DIABETES TESTING SERVICES

Assessing Diabetes in Your Patients

LabCorp and Endocrine Sciences, a member of LabCorp's Specialty Testing Group, provide clinicians with a comprehensive portfolio for diagnosing, differentiating, and monitoring diabetic patients.

Type 1 Diabetes (T1D) Type 2 Diabetes (T2D)Maturity-Onset Diabetes of

the Young (MODY)

Screening

Plasma blood glucose should be used instead of HbA1c to diagnose T1D in individuals with symptoms of hyperglycemia.

To test for T2D and prediabetes, the following tests are equally appropriate:• HbA1c• Fasting plasma glucose• 2-hour glucose tolerance test (GTT)

ADA Guidelines recommend screening for MODY1 in patients with atypical diabetes features.

Diagnosis

Type 1 diabetes is defined by the presence of one or more specific autoimmune markers.

The same testing can be used to screen and diagnose diabetes, as well as detect prediabetes in asymptomatic adults. Screening results should be confirmed by one of two methods:• Repeat the same glucose measure on a second sample Or,• utilize two different glucose measures on the same sample

The most common forms of MODY can be diagnosed with genetic testing.

The Centers for Disease Control and Prevention (CDC) estimates that more than 30 million Americans suffer from diabetes.4

2019 American Diabetes Association (ADA) Guidelines1

Diagnosing Diabetes MellitusLabCorp offers the American Diabetes Association (ADA) recommended tests for screening and diagnosis of type 1 and type 2 diabetes mellitus.1 Our complete test menu also includes testing and tools to confirm other forms of diabetes.

• Plasma blood glucose

• Hemoglobin A1c (HbA1c)

• Oral glucose tolerance tests based on ADA and WHO1,2 recommendations

• Two hour oral glucose tolerance tests for gestational diabetes based on ADA and WHO recommendations1,2

• Three hour oral glucose tolerance tests for gestational diabetes based on ACOG3 recommendations

• Stimulation testing requisitions for ease of ordering mixed meal tests

For Every 1,000 American Adults (20+ YEARS)2

1-5 Have Type 1 Diabetes

100 Have Type 2 Diabetes

300 Have Prediabetes

5

LabCorp offers a Diabetes Autoimmune Profile with 4 markers that can assist in differentiating T1D from other forms of diabetes. A diabetes autoantibodies assessment is helpful in identifying and managing patients at risk for development of type 1 diabetes.

• Includes testing for:

• GAD-65 antibodies• IA-2/ICA 512 antibodies• Insulin antibodies• ZnT8 antibodies

• Improved detection rate shown by combining these four markers, assisting with identifying and treating patients earlier in the disease onset

• Highly specific to T1D, with a study finding a 98% autoimmunity detection rate for these combined antibodies in new-onset type 1 diabetics. Less than 3% of type 2 diabetics were found to be positive for ZnT8 antibodies11

• A positive result for more than one antibody is associated with a higher likelihood of T1D

• Among new-onset diabetic patients11:

• 98% tested positive for one antibody and 82% tested positive for two or more antibodies11

• 100% of patients with two or more positive antibodies were found to have T1D, as well as 92% to 98% of patients with one positive antibody11

In addition to the Diabetes Autoimmune Profile, LabCorp has several other testing options available.

• Individual antibody test options:

• HLA DQA1 and DQB1 Intermediate Resolution

• T1D has strong HLA associations, 1 and LabCorp offers testing to identify patients with specific HLA genotypes

no

no no

yes

yes

negativepositive

yes

Diabetes in youth or early adulthood9-10

Ketosis, diabetic ketoacidosis, weight loss

Consider autoantibody testing GAD, IA-2A, ZnT8, IAA

Consider additional testing and other forms of diabetes

Obesity, signs and symptoms of insulin resistance

T2D T1D

T1D

Healthy BMI, no signs or symptoms of insulin resistance

Differentiating DiabetesDetermining which type of diabetes a patient has is critical to provide the proper care and treatment. Distinguishing between T1D and T2D is becoming increasingly challenging.6 Recent studies estimate that up to 40% of type 1 diabetics present after 30 years of age.7-8 A differentiation methodology might include the following:

Is it MODY? Up to 95% of MODY cases in the US may be misdiagnosed as T1D or T2D.12,13 Accurate diagnosis enables appropriate treatment.1

The ADA suggests screening be considered for MODY in patients who have atypical diabetes that is not characteristic of T1D or T2D. This includes patients who are or were diagnosed with diabetes in youth or early adulthood, but1:

• Test negative for diabetes-associated autoantibodies

• Are not obese and/or do not have a sedentary lifestyle

• Have stable, mild fasting hyperglycemia at diagnosis

• Have stable HbA1c between 5.6% and 7.6% at diagnosis

Other Forms of DiabetesAs part of a complete portfolio of diabetes services, LabCorp also offers testing to help you care for your patients, including:

• Gestational Diabetes

• Secondary diabetes as a result of:

• Cystic fibrosis• Hemochromatosis• Chronic pancreatitis• Polycystic ovary syndrome (PCOS)• Cushing's syndrome• Pancreatic cancer• Glucagonoma• Pancreatectomy

Monitoring Diabetic PatientsOnce diabetes has been diagnosed, appropriate lab testing is important to monitor treatment and complications of the disease. LabCorp offers a thorough menu of tests that may be beneficial when monitoring disease control and progression.

Current guidelines recommend measuring HbA1c at least two times per year in patients who are meeting treatment goals, or quarterly if not meeting treatment goals or treatment has changed. Some conditions affect red blood cell turnover and can cause discrepancies between the A1c result and the true average glucose level. Patients who have or have had anemia, recent blood transfusion, end-stage kidney disease, glucose-6-phosphate dehydrogenase deficiency, or are pregnant may have discordant HbA1c results. In these cases and for patients taking drugs that stimulate erythropoiesis or who have hemoglobin variants, clinicians may also want to consider other testing to assess glycemic control.1

Beyond HbA1c• Fructosamine—to assess short-term glycemic control

• Glycomark®—to identify postprandial spikes

• Β-hydroxybuterate—ADA recommended testing to monitor blood ketones6

• Ultrasensitive C-Peptide—for detection of very low levels of C-Peptide

• Free and Total Insulin—may be useful for diabetic patients who are treated with insulin analogs. Testing can detect the following exogenous insulin formulations:

MODY makes up about 1% of diabetes cases, affecting approximately 300,000 patients in the US.12

Cross-reactivity of Insulin DrugsInsulin Drug % Cross-reactivity

Human insulin 100%

Insulin aspart 85%

Insulin glargine 92%

Cross-reactivity of Insulin DrugsInsulin Drug % Cross-reactivity

Insulin lispro 79%

Insulin glulisine 14%

Insulin detemir 24%

• Every patient's antibodies are different, and the specificity and avidity of the antibodies may affect the test.

1%

3 – 16% of T1D patients develop celiac disease. The majority of these patients do not present with classic symptoms of celiac disease.14

Autoimimune thyroid disorders are the most prevalent immunologic disease in T1D. Screening is recommended every 1-2 years, or sooner if symptomatic.1,15

3- 16%

Evaluating for ComplicationsBeyond diagnosis and monitoring, LabCorp recognizes the importance of early detection of comorbidities associated with diabetes.

Type 2 diabetic patients are 2-4 times more likely to suffer a cardiovascular event.5 Additionally, diabetes and heart failure often occur together. Poor glycemic control further increases heart failure risk. For every 1% increase in HbA1c, cardiovascular mortality risk increases 11%.16

LabCorp offers a wide array of test options to help identify and manage this increased risk and other diabetes-associated complications.

• Lipid panel options that include insulin resistance (IR) markers and an IR score, lipoprotein particle number, and apolipoprotein

• NT-pro BNP test options to help confirm a heart failure diagnosis

• NASH FibroSure®: ADA-recommended testing for patients with elevated liver enzymes to evaluate for nonalcoholic fatty steato-hepatitis1

• Renal function testing to identify kidney disease

Special Considerations for T1DPatients with T1D are also at risk for other autoimmune diseases such as: thyroid disease, primary adrenal insufficiency, celiac disease, autoimmune gastritis, autoimmune hepatitis, dermatomyositis, and myasthenia gravis. As such, the ADA guidelines recommend considering for all newly diagnosed T1D patients screening for autoimmune thyroid disease and celiac disease.1

• Thyroid Antibodies Panel, including thyroid peroxidase (TPO) antibody and thyroglobulin antibody

• Celiac Antibodies Profile, including Deamidated gliadin antibodies; endomysial antibodies; tissue transglutaminase (tTG) antibodies; total IgA

Value Beyond TestingLabCorp offers several tools for patient education, including our clinical decision support report format, which incorporates patient test results into an easy-to-read, patient friendly handout.

Test

Your Results

Comments

Your Test Results

Blood SugarA1C measures your average blood sugarcontrol over the last 2-3 months.

YOUR A1C IS AT GOAL which means yourdiabetes is under control. To keep your diabetesunder control, remember to take all medicinesprescribed by your doctor and follow your current

diet. Regular exercise (30 minutes 5 times aweek) and weight loss also help keep it undercontrol.

6.6%

6.6%

Blood LipidsLDL CHOLESTEROL is the badcholesterol that can clog your arteries.

HAVING LOW LDL HELPS PROTECT YOURHEART AND BLOOD VESSELS. Remember totake any medications prescribed by your doctor.

Your doctor may recommend even lowercholesterol levels to reduce your risk of heartdisease. Weight loss, exercise (at least 30minutes 5 times a week), a diet low in trans andsaturated fats, and quitting smoking can keepcholesterol low.

98Ref. Range: 0 to 99 mg/dL

TRIGLYCERIDES are a type of fat andhigh levels may increase risk of heartdisease.

YOUR TRIGLYCERIDES ARE HIGH. Foods high

in carbohydrates and sugar, as well as alcohol,can raise your triglycerides. Try to limit the amount

of these you eat/drink.

251Ref. Range: 0 to 149 mg/dLLDL PARTICLE NUMBER (LDL-P) is

another measure thought to give a betterestimate of heart disease risk other thanjust measuring LDL cholesterol. YOUR LDL-P RESULT IS HIGH. Even though

your LDL cholesterol is controlled, a high LDL-Pmeans you may still be at risk for heart and blood

vessel disease. Remember to take all medicinesas prescribed. Weight loss, exercise, and a dietlow in red meat, sugar, and saturated fat and high

in produce, nuts, and other healthful foods canhelp lower LDL-P.

1359Ref. Range: 0 to 999 nmol/L

XX/XX/2016

MXX/XX/19XX

Patient Name

Litholink Patient Results Report

PATIENT

DATE OF BIRTHGENDER

DATE OF SERVICE PHYSICIAN

DISCLAIMER: You should discuss this information with your physician. Litholink does not have a doctor-patient relationship with you, nor does it have access to a complete

medical history or physical examination conducted by a physician that would be necessary for a complete diagnosis and comprehensive treatment plan. Neither you nor your

physician should rely solely on this guidance. Bolded result descriptions in "Comments" consider either the reference range or target range for the test result. Reference range

refers to the LabCorp reference interval. Target range refers to the guideline-suggested goal. REFERENCES:American Diabetes Association's Standards of Medical Care in

Diabetes-2014 (Diabetes Care, Vol 37, Supp 1, Jan 2014); National Diabetes Education Program's 4 Steps to Manage Your Diabetes for Life (2013, NIH publication 13-5492).

7.2.3.9Version:

Page: 1 of 1

Printed: 09/01/2016

Laboratory DirectorCLIA# 14D0897314 2250 West Campbell Park DriveChicago, Illinois 60612

www.litholink.com

866 361 7939 Facsimile

Chicago, Illinois 60612

CLIA# 14D0897314 2250 West Campbell Park Drive

Laboratory Director

Mitchell S. Laks, PhD Litholink, A LabCorp Company800 338 4333 Telephone

Diagnosis of DiabetesTest # Test Name

090400 Diabetes Risk Assessment in Asymptomatic Adults

001818 Glucose, Plasma

001032 Glucose, Serum

101200 Glucose Tolerance Test (GTT), Two-Hour (Oral WHO Protocol)

101000 Gestational Glucose Tolerance Screening and Diagnostic Test (Two-hour, ADA Recommendations)

102004 Gestational Glucose Tolerance Diagnostic Test (Three-hour, ACOG Recommendations)

001453 Hemoglobin (Hb) A1c

Differentiating DiabetesTest # Test Name

160721 Antipancreatic Islet Cells

504050 Diabetes Autoimmune Profile

143008 Glutamic Acid Decarboxylase (GAD) Autoantibodies

167146 HLA DQA1 and DQB1 Intermediate Resolution

141531* IA2 Autoantibodies

141598* Insulin Autoantibodies (IAA)

504603* MODY Genetic Profile

503995* ZnT8 (Ainc Transporter 8) Antibodies

Monitoring DiabetesTest # Test Name

140285 Albumin/Creatinine Ratio, Random Urine

503610* Β-Hydroxybutyrate

010108 C-Peptide

503830* C-Peptide, Ultrasensitive

100800 Fructosamine

004622 Glucagon, Plasma

500115* GlycoMark®

501561* Insulin, Free and Total

503068* Insulin

140822* Insulin-like Growth Factor-binding Protein 1 (IGFBP-1)

146712 Leptin, Serum or Plasma

140533 Proinsulin

500722* Proinsulin, ICMA

Evaluating ComplicationsTest # Test Name

165126 Celiac Antibodies Profile tTG IgA, tTG IgG, DGP IgA, DGP IgG, EMA IgA, and Total IgA

023400 Diabetes Comorbidity Assessment

303756 Lipid Panel

361946 Lipid Cascade with reflex to lipoprotein analysis by NMR

363676 Lipid Cascade with reflex to Apolipoprotein B

550140 NASH FibroSure®

884247 NMR LipoProfile®

361946 NMR LipoProfile® with IR Markers

143000 NT-proBNP

322777 Renal Function Panel

006684 Thyroid Antibodies

Frequently Used Tests

*Indicates testing performed at Endocrine Sciences

References 1. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2019. Diabetes Care. 2019;42(Supplement 1):S13-S28. doi:10.2337/dc19-S002. 2. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications, Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998 Jul; 15(7): 539-553. PubMed 9686693. 3. American College of Obstetricians and Gynecologists. Committee on Practice Bulletins—Obstetrics. Practice Bulletin N° 137: Gestational diabetes mellitus. Obstet Gynecol. 2013 Aug; 122(2 Pt 1):406-416. PubMed 23969827. 4. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017: Estimates of diabetes and its burden in the United States. 2017. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed May 1, 2019.5. Endocrine Society. Endocrine facts and figures: Diabetes. 2015. https://endocrinefacts.org/wp-content/uploads/2015/05/Diabetes-Final-PW-protected.pdf. Accessed May 1, 2019.6. Chiang JL, Maahs DM, Garvey KC, et al. Type 1 diabetes in children and adolescents: A position statement by the American Diabetes Association. Diabetes Care. 2018;41(9):2026-2044. doi:10.2337/dci18-0023.7. Caffrey M. One-third of type 1 diabetes cases misdiagnosed in those over age 30. AJMC. https://www.ajmc.com/newsroom/onethird-of-type-1-diabetes-cases-misdiagnosed-in-those-over-age-30. Accessed August 9, 2019. 8. Bruno G, Runzo C, Cavallo-Perin P, et al. Incidence of type 1 and type 2 diabetes in adults aged 30-49 years: The population-based registry in the province of Turin, Italy. Diabetes Care. 2005;28(11):2613-2619. doi:10.2337/diacare.28.11.2613.

9. Nair VV, Chapla A, Arulappan N, Thomas N. Molecular diagnosis of maturity onset diabetes of the young in India. Indian J Endocrinol Metab. 2013;17(3):430-441. doi:10.4103/2230-8210.111636. 10. Warncke K, Kummer S, Raile K, et al. Frequency and characteristics of MODY 1 (HNF4A mutation) and MODY 5 (HNF1B mutation): Analysis from the DPV database. J Clin Endocrinol Metab. 2019;104(3):845-855. doi:10.1210/jc.2018-01696.11. Wenzlau JM, Juhl K, Yu L, et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. PNAS. 2007;104(43):17040-17045. doi:10.1073/pnas.0705894104.12. Kleinberger JW, Pollin TI. Undiagnosed MODY: Time for action. Curr Diab Rep. 2015 December; 15(12):110.13. Pihoker C, Gilliam LK, Ellard S, et al. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: Results from the SEARCH for diabetes in youth. J Clin Endocrinol Metab. 2013;98(10):4055-4062. doi:10.1210/jc.2013-1279.14. Cohn A, Sofia AM, Kupfer SS. Type 1 diabetes and celiac disease: Clinical overlap and new insights into disease pathogenesis. Curr Diab Rep. 2014;14(8):517. doi:10.1007/s11892-014-0517-x.15. Umpierrez GE, Latif KA, Murphy MB, et al. Thyroid dysfunction in patients with type 1 diabetes: A longitudinal study. Diabetes Care. 2003;26(4):1181-1185. doi:10.2337/diacare.26.4.1181.16. Kasznicki J, Drzewoski J. Heart failure in the diabetic population - pathophysiology, diagnosis and management. Arch Med Sci. 2014;10(3):546–556. doi:10.5114/aoms.2014.43748.

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Diabetes Testing Services