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Diabetes Mellitus Diagnosis

The American Diabetes Association (ADA) published new Standards of Medical Care in Diabetes in 2011 (Diabetes Care 2011;34: Supplement 1, S11). Historically, the diagnosis of diabetes was based on fasting plasma glucose and 2 hour plasma glucose level after a 75 gram oral glucose tolerance test (OGTT). Despite being the gold standard, measurement of blood glucose is less accurate and precise than most physicians realize. Blood glucose measurements are also subject to several limitations including:

• 8-12 hour fasting specimen requirement
• Diurnal variation requiring morning collection to capture peak levels
• Large biological variation of 5-8%
• Nonstandardized instrument methods with >12% bias
• Glycolysis after collection, even in sodium fluoride tubes

In 2009, an International Expert Committee recommended the use of the HbA1c test to diagnose diabetes, with a threshold of 6.5% or greater (Diabetes Care 2009, 32 (7):1327-1334). The American Diabetes Association adopted this criterion in 2010. The diagnostic cutpoint of 6.5% was recommended based on the risk for developing microvascular complications such as retinopathy. This HbA1c criterion identifies one third fewer cases of undiagnosed diabetes than a fasting glucose cut point of 126 mg/dL or greater. However, the advantages of using HbA1c outweigh this limitation.

• Better index of overall glycemic exposure & risk of complications
• Low intraindividual variability (<2%)
• No requirement for fasting or timed specimen
• Standardized methods with precision <2%
• Less affected by acute illness or stress
• Good stability after blood collection
• Single test can be used for both diagnosis and monitoring

Today, the diagnostic criteria for diabetes include one of the following:

• HbA1c of 6.5% or greater
• Fasting plasma glucose of 126 mg/dL (7.0 mmol/L) or greater. Fasting is defined as no caloric intake for at least 8 hours.
• Two hour plasma glucose of 200 mg/dL (11.1 mmol/L) or greater during an OGTT with a 75 gram glucose load performed according to the World Health Organization (WHO)
• Random plasma glucose of 200 mg/dL or greater in an individual with symptoms of diabetes such as polyuria, polydipsia, and unexplained weight loss

There is less than 100% concordance between fasting plasma glucose, two hour plasma glucose and HbA1c. The HbA1c cut point of 6.5% identifies one third fewer cases of undiagnosed diabetes than a fasting glucose cut point of 126 mg/dL. If two different tests are run on an individual and the results are discordant, the test whose result is above the diagnostic cut point should be repeated and the diagnosis made on the basis of the confirmed test.

The Expert Committee on Diagnosis and Classification of Diabetes Mellitus recommends that testing for diabetes be considered in all adults age 45 and older. If results are normal, testing should be repeated at three year intervals. An abnormal result should be confirmed on a different day by any one of the recommended tests. Physicians should consider testing people at a younger age who are at risk of diabetes, including those who:

• are overweight or obese (BMI of 25 kg/m² or greater)
• have a first degree relative with diabetes
• are a member of a high risk ethnic group
• have a history of gestational diabetes or delivered a baby weighing greater than 9 pounds
• have hypertension (140/90 or higher)
• have HDL cholesterol of 35 mg/dLor less and/or triglyceride level of 250 mg/dL or greater
• have polycystic ovarian disease
• have other conditions associated with insulin resistance such as acanthosis nigricans
• have a history of cardiovascular disease
• have a history of HbA1c 5.7%, impaired fasting glucose or impaired glucose tolerance

The Expert Committee on Diagnosis and Classification of Diabetes Mellitus also recognizes an intermediate group of individuals whose glucose or HbA1c levels are higher than normal but do not meet the diagnostic criteria for diabetes. People with fasting glucose levels between 100 and 125 mg/dL (5.6-6.9 mmol/L) are defined as having impaired fasting glucose (IFG). Individuals who have a 2 hour glucose level between140 and 199 mg/dL (7.8-11.0 mmol/L) are defined as having impaired glucose tolerance (IGT). Individuals with any of these intermediate laboratory values are referred to as having prediabetes. Patients with HbA1c of 5.7 to 6.4% are also included in this category. People with prediabetes are at much higher risk of developing diabetes and cardiovascular disease. These patients often have abdominal obesity, dyslipidemia with low HDL cholesterol and high triglycerides and hypertension.

HbA1c <5.7% is considered normal while a result >6.5% on two separate tests suggests diabetes. An result between 5.7 and 6.4% may mean impaired fasting glucose (IFG) or impaired glucose tolerance (IGT).

Random plasma glucose <140 mg/dL is considered normal while a result >200 mg/dL indicate diabetes. A random value between 140 and 199 mg/dL suggests IFG or IGT.

Fasting plasma glucose level <100 mg/dL is considered normal while a value >126 mg/dL can mean diabetes. A fasting glucose level between 100 and 125 mg/dL can mean IFG or IGTl.

An oral glucose tolerance test result <140 mg/dL is considered normal while a result >200 mg/dL can mean diabetes. An OGTT result between 140 and 199 mg/dL is suggestive of IFG or IGT.

In 2014, The U.S. Preventive Services Task Force (USPSTF) issued a draft recommendation that expands screening for type 2 diabetes in adults who are considered to be at risk for diabetes. The Endocrine Society has endorsed the USPSTF recommendation.

The new recommendations include diabetes screening for people age 45 or older, those who are overweight or obese, or who have a first-degree relative who has diabetes. Also considered to be at risk for developing the disease are women who had gestational diabetes or polycystic ovarian syndrome, as well as African Americans, American Indians/Alaska Natives, Asian Americans, Hispanics/Latinos, and Native Hawaiians/Pacific Islanders.

Screening for blood glucose levels can be done in four different ways including HbA1c, random plasma glucose, fasting plasma glucose, or a glucose tolerance test. Results are interpreted using the criteria published by The Expert Committee on Diagnosis and Classification of Diabetes Mellitus.

The new recommendations take into account recent scientific evidence that shows measuring blood glucose in adults at increased risk for diabetes and treating those who have IFG or IGT with intensive lifestyle interventions has a moderate benefit in decreasing the risk for progression to diabetes. USPSTF found adequate evidence that intensive lifestyle modifications result in a lower incidence of diabetes, cardiovascular mortality and all-cause mortality. The level of evidence for screening was rated B, which qualifies it to become a covered preventive service without cost-sharing under the Affordable Care Act.

Specimen requirement is one lavender top (EDTA) tube of blood for HbA1c and one grey top tube of blood for glucose.