Diabetes Mellitus

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Content

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, dyslipidemiaPCOS, low birthweight)
    • Maternal history of DM or gestational diabetes mellitus (GDM) during pregnancy

Criteria for Diagnosis

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)
    • For evaluation of type 1 DM – recommended to order at least two antibodies when pursuing this testing (Insel, 2015)
  • C-peptide testing – not recommended to diagnose DM
    •  Low concentrations are suggestive of type 1 DM, but are not indicative

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

Adults (one of the following)

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



Fasting mg/dL

1-hr mg/dL

2-hr mg/dL

3-hr mg/dL

Two-step (50-g, 100-g load) (NIH consensus)

Carpenter & Coustan

95 (5.3 mmol/L)

180 (10.0 mmol/L)

155 (8.6 mmol/L)

140 (7.8 mmol/L)


105 (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)


≥92 (5.1 mmol/L)

≥180 (10 mmol/L)

≥153 (8.5 mmol/L)


NDDG = National Diabetes Data Group; IADPSG = International Association of Diabetes and Pregnancy Study Groups

Physical Examination

Laboratory Testing

    • 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)

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

Gestational Diabetes Mellitus

Type 1 DM

Clinical Background


  • 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 ADA, Insel, 2015)
        • Stage 1 – autoimmunity +/normoglycemia/presymptomatic type 1 DM
        • Stage 2 – autoimmunity +/dysglycemia/presymptomatic type 1 DM
        • Stage 3 – autoimmunity +/dysglycemia/symptomatic type 1 DM


  • 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 – order of appearance appears related to HLA-DQ genotype
        • 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 two or more of these antibodies is a major criteria for stage 1 DM 1 (presymptomatic stage)
      • Number of autoantibodies appears to correlate with risk of DM 1 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

 Type 2 DM

  • See Clinical Background section


Indications for Testing

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)
    • Random glucose measures have greater variability and less reproducibility in children
  • C-peptide or insulin concentrations to diagnose type 1 DM – not recommended
    • Consider insulin antibody testing – refer to Diagnosis section


  • 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

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


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


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


Variations in concentrations of serum proteins can affect results

High concentration of ascorbic acid interferes with the assay

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


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

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


Not recommended in routine evaluation or management of DM

IA-2 Antibody 0050202
Method: Quantitative Radioimmunoassay


Not recommended in routine evaluation or management of DM

Insulin Antibody 0099228
Method: Quantitative Radioimmunoassay


Not recommended in routine evaluation or management of DM

Zinc Transporter 8 Antibody 2006196
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay


Not recommended in routine evaluation or management of DM

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


Not recommended in routine evaluation or management of DM

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


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Medical Reviewers

Last Update: January 2016