Diabetes Mellitus

Diabetes mellitus (DM) is a group of metabolic diseases, including diabetes mellitus type 1, diabetes mellitus type 2, and impaired glucose tolerance. These diseases result from defects in insulin secretion and/or insulin resistance that can lead to significant morbidity and mortality in affected patients.

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Polyuria, polydipsia, polyphagia, weight loss, fatigue
  • Overweight/obesity (BMI ≥25 kg/m2 or ≥23 kg/m2 in Asian Americans)
  • Family history of type 2 diabetes mellitus (T2DM) 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, dyslipidemiapolycystic ovarian syndrome (PCOS), low birthweight)
  • Maternal history of DM or gestational DM (GDM) during pregnancy

Criteria for Diagnosis

Laboratory Testing

  • Initial testing – hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2-hour oral glucose tolerance test (OGTT), or plasma glucose (PG) are all acceptable tests to diagnose DM in nonpregnant adults (refer to Criteria for Diagnosis) (American Diabetes Association [ADA], 2017)
  • HbA1c – glycosylated hemoglobin, glycolated hemoglobin
    • Advantages
      • Not dependent on fasting (convenient)
      • Point of care testing available
      • Less daily variation
    • Limitations
      • Cost
      • Lower sensitivity
      • May be less available in some regions of world (usually not issue in U.S.)
      • Indirect measure
        • Impacted by age, race/ethnicity, anemia, and hemoglobinopathies
      • Point of care assays limited by proficiency of person conducting test
      • Cutoffs determined for adults; unclear whether these are transferrable to children
  • Autoimmune antibody testing
    • Use
      • Testing for autoantibodies should be performed
        • After diabetes diagnosis AND
        • If there is a concern for type 1 DM (T1DM) (aids in confirmation)
      • Individual antibody tests should not be ordered; instead, ≥2 antibodies should be ordered (Insel, 2015)
      • Most useful in newly diagnosed DM in children <18 years to establish autoimmune etiology (American Association of Clinical Endocrinologists [AACE], 2015)
      • May be useful in difficult adult cases when it is unclear if patient has T1DM or T2DM (Bingley, 2010)
      • Lack of antibodies suggests a genetic etiology (eg, monogenic DM, maturity-onset diabetes of the young [MODY]) in patients with DM  (Bingley, 2010; National Institutes of Health [NIH], 2014)
    • Tests
      • Demonstration of glutamic acid decarboxylase antibodies (GADA) and ≥1 of the following antibodies is highly suggestive of autoimmune T1DM
        • GADA/GAD 65
          • Also a marker for other autoimmune diseases
        • Islet antigen 2 (IA-2)
          • More specific than GAD 65 for diabetes
        • Islet cell cytoplasmic antibody (ICA), IgG
        • Zinc transporter 8 (ZnT8) 
        • Insulin antibody (IA) – less useful; essentially all individuals receiving insulin will develop insulin antibodies

Differential Diagnosis

  • T2DM
  • T1DM (ketoacidosis)
  • GDM
    • Infection
    • Acute surgical abdomen
      • Appendicitis
      • Cholecystitis/cholelithiasis
      • Pregnancy-related abdominal problem
        • Intrauterine infection
    • Thyroid disease
  • Tests that are used for diagnosis are also used for screening
    • Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2-hour oral glucose tolerance test (OGTT), or plasma glucose (PG)
    • Not all tests will detect diabetes mellitus (DM) in same individual
    • Imperfect concordance between these 3 tests 

Adults (1 of the Following Criteria)

Pregnant Women (Gestational DM)

  • All pregnant females not previously known to have diabetes should be screened for gestational DM (GDM) at 24-28 weeks gestation (American Diabetes Association [ADA], 2017; American Congress of Obstetricians and Gynecologists [ACOG], 2013; American Association of Clinical Endocrinologists [AACE]/American College of Endocrinology [ACE], 2015)
    • Screen if GDM identified 4-12 weeks postpartum using OGTT according to nonpregnant criteria (ADA, 2017)
    • Test for DM at least every 3 years thereafter (ADA, 2017)

Physical Examination

Laboratory Testing

  • Dyslipidemia
    • Lipid panel (fasting)
      • Premise of testing
        • Patients with diabetes mellitus (DM) have an increased incidence of lipid abnormalities, creating risk for atherosclerotic cardiovascular disease (ASCVD)
        • Lipid-lowering therapies have been demonstrated to reduce macrovascular disease; therefore, identification of dyslipidemia is important
        • ASCVD risk tracks more closely with LDL-P when there is discordance between LDL-C and LDL-P
      • Target goals (ADA, 2017)
      • Recommendations for Statin and Combination Treatment in People with Diabetes (ADA, 2017)

        Age

        Risk Factors

        Recommended Statin Intensitya

        <40 yrs

        None

        None

        ASCVD risk factor(s)b Moderate or high
        ASCVD High

        40-75 yrs

        None

        Moderate

        ASCVD risk factors High
        ASCVD High
        ACS and LDL cholesterol >50 mg/dL (1.3 mmol/L) in patients who cannot tolerate high-dose statins Moderate plus ezetimibe

        >75 yrs

        None

        Moderate

        ASCVD risk factors Moderate or high
        ASCVD High
        ACS and LDL cholesterol >50 mg/dL (1.3 mmol/L) in patients who cannot tolerate high-dose statins Moderate plus ezetimibe
      • Laboratory testing recommendations
        • Initial evaluation every 5 years in DM for those not taking statins
        • Lipid profile at initiation of statins and periodically thereafter
        • Treat aggressively with statins based on initial risk assessment (American College of Cardiology [ACC]/American Heart Association [AHA], 2013)
          • No target goals set by ACC/AHA
  • LipoFit and LipoFit particle count only by quantitative nuclear magnetic resonance spectroscopy (emerging testing)
    • Premise of testing
      • High risk patients with DM who have abnormal LDL levels
    • Laboratory testing recommendations
      • Monitor LDL particle number to guide therapy
  • 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 (elevated urinary albumin-to–creatinine ratio >30 mg/g creatinine) signifies the earliest stage of diabetic nephropathy
    • Target goal
      • <30 mg/24-hour urine (ADA, 2017; AACE/ACE, 2015)
    • Laboratory testing recommendations
      • Spot urine or 24-hour urine for microalbumin at least annually for the following patients
        • Type 1 DM (T1MD) ≥5 years
        • All patients with type 2 DM (T2DM)
        • All patients with hypertension
  • Antiplatelet agents (ADA, 2017)
    • Premise of testing
      • Patients with DM are at increased risk for stroke and heart attack
      • Consider acetylsalicylic acid in those with >10% 10-year cardiovascular risk
    • Laboratory testing recommendations
      • None
  • Hepatic function
    • Premise of testing
      • Patients with DM are at risk for steatohepatitis
    • Laboratory testing recommendations
      • Liver function tests –  aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and bilirubin
      • Initial evaluation and annually thereafter if values are normal on initial testing
  • Renal function (ADA, 2017)
    • 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 at least annually
          • For the following patients
            • T1DM ≥5 years
            • All patients with T2DM
            • All patients with hypertension
          • More frequent monitoring necessary for abnormal eGFRs (ADA, 2017)
          • Kidney Disease: Improving Global Outcomes (KIDGO) guidelines are useful for deciding intervals for abnormal values (KIDGO, 2011)
  • Thyroid function (ADA, 2017)
    • Thyroid-stimulating hormone (TSH), autoimmune antibodies
      • Premise of testing
      • Laboratory testing recommendations
        • Initial evaluation using TSH/antibody testing (for T1DM) and, if normal, TSH every 1-2 years thereafter (ADA, 2017)
  • Celiac testing (ADA, 2017)
    • tTG or DPG with documentation of normal IgA
    • Premise of testing
      • Other autoimmune diseases occur more frequently in individuals with T1DM
    • Laboratory testing recommendations
      • At initial diagnosis
      • If symptoms develop after diagnosis

Classification of Diabetes Mellitus

  • Type 1 DM (T1DM)
    • 90-95% in pediatric population; absolute insulin deficiency due to autoimmune destruction of islet cells
  • Type 2 DM (T2DM)
    • Most are teenagers or older; insulin resistance with or without insulin deficiency
  • Gestational DM (GDM)
    • Exclusive to pregnant females
  • Other types of DM due to other causes

Type 1 Diabetes Mellitus

Refer to Pediatrics section

Type 2 Diabetes Mellitus

Gestational Diabetes Mellitus

Type 1 Diabetes Mellitus (T1DM)

Clinical Background

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
      • HLA class II haplotypes most common (DRB-DQ2, DR4-DQ8)
      • Stages (Scientific statement JDF, Endocrine Society, American Diabetes Association [ADA], Insel, 2015)
        • Stage 1 – autoimmunity +/normoglycemia/presymptomatic T1DM
        • Stage 2 – autoimmunity +/dysglycemia/presymptomatic T1DM
        • Stage 3 – autoimmunity +/dysglycemia/symptomatic T1DM

Pathophysiology

  • Autoimmune-mediated destruction of insulin-producing beta (β)-cells of islets of Langerhans in pancreas with diminished or absent circulating insulin
  • Absolute insulin deficiency of T1DM is a result of
    • Chronic inflammatory response mediated against islet cells
    • Cell-mediated destruction of islet cells accompanied by production of islet cell antibodies
      • Autoantibodies – order of appearance appears related to HLA-DQ genotype
        • Islet cell antibodies (ICA)
          • May be detected years prior to clinical symptoms
        • Glutamic acid decarboxylase (GAD)
        • Insulinoma antigen 2 (IA-2)
        • Insulin autoantibodies (IAA)
        • Zinc transporter 8 (ZnT8)
      • Presence of 2 or more of these antibodies is a major criteria for stage 1 DM (presymptomatic stage)
      • Number of autoantibodies appears to correlate with risk of T1DM development (Insel, 2015)

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
    • Short term – diabetic ketoacidosis (~33% of affected individuals present with this)
    • Long term – refer to type 2 DM (T2DM) Clinical Background section

Type 2 Diabetes Mellitus (T2DM)

Diagnosis

Indications for Testing

  • Overweight or obese for age and sex plus ≥2 risk factors
    • Family history of T2DM
    • Race/ethnicity
    • Signs of insulin resistance
    • Maternal history of DM or gestational DM (GDM) during child’s gestation

Criteria for Diagnosis

Cutoffs for pediatrics are the same as for adults; however, studies that form the basis for these recommendations were based on adults.

Laboratory Testing

  • Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2-hour oral glucose tolerance test (OGTT), and plasma glucose (PG) are the preferred tests to diagnose diabetes in children (ADA, 2017)
    • Random glucose measures have greater variability and less reproducibility in children
  • Insulin antibody testing
    • No indication for routine evaluation or management (ADA, 2016)

Screening

  • Screening advocated because of increasing prevalence of T2DM in children
  • Recommended age to begin screening – 10 years (or at onset of puberty if puberty occurs at a younger age)
    • American Association of Clinical Endocrinologists (AACE), 2011 – screen every 3 years if overweight and have 2 other risk factors
      • Risk factors include family history, race/ethnicity recognized to increase risk, signs of insulin resistance, maternal history of diabetes, or GDM during child’s gestation

Monitoring

  • HbA1c
    • Premise of testing
      • Glycation of hemoglobin is nonlinear over time and occurs over the whole 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 (ADA, 2017)
      • <7.5% for all pediatric groups
    • Laboratory testing recommendations
      • ≥2 measurements per year for patients meeting target goal (ADA, 2017)
        • 3-month testing for those not meeting goals
        • If patient is not hypoglycemic, goal should be <7%
        • Blood glucose goals should be modified in children with frequent hypoglycemia or hypoglycemia unawareness
          • Hypoglycemia not infrequent when children are using insulin; diligence required for younger children
      • More frequent monitoring in patients with HbA1c ≥7.5%
        • Not more often than every 3 months (ADA, 2017; AACE/American College of Endocrinology [ACE], 2015)
      • False lowering – hemolytic anemias, sickle cell disease, acute blood loss
      • False elevation – splenectomy, iron deficiency anemia, hyperbilirubinemia, hypertriglyceridemia, uremia
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.

Hemoglobin A1c 0070426
Method: Quantitative High Performance Liquid Chromatography/Boronate Affinity

Limitations 

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

Glucose Tolerance Test 0020542
Method: Quantitative Enzymatic

Glucose Screen, Pregnancy 0020047
Method: Quantitative Enzymatic

Lipid Panel 0020421
Method: Quantitative Enzymatic

Microalbumin, Urine 0050203
Method: Quantitative Immunoturbidimetry

Glomerular Filtration Rate, Estimated 0020725
Method: Quantitative Enzymatic

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

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

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

Limitations 

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

Fructosamine 0099012
Method: Quantitative Spectrophotometry

Limitations 

Variations in concentrations of serum proteins can affect results

High concentration of ascorbic acid interferes with assay

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

LipoFit by NMR 2013716
Method: Quantitative Nuclear Magnetic Resonance Spectroscopy/ Quantitative Enzymatic/ Detergent Solubilization

LipoFit by NMR, Particle Count Only 2013715
Method: Quantitative Nuclear Magnetic Resonance Spectroscopy

Guidelines

American Diabetes Association. Standards of Medical Care in Diabetes–2017. Diabetes Care. 2017; 39(Suppl 1): S1-S112

Blumer I, Hadar E, Hadden DR, Jovanovič L, Mestman JH, Murad H, Yogev Y. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013; 98(11): 4227-49. PubMed

Committee on Practice Bulletins--Obstetrics. Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol. 2013; 122(2 Pt 1): 406-16. PubMed

Consensus Committee. Consensus statement on the worldwide standardization of the hemoglobin A1C measurement: the ADA, European Association for the Study of Diabetes, International Federation of Clinical Chemistry and Laboratory Medicine, and the IDF. Diabetes Care. 2007; 30(9): 2399-400. PubMed

de Leiva A, Mauricio D, Corcoy R. Diabetes-related autoantibodies and gestational diabetes. Diabetes Care. 2007; 30 Suppl 2: S127-33. PubMed

Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia. World Health Organization. Geneva, Switzerland [Accessed: Nov 2015]

Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Zimmerman RS, Bailey TS, Blonde L, Bray GA, Cohen J, Dagogo-Jack S, Davidson JA, Einhorn D, Ganda OP, Garber AJ, Garvey T, Henry RR, Hirsch IB, Horton ES, Hurley DL, Jellinger PS, Jovanovič L, Lebovitz HE, LeRoith D, Levy P, McGill JB, Mechanick JI, Mestman JH, Moghissi ES, Orzeck EA, Pessah-Pollack R, Rosenblit PD, Vinik AI, Wyne K, Zangeneh F. American Association of Clinical Endocrinologists and American College of Endocrinology - Clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract. 2015; 21 Suppl 1: 1-87. PubMed

Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, Greenbaum CJ, Herold KC, Krischer JP, Lernmark A, Ratner RE, Rewers MJ, Schatz DA, Skyler JS, Sosenko JM, Ziegler A. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015; 38(10): 1964-74. PubMed

International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, Dyer AR, de Leiva A, Hod M, Kitzmiler JL, Lowe LP, McIntyre D, Oats JJ, Omori Y, Schmidt MI. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010; 33(3): 676-82. PubMed

Lampasona V, Petrone A, Tiberti C, Capizzi M, Spoletini M, di Pietro S, Songini M, Bonicchio S, Giorgino F, Bonifacio E, Bosi E, Buzzetti R, Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study Group. Zinc transporter 8 antibodies complement GAD and IA-2 antibodies in the identification and characterization of adult-onset autoimmune diabetes: Non Insulin Requiring Autoimmune Diabetes (NIRAD) 4. Diabetes Care. 2010; 33(1): 104-8. PubMed

Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young. National Institutes of Health. Bethesda, MD [Accessed: Feb 2017]

Moyer VA, U.S. Preventive Services Task Force. Screening for gestational diabetes mellitus: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014; 160(6): 414-20. PubMed

National Collaborating Centre for Chronic Conditions (UK). Type 2 Diabetes: National Clinical Guideline for Management in Primary and Secondary Care (Update). London: Royal College of Physicians (UK); 2008. PubMed

National Collaborating Centre for Women's and Children's Health (UK) Type 1 Diabetes: Diagnosis and Management of Type 1 Diabetes in Children and Young People. London: RCOG Press. 2004; :PubMed

Nilsson C, Ursing D, Törn C, Aberg A, Landin-Olsson M. Presence of GAD antibodies during gestational diabetes mellitus predicts type 1 diabetes. Diabetes Care. 2007; 30(8): 1968-71. PubMed

Phillip M, Battelino T, Rodriguez H, Danne T, Kaufman F, European Society for Paediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, International Society for Pediatric and Adolescent Diabetes, American Diabetes Association, European Association for the Study of Diabetes. Use of insulin pump therapy in the pediatric age-group: consensus statement from the European Society for Paediatric Endocrinology, the Lawson Wilkins Pediatric Endocrine Society, and the International Society for Pediatric and Adolescent Diabetes. Diabetes Care. 2007; 30(6): 1653-62. PubMed

Qaseem A, Vijan S, Snow V, Cross T, Weiss KB, Owens DK, Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Glycemic control and type 2 diabetes mellitus: the optimal hemoglobin A1c targets. A guidance statement from the American College of Physicians. Ann Intern Med. 2007; 147(6): 417-22. PubMed

Sacks DB, Arnold M, Bakris GL, Bruns DE, Horvath AR, Kirkman S, Lernmark A, Metzger BE, Nathan DM. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem. 2011; 57(6): e1-e47. PubMed

Siu AL. Screening for Abnormal Blood Glucose and Type 2 Diabetes Mellitus: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2015; PubMed

Snow V, Aronson MD, Hornbake R, Mottur-Pilson C, Weiss KB, Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Lipid control in the management of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2004; 140(8): 644-9. PubMed

Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus. Abbreviated Report of a WHO Consultation. World Health Organization. Geneva, Switzerland [Accessed: Nov 2015]

Vandorsten JP, Dodson WC, Espeland MA, Grobman WA, Guise JM, Mercer BM, Minkoff HL, Poindexter B, Prosser LA, Sawaya GF, Scott JR, Silver RM, Smith L, Thomas A, Tita AT. NIH consensus development conference: diagnosing gestational diabetes mellitus. NIH Consens State Sci Statements. 2013; 29(1): 1-31. PubMed

General References

Adi S. Type 1 diabetes mellitus in adolescents. Adolesc Med State Art Rev. 2010; 21(1): 86-102, ix. PubMed

Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014; 383(9911): 69-82. PubMed

Backholer K, Chen L, Shaw J. Screening for diabetes. Pathology. 2012; 44(2): 110-4. PubMed

Bingley PJ. Clinical applications of diabetes antibody testing. J Clin Endocrinol Metab. 2010; 95(1): 25-33. PubMed

Dungan KM. 1,5-anhydroglucitol (GlycoMark) as a marker of short-term glycemic control and glycemic excursions. Expert Rev Mol Diagn. 2008; 8(1): 9-19. PubMed

Garrison A. Screening, diagnosis, and management of gestational diabetes mellitus. Am Fam Physician. 2015; 91(7): 460-7. PubMed

Inzucchi SE. Clinical practice. Diagnosis of diabetes. N Engl J Med. 2012; 367(6): 542-50. PubMed

Landon MB, Gabbe SG. Gestational diabetes mellitus. Obstet Gynecol. 2011; 118(6): 1379-93. PubMed

Little RR, La'ulu SL, Hanson SE, Rohlfing CL, Schmidt RL. Effects of 49 Different Rare Hb Variants on HbA1c Measurement in Eight Methods. J Diabetes Sci Technol. 2015; 9(4): 849-56. PubMed

Mohamadi A, Cooke DW. Type 2 diabetes mellitus in children and adolescents. Adolesc Med State Art Rev. 2010; 21(1): 103-19, x. PubMed

Nambam B, Aggarwal S, Jain A. Latent autoimmune diabetes in adults: A distinct but heterogeneous clinical entity. World J Diabetes. 2010; 1(4): 111-5. PubMed

National Kidney Disease Education Program (NKDEP). National Institute of Diabetes and Digestive and Kidney Diseases. Bethesda, MD [Accessed: Feb 2017]

Stenström G, Gottsäter A, Bakhtadze E, Berger B, Sundkvist G. Latent autoimmune diabetes in adults: definition, prevalence, beta-cell function, and treatment. Diabetes. 2005; 54 Suppl 2: S68-72. PubMed

Taplin CE, Barker JM. Autoantibodies in type 1 diabetes. Autoimmunity. 2008; 41(1): 11-8. PubMed

Vijan S. In the clinic. Type 2 diabetes. Ann Intern Med. 2010; 152(5): ITC31-15; quiz ITC316. PubMed

Wilson JF. In clinic. Diabetic ketoacidosis. Ann Intern Med. 2010; 152(1): ITC1-1 - ITC1-15, quiz ITC1-16. PubMed

Winter WE, Schatz DA. Autoimmune markers in diabetes. Clin Chem. 2011; 57(2): 168-75. PubMed

Zhang X, Gregg EW, Williamson DF, Barker LE, Thomas W, Bullard KM, Imperatore G, Williams DE, Albright AL. A1C level and future risk of diabetes: a systematic review. Diabetes Care. 2010; 33(7): 1665-73. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Anderson JL, Carlquist JF, Roberts WL, Horne BD, May HT, Schwarz EL, Pasquali M, Nielson R, Kushnir MM, Rockwood AL, Bair TL, Muhlestein JB, Intermountain Heart Collaborative Study Group. Asymmetric dimethylarginine, cortisol/cortisone ratio, and C-peptide: markers for diabetes and cardiovascular risk? Am Heart J. 2007; 153(1): 67-73. PubMed

Jasuja GK, Travison TG, Davda M, Rose AJ, Zhang A, Kushnir MM, Rockwood AL, Meikle W, Coviello AD, D'Agostino R, Vasan RS, Bhasin S. Circulating estrone levels are associated prospectively with diabetes risk in men of the Framingham Heart Study. Diabetes Care. 2013; 36(9): 2591-6. PubMed

Joo WS, Jeong JH, Nam K, Blevins KS, Salama ME, Kim SW. Polymeric delivery of therapeutic RAE-1 plasmid to the pancreatic islets for the prevention of type 1 diabetes. J Control Release. 2012; 162(3): 606-11. PubMed

Lin C, Emery TJ, Little RR, Hanson SE, Rohlfing CL, Jaisson S, Gillery P, Roberts WL. Effects of hemoglobin C, D, E, and S traits on measurements of HbA1c by six methods. Clin Chim Acta. 2012; 413(7-8): 819-21. PubMed

Little RR, Rohlfing CL, Hanson SE, Schmidt RL, Lin C, Madsen RW, Roberts WL. The effect of increased fetal hemoglobin on 7 common Hb A1c assay methods. Clin Chem. 2012; 58(5): 945-7. PubMed

McClain DA, Abuelgasim KA, Nouraie M, Salomon-Andonie J, Niu X, Miasnikova G, Polyakova LA, Sergueeva A, Okhotin DJ, Cherqaoui R, Okhotin D, Cox JE, Swierczek S, Song J, Simon C, Huang J, Simcox JA, Yoon D, Prchal JT, Gordeuk VR. Decreased serum glucose and glycosylated hemoglobin levels in patients with Chuvash polycythemia: a role for HIF in glucose metabolism. J Mol Med (Berl). 2013; 91(1): 59-67. PubMed

Owen WE, Roberts WL. Cross-reactivity of three recombinant insulin analogs with five commercial insulin immunoassays. Clin Chem. 2004; 50(1): 257-9. PubMed

Owen WE, Roberts WL. Performance characteristics of an HPLC assay for urinary albumin. Am J Clin Pathol. 2005; 124(2): 219-25. PubMed

Roberts WL. Hemoglobin constant spring can interfere with glycated hemoglobin measurements by boronate affinity chromatography. Clin Chem. 2007; 53(1): 142-3. PubMed

Medical Reviewers

Content Reviewed: 
May 2017

Last Update: October 2017