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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
February 19, 2011

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Association Between Enterovirus Infection and Type 1 Diabetes
Use of Hemoglobin A1c to Diagnose Diabetes
Updated Guidelines Issued for Women's Cardiovascular Disease Prevention
Diabetes Linked to Magnesium Lack
Automated vs. Manual BP Monitoring for Systolic Hypertension
Zinc Ameliorates Cold Symptoms, Meta-Analysis Finds
A 10-Year Look at C. difficile Infection in U.S. Hospitalized Children

BMJ 2011 Feb 3; 342:d35
Association Between Enterovirus Infection and Type 1 Diabetes
The clinically significant link probably involves viruses, pancreatic islet cells, and patients' immune systems and genotypes.
     Previous research has suggested a relation between enterovirus infection and subsequent development of type 1 diabetes. In this systematic review and meta-analysis, investigators assessed the association between active enterovirus infection, detected using molecular methods, and development of diabetes-related islet cell autoimmunity or type 1 diabetes. Most of the patients with diabetes had recent-onset or newly diagnosed diabetes.
     The analysis included 24 observational studies that involved more than 4400 patients. Most studies involved children, although some included adult participants as old as 53. Infection was diagnosed by measuring enterovirus RNA or viral protein in blood, stool, or tissue. Significant associations occurred between enterovirus infection and diabetes-related islet cell autoimmunity (odds ratio, 3.7) and type 1 diabetes (OR, 9.8).
     Comment: In this meta-analysis, enterovirus infection had a clinically significant association with diabetes-related autoimmunity and with type 1 diabetes. Editorialists speculate that the link between enteroviruses and the pathogenesis of type 1 diabetes involves interactions among viruses, pancreatic islet cells, and patients' immune systems and genotypes. These findings also could lead to novel preventive and therapeutic strategies for type 1 diabetes.
     Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine
February 15, 2011
     Citation(s): Yeung W-CG et al. Enterovirus infection and type 1 diabetes mellitus: Systematic review and meta-analysis of observational molecular studies. BMJ 2011 Feb 3; 342:d35. . (http://dx.doi.org/10.1136/bmj.d35) http://www.ncbi.nlm.nih.gov/pubmed/21292721?dopt=Abstract
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J Clin Endocrinol Metab 2010 Dec; 95:5289
Use of Hemoglobin A1c to Diagnose Diabetes
Cutoffs for glycosylated hemoglobin and fasting glucose levels don't identify the same people as having diabetes.

     In 2010, the American Diabetes Association (ADA) endorsed glycosylated hemoglobin (HbA1c) level as an acceptable method for diagnosing diabetes mellitus (Diabetes Care 2010; 33[Suppl 1]:S62). According to the ADA, diabetes should be diagnosed when HbA1c level is 6.5% or fasting plasma glucose (FPG) level is 126 mg/dL; prediabetes is diagnosed when HbA1c level is 5.7% to 6.4%, or FPG level is 100 to 125 mg/dL.
     Researchers measured both HbA1c and FPG in 1865 community-dwelling older adults (age range, 70–79) without diabetes. Eighty people (4.3%) met either the HbA1c or the FPG criterion for diabetes; about one third had elevated HbA1c only, one third had elevated FPG only, and one third had both. In addition, 596 people (32%) met one or both prediabetes criteria; again, about one third fell into each diagnostic group. In an analysis that reached borderline statistical significance, black participants were more likely to receive diagnoses of diabetes or prediabetes based on elevated HbA1c than based on elevated FPG; the reverse was true for white participants.
     Comment: Hemoglobin A1c measurement varies across assays. Moreover, genetic differences in hemoglobin glycation and heterogeneity in red cell life span could explain why correlations between HbA1c and plasma glucose differ across populations. The authors of the current study worry that clinicians will screen many patients with both HbA1c and FPG, which could result in overdiagnosis of diabetes. Along the same lines, editorialists suggest that the HbA1c cutoff for diagnosing diabetes should be raised to 7.0%.
Allan S. Brett, MD Published in Journal Watch General Medicine February 1, 2011
     Citation: Lipska KJ et al. Identifying dysglycemic states in older adults: Implications of the emerging use of hemoglobin A1c. J Clin Endocrinol Metab 2010 Dec; 95:5289.
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Updated Guidelines Issued for Women's Cardiovascular Disease Prevention
     The American Heart Association has released updated guidelines for preventing cardiovascular disease in women.
     Published in Circulation, the changes since the 2007 update include the following:

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Diabetes Linked to Magnesium Lack
Deficiency of the often-overlooked mineral is associated with increased risk and
severity of the disease
by Craig Weatherby
     Magnesium plays an essential part in the regulation of many cell and metabolic processes. This probably explains the accumulating evidence that magnesium improves blood sugar control. And judging by the results of a new study, having low magnesium blood levels worsens diabetes complications. The results show that magnesium intake was inadequate in 82 percent of the diabetics studied, with the lowest levels found in those with kidney complications. Further, about two-thirds (63 percent) of the subjects had low blood levels of magnesium.
    Last year, a USDA researcher published an evidence review, in which he made several key points (Nielsen FH 2010):

     Before we take a look at a recent Brazilian study that strengthens the link between diabetes and magnesium, let’s review the existing evidence… Low blood magnesium levels linked to diabetes risk and complications
Epidemiological studies suggest that adequate magnesium intake reduces the risk of developing diabetes significantly.
     But the links between low magnesium blood levels and greater risk of the disease and worse symptoms is even greater …possibly indicating that some diabetics have difficulty using magnesium they consume. The body’s capacity to produce insulin relies in part on magnesium, which is needed for the activation of insulin receptors and for stimulation of body chemicals involved in insulin “signaling”. And the chronically high blood sugar levels (hyperglycemia) that characterize diabetes lead to excessive loss of magnesium in the urine while increasing the risk of kidney damage and other complications associated with diabetes.
     New study puts more importance on magnesium: The new research, conducted in Brazil, examined magnesium intake and blood levels in 51 patients with type 2 diabetes. And the results tied the diabetics’ blood sugar (glucose) levels to their blood magnesium levels. Specifically, those with higher blood magnesium levels had lower fasting and after-meal blood glucose levels. In addition, higher urine levels of magnesium were linked to higher fasting glucose levels.
     The authors noted that because magnesium is essential to all reactions that use and supply energy, it is not very surprising that low blood levels of the mineral are implicated in metabolic dysfunctions like diabetes. They concluded that the impaired kidney function associated with diabetes may lead to high levels of magnesium in the urine, which, together with low magnesium intake, can cause a rise in blood sugar.
     Sources Sales CH, Pedrosa LF, Lima JG, Lemos TM, Colli C. Influence of magnesium status and magnesium intake on the blood glucose control in patients with type 2 diabetes. Clin Nutr. 2011 Jan 31. [Epub ahead of print] de Lordes Lima M, Cruz T, Pousada JC, Rodrigues LE, Barbosa K, Canguçu V. The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Diabetes Care. 1998 May;21(5):682-6. Kao WH, Folsom AR, Nieto FJ, Mo JP, Watson RL, Brancati FL. Serum and dietary magnesium and the risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. Arch Intern Med. 1999 Oct 11;159(18):2151-9. Wang JL, Shaw NS, Yeh HY, Kao MD. Magnesium status and association with diabetes in the Taiwanese elderly. Asia Pac J Clin Nutr. 2005;14(3):263-9. Nielsen FH. Magnesium, inflammation, and obesity in chronic disease. Nutr Rev. 2010 Jun;68(6):333-40. Review. Barbagallo M, Dominguez LJ. Magnesium and aging. Curr Pharm Des. 2010;16(7):832-9. Review.
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BMJ 2011 Feb 7;
Automated vs. Manual BP Monitoring for Systolic Hypertension
Automated blood pressure monitoring was more accurate.
     Office manual blood pressure (BP) monitoring is fraught with problems, including variable BP measuring skills among healthcare workers, "white-coat hypertension," and digit preference (readings ending in "0"). In this trial, Canadian investigators randomized 67 primary care practices to use either ongoing manual office BP monitoring (control) or automated office BP monitoring using the BpTRU device (intervention; after the BpTRU cuff is positioned properly, the patient is left alone, and the device automatically takes five BP readings and displays an average). Awake ambulatory BP monitoring was the gold standard.
     Overall, 555 patients with systolic hypertension participated in the study. Compared with manual office BP readings, automated office BP readings correlated more strongly with ambulatory BP monitoring. For example, the mean manual office systolic BP after enrollment was 6.5 mm Hg higher than ambulatory BP, whereas mean automated office systolic BP was only 2.3 mm Hg higher than ambulatory BP; this difference was significant. For diastolic BP, mean automated and manual office measurements were both about 4 mm Hg higher than ambulatory measurements. Another striking finding was a fall in automated systolic BP while the patient rested in the exam room: Mean systolic BP fell from 147 to 133 mm Hg during a 10-minute period.
     Comment: Automated BP monitoring (with multiple readings taken while the patient is resting) is more accurate than manual BP monitoring in primary care patients with systolic hypertension. The results have obvious clinical implications, such as limiting unnecessary treatment. Indeed, several years ago, my institution systematically eliminated manual BP monitoring in favor of automated BP monitoring.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine
February 17, 2011
     Citation(s): Myers MG et al. Conventional versus automated measurement of blood pressure in primary care patients with systolic hypertension: Randomised parallel design controlled trial. BMJ 2011 Feb 7; 342:d286. (http://dx.doi.org/10.1136/bmj.d286) http://www.ncbi.nlm.nih.gov/pubmed/21300709?dopt=Abstract
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Zinc Ameliorates Cold Symptoms, Meta-Analysis Finds
Sniffling people will likely ask about a Cochrane Library meta-analysis that finds zinc to be effective in shortening the duration of the common cold.
     In an update of a 1999 Cochrane review, the authors examined zinc's efficacy both in shortening the duration of colds and in preventing them. They considered the results of 15 randomized trials, totaling over 1300 participants.
     Zinc supplements significantly reduced the severity of cold symptoms as well as the length of illness. Among people taking zinc within 24 hours of the start of symptoms, the risk for still having symptoms at the 7-day mark was about half that of those not taking zinc. In preventing colds, zinc supplements taken for at least 5 months conferred a risk for catching a cold that was only two thirds that of controls.
     Zinc's side effects included a bad taste and nausea.
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Arch Pediatr Adolesc Med 2011 Jan 3
A 10-Year Look at C. difficile Infection in U.S. Hospitalized Children
Clostrdium difficile infection is becoming more common but not more severe.
     Clostridium difficile infections (CDIs) are a well-known cause of diarrhea in children older than 1 year. Although much is known about the increasing frequency and severity of CDIs in adults, less in known about these trends in the pediatric population. Researchers tracked the number and severity of CDIs in U.S. children, using a large nationwide inpatient database (the Triennial Healthcare Cost and Utilization Project Kids' Inpatient Databases) for 1997, 2000, 2003, and 2006.
     Between 1997 and 2006, the number of CDI cases in children older than 1 year more than doubled, from 3565 to 7779, while severity indicators (length of stay, mortality, and colectomy rates) for CDI did not increase. All severity indicators were higher in children with CDI compared with other hospitalized children. Patients with CDI were also younger (9.5 vs. 11.9 years) and more likely to be white (64% vs. 54%) and to have private insurance (56% vs. 49%). Multiple comorbidities, including inflammatory bowel disease, any immunodeficiency, and antimicrobial therapy, increased risk for CDI.
     Comment: This study represents more than 85% of pediatric inpatient stays in the U.S., indicating that the marked increase of CDI is widespread and not confined to tertiary care centers. Although data on antibiotic use prior to hospitalization were not available, overprescribing antibiotics leads to resistance and thus might account for the higher rates of infection among whites and those with private insurance. The data serve as a reminder about the judicious use of antibiotics and the importance of proper hand hygiene. Finally, although this study did not show an increase in disease severity, I am seeing more relapses and refractory CDI after children leave the hospital. Children who are still symptomatic should be retested and, if positive, treated again. Failure to respond to another course of therapy should prompt referral to an infectious diseases specialist or gastroenterologist.
Peggy Sue Weintrub, MD Published in Journal Watch Pediatrics and Adolescent Medicine February 16, 2011
Citation(s): Nylund CM et al. Clostridium difficile infection in hospitalized children in the United States. Arch Pediatr Adolesc Med 2011 Jan 3; [e-pub ahead of print].

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