Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus
Publication Date: July 19, 2023
Last Updated: July 24, 2023
GLUCOSE
- Fasting glucose should be measured in venous plasma when used to establish the diagnosis of diabetes, with a value ≥7.0 mmol/L (≥126 mg/dL) diagnostic of diabetes.
- A (high)
- Screening by hemoglobin A1c (Hb A1c), FPG or 2-h OGTT is recommended for individuals who are at high risk of diabetes. If Hb A1c is <5.7% (<39 mmol/mol), FPG is <5.6 mmol/L (<100 mg/dL), and/or 2-h plasma glucose is <7.8 mmol/L (<140 mg/dL), testing should be repeated at 3-year intervals.
- B (moderate)
- Glucose should be measured in venous plasma when used for screening of high-risk individuals.
- B (moderate)
- Plasma glucose should be measured in an accredited laboratory when used for diagnosis of or screening for diabetes.
- GPP (good practice point)
- Blood for fasting plasma glucose analysis should be drawn in the morning after the subject has fasted overnight (at least 8 h).
- B (low)
- To minimize glycolysis, a tube containing a rapidly effective glycolytic inhibitor such as granulated citrate buffer should be used for collecting the sample. If this cannot be achieved, the sample tube should immediately be placed in an ice-water slurry and subjected to centrifugation to remove the cells within 15 to 30 min. Tubes with only enolase inhibitors such as sodium fluoride should not be relied on to prevent glycolysis.
- B (moderate)
- Based on biological variation, glucose measurement should have analytical imprecision ≤2.4%, bias ≤2.1% and total error ≤6.1%. To avoid misclassification of individuals, the goal for glucose analysis should be to minimize total analytical error and methods should be without measurable bias.
- B (moderate)
GLUCOSE METERS
- Portable glucose meters should not be used in the diagnosis of diabetes, including gestational diabetes.
- B (moderate)
- Frequent blood glucose monitoring (BGM) is recommended for all people with diabetes who use intensive insulin regimens (with multiple daily injections or insulin pump therapy) and who are not using continuous glucose monitoring (CGM).
- A (high)
- Routine use of BGM is not recommended for people with type 2 diabetes treated with diet and/or oral agents alone.
- A (high)
- Individuals with diabetes should be instructed in the correct use of glucose meters, including technique of sample collection and use of quality control.
- GPP
- Glucose meters should report the glucose concentrations in plasma rather than in whole blood to facilitate comparison with plasma results of assays performed in accredited laboratories.
- GPP
- Glucose meters should meet relevant accuracy standards of the FDA in the US or comparable analytical performance specifications in other locations.
- GPP
- In hospitals and acute-care facilities, point-of-care testing personnel, including nurses, should use glucose meters that are intended for professional use.
- GPP
- When testing newborns, personnel should use only meters that are intended for use in newborns.
- GPP
- Unless CGM is used, people using multiple daily injections of insulin should be encouraged to perform BGM at a frequency appropriate for their insulin dosage regimen, typically at least 4 times per day.
- B (moderate)
- Manufacturers should continue to improve the analytical performance of meters.
- GPP
CONTINUOUS GLUCOSE MONITORS
- Real-time CGM should be used in conjunction with insulin as a tool to lower Hb A1c levels and/or reduce hypoglycemia in teens and adults with type 1 diabetes who are not meeting glycemic targets, have hypoglycemia unawareness, and/or episodes of hypoglycemia.
- A (high)
- Consider using intermittently scanned CGM in conjunction with insulin as a tool to lower Hb A1c levels and/or reduce hypoglycemia in adults with type 1 diabetes who are not meeting glycemic targets, have hypoglycemia unawareness and/or episodes of hypoglycemia.
- B (moderate)
- Consider using real-time continuous glucose monitoring to improve Hb A1c levels, time in range, and neonatal outcomes in pregnant women with type 1 diabetes.
- B (moderate)
- Consider using real-time CGM or intermittently scanned CGM to lower Hb A1c and/or reduce hypoglycemia in adults with type 2 diabetes who are using insulin and not meeting glycemic targets.
- B (moderate)
- Consider real-time CGM or intermittently scanned CGM in children with type 1 diabetes, based on regulatory approval, as an additional tool to help improve glucose control and reduce the risk of hypoglycemia.
- B (low)
- Consider using professional CGM data coupled with diabetes self-management education and medication dose adjustment to identify and address patterns of hyper- and hypoglycemia in people with type 1 or type 2 diabetes.
- GPP
- For individuals using CGM devices that require calibration by users, a blood glucose meter should be used to calibrate the CGM. Calibration should be done at a time when glucose is not rising or falling rapidly. For all individuals using CGM, BGM should be done during periods when CGM results are not available or are incomplete, or when the CGM results are inconsistent with the clinical state or suspected to be inaccurate.
- GPP
- CGM data reports should be available in consistent formats that include standard metrics such as time in range, time in hyperglycemia, time in hypoglycemia, mean glucose, and coefficient of variation.
- GPP
NONINVASIVE GLUCOSE SENSING
- Overall, noninvasive glucose measurement systems cannot be recommended as replacements for either BGM or CGM technologies at this time.
- C (very low)
GESTATIONAL DIABETES MELLITUS
- All pregnant women with risk factors for diabetes should be tested for undiagnosed prediabetes and diabetes at the first prenatal visit using standard diagnostic criteria.
- A (moderate)
- All pregnant women not previously known to have diabetes should be evaluated for GDM at 24 to 28 weeks of gestation.
- A (high)
- Either the 1-step or 2-step protocol may be used, depending on regional preferences.
- A (moderate)
- Women with GDM should perform fasting and postprandial BGM for optimal glucose control.
- B (low)
- Target glucose values are FPG <5.3 mmol/L (<95 mg/dL) and either 1-h postprandial <7.8 mmol/L (<140 mg/dL) or 2-h postprandial <6.7 mmol/L (<120 mg/dL).
- B (low)
- Women with GDM should be tested for prediabetes or diabetes 4 to 12 weeks postpartum using nonpregnant OGTT criteria.
- A (moderate)
- Lifelong screening for diabetes should be performed in women with a history of GDM using standard nonpregnant criteria at least every 3 years.
- A (high)
- There is ongoing research, but insufficient evidence at this time, to recommend testing for GDM before 20 weeks of gestation.
- C (low)
URINE GLUCOSE
- Urine glucose testing is not recommended for routine care of patients with diabetes mellitus.
- B (low)
KETONE TESTING
- Individuals who are prone to ketosis (those with type 1 diabetes, history of diabetic ketoacidosis [DKA], or treated with sodium-glucose co-transporter-2 (SGLT-2) inhibitors should measure ketones in urine or blood if they have unexplained hyperglycemia or symptoms of ketosis (abdominal pain, nausea), and implement sick day rules and/or seek medical advice if urine or blood ketones are increased.
- B (moderate)
- Specific measurement of β-hydroxybutyrate (βOHB) in blood should be used for diagnosis of DKA and may be used for monitoring during treatment of DKA.
- B (moderate)
- Blood ketone determinations that rely on the nitroprusside reaction should not be used to monitor treatment of DKA.
- B (low)
HEMOGLOBIN A1C
- Laboratory-based Hb A1c testing can be used to diagnose: (a) diabetes, with a value ≥6.5% (≥48 mmol/mol) diagnostic of diabetes, and (b) prediabetes (or high risk for diabetes) with an Hb A1c level of 5.7% to 6.4% (39to 46 mmol/mol). An NGSP-certified method should be performed in an accredited laboratory.
- A (moderate)
- Point-of-care Hb A1c testing for diabetes screening and diagnosis should be restricted to FDA-approved devices at CLIA-certified laboratories that perform testing of moderate complexity or higher.
- B (low)
- Hb A1c should be measured routinely (usually every 3 months until acceptable, individualized targets are achieved and then no less than every 6 months) in most individuals with diabetes mellitus to document their degree of glycemic control.
- A (moderate)
- Treatment goals should be based on ADA recommendations which include maintaining Hb A1c concentrations <7% (<53 mmol/mol) for many nonpregnant people with diabetes and more stringent goals in selected individuals if this can be achieved without significant hypoglycemia or other adverse effects of treatment. (Note that these values are applicable only if the assay method is certified by the NGSP as traceable to the DCCT reference.)
- A (high)
- Higher target ranges are recommended for children and adolescents, and are appropriate for individuals with limited life expectancy, extensive co-morbid illnesses, a history of severe hypoglycemia, and advanced complications.
- A (high)
- During pregnancy and in preparation for pregnancy, women with diabetes should try to achieve Hb A1c goals that are more stringent than in the nonpregnant state, aiming ideally for <6.0% (<42 mmol/mol) during pregnancy to protect the fetus from congenital malformations and the baby and mother from perinatal trauma and morbidity owing to large-for-date babies.
- A (moderate)
- Laboratories should be aware of potential interferences, including hemoglobin variants that may affect Hb A1c test results depending on the method used. In selecting assay methods, laboratories should consider the potential for interferences in their particular patient population.
- GPP
- Hb A1c measurements in individuals with disorders that affect red blood cell turnover may provide spurious (generally falsely low) results regardless of the method used and glucose testing will be necessary for screening, diagnosis, and management.
- GPP
- Assays of other glycated proteins, such as fructosamine or glycated albumin, may be used in clinical settings where abnormalities in red blood cell turnover, hemoglobin variants, or other interfering factors compromise interpretation of Hb A1c test results, although they reflect a shorter period of average glycemia than Hb A1c.
- GPP
- Hb A1c cannot be measured and should not be reported in individuals who do not have Hb A, e.g., those with homozygous hemoglobin variants, such as Hb SS or Hb EE; glycated proteins, such as fructosamine or glycated albumin, may be used.
- GPP
- Laboratories should use only Hb A1c assay methods that are certified by the NGSP as traceable to the DCCT reference. The manufacturers of Hb A1c assays should also show traceability to the IFCC reference method.
- GPP
- Laboratories that measure Hb A1c should participate in an accuracy-based proficiency-testing program that uses fresh whole blood samples with targets set by the NGSP Laboratory Network.
- GPP
- The goals for imprecision for Hb A1c measurement are intra-laboratory CV <1.5% and inter-laboratory CV <2.5% (using at least 2 control samples with different Hb A1c levels), and ideally no measurable bias.
- B (low)
- Hb A1c should be reported as a percentage of total hemoglobin or as mmol/mol of total hemoglobin.
- GPP
- Hb A1c may also be reported as estimated average glucose (eAG) to facilitate comparison with the home glucose monitoring results and make the interpretation of the Hb A1c more accessible to people with diabetes.
- GPP
- Laboratories should verify by repeat testing specimens with Hb A1c results below the lower limit of the reference interval or greater than 15% (140 mmol/mol) Hb A1c.
- GPP
GENETIC MARKERS
- Routine determination of genetic markers such as HLA genes or single nucleotide polymorphisms (SNP) is of no value at this time for the diagnosis or management of type 1 diabetes. Typing for genetic markers and the use of genetic risk scores are recommended for individuals who cannot be clearly classified as having type 1 or type 2 diabetes.
- A (moderate)
- For selected diabetes syndromes, including neonatal diabetes and MODY (maturity onset diabetes of the young), valuable information including treatment options can be obtained with definition of diabetes-associated mutations.
- A (moderate)
- There is no role for routine genetic testing in people with type 2 diabetes. These studies should be confined to the research setting and evaluation of specific syndromes.
- A (moderate)
AUTOIMMUNE MARKERS
- Standardized islet autoantibody tests are recommended for classification of diabetes in adults in whom there is phenotypic overlap between type 1 and type 2 diabetes and uncertainty as to the type of diabetes.
- GPP
- Islet autoantibodies are not recommended for routine diagnosis of diabetes.
- B (low)
- Longitudinal follow-up of subjects with 2 or more islet autoantibodies is recommended to stage diabetes into stage 1: two or more islet autoantibodies, normoglycemia, no symptoms; stage 2: two or more islet autoantibodies, dysglycemia, no symptoms; and stage 3: two or more islet autoantibodies, diabetes and symptoms.
- GPP
- Standardized islet autoantibody tests are recommended in prospective research studies of children at increased genetic risk of type 1 diabetes following HLA typing at birth or in first degree relatives of individuals with type 1 diabetes.
- B (low)
- Screening for islet autoantibodies in relatives of individuals with type 1 diabetes or in persons in the general population is recommended in the setting of a research study or can be offered as an option for first degree relatives of a proband with type 1 diabetes.
- B (low)
- Routine screening for islet autoantibodies in people with type 2 diabetes is not recommended at present.
- B (low)
- There is currently no role for measurement of islet autoantibodies in the monitoring of individuals with established type 1 diabetes.
- B (low)
- It is important that islet autoantibodies be measured only in an accredited laboratory with an established quality control program and participation in a proficiency testing program.
- GPP
URINE ALBUMIN
- Annual testing for albuminuria should begin in pubertal or post-pubertal individuals 5 years after diagnosis of type 1 diabetes and at the time of diagnosis of type 2 diabetes, regardless of treatment.
- A (high)
- Urine albumin should be measured annually in adults with diabetes using morning spot urine albumin:creatinine ratio (uACR).
- A (high)
- If eGFR is <60 mL/min/1.73 m2 and/or albuminuria is >30 mg/g creatinine in a spot urine sample, the uACR should be repeated every 6 months to assess change among people with diabetes and hypertension.
- A (moderate)
- First morning void urine sample should be used for measurement of albumin:creatinine ratio.
- A (moderate)
- If first morning void sample is difficult to obtain, to minimize variability in test results, all urine collections should be at the same time of day. The individual should be well hydrated and should not have ingested food within the preceding 2 h or have exercised.
- GPP
- Timed collection for urine albumin should be done only in research settings and should not be used to guide clinical practice.
- GPP
- The analytical performance goals for urine albumin measurement should be between-day precision ≤6%, bias ≤7% to 13%, and total allowable error of ≤24% to 30%.
- GPP
- Semi-quantitative uACR dipsticks can be used to detect early kidney disease and assess cardiovascular risk when quantitative tests are not available.
- B (moderate)
- Semi-quantitative or qualitative screening tests should be positive in >85% of individuals with moderately increased albuminuria to be useful for patient screening.
- B (moderate)
- Practitioners should strictly adhere to manufacturer's instructions when using the semi-quantitative uACR dipstick test and repeat it for confirmation to achieve adequate sensitivity for detecting moderately increased albuminuria.
- B (moderate)
- Positive urine albumin screening results by semi-quantitative tests should be confirmed by quantitative analysis in an accredited laboratory.
- GPP
- Currently available proteinuria dipstick tests should not be used to assess albuminuria.
- B (moderate)
MISCELLANEOUS POTENTIALLY IMPORTANT ANALYTES
- In most people with diabetes or risk for diabetes or cardiovascular disease, routine testing for insulin or proinsulin is not recommended. These assays are useful primarily for research purposes.
- B (moderate)
- Although differentiation between type 1 and type 2 diabetes can usually be made based on the clinical presentation and subsequent course, C-peptide measurements may help distinguish type 1 from type 2 diabetes in ambiguous cases, such as individuals who have a type 2 phenotype but present in ketoacidosis.
- B (moderate)
- If required by the payer for coverage of insulin pump therapy, measure fasting C-peptide level when simultaneous fasting plasma glucose is ≤220 mg/dL (12.5 mmol/L).
- GPP
- Insulin and C-peptide assays should be standardized to facilitate measures of insulin secretion and sensitivity that will be comparable across research studies.
- GPP
- There is no published evidence to support the use of insulin antibody testing for routine care of people with diabetes.
- C (very low)
Recommendation Grading
Disclaimer
The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.
Overview
Title
Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus
Authoring Organizations
Association for Diagnostics & Laboratory Medicine
American Diabetes Association
Publication Month/Year
July 19, 2023
Last Updated Month/Year
April 1, 2024
Document Type
Guideline
Country of Publication
US
Document Objectives
Diabetes can be diagnosed by demonstrating increased concentrations of glucose in venous plasma or increased hemoglobin A1c (Hb A1c) in the blood. Glycemic control is monitored by the people with diabetes measuring their own blood glucose with meters and/or with continuous interstitial glucose monitoring (CGM) devices and also by laboratory analysis of Hb A1c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of ketones, autoantibodies, urine albumin, insulin, proinsulin, and C-peptide are addressed. The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.
Inclusion Criteria
Male, Female, Adolescent, Adult, Child, Infant, Older adult
Health Care Settings
Ambulatory, Laboratory services
Intended Users
Laboratory technician, nurse, nurse practitioner, physician, physician assistant
Scope
Diagnosis, Assessment and screening, Management
Diseases/Conditions (MeSH)
D003920 - Diabetes Mellitus, D003922 - Diabetes Mellitus, Type 1, D003924 - Diabetes Mellitus, Type 2
Keywords
diabetes mellitus, type 2 diabetes mellitus, type 1 diabetes mellitus, Laboratory Analysis of Diabetes Mellitus
Source Citation
David B Sacks and others, Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus, Clinical Chemistry, 2023;, hvad080, https://doi.org/10.1093/clinchem/hvad080