Definition/Introduction

Screening for any disease is fruitful when there is benefit from its early diagnosis and intervention. This activity discusses the screening for diabetes mellitus, which is one of those diseases that affect millions worldwide.

Diabetes Mellitus includes three groups of diseases-

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus
• Gestational diabetes

Type 1 Diabetes

Type I diabetes is diagnosed after hyperglycemia symptoms like polyuria, polydipsia, weight loss, and lethargy. It can also present as diabetic ketoacidosis in resource-constrained areas. Screening for type I diabetes is still in its infancy, although trials with tests for insulin, zinc transporter 8, antibodies to islet cells, IA-2 and GAD65 are underway.[1][2]

Type 2 Diabetes

 Type 2 diabetes may initially have few symptoms; however, long-term effects lead to a myriad of different problems late in the course of the disease leading to debilitating sequelae. More than 30 million people in the US have diabetes.[3] Due to an initial silent course, it often remains undetected for quite a long time before the appearance of symptoms. The screening for the disease aims at prevention and early treatment of the disease with the assumption that there is a long term benefit for its identification early in the disease process. The long-term benefit of screening vs. clinically detected diabetes is being explored.[4] Several studies with weak evidence suggest merits with the use of screening tests.[5]

Screening for type 2 diabetes can be by either fasting blood sugar, hemoglobin (A1C), glucose tolerance testing, and random plasma sugar. Urine glucose may be useful, but it is an inferior test to screen for diabetes, although research is reconsidering this claim.[6]

The screening is said to be positive if there are two abnormal tests from the same sample or two separate samples for the first three tests below:[7]

1) HbA1C over 6.5 percent[8]

2) Fasting plasma glucose greater than or equal to 126 mg/dL 

3) 2-hour glucose greater than or equal to 200 mg/dL in an oral glucose tolerance test with 75 mg glucose load.

4) Random blood glucose greater than or equal to 200 mg/dL in symptomatic patients(thirst, polyuria, weight loss, blurry vision)

For the diagnosis of diabetes mellitus, symptomatic patients require no further tests.

HbA1C values can be affected by factors that increase or decrease the RBC lifespan. Anemic states falsely increase HbA1C values, whereas their treatment falsely decreases it.[9] Kidney disease can affect the values and may increase or decrease values based on the treatment the patient is getting. Erythropoietin can falsely lower HbA1c values. Hemoglobin variants like HbS and HbC also cause variation in HbA1c values.[10]

The US Preventive Services Task Force's recommendation is to screen for diabetes between 40 to 70 years who are overweight or obese and repeat testing every three years if results are normal. 

Risk factors for diabetes include: • Hypertension • HDL < 35 mg/dL or TG > 250 mg/dL • First-degree relative with diabetes • High-risk race/ethnicity (African American, Latino, Native American, Asian American, Pacific Islander) • Asian Americans with a BMI of greater than or equal to 23 kg/m • Women who have delivered child greater than 9 lbs (4 kg) or with gestational diabetes • HbA1c = 5.7%, impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) 

Other: acanthosis nigricans, PCOS, history of coronary vascular disease (CVD), physical inactivity[11][7]

The recommendations for those with a high risk of developing diabetes are candidates for more early/frequent screening, early behavior intervention, and intensive treatment.

The recommended interval for the screening of asymptomatic patients is three years. The interval can be short in patients who have obesity and other major risk factors for developing diabetes.

The American Diabetes Association recommends screening for diabetes in adults aged 45 years or older and screening in persons with multiple risk factors regardless of age.

The American Association of Clinical Endocrinologists, American Academy of Family Physicians, Diabetes Australia, Diabetes UK, and the Canadian Task Force on Preventive Health Care have recommendations that differ in their approach to screening but acknowledge and stress risk factors compared to an older age.

Gestational Diabetes

Gestational diabetes adversely impacts the lives of both fetus and mother, making screening for it an essential part of obstetric care. Screening is necessary with the presence of one of the risk factors for diabetes. In addition to the risk factors discussed above, others include: 

• History of prediabetes(impaired glucose tolerance/fasting glucose, HbA1C>5.7)
• Prior history of gestational diabetes
• BMI>30 kg/m^2
• Family history of diabetes
• Multiple gestations
• Old maternal age
• Glycosuria at the first prenatal visit
• History of unexplained miscarriage or malformation

In the US, all women are screened for gestational diabetes, as most of them have at least a few of these risk factors.

HbA1C and fasting blood glucose have not been found useful for the screening of gestational diabetes. A glucose tolerance test is helpful in effective screening for this condition.[12] There are two ways of screening for gestational diabetes can be done:

•  One-step method: Glucose tolerance test with 75 mg glucose load. (overnight fast required)
•  Two-step method: First, by 50 g glucose challenge test which, if positive, is followed by a confirmatory second 3-hour glucose tolerance test with 100 g glucose load.

The one-step 75 g glucose tolerance test is simpler and the most widely used method. The test is positive if it satisfies any one of the following:

• Fasting glucose ≥92 mg/dL (5.1 mmol/L)
• 1hr glucose ≥180 mg/dL (10.0 mmol/L)
• 2hr glucose ≥153 mg/dL (8.5 mmol/mol)

Issues of Concern

There are many ongoing attempts to predict type 1 diabetes mellitus; all of them are still in the research phases.

The level of evidence regarding the usefulness of screening for type 2 diabetes for long-term complications (especially macrovascular complications) has been a matter of debate. There are conflicting studies that show no mortality benefit of screening for diabetes compared to those who receive a diagnosis on a clinical basis. Newer studies dispute this claim as more data for greater than ten years becomes available in the future.[5] Although the screening may lead to an increase in patients receiving overtreatment and give rise to issues like polypharmacy, side effects, increased cost, etc., experts believe the benefit achieved from the treatment of this disorder to be far higher.[4][13]

The recommendations are, at present, based upon the different sets of risk factors to determine those who are considered moderate or high risk. Each such recommendation defines high-risk patients differently. As more data emerges, there may be more congruency in those definitions. Among the different methods to determine the level of risk in developing diabetes, one of the most popular is FINDRISC.[14] Further improvement in such scoring systems could lead to a better selection of patients who undergo screening, leading to improved care at scale. Such methods have the potential to bring uniformity in the screening process for diabetes.

Clinical Significance

There is compelling evidence that early treatment of diabetes can reduce microvascular complications of diabetes.[15] The prompt treatment of the disease has significantly improved mortality, especially related to vascular disease.[5] The evidence for the impact of screening for diabetes is increasing. It is considered to be one of the more straightforward ways that can lead to prevention and reduction in morbidity and mortality of this disease. Excess mortality related to type 2 diabetes results from cardiovascular events, and early screening has the potential to allow for early intervention. The UKPDS demonstrated a 14% reduction in myocardial infarctions for every 1% decrease in HbA1c value.[16]

Gestational diabetes is an identified cause of several adverse outcomes during pregnancy, like pre-eclampsia, macrosomia, birth trauma, perinatal mortality, neonatal cardiac, respiratory, and metabolic complications.[17] There is also a long-term risk of developing type 1/type 2 diabetes mellitus and cardiovascular disease in the mother, as well as metabolic syndrome, obesity, hypertension, impaired glucose tolerance in the child. Identifying this early and prompt management has a positive impact on the health of the mother as well as the child.[18]

Nursing, Allied Health, and Interprofessional Team Interventions

The screening process invariably involves nursing personnel who usually obtain finger stick readings and perform the blood draw.  Nurse Practitioners and Certified Diabetes Educators play a crucial role in education, medication reconciliation, and demonstrating the proper use of devices and medication. Their active involvement assists the medical team to recognize the cases that could benefit from screening assists with early detection.[19] A hematologist and the nephrologist may consult on the validity of a result where multiple factors could affect the test results. For example, a person with anemia or kidney disease could have altered HbA1C values. The endocrinologist may assist and identify a group of patients who potentially have a higher risk of diabetes and recommend early/more frequent screening, such as those with other autoimmune diseases such as thyroid disease.[20] Complex cases such as those with cystic fibrosis, HIV, and post-transplant patients can be discussed with an endocrinologist to decide the usefulness of screening in such patients to form an individualized management plan. Hence a team effort could lead to better screening outcomes and prevent the diagnosis from going undetected.