirmed RCCs identified by the State Health Registry of Iowa during 1985–1987, with 2,250 population-based controls, who were matched to the cases by gender and 5-year age groupings. Overall, 99% of the patients were white and had an age range of 40–85 years.
The researchers found that hypertension was associated with significantly higher odds (odds ratio 1.74) of developing RCC after adjustment for BMI, whereas BMI also was associated with significantly higher odds (OR 1.82) of developing RCC after adjusting for hypertension.
Risk of RCC steadily rose as BMI (kg/m
But there was little increase in the risk of RCC as the severity of obesity rose in patients with normal blood pressure.
Each analysis was adjusted for age, gender, and pack-years of smoking. A proxy respondent filled out a questionnaire on behalf of some patients because of death or illness, so the investigators also adjusted each analysis for proxy status.
Obesity and hypertension may interact to increase the risk of renal cell carcinoma to a greater degree than does either factor alone, according to results of a case-control study.
The findings “suggest synergistic action between obesity and elevated blood pressure, implying that control of either could be effective in lowering RCC risk,” wrote Kaye E. Brock, Ph.D., of the University of Sydney and her associates (Obesity Res. Clin. Pract. 2007;1:147–53).
Of the many case-control studies that have investigated the relationship among RCC, obesity, and hypertension, only two have reported synergism between hypertension and body mass index (BMI).
Lipid peroxidation in hypertensive and overweight patients has been proposed to explain the associations of obesity and hypertension with RCC because of its occurrence in clinical findings, animal models, and human renal cell tissue. Renal DNA is known to react with by-products of lipid peroxidation to form adducts, which, without proper DNA repair, may lead to carcinogenesis, the investigators said.
Dr. Brock and her colleagues compared 373 patients, who had histologically confirmed RCCs identified by the State Health Registry of Iowa during 1985–1987, with 2,250 population-based controls, who were matched to the cases by gender and 5-year age groupings. Overall, 99% of the patients were white and had an age range of 40–85 years.
The researchers found that hypertension was associated with significantly higher odds (odds ratio 1.74) of developing RCC after adjustment for BMI, whereas BMI also was associated with significantly higher odds (OR 1.82) of developing RCC after adjusting for hypertension.
Risk of RCC steadily rose as BMI (kg/m
But there was little increase in the risk of RCC as the severity of obesity rose in patients with normal blood pressure.
Each analysis was adjusted for age, gender, and pack-years of smoking. A proxy respondent filled out a questionnaire on behalf of some patients because of death or illness, so the investigators also adjusted each analysis for proxy status.
Modest Weight Loss Less Beneficial in PCOS
Overweight women with polycystic ovary syndrome may need to lose more than 5% of their weight to see improvement in inflammatory markers, reported Lisa J. Moran of the University of Adelaide (Australia) and her colleagues.
At the end of an 8-week, prospective study of the effect of dieting on metabolic risk factors and inflammatory markers, 15 women with polycystic ovary syndrome (PCOS) and 17 women without PCOS lost weight (mean of 3.9 kg [4%] vs. 4.5 kg [4.7%], respectively) and reduced fasting insulin and triglyceride to similar levels. But significantly more women with PCOS had insulin resistance (IR) after weight loss than did women without PCOS.
Women with PCOS tended to have higher levels of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α after weight loss than did those women without PCOS, and none of the women in either group had a reduction in the markers' levels after weight loss, according to Ms. Moran and her associates (J. Clin. Endocrinol. Metab. 2007;92:2944–51).
The lack of a reduction in those inflammatory markers in all patients was “surprising,” even though the investigators expected a similar response between groups given their comparable reductions in weight and waist circumference.
“The metabolic benefits conferred by weight loss, specifically reductions in insulin resistance, may therefore be contingent on reduction on a key level of abdominal or visceral abdominal fat,” they wrote.
But in a post hoc analysis, women who had below-median C-reactive protein (CRP) levels at baseline had significantly higher increases in adiponectin—which is thought to have insulin-sensitizing, antiatherogenic, and anti-inflammatory properties—and greater reductions in triglycerides after weight loss, regardless of PCOS status. “This suggests that subjects with an adverse inflammatory profile may demonstrate less favorable metabolic improvements after weight loss,” the researchers wrote.
The lack of differences in response to weight loss between the groups could mean that the participants in the study were “not representative of the general population where differences in cardiovascular risk profiles are commonly observed between women with and without PCOS.” Therefore, in cases “where women with PCOS display an elevated cardiovascular risk profile in association with elevated inflammatory markers, a greater degree of weight loss [more than 5%] may be required to achieve metabolic benefits similar to subjects without PCOS,” Ms. Moran and her coinvestigators wrote.
The need for greater weight loss in PCOS to reduce inflammatory markers “may be related to the elevated IR commonly observed in PCOS,” the researchers wrote, because PCOS-associated IR is “predominantly associated with postreceptor defects in insulin signaling and is thus metabolically distinct from obesity-associated IR.” It has been suggested that “obesity-associated increases in TNF-α and IL-6 reduce adiponectin expression and thus insulin sensitivity,” making it possible that “adiponectin, IL-6, and TNF-α may not be involved in the mediation of IR in PCOS.”
On the other hand, IR in women with PCOS “may require a greater reduction in weight, abdominal or visceral adiposity, and androgens to be ameliorated,” the researchers noted.
“It is possible that despite the similar waist circumferences, differences in visceral abdominal fat existed between subjects with and without PCOS. This could account for the differences in fasting insulin and HOMA [homeostatic model assessment] and the differential effect of weight loss on CRP in PCOS in this study,” the investigators wrote. But they thought it more likely that alterations in IR “are primarily responsible for mediating changes in cytokines and adipocytokines with weight loss.”
Both groups of women, all of whom were white, had an average body mass index of about 35 kg/m
The investigators noted that weaknesses of the trial included not controlling for age and menstrual cycle stage.
Overweight women with polycystic ovary syndrome may need to lose more than 5% of their weight to see improvement in inflammatory markers, reported Lisa J. Moran of the University of Adelaide (Australia) and her colleagues.
At the end of an 8-week, prospective study of the effect of dieting on metabolic risk factors and inflammatory markers, 15 women with polycystic ovary syndrome (PCOS) and 17 women without PCOS lost weight (mean of 3.9 kg [4%] vs. 4.5 kg [4.7%], respectively) and reduced fasting insulin and triglyceride to similar levels. But significantly more women with PCOS had insulin resistance (IR) after weight loss than did women without PCOS.
Women with PCOS tended to have higher levels of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α after weight loss than did those women without PCOS, and none of the women in either group had a reduction in the markers' levels after weight loss, according to Ms. Moran and her associates (J. Clin. Endocrinol. Metab. 2007;92:2944–51).
The lack of a reduction in those inflammatory markers in all patients was “surprising,” even though the investigators expected a similar response between groups given their comparable reductions in weight and waist circumference.
“The metabolic benefits conferred by weight loss, specifically reductions in insulin resistance, may therefore be contingent on reduction on a key level of abdominal or visceral abdominal fat,” they wrote.
But in a post hoc analysis, women who had below-median C-reactive protein (CRP) levels at baseline had significantly higher increases in adiponectin—which is thought to have insulin-sensitizing, antiatherogenic, and anti-inflammatory properties—and greater reductions in triglycerides after weight loss, regardless of PCOS status. “This suggests that subjects with an adverse inflammatory profile may demonstrate less favorable metabolic improvements after weight loss,” the researchers wrote.
The lack of differences in response to weight loss between the groups could mean that the participants in the study were “not representative of the general population where differences in cardiovascular risk profiles are commonly observed between women with and without PCOS.” Therefore, in cases “where women with PCOS display an elevated cardiovascular risk profile in association with elevated inflammatory markers, a greater degree of weight loss [more than 5%] may be required to achieve metabolic benefits similar to subjects without PCOS,” Ms. Moran and her coinvestigators wrote.
The need for greater weight loss in PCOS to reduce inflammatory markers “may be related to the elevated IR commonly observed in PCOS,” the researchers wrote, because PCOS-associated IR is “predominantly associated with postreceptor defects in insulin signaling and is thus metabolically distinct from obesity-associated IR.” It has been suggested that “obesity-associated increases in TNF-α and IL-6 reduce adiponectin expression and thus insulin sensitivity,” making it possible that “adiponectin, IL-6, and TNF-α may not be involved in the mediation of IR in PCOS.”
On the other hand, IR in women with PCOS “may require a greater reduction in weight, abdominal or visceral adiposity, and androgens to be ameliorated,” the researchers noted.
“It is possible that despite the similar waist circumferences, differences in visceral abdominal fat existed between subjects with and without PCOS. This could account for the differences in fasting insulin and HOMA [homeostatic model assessment] and the differential effect of weight loss on CRP in PCOS in this study,” the investigators wrote. But they thought it more likely that alterations in IR “are primarily responsible for mediating changes in cytokines and adipocytokines with weight loss.”
Both groups of women, all of whom were white, had an average body mass index of about 35 kg/m
The investigators noted that weaknesses of the trial included not controlling for age and menstrual cycle stage.
Overweight women with polycystic ovary syndrome may need to lose more than 5% of their weight to see improvement in inflammatory markers, reported Lisa J. Moran of the University of Adelaide (Australia) and her colleagues.
At the end of an 8-week, prospective study of the effect of dieting on metabolic risk factors and inflammatory markers, 15 women with polycystic ovary syndrome (PCOS) and 17 women without PCOS lost weight (mean of 3.9 kg [4%] vs. 4.5 kg [4.7%], respectively) and reduced fasting insulin and triglyceride to similar levels. But significantly more women with PCOS had insulin resistance (IR) after weight loss than did women without PCOS.
Women with PCOS tended to have higher levels of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α after weight loss than did those women without PCOS, and none of the women in either group had a reduction in the markers' levels after weight loss, according to Ms. Moran and her associates (J. Clin. Endocrinol. Metab. 2007;92:2944–51).
The lack of a reduction in those inflammatory markers in all patients was “surprising,” even though the investigators expected a similar response between groups given their comparable reductions in weight and waist circumference.
“The metabolic benefits conferred by weight loss, specifically reductions in insulin resistance, may therefore be contingent on reduction on a key level of abdominal or visceral abdominal fat,” they wrote.
But in a post hoc analysis, women who had below-median C-reactive protein (CRP) levels at baseline had significantly higher increases in adiponectin—which is thought to have insulin-sensitizing, antiatherogenic, and anti-inflammatory properties—and greater reductions in triglycerides after weight loss, regardless of PCOS status. “This suggests that subjects with an adverse inflammatory profile may demonstrate less favorable metabolic improvements after weight loss,” the researchers wrote.
The lack of differences in response to weight loss between the groups could mean that the participants in the study were “not representative of the general population where differences in cardiovascular risk profiles are commonly observed between women with and without PCOS.” Therefore, in cases “where women with PCOS display an elevated cardiovascular risk profile in association with elevated inflammatory markers, a greater degree of weight loss [more than 5%] may be required to achieve metabolic benefits similar to subjects without PCOS,” Ms. Moran and her coinvestigators wrote.
The need for greater weight loss in PCOS to reduce inflammatory markers “may be related to the elevated IR commonly observed in PCOS,” the researchers wrote, because PCOS-associated IR is “predominantly associated with postreceptor defects in insulin signaling and is thus metabolically distinct from obesity-associated IR.” It has been suggested that “obesity-associated increases in TNF-α and IL-6 reduce adiponectin expression and thus insulin sensitivity,” making it possible that “adiponectin, IL-6, and TNF-α may not be involved in the mediation of IR in PCOS.”
On the other hand, IR in women with PCOS “may require a greater reduction in weight, abdominal or visceral adiposity, and androgens to be ameliorated,” the researchers noted.
“It is possible that despite the similar waist circumferences, differences in visceral abdominal fat existed between subjects with and without PCOS. This could account for the differences in fasting insulin and HOMA [homeostatic model assessment] and the differential effect of weight loss on CRP in PCOS in this study,” the investigators wrote. But they thought it more likely that alterations in IR “are primarily responsible for mediating changes in cytokines and adipocytokines with weight loss.”
Both groups of women, all of whom were white, had an average body mass index of about 35 kg/m
The investigators noted that weaknesses of the trial included not controlling for age and menstrual cycle stage.
Statins Urged for Diabetes Patients in Their 40s
A public health strategy of prescribing statins to patients with diabetes to prevent cardiovascular disease would be most effectively and efficiently carried out at about 40 years of age in men and 45 years in women, according to a recent study.
“From this study, we advocate that in the absence of specific indications for statin therapy (e.g., microalbuminuria, strong family or personal history of CVD risk), statins should still be routinely prescribed to all men and women with diabetes aged [older than] 40 years and 45 years, respectively, for primary CVD prevention,” Dr. Sajith Siyambalapitiya, of the University of Sheffield (England), and colleagues wrote.
To determine which of four strategies would be the most effective at reducing CVD in diabetes patients while also being the most efficient, Dr. Siyambalapitiya and coinvestigators conducted a cross-sectional cohort study with anonymous patient data from the U.K. Health Improvement Network, which comprises 304 general practices throughout England and Wales.
The four strategies considered involved using statins to treat patients belonging to one or more of the following groups:
▸ All patients with diabetes aged 30–74 years.
▸ Patients whose baseline CVD risk was moderate (10-year CVD risk of greater than 10%) or high (10-year CVD risk of greater than 20%).
▸ Patients whose cholesterol level was greater than 5 mmol/L.
▸ Patients older than a sex-specific age cutoff (determined by combining the first and second strategies).
The investigators found 62,258 patients in the network with type 1 or 2 diabetes, and included 11,005 of them in the study. All of the patients were aged 30–74 years (average 54 years) and had no history of taking lipid-lowering drugs or of having atherosclerotic disease, according to the study (Diabetes Care 2007;30:2025–9).
The investigators found that for diabetic patients with a 10-year CVD risk greater than 10%, a strategy of prescribing statins to men older than 40 years and to women age 45 years “would potentially prevent the largest number of CVD events and would recommend treatment to the least number of patients.”
The use of those ages as the cutoffs for prescribing a statin—representing the age of transition from low baseline risk to moderate to high baseline risk of developing CVD—gave 92% sensitivity and 84% specificity in men and 90% sensitivity and 81% specificity in women.
A strategy of prescribing statins to all patients with diabetes aged 30–74 years was highly effective in that it prevented a large number of CVD events, but it was not efficient and would have involved treating the largest number of patients to prevent one CVD event. On the other hand, a strategy in which all patients with a 10-year CVD risk greater than 20% were treated with statins was less effective, but was the most efficient because it involved the lowest number needed to treat to prevent one CVD event. The strategy of treating all patients with cholesterol levels greater than 5 mmol/L was the least effective and nearly the least efficient.
For each strategy, the researchers calculated the number of CVD events that were potentially avoided by multiplying the patients' 5-year baseline risk and an estimate of 33% relative reduction of CVD events, which was based on the effect of 40 mg simvastatin (Zocor) in the primary prevention of CVD events over 5 years in the U.K. Heart Protection Study. They estimated the efficiency of the strategy—or the number needed to treat to prevent one CVD event over 5 years—by dividing the number of patients treated by the number of CVD events prevented.
The investigators added that further studies “are required to clarify whether this treatment strategy can be extrapolated to diabetic patients outside the [United Kingdom], and longitudinal data are required to confirm the absolute risk reduction estimated using this strategy.”
A public health strategy of prescribing statins to patients with diabetes to prevent cardiovascular disease would be most effectively and efficiently carried out at about 40 years of age in men and 45 years in women, according to a recent study.
“From this study, we advocate that in the absence of specific indications for statin therapy (e.g., microalbuminuria, strong family or personal history of CVD risk), statins should still be routinely prescribed to all men and women with diabetes aged [older than] 40 years and 45 years, respectively, for primary CVD prevention,” Dr. Sajith Siyambalapitiya, of the University of Sheffield (England), and colleagues wrote.
To determine which of four strategies would be the most effective at reducing CVD in diabetes patients while also being the most efficient, Dr. Siyambalapitiya and coinvestigators conducted a cross-sectional cohort study with anonymous patient data from the U.K. Health Improvement Network, which comprises 304 general practices throughout England and Wales.
The four strategies considered involved using statins to treat patients belonging to one or more of the following groups:
▸ All patients with diabetes aged 30–74 years.
▸ Patients whose baseline CVD risk was moderate (10-year CVD risk of greater than 10%) or high (10-year CVD risk of greater than 20%).
▸ Patients whose cholesterol level was greater than 5 mmol/L.
▸ Patients older than a sex-specific age cutoff (determined by combining the first and second strategies).
The investigators found 62,258 patients in the network with type 1 or 2 diabetes, and included 11,005 of them in the study. All of the patients were aged 30–74 years (average 54 years) and had no history of taking lipid-lowering drugs or of having atherosclerotic disease, according to the study (Diabetes Care 2007;30:2025–9).
The investigators found that for diabetic patients with a 10-year CVD risk greater than 10%, a strategy of prescribing statins to men older than 40 years and to women age 45 years “would potentially prevent the largest number of CVD events and would recommend treatment to the least number of patients.”
The use of those ages as the cutoffs for prescribing a statin—representing the age of transition from low baseline risk to moderate to high baseline risk of developing CVD—gave 92% sensitivity and 84% specificity in men and 90% sensitivity and 81% specificity in women.
A strategy of prescribing statins to all patients with diabetes aged 30–74 years was highly effective in that it prevented a large number of CVD events, but it was not efficient and would have involved treating the largest number of patients to prevent one CVD event. On the other hand, a strategy in which all patients with a 10-year CVD risk greater than 20% were treated with statins was less effective, but was the most efficient because it involved the lowest number needed to treat to prevent one CVD event. The strategy of treating all patients with cholesterol levels greater than 5 mmol/L was the least effective and nearly the least efficient.
For each strategy, the researchers calculated the number of CVD events that were potentially avoided by multiplying the patients' 5-year baseline risk and an estimate of 33% relative reduction of CVD events, which was based on the effect of 40 mg simvastatin (Zocor) in the primary prevention of CVD events over 5 years in the U.K. Heart Protection Study. They estimated the efficiency of the strategy—or the number needed to treat to prevent one CVD event over 5 years—by dividing the number of patients treated by the number of CVD events prevented.
The investigators added that further studies “are required to clarify whether this treatment strategy can be extrapolated to diabetic patients outside the [United Kingdom], and longitudinal data are required to confirm the absolute risk reduction estimated using this strategy.”
A public health strategy of prescribing statins to patients with diabetes to prevent cardiovascular disease would be most effectively and efficiently carried out at about 40 years of age in men and 45 years in women, according to a recent study.
“From this study, we advocate that in the absence of specific indications for statin therapy (e.g., microalbuminuria, strong family or personal history of CVD risk), statins should still be routinely prescribed to all men and women with diabetes aged [older than] 40 years and 45 years, respectively, for primary CVD prevention,” Dr. Sajith Siyambalapitiya, of the University of Sheffield (England), and colleagues wrote.
To determine which of four strategies would be the most effective at reducing CVD in diabetes patients while also being the most efficient, Dr. Siyambalapitiya and coinvestigators conducted a cross-sectional cohort study with anonymous patient data from the U.K. Health Improvement Network, which comprises 304 general practices throughout England and Wales.
The four strategies considered involved using statins to treat patients belonging to one or more of the following groups:
▸ All patients with diabetes aged 30–74 years.
▸ Patients whose baseline CVD risk was moderate (10-year CVD risk of greater than 10%) or high (10-year CVD risk of greater than 20%).
▸ Patients whose cholesterol level was greater than 5 mmol/L.
▸ Patients older than a sex-specific age cutoff (determined by combining the first and second strategies).
The investigators found 62,258 patients in the network with type 1 or 2 diabetes, and included 11,005 of them in the study. All of the patients were aged 30–74 years (average 54 years) and had no history of taking lipid-lowering drugs or of having atherosclerotic disease, according to the study (Diabetes Care 2007;30:2025–9).
The investigators found that for diabetic patients with a 10-year CVD risk greater than 10%, a strategy of prescribing statins to men older than 40 years and to women age 45 years “would potentially prevent the largest number of CVD events and would recommend treatment to the least number of patients.”
The use of those ages as the cutoffs for prescribing a statin—representing the age of transition from low baseline risk to moderate to high baseline risk of developing CVD—gave 92% sensitivity and 84% specificity in men and 90% sensitivity and 81% specificity in women.
A strategy of prescribing statins to all patients with diabetes aged 30–74 years was highly effective in that it prevented a large number of CVD events, but it was not efficient and would have involved treating the largest number of patients to prevent one CVD event. On the other hand, a strategy in which all patients with a 10-year CVD risk greater than 20% were treated with statins was less effective, but was the most efficient because it involved the lowest number needed to treat to prevent one CVD event. The strategy of treating all patients with cholesterol levels greater than 5 mmol/L was the least effective and nearly the least efficient.
For each strategy, the researchers calculated the number of CVD events that were potentially avoided by multiplying the patients' 5-year baseline risk and an estimate of 33% relative reduction of CVD events, which was based on the effect of 40 mg simvastatin (Zocor) in the primary prevention of CVD events over 5 years in the U.K. Heart Protection Study. They estimated the efficiency of the strategy—or the number needed to treat to prevent one CVD event over 5 years—by dividing the number of patients treated by the number of CVD events prevented.
The investigators added that further studies “are required to clarify whether this treatment strategy can be extrapolated to diabetic patients outside the [United Kingdom], and longitudinal data are required to confirm the absolute risk reduction estimated using this strategy.”
Modest Weight Losses Fail to Benefit in PCOS
Overweight women with polycystic ovary syndrome may need to lose more than 5% of their weight to see improvement in inflammatory markers, reported Lisa J. Moran of the University of Adelaide (Australia) and her colleagues.
At the end of an 8-week, prospective study of the effect of dieting on metabolic risk factors and inflammatory markers, 15 women with polycystic ovary syndrome (PCOS) and 17 women without PCOS lost weight (mean of 3.9 kg [4%] vs. 4.5 kg [4.7%], respectively) and reduced fasting insulin and triglyceride to similar levels. But significantly more women with PCOS had insulin resistance (IR) after weight loss than did women without PCOS.
Women with PCOS tended to have higher levels of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α after weight loss than did those without PCOS, and none of the women in either group had a reduction in the markers' levels after weight loss, according to Ms. Moran and her associates (J. Clin. Endocrinol. Metab. 2007;92:2944-51).
The lack of a reduction in those inflammatory markers in all patients was “surprising,” even though the investigators expected a similar response between groups given their comparable reductions in weight and waist circumference.
“The metabolic benefits conferred by weight loss, specifically reductions in IR, may therefore be contingent on reduction on a key level of abdominal or visceral abdominal fat,” they wrote.
But in a post hoc analysis, women who had below-median C-reactive protein (CRP) levels at baseline had significantly higher increases in adiponectin—which is thought to have insulin-sensitizing, antiatherogenic, and anti-inflammatory properties—and greater reductions in triglycerides after weight loss, regardless of PCOS status. “This suggests that subjects with an adverse inflammatory profile may demonstrate less favorable metabolic improvements after weight loss,” the researchers wrote.
The lack of differences in response to weight loss between the groups could mean that the participants in the study were “not representative of the general population where differences in cardiovascular risk profiles are commonly observed between women with and without PCOS.” Therefore, in cases “where women with PCOS display an elevated cardiovascular risk profile in association with elevated inflammatory markers, a greater degree of weight loss [more than 5%] may be required to achieve metabolic benefits similar to subjects without PCOS,” Ms. Moran and her coinvestigators wrote.
The need for greater weight loss in PCOS to reduce inflammatory markers “may be related to the elevated IR commonly observed in PCOS,” the researchers wrote, because PCOS-associated IR is “predominantly associated with postreceptor defects in insulin signaling and is thus metabolically distinct from obesity-associated IR.” It has been suggested that “obesity-associated increases in TNF-α and IL-6 reduce adiponectin expression and thus insulin sensitivity,” making it possible that “adiponectin, IL-6, and TNF-α may not be involved in the mediation of IR in PCOS.”
On the other hand, IR in women with PCOS “may require a greater reduction in weight, abdominal or visceral adiposity, and androgens to be ameliorated,” the researchers noted.
“It is possible that despite the similar waist circumferences, differences in visceral abdominal fat existed between subjects with and without PCOS. This could account for the differences in fasting insulin and HOMA [homeostatic model assessment] and the differential effect of weight loss on CRP in PCOS in this study,” the investigators wrote. But they thought it more likely that alterations in IR “are primarily responsible for mediating changes in cytokines and adipocytokines with weight loss.”
Both groups of women, all of whom were white, had an average body mass index of about 35 kg/m
The investigators noted that besides a lack of a measurement of the ratio between the high- and low-molecular-weight forms of adiponectin, an additional weakness of the trial included not controlling for age and menstrual cycle stage.
Overweight women with polycystic ovary syndrome may need to lose more than 5% of their weight to see improvement in inflammatory markers, reported Lisa J. Moran of the University of Adelaide (Australia) and her colleagues.
At the end of an 8-week, prospective study of the effect of dieting on metabolic risk factors and inflammatory markers, 15 women with polycystic ovary syndrome (PCOS) and 17 women without PCOS lost weight (mean of 3.9 kg [4%] vs. 4.5 kg [4.7%], respectively) and reduced fasting insulin and triglyceride to similar levels. But significantly more women with PCOS had insulin resistance (IR) after weight loss than did women without PCOS.
Women with PCOS tended to have higher levels of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α after weight loss than did those without PCOS, and none of the women in either group had a reduction in the markers' levels after weight loss, according to Ms. Moran and her associates (J. Clin. Endocrinol. Metab. 2007;92:2944-51).
The lack of a reduction in those inflammatory markers in all patients was “surprising,” even though the investigators expected a similar response between groups given their comparable reductions in weight and waist circumference.
“The metabolic benefits conferred by weight loss, specifically reductions in IR, may therefore be contingent on reduction on a key level of abdominal or visceral abdominal fat,” they wrote.
But in a post hoc analysis, women who had below-median C-reactive protein (CRP) levels at baseline had significantly higher increases in adiponectin—which is thought to have insulin-sensitizing, antiatherogenic, and anti-inflammatory properties—and greater reductions in triglycerides after weight loss, regardless of PCOS status. “This suggests that subjects with an adverse inflammatory profile may demonstrate less favorable metabolic improvements after weight loss,” the researchers wrote.
The lack of differences in response to weight loss between the groups could mean that the participants in the study were “not representative of the general population where differences in cardiovascular risk profiles are commonly observed between women with and without PCOS.” Therefore, in cases “where women with PCOS display an elevated cardiovascular risk profile in association with elevated inflammatory markers, a greater degree of weight loss [more than 5%] may be required to achieve metabolic benefits similar to subjects without PCOS,” Ms. Moran and her coinvestigators wrote.
The need for greater weight loss in PCOS to reduce inflammatory markers “may be related to the elevated IR commonly observed in PCOS,” the researchers wrote, because PCOS-associated IR is “predominantly associated with postreceptor defects in insulin signaling and is thus metabolically distinct from obesity-associated IR.” It has been suggested that “obesity-associated increases in TNF-α and IL-6 reduce adiponectin expression and thus insulin sensitivity,” making it possible that “adiponectin, IL-6, and TNF-α may not be involved in the mediation of IR in PCOS.”
On the other hand, IR in women with PCOS “may require a greater reduction in weight, abdominal or visceral adiposity, and androgens to be ameliorated,” the researchers noted.
“It is possible that despite the similar waist circumferences, differences in visceral abdominal fat existed between subjects with and without PCOS. This could account for the differences in fasting insulin and HOMA [homeostatic model assessment] and the differential effect of weight loss on CRP in PCOS in this study,” the investigators wrote. But they thought it more likely that alterations in IR “are primarily responsible for mediating changes in cytokines and adipocytokines with weight loss.”
Both groups of women, all of whom were white, had an average body mass index of about 35 kg/m
The investigators noted that besides a lack of a measurement of the ratio between the high- and low-molecular-weight forms of adiponectin, an additional weakness of the trial included not controlling for age and menstrual cycle stage.
Overweight women with polycystic ovary syndrome may need to lose more than 5% of their weight to see improvement in inflammatory markers, reported Lisa J. Moran of the University of Adelaide (Australia) and her colleagues.
At the end of an 8-week, prospective study of the effect of dieting on metabolic risk factors and inflammatory markers, 15 women with polycystic ovary syndrome (PCOS) and 17 women without PCOS lost weight (mean of 3.9 kg [4%] vs. 4.5 kg [4.7%], respectively) and reduced fasting insulin and triglyceride to similar levels. But significantly more women with PCOS had insulin resistance (IR) after weight loss than did women without PCOS.
Women with PCOS tended to have higher levels of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α after weight loss than did those without PCOS, and none of the women in either group had a reduction in the markers' levels after weight loss, according to Ms. Moran and her associates (J. Clin. Endocrinol. Metab. 2007;92:2944-51).
The lack of a reduction in those inflammatory markers in all patients was “surprising,” even though the investigators expected a similar response between groups given their comparable reductions in weight and waist circumference.
“The metabolic benefits conferred by weight loss, specifically reductions in IR, may therefore be contingent on reduction on a key level of abdominal or visceral abdominal fat,” they wrote.
But in a post hoc analysis, women who had below-median C-reactive protein (CRP) levels at baseline had significantly higher increases in adiponectin—which is thought to have insulin-sensitizing, antiatherogenic, and anti-inflammatory properties—and greater reductions in triglycerides after weight loss, regardless of PCOS status. “This suggests that subjects with an adverse inflammatory profile may demonstrate less favorable metabolic improvements after weight loss,” the researchers wrote.
The lack of differences in response to weight loss between the groups could mean that the participants in the study were “not representative of the general population where differences in cardiovascular risk profiles are commonly observed between women with and without PCOS.” Therefore, in cases “where women with PCOS display an elevated cardiovascular risk profile in association with elevated inflammatory markers, a greater degree of weight loss [more than 5%] may be required to achieve metabolic benefits similar to subjects without PCOS,” Ms. Moran and her coinvestigators wrote.
The need for greater weight loss in PCOS to reduce inflammatory markers “may be related to the elevated IR commonly observed in PCOS,” the researchers wrote, because PCOS-associated IR is “predominantly associated with postreceptor defects in insulin signaling and is thus metabolically distinct from obesity-associated IR.” It has been suggested that “obesity-associated increases in TNF-α and IL-6 reduce adiponectin expression and thus insulin sensitivity,” making it possible that “adiponectin, IL-6, and TNF-α may not be involved in the mediation of IR in PCOS.”
On the other hand, IR in women with PCOS “may require a greater reduction in weight, abdominal or visceral adiposity, and androgens to be ameliorated,” the researchers noted.
“It is possible that despite the similar waist circumferences, differences in visceral abdominal fat existed between subjects with and without PCOS. This could account for the differences in fasting insulin and HOMA [homeostatic model assessment] and the differential effect of weight loss on CRP in PCOS in this study,” the investigators wrote. But they thought it more likely that alterations in IR “are primarily responsible for mediating changes in cytokines and adipocytokines with weight loss.”
Both groups of women, all of whom were white, had an average body mass index of about 35 kg/m
The investigators noted that besides a lack of a measurement of the ratio between the high- and low-molecular-weight forms of adiponectin, an additional weakness of the trial included not controlling for age and menstrual cycle stage.
DMARD Combo Works Best in Anti-CCP-Negative Patients
BARCELONA — The treatment of early rheumatoid arthritis with a combination of disease-modifying antirheumatic drugs slows radiographic progression faster in patients without antibodies against cyclic citrullinated peptide than in those patients with the antibodies, Dr. Markku Korpela said at the annual European Congress of Rheumatology.
In a subset of patients from the randomized Finnish RA Combination Therapy (FIN-RACo) trial whose anti-cyclic citrullinated peptide (CCP) status was known, 69 patients were treated initially with a drug combination that included methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone; another 60 patients were treated with sulfasalazine, with or without prednisolone.
The DMARD and prednisolone treatments were allowed to change after 2 years, according to Dr. Korpela, a rheumatologist at Tampere (Finland) University Hospital. Dr. Korpela and his colleagues found that a combination of DMARDs could significantly slow radiographic signs of RA progression (as defined by the Larsen score in hands and feet) in the absence of anti-CCP antibodies, but treatment with a single DMARD could not.
Radiographic RA progression occurred at similar rates in anti-CCP-positive and -negative patients when only one DMARD was used.
“This means that patients without CCP antibodies should be treated aggressively,” Dr. Korpela said in an interview during a poster presentation at the congress. Of the 129 patients, 92 (71%) tested positive for anti-CCP antibodies. Compared with anti-CCP-negative patients, those who tested positive for the antibodies also were significantly more likely to test positive for rheumatoid factor (83% vs. 22%) or erosive disease at baseline (54% vs. 22%).
And anti-CCP positivity predicted radiographic progression in the combination-DMARD group even when the investigators adjusted the comparison for the presence of rheumatoid factor.
BARCELONA — The treatment of early rheumatoid arthritis with a combination of disease-modifying antirheumatic drugs slows radiographic progression faster in patients without antibodies against cyclic citrullinated peptide than in those patients with the antibodies, Dr. Markku Korpela said at the annual European Congress of Rheumatology.
In a subset of patients from the randomized Finnish RA Combination Therapy (FIN-RACo) trial whose anti-cyclic citrullinated peptide (CCP) status was known, 69 patients were treated initially with a drug combination that included methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone; another 60 patients were treated with sulfasalazine, with or without prednisolone.
The DMARD and prednisolone treatments were allowed to change after 2 years, according to Dr. Korpela, a rheumatologist at Tampere (Finland) University Hospital. Dr. Korpela and his colleagues found that a combination of DMARDs could significantly slow radiographic signs of RA progression (as defined by the Larsen score in hands and feet) in the absence of anti-CCP antibodies, but treatment with a single DMARD could not.
Radiographic RA progression occurred at similar rates in anti-CCP-positive and -negative patients when only one DMARD was used.
“This means that patients without CCP antibodies should be treated aggressively,” Dr. Korpela said in an interview during a poster presentation at the congress. Of the 129 patients, 92 (71%) tested positive for anti-CCP antibodies. Compared with anti-CCP-negative patients, those who tested positive for the antibodies also were significantly more likely to test positive for rheumatoid factor (83% vs. 22%) or erosive disease at baseline (54% vs. 22%).
And anti-CCP positivity predicted radiographic progression in the combination-DMARD group even when the investigators adjusted the comparison for the presence of rheumatoid factor.
BARCELONA — The treatment of early rheumatoid arthritis with a combination of disease-modifying antirheumatic drugs slows radiographic progression faster in patients without antibodies against cyclic citrullinated peptide than in those patients with the antibodies, Dr. Markku Korpela said at the annual European Congress of Rheumatology.
In a subset of patients from the randomized Finnish RA Combination Therapy (FIN-RACo) trial whose anti-cyclic citrullinated peptide (CCP) status was known, 69 patients were treated initially with a drug combination that included methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone; another 60 patients were treated with sulfasalazine, with or without prednisolone.
The DMARD and prednisolone treatments were allowed to change after 2 years, according to Dr. Korpela, a rheumatologist at Tampere (Finland) University Hospital. Dr. Korpela and his colleagues found that a combination of DMARDs could significantly slow radiographic signs of RA progression (as defined by the Larsen score in hands and feet) in the absence of anti-CCP antibodies, but treatment with a single DMARD could not.
Radiographic RA progression occurred at similar rates in anti-CCP-positive and -negative patients when only one DMARD was used.
“This means that patients without CCP antibodies should be treated aggressively,” Dr. Korpela said in an interview during a poster presentation at the congress. Of the 129 patients, 92 (71%) tested positive for anti-CCP antibodies. Compared with anti-CCP-negative patients, those who tested positive for the antibodies also were significantly more likely to test positive for rheumatoid factor (83% vs. 22%) or erosive disease at baseline (54% vs. 22%).
And anti-CCP positivity predicted radiographic progression in the combination-DMARD group even when the investigators adjusted the comparison for the presence of rheumatoid factor.
Merck Updates Vaccine Supply Delays, Shortages
Merck & Co. has issued an update on the status of its vaccine delays and shortages in a letter to physicians.
Merck announced that ProQuad (measles, mumps, rubella, and varicella virus vaccine live) will be unavailable for ordering through the rest of 2007, although existing back orders were filled through August. In the letter, the company said that it was too early to determine if ProQuad will be available in 2008.
Merck had earlier requested that customers transition from ProQuad to M-M-R II and Varivax (varicella vaccine). The Centers for Disease Control and Prevention continues to report that current projections forecast an adequate supply to implement the recommended immunization schedule fully for varicella vaccine for all age groups.
Varivax is currently available in adequate supply, according to Merck, but customers should expect shipping delays of up to 15–20 business days. The company expects to return to normal delivery schedules in late September or early October, but in the meantime two additional shipping days have been added (Thursday for Friday delivery and Saturday for Monday delivery) and at least one order per office is being shipped—instead of the normal first-in, first-out model—to minimize the impact on customers with no supply of Varivax.
Production delays also have plagued Merck in manufacturing its pediatric and adult hepatitis A vaccine (Pediatric and Adult Vaqta). A manufacturing change that is under regulatory review started the delays, which have caused customers to experience 6- to 7-week shipment delays since late July 2007. The company said that orders for the vaccine that it received through early- to mid-September will continue to be filled on a 6- to 7-week back order, but orders that are received after mid-September will not be available for shipment until near the end of the first quarter of 2008.
The supply of GlaxoSmithKline's pediatric and adult hepatitis A vaccine (Pediatric and Adult Havrix) is adequate enough to meet demand; GSK has initiated plans to produce more Havrix to help ensure uninterrupted supply for the U.S. market, according to the CDC.
Merck & Co. has issued an update on the status of its vaccine delays and shortages in a letter to physicians.
Merck announced that ProQuad (measles, mumps, rubella, and varicella virus vaccine live) will be unavailable for ordering through the rest of 2007, although existing back orders were filled through August. In the letter, the company said that it was too early to determine if ProQuad will be available in 2008.
Merck had earlier requested that customers transition from ProQuad to M-M-R II and Varivax (varicella vaccine). The Centers for Disease Control and Prevention continues to report that current projections forecast an adequate supply to implement the recommended immunization schedule fully for varicella vaccine for all age groups.
Varivax is currently available in adequate supply, according to Merck, but customers should expect shipping delays of up to 15–20 business days. The company expects to return to normal delivery schedules in late September or early October, but in the meantime two additional shipping days have been added (Thursday for Friday delivery and Saturday for Monday delivery) and at least one order per office is being shipped—instead of the normal first-in, first-out model—to minimize the impact on customers with no supply of Varivax.
Production delays also have plagued Merck in manufacturing its pediatric and adult hepatitis A vaccine (Pediatric and Adult Vaqta). A manufacturing change that is under regulatory review started the delays, which have caused customers to experience 6- to 7-week shipment delays since late July 2007. The company said that orders for the vaccine that it received through early- to mid-September will continue to be filled on a 6- to 7-week back order, but orders that are received after mid-September will not be available for shipment until near the end of the first quarter of 2008.
The supply of GlaxoSmithKline's pediatric and adult hepatitis A vaccine (Pediatric and Adult Havrix) is adequate enough to meet demand; GSK has initiated plans to produce more Havrix to help ensure uninterrupted supply for the U.S. market, according to the CDC.
Merck & Co. has issued an update on the status of its vaccine delays and shortages in a letter to physicians.
Merck announced that ProQuad (measles, mumps, rubella, and varicella virus vaccine live) will be unavailable for ordering through the rest of 2007, although existing back orders were filled through August. In the letter, the company said that it was too early to determine if ProQuad will be available in 2008.
Merck had earlier requested that customers transition from ProQuad to M-M-R II and Varivax (varicella vaccine). The Centers for Disease Control and Prevention continues to report that current projections forecast an adequate supply to implement the recommended immunization schedule fully for varicella vaccine for all age groups.
Varivax is currently available in adequate supply, according to Merck, but customers should expect shipping delays of up to 15–20 business days. The company expects to return to normal delivery schedules in late September or early October, but in the meantime two additional shipping days have been added (Thursday for Friday delivery and Saturday for Monday delivery) and at least one order per office is being shipped—instead of the normal first-in, first-out model—to minimize the impact on customers with no supply of Varivax.
Production delays also have plagued Merck in manufacturing its pediatric and adult hepatitis A vaccine (Pediatric and Adult Vaqta). A manufacturing change that is under regulatory review started the delays, which have caused customers to experience 6- to 7-week shipment delays since late July 2007. The company said that orders for the vaccine that it received through early- to mid-September will continue to be filled on a 6- to 7-week back order, but orders that are received after mid-September will not be available for shipment until near the end of the first quarter of 2008.
The supply of GlaxoSmithKline's pediatric and adult hepatitis A vaccine (Pediatric and Adult Havrix) is adequate enough to meet demand; GSK has initiated plans to produce more Havrix to help ensure uninterrupted supply for the U.S. market, according to the CDC.
Five Factors Help Guide Nail Streak Management
WASHINGTON — The technique used to biopsy and treat a nail streak depends on the width of the streak and its location in the nail matrix, Dr. Bertrand Richert said at the annual meeting of the American Academy of Dermatology.
If there is no clue to the etiology of a pigmented band, the decision to perform a biopsy for diagnosis and treatment depends on five factors: the width of the pigmented band, the anatomical location of the band on the nail plate, the site of melanin production in the matrix, the presence or absence of periungual spread of pigmentation (Hutchinson's sign), and the presence or absence of partial nail dystrophy, said Dr. Richert of the nail unit in the department of dermatology at the University of Liège (Belgium).
Most (85%–90%) pigmented bands arise in the distal matrix, which creates the underlying layer of the nail plate. The overlying section of the nail plate, which grows from the proximal matrix, in most cases will then cover defects created in the distal matrix, making it a less likely site for nail dystrophy, he said.
In the distal matrix, pigmented bands narrower than 3 mm can be excised with a punch biopsy. Dr. Richert said that he reclines the proximal nail fold to punch out the origin of the band, but then he reclines “the whole proximal part of the nail plate to visualize the whole matrix area” and to check for any remaining pigment.
It is important to check the underside of the proximal nail plate for pigmentation because the superficial epithelium of the matrix may have been pulled up with the nail plate. The matching point on the matrix will correspond to the origin of the pigmented band. It may be helpful to keep track of the size of the band by marking the skin because little pigment may remain in the matrix once the nail is removed, he said.
For pigmented bands wider than 3 mm, a crescent-shaped biopsy can remove the pigmented area.
Pigmented bands that are located in the lateral third of the nail plate can be removed in one entire piece. Bands that are broader and/or irregular may require removal of the whole band, which creates a large defect that can be repaired with a flap and a relaxing incision to close the defect.
If there is periungual spread of pigmentation, then the whole nail unit should be removed with a 6-mm margin all around the nail apparatus because the lesion is “very likely to be melanoma,” Dr. Richert said. Amputation may be necessary for melanoma.
In many cases, toes can be healed by secondary intention when the whole nail bed is removed, but Dr. Richert “highly recommends” a full-thickness graft for fingers.
A Schernberg and Amiel releasing flap is required to close a defect that is created from the removal of a pigmented band in the proximal matrix less than 6 mm wide, but the flap “almost always results in a split nail,” he said.
It is necessary to remove the whole nail unit for bands in the proximal matrix that are greater than 6 mm in width, even if the malignancy status of the lesion is unknown.
Patients may be distressed to lose much or all of the nail apparatus for the removal of only a nevus, but they also are relieved to know they do not have melanoma, Dr. Richert said. In an effort to reduce disfiguring surgery for what may be a benign pigmented lesion, he has experimented with shave biopsy to remove pigmented areas of the proximal matrix. A shave biopsy removes material to a depth of about 0.5 mm, whereas the average thickness of the punch biopsy is 2.5 mm. He has used the shave biopsy method to diagnose melanocytic activation and melanocytic hyperplasia in the proximal matrix, but has not yet detected in situ melanoma.
The shave biopsy technique is easier to perform if a small incision is made next to the site of melanin production in the matrix. This will allow the specimen to “pop out a little bit so it's easy to shave,” he said.
It may be difficult to get all areas of pigmentation with the shave biopsy technique because it is hard to obtain an even shave across curved surfaces of the nail matrix. This makes it important to recline the whole proximal nail fold to expose the entire matrix to perform a correct shave, Dr. Richert said.
The not-yet-validated technique may not be good for shaving the lateral horns of the matrix because it is “very difficult” to perform a complete shave of the pigmented area, he said.
WASHINGTON — The technique used to biopsy and treat a nail streak depends on the width of the streak and its location in the nail matrix, Dr. Bertrand Richert said at the annual meeting of the American Academy of Dermatology.
If there is no clue to the etiology of a pigmented band, the decision to perform a biopsy for diagnosis and treatment depends on five factors: the width of the pigmented band, the anatomical location of the band on the nail plate, the site of melanin production in the matrix, the presence or absence of periungual spread of pigmentation (Hutchinson's sign), and the presence or absence of partial nail dystrophy, said Dr. Richert of the nail unit in the department of dermatology at the University of Liège (Belgium).
Most (85%–90%) pigmented bands arise in the distal matrix, which creates the underlying layer of the nail plate. The overlying section of the nail plate, which grows from the proximal matrix, in most cases will then cover defects created in the distal matrix, making it a less likely site for nail dystrophy, he said.
In the distal matrix, pigmented bands narrower than 3 mm can be excised with a punch biopsy. Dr. Richert said that he reclines the proximal nail fold to punch out the origin of the band, but then he reclines “the whole proximal part of the nail plate to visualize the whole matrix area” and to check for any remaining pigment.
It is important to check the underside of the proximal nail plate for pigmentation because the superficial epithelium of the matrix may have been pulled up with the nail plate. The matching point on the matrix will correspond to the origin of the pigmented band. It may be helpful to keep track of the size of the band by marking the skin because little pigment may remain in the matrix once the nail is removed, he said.
For pigmented bands wider than 3 mm, a crescent-shaped biopsy can remove the pigmented area.
Pigmented bands that are located in the lateral third of the nail plate can be removed in one entire piece. Bands that are broader and/or irregular may require removal of the whole band, which creates a large defect that can be repaired with a flap and a relaxing incision to close the defect.
If there is periungual spread of pigmentation, then the whole nail unit should be removed with a 6-mm margin all around the nail apparatus because the lesion is “very likely to be melanoma,” Dr. Richert said. Amputation may be necessary for melanoma.
In many cases, toes can be healed by secondary intention when the whole nail bed is removed, but Dr. Richert “highly recommends” a full-thickness graft for fingers.
A Schernberg and Amiel releasing flap is required to close a defect that is created from the removal of a pigmented band in the proximal matrix less than 6 mm wide, but the flap “almost always results in a split nail,” he said.
It is necessary to remove the whole nail unit for bands in the proximal matrix that are greater than 6 mm in width, even if the malignancy status of the lesion is unknown.
Patients may be distressed to lose much or all of the nail apparatus for the removal of only a nevus, but they also are relieved to know they do not have melanoma, Dr. Richert said. In an effort to reduce disfiguring surgery for what may be a benign pigmented lesion, he has experimented with shave biopsy to remove pigmented areas of the proximal matrix. A shave biopsy removes material to a depth of about 0.5 mm, whereas the average thickness of the punch biopsy is 2.5 mm. He has used the shave biopsy method to diagnose melanocytic activation and melanocytic hyperplasia in the proximal matrix, but has not yet detected in situ melanoma.
The shave biopsy technique is easier to perform if a small incision is made next to the site of melanin production in the matrix. This will allow the specimen to “pop out a little bit so it's easy to shave,” he said.
It may be difficult to get all areas of pigmentation with the shave biopsy technique because it is hard to obtain an even shave across curved surfaces of the nail matrix. This makes it important to recline the whole proximal nail fold to expose the entire matrix to perform a correct shave, Dr. Richert said.
The not-yet-validated technique may not be good for shaving the lateral horns of the matrix because it is “very difficult” to perform a complete shave of the pigmented area, he said.
WASHINGTON — The technique used to biopsy and treat a nail streak depends on the width of the streak and its location in the nail matrix, Dr. Bertrand Richert said at the annual meeting of the American Academy of Dermatology.
If there is no clue to the etiology of a pigmented band, the decision to perform a biopsy for diagnosis and treatment depends on five factors: the width of the pigmented band, the anatomical location of the band on the nail plate, the site of melanin production in the matrix, the presence or absence of periungual spread of pigmentation (Hutchinson's sign), and the presence or absence of partial nail dystrophy, said Dr. Richert of the nail unit in the department of dermatology at the University of Liège (Belgium).
Most (85%–90%) pigmented bands arise in the distal matrix, which creates the underlying layer of the nail plate. The overlying section of the nail plate, which grows from the proximal matrix, in most cases will then cover defects created in the distal matrix, making it a less likely site for nail dystrophy, he said.
In the distal matrix, pigmented bands narrower than 3 mm can be excised with a punch biopsy. Dr. Richert said that he reclines the proximal nail fold to punch out the origin of the band, but then he reclines “the whole proximal part of the nail plate to visualize the whole matrix area” and to check for any remaining pigment.
It is important to check the underside of the proximal nail plate for pigmentation because the superficial epithelium of the matrix may have been pulled up with the nail plate. The matching point on the matrix will correspond to the origin of the pigmented band. It may be helpful to keep track of the size of the band by marking the skin because little pigment may remain in the matrix once the nail is removed, he said.
For pigmented bands wider than 3 mm, a crescent-shaped biopsy can remove the pigmented area.
Pigmented bands that are located in the lateral third of the nail plate can be removed in one entire piece. Bands that are broader and/or irregular may require removal of the whole band, which creates a large defect that can be repaired with a flap and a relaxing incision to close the defect.
If there is periungual spread of pigmentation, then the whole nail unit should be removed with a 6-mm margin all around the nail apparatus because the lesion is “very likely to be melanoma,” Dr. Richert said. Amputation may be necessary for melanoma.
In many cases, toes can be healed by secondary intention when the whole nail bed is removed, but Dr. Richert “highly recommends” a full-thickness graft for fingers.
A Schernberg and Amiel releasing flap is required to close a defect that is created from the removal of a pigmented band in the proximal matrix less than 6 mm wide, but the flap “almost always results in a split nail,” he said.
It is necessary to remove the whole nail unit for bands in the proximal matrix that are greater than 6 mm in width, even if the malignancy status of the lesion is unknown.
Patients may be distressed to lose much or all of the nail apparatus for the removal of only a nevus, but they also are relieved to know they do not have melanoma, Dr. Richert said. In an effort to reduce disfiguring surgery for what may be a benign pigmented lesion, he has experimented with shave biopsy to remove pigmented areas of the proximal matrix. A shave biopsy removes material to a depth of about 0.5 mm, whereas the average thickness of the punch biopsy is 2.5 mm. He has used the shave biopsy method to diagnose melanocytic activation and melanocytic hyperplasia in the proximal matrix, but has not yet detected in situ melanoma.
The shave biopsy technique is easier to perform if a small incision is made next to the site of melanin production in the matrix. This will allow the specimen to “pop out a little bit so it's easy to shave,” he said.
It may be difficult to get all areas of pigmentation with the shave biopsy technique because it is hard to obtain an even shave across curved surfaces of the nail matrix. This makes it important to recline the whole proximal nail fold to expose the entire matrix to perform a correct shave, Dr. Richert said.
The not-yet-validated technique may not be good for shaving the lateral horns of the matrix because it is “very difficult” to perform a complete shave of the pigmented area, he said.
Modest Weight Loss Is of Little Benefit in PCOS
Overweight women with polycystic ovary syndrome may need to lose more than 5% of their weight to see improvement in inflammatory markers, reported Lisa J. Moran of the University of Adelaide (Australia) and her colleagues.
At the end of an 8-week, prospective study of the effect of dieting on metabolic risk factors and inflammatory markers, 15 women with polycystic ovary syndrome (PCOS) and 17 women without PCOS lost weight (mean of 3.9 kg [4%] vs. 4.5 kg [4.7%], respectively) and reduced fasting insulin and triglyceride to similar levels. But significantly more women with PCOS had insulin resistance (IR) after weight loss than did women without PCOS.
Women with PCOS tended to have higher levels of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α after weight loss than did those without PCOS, and none of the women in either group had a reduction in the markers' levels after weight loss, according to Ms. Moran and her associates (J. Clin. Endocrinol. Metab. 2007;92:2944-51).
The lack of a reduction in those inflammatory markers in all patients was “surprising,” even though the investigators expected a similar response between groups given their comparable reductions in weight and waist circumference.
“The metabolic benefits conferred by weight loss, specifically reductions in IR, may therefore be contingent on reduction on a key level of abdominal or visceral abdominal fat,” they wrote.
But in a post hoc analysis, women who had below-median C-reactive protein (CRP) levels at baseline had significantly higher increases in adiponectin—which is thought to have insulin-sensitizing, antiatherogenic, and anti-inflammatory properties—and greater reductions in triglycerides after weight loss, regardless of PCOS status. “This suggests that subjects with an adverse inflammatory profile may demonstrate less favorable metabolic improvements after weight loss,” the researchers wrote.
The lack of differences in response to weight loss between the groups could mean that the participants in the study were “not representative of the general population where differences in cardiovascular risk profiles are commonly observed between women with and without PCOS.” Therefore, in cases “where women with PCOS display an elevated cardiovascular risk profile in association with elevated inflammatory markers, a greater degree of weight loss [more than 5%] may be required to achieve metabolic benefits similar to subjects without PCOS,” Ms. Moran and her coinvestigators wrote.
The need for greater weight loss in PCOS to reduce inflammatory markers “may be related to the elevated IR commonly observed in PCOS,” the researchers wrote, because PCOS-associated IR is “predominantly associated with postreceptor defects in insulin signaling and is thus metabolically distinct from obesity-associated IR.” It has been suggested that “obesity-associated increases in TNF-α and IL-6 reduce adiponectin expression and thus insulin sensitivity,” making it possible that “adiponectin, IL-6, and TNF-α may not be involved in the mediation of IR in PCOS.”
On the other hand, IR in women with PCOS “may require a greater reduction in weight, abdominal or visceral adiposity, and androgens to be ameliorated,” the researchers noted.
“It is possible that despite the similar waist circumferences, differences in visceral abdominal fat existed between subjects with and without PCOS. This could account for the differences in fasting insulin and HOMA [homeostatic model assessment] and the differential effect of weight loss on CRP in PCOS in this study,” the investigators wrote. But they thought it more likely that alterations in IR “are primarily responsible for mediating changes in cytokines and adipocytokines with weight loss.”
Both groups of women, all of whom were white, had an average body mass index of about 35 kg/m
The investigators noted that besides a lack of a measurement of the ratio between the high- and low-molecular-weight forms of adiponectin, an additional weakness of the trial included not controlling for age and menstrual cycle stage.
Overweight women with polycystic ovary syndrome may need to lose more than 5% of their weight to see improvement in inflammatory markers, reported Lisa J. Moran of the University of Adelaide (Australia) and her colleagues.
At the end of an 8-week, prospective study of the effect of dieting on metabolic risk factors and inflammatory markers, 15 women with polycystic ovary syndrome (PCOS) and 17 women without PCOS lost weight (mean of 3.9 kg [4%] vs. 4.5 kg [4.7%], respectively) and reduced fasting insulin and triglyceride to similar levels. But significantly more women with PCOS had insulin resistance (IR) after weight loss than did women without PCOS.
Women with PCOS tended to have higher levels of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α after weight loss than did those without PCOS, and none of the women in either group had a reduction in the markers' levels after weight loss, according to Ms. Moran and her associates (J. Clin. Endocrinol. Metab. 2007;92:2944-51).
The lack of a reduction in those inflammatory markers in all patients was “surprising,” even though the investigators expected a similar response between groups given their comparable reductions in weight and waist circumference.
“The metabolic benefits conferred by weight loss, specifically reductions in IR, may therefore be contingent on reduction on a key level of abdominal or visceral abdominal fat,” they wrote.
But in a post hoc analysis, women who had below-median C-reactive protein (CRP) levels at baseline had significantly higher increases in adiponectin—which is thought to have insulin-sensitizing, antiatherogenic, and anti-inflammatory properties—and greater reductions in triglycerides after weight loss, regardless of PCOS status. “This suggests that subjects with an adverse inflammatory profile may demonstrate less favorable metabolic improvements after weight loss,” the researchers wrote.
The lack of differences in response to weight loss between the groups could mean that the participants in the study were “not representative of the general population where differences in cardiovascular risk profiles are commonly observed between women with and without PCOS.” Therefore, in cases “where women with PCOS display an elevated cardiovascular risk profile in association with elevated inflammatory markers, a greater degree of weight loss [more than 5%] may be required to achieve metabolic benefits similar to subjects without PCOS,” Ms. Moran and her coinvestigators wrote.
The need for greater weight loss in PCOS to reduce inflammatory markers “may be related to the elevated IR commonly observed in PCOS,” the researchers wrote, because PCOS-associated IR is “predominantly associated with postreceptor defects in insulin signaling and is thus metabolically distinct from obesity-associated IR.” It has been suggested that “obesity-associated increases in TNF-α and IL-6 reduce adiponectin expression and thus insulin sensitivity,” making it possible that “adiponectin, IL-6, and TNF-α may not be involved in the mediation of IR in PCOS.”
On the other hand, IR in women with PCOS “may require a greater reduction in weight, abdominal or visceral adiposity, and androgens to be ameliorated,” the researchers noted.
“It is possible that despite the similar waist circumferences, differences in visceral abdominal fat existed between subjects with and without PCOS. This could account for the differences in fasting insulin and HOMA [homeostatic model assessment] and the differential effect of weight loss on CRP in PCOS in this study,” the investigators wrote. But they thought it more likely that alterations in IR “are primarily responsible for mediating changes in cytokines and adipocytokines with weight loss.”
Both groups of women, all of whom were white, had an average body mass index of about 35 kg/m
The investigators noted that besides a lack of a measurement of the ratio between the high- and low-molecular-weight forms of adiponectin, an additional weakness of the trial included not controlling for age and menstrual cycle stage.
Overweight women with polycystic ovary syndrome may need to lose more than 5% of their weight to see improvement in inflammatory markers, reported Lisa J. Moran of the University of Adelaide (Australia) and her colleagues.
At the end of an 8-week, prospective study of the effect of dieting on metabolic risk factors and inflammatory markers, 15 women with polycystic ovary syndrome (PCOS) and 17 women without PCOS lost weight (mean of 3.9 kg [4%] vs. 4.5 kg [4.7%], respectively) and reduced fasting insulin and triglyceride to similar levels. But significantly more women with PCOS had insulin resistance (IR) after weight loss than did women without PCOS.
Women with PCOS tended to have higher levels of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α after weight loss than did those without PCOS, and none of the women in either group had a reduction in the markers' levels after weight loss, according to Ms. Moran and her associates (J. Clin. Endocrinol. Metab. 2007;92:2944-51).
The lack of a reduction in those inflammatory markers in all patients was “surprising,” even though the investigators expected a similar response between groups given their comparable reductions in weight and waist circumference.
“The metabolic benefits conferred by weight loss, specifically reductions in IR, may therefore be contingent on reduction on a key level of abdominal or visceral abdominal fat,” they wrote.
But in a post hoc analysis, women who had below-median C-reactive protein (CRP) levels at baseline had significantly higher increases in adiponectin—which is thought to have insulin-sensitizing, antiatherogenic, and anti-inflammatory properties—and greater reductions in triglycerides after weight loss, regardless of PCOS status. “This suggests that subjects with an adverse inflammatory profile may demonstrate less favorable metabolic improvements after weight loss,” the researchers wrote.
The lack of differences in response to weight loss between the groups could mean that the participants in the study were “not representative of the general population where differences in cardiovascular risk profiles are commonly observed between women with and without PCOS.” Therefore, in cases “where women with PCOS display an elevated cardiovascular risk profile in association with elevated inflammatory markers, a greater degree of weight loss [more than 5%] may be required to achieve metabolic benefits similar to subjects without PCOS,” Ms. Moran and her coinvestigators wrote.
The need for greater weight loss in PCOS to reduce inflammatory markers “may be related to the elevated IR commonly observed in PCOS,” the researchers wrote, because PCOS-associated IR is “predominantly associated with postreceptor defects in insulin signaling and is thus metabolically distinct from obesity-associated IR.” It has been suggested that “obesity-associated increases in TNF-α and IL-6 reduce adiponectin expression and thus insulin sensitivity,” making it possible that “adiponectin, IL-6, and TNF-α may not be involved in the mediation of IR in PCOS.”
On the other hand, IR in women with PCOS “may require a greater reduction in weight, abdominal or visceral adiposity, and androgens to be ameliorated,” the researchers noted.
“It is possible that despite the similar waist circumferences, differences in visceral abdominal fat existed between subjects with and without PCOS. This could account for the differences in fasting insulin and HOMA [homeostatic model assessment] and the differential effect of weight loss on CRP in PCOS in this study,” the investigators wrote. But they thought it more likely that alterations in IR “are primarily responsible for mediating changes in cytokines and adipocytokines with weight loss.”
Both groups of women, all of whom were white, had an average body mass index of about 35 kg/m
The investigators noted that besides a lack of a measurement of the ratio between the high- and low-molecular-weight forms of adiponectin, an additional weakness of the trial included not controlling for age and menstrual cycle stage.