Diabetes Risk Assessment / Prediabetes Screen

Screening for prediabetes and type 2 diabetes is important in all patients 45 years of age and older and others (see below) because both are common and often have a long, pre-symptomatic stage. Additionally, both conditions meet criteria for which early detection is appropriate and advantageous, especially since simple tests are readily available and effective interventions exist.

Current American Diabetes Association (ADA) testing criteria for prediabetes and diabetes in asymptomatic adults includes:

• All patients 45 years of age or older

• Consider in overweight or obese (BMI greater than or equal to 25 kg/m² or greater than or equal to 23 kg/m² in Asian Americans) adults of any age with one or more of the following risk factors:

- 1st degree relative with diabetes

- High risk race/ethnicity (eg, African American, Latino, Native American, Asian American, Pacific Islander)

- History of CVD

- Hypertension or on therapy for hypertension

- HDL-C value < 35 mg/dL and/or triglyceride value > 250 mg/dL

- Polycystic ovary syndrome

- Physical inactivity

- Conditions associated with insulin resistance (eg, severe obesity, acanthosis nigrans)

Fasting plasma glucose (FPG), plasma glucose after 75-gram oral glucose tolerance test (OGTT) and hemoglobin A1c (A1c) are equally appropriate assays for prediabetes and diabetes screening. 2018 ADA standards of medical care mandate that two abnormal test results (ie, both FPG and A1c) are needed for diagnosis unless there is a clear clinical diagnosis (ie, random plasma glucose greater than or equal to 200 mg/dL). A single abnormal test can be repeated using a new blood sample for confirmation.

Hemoglobin A1c: Factors such as duration of diabetes, adherence to therapy, and age of patient should also be considered in assessing the degree of blood glucose control.

FPG: Recent evidence revealed diurnal variation in FPG, with mean FPG higher in the morning than in the afternoon, indicating that many cases of undiagnosed diabetes would be missed in patients seen in the afternoon. Glucose concentrations decrease ex vivo with time in whole blood because of glycolysis. For this reason, samples should be centrifuged promptly. The rate of glycolysis, reported to average 5% to 7% [approximately 0.6 mmol/L (10 mg/dL)] per hour, varies with the glucose concentration, temperature, white blood cell count, and other factors. Glycolysis can be attenuated by inhibition of enolase with sodium fluoride (2.5 mg fluoride/mL of blood) or, less commonly, lithium iodoacetate (0.5 mg/mL of blood). These reagents can be used alone or, more commonly, with anticoagulants such as potassium oxalate, EDTA, citrate, or lithium heparin. Although fluoride maintains long-term glucose stability, the rate of decline of glucose in the first hour after sample collection in tubes with and without fluoride is virtually identical. (Note that leukocytosis will increase glycolysis even in the presence of fluoride if the white cell count is very high). After four hours, the glucose concentration is stable in whole blood for 72 hours at room temperature in the presence of fluoride. In separated, non-hemolyzed, sterile serum without fluoride, the glucose concentration is stable for eight hours at 25°C and 72 hours at 4°C.

Glucose can be measured in serum, or plasma, but plasma is recommended for diagnosis. Glucose concentrations in heparinized plasma are reported to be 5% lower than in serum. The reasons for the latter difference are not apparent, but may be attributable to the shift in fluid from erythrocytes to plasma caused by anticoagulants. The glucose concentrations during an OGTT in capillary blood are significantly higher than those in venous blood [mean of 1.7 mmol/L (30 mg/dL), equivalent to 20% to 25%], but the mean difference in fasting samples is only 0.1 mmol/L (2 mg/dL).

Although methods for glucose analysis exhibit low imprecision at the diagnostic decision limits of 7.0 mmol/L [(126 mg/dL), fasting] and 11.1 mmol/L [(200 mg/dL), post-glucose load], the relatively large intraindividual biological variability (Coefficients of variation of approximately 5% to 7%) may produce classification errors.