Reviews/Commentaries/ADA Statements POSITION STATEMENT Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus 1 6 DAVID B. SACKS M. SUE KIRKMAN mellitus, formerly known as insulin- 2 7 MARK ARNOLD AKE LERNMARK 3 8 dependent diabetes mellitus (IDDM) or GEORGE L. BAKRIS BOYD E. METZGER 4 9 juvenile-onset diabetes mellitus, is usu- DAVID E. BRUNS DAVID M. NATHAN 5 ally caused by autoimmune destruction ANDREA RITA HORVATH of the pancreatic islet b-cells, rendering the pancreas unable to synthesize and se- crete insulin (2). Type 2 diabetes mellitus, 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 formerly known as non-IDDM or adult- substantially. onset diabetes, is caused by a combina- tion of insulin resistance and inadequate APPROACH—An expert committee compiled evidence-based recommendations for the use of insulin secretion (3,4). Gestational diabe- laboratory testing for patients with diabetes. A new system was developed to grade the overall quality tes mellitus (GDM), which resembles type of the evidence and the strength of the recommendations. Draft guidelines were posted on the fi 2diabetesmorethantype1,develops Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modi ed in during approximately 7% (range, 5%– 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- 15%) of pregnancies, usually remits after Based Laboratory Medicine Committee of the American Association for Clinical Chemistry jointly delivery, and constitutes a major risk fac- reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee tor for the development of type 2 diabetes and subsequently approved by the Executive Committee of the American Diabetes Association. later in life. Other types of diabetes are rare. Type 2 is the most common form, — CONTENT In addition to long-standing criteria based on measurement of plasma glucose, accounting for 85%–95% of diabetes in diabetes can be diagnosed by demonstrating increased blood hemoglobin A1c (HbA1c) concen- developed countries. Some patients can- trations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood not be clearly classified as type 1 or type 2 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, diabetes (5). proinsulin, C-peptide, and other analytes are addressed. Diabetes is a common disease. The current worldwide prevalence is esti- SUMMARY—The guidelines provide specific recommendations that are based on published mated to be approximately 250 x 106, data or derived from expert consensus. Several analytes have minimal clinical value at present, and it is expected to reach 380 x 106 by and their measurement is not recommended. 2025 (6). The prevalence of diabetes Diabetes Care 34:e61–e99, 2011 [based on fasting plasma glucose (FPG) results] in U.S. adults in 1999–2002 was 9.3%, of which 30% of the cases were un- fi iabetes mellitus is a group of met- hyperglycemia. The disease is classi ed diagnosed (7). The most recent data, abolic disorders of carbohydrate into several categories. The revised clas- – D fi which were derived from the 2005 metabolism in which glucose is si cation, published in 1997 (1), is pre- 2006 National Health and Nutrition Ex- underutilized and overproduced, causing sented in Table 1. Type 1 diabetes amination Survey (NHANES) with both ccccccccccccccccccccccccccccccccccccccccccccccccc FPG and 2-h oral glucose tolerance test (OGTT) results, show a prevalence of di- From the 1Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland; the 2Department 3 abetes in U.S. persons $20 years old of of Chemistry, University of Iowa, Iowa City, Iowa; the Department of Medicine, Hypertensive Disease Unit, 6 Section of Endocrinology, Diabetes and Metabolism, University of Chicago, Chicago, Illinois; the 4Department 12.9% (approximately 40 x 10 )(8).Of of Pathology, University of Virginia Medical School, Charlottesville, Virginia; the 5Screening and Test Evaluation these individuals, 40% (approximately 16 Program, School of Public Health, University of Sydney, SEALS Department of Clinical Chemistry, Prince million) are undiagnosed. The prevalence of Wales Hospital, Sydney, Australia; the 6American Diabetes Association, Alexandria, Virginia; the 7Department of Clinical Sciences, Lund University/CRC, Skane University Hospital Malmö, Malmö, Sweden; the 8Division of of diabetes has also increased in other Endocrinology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois; and 9Massachusetts parts of the world. For example, recent General Hospital and Harvard Medical School, Diabetes Center, Boston, Massachusetts. estimates suggest 110 x 106 diabetic indi- Corresponding author: David B. Sacks, [email protected]. viduals in Asia in 2007 (9), but the true Received 30 December 2010 and accepted 28 February 2011. DOI: 10.2337/dc11-9998 number is likely to be substantially This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10. greater, because China alone was thought 6 2337/dc11-9998/-/DC1. to have 92.4 x 10 adults with diabetes in This article is simultaneously published in Clinical Chemistry and Diabetes Care, under joint copyright, and by 2008 (10). the National Academy of Clinical Biochemistry. The worldwide costs of diabetes were © 2011 by the American Diabetes Association and the American Association for Clinical Chemistry. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the approximately $232 billion in 2007 and work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. are likely to be $302 billion by 2025 (6). See accompanying article, p. 1419. In 2007, the costs of diabetes in the U.S. care.diabetesjournals.org DIABETES CARE, VOLUME 34, JUNE 2011 e61 Position Statement Table 1—Classification of diabetes quality of the evidence (Table 2) and the several headings and subheadings (in mellitusa strength of recommendations (Table 3). parentheses), which are as follows: use This guideline focuses primarily on (diagnosis, screening, monitoring, and I. Type 1 diabetes the laboratory aspects of testing in di- prognosis); rationale (diagnosis and A. Immune-mediated abetes. It does not address any issues screening); analytical considerations (pre- B. Idiopathic related to the clinical management of analytical, including reference intervals; II. Type 2 diabetes diabetes, which are already covered in and analytical, such as methods); inter- III. Other specifictypes the American Diabetes Association (ADA) pretation (including frequency of mea- A. Genetic defects of b-cell function guidelines. The NACB guideline intends surement and turnaround time); and, B. Genetic defects in insulin action to supplement the ADA guidelines in where applicable, emerging considera- C. Diseases of the exocrine pancreas order to avoid duplication or repetition tions, which alert the reader to ongoing D. Endocrinopathies of information. Therefore, it focuses on studies and potential future aspects rele- E. Drug- or chemical-induced practical aspects of care to assist with vant to that analyte. F. Infections decisions related to the use or interpreta- G. Uncommon forms of immune-mediated tion of laboratory tests while screening, diabetes GLUCOSE diagnosing, or monitoring patients with H. Other genetic syndromes sometimes diabetes. Additional details concerning 1. Use associated with diabetes the scope, purpose, key topics, and tar- IV. GDM a gets of this guideline are described in the From the ADA (378). accompanying Supplementary Data. RECOMMENDATION: WHEN GLUCOSE IS To facilitate comprehension and as- USED TO ESTABLISH THE DIAGNOSIS were estimated to be $174 billion (11). sist the reader, we divide each analyte into OF DIABETES, IT SHOULD BE MEASURED IN The mean annual per capita healthcare VENOUS PLASMA costs for an individual with diabetes are A(high). approximately 2.3-fold higher than those Table 2—Rating scale for the quality of for individuals who do not have diabetes evidence RECOMMENDATION: WHEN GLUCOSE IS (11). Similarly, diabetes in the U.K. ac- USED FOR SCREENING OF HIGH-RISK counts for roughly 10% of the National High: Further research is very unlikely to INDIVIDUALS, IT SHOULD BE MEASURED Health Service budget (equivalent in change our confidence in the estimate of effect. The body of evidence comes from IN VENOUS PLASMA 2008 to £9 billion/year). The high costs B (moderate). of diabetes are attributable to care for both high-level individual studies that are acute conditions (such as hypoglycemia sufficiently powered and provide precise, consistent, and directly applicable results in and ketoacidosis) and debilitating compli- RECOMMENDATION: PLASMA GLUCOSE a relevant population. cations (12). The latter include both micro- SHOULD BE MEASURED IN AN — Moderate: Further research is likely to have an vascular complications predominantly ACCREDITED LABORATORY WHEN USED — important impact on our confidence in the retinopathy, nephropathy, and neuropathy FOR DIAGNOSIS OF OR SCREENING