Glucose Intolerance Workup
- Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD more...
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.
Plasma glucose measurement is used as a screening test and for confirmation of a previously detected abnormality of glucose tolerance. Fasting plasma glucose studies are the preferred diagnostic test of the American Diabetes Association (ADA). A random plasma glucose measurement in the presence of classic diabetes symptoms is also acceptable.
Oral Glucose Tolerance Test
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.
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.
The ADA diagnostic criteria include the following:
Normal glucose homeostasis: Fasting plasma glucose (FPG) less than 100 mg/dL and 2-hour OGTT result less than 140 mg/dL, after a 75-g oral glucose load
Impaired fasting glucose: FPG of 100 mg/dL or more (the ADA reduced the cut-point from 110 mg/dL to identify more individuals who are at risk for developing diabetes) but less than 126 mg/dL
Impaired glucose tolerance: 2-h OGTT result of 140 mg/dL or more and less than 200 mg/dL
Diabetes mellitus: FPG of 126 mg/dL or more and a casual plasma glucose of 200 mg/dL or more; a casual plasma glucose level of 200 mg/dL or more on 2 occasions; or the classic symptoms plus a 2-hour OGTT result of 200 mg/dL or more
Gestational diabetes mellitus (GDM): The ADA has recommended the use of the IADPSG (International Association of Diabetes and Pregnancy Study Group) criteria based on the data from a large-scale multinational cohort, the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) study.  The diagnostic tool is used in many parts of the world. It is a one-step strategy which involves performing a 75-g OGTT in all pregnant women at 24-28 weeks' gestation. The diagnosis of GDM is made when any of the following is obtained: fasting plasma glucose greater than or equal to 92 mg/dL, 1-h value of 180 mg/dL or greater, and 2-h value of 153 mg/dL or greater. Furthermore, 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 DM.
It is important to note that in the United States, the most popular screening test for GDM is still a two-step strategy, 1-h plasma glucose measurement after a 50-g oral glucose load followed by (if necessary) 3-h diagnostic testing using a 100-g load. This approach is favored by the American Congress of Obstetricians and Gynecologists (ACOG). 
Women with a history of GDM should have lifelong screening for the development of diabetes or prediabetes at least every 3 years. 
Screening tests for type 2 diabetes should be considered at 3-year intervals in all individuals older than 45 years, particularly if the body mass index (BMI) is 25 kg/m2 (23 kg/m2 cutpoint is used for Asian Americans) or higher. Testing is indicated at a younger age or more frequently in individuals who are overweight (BMI 25 kg/m2 or higher, 23 kg/m2 in Asian Americans) and have additional risk factors, including the following:
First-degree relative with diabetes
High-risk ethnic background (eg, African American, Latino, Native American, Asian American, Pacific Islander)
Women who delivered a baby weighing more than 9 lb or who were diagnosed with gestational DM
Hypertension of 140/90 mm Hg and greater or on therapy for hypertension
Women with polycystic ovarian syndrome (PCOS)
A1C greater than or equal to 5.7%, IGT, or IFG on previous testing
History of cardiovascular disease
In the absence of the above criteria, testing for prediabetes and diabetes should begin at age 45 years. If results are normal, testing should be repeated at least every 3 years, with consideration of more frequent testing depending on initial results and risk status.
Previously, the glycated hemoglobin test was not recommended as a diagnostic test for diabetes. Recently, the ADA approved its use 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. It primarily serves as an index of the severity of hyperglycemia throughout the 6-8 weeks that precede the measurement. HBA1C testing alone may not always be sufficient in detecting presence of glucose intolerance. 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.
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.
Serum Electrolytes, BUN, Creatinine, Uric Acid, and Blood Gases
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.
Liver Function Tests
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.
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.
Complete Blood Cell Count
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 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.
Plasma Plasminogen Activator Inhibitor Type 1
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.[37, 38]
An increased plasma homocysteine level is a risk factor for atherosclerosis. The homocysteine level should therefore be measured in selected patients.
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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