Diabetes Mellitus

Diagnosis

Indications for Testing

  • Known risk factors for type 2 diabetes mellitus (DM)
    • Obesity (BMI ≥25 kg/m2 or ≥23 kg/m2 in Asian Americans)
    • Family history of type 2 DM in first- or second-degree relative
    • At risk race/ethnicity – Native American, African American, Latino, Asian American, Pacific Islander
    • Signs of insulin resistance or conditions associated with insulin resistance (eg, acanthosis nigricans, hypertension, dyslipidemia, PCOS, low birthweight)
    • Maternal history of DM or gestational diabetes mellitus (GDM) during pregnancy

Criteria for Diagnosis

  • Criteria for diagnosis of DM

    Criteria for Diagnosis of DM (ADA, 2015; AACE/ACE, 2015)*

    Test

    Result Confirming DM

    Comment

    HbA1c

    ≥6.5%

    If patient has discordant results on two tests (eg, FPG versus HbA1c), then the higher of the two values should be used

    FPG

    ≥126 mg/dL (7.0 mmol/L)

    Fasting is defined as no caloric intake for at least 8 hours

    2-hr PG during OGTT

    ≥200 mg/dL (11.1 mmol/L)

    Test should be performed as described by WHO, using a glucose load containing the equivalent of 75-g of anhydrous glucose dissolved in water

    Random PG

    ≥200 mg/dL (11.1 mmol/L)

     

    Abbreviations: HbA1c = glycosylated hemoglobin, type A1c; FPG = fasting plasma glucose; PG = plasma glucose; OGTT = oral glucose tolerance test

    *One of the following must be met to diagnose DM

    Categories of increased risk for diabetes (prediabetes or impaired glucose tolerance)
    Criteria for Diagnosis of Prediabetes (ADA, 2015; AACE/ACE, 2015)
    TestResult Confirming Prediabetes or Impaired Glucose Tolerance

    FPG

    100-125 mg/dL (5.6-6.9 mmol/L)

    2-hr PG during 75-g OGTT

    140-199 mg/dL (7.8-11.0 mmol/L)

    HbA1c

    5.7-6.4%

    Abbreviations: HbA1c = glycosylated hemoglobin, type A1c; FPG = fasting plasma glucose; PG = plasma glucose; OGTT = oral glucose tolerance test

Laboratory Testing

  • Initial testing – HbA1c, FPG, 2-hr OGTT, or random PG are the preferred tests to diagnose diabetes in nonpregnant adults (see Criteria for Diagnosis)
    • If tests are normal, repeat at minimum of 3 year intervals (ADA, 2015)
  • Insulin antibodies  – not recommended for routine evaluation or management of DM (ADA, 2014)
    • Type 1 DM
      • Presence of multiple insulin antibodies is highly suggestive of type 1 DM
      • Absence of antibodies does not rule out type 1 DM
  • C-peptide testing – not recommended to diagnose DM
    •  Low concentrations are suggestive of type 1 DM, but are not indicative
    • Antibody tests

      Antibody Test

      Indications

      Insulinoma antigen 2 (IA-2)

      Distinguish type 1 from type 2 DM in in children for insulin therapy initiation at the time of diagnosis

      Identify subset of adults with type 2 DM phenotype who progress rapidly to insulin dependency

      May be used in combination with GAD for initial screening of suspected cases of type 1 DM

      Screen nondiabetic family members who wish to donate a kidney or partial pancreas

      Screen women with GDM to identify those at high risk of progression to type 1 DM

      Glutamic acid decarboxylase (GAD)

      Same as IA-2 indications

      Insulin autoantibodies  (IAA)

      Distinguish type 1 from type 2 DM in in children for insulin therapy initiation at the time of diagnosis

      Identify subset of adults with type 2 DM phenotype who progress rapidly to insulin dependency

      Screen nondiabetic family members who wish to donate a kidney or partial pancreas

      Screen women with GDM to identify those at high risk of progression to type 1 DM

      Zinc transporter 8 (ZnT8)

      Differentiate latent autoimmune diabetes in adults (LADA) from type 2 DM

      Monitor progression to type 1 DM in preclinical phase

      Should be used in conjunction with GAD, insulin, and IA-2

      Islet cell antibody (ICA)

      Acceptable second-line test for identifying type 1 DM if tests for GAD, IA-2, and ZnT8 antibodies are negative

      May be useful in identifying children at risk for type 1 DM

Differential Diagnosis

  • Type 2 DM
  • Type 1 DM (ketoacidosis)
  • GDM
    • Infection
    • Acute surgical abdomen
      • Appendicitis
      • Cholecystitis/cholelithiasis
      • Pregnancy-related abdominal problem
        • Intrauterine infection
    • Thyroid disease

Screening

Adults (one of the following)

  • Screening criteria for diabetes mellitus

    Screening Criteria for Diabetes Mellitus

    American Diabetes Association (2015)

    U.S. Preventive Services Task Force (2014)

    Testing should be considered in all adults who are overweight (BMI ≥25 kg/m2) and have additional risk factors:

    • Physical inactivity
    • First-degree relative with DM
    • Member of high-risk ethnic population (eg, African American, Latino)
    • Women who delivered a baby weighing >9 lb or were diagnosed with GDM
    • Hypertension (≥140/90 mmHg) or on antihypertensive therapy
    • HDL-C concentration <35 mg/dL and/or triglyceride concentration >250 mg/dL
    • Women with PCOS
    • HbA1c ≥5.7%, impaired glucose tolerance (IGT), or impaired fasting glucose (IFG) on previous testing
    • Other clinical conditions associated with insulin resistance (eg, severe obesity, acanthosis nigricans)
    • History of CVD

    In the absence of the above criteria, testing for DM should begin at 45 yrs

    • If results are normal, testing should be repeated at least every 3 yrs, with consideration of more frequent testing depending on initial results and risk status
    • Screening is recommended for type 2 DM in asymptomatic adults with sustained blood pressure (either treated or untreated) >135/80 mmHg
    • No recommendation for asymptomatic adults with blood pressure ≤135/80 mmHg

Pregnant women (gestational DM)

  • All pregnant females 24-28 weeks gestation should be screened for gestational DM (GDM) (ADA, 2015; ACOG, 2013; AACE/ACE, 2015)
    • Screen if GDM identified 6-12 weeks postpartum using OGTT according to nonpregnant criteria (ADA, 2015)
  • Two approaches may be utilized – two-step or one-step 
  • ApproachCriteriaFasting mg/dL1-hr mg/dL2-hr mg/dL3-hr mg/dL
    Two-step (50-g, 100-g load) (NIH consensus)Carpenter & Coustan95 (5.3 mmol/L)180 (10.0 mmol/L)155 (8.6 mmol/L)140 (7.8 mmol/L)
    NDDG105 (5.8 mmol/L)190 (10.6 mmol/L)165 (9.2 mmol/L)145 (8.0 mmol/L)

    One-step (75-g load) (IADPSG consensus)

    IADPSG≥92 (5.1 mmol/L)≥180 (10 mmol/L)≥153 (8.5 mmol/L)n/a
    NDDG = National Diabetes Data Group; IADPSG = International Association of Diabetes and Pregnancy Study Groups
    Comparison of Diagnostic Testing Recommendations for GDM

    Comparison of Diagnostic Testing Recommendations for GDM

    Guidelines

    Glucose Load

    Diagnostic Threshold (mg/dL)

    IADPSG (2010)

    75-g, 2-hr OGTT performed at 24-28 weeks gestation in women not previously diagnosed with overt diabetes

    OGTT should be performed in morning after overnight fast of at least 8 hrs

    FPG ≥92, 1 hr ≥180, 2 hr ≥153

    Criteria met when any single point exceeded

    American Congress of Obstetricians and Gynecologists  (2013)

    Screen women early if high risk

    If using 1-hr screening, glucose threshold should be between 130-140 (130 threshold more sensitive but less specific)

    Recommend 75-g, 2-hr OGTT performed at 24-28 weeks gestation

    FPG ≥92, 1 hr ≥180, 2 hr ≥153

    Criteria met when any single point exceeded [IADPSG criteria]

    U.S. Preventive Services Task Force (2014)

    One- or two-step screening (see ADA below)

    See ADA below

    American Diabetes Association (2014)

    One-step screening (IADPSG consensus) – 75-g, 2 hr OGTT

    OR

    Two-step screening (NIH consensus) – 50-g, 1 hr OGTT at step 1; 100-g, 3 hr OGTT at step 2 (two abnormal values)

    One-step criteria

    • FPG ≥92, 1 hr ≥180, 2 hr ≥153

    Two-step criteria

    • 50 g challenge
      • 1 hour – 130-140 mg/dL (130 more sensitive but less specific
    • 100 g challenge
      • Positive if ≥2 values exceed threshold
      • CC: FPG ≥95, 1 hr ≥180, 2 hr ≥155, 3 hr ≥140
      • NDDG: FPG ≥105, 1 hr ≥190, 2 hr ≥165, 3 hr ≥145

    Use of either criteria is acceptable

    Endocrine Society (2013)

    75-g, 2-hr OGTT performed at 24-28 weeks gestation

    FPG ≥92, 1 hr ≥180, 2 hr ≥153

    Criteria met when any single point exceeded [IADPSG criteria]

    NDDG = National Diabetes Data Group; IADPSG = International Association of Diabetes and Pregnancy Study Groups, CC = Carpenter/Coustan

Monitoring

Physical Examination

Recommendations for physical examination (ADA, 2015; AACE/ACE, 2015)
Recommendations for Physical Examination
ExamTimingCommentsGoals

Blood pressure

Every visit

Include orthostatic measurements

<130-140/80 mmHg

Weight

Every visit

Bariatric surgery may be considered if BM ≥35 kg/m2

<25 kg/m2

Ophthalmologic

Within 5 yrs of onset of DM for all adults and children ≥10 yrs (if first exam is normal then every 2 yrs)

Dilated exam

N/A

Thyroid palpitation

Every visit

Consider antibody screening, especially in Type 2 DM

N/A

Skin

Every visit

Evaluate for skin ulcers

N/A

Neurological/foot examination

At diagnosis of type 2 DM; within 5 yrs after diagnosis of type 1 DM

Inspection of feet for lesions

Palpation of dorsalis pedis (DP) and posterior tibial (PT) artery pulses

Presence/absence of patellar and Achilles reflexes

Determination of proprioception, vibration (using 128 Hz tuning fork) and monofilament sensation testing

N/A

Celiac testing

Consider in patients with type 1 DM (particularly children)

N/A

Laboratory Testing

Glycemic control

Glycemic Control

HbA1c

  • Premise of testing
    • Glycation of hemoglobin is non-linear over time and occurs over the lifespan of the red blood cell (~120 days)
    • Correlates with risk of long-term complications and with DM control over previous 2-3 months
  • Target goal – ≤6.5-7% of glycated hemoglobin for most patients (ADA, 2015; AACE/ACE, 2015)
  • Laboratory testing recommendations 
    • 2 measurements per year for patients meeting goal of <6.5-7% (ADA, 2015) or ≤6.5% (AACE/ACE, 2015)
      • If patient is not hypoglycemic, goal should be <6.5%
    • More frequent monitoring in patients with HbA1c ≥7%
      • Not more often than every 3 months (ADA, 2015; AACE, 2015)
    • Diseases affecting red cell survival will alter HbA1c (eg, sickle cell disease)

1,5-Anhydroglucitol (GlycoMark)

  • Premise of testing
    • Renal reabsorption of 1,5-anhydroglucitol (AG) is competitively inhibited by glucose and excreted in the urine when the concentration of plasma glucose exceeds renal threshold (~180 mg/dL)
    • Poor glycemic control leads to decreased concentrations of plasma 1,5-AG
    • Less sensitive to small changes in glycemic control at high HbA1c concentrations
      • 1,5-AG reflects postprandial glycemic changes better than other glycemic indicators and measurements may be useful for assessing postprandial hyperglycemia
  • Laboratory testing recommendations
    • Not recommended for monitoring DM
    • May be useful for identifying postprandial hyperglycemia and assessing glycemic control in patients with moderately controlled diabetes
      • In patients with normal 1,5-AG (HbA1c 6.1-7.9%), treatment should be aimed at normalizing fasting blood glucose
      • In patients with low 1,5-AG, treatment should be aimed at normalizing postprandial glucose

Fructosamine

  • Premise of testing
    • Marker of short-term glycemia
      • Provides glycemia index over 20-day period
    • Carbonyl group of glucose reacts with an amino group of a protein
  • Laboratory testing recommendations
    • May be useful in monitoring GDM; not recommended for other types of DM
    • May be used in patients with shortened red cell survival (eg, sickle cell disease and other hemoglobinopathies)

Albumin, glycated

  • Premise of testing
    • Marker of short-term glycemia
      • Provides glycemia index over 20-day period
    • Measures glycation of serum albumin
  • Laboratory testing recommendations
    • May be useful in monitoring GDM; not recommended for other types of DM
    • May be useful for patients with shortened red cell survival (eg, sickle cell disease)

Insulin

  • Premise of testing
    • Circulating concentrations of insulin may be prognostic for likelihood of progression to insulin dependence in DM
  • Laboratory testing recommendations
    • Not recommended for monitoring or diagnosis of DM

C-peptide

  • Premise of testing
    • C-peptide connects the A & B chains of proinsulin
    • Released in equimolar concentrations with insulin
    • Reflects endogenous insulin production
  • Laboratory testing recommendations
    • Not recommended for monitoring or diagnosis of DM
    • May be useful for assessing endogenous insulin production to confirm need for insulin therapy
  • Dyslipidemia
    • Lipid panel (fasting)
      • Premise of testing
        • Patients with DM have an increased incidence of lipid abnormalities, creating risk for CVD
        • Lipid-lowering therapies have been demonstrated to reduce macrovascular disease; therefore, identification of dyslipidemia is important
      • Target goals (ADA, 2015; AACE/ACE, 2015)
        • LDL
          • <100 mg/dL – low, moderate risk patient
          • <70 mg/dL  – high risk patient
        • HDL
          • >40 mg/dL (men)
          • >50 mg/dL (women)
        • Triglycerides <150 mg/dL
      • Laboratory testing recommendations
        • Initial evaluation and annually thereafter if goals are met
          • More frequently if goals are not met
          • Adult with low values (LDL <100 mg/dL, HDL >50 mg/dL, triglycerides <150 mg/dL) – assessments up to two years apart
        • Treat aggressively with statins based on initial risk assessment (ACC/AHA 2013 guidelines)
          • No target goals set by ACC/AHA
  • Hepatic function
    • Premise of testing
      • Patients with DM are at risk for steatohepatitis
    • Laboratory testing recommendations
      • Liver function tests –  AST, ALT, alkaline phosphatase, and bilirubin
      • Initial evaluation and annually thereafter if values are normal on initial testing
  • Renal function
    • Creatinine and estimated glomerular filtration rates (eGFR)
      • Premise of testing
        • Many drugs require adjusted dosing based on creatinine, creatinine clearance or eGFR and DM may affect renal function in the course of the disease
        • Absolute creatinine values do not reflect glomerular filtration rates in many patients
          • Diabetic nephropathy diminishes creatinine clearance
          • Renal function thereby diminishes clearance and glomerular filtration rate
        • Creatinine and eGFR are broad measures of renal function
      • Laboratory testing recommendations
        • Serum creatinine and eGFR annually
          • More frequent monitoring necessary for abnormal eGFRs (ADA, 2015)
          • KIDGO guidelines are useful for deciding intervals for abnormal values (KIDGO, 2011)
    • Albuminuria
      • Premise of testing
        • Diabetic nephropathy occurs in 20-40% of patients with DM and is the single leading cause of end-stage renal disease – adding angiotensin converting enzyme (ACE) inhibitors reduces progression
        • Persistent albuminuria (range 30-299 mg/24 hours and concentrations ≥300 mg/24 hours) signifies the earliest stage of diabetic nephropathy
      • Target goal
        • <30 mg/24 hour urine (ADA, 2015; AACE/ACE, 2015)
      • Laboratory testing recommendations
        • Spot urine or 24-hour urine for microalbumin annually
  • Thyroid function
    • TSH, autoimmune antibodies
      • Premise of testing
      • Laboratory testing recommendations
        • Initial evaluation using TSH/antibody testing (for type 1 DM) and, if normal, TSH every 3 years thereafter (ADA, 2015)

Clinical Background

Diabetes mellitus (DM) is a group of metabolic diseases resulting from defects in insulin secretion and/or insulin resistance that can lead to significant morbidity and mortality in affected patients.

Classification of Diabetes Mellitus

  • Type 1 DM – 90-95% in pediatric population; absolute insulin deficiency
  • Type 2 DM – most are teenagers or older; insulin resistance with or without insulin deficiency
  • Gestational diabetes mellitus (GDM) – exclusive to pregnant females
  • Other types of DM due to other causes (eg, cystic fibrosis, drug-induced)

Diabetes Mellitus Type 1

  • See Pediatrics tab

Diabetes Mellitus Type 2

  • Type 2 DM

    Epidemiology

    • Prevalence – affects >20 million in U.S.
      • 6.5% of population
    • Age – usually diagnosed >30 yrs
    • Sex – M:F, equal
    • Occurrence – increase in teenage obesity has been associated with increased occurrence of DM type 2

    Inheritance

    • 75% concordance rate between identical twins
    • Several susceptibility genes have been identified

    Risk Factors

    • Obesity (BMI >25 kg/m2)
    • Family history of DM type 2 in first- or second-degree relative
    • Race/ethnicity – Native American, African American, Latino, Asian American, Pacific Islander
    • Signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, polycystic ovarian syndrome (PCOS), low birth weight)
    • Maternal history of DM or GDM during child’s gestation

    Pathophysiology

    • Combination of progressive β-cell dysfunction with insulin secretory defect in a background of insulin resistance
    • Autoimmune destruction of the pancreas does not appear to occur

    Clinical Presentation

    • May have polyuria, polydipsia, or polyphagia
    • Headache, fatigue, blurred vision, recurring Candida spp infections
    • More common presentations – microvascular, macrovascular, and neuropathic complications
      • Tingling, numbness in extremities (particularly lower extremities)
      • Dyslipidemia
      • Renal insufficiency
      • Angina, myocardial infarction
    • Complications
      • Short term – hyperosmolar coma (uncommon)
      • Long term

Gestational Diabetes Mellitus

  • GDM

    Epidemiology

    • Prevalence – 6-7% of all pregnancies (USPTSF, 2014)

    Risk Factors (Garrison, 2015)

    • History of previous GDM
    • Macrosomia in previous pregnancy
    • Obesity – BMI >25 kg/m2
    • Diabetes in first-degree relative
    • Maternal age >35 yrs
    • Ethnicity at risk – Asian, Native American, Hispanic, Black American, Pacific Islander
    • Weight gain >5kg since 18 yrs
    • Excess weight gain in pregnancy as per Institute of Medicine guidelines

    Clinical Presentation

    • Fetal
    • Maternal
      • Post-term delivery
      • Premature labor
      • Preeclampsia
      • Caesarian delivery
      • Gestational hypertension

Pediatrics

Type 1 DM

Epidemiology

  • Prevalence
    • Varies by nationality – common in Northern European populations; uncommon in Chinese, Indian populations
    • 1/400-600 children and adolescents
  • Age
    • Majority diagnosed before or during adolescence
    • Peaks at 5-7 years and adolescence
  • Sex – M>F (slightly)
  • Inheritance
    • Interplay between genetic susceptibility and environmental factors

Pathophysiology

  • Caused by autoimmune mediated destruction of insulin-producing β-cells of the islets of Langerhans in the pancreas with diminished or absent circulating insulin
  • Absolute insulin deficiency of type 1 DM is a result of the following
    • Chronic inflammatory response mediated against the islet cells
    • Cell-mediated destruction of islet cells accompanied by production of islet cell antibodies 
      • Autoantibodies
        • Islet cell antibodies (ICA)
          • May be detected years prior to clinical symptoms
        • Glutamic acid decarboxylase (GAD65)
        • Insulinoma antigen 2 (IA-2)
        • Insulin autoantibodies (IAA)
        • Zinc transporter 8 (ZnT8)
      • Presence of these antibodies in individuals with diabetes confirms autoimmune etiology

Clinical Presentation

  • Polydipsia, polyuria, polyphagia
  • Nonspecific symptoms
    • Fatigue
    • Nausea, emesis
    • Weight loss
    • Blurred vision
  • Length of time from clinical presentation to diagnosis is typically a few weeks
  • Complications

 Type 2 DM

  • See Clinical Background section

Diagnosis

Indications for Testing

  • Testing for type 2 DM or prediabetes in asymptomatic children (ADA, 2015)
    Testing for Type 2 Diabetes or Prediabetes in Asymptomatic Children (≤18 yrs)
    Criteria – overweightBMI >85% for age and sex, weight for height >85%, or weight >120% of ideal for height
    Plus any two of the following risk factors
    • Family history of type 2 DM in first- or second-degree relative
    • Race/ethnicity – Native American, African American, Latino, Asian American, Pacific Islander
    • Signs of insulin resistance or conditions associated with insulin resistance – acanthosis nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, or small for gestational age birth weight
    • Maternal history of DM or GDM during the child’s gestation
    Age of initiationAge 10 yrs or at onset of puberty if puberty occurs at a younger age
    FrequencyEvery 3 yrs

Criteria for Diagnosis

  • Refer to Diagnosis section

Laboratory Testing

  • HbA1c fasting plasma glucose, 2-hour oral glucose tolerance test (OGTT), and random glucose are the preferred tests to diagnose diabetes in children (ADA,2014)
  • C-peptide or insulin concentrations to diagnose type 1 DM diabetes – not recommended
    • Consider insulin antibody testing – refer to Diagnosis section

Monitoring

  • HbA1c
    • Premise of testing
      • Glycation of hemoglobin is non-linear over time and occurs over the whole lifespan of the red blood cell
      • Correlates with risk of long-term complications and with diabetes control over previous 2-3 months
    • Target goal (ADA, 2015)
      • <7.5% for all pediatric groups
    • Laboratory testing recommendations 
      • 2 measurements per year for patients meeting goal of <6.5-7% (ADA, 2014), ≤6.5% (ACE/AACE, 2015)
        • If patient is not hypoglycemic, goal should be <6%
      • More frequent monitoring in patients with HbA1c ≥7%; however, not more often than every 3 months (ADA, 2015; AACE/ACE, 2015)
  • Hypoglycemia
    • Not infrequent when children are using insulin
      • Diligence required for younger children

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Hemoglobin A1c 0070426
Method: Quantitative High Performance Liquid Chromatography/Boronate Affinity

Diagnose or monitor DM

Diagnosis should be confirmed with a repeated test

Monitor prediabetes

Unstable hemoglobins or hemolytic anemia may yield falsely low results

Iron deficiency anemia may yield falsely high results

 
Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Diagnose and manage DM and other carbohydrate metabolism disorders

Diagnosis of DM should be confirmed with a repeated test

   
Glucose Tolerance Test 0020542
Method: Quantitative Enzymatic

Diagnose DM, GDM, or impaired glucose tolerance

Components include glucose, fasting and glucose, 2-hour

   
Glucose Screen, Pregnancy 0020047
Method: Quantitative Enzymatic

Screen for GDM

   
Lipid Panel 0020421
Method: Quantitative Enzymatic

Use to assess cardiovascular disease risk and guide therapy

Panel includes total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol (calculated), appearance, VLDL cholesterol (calculated)

   
Microalbumin, Urine 0050203
Method: Quantitative Immunoturbidimetry

Monitor for diabetic nephropathy in DM

   
Glomerular Filtration Rate, Estimated 0020725
Method: Quantitative Enzymatic

Use for monitoring for renal insufficiency in DM

   
Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Assess and monitor risk for steatohepatitis

Panel includes albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin, and protein

   
Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

Use to assess thyroid function

Reflex pattern - if the Thyroid Stimulating Hormone is outside the reference interval, then Thyroxine, Free (Free T4) testing will be added

   
Thyroid Stimulating Immunoglobulin 0099430
Method: Quantitative Bioassay/Quantitative Chemiluminescent Immunoassay

Acceptable testing for autoimmune thyroid disease

Blocking antibodies specific to TSHR may decrease TSI antibody concentrations; net response is most likely physiologic

TSH serum concentration ≥6 mU/L may cause a false-positive result

 
Thyroid Stimulating Hormone Receptor Antibody (TRAb) 2002734
Method: Quantitative Electrochemiluminescent Immunoassay

Acceptable testing for autoimmune thyroid disease

Analytical sensitivity – 0.9 IU/L limit of detection

Analytical specificity – 88.9%

   
Albumin, Glycated 0080700
Method: Quantitative Boronate Affinity Chromatography/Immunoturbidimetry

Use for monitoring GDM or shortened red-cell survival

   
Fructosamine 0099012
Method: Quantitative Spectrophotometry

May aid in monitoring glucose control for diabetes in specific disorders

Not recommended as a substitute for hemoglobin A1c except in specific populations

Variations in concentrations of serum proteins can affect results

High concentration of ascorbic acid interfere with the assay

 
1,5 Anhydroglucitol Quantitative, Serum or Plasma 0081335
Method: Quantitative Enzymatic

Monitoring postprandial hyperglycemia and short-term glycemic control when hemoglobin A1c is 6.1-7.9%

Do not use in poorly controlled disease because test is not sensitive

In patients with poorly controlled DM 1,5-AG is less sensitive to modest changes in glycemic control due to continuous glycosuria

Decreased in individuals with renal glucose thresholds that are markedly different from 180 mg/dL (eg, chronic renal failure, pregnancy, dialysis) and in those undergoing steroid therapy

Alpha-glucosidase inhibitors can decrease 1,5-AG by interfering with intestinal absorption

 
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Zinc Transporter 8 Antibody 2006196
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Not recommended in routine evaluation or management of DM

Combined testing with glutamic acid decarboxylase antibody and IA-2 antibody improves diagnostic sensitivity in suspected cases of type 1 DM

Should be used in conjunction with tests for GAD65, insulin, and IA-2

Negative results do not rule out autoimmune diabetes; autoantibody response varies in individuals

Presence of autoantibodies is predictive of DM1, but not all individuals with antibodies will develop DM1

Not useful in DM monitoring

Insulin antibody RIA test does not differentiate between endogenous or exogenous form of insulin

Clinical sensitivity

  • Moderate sensitivity for DM1 for newly diagnosed diabetes
  • Improves diagnostic sensitivity when used in conjunction with GADA and IA-2

 Clinical specificity

  • Highly specific for DM1 for newly diagnosed diabetes

More specific for pancreatic islet beta cells than GADA or IA-2 autoantibody screening

Glutamic Acid Decarboxylase Antibody 2001771
Method: Semi-quantitative Enzyme-Linked Immunosorbent Assay

Not recommended in routine evaluation or management of DM

Glutamic acid decarboxylase antibody and IA-2 antibody recommended for initial screening of suspected cases of type 1 DM

Negative results do not rule out autoimmune diabetes; autoantibody response varies in individuals

Presence of autoantibodies is predictive of DM1, but not all individuals with antibodies will develop DM1

Not useful in DM monitoring

Insulin antibody RIA test does not differentiate between endogenous or exogenous form of insulin

Clinical sensitivity – moderate sensitivity (70-90%) for DM1 for newly diagnosed diabetes

Clinical specificity – highly specific for DM1 for newly diagnosed diabetes

IA-2 Antibody 0050202
Method: Quantitative Radioimmunoassay

Not recommended in routine evaluation or management of DM

Glutamic acid decarboxylase antibody and IA-2 antibody recommended for initial screening of suspected cases of type 1 DM

Negative results do not rule out autoimmune diabetes; autoantibody response varies in individuals

Presence of autoantibodies is predictive of DM1, but not all individuals with antibodies will develop DM1

Not useful in DM monitoring

Insulin antibody RIA test does not differentiate between endogenous or exogenous form of insulin

Clinical sensitivity – moderate sensitivity (50-70%) for DM1 for newly diagnosed diabetes

Clinical specificity – highly specific for DM1 for newly diagnosed diabetes

Insulin Antibody 0099228
Method: Quantitative Radioimmunoassay

Not recommended in routine evaluation or management of DM

Glutamic acid decarboxylase antibody and IA-2 antibody recommended for initial screening of suspected cases of type 1 DM

Not useful in patients receiving insulin

Negative results do not rule out autoimmune diabetes; autoantibody response varies in individuals

Presence of autoantibodies is predictive of DM1, but not all individuals with antibodies will develop DM1

Not useful in DM monitoring

Insulin antibody RIA test does not differentiate between endogenous or exogenous form of insulin

Clinical sensitivity – sensitive in individuals who are insulin naïve

Clinical specificity – highly specific for DM1 for newly diagnosed diabetes

Islet Cell Cytoplasmic Antibody, IgG 0050138
Method: Semi-Quantitative Indirect Fluorescent Antibody

Not recommended in routine evaluation or management of DM

Glutamic acid decarboxylase antibody and IA-2 antibody recommended for initial screening of suspected cases of type 1 DM

Should be used in conjunction with tests for GAD65, insulin, and IA-2

Negative results do not rule out autoimmune diabetes; autoantibody response varies in individuals

Presence of autoantibodies is predictive of DM1, but not all individuals with antibodies will develop DM1

Not useful in DM monitoring

Insulin antibody RIA test does not differentiate between endogenous or exogenous form of insulin

Clinical sensitivity – moderate sensitivity for DM1 for newly diagnosed diabetes

Clinical specificity – highly specific for DM1 for newly diagnosed diabetes

C-Peptide, Serum or Plasma 0070103
Method: Quantitative Chemiluminescent Immunoassay

Aids in the detection of insulinoma

May aid in distinguishing type 1 from type 2 DM in ambiguous cases

Do not use to diagnose DM

Insulin, Free and Total 0070155
Method: Quantitative Ultrafiltration/Quantitative Chemiluminescent Immunoassay

Not recommended to diagnose DM

Insulin, Random 0070107
Method: Quantitative Chemiluminescent Immunoassay

Aids in the detection of insulinoma

Do not use to diagnose DM

Insulin, Fasting 0070063
Method: Quantitative Chemiluminescent Immunoassay

Aids in the detection of insulinoma

Do not use to diagnose DM