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Am Fam Physician. 2003;67(1):181-182

Diabetes is a major medical problem with high morbidity and mortality. The American Diabetes Association (ADA) divides diabetes into two types: the more common type 2 diabetes, which occurs most frequently among obese older adults and is characterized by insulin resistance and slightly decreased insulin secretion, and type 1 diabetes, which occurs among younger persons and is characterized by clearly deficient insulin production. Barr and associates reviewed the diagnostic tests for diabetes.

The most recent ADA guidelines made fasting plasma glucose the main tool to diagnose diabetes in nonpregnant adults and defined a new category of “impaired fasting glucose” (see accompanying table), which includes persons with fasting glucose levels between 110 mg per dL (6.1 mmol per L) and 126 mg per dL (7.0 mmol per L). This latter category replaced the previous classification of “impaired glucose tolerance,” which was diagnosed by abnormal oral glucose-tolerance tests and identified persons likely to develop diabetes. Classically, these diagnostic thresholds have been identified using population studies of mean glucose values or thresholds above which microvascular complications occur more frequently. This method of determining thresholds may not be appropriate because it is not exact and does not consider the onset of macrovascular (including cardiovascular) complications. In addition, the threshold should be based on the clear benefit of initiating treatment at a specific glycemic level. The clinical risks of sensitivity and specificity also should be considered in identifying the threshold glycemic level.

Current diagnostic tests of diabetes include random plasma glucose, fasting plasma glucose, glycosylated hemoglobin (HbA1c) measurements, and oral glucose-tolerance testing. Random glucose testing is easy and inexpensive; elevated levels in patients with classic symptoms should be confirmed by a second test. Fasting plasma glucose testing is inexpensive and fairly reproducible, but the implications for diabetes prevalence and management with a lowered threshold (from 140 mg per dL [7.8 mmol per L] to 126 mg per dL) are unclear. Oral glucose-tolerance testing is less reproducible and is no longer recommended in nonpregnant adults. HbA1c testing is recommended for monitoring glycemic control in patients already diagnosed with diabetes. Recent advances in HbA1c testing technique have led to high reproducibility, and results offer a measure of blood glucose levels over time, weighted slightly higher toward recent levels and correlating well with fasting plasma glucose levels. Results also predict diabetes complications. The major problem with using HbA1c as a diagnostic test is its limited sensitivity at very mild glycemic elevations.

In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be confirmed by repeated testing on different days to establish the diagnosis of diabetes mellitus.
1. Symptoms of diabetes plus casual plasma glucose level 200 mg per dL (11.1 mmol per L). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss.
2. Fasting plasma glucose level 126 mg per dL (7.0 mmol per L). Fasting is defined as no caloric intake for at least eight hours.
3. Two-hour plasma glucose level 200 mg per dL during an oral glucose-tolerance test. The test should be performed using a glucose load containing the equivalent of 75 g of anhydrous glucose dissolved in water. This test is not recommended for routine clinical use.

The authors conclude that an HbA1c level that is two standard deviations above the mean is highly suggestive of diabetes, but that the diagnosis requires confirmation by finding either a random plasma glucose level higher than 200 mg per dL (11.1. mmol per L) or a fasting plasma glucose level higher than 126 mg per dL. This might easily be done in the office setting by testing random glucose and HbA1c levels at the same time. If both tests are positive, the diagnosis is made. If only one test is positive, a fasting test can evaluate for diabetes or impaired glucose tolerance.

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