Abstract
An International Expert Committee with members appointed by the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation was convened in 2008 to consider the current and future means of diagnosing diabetes in nonpregnant individuals. The report of the International Expert Committee represents the consensus view of its members and not necessarily the view of the organizations that appointed them. The International Expert Committee hopes that its report will serve as a stimulus to the international community and professional organizations to consider the use of the A1C assay for the diagnosis of diabetes.
Introduction
Diabetes is a disease characterized by abnormal metabolism, most notably hyperglycemia, and an associated heightened risk for relatively specific long-term complications affecting the eyes, kidney, and nervous system. Although diabetes also substantially increases the risk for cardiovascular disease, cardiovascular disease is not specific to diabetes and the risk for cardiovascular disease has not been incorporated into previous definitions or classifications of diabetes or of subdiabetic hyperglycemia.
Can the A1C Test Be Used to Diagnose Diabetes?
If chronic hyperglycemia sufficient to cause diabetes-specific complications is the hallmark of diabetes, common sense would dictate that laboratory measures that capture long-term glycemic exposure should provide a better marker for the presence and severity of the disease than single measures of glucose concentration. Observational studies that have assessed glycemia with measures that capture longer-term exposure (i.e., A1C) or with single or longitudinal measurements of glucose levels have consistently demonstrated a strong correlation between retinopathy and A1C[24-26] but a less consistent relationship with fasting glucose levels.[27] In one study that measured both FPG and A1C, there was a stronger correlation between A1C and retinopathy than between fasting glucose levels and retinopathy.[25] The correlation between A1C levels and complications has also been shown in the setting of controlled clinical trials in type 1[28] and type 2[29] diabetes, and these findings have been used to establish the widely accepted A1C treatment goals for diabetes care.[30]
All of these observations suggest that a reliable measure of chronic glycemic levels such as A1C, which captures the degree of glucose exposure over time[31,32] and which is related more intimately to the risk of complications than single or episodic measures of glucose levels, may serve as a better biochemical marker of diabetes and should be considered a diagnostic tool. Although the 1997 expert committee report considered this option, it recommended against using A1C values for diagnosis in part because of the lack of assay standardization.[17] The 2003 follow-up report noted that, while the National Glycohemoglobin Standardization Program [33] had succeeded in standardizing the vast majority of assays used in the U.S., the use of A1C for diagnosis still had "disadvantages," and it reaffirmed the previous recommendation that A1C not be used to diagnose diabetes.[21]
An updated examination of the laboratory measurements of glucose and A1C by the current International Expert Committee indicates that with advances in instrumentation and standardization, the accuracy and precision of A1C assays at least match those of glucose assays. The measurement of glucose itself is less accurate and precise than most clinicians realize.[34] A recent analysis of the performance of a variety of clinical laboratory instruments and methods that measure glucose revealed that 41% of instruments have a significant bias from the reference method that would result in potential misclassification of >12% of patients.[35] There are also potential preanalytic errors owing to sample handling and the well-recognized lability of glucose in the collection tube at room temperature.[36,37] Even when whole blood samples are collected in sodium fluoride to inhibit in vitro glycolysis, storage at room temperature for as little as 1 to 4 h before analysis may result in decreases in glucose levels by 3-10 mg/dl in nondiabetic individuals.[36-39]
By contrast, A1C values are relatively stable after collection,[40] and the recent introduction of a new reference method to calibrate all A1C assay instruments should further improve A1C assay standardization in most of the world.[41-43] In addition, between- and within-subject coefficients of variation have been shown to be substantially lower for A1C than for glucose measurements.[44] The variability of A1C values is also considerably less than that of FPG levels, with day-to-day within-person variance of <2% for A1C but 12-15% for FPG.[45-47] The convenience for the patient and ease of sample collection for A1C testing (which can be obtained at any time, requires no patient preparation, and is relatively stable at room temperature) compared with that of FPG testing (which requires a timed sample after at least an 8-h fast and which is unstable at room temperature) support using the A1C assay to diagnose diabetes.
In summary, compared with the measurement of glucose, the A1C assay is at least as good at defining the level of hyperglycemia at which retinopathy prevalence increases; has appreciably superior technical attributes, including less preanalytic instability and less biologic variability; and is more clinically convenient. A1C is a more stable biological index than FPG, as would be expected with a measure of chronic glycemia levels compared with glucose concentrations that are known to fluctuate within and between days ( Table 1 ).
Table 1. Advantages of A1C Testing Compared With FPG or 2HPG for the Diagnosis of Diabetes
* Standardized and aligned to the DCCT/UKPDS; measurement of glucose is less well standardized
* Better index of overall glycemic exposure and risk for long-term complications
* Substantially less biologic variability
* Substantially less preanalytic instability
* No need for fasting or timed samples
* Relatively unaffected by acute (e.g., stress or illness related) perturbations in glucose levels
* Currently used to guide management and adjust therapy
Tuesday, September 29, 2009
Saturday, September 26, 2009
CDC Guidelines for Use of Influenza A (H1N1) 2009 Monovalent Vaccine
August 27, 2009 — The US Centers for Disease Control and Prevention's (CDC's) Advisory Committee on Immunization Practices (ACIP) has issued guidelines regarding the use of vaccine against infection with novel influenza A (H1N1) virus. The new recommendations were posted online August 21 in the Morbidity and Mortality Weekly Report.
"Because novel influenza A (H1N1) virus is continuing to cause illness in the United States and worldwide, the primary focus of vaccination efforts should be to vaccinate as many persons as possible in the recommended target groups as quickly as possible once vaccine becomes available," write Anne Schuchat, MD, and colleagues from the National Center for Immunization and Respiratory Diseases, CDC.
H1N1 Vaccine Use
"As vaccine availability increases, additional groups are recommended for vaccination.... These recommendations are intended to provide vaccination programs and providers with information to assist in planning and to alert providers and the public about target groups comprising an estimated 159 million persons who are recommended to be first to receive influenza A (H1N1) 2009 monovalent vaccine," write Dr. Schuchat and colleagues.
To assess which population groups should first be targeted for vaccination, the ACIP reviewed epidemiologic and clinical data on July 29, 2009. The ACIP also evaluated the projected supply likely to be available when the vaccine first becomes available, as well as the anticipated increase in vaccine availability during the following 6 months. By mid-October 2009, it is anticipated that licensed H1N1 vaccine will be available.
The guidelines recommend that vaccination efforts begin as soon as the vaccine is available. In accordance with state and local conditions, state and local health officials and vaccination providers should make decisions concerning vaccine administration and distribution.
Vaccination and healthcare providers should be vigilant about following announcements and other information forthcoming from state and local health departments and the CDC regarding vaccination against H1N1 virus infection. The CDC's influenza Web site and state and local health departments may provide additional information.
ACIP H1N1 Vaccine Recommendations
Key points of the ACIP recommendations include the following 3 items.
* First, 5 general population groups that should be targeted as an initial focus of vaccination efforts are pregnant women, household contacts or caregivers for infants younger than 6 months (such as parents, siblings, and daycare providers), healthcare and emergency medical services personnel, children and young adults 6 months to 24 years of age, and persons aged 25 to 64 years who are at greater risk for influenza-related complications because of underlying medical conditions. These medical conditions increasing risk for influenza-related complications include chronic pulmonary conditions, including asthma; cardiovascular conditions except for hypertension; renal, hepatic, cognitive, neurologic/neuromuscular, hematologic, or metabolic disorders, including diabetes mellitus; and immunosuppression caused by medications or by human immunodeficiency virus.
* Second, if initial vaccine availability is insufficient to meet demand, priority is established for a subset of persons within the initial target groups. These persons who are to receive priority for vaccination (order of target groups does not indicate priority) include pregnant women, household contacts or caregivers for infants younger than 6 months, healthcare and emergency medical services personnel in direct contact with patients or infectious material, children 6 months to 4 years of age, and children and adolescents aged 5 to 18 years who are at greater risk for influenza-related complications because of underlying medical conditions.
* Third, as vaccine availability increases, other adult population groups should receive H1N1 vaccine in accordance with the guidelines recommendations.
In addition, ACIP made additional recommendations concerning the use of influenza A (H1N1) 2009 monovalent vaccine, as follows:
* The number of doses of vaccine needed for immunization against H1N1 has not been determined. Vaccine should not be stockpiled for patients who already have received 1 dose but might require a second dose, because vaccine availability is expected to increase over time.
* If different anatomic sites are used, inactivated vaccines against seasonal and H1N1 viruses may be administered simultaneously. However, ACIP does not recommend simultaneous administration of live, attenuated vaccines against seasonal and H1N1 virus.
* All persons, including those older than 65 years of age, who are currently recommended for seasonal influenza vaccine should receive the seasonal vaccine as soon as it is available. Recommendations for use of the 2009 to 2010 seasonal influenza vaccine were previously published.
"The guiding principle of these recommendations is to vaccinate as many persons as possible as quickly as possible," the guidelines authors state."ACIP will review new epidemiologic and clinical data as they become available and might revise these recommendations."
Morb Mortal Wkly Rep. Published online August 21, 2009.
"Because novel influenza A (H1N1) virus is continuing to cause illness in the United States and worldwide, the primary focus of vaccination efforts should be to vaccinate as many persons as possible in the recommended target groups as quickly as possible once vaccine becomes available," write Anne Schuchat, MD, and colleagues from the National Center for Immunization and Respiratory Diseases, CDC.
H1N1 Vaccine Use
"As vaccine availability increases, additional groups are recommended for vaccination.... These recommendations are intended to provide vaccination programs and providers with information to assist in planning and to alert providers and the public about target groups comprising an estimated 159 million persons who are recommended to be first to receive influenza A (H1N1) 2009 monovalent vaccine," write Dr. Schuchat and colleagues.
To assess which population groups should first be targeted for vaccination, the ACIP reviewed epidemiologic and clinical data on July 29, 2009. The ACIP also evaluated the projected supply likely to be available when the vaccine first becomes available, as well as the anticipated increase in vaccine availability during the following 6 months. By mid-October 2009, it is anticipated that licensed H1N1 vaccine will be available.
The guidelines recommend that vaccination efforts begin as soon as the vaccine is available. In accordance with state and local conditions, state and local health officials and vaccination providers should make decisions concerning vaccine administration and distribution.
Vaccination and healthcare providers should be vigilant about following announcements and other information forthcoming from state and local health departments and the CDC regarding vaccination against H1N1 virus infection. The CDC's influenza Web site and state and local health departments may provide additional information.
ACIP H1N1 Vaccine Recommendations
Key points of the ACIP recommendations include the following 3 items.
* First, 5 general population groups that should be targeted as an initial focus of vaccination efforts are pregnant women, household contacts or caregivers for infants younger than 6 months (such as parents, siblings, and daycare providers), healthcare and emergency medical services personnel, children and young adults 6 months to 24 years of age, and persons aged 25 to 64 years who are at greater risk for influenza-related complications because of underlying medical conditions. These medical conditions increasing risk for influenza-related complications include chronic pulmonary conditions, including asthma; cardiovascular conditions except for hypertension; renal, hepatic, cognitive, neurologic/neuromuscular, hematologic, or metabolic disorders, including diabetes mellitus; and immunosuppression caused by medications or by human immunodeficiency virus.
* Second, if initial vaccine availability is insufficient to meet demand, priority is established for a subset of persons within the initial target groups. These persons who are to receive priority for vaccination (order of target groups does not indicate priority) include pregnant women, household contacts or caregivers for infants younger than 6 months, healthcare and emergency medical services personnel in direct contact with patients or infectious material, children 6 months to 4 years of age, and children and adolescents aged 5 to 18 years who are at greater risk for influenza-related complications because of underlying medical conditions.
* Third, as vaccine availability increases, other adult population groups should receive H1N1 vaccine in accordance with the guidelines recommendations.
In addition, ACIP made additional recommendations concerning the use of influenza A (H1N1) 2009 monovalent vaccine, as follows:
* The number of doses of vaccine needed for immunization against H1N1 has not been determined. Vaccine should not be stockpiled for patients who already have received 1 dose but might require a second dose, because vaccine availability is expected to increase over time.
* If different anatomic sites are used, inactivated vaccines against seasonal and H1N1 viruses may be administered simultaneously. However, ACIP does not recommend simultaneous administration of live, attenuated vaccines against seasonal and H1N1 virus.
* All persons, including those older than 65 years of age, who are currently recommended for seasonal influenza vaccine should receive the seasonal vaccine as soon as it is available. Recommendations for use of the 2009 to 2010 seasonal influenza vaccine were previously published.
"The guiding principle of these recommendations is to vaccinate as many persons as possible as quickly as possible," the guidelines authors state."ACIP will review new epidemiologic and clinical data as they become available and might revise these recommendations."
Morb Mortal Wkly Rep. Published online August 21, 2009.
WHO Guidelines for Antiviral Treatment for H1N1 and Other Influenza
August 25, 2009 — The World Health Organization (WHO) has issued guidelines for antiviral treatment for novel influenza A (H1N1) and other influenza. The purpose of the new recommendations, which were posted online August 20, is to provide a basis for advice to clinicians regarding the use of the currently available antivirals for patients presenting with illness caused by influenza virus infection, as well as considerations regarding potential use of these antiviral medications for chemoprophylaxis.
On the basis of a review of data collected with previously circulating strains, and treatment of human H5N1 influenza virus infections, the new guidelines expand on recommendations published in May 2009, titled ʺClinical management of human infection with new influenza A (H1N1) virus: Initial guidance." These new guidelines do not change recommendations in the WHO rapid advice guidelines on pharmacological management of humans infected with highly pathogenic avian influenza A (H5N1) virus.
"In April 2009, the [WHO] received reports of sustained person to person infections with [H1N1] virus in Mexico and the United States," write Edgar Bautista, from Médico Neumólogo Intensivista, Jefe de UCI-INER in Mexico, and colleagues. "Subsequent international spread led WHO to declare on 11 June 2009 that the first influenza pandemic in 41 years had occurred. This 2009 pandemic H1N1 influenza virus has now spread worldwide, with confirmed cases of pandemic H1N1 virus infection reported in more than 100 countries in all 6 WHO regions[, which] has led to the need to add to the existing guidance on the use of antivirals."
The new recommendations highlight oseltamivir and zanamivir, which are neuraminidase inhibitors, and amantadine and rimantadine, which are M2 inhibitors. Suggestions are also provided regarding the use of some other potential pharmacological treatments, such as ribavirin, interferons, immunoglobulins, and corticosteroids.
Management of patients with pandemic influenza (H1N1) 2009 virus infection is the primary focus of the statement, although it also includes guidance regarding the use of the antivirals for treatment of other seasonal influenza virus strains, as well as for infections resulting from novel influenza A virus strains.
The guidelines urge country and local public health authorities to issue local recommendations for clinicians periodically, based on epidemiological and antiviral susceptibility data on the locally circulating influenza strains. As the prevalence and severity of the current pandemic evolves, WHO anticipates that additional data will be forthcoming that may require revision of the current recommendations. WHO therefore plans to review the guidance no later than September 2009 to determine whether modifications to the recommendations are needed.
Recommendations for Antiviral Treatment of H1N1
For patients with confirmed or strongly suspected infection with influenza pandemic (H1N1) 2009, when antiviral medications for influenza are available, specific recommendations regarding use of antivirals for treatment of pandemic (H1N1) 2009 influenza virus infection are as follows:
* Oseltamivir should be prescribed, and treatment started as soon as possible, for patients with severe or progressive clinical illness (strong recommendation, low-quality evidence). Depending on clinical response, higher doses of up to 150 mg twice daily and longer duration of treatment may be indicated. This recommendation is intended for all patient groups, including pregnant women, neonates, and children younger than 5 years of age.
* Zanamivir is indicated for patients with severe or progressive clinical illness when oseltamivir is not available or not possible to use, or when the virus is resistant to oseltamivir but known or likely to be susceptible to zanamivir (strong recommendation, very low quality evidence).
* Antiviral treatment is not required in patients not in at-risk groups who have uncomplicated illness caused by confirmed or strongly suspected influenza virus infection (weak recommendation, low-quality evidence). Patients considered to be at risk are infants and children younger than 5 years of age; adults older than 65 years of age; nursing home residents; pregnant women; patients with chronic comorbid disease including cardiovascular, respiratory, or liver disease and diabetes; and immunosuppressed patients because of malignancy, HIV infection, or other diseases.
* Oseltamivir or zanamivir treatment should be started as soon as possible after the onset of illness in patients in at-risk groups who have uncomplicated illness caused by influenza virus infection (strong recommendation, very low quality evidence).
Recommendations for Chemoprophylaxis of H1N1
Specific recommendations regarding the use of antivirals for chemoprophylaxis of pandemic (H1N1) 2009 influenza virus infection are as follows:
* When risk for human-to-human transmission of influenza is high or low, and the probability of complications of infection is high, either because of the influenza strain or because of the baseline risk of the exposed group, use of oseltamivir or zanamivir may be considered as postexposure chemoprophylaxis for the affected community or group, for individuals in at-risk groups, or for healthcare workers (weak recommendation, moderate-quality evidence).
* Individuals in at-risk groups or healthcare personnel need not be offered antiviral chemoprophylaxis if the likelihood of complications of infection is low. This recommendation should be applied independent of risk for human-to-human transmission (weak recommendation, low-quality evidence).
For treatment of mild to moderate uncomplicated clinical presentation of infection with multiple cocirculating influenza A subtypes or viruses with different antiviral susceptibilities, patients in at-risk groups should be treated with zanamivir or oseltamivir plus M2 inhibitor (noting that amantadine should not be used in pregnant women). Otherwise-healthy patients with this presentation need not be treated.
When the clinical presentation of infection with multiple cocirculating influenza A subtypes or viruses with different antiviral susceptibilities is severe or progressive, all patients should be treated with oseltamivir plus M2 inhibitor, or zanamivir.
For treatment of mild to moderate uncomplicated clinical presentation of infection with sporadic zoonotic influenza A viruses including H5N1, the at-risk population should be treated with oseltamivir or zanamivir, and the otherwise-healthy population with oseltamivir. All patients, regardless of risk status, with severe or progressive presentation of infection with sporadic zoonotic influenza A viruses including H5N1 should be treated with oseltamivir plus an M2 inhibitor.
WHO Rapid Advice Guidelines on Pharmacological Management of Influenza Virus. Published online August 20, 2009.
On the basis of a review of data collected with previously circulating strains, and treatment of human H5N1 influenza virus infections, the new guidelines expand on recommendations published in May 2009, titled ʺClinical management of human infection with new influenza A (H1N1) virus: Initial guidance." These new guidelines do not change recommendations in the WHO rapid advice guidelines on pharmacological management of humans infected with highly pathogenic avian influenza A (H5N1) virus.
"In April 2009, the [WHO] received reports of sustained person to person infections with [H1N1] virus in Mexico and the United States," write Edgar Bautista, from Médico Neumólogo Intensivista, Jefe de UCI-INER in Mexico, and colleagues. "Subsequent international spread led WHO to declare on 11 June 2009 that the first influenza pandemic in 41 years had occurred. This 2009 pandemic H1N1 influenza virus has now spread worldwide, with confirmed cases of pandemic H1N1 virus infection reported in more than 100 countries in all 6 WHO regions[, which] has led to the need to add to the existing guidance on the use of antivirals."
The new recommendations highlight oseltamivir and zanamivir, which are neuraminidase inhibitors, and amantadine and rimantadine, which are M2 inhibitors. Suggestions are also provided regarding the use of some other potential pharmacological treatments, such as ribavirin, interferons, immunoglobulins, and corticosteroids.
Management of patients with pandemic influenza (H1N1) 2009 virus infection is the primary focus of the statement, although it also includes guidance regarding the use of the antivirals for treatment of other seasonal influenza virus strains, as well as for infections resulting from novel influenza A virus strains.
The guidelines urge country and local public health authorities to issue local recommendations for clinicians periodically, based on epidemiological and antiviral susceptibility data on the locally circulating influenza strains. As the prevalence and severity of the current pandemic evolves, WHO anticipates that additional data will be forthcoming that may require revision of the current recommendations. WHO therefore plans to review the guidance no later than September 2009 to determine whether modifications to the recommendations are needed.
Recommendations for Antiviral Treatment of H1N1
For patients with confirmed or strongly suspected infection with influenza pandemic (H1N1) 2009, when antiviral medications for influenza are available, specific recommendations regarding use of antivirals for treatment of pandemic (H1N1) 2009 influenza virus infection are as follows:
* Oseltamivir should be prescribed, and treatment started as soon as possible, for patients with severe or progressive clinical illness (strong recommendation, low-quality evidence). Depending on clinical response, higher doses of up to 150 mg twice daily and longer duration of treatment may be indicated. This recommendation is intended for all patient groups, including pregnant women, neonates, and children younger than 5 years of age.
* Zanamivir is indicated for patients with severe or progressive clinical illness when oseltamivir is not available or not possible to use, or when the virus is resistant to oseltamivir but known or likely to be susceptible to zanamivir (strong recommendation, very low quality evidence).
* Antiviral treatment is not required in patients not in at-risk groups who have uncomplicated illness caused by confirmed or strongly suspected influenza virus infection (weak recommendation, low-quality evidence). Patients considered to be at risk are infants and children younger than 5 years of age; adults older than 65 years of age; nursing home residents; pregnant women; patients with chronic comorbid disease including cardiovascular, respiratory, or liver disease and diabetes; and immunosuppressed patients because of malignancy, HIV infection, or other diseases.
* Oseltamivir or zanamivir treatment should be started as soon as possible after the onset of illness in patients in at-risk groups who have uncomplicated illness caused by influenza virus infection (strong recommendation, very low quality evidence).
Recommendations for Chemoprophylaxis of H1N1
Specific recommendations regarding the use of antivirals for chemoprophylaxis of pandemic (H1N1) 2009 influenza virus infection are as follows:
* When risk for human-to-human transmission of influenza is high or low, and the probability of complications of infection is high, either because of the influenza strain or because of the baseline risk of the exposed group, use of oseltamivir or zanamivir may be considered as postexposure chemoprophylaxis for the affected community or group, for individuals in at-risk groups, or for healthcare workers (weak recommendation, moderate-quality evidence).
* Individuals in at-risk groups or healthcare personnel need not be offered antiviral chemoprophylaxis if the likelihood of complications of infection is low. This recommendation should be applied independent of risk for human-to-human transmission (weak recommendation, low-quality evidence).
For treatment of mild to moderate uncomplicated clinical presentation of infection with multiple cocirculating influenza A subtypes or viruses with different antiviral susceptibilities, patients in at-risk groups should be treated with zanamivir or oseltamivir plus M2 inhibitor (noting that amantadine should not be used in pregnant women). Otherwise-healthy patients with this presentation need not be treated.
When the clinical presentation of infection with multiple cocirculating influenza A subtypes or viruses with different antiviral susceptibilities is severe or progressive, all patients should be treated with oseltamivir plus M2 inhibitor, or zanamivir.
For treatment of mild to moderate uncomplicated clinical presentation of infection with sporadic zoonotic influenza A viruses including H5N1, the at-risk population should be treated with oseltamivir or zanamivir, and the otherwise-healthy population with oseltamivir. All patients, regardless of risk status, with severe or progressive presentation of infection with sporadic zoonotic influenza A viruses including H5N1 should be treated with oseltamivir plus an M2 inhibitor.
WHO Rapid Advice Guidelines on Pharmacological Management of Influenza Virus. Published online August 20, 2009.
Subscribe to:
Posts (Atom)
