<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_391"
                     title="Rare Genetic Deletion Linked to Morbid Obesity (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/Genetics/GeneralGenetics/tb/18286?impressionId=1265798703153"
                     
      &lt;p&gt;Missing sections of DNA may have a powerful impact on weight for a small segment of the population, researchers said.&lt;/p&gt;
&lt;p&gt;Nearly all teens and adults found to have a particular deletion of roughly 30-genes on chromosome 16p11.2 were obese  --  most morbidly so  --  with a body mass index of at least 40 kg/m&lt;sup&gt;2&lt;/sup&gt;, Philippe Froguel, MD, PhD, of Imperial College London, and colleagues reported in &lt;em&gt;Nature&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;While the variant appeared to explain only a small proportion of morbid obesity  --  0.7% in the study population  --  it was never present in healthy, normal-weight controls.&lt;/p&gt;
&lt;p&gt;&quot;Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic,&quot; Froguel said in a prepared statement.&lt;/p&gt;
&lt;p&gt;But with further findings like these, it may be possible to identify such individuals through genetic testing, he said.&lt;/p&gt;
&lt;p&gt;If so, &quot;We can then offer them appropriate support and medical interventions, such as the option of weight-loss surgery, to improve their long-term health,&quot; Froguel declared.&lt;/p&gt;
&lt;p&gt;Although researchers speculate that one in 20 cases of obesity may have a genetic cause, the genetic component remains largely elusive.&lt;/p&gt;
&lt;p&gt;Even accounting for such a small fraction of cases, the newly discovered 16p11.2 variant would be the second most frequent known genetic cause of obesity, Froguel&apos;s group said.&lt;/p&gt;
&lt;p&gt;Extensive genome-wide association studies have linked numerous single nucleotide polymorphisms (SNPs) to obesity, but added all together they account for only a small fraction of the known heritable component, the researchers said.&lt;/p&gt;
&lt;p&gt;&quot;The &apos;common disease, common variant&apos; hypothesis is increasingly coming under challenge,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Their team first identified the genetic deletion in teen and adults with learning difficulties or delayed development.&lt;/p&gt;
&lt;p&gt;Because the 31 individuals who had the nearly identical deletions of at least 593 kilobases at chromosome 16p11.2 in one copy of their DNA all had a BMI of over 30 kg/m&lt;sup&gt;2&lt;/sup&gt;, the researchers decided to dig a little deeper.&lt;/p&gt;
&lt;p&gt;&quot;Cohorts with extreme phenotypes that include obesity may be enriched for rare but very potent risk variants,&quot; making them easier to discover, they wrote.&lt;/p&gt;
&lt;p&gt;So they undertook a case-control study among 312 patients at three centers in Britain and France who presented with congenital malformations, developmental delay, or both, in addition to obesity.&lt;/p&gt;
&lt;p&gt;The same deletions were seen in 2.9% of these individuals.&lt;/p&gt;
&lt;p&gt;The function of the missing genes are not well known, but some have previously been associated with delayed development, autism, and schizophrenia.&lt;/p&gt;
&lt;p&gt;Notably, though, the frequency of deletion of these genes in the obese case-control cohort was &quot;appreciably higher&quot; than the less than 1% seen in the autism and other studies that didn&apos;t include obesity as an inclusion criteria, the researchers said.&lt;/p&gt;
&lt;p&gt;A second independent survey of genetic data at eight cytogenetic centers in France, Switzerland, and Estonia turned up a 0.6% rate among 3,947 people with developmental delay, malformations, or both, but who were not selected for obesity (&lt;em&gt;P&lt;/em&gt;=0.00022 versus the cohort selected for obesity).&lt;/p&gt;
&lt;p&gt;Analysis of those with the missing genes revealed an age-dependent link to weight: All four teens and adults were obese. Children were often obese (four of 15) or overweight (two of 15). Children under 2 years all had normal weight.&lt;/p&gt;
&lt;p&gt;So to see whether the deletion was independent of neurodevelopmental problems, Froguel&apos;s group examined genome-wide association study data from general population cohorts totaling 11,856 individuals along with 2,772 from childhood obesity and adult morbid obesity case-control studies, 931 in an extreme early-onset obesity study, and 141 who had bariatric weight-loss surgery.&lt;/p&gt;
&lt;p&gt;All adult carriers of the deletion were obese with the exception of one who was apparently diabetic. Each of the seven children and adolescents who carried the variant had a BMI in the top 0.1% for their age and gender.&lt;/p&gt;
&lt;p&gt;None had any reported developmental or cognitive problems. Four had reported hyperphagia with excessive hunger and food intake.&lt;/p&gt;
&lt;p&gt;Altogether, the 16p11.2 deletions predicted 29.8-fold elevated risk of obesity (&lt;em&gt;P&lt;/em&gt;=0.00000058) and 43.0-fold elevated risk of morbid obesity (&lt;em&gt;P&lt;/em&gt;=0.000000064) compared with lean or normal weight.&lt;/p&gt;
&lt;p&gt;By extrapolation, the researchers extrapolated that about 0.4% of all morbidly obese cases are attributable to an inherited 16p11.2 deletion, with 0.3% arising from a de novo deletion in the same genetic region.&lt;/p&gt;
&lt;p&gt;&quot;Although they may be heterogeneous in nature, these deletions are highly likely to be the causal variants,&quot; they wrote.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by &quot;Le Conseil Regional Nord Pas de Calais/FEDER&quot; along with various governmental and industry supporters for the various component studies.&lt;/p&gt;&lt;p&gt;The researchers reported no financial conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_359"
                     title="Fish Oil May Prevent Psychotic Episodes (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/Psychiatry/Schizophrenia/tb/18242?impressionId=1265798703153"
                     
      &lt;p&gt;High-risk psychiatric patients were less likely to have psychotic episodes when they took daily doses of omega-3 (&amp;#969;-3) polyunsaturated fatty acids (PUFAs), according to results of a small, randomized clinical trial.&lt;/p&gt;
&lt;p&gt;Fewer than 5% of patients had psychotic episodes with &amp;#969;-3 PUFAs, versus more than 25% of patients given placebo (&lt;em&gt;P&lt;/em&gt;=0.007), investigators reported in the February &lt;em&gt;Archives of General Psychiatry&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The &amp;#969;-3 PUFAs, derived from fish among other sources, also reduced positive, negative, and general symptoms and improved functioning compared with placebo, the researchers found.&lt;/p&gt;
&lt;p&gt;&quot;The present trial strongly suggests that &amp;#969;-3 PUFAs may offer a viable prevention and treatment strategy with minimal associated risk in young people at ultra-high risk of psychosis, which should be further explored,&quot; G. Paul Amminger, MD, of the Medical University of Vienna in Austria, and co-authors concluded.&lt;/p&gt;
&lt;p&gt;Early treatment of schizophrenia and other psychotic conditions may lead to better outcomes, the researchers noted. Subclinical psychotic symptoms may predict psychotic disorder, and the propensity for psychosis in a particular population may influence the prevalence and incidence of psychotic disorders.&lt;/p&gt;
&lt;p&gt;Intervention in at-risk populations, therefore, may lead to even better outcomes, they asserted.&lt;/p&gt;
&lt;p&gt;Dysfunctional fatty acid metabolism has been proposed as a contributing factor in psychotic conditions, and several clinical trials have demonstrated beneficial effects of &amp;#969;-3 PUFA supplementation in patients with schizophrenia. Some studies, however, yielded negative results.&lt;/p&gt;
&lt;p&gt;Data from the schizophrenia studies, evidence of neuroprotective properties, and an absence of clinically relevant adverse effects make &amp;#969;-3 PUFAs &quot;an ideal candidate for indicated prevention in young people at risk of psychosis, in whom the use of antipsychotic medication is controversial, the authors wrote.&lt;/p&gt;
&lt;p&gt;To evaluate potential benefits of &amp;#969;-3 PUFAs in subclinical psychosis, investigators enrolled patients ages 13 to 25 who met criteria for one of three operationally-defined, high-risk groups: attenuated positive psychotic symptoms, transient psychosis, and genetic risk plus a decrease in functioning.&lt;/p&gt;
&lt;p&gt;&quot;These criteria comprise a combination of trait and state factors that identify people whose risk of becoming psychotic may approach 40% within a 12-month period,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;The study included 81 patients, who were randomized to 1.2 g/d &amp;#969;-3 PUFA or matching placebo for 12 weeks, plus 12-months of follow-up.&lt;/p&gt;
&lt;p&gt;The authors reported that 76 patients (38 in each group) completed the 12-week intervention phase and 67 completed the 12-month follow-up. The primary outcome was conversion to a psychotic episode, defined by the Positive and Negative Syndrome Scale (PANSS) and sustained for one week.&lt;/p&gt;
&lt;p&gt;At 12 months, two of 41 patients assigned to &amp;#969;-3 PUFA therapy (4.9%) converted to psychotic episodes, compared with 11 of 40 (27.5%) in the placebo group.&lt;/p&gt;
&lt;p&gt;The &amp;#969;-3 group also had significantly lower PANSS positive, negative, general, and total scores at 12 weeks, six months, and 12 months (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;=0.01). Patients in the &amp;#969;-3 group also had significantly better functioning (&lt;em&gt;P&lt;/em&gt;=0.002).&lt;/p&gt;
&lt;p&gt;Calculation of number needed to treat (NNT) showed that four at-risk patients would have to be treated to prevent one psychotic episode during one year, which the authors said is comparable to the NNT from trials of antipsychotic medications.&lt;/p&gt;
&lt;p&gt;The authors noted several limitations, including the relatively small size of the study and the fact that this was a highly selected population, so the results cannot be generalized.&lt;/p&gt;
&lt;p&gt;In addition, they pointed out that efficacy beyond the 12 month study period is unknown and it is possible that the transition to a first episode of psychosis may have been delayed rather than prevented.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the Stanley Medical Research Institute.&lt;/p&gt;&lt;p&gt;The authors reported no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_356"
                     title="Exercise Builds Brain Volume in Schizophrenia (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/Psychiatry/Schizophrenia/tb/18236?impressionId=1265798703153"
                     
      &lt;p&gt;Three months of aerobic exercise significantly increased the volume of the hippocampus in patients with chronic schizophrenia, researchers said.&lt;/p&gt;
&lt;p&gt;The increase was accompanied by &quot;modest&quot; increases in short-term memory and markers of neuron production, according to Frank-Gerald Pajonk, MD, of Dr K. Fontheim&apos;s Hospital for Mental Health in Liebenburg, Germany, and colleagues.&lt;/p&gt;
&lt;p&gt;But it&apos;s too early to say whether incorporating aerobic exercise into treatment programs might reduce the disability associated with schizophrenia, the researchers said in the February&lt;em&gt; Archives of General Psychiatry&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Among schizophrenics, the hippocampus, which plays important roles in memory and spatial navigation, is known to be reduced in volume, Pajonk and colleagues noted.&lt;/p&gt;
&lt;p&gt;Unlike other forms of psychosis, they added in the journal, schizophrenia is characterized by persistent disability, perhaps because the production of new neurons is impaired.&lt;/p&gt;
&lt;p&gt;As well, they noted, in healthy humans it has been shown that exercise stimulates the production of new neurons.&lt;/p&gt;
&lt;p&gt;For those reasons, they speculated that aerobic exercise might increase the volume of the hippocampus in people with chronic schizophrenia, perhaps leading to clinical benefits.&lt;/p&gt;
&lt;p&gt;To test the idea, they enrolled 24 schizophrenia patients and eight healthy controls.&lt;/p&gt;
&lt;p&gt;Thirteen of the patients, selected randomly, were assigned to a three-month program of aerobic exercise  --  cycling three times a week for 30 minutes. The controls also took part in the cycling program.&lt;/p&gt;
&lt;p&gt;The remaining patients were assigned to play table soccer, again for 30 minutes three times a week.&lt;/p&gt;
&lt;p&gt;The primary endpoint was the change in hippocampal volume, assessed by magnetic resonance imaging, but the researchers also looked at changes in schizophrenia symptom scores, memory, and the ratio of N-acetylaspartate to creatine in the hippocampus. The latter is a regarded as a marker of neuron production.&lt;/p&gt;
&lt;p&gt;They found: &lt;ul&gt; &lt;li&gt;Compared to baseline, hippocampal volume increased 12% in the exercise group and 16% in the controls, changes that were significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001.&lt;/li&gt; &lt;li&gt;On the other hand, there was a nonsignificant 1% drop in volume among patients who did not take exercise.&lt;/li&gt; &lt;li&gt;The changes in hippocampal volume in the exercise group were significantly correlated (at r=0.71 and &lt;em&gt;P&lt;/em&gt;=0.003) with better aerobic fitness, as measured by change in maximum oxygen consumption.&lt;/li&gt; &lt;li&gt;Among patients in the exercise group, change in hippocampal volume was associated with a 35% increase in the N-acetylaspartate to creatine ratio, which was significant (in a post-hoc analysis) at &lt;em&gt;P&lt;/em&gt;=0.04. There was no significant change in the healthy controls.&lt;/li&gt; &lt;li&gt;And short-term memory improvements among the patients were correlated (at r=0.51 and &lt;em&gt;P&lt;/em&gt;&amp;lt;0.05) with changes in hippocampal volume.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The change in hippocampal volume was the &quot;most robust&quot; of the findings, Pajonk and colleagues said, and is roughly comparable with what is seen in other subcortical structures when schizophrenia patients switch from typical to atypical medications.&lt;/p&gt;
&lt;p&gt;The study was limited by its small size, they said, and the volunteers were selected for their willingness to take part in three months of an exercise program.&lt;/p&gt;
&lt;p&gt;As well, patients had to have chronic disease and be on stable medication programs, they said.&lt;/p&gt;
&lt;p&gt;They also noted that while the main finding was robust, the statistical significance of the secondary results would not have survived a correction for multiple testing.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The researchers did not report any industrial support for the study. Pajonk reported financial links with AstraZeneca, Eli Lilly, Janssen, Novartis, Wyeth, Bristol-Myers Squibb, Pfizer, Sanofi-Synth&amp;#233;labo, and Merz.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_301"
                     title="Tight Glucose Control Fails in Septic Shock (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/CriticalCare/Sepsis/tb/18160?impressionId=1265798703153"
                     
      Septic shock patients treated with a corticosteroid get no survival advantage from tight glucose control or addition of a second corticosteroid to provide more mineralocorticoid activity, according to results of a randomized trial.&lt;br&gt;
&lt;br&gt;Aiming for normoglycemia at 80 to 110 mg/dL rather than the standard 150 mg/dL had no impact on inhospital mortality rates (45.9% versus 42.9%, &lt;em&gt;P&lt;/em&gt;=0.50), Djillali Annane, MD, of H&amp;#244;pital Raymond Poincar&amp;#233; in Garches, France, and colleagues found.&lt;br&gt;
&lt;br&gt;Inhospital mortality was likewise similar whether patients got hydrocortisone (Solu-Cortef) alone or with the addition of fludrocortisone ([Florinef] 42.9% versus 45.8%, &lt;em&gt;P&lt;/em&gt;=0.50), they reported in the Jan. 27 issue of the &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;This aggressive treatment strategy should not be routine, the researchers recommended.&lt;/p&gt;
&lt;p&gt;These findings largely match the general lack of benefit seen with tight glycemic control in recent studies with ICU patients overall.&lt;/p&gt;
&lt;p&gt;The prematurely terminated &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/SCCM/5096&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/SCCM/5096&quot; target=&quot;_blank&quot;&gt;European Glucontrol Trial&lt;/a&gt; found no mortality benefit but a seven-fold higher risk of hypoglycemia with an 80 to 110 mg/dL target in the ICU.&lt;/p&gt;
&lt;p&gt;In the &lt;a href=&quot;http://www.medpagetoday.com/CriticalCare/Intensivists/13397&quot; mce_href=&quot;http://www.medpagetoday.com/CriticalCare/Intensivists/13397&quot; target=&quot;_blank&quot;&gt;NICE-SUGAR&lt;/a&gt; study, 90-day mortality was actually higher in the tight glucose control group (27.9% versus 24.9%, &lt;em&gt;P&lt;/em&gt;=0.02), although there was a trend for benefit in patients who got corticosteroids (&lt;em&gt;P&lt;/em&gt;=0.06).&lt;/p&gt;
&lt;p&gt;Glucose targets are being re-evaluated across medicine as the &quot;lower is better&quot; paradigm has had a safety asterisk added everywhere from diabetes care to the ICU, noted Richard Bergenstal, MD, American Diabetes Association president for medicine and science.&lt;/p&gt;
&lt;p&gt;&quot;All of a sudden it&apos;s becoming more than a single number,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;Now be it inpatient or outpatient, we&apos;re realizing that ... you have to do it while you&apos;re minimizing hypoglycemia.&quot;&lt;/p&gt;
&lt;p&gt;A more nuanced and &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; target=&quot;_blank&quot;&gt;individualized&lt;/a&gt; strategy is prudent, Bergenstal agreed.&lt;/p&gt;
&lt;p&gt;The current clinical uncertainty underscores the need for large-scale international cooperation to get adequately powered trials, according to an accompanying editorial.&lt;/p&gt;
&lt;p&gt;In it, Greet Van den Berghe, MD, PhD, of the Catholic University of Leuven, Belgium, cautioned that Annane&apos;s Corticosteroids and Intensive Insulin Therapy for Septic Shock (COIITSS) study was grossly underpowered.&lt;/p&gt;
&lt;p&gt;The initial studies that led to rapid adoption of intensive insulin therapy in ICUs around the world had suggested an absolute reduction in mortality of only 3%, whereas the COIITSS study projected a 12.5% absolute benefit.&lt;/p&gt;
&lt;p&gt;More importantly, the study achieved mean glucose levels of only between 120 and 130 mg/dL in the intervention group for whom the aim was 80 to 110 mg/dL, which resulted in considerable overlap with the standard care group for whom mean levels were about 145 mg/dL.&lt;/p&gt;
&lt;p&gt;This could account for the lack of difference in outcome, Van den Berghe said.&lt;/p&gt;
&lt;p&gt;But the intensive insulin group did have &quot;markedly&quot; lower blood glucose levels for the duration of their ICU stay and spent more time in the 80 to 110 mg/dL range compared with the standard care group (both &lt;em&gt;P&lt;/em&gt;&amp;lt;0.00001), the researchers noted.&lt;/p&gt;
&lt;p&gt;Because corticosteroids further aggravate the &quot;diabetes of injury&quot; seen with septic shock, Annane&apos;s group undertook a multicenter trial of 509 adults treated for septic shock with multiple organ dysfunction over a three year period at 11 ICUs in France.&lt;/p&gt;
&lt;p&gt;Patients were randomly assigned to tight glucose control using continuous intravenous insulin infusion to target a glucose level of 80 to 110 mg/dL or conventional insulin therapy targeted to guidelines-recommended 150 mg/dL or under. They were additionally randomized to receive hydrocortisone alone (50-mg bolus every six hours) or in combination with fludrocortisone (50-&amp;#956;g tablets once daily) for seven days.&lt;/p&gt;
&lt;p&gt;Aside from the lack of inhospital mortality advantage, tight glucose control also failed to produce a benefit for the following secondary endpoints: &lt;ul&gt; &lt;li&gt;Overall survival (hazard ratio 1.04, &lt;em&gt;P&lt;/em&gt;=0.78) &lt;/li&gt; &lt;li&gt; ICU length of stay for survivors (median 10 versus nine days, &lt;em&gt;P&lt;/em&gt;=0.68)&lt;/li&gt; &lt;li&gt;Duration of hospital stay overall (24 versus 22 days, &lt;em&gt;P&lt;/em&gt;=0.87)&lt;/li&gt; &lt;li&gt;Median vasopressor-free days (four for both, P=0.58)&lt;/li&gt; &lt;li&gt;Median mechanical ventilation-free days (10 versus 13, &lt;em&gt;P&lt;/em&gt;=0.51)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Nor was there evidence for interaction with fludrocortisone in the primary endpoint (relative risk 0.89 versus 0.91 hydrocortisone alone, &lt;em&gt;P&lt;/em&gt;=0.31) or benefit in any other endpoint.&lt;/p&gt;
&lt;p&gt;The one effect of intensive insulin appeared to be an increase in episodes of severe hypoglycemia, defined by glucose falling below 40 mg/dL (mean 0.29 versus 0.14 episodes per patient, &lt;em&gt;P&lt;/em&gt;=0.003).&lt;/p&gt;
&lt;p&gt;However, having hypoglycemia did not increase the risk of death in intervention group patients compared with controls (45.2% versus 50%).&lt;/p&gt;
&lt;p&gt;The researchers cautioned that the study did not rule out a benefit from some degree of glucose control compared with none.&lt;/p&gt;
&lt;p&gt;They also noted that healthcare providers were not blinded to administration of fludrocortisone, for which no placebo was available.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by the Assistance Publique&amp;#8211;H&amp;#244;pitaux de Paris. The researchers reported no conflicts of interest.&lt;/p&gt;&lt;p&gt;Van den Berghe, through the Catholic University of Leuven, reported receiving structural research financing from the Methusalem program, funded by the Flemish government.&lt;/p&gt;&lt;p&gt;Bergenstal reported receiving research funding and serving on advisory boards for various pharmaceutical companies related to novel diabetes drugs but without any personal financial compensation.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_291"
                     title="Obese Kids at Risk for Adult CVD (CME/CE)"
                     score="0.001"
                     href="http://www.medpagetoday.com/Endocrinology/MetabolicSyndrome/tb/18153?impressionId=1265798703153"
                     
      Obesity in children as young as 7 years old may put them at higher risk of heart disease and stroke later in life, even if they lack other cardiovascular risk factors such as high blood pressure, a new study found.&lt;br&gt;
&lt;br&gt;Obese children had higher levels of biomarkers for inflammation and prothrombosis than thin children. These included 10 times higher concentrations of high sensitivity C-reactive protein, a marker associated with increased risk of developing heart disease, cardiovascular disease, or other processes involving inflammation (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01), according to an online report published Jan. 26 in the &lt;em&gt;Journal of Clinical Endocrinology and Metabolism&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;Fibrinogen, interleukin-6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1), other markers associated with inflammation and elevated blood clotting risk, were also elevated in obese children (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;These observations reflect the unhealthy status of many youth at risk for adult cardiovascular disease in our catchment area in the southeastern U.S.,&quot; Nelly Mauras, MD, of Nemours Children&apos;s Clinic in Jacksonville, Fla., and colleagues wrote.&lt;/p&gt;
&lt;p&gt;The number of overweight children in the U.S. has tripled in the last 30 years, and more than 17% of children between the ages of 6 and 19 are overweight, according to the authors.&lt;/p&gt;
&lt;p&gt;Overweight children often develop metabolic syndrome, a collection of findings that includes abdominal obesity, elevated triglyceride and decreased HDL concentrations, hypertension, and impaired glucose tolerance. These put the youngsters at risk for early adult cardiovascular disease. Yet the exact definition of metabolic syndrome is a matter of ongoing debate.&lt;/p&gt;
&lt;p&gt;While children are typically considered to be at low risk of tissue damage if they show no signs of carbohydrate intolerance, hypertension, and dyslipidemia, Mauras and colleagues theorized that obese children without other risk factors for metabolic syndrome could still be at risk for later cardiovascular disease.&lt;/p&gt;
&lt;p&gt;To test this, they compared markers for inflammation and prothrombosis in 115 obese children and 88 lean children between the ages of 7 and 18 years. The study was conducted at Wolfson Children&apos;s Hospital, in Jacksonville, Fla.&lt;/p&gt;
&lt;p&gt;&quot;Children with obesity show a marked increase in the concentrations of hsCRP, 351 fibrinogen, IL-6 and PAI-1, reflective of a proinflammatory and prothrombotic state, even before the comorbidities of the Metabolic Syndrome are present, and even before the onset of puberty,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&quot;These data support the need for more aggressive interventions in very young children with obesity regardless of the absence of associated comorbidities.&quot;&lt;/p&gt;
&lt;p&gt;They also found that elevated levels of hsCRP and fibrinogen correlated with a wider waist circumference (R=0.73 and 0.40, respectively) and the percent of fat mass (r= 0.76 and 0.47) (&lt;em&gt;P&lt;/em&gt;=0.0001). Prepubertal obese children were taller than their lean counterparts (&lt;em&gt;P&lt;/em&gt;=0.005) and had higher systolic blood pressure.&lt;/p&gt;
&lt;p&gt;The authors noted that their study did not address whether the abnormalities they found are reversible with early therapeutic interventions.&lt;/p&gt;
&lt;p&gt;&quot;Weight reduction (or weight maintenance in many growing children) remains the cornerstone of any intervention in childhood obesity,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&quot;However, further longitudinal studies adding pharmacological interventions, in addition to lifestyle changes, will soon offer much needed insight as to whether a decrease in the proinflammatory and prothrombotic state will improve long-term cardiovascular risk of obese children, even in preadolescence and before the development of the Metabolic Syndrome.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The authors reported no sources of funding for the study and no financial conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>