Endocrinology

Diabetes Mellitus: Classification and Diagnosis

Classification

1. Most common types of diabetes mellitus
   • Type 1 DM
     • Autoimmune ß-cell destruction
   • Type 2 DM
     • Secondary to a loss of insulin secretion with a concurrent background of insulin resistance
   • Gestational diabetes mellitus
     • Diagnosed during the second or third trimester that is not overt diabetes mellitus
   • Specific types due to other causes
     • Monogenic diabetes syndromes
       • Maturity-Onset Diabetes of the Young (MODY; listed by gene defect)
         • Autosomal dominant inheritance pattern
         • GCK-MODY: stable, nonprogressive elevated FBG; microvascular complications are rare
         • HNF1A-MODY: progressive insulin secretory defect with a presentation in adolescence or early adulthood
           • Sensitive to sulfonylureas
         • HNF4A-MODY: progressive insulin secretory defect with a presentation in adolescence or early adulthood
           • May have a history of macrosomia and transient neonatal hypoglycemia
         • HNF1B-MODY: developmental renal disease (usually cystic), genitourinary abnormalities, hyperuricemia, gout, atrophy of the pancreas
       • Neonatal diabetes (listed by gene defect)
         • Autosomal dominant inheritance pattern unless otherwise noted
         • KCNJ11: intrauterine growth restriction (IUGR), possibly developmental delay and seizures, responsive to sulfonylureas
         • INS: IUGR, requires insulin
         • ABCC8: IUGR, possible developmental delay, responsive to sulfonylureas
         • 6q24: IUGR, macroglossia, umbilical hernia, mechanisms include UPD6, paternal duplication or maternal methylation defect
           • Maybe sensitive to non-insulin therapy
         • GATA6: pancreatic hypoplasia with exocrine insufficiency, cardiac malformations, requires insulin
         • EIF2AK3: autosomal recessive, epiphyseal dysplasia, pancreatic exocrine insufficiency, requires insulin (Wolcott-Rallison syndrome)
         • FOXP3: x-linked, immune dysregulation, polyendocrinopathy, exfoliative dermatitis, requires insulin
     • Diseases of the exocrine pancreas
     • Drug-chemical-induced diabetes
2. Diagnostic criteria (any one of the following)
   • Fasting plasma glucose (FPG) ≥ 126 mg/dL (≥ 7.0 mmol/L)
     • Fasting: no caloric intake for ≥ 8 hrs (if no unequivocal hyperglycemia, confirm results by repeat testing)
   • Random plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L) if classic symptoms of hyperglycemia or hyperglycemic crisis
   • 2-hr plasma glucose (PG) ≥ 200 mg/dL (≥ 11.1 mmol/L) during an oral glucose tolerance test (OGTT)
     • Perform as described by the World Health Organization (WHO): glucose load with an equivalent of 75 g anhydrous glucose dissolved in water
   • Hemoglobin A₁C ≥ 6.5% (48 mmol/mol)
     • Perform in a laboratory using NGSP (National Glycohemoglobin Standardization Program) certified and standardized to DCCT (Diabetes Control and Complications Trial) assay
     • A₁C levels vary with race/ethnicity despite similar fasting and post-glucose load levels
     • Certain hemoglobinopathies and anemia may affect accuracy
     • Do not use the A₁C test if conditions with increased RBC turnover, such as
       • Pregnancy
       • Recent blood loss or transfusions
       • Erythropoietin therapy
       • Hemolysis
3. Confirmation of Diagnosis
   • Recommended the same test be repeated for confirmation unless clear clinical diagnosis
     • Hyperglycemic crisis or classic symptomatology with a random plasma glucose ≥ 200 mg/dL [≥ 11.1 mmol/L])
   • If discordant results from 2 different tests, repeat the test that is above the diagnostic cut-off point
   • All tests have analytic variability; abnormal result possible, when repeated, to yield a normal result
     • This variability is least likely with the A₁C test
     • This variability is more likely with FPG
     • This variability is more likely with the 2-hr PG (especially if samples remained at room temp and not centrifuged promptly)
4. Criteria for testing in asymptomatic adults
   • Consider screening asymptomatic adults who are
     • Overweight (BMI ≥ 25 kg/m²; or if Asian American, BMI ≥ 23 kg/m²), and
     • Have any additional risk factor
       • Physical inactivity
       • First-degree relative with diabetes mellitus
       • High-risk race/ethnicity
         • African American
         • Asian American
         • Latino
         • Native American
         • Pacific Islander
       • Delivered a baby weighing > 9 lbs or were diagnosed with GDM
       • Polycystic ovary syndrome
       • HTN (≥ 140/90 mmHg, or on therapy for HTN)
       • HDL < 35 mg/dL (0.90 mmol/L) and/or a triglyceride level > 250 mg/dL (2.82 mmol/L)
       • A1C level ≥ 5.7% (39 mmol/mol), impaired glucose tolerance, or impaired fasting glucose on previous testing
       • Any clinical condition associated with insulin resistance, such as
         • Acanthosis nigricans
         • Severe obesity
       • History of cardiovascular disease
   • For all other adult patients, screening should begin at 45 years old
     • For children and adolescent screening, see below
     • If screening tests are normal, repeat at a minimum 3-year interval
   • To screen for prediabetes
     • Fasting plasma glucose (FPG)
     • 2-hr plasma 75-g oral glucose tolerance test
     • A1C
   • Increased risk for diabetes (prediabetes)
     • FPG 100-125 mg/dL (5.6-6.9 mmol/L) (=IFG)
       or
     • 2-hr PG during 75-g OGTT 140-199 mg/dL (7.8-11.0 mmol/L) (=IGT)
       or
     • A1C 5.7-6.4% (39-47 mmol/mol)
   • If prediabetes is detected
     • Identify and treat other cardiovascular disease risk factors
   • To screen for DM Type 1 using antibody testing
     • Current lack of accepted screening programs; limited to clinical research settings
     • Most patients present with acute symptoms of elevated glucose levels
       • 1/3 present with life-threatening ketoacidosis
     • Some studies indicate screening relatives of those with Type 1 DM
       • Helps identify those at risk to provide counseling
         • Leads to limiting acute complications
5. Criteria for testing for DM Type 2 (or prediabetes) in asymptomatic individuals < 18 years old
   • Overweight
     • BMI > 85th percentile for age and sex, or
     • Weight and height > 85th percentile, or
     • Weight > 120% of ideal for height
   • PLUS any ≥ 1 of the following
     • Maternal history of DM or GDM during the child's gestation
     • Family history of DM Type 2 in first- or second-degree relatives
     • High-risk race/ethnicity
       • African American
       • Asian American
       • Native American
       • Latino
       • Pacific Islander
     • Conditions associated with insulin resistance
       • Acanthosis nigricans
       • Hypertension
       • Dyslipidemia
       • Polycystic ovary syndrome
       • Small-for-gestational-age birth weight
   • Screening should begin at age 10 years (or at the onset of puberty if puberty occurs at a younger age)
   • If screening tests are normal, repeat at a minimum 3-year interval
6. Monogenic diabetes
   • Consider a diagnosis of monogenic diabetes in any of the following
     • Diabetes mellitus diagnosed within the first 6 months of life
     • If mild fasting hyperglycemia (100-150 mg/dL [5.5-8.5 mmol/L]), young, obese, and have family members with DM not characteristic of Type 1 or Type 2 DM
     • If negative diabetes-associated autoantibodies and without typical features of Type 2 DM
7. Cystic fibrosis-related diabetes (CFRD)
   • Annually screen for DM using OGTT if cystic fibrosis patients, beginning at 10 years old, who do not have a diagnosis of CFRD
   • A1C screening not recommended in this patient population
   • Agent of choice is insulin
   • If cystic fibrosis patient and impaired glucose tolerance without confirmed DM, prandial insulin therapy should be used to maintain weight
   • Annual monitoring for complications should begin 5 years after diagnosis of CFRD made
8. Posttransplantation diabetes mellitus
   • All patients should be screen for hyperglycemia after organ transplant
     • Once the patient is stable on an immunosuppressive therapy and without signs of acute infection
   • OGT is the preferred tests
   • Immunosuppressive therapy regimens demonstrate to provide the best outcomes for patient and graft survival should be used, irrespective of posttransplantation DM risk
9. Screening and diagnosing gestational diabetes mellitus
   • One-step strategy
     • 75-g OGTT at 24-48 weeks of gestation
       • Fasting Plasma Glucose measurement, and at 1 and 2 hrs after meal
       • Perform in the morning after an overnight fast of ≥ 8 hrs
     • Diagnosis is made if any of the following values are met or exceeded
       • Fasting: 92 mg/dL (5.1 mmol/L)
       • 1-hr: 180 mg/dL (10.0 mmol/L)
       • 2-hr: 153 mg/dL (8.5 mmol/L)
   • Two-step strategy
     • Step 1
       • 50 g nonfasting glucose load test at 24-48 weeks of gestation
         • Plasma glucose measurement at 1 hr
           • If plasma glucose level is ≥ 130 mg/dL* (7.2 mmol/L), proceed with 100 g OGTT (step 2)
     • Step 2
       • 100 g OGTT (Perform when the patient is fasting)
         • Measure fasting level, and 1 hr, 2 hrs, 3 hrs and 4 hrs after meal
       • Diagnosis of GDM is made if ≥ 2 of 4 values are met or exceeded (Carpenter-Coustan)
         • Fasting: 95 mg/dL (5.3 mmol/L)
         • 1-hr: 180 mg/dL (10.0 mmol/L)
         • 2-hr: 155 mg/dL (8.6 mmol/L)
         • 3-hr: 140 mg/dL (7.8 mmol/L)
           OR
       • Diagnosis of GDM is made if ≥ 2 of 4 values are met or exceeded (National Diabetes Data Group)
         • Fasting: 105 mg/dL (5.8 mmol/L)
         • 1-hr: 190 mg/dL (10.6 mmol/L)
         • 2-hr: 165 mg/dL (9.2 mmol/L)
         • 3-hr: 145 mg/dL (8.0 mmol/L)

References

1. American Diabetes A. Standards of Medical Care in Diabetes-2018 Abridged for Primary Care Providers. Clinical Diabetes. Jan 2018;36(1):14-37
2. American Diabetes A. Standards of Medical Care in Diabetes-2018. Diabetes Care. Jan 2018;41(Suppl 1): S1-S159
3. American Diabetes A. Standards of Medical Care in Diabetes-2019. Diabetes Care. Jan 2019; 42(1): S4-S6.

Contributor(s)

1. Pacheco, Caleb, S. MD
2. Hernandez, James, DO

Updated/Reviewed: March 2019