Radio Show Articles:
November 17, 2012

• No Need to Fast Before Lipid Measurements, Study Suggests
• Meta-Analysis: Probiotics Safely Reduce Risk for C. difficile–Associated Diarrhea
• Genetic Variation in Vitamin D Receptor Affects Health Outcomes
• Poor Physical Performance Associated with Dementia, Again
• Intensive and Standard BP Targets in Patients with Longstanding Type 2 Diabetes
• Widespread Screening for Type 2 Diabetes Might Not Lower 10-Year Mortality
• Mortality Increases as Renal Function Declines, Regardless of Comorbid Diabetes
  or Hypertension
• CVS' PBM Plans to Stop Coverage of Certain Drugs
• FDA Investigating Reports of Deaths Tied to 5-Hour Energy Drink
• Black Women Have Higher Death Rates from Breast Cancer Than White Women
• Moderate Alcohol Consumption in Pregnancy Linked to Lower Childhood IQ,
   Genotypying Study Suggests
• Like Girls, Boys Are Now Entering Puberty Earlier
• Diabetes Prevalence in the U.S. Nearly Doubles in 15 Years
• Obstet Gynecol 2012 Nov; 120:1085
• No Benefit of Multivitamins for Preventing Cardiovascular Disease in Men
• Presentation of Celiac Disease with Immunoglobulin A Deficiency
• Hypoglycemia Raises Risk for Death in Critically Ill Patients
• Alzheimer’s Linked to Vitamin D Lack

MM: This is great news for those of us who cannot get that early appointment at the doctor’s office for our yearly physicals. No longer must we ignore, “the most important meal of the day” just because we are going in for that battery of “standard” blood tests that will make us feel either wonderful or miserable about ourselves.
  
No Need to Fast Before Lipid Measurements, Study Suggests
A cross-sectional study in the Archives of Internal Medicine calls into question the need for fasting before lipid measurements, as current guidelines recommend.
Researchers in Canada used laboratory data to measure variations in lipid measurements according to the time since a patient's last meal (range, 1-16 hours). Nearly 210,000 individuals were included.
Overall, mean total and HDL cholesterol levels varied little, by less than 2%, with differing fasting times. LDL and triglyceride levels varied more, by less than 10% and 20%, respectively.
An editorialist concludes: "The incremental gain in information of a fasting profile is exceedingly small for total and HDL cholesterol values and likely does not offset the logistic impositions placed on our patients, the laboratories, and our ability to provide timely counseling to our patients. This, in my opinion, tips the balance toward relying on nonfasting lipid profiles as the preferred practice."
http://archinte.jamanetwork.com/article.aspx?articleid=224849
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MM: It’s been over a decade that I have been recommending probiotics as a prophyactic measure when taking antibiotics. It makes me feel great when the peer-reviewed literature supports the actions of my integrative and restorative medicine colleagues and me.
  
Meta-Analysis: Probiotics Safely Reduce Risk for C. difficile–Associated Diarrhea
Probiotic therapy helps prevent Clostridium difficile–associated diarrhea (CDAD) in patients on antibiotics, according to a meta-analysis in the Annals of Internal Medicine.
Researchers analyzed 20 randomized trials that compared probiotics with placebo or no treatment in some 3800 children and adults who were taking antibiotics. The following probiotic species were included: Bifidobacterium, Lactobacilli, Saccharomyces, and Streptococcus. (Roughly half the studies excluded patients who were immunocompromised.)
Probiotics cut the risk for CDAD by 66%, with similar effects seen in both children and adults and with different probiotic species. Adverse events (e.g., nausea, fever) occurred in 13% of the control group and just 9% of the treated group.
The researchers conclude: "Moderate quality evidence supports a large protective effect of probiotics in preventing CDAD. Given the low cost of probiotics and the moderate quality evidence suggesting the absence of important adverse effects, there seems little reason not to encourage the use of probiotics in patients receiving antibiotics who are at appreciable risk of CDAD."
http://annals.org/article.aspx?articleid=1390418
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MM: It seems that every time a new study comes out there are more questions that are raised than answers that are provided. When it comes to Vitamin D, I will continue to recommend 5000-10,000 IU daily to almost all of my adult patients. Irrespective of the small number that may benefit more from much ghigher doses than the general public, it is still important, in my opinion, to maintain 25-OH-D blood levels that are closer to the top of the 30-100ng/ml blood range than to the lower quadrant.
  
Genetic Variation in Vitamin D Receptor Affects Health Outcomes
Variations in the vitamin D receptor gene are associated with increased vulnerability to conditions such as hip fracture and myocardial infarction, according to a JAMA study.
Researchers identified small variations (called single nucleotide polymorphisms, or SNPs) in the gene governing the action of the vitamin D receptor in a cohort of adults aged 65 and older. In participants with low levels of 25-hydroxyvitamin D, the presence of one SNP in particular was associated with an increased hazard ratio for a composite outcome of hip fracture, MI, cancer, or death from any cause. Individuals with two copies of the SNP showed higher risks.
The researchers conclude that similar studies could "help pave the way toward identifying individual patients who may benefit most from vitamin D interventions."
http://jama.jamanetwork.com/article.aspx?articleid=1391914
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MM: The key appears to get mom and dad, Nana and Papa up and moving. Once again, irrespective of age, it appears that both aerobic and weight resistant exercise are potentially beneficial to both the body and the mind.
  
Arch Neurol 2012 Oct 22
Poor Physical Performance Associated with Dementia, Again
The "oldest old" are more likely to have dementia if they have physical impairments.
Poor physical performance and impaired cognition have been associated with each other in both cross-sectional and prospective analyses. This study adds support for the connection, focusing on a specific population aged 90 and older. The 629 participants (mean age, 94; 73% women; 74% with more than a high school education) in the main analysis were part of a cohort-based study of aging. Between 2003 and 2009, participants underwent assessment of physical performance, including objective measures of walking speed, ability to arise from the seated position, balance, and grip strength.
Dementia was diagnosed in 162 participants (25.8%) according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria using neurological evaluation, a cognitive screening test (Mini-Mental State Exam), and functional rating scales (Clinical Dementia Rating Scale and Functional Activities Questionnaire). Poor performance on each of the physical tasks was independently associated with an approximate doubling in the odds of all-cause dementia diagnosis. Secondary analyses that included 218 additional cohort members with partial physical performance datasets did not significantly affect the results.
Comment: Although these results are unique because of the age demographic of the participants, as the authors point out, the generalizability of the results may be challenged by the homogeneity of the study population of highly educated, Caucasian women aged 90 and older. Moreover, as with all cross-sectional studies, one cannot determine causation from these findings.
— Brandy R. Matthews, MD  Published in Journal Watch Neurology November 13, 2012
CITATION(S):  Bullain SS et al. Poor physical performance and dementia in the oldest old: The 90+ study. Arch Neurol 2012 Oct 22; [e-pub ahead of print].
(http://dx.doi.org/10.1001/jamaneurol.2013.583)
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MM: The Synergy Blends line of nutritional, functional medicine products found at Mark Drugs are milder than most prescription alternatives while still having a similar net effect on blood pressure, cholesterol and blood sugar levels. This “softer, gentler” approach has proven itself to be effective and without adverse effects. Now the peer-reviewed literature seems to be supporting this gentler approach.
  
Arch Intern Med 2012 Sep 24; 172:1296
Intensive and Standard BP Targets in Patients with Longstanding Type 2 Diabetes
Intensive blood pressure control lowered stroke risk but not risk for myocardial infarctions.
The ACCORD blood pressure trial showed that intensive blood pressure control (target systolic BP, <120 mm Hg), compared with standard BP control (target SBP, <140 mm Hg), was not associated with lower risk for fatal and nonfatal cardiovascular events in patients with longstanding type 2 diabetes (JW Cardiol Mar 14 2010). In this meta-analysis, investigators evaluated outcomes of treating to intensive BP targets (SBP, 130 mm Hg; diastolic BP, 80 mm Hg) or to standard BP targets (upper limits: SBP, 140–160 mm Hg; DBP, 85–100 mm Hg) in such patients.
Five randomized trials that involved more than 7300 participants (mean ages, 53–62; mean duration of diabetes, 7–10 years) were included in the analysis. Achieved BPs in intensive-target groups were SBP, 118 to 140 mm Hg, and DBP, 64 to 81 mm Hg; achieved BPs in standard-target groups were SBP, 124 to 144 mm Hg, and DBP, 70 to 86 mm Hg. Overall, treating patients to intensive BP targets was not associated with fewer deaths or myocardial infarctions. Although treating to intensive BP targets was associated with a 35% lower relative risk for stroke, the absolute risk reduction was only 1%. Adverse effects were more common in the intensive-target groups (3.3%) than in the standard-target groups (1.7%).
Comment: A recent American Diabetes Association (ADA) guideline recommends that "most patients with diabetes" receive treatment to reach systolic BP of 130 mm Hg and diastolic BP of80 mm Hg (Diabetes Care 2012; 35 (Suppl 1):S11). The results of this meta-analysis, however, do not affirm this recommendation and suggest that treating to standard systolic and diastolic BP targets is sufficient. Notably, the ADA guideline does allow for "higher or lower" SBP targets based on patient characteristics (e.g., stroke risk).
— Paul S. Mueller, MD, MPH, FACP  Published in Journal Watch General Medicine November 6, 2012
CITATION(S): McBrien K et al. Intensive and standard blood pressure targets in patients with type 2 diabetes mellitus: Systematic review and meta-analysis. Arch Intern Med 2012 Sep 24; 172:1296. (http://dx.doi.org/10.1001/archinternmed.2012.3147)
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Lancet 2012 Oct 4
Widespread Screening for Type 2 Diabetes Might Not Lower 10-Year Mortality
In a population-based U.K. study, screening all middle-aged high-risk patients did not help.
Early diagnosis of type 2 diabetes can improve clinical outcomes, and mathematical models have suggested that widespread screening might lower diabetes-related mortality. To test this hypothesis, researchers cluster-randomized 33 general practices in eastern England to offer either a single round of formal screening to all middle-aged patients (age range, 40–69) considered to be at high risk for diabetes according to specified clinical characteristics (28 practices with approximately 16,000 high-risk patients) or to continue diagnosing diabetes in such patients through routine clinical assessment (5 practices with approximately 4000 high-risk patients).
Overall, 73% of invited patients participated in screening, and 3% of patients in both groups received diabetes diagnoses. After a median 9.6 years of follow-up, overall mortality among high-risk patients was similar in the screening and no-screening practices (10.5 and 9.9 deaths per 1000 person-years, respectively). Rates of cardiovascular- and cancer-related mortality also were similar in the two groups.
Comment: The study population was of above-average socioeconomic status; these results might not be generalizable to less-affluent populations in which the prevalence of undiagnosed diabetes might be higher. In addition, multiple rounds of screening and longer follow-up might be necessary to detect mortality differences attributable to screening. Furthermore, important outcomes other than mortality might be modifiable by screening. Regardless, these data suggest that population screening for diabetes might be less effective than expected and should be evaluated carefully before widespread implementation.
— Bruce Soloway, MD  Published in Journal Watch General Medicine October 23, 2012
CITATION(S): Simmons RK et al. Screening for type 2 diabetes and population mortality over 10 years (ADDITION-Cambridge): A cluster-randomised controlled trial. Lancet 2012 Oct 4; [e-pub ahead of print].
(http://viajwat.ch/S0I8SI)
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Lancet 2012 Sep 24
Mortality Increases as Renal Function Declines, Regardless of Comorbid Diabetes or Hypertension
Kidney function is an important prognostic indicator.
Chronic kidney disease (CKD) is associated with mortality, cardiovascular disease, and end-stage renal disease (ESRD), but most studies on the prognostic implications of increasing albuminuria and decreasing estimated glomerular filtration rate (eGFR) are confounded by the high prevalence of hypertension and diabetes in populations with CKD. To determine the influence of hypertension and diabetes on risk estimates derived from CKD markers, researchers performed two parallel meta-analyses of combined data from 45 cohort studies that involved more than 1 million patients, each with baseline data on eGFR, albuminuria, and presence of diabetes or hypertension, and outcome data on mortality or ESRD.
Low eGFR and high albuminuria were associated strongly with higher risk for all-cause and cardiovascular-related death and ESRD, regardless of the presence or absence of hypertension or diabetes. Among patients with eGFR >75 mL/minute/1.73 m2, those with hypertension had slightly higher risk for death than those without hypertension, but, when eGFR fell below 60 mL/minute/1.73 m2, mortality risk was similar, regardless of hypertension status. Similarly, mortality risk was comparable in both groups when albumin–creatinine ratio (ACR) was <300 mg/g, but, above this level, mortality risk rose more rapidly in patients without hypertension. Risk for ESRD was similar for patients with and without hypertension at all levels of eGFR and ACR.
Risks for mortality and ESRD were significantly higher for patients with diabetes than without diabetes at all levels of baseline eGFR and albuminuria, and risk increased similarly for patients with and without diabetes as renal function declined.
Comment: The greater mortality risk associated with declining renal function among patients without hypertension compared with those with hypertension might reflect a higher prevalence of high-risk nonhypertensive renal diseases, presence of other cardiovascular disease (e.g., heart failure) masking hypertension, or a protective effect of antihypertensive medications. Although these meta-analyses are limited by the observational nature of the data, they clearly demonstrate the important prognostic risks associated with declining renal function, independent of the presence of diabetes or hypertension.
— Bruce Soloway, MD  Published in Journal Watch General Medicine October 23, 2012
CITATION(S):  Mahmoodi BK et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: A meta-analysis. Lancet 2012 Sep 24; [e-pub ahead of print].
(http://dx.doi.org/10.1016/S0140-6736(12)61272-0)
Fox CS et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: A meta-analysis. Lancet 2012 Sep 24; [e-pub ahead of print].
(http://dx.doi.org/10.1016/S0140-6736(12)61350-6)
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CVS' PBM Plans to Stop Coverage of Certain Drugs
CVS Caremark pharmacy-benefit business is targeting certain treatments for low testosterone and glaucoma, among other conditions, in its latest push to promote available alternatives to what it says are expensive drugs. It plans to block coverage for 17 more drugs starting January 1, 2013, including Abbott's testosterone treatment Androgel and Pfizer's overactive-bladder drug Detrol LA.
This move adds to its list of more than 30 drugs blocked for 2012—while also reinstating a few—in what industry consultants say was a particularly aggressive effort to secure pricing deals from drug makers. They will cover equally effective products with lower overall costs including many generics that remain available on the formulary.
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FDA Investigating Reports of Deaths Tied to 5-Hour Energy Drink
The FDA is investigating 13 reports of deaths after people consumed 5-Hour Energy drink, theNew York Times reports.
In the past 4 years, the agency has received 90 incident reports that cite 5-Hour Energy. Over 30 of these filings mentioned serious or life-threatening problems, such as myocardial infarctions, convulsions, and one spontaneous abortion. An FDA official told the Times that some of the reports may not contain enough information to determine whether the supplement played a role in the adverse event.
The drink, which comes as a 2-oz "shot," contains about 215 mg of caffeine, according toConsumer Reports. Eight ounces of coffee may contain about half that amount, depending on the preparation method.
Recently, the FDA also acknowledged that it had received five fatality reports involving Monster Energy drink
http://www.nytimes.com/2012/11/15/business/5-hour-energy-is-cited-in-13-death-reports.html
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Black Women Have Higher Death Rates from Breast Cancer Than White Women
Black women have a higher risk for death from breast cancer than white women, even though they have a lower incidence of the disease, according to an MMWR article.
Using data from population-based cancer registries and death certificates from 2005–2009, researchers calculated that black women had a lower incidence rate of breast cancer than white women (116.9 vs. 122.1 cases per 100,000). However, black women had a 41% higher risk for breast cancer mortality. Black women also were more likely than white women to be diagnosed at a regional or distant cancer stage (45% vs. 35%).
The authors note: "Black women experience inequities in breast cancer screening, follow-up, and treatment after diagnosis, leading to greater mortality. At the individual level, the maximal effectiveness of screening for breast cancer can only be achieved when all women have timely follow-up to breast cancer exams and state-of-the-art treatment."
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6145a5.htm?s_cid=mm6145a5_w
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Moderate Alcohol Consumption in Pregnancy Linked to Lower Childhood IQ, Genotypying Study Suggests
A new study in PLoS One adds fuel to the debate on whether moderate alcohol consumption during pregnancy is linked to reduced cognition in offspring.
Nearly 4200 U.K. women reported their alcohol consumption twice during pregnancy, and their offspring had cognitive testing at age 8 years. Both mothers and children underwent genotyping for four genes that influence ethanol metabolism — genes encoding alcohol dehydrogenase (ADH) enzymes.
Researchers found that four ADH variants in children and one variant in mothers were associated with reduced childhood IQ — but only among children whose mothers drank moderately (up to 6 units weekly) during pregnancy.
The researchers say their finding "suggests that, even amongst women drinking moderate amounts of alcohol, subtle changes in exposure to alcohol due to an ability to metabolize the substrate may be important, and offers some support to the hypothesis that even small amounts of alcohol in utero have an effect on future cognitive outcomes."
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0049407
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Pediatrics 2012 Nov 1; 130:e1058
Like Girls, Boys Are Now Entering Puberty Earlier
Depending on race and ethnicity, boys are entering puberty 6 to 24 months earlier than they were 40 years ago.
Data from three U.S. office-based research networks using standardized assessments of pubertal development demonstrated a trend toward earlier puberty in girls (Pediatrics1997; 99:505). Comparable data are now available for boys.
Researchers enrolled 5355 boys from 144 sites between 2005 and 2010. After excluding boys with missing data or who had medical conditions or medication histories that might affect pubertal development, 4131 boys (50% white) remained for analysis. Mean ages (and standard deviations) for reaching Tanner stage 2 genital development (e.g., thinning or reddening of the skin of the scrotum) and pubic hair development and testicular volume 3 mL are provided in the table.
Black boys reached stage 2 genital and pubic hair development significantly earlier than white or Hispanic boys. Boys with body-mass index (BMI) <15th percentile had later mean ages of genital and pubic hair development than boys with BMI >85th percentile. Mean age of pubertal events was 6 to 24 months earlier than the mean age of such events in Tanner's classic study of white institutionalized boys in England (Arch Dis Child1970; 45:13).
Comment: Like girls, boys now appear to be entering puberty at younger ages than in previous generations. Studies from Denmark, Sweden, Great Britain, Italy, and China indicate similar trends. The etiology of this phenomenon remains to be elucidated.
— Alain Joffe, MD, MPH, FAAP  Published in Journal Watch Pediatrics and Adolescent MedicineNovember 14, 2012
CITATION(S):  Herman-Giddens ME et al. Secondary sexual characteristics in boys: Data from the Pediatric Research in Office Settings network. Pediatrics 2012 Nov 1; 130:e1058.
(http://dx.doi.org/10.1542/peds.2011-3291)
htpt://www.ncbi.nlm.nih.gov/pubmed/23085608?dopt=Abstract
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Diabetes Prevalence in the U.S. Nearly Doubles in 15 Years
The age-adjusted prevalence of diagnosed diabetes in U.S. adults nearly doubled from 1995 to 2010, from 4.5% to 8.2%, according to an article in MMWR.
The report, based on data from the Behavioral Risk Factor Surveillance System, found that the prevalence of diabetes is 6% or higher in every state. At least 10% of the population has been diagnosed with diabetes in Alabama, Mississippi, Puerto Rico, South Carolina, Tennessee, Texas, and West Virginia.
The authors say that the dramatic increase is likely due to people living longer with diabetes in addition to an increase in incidence.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6145a4.htm?s_cid=mm6145a4_w
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Obstet Gynecol 2012 Nov; 120:1085
Obstructive Sleep Apnea, Obesity, and Obstetric Consequences
Preeclampsia, cesarean deliveries, and admissions to neonatal intensive care units were more common with maternal OSA.
Maternal obesity raises risk for cesarean delivery, anesthesia complications, venous thromboembolism, preterm birth, and fetal macrosomia. Obesity is also associated with obstructive sleep apnea (OSA), but the effects of OSA on obstetric outcomes are unclear. The Sleep Apnea in Pregnancy Screening Study was designed to identify risk factors and pregnancy outcomes in obese women with OSA. Pregnant obese women (body-mass index [BMI] 30 kg/m2) seen at an urban tertiary center were home-screened for OSA with portable polysomnography. OSA was defined as 5 instances hourly of airflow cessation for 10 seconds.
Prevalence of OSA among the 182 participants was 15.4%. Women with OSA had a median of 12.9 hypopneic episodes per hour of sleep and spent a mean of 6.5% of the night with oxygen saturation <90%. They were significantly older, had higher mean BMI, and were more likely to have asthma or chronic hypertension than women without OSA. Rates of pregestational diabetes were similar in both groups. The cesarean rate was 38% for the entire cohort and was higher in women with OSA (65% vs. 33%). Women with OSA also were more likely than non-OSA participants to have preeclampsia (42% vs.17%) and to have babies that required neonatal intensive care (46% vs. 18%).
Comment: In this cohort study, obstructive sleep apnea was associated with significantly higher rates of several comorbid conditions during pregnancy, as well as adverse neonatal outcomes. However, the women with OSA also had significantly higher mean body-mass index than those without OSA, so some of these results could be attributable to the effects of obesity. Nevertheless, these findings suggest that OSA presents additional obstetric challenges for obese women, and that pregnant patients who are obese probably should be screened for OSA.
— Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC  Published in Journal Watch Women's Health November 15, 2012
CITATION(S):  Louis J et al. Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women. Obstet Gynecol 2012 Nov; 120:1085.
(http://viajwat.ch/ZB4XyV)
http://www.ncbi.nlm.nih.gov/pubmed/23090526?dopt=Abstract
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JAMA 2012 Nov 7; 308:1751
No Benefit of Multivitamins for Preventing Cardiovascular Disease in Men
A randomized, controlled trial showed that myocardial infarction, stroke, and death were not affected.
Observational studies of multivitamins for preventing cardiovascular disease (CVD) have yielded inconsistent and mostly negative results, as have randomized controlled trials of individual vitamins and minerals (including β-carotene, selenium, and vitamins B, C, and E). This randomized controlled trial that involved nearly 15,000 male physicians (mean age, 64) who were randomized to commercial daily multivitamins (Centrum Silver) or placebo is a companion analysis to a recently published study that showed a small benefit of multivitamin supplementation for preventing cancer (JW Gen Med Oct 25 2012). Follow-up continued for a median of 11 years.
No difference was found between the groups in risk for any major adverse CVD event, including myocardial infarction, stroke, or cardiac-related mortality. Multivitamin supplementation also was not beneficial in the small subgroup of men with histories of CVD at study entry (5% of participants).
Comment: These findings appear to disprove the suggestion (or hope) that vitamin supplementation prevents CVD, at least in men. The cardiovascular and cancer outcomes from this trial will help clinicians answer patients' questions about the value of multivitamins; additional results from this study (i.e., on preventing eye disease and cognitive decline) are forthcoming.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine November 15, 2012
Citation(s): Sesso HD et al. Multivitamins in the prevention of cardiovascular disease in men: The Physicians' Health Study II randomized controlled trial. JAMA 2012 Nov 7; 308:1751. (http://dx.doi.org/10.1001/jama.2012.14805)
http://www.ncbi.nlm.nih.gov/pubmed/23117775?dopt=Abstract
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J Clin Gastroenterol 2012 Nov/Dec; 46:850
Presentation of Celiac Disease with Immunoglobulin A Deficiency
IgA deficiency in this patient group was associated with a higher rate of autoimmune disease.
Immunoglobulin A (IgA) antibodies, such as anti-tissue transglutaminase and anti-endomysial antibodies, are used to screen for and diagnose celiac disease. Approximately 2% to 3% of the general population is deficient in total serum IgA; therefore, when screening for celiac disease, it is common to measure both anti-tissue transglutaminase IgA as well as total serum IgA. Patients deficient in total serum IgA can be screened for celiac disease using immunoglobulin G (IgG) antibodies.
To characterize clinical features of celiac disease in patients with IgA deficiency, investigators conducted a single-center, retrospective cohort study of 1815 patients with celiac disease. Patients with IgA deficiency were more likely than those with normal IgA levels to have concomitant autoimmune diseases (29% vs. 12%; P=0.008). In addition, some patients with IgA deficiency and celiac disease had persistently positive IgG celiac serologies despite being on a gluten-free diet and having a normal repeat biopsy.
Comment: This study provides useful clinical information about the occasional patient with celiac disease who has IgA deficiency.
— Douglas K. Rex, MD  Published in Journal Watch Gastroenterology November 16, 2012
CITATION(S):  Chow MA et al. Immunoglobulin A deficiency in celiac disease. J Clin Gastroenterol 2012 Nov/Dec; 46:850.
http://www.ncbi.nlm.nih.gov/pubmed/22476042?dopt=Abstract
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N Engl J Med 2012 Sep 20; 367:1108
Hypoglycemia Raises Risk for Death in Critically Ill Patients
Risk associated with hypoglycemia outweighs benefits of tight glucose control.
Hyperglycemia in critically ill patients is associated with morbidity and mortality. In light of this fact, investigators have spent more than a decade trying to determine the "right" blood glucose target for patients in intensive care units (ICUs). An initial trial suggested that intensive glucose control (target blood glucose, 80–110 mg/dL) lowered mortality in surgical ICU patients, but a subsequent large multicenter randomized trial (NICE-SUGAR) showed the opposite effect — tighter glucose control raised risk for death (JW Gen Med Mar 24 2009). Now researchers have analyzed data from 6026 NICE-SUGAR patients further to examine the relation between hypoglycemic events and mortality.
Moderate hypoglycemia (blood glucose level, 41–70 mg/dL) was significantly more common in the intensive-control group than in the conventional control group (74% vs. 16%). Almost all (93%) of the 223 patients who experienced severe hypoglycemia (blood glucose level <40 mg/dL) were in the intensive-control group. Hypoglycemia was associated with longer ICU stay, longer hospital stay, and mortality. Patients with worse outcomes included those who experienced more than one episode of hypoglycemia and those with severe hypoglycemia despite not having received insulin (reflecting that hypoglycemia can result from severe illness). The adjusted hazard ratios for death were 1.41 in patients with moderate hypoglycemia and 2.10 in patients with severe hypoglycemia.
Comment: These results support use of ICU protocols with target glucose levels of 140 to 180 mg/dL (i.e., the conventional glucose control group in NICE-SUGAR). Until we develop ways to monitor glucose levels more accurately and consistently, risks of hypoglycemia outweigh benefits of tight glucose control.
— Patricia Kritek, MD  Published in Journal Watch Hospital Medicine October 22, 2012
CITATION(S):  The NICE-SUGAR Study Investigators. Hypoglycemia and risk of death in critically ill patients. N Engl J Med 2012 Sep 20; 367:1108.
(http://dx.doi.org/10.1056/NEJMoa1204942)
http://www.ncbi.nlm.nih.gov/pubmed/22992074?dopt=Abstract
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http://www.vitalchoice.com/shop/pc/articlesView.asp?id=1955
Alzheimer’s Linked to Vitamin D Lack
Dementia victims had low vitamin D blood levels vs. healthy people; levels seen a bit better in people on common AD drugs  By Craig Weatherby

Vitamin D holds promise – yet unproven – as a deterrent to dementia. Epidemiological studies almost uniformly link low vitamin D levels to the presence of Alzheimer's … or greater risk of developing this common kind of dementia. And as French researchers noted, this apparent link is biologically plausible: “… vitamin D simultaneously targets several factors leading to neurodegeneration [and dementia] …” (Annweiler C et al. 2010) They cited the hormone-like vitamin’s healthy influences on a variety of processes affecting brain health:

• Help avoid thyroid problems.
• Help maintain blood flow in the brain.
• Support the body’s inflammation/oxidation control systems.
• Support growth and survival and maintenance of neurons (brain cells).
• Help maintain healthy levels of the key neurotransmitter called acetylcholine.
• Help clear the pro-inflammatory amyloid beta plaque associated with Alzheimer's disease.

For an overview of the relevant evidence, see “Vitamin D May Help Deter Alzheimer's”, “Vitamin D Shows More Brain Protection Potential”, “Vitamin D May Deter Dementia”, and “Vitamin D May Diminish Risk of Alzheimer’s and Depression”.
For sure, we need clinical trials to test whether vitamin D supplements – or diets high in fatty fish, which are its only good food source – can reduce the risk of dementia. In the meantime, evidence linking lack of the “sunshine-and-seafood” vitamin to Alzheimer's disease (AD) continues to accumulate. Most recently, scientists from two British academic centers – Kingston University and Brighton and Sussex Medical School – uncovered more evidence linking Alzheimer's to a lack of vitamin D (Shah I et al. 2012).

British study links vitamin D lack to Alzheimer’s
As lead researcher Declan Naughton said, his team came up with some novel findings about the different forms of vitamin D. “There are several different types of vitamin D that can be active in the body … a blood test, which we developed at Kingston University, was for the first time able to accurately measure which, if any, of the different variations of vitamin D were present in Alzheimer's patients.” (KU 2012)

The Kingston-led scientists analyzed blood samples from three groups:

• Controls free of dementia
• Un-medicated Alzheimer's patients
• Medicated Alzheimer's patients taking standard AD drugs

They measured the participants’ total vitamin D levels and the levels of the two forms of vitamin D obtainable from foods or supplements … vitamin D3 and vitamin D2:

• Vitamin D3 is made in the skin following exposure to sunlight (UVB) and fatty fish are the only good food sources (see our sidebar, “Fish fit the vitamin D bill”).
• Vitamin D2 is even rarer in foods, with low levels found mostly in fungi (yeast and mushrooms), and higher levels (e.g., 100 IU per serving) added to some fortified foods (milk, yogurt, etc.).

As seen in other studies, the overall vitamin D levels and vitamin D3 levels in the Alzheimer's patients were lower than in the healthy controls. And the UK team found that the un-medicated Alzheimer's patients had very low levels of vitamin D2. As professor Naughton said, “The vitamin [D2] was either non-existent or in such low quantities that it could barely be measured. In comparison, people in the study who were either being treated with drugs to control their Alzheimer’s or who didn't have the condition at all showed far higher levels.” (KU 2012)

Vitamin D2 conversion seen as potential problem
As we said, there’s ample if inconclusive evidence that lack of vitamin D might promote the development of Alzheimer's. However, according to professor Naughton, this was the first evidence of a possible link between Alzheimer’s and failure to convert the D2 dietary form of this vitamin into the usable, storage form. The UK team’s findings suggest that it may be unwise to use supplemental vitamin D2 as a dementia-deterrent. Clearly, more research is needed to confirm that hypothesis, but if confirmed, these findings could pave the way for a focus on the most effective way to maintain ample body levels of usable vitamin D. As Professor Naughton said, “Further investigations are now needed to determine whether simple dietary advice or giving a specific supplement could restore beneficial levels in Alzheimer's patients.” (KU 2012)

How much “D” do we need?
A recent report by the Institute of Medicine recommended maintaining a blood level of 20 to 50 ng/mL. But many experts in the field say that people need a blood level of 30 to 100 ng/mL to achieve true vitamin D “sufficiency” … a conclusion embodied in the Endocrine Society’s 2011 clinical practice guidelines (Holick MF et al. 2011; Heaney RP et al. 2011). If a doctor tests your vitamin D levels, make sure that he orders a 25-hydroxyvitamin D test. In addition, many doctors will call a result of 30 ng/mL (75 nmol/L) “sufficient”, so ask to see your test results. Vitamin D3 is the “natural” form created when sunrays hit human skin, but it’s abundant only in fatty fishy such as wild salmon (especially sockeye), albacore tuna, herring, mackerel, sablefish, and sardines … see our sidebar, “Fish fit the vitamin D bill”. The body uses D3 more readily than D2, and D3 is more potent than D2 for producing the “storage” form of vitamin D (25-hydroxyvitamin D), which fulfills the body’s vitamin D functions.

The Endocrine Society currently recommends the following vitamin D intakes, preferable vitamin D3 (Holick MF et al. 2011):

• Age 0 to 1 year: 400 to 1,000 IU/day
• Age 1 to 18 years: 600 to 1,000 IU/day
• All adults over age 18: 1,500 to 2,000 IU/day
• Pregnant or nursing women under age 18: 600 to 1,000 IU/day
• Pregnant or nursing women over age 18: 1,500 to 2,000 IU/day

There's also general agreement among expert researchers that vitamin D intakes of up to 4000 IU/day are safe. However, when it raised the vitamin D RDAs in 2010, the IOM only raised the upper intake limit to 2,000 IU. Frankly, we rely more on advice from the vitamin D and hormone experts at the Endocrine Society, but you must make your own judgment.

Sources: Annweiler C, Beauchet O. Vitamin D-mentia: randomized clinical trials should be the next step. Neuroepidemiology. 2011;37(3-4):249-58. Epub 2011 Dec 7. Annweiler C, Llewellyn DJ, Beauchet O. Low Serum Vitamin D Concentrations in Alzheimer's Disease: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2012 Oct 5. [Epub ahead of print]; Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Herrmann FR, Beauchet O. Higher Vitamin D Dietary Intake Is Associated With Lower Risk of Alzheimer's Disease: A 7-Year Follow-up. J Gerontol A Biol Sci Med Sci. 2012 Apr 13. [Epub ahead of print]; Annweiler C, Schott AM, Allali G, Bridenbaugh SA, Kressig RW, Allain P, Herrmann FR, Beauchet O. Association of vitamin D deficiency with cognitive impairment in older women: cross-sectional study. Neurology. 2010 Jan 5;74(1):27-32. Epub 2009 Sep 30.; Annweiler C, Schott AM, Rolland Y, Blain H, Herrmann FR, Beauchet O. Dietary intake of vitamin D and cognition in older women: a large population-based study. Neurology. 2010 Nov 16;75(20):1810-6.; Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, Raina P. Vitamin D, cognition, and dementia: A systematic review and meta-analysis. Neurology. 2012 Sep 25;79(13):1397-405.; Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. Review.; Buell JS, Dawson-Hughes B, Scott TM, Weiner DE, Dallal GE, Qui WQ, Bergethon P, Rosenberg IH, Folstein MF, Patz S, Bhadelia RA, Tucker KL. 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology. 2010 Jan 5;74(1):18-26. Epub 2009 Nov 25.; Buell JS, Scott TM, Dawson-Hughes B, Dallal GE, Rosenberg IH, Folstein MF, Tucker KL. Vitamin D is associated with cognitive function in elders receiving home health services. J Gerontol A Biol Sci Med Sci. 2009 Aug;64(8):888-95. Epub 2009 Apr 17.; Buell JS, Tucker KL. The value of physiologic vitamin D as a biomarker of dementia. Drugs Today (Barc). 2011 Mar;47(3):223-31. Review.; Constans T, Mondon K, Annweiler C, Hommet C. [Vitamin D and cognition in the elderly]. Psychol Neuropsychiatr Vieil. 2010 Dec;8(4):255-62. Review. French.; Dickens AP, Lang IA, Langa KM, Kos K, Llewellyn DJ. Vitamin D, cognitive dysfunction and dementia in older adults. CNS Drugs. 2011 Aug;25(8):629-39. doi: 10.2165/11593080-000000000-00000.; Gezen-Ak D, Dursun E, Bilgiç B, Hanagasi H, Ertan T, Gürvit H, Emre M, Eker E, Ulutin T, Uysal O, Yilmazer S. Vitamin d receptor gene haplotype is associated with late-onset Alzheimer's disease. Tohoku J Exp Med. 2012;228(3):189-96.; Heaney RP, Holick MF. Why the IOM recommendations for vitamin D are deficient. J Bone Miner Res. 2011 Mar;26(3):455-7. doi: 10.1002/jbmr.328.; Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. Epub 2011 Jun 6. Erratum in: J Clin Endocrinol Metab. 2011 Dec;96(12):3908.; Kumar PT, Antony S, Nandhu MS, Sadanandan J, Naijil G, Paulose CS. Vitamin D3 restores altered cholinergic and insulin receptor expression in the cerebral cortex and muscarinic M3 receptor expression in pancreatic islets of streptozotocin induced diabetic rats. J Nutr Biochem. 2011 May;22(5):418-25. Epub 2010 Jul 23.; Shah I, Petroczi A, Tabet N, Klugman A, Isaac M, Naughton DP. Low 25OH vitamin D2 levels found in untreated Alzheimer's patients, compared to acetylcholinesterase-inhibitor treated and controls. Curr Alzheimer Res. 2012 Aug 8. [Epub ahead of print]

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