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      Drugs & Diseases > Endocrinology

      Glucose Intolerance Workup

      Updated: Jul 08, 2020
      • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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      Workup

      Approach Considerations

      ADA Diagnostic Criteria

      According to the 2019 American Diabetic Association (ADA) guidelines, the following diagnostic criteria are required for the three stages of type 1 diabetes [4] :

      • Stage 1: multiple autoantibodies; no impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)
      • Stage 2: multiple autoantibodies; dysglycemia (IFG and/or IGT); fasting plasma glucose (FPG) of 100-125 mg/dL (5.6-6.9 mmol/L); 2-hour  plasma glucose (PG) of 140-199 mg/dL (7.8-11.0 mmol/L); HBA1C of 5.7%-6.4% (39-47 mmol/mol) or ≥10% increase in HBA1C
      • Stage 3: clinical symptoms; diabetes by standard criteria
      • Use plasma glucose rather than HBA1C to diagnose the acute onset of type 1 diabetes in those with hyperglycemia symptoms
      • The persistence of two or more autoantibodies predicts clinical diabetes and may indicate intervention is needed in the setting of a clinical trial

      One of the following criteria must be met for a diagnosis of diabetes [4] :

      • FPG ≥126 mg/dL (7.0 mmol/L), OR 
      • 2-hour PG ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT), OR
      • HBA1C ≥6.5% (48 mmol/mol), OR
      • Random plasma glucose ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis

      To avoid misdiagnosis or missed diagnosis, perform HBAIC testing with  a method that is certified by the NGSP and standardized to the Diabetes Control and Complications Trial (DCCT) assay. [4]

      In the presence of marked discordance between measured and plasma glucose levels of HBA1C, consider the possibility of HBA1C assay interference from hemoglobin variants (ie, hemoglobinopathies), and consider use of an assay without interference or plasma glucose criteria to diagnose diabetes. [4]  Use only plasma glucose criteria to diagnose diabetes in the setting of conditions associated with an altered relationship between HBA1C and glycemia (eg, sickle cell disease, second and third pregnancy trimesters and the postpartum period, glucose-6-phosphate dehydrogenase deficiency, infection with human immunodeficiency virus, hemodialysis, recent blood loss or transfusion, or erythropoietin therapy). [4]

      If unequivocal hyperglycemia is absent, the diagnosis requires two abnormal test results from the same sample or in two separate test samples. [4]

      A diagnosis of prediabetes is made if one of the following criteria are met [1] :

      • IFG: FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) 
      • IGT: OGTT 2-hour PG 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) 
      • HBA1C 5.7−6.4% (39−47 mmol/mol)

      The ADA notes that for all three tests, risk extends below the lower limit of the range and becomes greater at the higher end of the range.

      WHO Diagnostic Criteria

      The World Health Organization diagnostic criteria for diabetes and impaired glucose tolerance are as follows [3] :

      • Diabetes: FPG ≥126 mg/dL (7.0 mmol/L) OR OGTT 2-hour PG ≥200 mg/dL (11.1 mmol/L)
      • Impaired fasting glucose (IFG):  FPG 110 mg/dL to 125mg/dL (6.1 to 6.9mmol/L) AND OGTT 2-hour PG < 140mg/dL (< 7.8mmol/L) 
      • Impaired glucose tolerance (IGT): FPG < 126 mg/dL (< 7.0 mmol/L) AND OGTT 2-hour PG 140mg/dl to 200mg/dl (≥7.8 and < 11.1mmol/L) 

      Gestational Diabetes

      The ADA has recommended the use of either the one- or two-step approach at 24–28 weeks of gestation in pregnant women not previously known to have diabetes. [1, 4] The one-step approach involves performing a 75-g OGTT, with plasma glucose measurement when the patient is fasting and at 1 and 2 hours in this group of gravida at 24-28 weeks' gestation. Optimally, perform the OGTT in the morning after an overnight fast of at least 8 hours. The diagnosis of GDM is made when any of the following is met or exceeded [1, 4] :

      • Fasting: 92 mg/dL (5.1 mmol/L) 
      • 1 hour: 180 mg/dL (10.0 mmol/L) 
      • 2 hour: 153 mg/dL (8.5 mmol/L)

      The two-step approach is a 1-hour (nonfasting) plasma glucose measurement after a 50-g oral glucose load in women at 24-48 weeks' gestation who were not previously diagnosed with diabetes. If the plasma glucose level after 1 hours is ≥130 mg/dL, 135 mg/dL, or 140 mg/dL (7.2 mmol/L, 7.5 mmol/L, or 7.8 mmol/L, respectively), perform a fasting 100-g OGTT.

      The diagnosis of GDM is made if at least two of the following four plasma glucose levels (measured during OGTT) are met or exceeded [1] : 

      • Fasting: 95 mg/dL (5.3 mmol/L)
      • 1 hour: 180 mg/dL (10.0 mmol/L) 
      • 2 hour: 155 mg/dL (8.6 mmol/L) 
      • 3 hour: 140 mg/dL (7.8 mmol/L) 

      This two-step approach is favored by the American Congress of Obstetricians and Gynecologists (ACOG) with the recommendation of either 135 mg/dL (7.5 mmol/L) or 140 mg/dL (7.8 mmol/L). [43]

      Women with risk factors for type 2 diabetes are to be screened during the first prenatal visit, using standard diagnostic criteria; if positive, patients should receive a diagnosis of overt, not gestational, diabetes mellitus. Women with a history of GDM should have lifelong screening for the development of diabetes or prediabetes at least every 3 years. [1, 4]

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      Glucose Testing

      Plasma glucose (PG) measurement is used as a screening test and for confirmation of a previously detected abnormality of glucose tolerance.

      Fasting Plasma Glucose (FPG)

      Fasting plasma glucose studies are the preferred diagnostic test of the American Diabetes Association (ADA). The ADA diagnostic criteria, which emphasize fasting plasma glucose, facilitate the screening of individuals with undiagnosed diabetes; the criteria help to identify fewer people with diabetes than does OGTT, however.

      Oral Glucose Tolerance Test (OGTT)

      The standard oral glucose tolerance test (OGTT) involves measurement of plasma glucose concentration 2 hours after a 75-g oral glucose load. It is seldom used as a confirmatory test in the diagnosis of diabetes, but it may be helpful in situations where fasting or random glucose results are equivocal. It is required for diagnosing impaired glucose tolerance (IGT), though it is increasingly reserved for research purposes.

      A provisional diagnosis of diabetes must be confirmed on a subsequent day by any of three methods: fasting, casual, and OGTT.

      A1C Testing

      The ADA has approved the use of the glycated hemoglobin  as an additional tool for the diagnosis of diabetes, based on HBA1C equal to or greater than 6.5%, with 5.7-6.4% categorized as prediabetes. [1] However, the WHO does not recognize HbA1C aa a diagnostic test for diabetes or IFG or IGT [3]  HBA1C testing alone may not always be sufficient in detecting presence of glucose intolerance and primarily serves as an index of the severity of hyperglycemia throughout the 6-8 weeks that precede the measurement. [44]  Obtaining at least fasting plasma glucose levels along with HBA1C measurement is probably prudent when screening an individual for glucose intolerance. The HBA1C is highly specific as evidence of chronic hyperglycemia. It is a predictor of chronic complications. [45]

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      Laboratory Studies

      Workup for the diagnosis of glucose intolerance include plasma glucose level, oral glucose tolerance testing, other screening tests, urinalysis, complete blood count, lipid profile, liver function testing, and measurement of serum electrolytes, BUN, creatinine, uric acid, and blood gases.

      Urinalysis is important because ketonuria and massive glycosuria are indicators of acute decompensation. Significant proteinuria may be present in patients with diabetic nephropathy. Abnormalities of specific gravity and pH can be found in patients with uremia. Urine microalbumin is a marker of early renal impairment and endothelial dysfunction.

      A complete blood cell count is obtained, because an increased white blood cell count is common during acute infection. Ketoacidosis also is a cause of leukocytosis.

      A lipid profile is necessary to detect an increased triglyceride level, often a reflection of poor glycemic control that may normalize on attainment of euglycemia. Other lipid abnormalities, such as increased total cholesterol and low-density lipoprotein levels, are commonly found.

      Liver function tests assessing baseline liver function are used to exclude hepatic disease prior to commencing certain antihyperglycemic agents (eg, biguanides, thiazolidinediones). Periodic measurements are required during treatment with thiazolidinediones. Liver cirrhosis is a cause of glucose intolerance.

      Serum electrolytes, BUN, creatinine, uric acid, and blood gases are evaluated, because during acute decompensation, metabolic derangement from loss of water, sodium, potassium, and other electrolytes, as well as anion gap and osmolality abnormalities, are very common. Normal renal and hepatic function must be confirmed before therapy is started with some oral antidiabetic agents.

      A C-peptide profile is needed, because an undetectable plasma level indicates type 1 diabetes (in the absence of hypoglycemia). C-peptide profiling may also be helpful in deciding treatment in some cases of type 2 diabetes. It is not routinely used in clinical practice.

      Increased levels of plasma plasminogen activator inhibitor type 1, a marker of impaired fibrinolysis, are frequently found in patients with glucose intolerance and are a correlate of insulin resistance syndrome. [46, 47]  An increased plasma homocysteine level is a risk factor for atherosclerosis. The homocysteine level should therefore be measured in selected patients.

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      Electrocardiography and Other Cardiac Workup

      Perform ECG and other tests, depending on the patient's cardiovascular risk profile. Features of left ventricular hypertrophy and/or cardiomegaly are common in patients with hypertension. Low-risk patients may have normal test results, whereas with appropriate cardiac testing, patients with significant cardiovascular disease may show evidence of ischemia.

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