Introduction

Blood glucose monitoring helps to identify patterns in the fluctuation of blood glucose (sugar) levels that occur in response to diet, exercise, medications, and pathological processes associated with blood glucose fluctuations, such as diabetes mellitus. Unusually high or low blood glucose levels can potentially lead to life-threatening conditions, both acute and chronic. Blood glucose level (BGL) or blood sugar level (BSL) monitoring conducted outside of clinical facilities, such as the home, are often referred to as capillary blood glucose (CBG) tests. In contrast, blood glucose tests performed at clinical facilities may include CBG and plasma glucose venous blood tests.[1][2]

Pathophysiology

Most food products contain complex carbohydrates, which are broken down to supply energy to the cells in our body. Once ingested, food containing carbohydrates is broken down in the gastrointestinal system into simpler sugars such as glucose. In the small intestine, glucose molecules are absorbed into the bloodstream and transported to cells across the body, including the liver.[3] Pancreatic beta-cells produce insulin in response to elevated blood glucose levels.

In the postprandial phase, insulin facilitates the transportation of glucose from the bloodstream into cells.[4] Insulin also inhibits gluconeogenesis in the liver and facilitates the storage of glucose in the form of glycogen (glycogenesis) and fats (de novo lipogenesis (DNL)), which serve as short- and long-term stores of energy, respectively.[4] The human body attempts to maintain homeostasis in blood glucose levels (4 to 6 mmol or about 72 to 108 mg/dL). Homeostasis is influenced by the functional capacity of pancreatic beta-cells and cellular (skeletal muscles, liver, and adipose tissue) sensitivity to insulin.[4]

In conditions like diabetes mellitus, there is either a lack of insulin or the body does not appropriately respond to the actions of insulin; the latter is termed insulin resistance, wherein cellular uptake of glucose or storage of excess glucose is impaired. Dysfunction in the production or uptake of insulin can potentiate impaired blood glucose levels. Patients with impaired blood glucose homeostasis and elevated fasting blood glucose are at high risk for developing diabetes mellitus. Patients may be diagnosed with diabetes mellitus if their blood glucose levels are high.[5] Some organs, such as the brain, kidneys, liver, and erythrocytes, do not have insulin receptors and do not require insulin for glucose uptake. These organs, especially the brain, are significantly affected by acute, chronic, or recurrent drops in blood glucose levels; morbidity in such situations may be significant.[6][7]

Insulin is used to manage type 1 diabetes mellitus and some cases of type 2 diabetes mellitus. Insulin therapy has the well-known adverse side effect of hypoglycemia if its administration is not managed effectively. Patients with insulin-dependent diabetes will benefit from regular blood glucose monitoring. Regular daily blood glucose monitoring is recommended for those with diabetes mellitus using insulin therapy. 

Blood glucose monitoring may support diagnosing and managing the client with impaired glucose metabolism or diabetes. Regular monitoring of blood glucose levels may not be recommended for all patients with type 2 diabetes mellitus on oral antidiabetic drugs or dietary management alone. However, blood glucose monitoring may be warranted during titration of oral hypoglycemic medications known to cause hypoglycemia, such as sulfonylureas.[8]

Diagnostic Tests

Capillary Blood Glucose Test

A blood drop sample is usually collected from a fingertip prick.

Blood samples can also be sourced from alternate sites such as the earlobe, heel, forearm, and palm. Alternate site testing provides similar results to finger-prick testing, especially when fasting and at two-hour post-meal times. Using alternate sites may be less painful for the patient but may need a deeper lancet. Check with the glucometer manufacturer to determine if the machine may be used for alternate site testing.

The equipment used in capillary blood glucose testing includes a lancet to prick the skin, a glucometer, and test strips. Glucometers have a range of features. Modern "smart" machines require a very small sample of blood (from 0.3 to 1 microL) and have Bluetooth capabilities that synchronize data with paired applications (apps) on smartphones. These machines and apps record data and provide trends in glucose measurements. Further, some apps also offer options to record diet, medications used, and type of physical activity undertaken, which may be helpful to the health care practitioner when managing the care plan for the client with diabetes.

Advantages: Small blood sample, range of alternate testing sites, short testing time, prominent display on glucometer, less painful than venipuncture. 

Disadvantages: Manufacturers often provide low-cost or subsidized glucometers but sell testing strips and accessories at a significant profit margin. The test strips are expensive, time-limited with short expiry dates, and are affected by a range of variables, including temperature, humidity, size, and quality of blood samples. The clinical presentation of the patient will affect the accuracy of the test result. The reliability of results may vary in clients with hypoglycemia, anemia, altered hematocrit, hypotension, or critically ill patients. Older machines may need calibration with test strips, and results could be compromised if the calibration is not undertaken appropriately.[9][10]

Venous (Plasma) Blood Sample

Venous blood is collected via venipuncture, and the sample is processed in a commercial-grade laboratory with appropriate sophisticated quality control checks. 

Advantages: This method provides results superior to the capillary blood glucose test. However, this is dependent on the laboratory meeting established industry standards. 

Disadvantages: Painful procedure, risk of local tissue damage, unsuitable for frequent specimen collection.[11]

Continuous Glucose Monitoring (CGM)

Flash blood glucose monitoring (continuous interstitial fluid glucose monitoring) involves applying a water-resistant disposable sensor on the back of the upper arm or abdomen. Depending on the product, the sensor can remain on the patient for 3 to 14 days. The sensor can be scanned with a reader, which displays the current interstitial fluid glucose level and trends over the previous eight hours. CGM machines can store 90 days of glucose data. Data from the CGM device can be shared with family and care providers via a smartphone application; these devices are often capable of sending alarms or alert messages, including during episodes of hypoglycemia. In addition, some CGMs are compatible with insulin delivery devices and can stop insulin delivery if the machine predicts or recognizes a drop in BSL. Some older CGM machines require twice daily finger-prick tests for calibration. However, the more recently introduced devices do not require this calibration.

Advantages: In patients with type 1 diabetes mellitus and patients with type 2 diabetes mellitus who require intensive insulin therapy or sulfonylureas, flash monitoring has been demonstrated to be cost-effective when compared to CBG self-monitoring of blood glucose (SMBG). Interstitial glucose measurements are recorded as frequently as every 5 minutes every hour, which has the benefit of monitoring for hypoglycemia during sleep.

Disadvantages: Glucose is present in the blood before it is seen in the interstitial fluid, which the CGM measures. Hence sole monitoring of the interstitial fluid may not always be a reliable indicator of rapidly changing blood glucose levels. The high cost of sensors and machines (approximately $5000 per annum) may not make this a viable option in economically less advantaged clients and communities where health care is not subsidized by insurance or the government.[12][13][14]

Testing Procedures

Capillary Blood Glucose (CBG) Testing

Steps in undertaking a capillary blood glucose test with a glucometer are outlined below.

Collect all necessary equipment.

Wash and dry the site to be tested.

Prepare the skin or site, if required. The recommended testing site on the palm is the side of the distal fingertips to minimize injury to the underlying bone. Use of the fifth finger should be avoided, as the tissue may not be deep enough to prevent said injury. The thumb and first finger should also be avoided as these are sensitive areas compared to other fingers. Avoid the arm if a recent ipsilateral mastectomy, if any, was performed or an intravenous infusion is underway.[15] A heel stick stab, if done, can be more painful and may require resampling. Pain management should be considered in the neonate. The preferred site on the heel is the lateral or medial plantar surface for babies up to one year of age. 

Prepare equipment.

Prime the lancet to no more than 2.0 mm to minimize the risk of bone injury.

Remove the glucose testing strip from its container without touching the sensor tip. Next, insert the glucose testing strip into the glucometer; this often leads to the glucometer turning itself on.

Firmly apply the lancet to the sample collection site and release the trigger on the lancet to pierce the skin.

Recommendations are to wipe away the first drop of blood with clean gauze or tissue as this drop of blood may contain intracellular or interstitial fluid or be hemolyzed, both of which could affect the blood sample. Applying gentle downward pressure close to the puncture site may facilitate blood flow and collection of the second drop of blood.

Collect the second drop of blood as it forms by touching the tip of the glucose testing strip. 

Place the glucometer down and cover the skin puncture site with clean gauze or tissue. Pressure may be applied to stop further bleeding from the puncture site.

The machine normally provides a result at this stage unless there have been errors during collection; for example, insufficient sample, low battery, wrong code, or the machine times itself out. If an error displays on the glucometer, troubleshoot as appropriate.

Wash hands and replace equipment in storage bag container. Note test results relative to diet, exercise, and medication use as appropriate.[16][17][15]

Results, Reporting, and Critical Findings

Blood glucose is measured in mmol/L (millimoles per liter) or mg/dL (milligrams per deciliter).

Normal range: 4 to 6 mmol/L or 72 to 108 mg/dL. 

Lab-Based Blood Glucose Testing

Lab-based testing is required for the appropriate diagnosis of diabetes mellitus.

Prediabetes

Impaired fasting glucose range: 5.7 to 6.4 mmol/L or 100 to 125 mg/dL. 

Impaired oral glucose tolerance test range at two hours post 75-gram oral glucose ingestion: 7.8 to 11.0 mmol/L or 140 to 199 mg/dL.

Diabetes

Further testing may involve an oral glucose tolerance test to confirm the diagnosis. Advise the client to eat and drink over 150 grams per day of carbohydrate foods for the three days before testing. In addition, the client must fast overnight for at least 8 to 16 hours before this test. A fasting blood sample is collected, and a sweet drink containing 75 grams of glucose is given to the client after collecting the fasting blood sample. A second blood sample is collected two hours after consuming the glucose drink.

Oral glucose tolerance test: Glucose tolerance range at two hours post 75-gram oral glucose ingestion: ≥11.1 mmol/L, or ≥200 mg/dL.

A random venous blood glucose of at or above 11.1 mmol/L (≥200 mg/dL) or a fasting blood glucose at or above 7 mmol/L (≥126 mg/dL) on two or more separate occasions indicates the client is likely to have diabetes mellitus.

Other Tests

HbA1c: Glucose molecules tend to attach to hemoglobin. This test interprets the percentage of glucose molecules that combine with hemoglobin to form glycated hemoglobin. Once glucose molecules combine with the hemoglobin, the glycated hemoglobin remains for the life of the red blood cell, which is, on average and in health, approximately 120 days. Therefore, analyses of the red blood cell and its glycated hemoglobin reveal the average blood glucose levels in the client over that time frame.

Normal HbA1c: 3.5% to 5.6% or 15 to 42 mmol/mol.

Prediabetes is a possible diagnosis when the glycosylated hemoglobin is between 5.7% and 6.4%. 

A HbA1c result >6.5% usually confirms the presence of diabetes mellitus. Pharmacological intervention is required in clients with HbA1c levels greater than 7.0%. The HbA1c is the recommended diagnostic test for diabetes mellitus and can also inform the appropriate ongoing management of the diabetic client.[18][19][20][21]

Note: There is a small but significant difference between capillary blood glucose measurements undertaken at home and the venous or arterial blood sampling done in clinical facilities. Care must be taken when using the results from capillary and venous tests either exclusively or together.[22][23][24].  Additionally, blood glucose test results may be different in gestational diabetes; notably, high blood glucose early in the pregnancy may indicate the presence of type 1 or type 2 diabetes mellitus.

Clinical Significance

Blood glucose monitoring is an essential part of management in clients with diabetes mellitus. Very high or very low blood glucose levels could impair cellular function and may be lethal if not managed appropriately. Stress-related hyperglycemia may also be seen in clients who have experienced an acute medical or surgical event.

Hyperglycemia

The etiologies of hyperglycemia include but are not limited to:

• Inadequate insulin administration in clients with type 1 diabetes mellitus
• Insulin resistance with or without frank type 2 diabetes mellitus[25]
• Stress-related experiences such as critical illness[26]
• The dawn phenomena - a hormone surge between 4 am and 5 am that causes a spike in blood glucose levels[27]

Symptoms of hyperglycemia include polyuria (increased and frequent urination), polydipsia (increased thirst), blurred vision, headache, fatigue, and glucosuria. Acute symptoms of hyperglycemia are not usually seen at levels below 14 mmol/L or 250 mg/dL. 

Episodes of hyperglycemia over an extended period may lead to either diabetic ketoacidosis or a hyperglycemic hyperosmolar state. Untreated hyperglycemia may cause the client to enter ketoacidosis, using fatty acids for gluconeogenesis to produce the energy required for cellular function. Ketoacidosis may be due to decreased insulin production, as seen in type 1 diabetes mellitus; this clinical condition is termed diabetic ketoacidosis and is a life-threatening scenario. The lack of insulin production may result in high serum levels of ketones and ketoacids. Symptoms of diabetic ketoacidosis may include fruity breath, ketonuria, tachypnea, tachycardia, dyspnea, nausea, vomiting, altered mentation, and coma. 

Untreated hyperglycemia may also result in a hyperglycemic hyperosmolar state. This is a rare condition seen most commonly in clients with type 2 diabetes mellitus. Profound hyperglycemia can result in significant glucosuria; because glucose is hydrophilic, the kidney produces exceedingly large volumes of urine, resulting in life-threatening dehydration and potential coma. Both diabetic ketoacidosis and hyperosmolar state require emergent management to reduce elevated blood glucose levels with insulin therapy.

Long-term hyperglycemia can potentially delay wound healing and damage nerves (peripheral neuropathy) and end-organs such as the eyes (diabetic retinopathy), kidneys (renal failure), the brain (stroke), and the heart (myocardial infarction).[28]

Hypoglycemia

Symptoms of hypoglycemia are seen when low blood glucose levels deprive the body of essential fuel to sustain life. 

Causes of hypoglycemia include but are not limited to insulin overdose, inadequate carbohydrate intake in relation to insulin use, and an imbalance between insulin administration, carbohydrate intake, and exercise.

Clients with hypoglycemia may present with confusion, sweating, tachycardia, blurred vision, lightheadedness, clumsiness, or seizure activity. Often clients do not recognize the onset of symptoms of hypoglycemia which may put them at high risk of injury while undertaking regular activities such as driving or while asleep.

Emergent treatment to restore normal blood glucose levels is imperative as some organs, such as the brain, do not store glucose and need a constant supply of blood glucose to sustain life. Antidiabetic therapy needs re-evaluation when BSL falls below 5.6 mmol/liter (100 mg/dL), and modification of antidiabetic treatment is essential if BSL drops below 3.9 mmol/liter (70 mg/dL).[29] 

Clients across the lifespan with diabetes mellitus have varying clinical presentations and underlying clinical pathologies. They may not always report the effects of hypoglycemia or hyperglycemia, which should involve monitoring for other signs and symptoms. Clients with renal insufficiency are at risk of hypoglycemia as the kidneys are primarily responsible for metabolizing exogenous insulin.

Glycemic Care in the Clinical Setting

For appropriate glycemic control in clients with diabetes mellitus in non-critical care settings, capillary blood glucose testing is the recommended testing method. Blood glucose testing is recommended before meals and bedtime for clients who can eat. Clients receiving enteral feeds or are nil by oris (NPO) should be tested every 4 to 6 hours. All hospitalized patients will benefit from an initial assessment of blood glucose, irrespective of a history of diabetes mellitus. Using glucose management protocols, with nurse-initiated treatment protocols, is ideal for managing hypoglycemia in the hospital setting.

Community and Rehabilitation Setting-based Care

Clients need education on the importance of regulating diet, exercise, and medications to prevent acute or chronic complications in extreme blood glucose fluctuations in conditions like diabetes mellitus. Further, clients need specific education to test for blood glucose, including appropriate handwashing before testing, calibrating the glucometer if required, using the lancet, acquiring a blood sample, interpreting results, and reporting and following up on results.[30][31][32][33][34]

Enhancing Healthcare Team Outcomes

Managing diabetes mellitus to improve patient outcomes requires a complex multidisciplinary approach.[35] Blood glucose monitoring is a critical measurement of ongoing diabetes management. However, these blood test results should be viewed considering the complex socioeconomic disease process impact diabetes has on various body systems. Implementing a systematic process to manage altered blood glucose levels requires input and active collaboration with the client as a consumer, endocrinologists, diabetes nurse educators, pharmacists, clinical nurse specialists, dieticians, and data analysts.[31][36][37][35][33][38]

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Disclosure: Thomas Mathew declares no relevant financial relationships with ineligible companies.

Disclosure: Muhammad Zubair declares no relevant financial relationships with ineligible companies.

Disclosure: Prasanna Tadi declares no relevant financial relationships with ineligible companies.