<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_3248"
                     title="Increased Cardiac Events Seen With Sibutramine (CME/CE)"
                     score="0.014"
                     href="http://www.medpagetoday.com/Cardiology/MyocardialInfarction/tb/22008?impressionId=1283456793109"
                     
      &lt;p&gt;Overweight patients with cardiovascular risks who took the weight-loss drug sibutramine (Meridia) had a 16% increased likelihood of experiencing a cardiac event, a large randomized trial found.&lt;/p&gt;
&lt;p&gt;The overall hazard ratio for a fatal or nonfatal cardiovascular event was 1.16 (95% CI 1.03 to 1.31, &lt;em&gt;P&lt;/em&gt;=0.02) among patients receiving sibutramine compared with those receiving placebo, according to W. Philip T. James, MD, of the London School of Hygiene and Tropical Medicine, and colleagues.&lt;/p&gt;
&lt;p&gt;Specifically, the hazard ratio for nonfatal myocardial infarction was 1.28 (95% CI 1.04 to 1.57, &lt;em&gt;P&lt;/em&gt;=0.02), and the hazard ratio for nonfatal stroke was 1.36 (95% CI 1.04 to 1.77, &lt;em&gt;P&lt;/em&gt;=0.03), the researchers reported in the Sept. 1 &lt;em&gt;New England Journal of Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;A &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/17147&quot; mce_href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/17147&quot; target=&quot;_blank&quot;&gt;preliminary analysis&lt;/a&gt;&lt;a target=&quot;_blank&quot;&gt; &lt;/a&gt;of data from the SCOUT (Sibutramine Cardiovascular Outcomes) trial previously suggested this increased risk, and the FDA required stronger &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/18088&quot; mce_href=&quot;http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/18088&quot; target=&quot;_blank&quot;&gt;cautionary language&lt;/a&gt; in the drug&apos;s labeling.&lt;/p&gt;
&lt;p&gt;The final publication has now confirmed it, with James and colleagues stating, &quot;On the basis of these results, sibutramine should continue to be excluded from use in patients with preexisting cardiovascular disease.&quot;&lt;/p&gt;
&lt;p&gt;Sibutramine is a norepinephrine and serotonin reuptake inhibitor that has sympathomimetic effects and therefore can increase blood pressure and pulse rate. Because even small increases in blood pressure and pulse rate are associated with an increased likelihood of cardiovascular events, the SCOUT investigators wanted to determine the drug&apos;s long-term cardiovascular risk.&lt;/p&gt;
&lt;p&gt;They enrolled 9,804 obese or overweight patients who were at least 55 years old. All participants had a history of cardiovascular disease and/or type 2 diabetes.&lt;/p&gt;
&lt;p&gt;The study consisted of a six-week lead-in period in which all patients received 10 mg/day of sibutramine, after which they were randomized to the active treatment or placebo.&lt;/p&gt;
&lt;p&gt;Mean duration of treatment was 3.4 years, and slightly more than 40% of patients in both groups discontinued treatment.&lt;/p&gt;
&lt;p&gt;All patients also participated in individualized diet and exercise programs designed for cardioprotection, and blood pressure decreased in both groups during the lead-in phase.&lt;/p&gt;
&lt;p&gt;However, after randomization the sibutramine group had small but consistent increases in blood pressure and resting pulse rate.&lt;/p&gt;
&lt;p&gt;While there were increases in the nonfatal events, there was no between-group difference for cardiovascular death (HR 0.99, 95% CI 0.82 to 1.19, &lt;em&gt;P&lt;/em&gt;=0.90) or death from any cause (HR 1.04, 95% CI 0.91 to 1.20, &lt;em&gt;P&lt;/em&gt;=0.54).&lt;/p&gt;
&lt;p&gt;The investigators noted that fewer than half of the events they had expected at the outset of the trial occurred during its six-year overall duration, and that during that time the incidence of cardiovascular disease decreased in most of Europe and Australia, where most of the study centers were located.&lt;/p&gt;
&lt;p&gt;They also pointed out that the study was limited by the lack of a true placebo group, the inclusion of only high-risk patients, and the longer-than-recommended time of treatment (one to two years).&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, Gregory D. Curfman, MD, executive editor of &lt;em&gt;NEJM, &lt;/em&gt;and colleagues commented that the cardiovascular risk findings of SCOUT need to be considered in light of the potential clinical benefit of the weight loss seen among those on sibutramine.&lt;/p&gt;
&lt;p&gt;Patients on the drug lost 4.3 kg at one year, but regained about 0.5 kg thereafter, for a net loss of less than 4 kg from a baseline average weight of 96 kg.&lt;/p&gt;
&lt;p&gt;In January 2010, after the preliminary analysis of the SCOUT data, the European Medicines Agency suspended marketing authorizations for sibutramine-containing medications throughout the European Union.&lt;/p&gt;
&lt;p&gt;On Sept. 15, an advisory committee of the FDA plans to meet to decide whether additional regulatory action should be taken here as well.&lt;/p&gt;
&lt;p&gt;Curfman and colleagues concluded, &quot;Given that sibutramine has minimal efficacy for weight loss, no apparent benefit for clinical outcomes, a worrisome cardiovascular risk profile, and a plausible mechanism to explain the cardiovascular risk, it is difficult to discern a credible rationale for keeping this medication on the market.&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 study was funded by Abbott Laboratories.&lt;/p&gt;&lt;p&gt;Several of the SCOUT investigators reported serving on advisory boards and receiving fees from multiple pharmaceutical companies, including Abbott, sanofi-aventis, Merck, Johnson &amp;amp; Johnson, Novo Nordisk, GlaxoSmithKline, and Boehringer Ingelheim.&lt;/p&gt;&lt;p&gt;In addition, three of the investigtors were full-time employees of Abbott and had equity interest in the company.&lt;/p&gt;&lt;p&gt;Aside from Curfman&apos;s position with &lt;em&gt;NEJM&lt;/em&gt;, the editorialists had no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3235"
                     title="ESC: New Anticoagulants Create Buzz"
                     score="0.014"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/21988?impressionId=1283456793109"
                     
      &lt;p&gt;STOCKHOLM  --  After years of waiting for an alternative to warfarin (Coumadin), there are now three wending their way through the regulatory process. In this exclusive InFocus video report we review each of these new agents.&lt;/p&gt;
&lt;p&gt;Two factor Xa inhibitors  --  apixiban and rivaroxaban  --  along with the direct thrombin inhibitor, dabigatran, are competing to be the first warfarin alternatives to gain FDA approval and that is good news according to Fausto Pinto, MD, PhD, the program chair at this year&apos;s European Society of Cardiology congress, where the new agents were featured in a number of sessions.&lt;/p&gt;
&lt;p&gt;Ralph L. Sacco, MD, president of the American Heart Association agreed that the news was good, but noted that, as the agents come to market, developing new guidelines for their use will be a critical task for the AHA and the ESC.&lt;/p&gt;
&lt;p&gt;Pinto and Sacco discussed the potential benefits  --  and challenges  --  of the new agents with &lt;em&gt;MedPage Today&lt;/em&gt; executive editor Peggy Peck.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_3223"
                     title="ESC: EINSTEIN DVT Data Positive for Factor Xa Inhibitor (CME/CE)"
                     score="0.014"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/21976?impressionId=1283456793109"
                     
      &lt;p&gt;STOCKHOLM  --  An investigational oral anticoagulant appears to be as effective and safe as treatment with enoxaparin (Lovenox) plus warfarin (Coumadin) to prevent recurrent deep vein thrombosis, researchers reported.&lt;/p&gt;
&lt;p&gt;In a study conducted in the Netherlands among more than 3,400 older adults with symptomatic DVT, 2.1% (n=36) of the rivaroxaban patients experienced recurrent DVT versus 3.0% (n=51) of controls  --  a difference that was statistically significant for noninferiority (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001 one-sided)  --  said Harry R. Buller, MD, of the Academic Medical Center in Amsterdam.&lt;/p&gt;
&lt;p&gt;Moreover, the net clinical benefit  --  the primary efficacy endpoint of symptomatic DVT (a composite of recurrent DVT, nonfatal pulmonary embolism, or fatal PE) plus major bleeding  --  also favored rivaroxaban, HR 0.67 (95% confidence interval 0.47 to 0.95), Buller reported at the European Society of Cardiology Congress here.&lt;/p&gt;
&lt;p&gt;The safety endpoint  --  a combination of major and minor clinically-relevant nonmajor bleeding  --  was the same in both arms, 8.1% (&lt;em&gt;P&lt;/em&gt;=0.77).&lt;/p&gt;
&lt;p&gt;Buller said there was &quot;no evidence of liver toxicity and no cardiovascular signal.&quot; Liver toxicity has been a concern with factor Xa inhibitors because the first agent to reach clinical trials, ximelagatran, failed to receive FDA approval due to liver toxicity.&lt;/p&gt;
&lt;p&gt;The appeal of rivaroxaban is its simplicity  --  a pill that doesn&apos;t require a special diet or blood tests to confirm clotting time, both of which are required with warfarin, said Clyde Yancy, MD, of Baylor Medical Center in Dallas.&lt;/p&gt;
&lt;p&gt;Yancy told &lt;em&gt;MedPage Today &lt;/em&gt;that it is the simplicity of the new agents that has him concerned because there is a possibility that they will be used universally &quot;for indications that have not been studied simply because they are easier than warfarin.&quot;&lt;/p&gt;
&lt;p&gt;Elliot Antman, MD, a senior investigator with the TIMI group at Brigham and Women&apos;s Hospital and professor of medicine at Harvard Medical School, said the EINSTEIN DVT results were encouraging, but he noted that there is a concern with all of the new anticoagulants, &quot;how to reverse the anticoagulant effect?&quot;&lt;/p&gt;
&lt;p&gt;Vitamin K is an antidote for warfarin, but there is at present no antidote for drugs like rivaroxaban and other new oral anticoagulants, he said.&lt;/p&gt;
&lt;p&gt;Antman used a scenario to illustrate his point: &quot;Suppose you have patient on rivaroxaban for DVT, and that patient develops acute cholecystitis, and he or she needs immediate gall bladder surgery? What do you do?&quot;&lt;/p&gt;
&lt;p&gt;The possible options would be fresh frozen plasma or wait until the drug clears, &quot;but that might be 12, 24, 36 hours.&quot;&lt;/p&gt;
&lt;p&gt;He said that every company that is developing an oral anticoagulant is looking at ways to reverse the drugs, including Daiichi Sankyo, which is developing edoxaban, an oral factor Xa inhibitor. Antman is the principal investigator of phase III trial of edoxaban.&lt;/p&gt;
&lt;p&gt;But the concern about reversibility &quot;should not dampen the enthusiasm for these agents,&quot; Antman said.&lt;/p&gt;
&lt;p&gt;The EINSTEIN DVT trial randomized 1,731 patients to rivaroxaban 15 mg twice daily for three weeks followed by 20 mg maintenance dose. Patients were treated for three, six, or 12 months, at the discretion of the investigator.&lt;/p&gt;
&lt;p&gt;The trial design did not allow for identification of an ideal treatment duration said discussant Harald Darius, MD, of Vivantes Klinikum Neuk&amp;#246;lln Hospital in Berlin. Darius said it looked like treatment wasn&apos;t needed after six months, but it wasn&apos;t clear.&lt;/p&gt;
&lt;p&gt;Another 1,718 patients were enrolled in the control arm, which received enoxaparin 1 mg/kg/bid &amp;#8805;5 days, followed by warfarin.&lt;/p&gt;
&lt;p&gt;Patients were in their mid-50s and more than half were men.&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 Bayer AG.&lt;/p&gt;&lt;p&gt;B&amp;#252;ller disclosed grants for clinical research from: Bayer HealthCare Pharmaceuticals, Daiichi Sankyo, Merck Sharpe &amp;amp; Dohme, Pfizer, and sanofi-aventis. He also served as a consultant for Bayer HealthCare Pharmaceuticals, Daiichi Sankyo, Merck Sharpe &amp;amp; Dohme, Pfizer, and sanofi-aventis.&lt;/p&gt;&lt;p&gt;Darius said he had no relevant disclosures.&lt;/p&gt;&lt;p&gt;Yancy said he had no conflicts.&lt;/p&gt;&lt;p&gt;Antman is a principal investigator of ENGAGE AF-TIMI 48 a phase III trial of the oral factor Xa inhibitor edoxaban which is being developed by Daiichi Sankyo.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3191"
                     title="ESC: It&apos;s Not Butter and It&apos;s Not Better (CME/CE)"
                     score="0.014"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/21921?impressionId=1283456793109"
                     
      STOCKHOLM  --  Adding margarine enriched with omega-3 fatty acids as a dietary intervention did not prevent second heart attacks in older men and women at risk for worsening heart disease, researchers said here.&lt;br&gt;
&lt;br&gt;The study results are doubly disappointing since the margarine intervention did initially reduce events, but by 30 months the evidence of that benefit had disappeared, said Daan Kromhout, MPH, PhD, of Wageningen University in the Netherlands.&lt;br&gt;
&lt;br&gt;After more than 40 months, consumption of the omega-3 fatty acid fortified margarines &quot;had no effect on the rate of major cardiovascular events,&quot; he reported at a Hot Line session today at the European Society of Cardiology meeting. The findings were simultaneously published online by the &lt;em&gt;New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;The ALPHA-OMEGA trial randomized 4,837 MI survivors, 60 to 80 years old, to margarine supplemented with a combination of eicosapentaenoic acid and docosahexaenoic acid (EPA and DHA), or with 2 grams of the plant-derived fatty acid alpha-linolenic acid (ALA), or a third supplemented with all three versus a placebo margarine.&lt;/p&gt;
&lt;p&gt;The primary endpoint was the combined rate of fatal and non-fatal cardiovascular events and cardiac interventions.&lt;/p&gt;
&lt;p&gt;Neither EPA-DHA nor ALA reduced this endpoint, the researchers reported (hazard ratio with EPA-DHA, 1.01; 95% confidence interval 0.87 to 1.17, &lt;em&gt;P &lt;/em&gt;=0.93).&lt;/p&gt;
&lt;p&gt;A prespecified subgroup analysis in women found that use of the ALA-fortified margarine reduced the rate of cardiovascular events compared with placebo or with the EPA-DHA margarine, but the difference failed to reach statistical significance (HR 0.73, 95% CI 0.51 to 1.03, &lt;em&gt;P&lt;/em&gt;=0.07).&lt;/p&gt;
&lt;p&gt;Alfred Bove, MD, of Temple University in Philadelphia, said the findings surprised him &quot;because most of the data on omega-3 fatty acids come from epidemiologic studies and those were positive.&quot;&lt;/p&gt;
&lt;p&gt;He likened the situation to hormone therapy, which had been widely recommended to reduce cardiovascular risk in postmenopausal women based on data from epidemiologic studies.&lt;/p&gt;
&lt;p&gt;That hypothesis was initially questioned when a randomized controlled trial (Estrogen/Progestin Replacement Study [HERS]) linked hormones to increased risk of events. The HERS finding was confirmed in the landmark Women&apos;s Health Initiative trial in which ischemic events were more common among women randomized to estrogen/progestin.&lt;/p&gt;
&lt;p&gt;R. Scott Wright, MD, of the Mayo Clinic in Rochester, Minn., told &lt;em&gt;MedPage Today&lt;/em&gt; that the trial design was faulty, in that margarine was a bad choice of vehicle for omega-3 fatty acids.&lt;/p&gt;
&lt;p&gt;&quot;It needs to be combined with another food  --  bread,&quot; he said. &quot;So this not a good option for Americans because it would mean eating more bread, which is likely to lead to weight gain and bread is high in sodium, so blood pressure would be a factor.&quot;&lt;/p&gt;
&lt;p&gt;Wright noted that the ALPHA-OMEGA study did not include information on weight or blood pressure, so he considered the findings at best incomplete.&lt;/p&gt;
&lt;p&gt;All of the patients received &quot;state-of-the-art antihypertensive, antithrombotic, and lipid-modifying therapy,&quot; according to Kromhout and colleagues, in addition to margarine, and it may have been that optimal therapy that limited the potential for an omega-3 benefit.&lt;/p&gt;
&lt;p&gt;Statin therapy, along with other improvements in cardiovascular care, means &quot;a beneficial effect of low doses of EPA-DHA is difficult to prove,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Wright said he wasn&apos;t persuaded by that explanation since, even after optimal therapy, there is about a 30% residual risk. &quot;There is plenty of room to show a benefit,&quot; he declared.&lt;/p&gt;
&lt;p&gt;Most of the patients in ALPHA-OMEGA were men (78%) and 24% were obese, but they differed from the typical high-risk American in at least one way: at baseline they consumed about three times more fish than does the typical American, a median of 15 grams a day.&lt;/p&gt;
&lt;p&gt;According to a report from the Environmental Protection Agency, average fish consumption in the U.S. works out to 4.58 &amp;#177; 0.42 grams a day.&lt;/p&gt;
&lt;p&gt;The authors conducted a post hoc exploratory analysis in patients with diabetes, finding significant reductions in events among patients in the EPA-DHA group. But the authors noted that &quot;[the] results with respect to patients with diabetes are only hypothesis-generating and do not permit definitive conclusions to be drawn.&quot;&lt;/p&gt;
&lt;p&gt;Bove, a former president of the American College of Cardiology, added that the results from the subset analysis in diabetics was reassuring, since patients with diabetes and elevated triglycerides are the patients that &quot;we have believed would be most likely to benefit&quot; from omega-3 fatty acids.&lt;/p&gt;
&lt;p&gt;The margarines used in the trial were supplied by Unilever, an international maker of food and consumer goods, and included the well-known &quot;I Can&apos;t Believe It&apos;s Not Butter,&quot; which contains 420 mg of ALA per serving.&lt;/p&gt;

&lt;p&gt;In a statement released after the ALPHA-OMEGA trial findings were presented, Unilever said the &quot;study outcome for EPA and DHA is surprising considering the weight of evidence published to date. This could be the result of methodological issues such as the relatively low daily dosage compared with previous studies or the fact that in this study serious cardiovascular events were much lower than in studies performed in the past. This is probably due to extensive drug treatment that is nowadays applied. The finding needs further study, but given the totality of evidence does not immediately impact the current advice on fish and fish oil consumption for prevention of cardiovascular disease.&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 trial was supported by the Netherlands Heart Foundation, the National Institutes of Health, and Unilever.&lt;/p&gt;&lt;p&gt;Kromhout reported that his institution received grant support form Unilever to cover distribution of the trial margarines to patients. His institution also received a grant from the Product Board for Margarine Fats and Oils to support research on polyunsaturated fats and cardiovascular diseases done by a PhD student.&lt;/p&gt;&lt;p&gt;Bove said he had no financial conflicts.&lt;/p&gt;&lt;p&gt;Wright said he consults for Roche and Genentech and conducts trial work for 3M/Littman.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3174"
                     title="Diabetes, Insulin Resistance Linked to Alzheimer&apos;s (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/Neurology/AlzheimersDisease/tb/21902?impressionId=1283456793109"
                     
      Insulin resistance and type 2 diabetes may contribute to the development of one type of brain plaque linked to Alzheimer&apos;s disease, according to an autopsy study.&lt;br&gt;
&lt;br&gt;An analysis of autopsy samples from 135 Japanese men and women found that high insulin and glucose levels appeared to accelerate the formation of neuritic plaques, especially among those carrying a high-risk gene for Alzheimer&apos;s, Kensuke Sasaki, MD, PhD, of Kyushu University in Fukuoka City, Japan, and colleagues, reported.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;The association of neuritic plaques with higher levels of two-hour post-load plasma glucose, fasting insulin, and insulin resistance measured in the decade before death was found to be independent of other risk factors like age, blood pressure, smoking, and cerebrovascular disease, Sasaki and co-authors wrote in the Aug. 25 issue of &lt;em&gt;Neurology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Thus, &quot;adequate control of diabetes might contribute to a strategy for the prevention of Alzheimer&apos;s disease,&quot; they concluded.&lt;/p&gt;
&lt;p&gt;Although these findings strengthen evidence for a causal link with dementia, an accompanying editorial by Jos&amp;#233; A. Luchsinger, MD, MPH, of Columbia University Medical Center and School of Public Health in New York City, cautioned that alternative explanations must be considered.&lt;/p&gt;
&lt;p&gt;For example, Luchsinger noted, the relatively small sample size selected from a much larger pool of participants who did not have an autopsy may have led to selection bias or to chance findings.&lt;/p&gt;
&lt;p&gt;Reverse causality was also a possibility since brain pathology and metabolic changes may precede dementia diagnosis by decades and diabetes and insulin resistance could result from or correlate with Alzheimer&apos;s, he added.&lt;/p&gt;
&lt;p&gt;On the assumption that the association may be causal, though, several randomized trials are already testing insulin sensitizers in older adults or those with mild cognitive impairment to see if the strategy has an effect on cognition.&lt;/p&gt;
&lt;p&gt;&quot;This is urgent considering that over half the U.S. population in the age group most at risk for cognitive impairment has prediabetes or type 2 diabetes, preceded or accompanied by insulin resistance and hyperinsulinemia,&quot; Luchsinger concluded in the editorial.&lt;/p&gt;
&lt;p&gt;The researchers analyzed autopsy results from 74 men and 64 women (average age 67) who died between 1998 and 2003 after participating in the long-term prospective Hisayama Study, which looked at cerebro-cardiovascular diseases among almost 3,400 residents of the Japanese town. During this period 290 Hisayama residents died and 214 were autopsied (73.8%).&lt;/p&gt;
&lt;p&gt;A total of 2,520 participants had received oral glucose tolerance tests in 1988 and were free of signs of dementia at that time. During the ensuing decades, 15.6% developed Alzheimer&apos;s-type dementia.&lt;/p&gt;
&lt;p&gt;However, among the 135 participants autopsied, 65% actually had neuritic plaques characteristic of Alzheimer&apos;s disease.&lt;/p&gt;
&lt;p&gt;Presence of these plaques was associated with significantly higher levels of the following after adjustment for age, sex, and a full set of potential confounders: &lt;ul&gt; &lt;li&gt;Two-hour post-load plasma glucose in a 75-g oral glucose tolerance test (odds ratio 1.71, &lt;em&gt;P&lt;/em&gt;=0.03) &lt;/li&gt; &lt;li&gt;Fasting insulin (OR 2.03, &lt;em&gt;P&lt;/em&gt;=0.02)&lt;/li&gt; &lt;li&gt;Insulin resistance measured by the homeostasis model of assessment (HOMA-IR, OR 2.11, &lt;em&gt;P&lt;/em&gt;=0.01)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;These endocrine factors also appeared to combine with genetic risk to accelerate formation of neuritic&lt;strong&gt; &lt;/strong&gt;plaques.&lt;/p&gt;
&lt;p&gt;Those with low glucose levels on the glucose tolerance test who didn&apos;t carry the &lt;em&gt;apolipoprotein E-4 &lt;/em&gt;gene&lt;em&gt; (APOE-4)&lt;/em&gt; allele associated with Alzheimer&apos;s disease were least likely to show neuritic plaques in their brain on autopsy whereas hyperglycemia alone was associated with 1.5-fold risk and the &lt;em&gt;APOE&lt;/em&gt; carriers had 19.7-fold risk.&lt;/p&gt;
&lt;p&gt;The greatest likelihood of neuritic plaques was seen in those with both hyperglycemia and the &lt;em&gt;APOE&lt;/em&gt; allele (38.0-fold compared with neither).&lt;/p&gt;
&lt;p&gt;The pattern was similar for fasting insulin and insulin resistance, although the interactions with the &lt;em&gt;APOE&lt;/em&gt; genotype weren&apos;t statistically significant.&lt;/p&gt;
&lt;p&gt;Neurofibrillary tangles  --  another type of brain pathology seen with Alzheimer&apos;s disease considered to be due to beta-amyloid plaque deposition  --  correlated neither with any insulin or glucose measures nor with the presence of neuritic plaques.&lt;/p&gt;
&lt;p&gt;&quot;The diabetes-related factors may act upstream of the cascade, and might trigger the Alzheimer&apos;s disease pathogenesis,&quot; Sasaki&apos;s group suggested in the paper.&lt;/p&gt;
&lt;p&gt;The authors cited several limitations to their study: First, the crude, semiquantitative evaluations of neuritic plaques could have affected the statistical analyses, and &quot;the medical history of diabetes, such as disease duration, glucose control, and complications, were not considered in this study,&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 a grants from the Ministry of Health, Labour and Welfare of Japan and the Ministry of Education, Culture, Sports, Science and Technology of Japan.&lt;/p&gt;&lt;p&gt;Matsuzaki reported having no conflicts of interest to disclose.&lt;/p&gt;&lt;p&gt;Co-authors reported having received research support from the Ministry of Health, Labor and Welfare of Japan; having served on scientific advisory boards for Eli Lilly, GlaxoSmithKline, Pfizer, Mitsubishi Tanabe Pharma, Ono Pharmaceutical, Astellas Pharma, Asahi Kasei, Shionogi, and Otsuka Pharmaceutical; having served on the editorial boards of multiple journals; having received speaker honoraria from Eli Lilly, GlaxoSmithKline, Pfizer, Asahi Kasei, Janssen, Tsumura, Ajinomoto, Mitsubishi Tanabe Pharma, Meiji Techno, Kyowa Hakko Kirin Pharma, Dainippon Sumitomo Pharma, Organon International (Schering-Plough), Otsuka Pharmaceutical, and Astellas Pharma; and having received research support from Eli Lilly, GlaxoSmithKline, Pfizer, Asahi Kasei, Janssen, Tsumura, Ajinomoto, Mitsubishi Tanabe Pharma, Meiji Techno, Kyowa Hakko Kirin Pharma, Dainippon Sumitomo Pharma, Organon International (Schering-Plough), Otsuka Pharmaceutical, and the Ministry of Education, Culture, Sports, Science and Technology of Japan.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>