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Diabetes mellitus, a global epidemic, is increasing at an alarming rate and is associated with both increased morbidity and mortality. Globally, 589 million adults between the ages of 20 and 79 are living with diabetes mellitus, which is approximately 1 in every 9 people. This number is projected to rise to 853 million by 2050.[1] As of 2024, the United States has 38.5 million adults in this age group living with diabetes mellitus, ranking third worldwide in terms of diabetes prevalence. The United States also accounts for the highest total diabetes mellitus–related health expenditure globally.[2] Currently, only plasma glucose and glycated hemoglobin (HbA1c) are universally accepted as reliable measures of diabetes control. In certain conditions, the HbA1c measurement is not reliable. An example is in patients with red blood cell (RBC) disorders and renal disease. Fructosamine, which is a measure of non-enzymatic glycation of circulating proteins, including albumin, globulins, and lipoproteins, has evolved to be a reasonable alternative to HbA1c measurement in situations where HbA1c is not reliable. Because albumin is the most abundant of the serum proteins, fructosamine is predominantly a measure of glycated albumin, which represents the percentage of albumin that is glycated. Fructosamine and glycated albumin have a potential role in the diagnosis, monitoring, and management of diabetes mellitus.[3][4][5]

HbA1c is a product of nonenzymatic glycation of hemoglobin. RBCs have a lifespan of approximately 90 to 120 days; hence, HbA1c indicates the mean blood glucose concentration over the lifespan of the RBC. HbA1c is influenced by conditions affecting RBC survival. Conditions causing low RBC turnover, such as untreated iron, vitamin B12, or folic acid deficiency anemias, result in falsely high HbA1c  values. On the other hand, conditions causing high RBC turnover, such as hemolytic anemia, can result in falsely low HbA1c values. This phenomenon can occur in patients treated for iron, vitamin B12, or folate deficiencies, as well as in those treated with erythropoietin, such as individuals with chronic kidney disease. Fructosamine (1-amino-1-deoxy fructose) is a stable ketoamine formed by the reaction between glucose and the amino group of protein, predominantly albumin, but also including globulins and lipoproteins. The attachment of the aldehyde group of the carbohydrate with the N-terminal amino acid of the protein forms the reversible Schiff base product, the aldimine intermediate. The Schiff base product may be converted back to glucose and protein, or undergo the Amadori rearrangement to form stable fructosamine. This process is known as nonenzymatic glycation and is also referred to as the Maillard reaction. The Maillard reaction causes the browning phenomenon that occurs in milk and other food products when heated. Glycated albumin refers to the formation of ketoamine, specifically involving the major circulating protein albumin (3.5-5 g/dL). Glycated albumin is an example of a fructosamine. Because albumin is the most abundant of the serum proteins, fructosamine is predominantly a measure of glycated albumin. The formation of fructosamine and glycated albumin represents post-translational protein modifications. Non-immunoglobulin serum proteins have a much lower half-life, approximately 14 to 21 days.[6] The measurement of fructosamine or glycated albumin provides information on glucose control within the previous 2 to 3 weeks. Another important difference with HbA1c is the rate of nonenzymatic glycation of albumin, which is approximately 9- to 10-fold higher than that of HbA1c.[7][8]

Healthcare professionals, including nurse practitioners, should be familiar with the diagnosis of diabetes mellitus. Fructosamine and glycated albumin can be used as alternative markers in patients where the HbA1c assay is unreliable. Additionally, they can identify poor glucose control more rapidly than HbA1c, ie, short-term hyperglycemia. A major promise of the tests is their ability to predict those pre-diabetic patients who progress to clinical diabetes, as this could lead to major lifestyle and pharmacological interventions to prevent the onset of diabetes and its complications. Finally, they may also have a role in the management of diabetes mellitus during pregnancy, as pregnant patients need frequent glucose monitoring. Unlike HbA1c, which reflects glycemia over 8 to 12 weeks, fructosamine and glycated albumin provide insight into glucose levels over a shorter period of 2 to 3 weeks.[24] Glycated albumin has been reported to be a better marker than HbA1c for the assessment of glucose control in people with diabetes mellitus who have chronic kidney disease and those on hemodialysis and peritoneal dialysis.[25][26]