Glucose concentrations decrease in the test tube by 5-7% per hour due to glycolysis (13). ... a sample with a true blood glucose value of 126 mg/dL would have a glucose concentration of - 110 mg/dL ...after 2 h at room temperature. The significant reduction in microvascular complications with lower AlC and the absence of sample lability, combined with several other advantages (Table 3), have led to the recommendation by some organizations that AlC be used for screening and diagnosis of diabetes (1).
Trends in the prevalence and control of diabetes defined by hemoglobin A1c (HbA1c) levels are important for health care policy and planning.
To update trends in the prevalence of diabetes, ...prediabetes, and glycemic control.
Cross-sectional.
NHANES (National Health and Nutrition Examination Survey) in 1988-1994 and 1999-2010.
Adults aged 20 years or older.
We used calibrated HbA1c levels to define undiagnosed diabetes (≥6.5%); prediabetes (5.7% to 6.4%); and, among persons with diagnosed diabetes, glycemic control (<7.0% or <8.0%). Trends in HbA1c categories were compared with fasting glucose levels (≥7.0 mmol/L ≥126 mg/dL and 5.6 to 6.9 mmol/L 100 to 125 mg/dL).
In 2010, approximately 21 million U.S. adults aged 20 years or older had total confirmed diabetes (self-reported diabetes or diagnostic levels for both fasting glucose and calibrated HbA1c). During 2 decades, the prevalence of total confirmed diabetes increased, but the prevalence of undiagnosed diabetes remained fairly stable, reducing the proportion of total diabetes cases that are undiagnosed to 11% in 2005-2010. The prevalence of prediabetes was lower when defined by calibrated HbA1c levels than when defined by fasting glucose levels but has increased from 5.8% in 1988-1994 to 12.4% in 2005-2010 when defined by HbA1c levels. Glycemic control improved overall, but total diabetes prevalence was greater and diabetes was less controlled among non-Hispanic blacks and Mexican Americans compared with non-Hispanic whites.
Cross-sectional design.
Over the past 2 decades, the prevalence of total diabetes has increased substantially. However, the proportion of undiagnosed diabetes cases decreased, suggesting improvements in screening and diagnosis. Among the growing number of persons with diagnosed diabetes, glycemic control improved but remains a challenge, particularly among non-Hispanic blacks and Mexican Americans.
National Institutes of Health.
While A1C is well established as an important risk marker for diabetes complications, with the increasing use of continuous glucose monitoring (CGM) to help facilitate safe and effective diabetes ...management, it is important to understand how CGM metrics, such as mean glucose, and A1C correlate. Estimated A1C (eA1C) is a measure converting the mean glucose from CGM or self-monitored blood glucose readings, using a formula derived from glucose readings from a population of individuals, into an estimate of a simultaneously measured laboratory A1C. Many patients and clinicians find the eA1C to be a helpful educational tool, but others are often confused or even frustrated if the eA1C and laboratory-measured A1C do not agree. In the U.S., the Food and Drug Administration determined that the nomenclature of eA1C needed to change. This led the authors to work toward a multipart solution to facilitate the retention of such a metric, which includes renaming the eA1C the glucose management indicator (GMI) and generating a new formula for converting CGM-derived mean glucose to GMI based on recent clinical trials using the most accurate CGM systems available. The final aspect of ensuring a smooth transition from the old eA1C to the new GMI is providing new CGM analyses and explanations to further understand how to interpret GMI and use it most effectively in clinical practice. This Perspective will address why a new name for eA1C was needed, why GMI was selected as the new name, how GMI is calculated, and how to understand and explain GMI if one chooses to use GMI as a tool in diabetes education or management.
Abstract
BACKGROUND
Measurement of hemoglobin A1c (HbA1c) in the blood is integral to and essential for the treatment of patients with diabetes mellitus. HbA1c reflects the mean blood glucose ...concentration over the preceding 8 to 12 weeks. Although the clinical value of HbA1c was initially limited by large differences in results among various methods, the investment of considerable effort to implement standardization has brought about a marked improvement in analysis.
CONTENT
The focus of this review is on the substantial progress that has been achieved in enhancing the accuracy and, therefore, the clinical value of HbA1c assays.
SUMMARY
The interactions between the National Glycohemoglobin Standardization Program and manufacturers of HbA1c methods have been instrumental in standardizing HbA1c. Proficiency testing using whole blood has allowed accuracy-based assessment of methods in individual clinical laboratories that has made an important contribution to improving the HbA1c measurement in patient samples. These initiatives, supported by the efforts of the IFCC network, have led to a continuing enhancement of HbA1c methods.
Many of the factors that previously influenced HbA1c results independently of blood glucose have been eliminated from most modern methods. These include carbamylation, labile intermediates, and common hemoglobin variants. Nevertheless, some factors (e.g., race and aging) may alter HbA1c interpretation, but whether these differences have clinical implications remains contentious. HbA1c has a fundamental role in the diagnosis and management of diabetes. Ongoing improvements in HbA1c measurement and quality will further enhance the clinical value of this analyte.
This patient presented with symptoms typical of diabetes mellitus, namely polyuria, polydipsia, and weight loss. Together with the increased blood glucose concentration (200 mg/dL (11.1 mmol/L)), ...these findings establish the diagnosis of diabetes. The rapid onset combined with the magnitude of the glucose rise point to type 1 diabetes.
The Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) established the importance of hemoglobin A(1c) (Hb A(1c)) as a predictor of outcome in ...patients with diabetes mellitus. In 1994, the American Diabetes Association began recommending specific Hb A(1c) targets, but lack of comparability among assays limited the ability of clinicians to use these targets. The National Glycohemoglobin Standardization Program (NGSP) was implemented in 1996 to standardize Hb A(1c) results to those of the DCCT/UKPDS.
The NGSP certifies manufacturers of Hb A(1c) methods as traceable to the DCCT. The certification criteria have been tightened over time and the NGSP has worked with the College of American Pathologists in tightening proficiency-testing requirements. As a result, variability of Hb A(1c) results among clinical laboratories has been considerably reduced. The IFCC has developed a reference system for Hb A(1c) that facilitates metrological traceability to a higher order. The NGSP maintains traceability to the IFCC network via ongoing sample comparisons. There has been controversy over whether to report Hb A(1c) results in IFCC or NGSP units, or as estimated average glucose. Individual countries are making this decision.
Variability among Hb A(1c) results has been greatly reduced. Not all countries will report Hb A(1c) in the same units, but there are established equations that enable conversion between different units. Hb A(1c) is now recommended for diagnosing diabetes, further accentuating the need for optimal assay performance. The NGSP will continue efforts to improve Hb A(1c) testing to ensure that clinical needs are met.
The Hippo signaling pathway is a master regulator of organ size and tissue homeostasis. Hippo integrates a broad range of cellular signals to regulate numerous processes, such as cell proliferation, ...differentiation, migration and mechanosensation. Ca2+ is a fundamental second messenger that modulates signaling cascades involved in diverse cellular functions, some of which are also regulated by the Hippo pathway. Studies published over the last five years indicate that Ca2+ can influence core Hippo pathway components. Nevertheless, comprehensive understanding of the crosstalk between Ca2+ signaling and the Hippo pathway, and possible mechanisms through which Ca2+ regulates Hippo, remain to be elucidated. In this review, we summarize the multiple intersections between Ca2+ and the Hippo pathway and address the biological consequences.
•The Hippo signaling pathway is a master regulator of organ size and tissue homeostasis.•Ca2+ is a fundamental second messenger that modulates diverse signaling cascades.•Ca2+ can influence Hippo pathway components.•This review summarises the biological consequences of the intersections between Ca2+ and Hippo.
BACKGROUND: Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially. ...APPROACH: An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association. CONTENT: In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A₁c (HbA₁c) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of HbA₁c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. SUMMARY: The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended.
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