Last updated March 15, 2022

Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

Recommendations

Glucose

WHEN GLUCOSE IS USED TO ESTABLISH THE DIAGNOSIS OF DIABETES, IT SHOULD BE MEASURED IN VENOUS PLASMA. (High, A)
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WHEN GLUCOSE IS USED FOR SCREENING OF HIGH-RISK INDIVIDUALS, IT SHOULD BE MEASURED IN VENOUS PLASMA.  (Moderate, B)
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PLASMA GLUCOSE SHOULD BE MEASURED IN AN ACCREDITED LABORATORY WHEN USED FOR DIAGNOSIS OF OR SCREENING FOR DIABETES. (, GPP)
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OUTCOME STUDIES ARE NEEDED TO DETERMINE THE EFFECTIVENESS OF SCREENING. (Moderate, C)
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ROUTINE MEASUREMENT OF PLASMA GLUCOSE CONCENTRATIONS IN AN ACCREDITED LABORATORY IS NOT RECOMMENDED AS THE PRIMARY MEANS OF MONITORING OR EVALUATING THERAPY IN INDIVIDUALS WITH DIABETES. (Low, B)
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ANALYTICAL CONSIDERATIONS

BLOOD FOR FPG ANALYSIS SHOULD BE DRAWN IN THE MORNING AFTER THE INDIVIDUAL HAS FASTED OVERNIGHT (AT LEAST 8 h). (Low, B)
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TO MINIMIZE GLYCOLYSIS, ONE SHOULD PLACE THE SAMPLE TUBE IMMEDIATELY IN AN ICE–WATER SLURRY, AND THE PLASMA SHOULD BE SEPARATED FROM THE CELLS WITHIN 30 MIN. IF THAT CANNOT BE ACHIEVED, A TUBE CONTAINING A RAPIDLY EFFECTIVE GLYCOLYSIS INHIBITOR, SUCH AS CITRATE BUFFER, SHOULD BE USED FOR COLLECTING THE SAMPLE. TUBES WITH ONLY ENOLASE INHIBITORS, SUCH AS SODIUM FLUORIDE, SHOULD NOT BE RELIED ON TO PREVENT GLYCOLYSIS. (Moderate, B)
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ON THE BASIS OF BIOLOGICAL VARIATION, GLUCOSE MEASUREMENT SHOULD HAVE AN ANALYTICAL IMPRECISION <2.9%, A BIAS <2.2%, AND A TOTAL ERROR <6.9%. TO AVOID MISCLASSIFICATION OF PATIENTS, THE GOAL FOR GLUCOSE ANALYSIS SHOULD BE TO MINIMIZE TOTAL ANALYTICAL ERROR, AND METHODS SHOULD BE WITHOUT MEASURABLE BIAS. (Low, B)
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INTERPRETATION

Glucose Meters

THERE ARE INSUFFICIENT PUBLISHED DATA OUTCOME TO SUPPORT A ROLE FOR PORTABLE METERS AND SKIN-PRICK (FINGER-STICK) BLOOD SAMPLES IN THE DIAGNOSIS OF DIABETES OR FOR POPULATION SCREENING. (Moderate, C)
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THE IMPRECISION OF THE RESULTS, COUPLED WITH THE SUBSTANTIAL DIFFERENCES AMONG METERS, PRECLUDES THE USE OF GLUCOSE METERS FROM THE DIAGNOSIS OF DIABETES AND LIMITS THEIR USEFULNESS IN SCREENING FOR DIABETES. (Moderate, A)
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SMBG IS RECOMMENDED FOR ALL INSULIN-TREATED PATIENTS WITH DIABETES. (High, A)
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IN PATIENTS WITH TYPE 2 DIABETES TREATED WITH DIET AND ORAL AGENTS, SMBG MAY HELP ACHIEVE BETTER CONTROL, PARTICULARLY WHEN THERAPY IS INITIATED OR CHANGED. DATA ARE INSUFFICIENT, HOWEVER, TO CLAIM AN ASSOCIATED IMPROVEMENT OF HEALTH OUTCOMES. THE ROLE OF SMBG IN PATIENTS WITH STABLE TYPE 2 DIABETES CONTROLLED BY DIET ALONE IS NOT KNOWN. (High, C)
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ANALYTICAL CONSIDERATIONS

PATIENTS SHOULD BE INSTRUCTED IN THE CORRECT USE OF GLUCOSE METERS, INCLUDING QUALITY CONTROL. COMPARISON BETWEEN SMBG AND CONCURRENT LABORATORY GLUCOSE ANALYSIS SHOULD BE PERFORMED AT REGULAR INTERVALS TO EVALUATE THE PERFORMANCE OF THE METERS IN THE PATIENT’S HANDS. (Moderate, B)
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MULTIPLE PERFORMANCE GOALS FOR PORTABLE GLUCOSE METERS HAVE BEEN PROPOSED. THESE TARGETS VARY WIDELY AND ARE HIGHLY CONTROVERSIAL. MANUFACTURERS SHOULD WORK TO IMPROVE THE IMPRECISION OF CURRENT METERS, WITH AN INTERMEDIATE GOAL OF LIMITING TOTAL ERROR FOR 95% OF SAMPLES TO <15% AT GLUCOSE CONCENTRATIONS >5.6 mmol/L (100 mg/dL) AND TO <0.8 mmol/L (15 mg/dL) AT GLUCOSE CONCENTRATIONS <5.6 mmol/L (100 mg/dL). LOWER TOTAL ERROR WOULD BE DESIRABLE AND MAY PROVE NECESSARY IN TIGHT GLUCOSE-CONTROL PROTOCOLS AND FOR AVOIDING HYPOGLYCEMIA IN ALL SETTINGS. (Low, C)
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METERS SHOULD MEASURE AND REPORT PLASMA GLUCOSE CONCENTRATIONS TO FACILITATE COMPARISON WITH ASSAYS PERFORMED IN ACCREDITED LABORATORIES. (, GPP)
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STUDIES ARE NEEDED TO DETERMINE THE ANALYTICAL GOALS (QUALITY SPECIFICATIONS) FOR GLUCOSE METERS IN SMBG AND IN ICUs. (Moderate, C)
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RECOMMENDATIONS FOR FUTURE RESEARCH: IMPORTANT END POINTS IN STUDIES OF SMBG SHOULD INCLUDE, AT A MINIMUM, HbA1c AND FREQUENCY OF HYPOGLYCEMIC EPISODES TO ASCERTAIN WHETHER IMPROVED METER  ENABLE PATIENTS TO ACHIEVE BETTER GLUCOSE CONTROL.  FOR STUDIES OF METER USE IN INTENSIVE OR CRITICAL CARE, IMPORTANT END POINTS INCLUDE MEAN BLOOD GLUCOSE, FREQUENCY OF HYPOGLYCEMIA, AND VARIATION OF GLUCOSE CONTROL. IDEALLY, OUTCOMES (e.g., LONGTERM COMPLICATIONS) SHOULD ALSO BE EXAMINED.
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Continuous Minimally Invasive Glucose Analyses

REAL-TIME CONTINUOUS GLUCOSE MONITORING (CGM) IN CONJUNCTION WITH INTENSIVE INSULIN REGIMENS CAN BE A USEFUL TOOL TO LOWER Hb A1c IN SELECTED ADULTS (AGE >25 YEARS) WITH TYPE 1 DIABETES. (High, A)
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ALTHOUGH THE EVIDENCE FOR LOWERING Hb A1c IS NOT AS STRONG FOR CHILDREN, TEENS, AND YOUNGER ADULTS, REAL-TIME CGM MAY BE HELPFUL IN THESE GROUPS. SUCCESS CORRELATES WITH ADHERENCE TO ONGOING USE OF THE DEVICE. (Moderate, B)
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REAL-TIME CGM MAY BE A SUPPLEMENTAL TOOL TO SMBG IN INDIVIDUALS WITH HYPOGLYCEMIA UNAWARENESS AND/OR FREQUENT EPISODES OF HYPOGLYCEMIA. (Low, B)
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PATIENTS REQUIRE EXTENSIVE TRAINING IN USING THE DEVICE. AVAILABLE DEVICES MUST BE CALIBRATED WITH SMBG READINGS, AND THE LATTER ARE RECOMMENDED FOR MAKING TREATMENT CHANGES.
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Noninvasive Glucose Analysis

NO NONINVASIVE SENSING TECHNOLOGY IS CURRENTLY APPROVED FOR CLINICAL GLUCOSE MEASUREMENTS OF ANY KIND. MAJOR TECHNOLOGICAL HURDLES MUST BE OVERCOME BEFORE NONINVASIVE SENSING TECHNOLOGY WILL BE SUFFICIENTLY RELIABLE TO REPLACE EXISTING PORTABLE METERS, IMPLANTABLE BIOSENSORS, OR MINIMALLY INVASIVE TECHNOLOGIES. (Very Low, C)
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Gestational Diabetes Mellitus

ALL PREGNANT WOMEN NOT PREVIOUSLY KNOWN TO HAVE DIABETES SHOULD UNDERGO TESTING FOR GDM AT 24–28 WEEKS OF GESTATION. (High, A)
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GDM SHOULD BE DIAGNOSED BY A 75-g OGTT ACCORDING TO THE IADPSG CRITERIA DERIVED FROM THE HAPO STUDY. (Moderate, A)
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Urinary Glucose

SEMIQUANTITATIVE URINE GLUCOSE TESTING IS NOT RECOMMENDED FOR ROUTINE CARE OF PATIENTS WITH DIABETES MELLITUS. (Low, B)
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Ketone Testing

KETONES MEASURED IN URINE OR BLOOD IN THE HOME SETTING BY PATIENTS WITH DIABETES AND IN THE CLINIC/HOSPITAL SETTING SHOULD BE CONSIDERED ONLY AN ADJUNCT TO THE DIAGNOSIS OF DKA. (, GPP)
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URINE KETONE MEASUREMENTS SHOULD NOT BE USED TO DIAGNOSE OR MONITOR THE COURSE OF DKA. (, GPP)
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BLOOD KETONE DETERMINATIONS THAT RELY ON THE NITROPRUSSIDE REACTION SHOULD BE USED ONLY AS AN ADJUNCT TO DIAGNOSE DKA AND SHOULD NOT BE USED TO MONITOR DKA TREATMENT. SPECIFIC MEASUREMENT OF HBA IN BLOOD CAN BE USED FOR DIAGNOSIS AND MONITORING OF DKA. (Moderate, B)
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Hb A1c

HbA1c SHOULD BE MEASURED ROUTINELY IN ALL PATIENTS WITH DIABETES MELLITUS TO DOCUMENT THEIR DEGREE OF GLYCEMIC CONTROL. (Moderate, A)
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LABORATORIES SHOULD USE ONLY HbA1c ASSAY METHODS THAT ARE CERTIFIED BY THE NATIONAL GLYCOHEMOGLOBIN STANDARDIZATION PROGRAM (NGSP) AS TRACEABLE TO THE DCCT REFERENCE. THE MANUFACTURERS OF HbA1c ASSAYS SHOULD ALSO SHOW TRACEABILITY TO THE IFCC REFERENCE METHOD.
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LABORATORIES THAT MEASURE HbA1c SHOULD PARTICIPATE IN A PROFICIENCY-TESTING PROGRAM, SUCH AS THE COLLEGE OF AMERICAN PATHOLOGISTS (CAP) HbA1c SURVEY, THAT USES FRESH BLOOD SAMPLES WITH TARGETS SET BY THE NGSP LABORATORY NETWORK.
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LABORATORIES SHOULD BE AWARE OF POTENTIAL INTERFERENCES, INCLUDING HEMOGLOBINOPATHIES, THAT MAY AFFECT HbA1c TEST RESULTS, DEPENDING ON THE METHOD USED. IN SELECTING ASSAY METHODS, LABORATORIES SHOULD CONSIDER THE POTENTIAL FOR INTERFERENCES IN THEIR PARTICULAR PATIENT POPULATION. IN ADDITION, DISORDERS THAT AFFECT ERYTHROCYTE TURNOVER MAY CAUSE SPURIOUS RESULTS, REGARDLESS OF THE METHOD USED.
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DESIRABLE SPECIFICATIONS FOR HbA1c MEASUREMENT ARE AN INTRALABORATORY CV <2% AND AN INTERLABORATORY CV <3.5%. AT LEAST 2 CONTROL MATERIALS WITH DIFFERENT MEAN VALUES SHOULD BE ANALYZED AS AN INDEPENDENT MEASURE OF ASSAY PERFORMANCE. (Low, B)
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SAMPLES WITH HbA1c RESULTS BELOW THE LOWER LIMIT OF THE REFERENCE INTERVAL OR >15% HbA1c SHOULD BE VERIFIED BY REPEAT TESTING. (Low, B)
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Hb A1c VALUES THAT ARE INCONSISTENT WITH THE CLINICAL PRESENTATION SHOULD BE INVESTIGATED FURTHER. (, GPP)
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TREATMENT GOALS SHOULD BE BASED ON ADA RECOMMENDATIONS, WHICH INCLUDE GENERALLY MAINTAINING HbA1c CONCENTRATIONS AT <7% AND MORE-STRINGENT GOALS IN SELECTED INDIVIDUAL PATIENTS IF THEY CAN BE ACHIEVED WITHOUT SIGNIFICANT HYPOGLYCEMIA OR OTHER ADVERSE TREATMENT EFFECTS. SOMEWHAT HIGHER INTERVALS ARE RECOMMENDED FOR CHILDREN AND ADOLESCENTS AND MAY BE APPROPRIATE FOR PATIENTS WITH A LIMITED LIFE EXPECTANCY, EXTENSIVE COMORBID ILLNESSES, A HISTORY OF SEVERE HYPOGLYCEMIA, OR ADVANCED COMPLICATIONS (NOTE THAT THESE VALUES ARE APPLICABLE ONLY IF THE NGSP HAS CERTIFIED THE ASSAY METHOD AS TRACEABLE TO THE DCCT REFERENCE). (High, A)
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HbA1c TESTING SHOULD BE PERFORMED AT LEAST BIANNUALLY IN ALL PATIENTS AND QUARTERLY FOR PATIENTS WHOSE THERAPY HAS CHANGED OR WHO ARE NOT MEETING TREATMENT GOALS. (Low, B)
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HbA1c MAY BE USED FOR THE DIAGNOSIS OF DIABETES, WITH VALUES >6.5% BEING DIAGNOSTIC. AN NGSP-CERTIFIED METHOD SHOULD BE PERFORMED IN AN ACCREDITED LABORATORY. ANALOGOUS TO ITS USE IN THE MANAGEMENT OF DIABETES, FACTORS THAT INTERFERE WITH OR ADVERSELY AFFECT THE Hb A1c ASSAY WILL PRECLUDE ITS USE IN DIAGNOSIS. (Moderate, A)
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POINT-OF-CARE HbA1c ASSAYS ARE NOT SUFFICIENTLY ACCURATE TO USE FOR THE DIAGNOSIS OF DIABETES. (Moderate, B)
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Genetic Markers

ROUTINE MEASUREMENT OF GENETIC MARKERS IS NOT OF VALUE AT THIS TIME FOR THE DIAGNOSIS OR MANAGEMENT OF PATIENTS WITH TYPE 1 DIABETES. FOR SELECTED DIABETIC SYNDROMES, INCLUDING NEONATAL DIABETES, VALUABLE INFORMATION CAN BE OBTAINED WITH DEFINITION OF DIABETES-ASSOCIATED MUTATIONS. (Moderate, A)
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THERE IS NO ROLE FOR ROUTINE GENETIC TESTING IN PATIENTS WITH TYPE 2 DIABETES. THESE STUDIES SHOULD BE CONFINED TO THE RESEARCH SETTING AND EVALUATION OF SPECIFIC SYNDROMES. (Moderate, A)
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Autoimmune Markers

ISLET CELL AUTOANTIBODIES ARE RECOMMENDED FOR SCREENING NONDIABETIC FAMILY MEMBERS WHO WISH TO DONATE PART OF THEIR PANCREAS FOR TRANSPLANTATION INTO A RELATIVE WITH END-STAGE TYPE 1 DIABETES. (Low, B)
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ISLET CELL AUTOANTIBODIES ARE NOT RECOMMENDED FOR ROUTINE DIAGNOSIS OF DIABETES, BUT STANDARDIZED ISLET CELL AUTOANTIBODY TESTS MAY BE USED FOR CLASSIFICATION OF DIABETES IN ADULTS AND IN PROSPECTIVE STUDIES OF CHILDREN AT GENETIC RISK FOR TYPE 1 DIABETES AFTER HLA TYPING AT BIRTH. (Low, B)
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SCREENING PATIENTS WITH TYPE 2 DIABETES FOR ISLET CELL AUTOANTIBODIES IS NOT RECOMMENDED AT PRESENT. STANDARDIZED ISLET CELL AUTOANTIBODIES ARE TESTED IN PROSPECTIVE CLINICAL STUDIES OF TYPE 2 DIABETES PATIENTS TO IDENTIFY POSSIBLE MECHANISMS OF SECONDARY FAILURES OF TREATMENT OF TYPE 2 DIABETES. (Low, B)
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SCREENING FOR ISLET CELL AUTOANTIBODIES IN RELATIVES OF PATIENTS WITH TYPE 1 DIABETES OR IN PERSONS FROM THE GENERAL POPULATION IS NOT RECOMMENDED AT PRESENT. STANDARDIZED ISLET CELL AUTOANTIBODIES ARE TESTED IN PROSPECTIVE CLINICAL STUDIES. (Low, B)
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THERE IS CURRENTLY NO ROLE FOR MEASUREMENT OF ISLET CELL AUTOANTIBODIES IN THE MONITORING OF PATIENTS IN CLINICAL PRACTICE. ISLET CELL AUTOANTIBODIES ARE MEASURED IN RESEARCH PROTOCOLS AND IN SOME CLINICAL TRIALS AS SURROGATE END POINTS. (Low, B)
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IT IS IMPORTANT THAT ISLET CELL AUTOANTIBODIES BE MEASURED ONLY IN AN ACCREDITED LABORATORY WITH AN ESTABLISHED QUALITY-CONTROL PROGRAM AND PARTICIPATION IN A PROFICIENCY-TESTING PROGRAM. (, GPP)
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Albuminuria (Formerly Microalbuminuria)

ANNUAL TESTING FOR ALBUMINURIA IN PATIENTS WITHOUT CLINICAL PROTEINURIA SHOULD BEGIN IN PUBERTAL OR POSTPUBERTAL INDIVIDUALS 5 YEARS AFTER DIAGNOSIS OF TYPE 1 DIABETES AND AT THE TIME OF DIAGNOSIS OF TYPE 2 DIABETES, REGARDLESS OF TREATMENT. (Moderate, B)
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URINE ALBUMIN AT CONCENTRATIONS >30 mg/g CREATININE SHOULD BE CONSIDERED A CONTINUOUS RISK MARKER FOR CARDIOVASCULAR EVENTS. (Moderate, B)
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THE ANALYTICAL CV OF METHODS TO MEASURE LOW LEVELS OF ALBUMINURIA SHOULD BE <15%. (Moderate, B)
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SEMIQUANTITATIVE OR QUALITATIVE SCREENING TESTS SHOULD BE POSITIVE IN >95% OF PATIENTS WITH LOW LEVELS OF ALBUMINURIA TO BE USEFUL FOR SCREENING. POSITIVE RESULTS MUST BE CONFIRMED BY ANALYSIS IN AN ACCREDITED LABORATORY. (-, GPP)
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CURRENTLY AVAILABLE DIPSTICK TESTS DO NOT HAVE ADEQUATE ANALYTICAL SENSITIVITY TO DETECT LOW LEVELS OF ALBUMINURIA. (Moderate, B)
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ACCEPTABLE SAMPLES TO TEST FOR INCREASED URINARY ALBUMIN EXCRETION ARE TIMED COLLECTIONS (e.g., 12 OR 24 h) FOR MEASUREMENT OF THE ALBUMIN CONCENTRATION AND TIMED OR UNTIMED SAMPLES FOR MEASUREMENT OF THE ALBUMIN–CREATININE RATIO. (Moderate, B)
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THE OPTIMAL TIME FOR SPOT URINE COLLECTION IS THE EARLY MORNING. ALL COLLECTIONS SHOULD BE AT THE SAME TIME OF DAY TO MINIMIZE VARIATION. THE PATIENT SHOULD NOT HAVE INGESTED FOOD WITHIN THE PRECEDING 2 h BUT SHOULD BE WELL HYDRATED (i.e., NOT VOLUME DEPLETED).
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LOW URINE ALBUMIN CONCENTRATIONS (i.e., <30 mg/g CREATININE) ARE NOT ASSOCIATED WITH HIGH CARDIOVASCULAR RISK IF THE eGFR IS >60 mL min1 (1.73 m2)1 AND THE PATIENT IS NORMOTENSIVE. IF THE eGFR IS <60 mL min1 (1.73 m2)1 AND/OR THE LEVEL OF ALBUMINURIA IS >30 mg/g CREATININE ON A SPOT URINE SAMPLE, A REPEAT MEASUREMENT SHOULD BE TAKEN WITHIN THE YEAR TO ASSESS CHANGE AMONG PEOPLE WITH HYPERTENSION. (Moderate, A)
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THERE IS NO ROLE FOR ROUTINE TESTING FOR INSULIN, C-PEPTIDE, OR PROINSULIN IN MOST PATIENTS WITH DIABETES. DIFFERENTIATION BETWEEN TYPE 1 AND TYPE 2 DIABETES MAY BE MADE IN MOST CASES ON THE BASIS OF THE CLINICAL PRESENTATION AND THE SUBSEQUENT COURSE. THESE ASSAYS ARE USEFUL PRIMARILY FOR RESEARCH PURPOSES. OCCASIONALLY, C-PEPTIDE MEASUREMENTS MAY HELP DISTINGUISH TYPE 1 FROM TYPE 2 DIABETES IN AMBIGUOUS CASES, SUCH AS PATIENTS WHO HAVE A TYPE 2 PHENOTYPE BUT PRESENT IN KETOACIDOSIS. (Moderate, B)
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THERE IS NO ROLE FOR MEASUREMENT OF INSULIN CONCENTRATION IN THE ASSESSMENT OF CARDIOMETABOLIC RISK, BECAUSE KNOWLEDGE OF THIS VALUE DOES NOT ALTER THE MANAGEMENT OF THESE PATIENTS. (Moderate, B)
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BECAUSE CURRENT MEASURES OF INSULIN ARE POORLY HARMONIZED, A STANDARDIZED INSULIN ASSAY SHOULD BE DEVELOPED TO ENCOURAGE THE DEVELOPMENT OF MEASURES OF INSULIN SENSITIVITY THAT WILL BE PRACTICAL FOR CLINICAL CARE. (, GPP)
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THERE IS NO PUBLISHED EVIDENCE TO SUPPORT THE USE OF INSULIN ANTIBODY TESTING FOR ROUTINE CARE OF PATIENTS WITH DIABETES. (Very Low, C)
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Recommendation Grading

Overview

Title

Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

Authoring Organization

Publication Month/Year

January 1, 2011

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Infant, Older adult

Health Care Settings

Ambulatory, Laboratory services, Outpatient

Intended Users

Medical techologist technician, laboratory technician, clinical researcher, nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Diagnosis, Management

Diseases/Conditions (MeSH)

D003920 - Diabetes Mellitus, D003922 - Diabetes Mellitus, Type 1, D003924 - Diabetes Mellitus, Type 2

Keywords

diabetes mellitus, Laboratory Analysis of Diabetes Mellitus