Fructosamine
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Fructosamines are compounds that result from
glycation Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic proces ...
reactions between a sugar (such as fructose or
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
) and a
primary amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...
, followed by
isomerization In chemistry, isomerization or isomerisation is the process in which a molecule, polyatomic ion or molecular fragment is transformed into an isomer with a different chemical structure. Enolization is an example of isomerization, as is tautomeriz ...
via the
Amadori rearrangement The Amadori rearrangement is an organic reaction describing the acid or base catalyzed isomerization or rearrangement reaction of the ''N''-glycoside of an aldose or the glycosylamine to the corresponding 1-amino-1-deoxy-ketose. The reaction is i ...
. Biologically, fructosamines are recognized by fructosamine-3-kinase, which may trigger the degradation of
advanced glycation end-products Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, ath ...
(though the true clinical significance of this pathway is unclear). Fructosamine can also refer to the specific compound 1-amino-1-deoxy-D-fructose ( isoglucosamine), first synthesized by Nobel laureate
Hermann Emil Fischer Hermann Emil Louis Fischer (; 9 October 1852 – 15 July 1919) was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He also developed the Fischer projection, a symbolic way of dra ...
in 1886. Most commonly, fructosamine refers to a laboratory test for
diabetes management The term ''diabetes'' includes several different metabolic disorders that all, if left untreated, result in abnormally high concentration of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces ...
that is rarely used in human clinical practice (simple
blood glucose monitoring Blood glucose monitoring is the use of a glucose meter for testing the concentration of glucose in the blood ( glycemia). Particularly important in diabetes management, a blood glucose test is typically performed by piercing the skin (typically, ...
or
hemoglobin A1c Glycated hemoglobin, also known as HbA1c, glycohemoglobin, hemoglobin A1c, A1C, is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose and fructose, spontaneously (i.e. non-enzymat ...
testing are preferred). In small animal veterinary practice however it is part of the diabetic cat or dog diagnosis and monitoring giving an indication of blood glucose levels over the previous week. Many direct-to-consumer lab testing companies sell fructosamine tests.


Use in medicine

In
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, maintaining a normal
blood glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
is essential to preventing many medical complications, including
heart attacks A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...
,
diabetic nephropathy Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease ...
, diabetic neuropathy and also
diabetic retinopathy Diabetic retinopathy (also known as diabetic eye disease), is a medical condition in which damage occurs to the retina due to diabetes mellitus. It is a leading cause of blindness in developed countries. Diabetic retinopathy affects up to 80 perc ...
eventually leading to
blindness Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment†...
. Most commonly, blood sugars are measured by either
blood glucose monitoring Blood glucose monitoring is the use of a glucose meter for testing the concentration of glucose in the blood ( glycemia). Particularly important in diabetes management, a blood glucose test is typically performed by piercing the skin (typically, ...
which measures the current blood glucose level, or by
glycated hemoglobin Glycated hemoglobin, also known as HbA1c, glycohemoglobin, hemoglobin A1c, A1C, is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose and fructose, spontaneously (i.e. non-enzymat ...
(HbA1c) which measures average glucose levels over approximately 3 months. In a similar way to hemoglobin A1c testing (which measures the
glycation Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic proces ...
of hemoglobin), fructosamine testing determines the fraction of total serum proteins that have undergone glycation (the ''glycated serum proteins''). Since albumin is the most abundant protein in blood, fructosamine levels typically reflect albumin glycation. (Some fructosamine tests specifically quantify the glycation of albumin, or ''glycated serum albumin'' instead of all proteins.). Because albumin has a
half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...
of approximately 20 days, the plasma fructosamine concentration reflects relatively recent (1–2 week) changes in blood glucose. In patients with diseases that reduce red blood cell lifespan, such as
hemolytic anaemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
or hemoglobinopathies such as
sickle-cell disease Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...
, a hemoglobin-based A1c test can be misleadingly low. A1c results may also be falsely high or low in hemoglobinopathies because abnormal hemoglobin variants can interfere in the analysis. In these cases, fructosamine measurement can be used as a marker of
blood sugar Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
levels, as its measurements are based on albumin instead of hemoglobin. However, any condition that changes serum albumin (such as the nephrotic syndrome) will affect the fructosamine result. In practice, fructosamine is rarely measured clinically (even in individuals with hemoglobinopathies or other red cell disorders) due to a number of pragmatic concerns. First, diabetes care is rarely changed in short (1–4 week) intervals, since diabetes medications can take months to reach a
steady state In systems theory, a system or a process is in a steady state if the variables (called state variables) which define the behavior of the system or the process are unchanging in time. In continuous time, this means that for those properties ''p' ...
. An exception to this is pregnancy, where medication needs can change more rapidly and fructosamine may help provide closer short-term monitoring. Second, fructosamine has higher variability than A1c tests. Third, the overwhelming majority of studies in diabetes care are based on A1c measurements, which can make fructosamine results difficult to interpret. Fourth, the A1c test is very well standardized and trusted due to its nearly universal use. A variety of more advanced forms of the A1c test (e.g. some types of HPLC,
immunoassay An immunoassay (IA) is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody (usually) or an antigen (sometimes). The molecule detected by the immunoass ...
and
capillary electrophoresis Capillary electrophoresis (CE) is a family of electrokinetic separation methods performed in submillimeter diameter capillaries and in micro- and nanofluidic channels. Very often, CE refers to capillary zone electrophoresis (CZE), but other elect ...
) can more accurately assay A1c levels during complex hemoglobinopathies and other conditions. However this does not overcome the effect of shortened red blood cell lifespan on A1c results.


In End Stage Renal Disease (ESRD)

Because glycated albumin (GA) has a shorter half-life than glycated hemoglobin (HbA1c), glycated albumin reflects recent glycemic control more accurately and usefully for monitoring patients with diabetic end stage renal disease (ESRD) (
hemodialysis Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...
and
peritoneal dialysis Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte pro ...
patients). It can be used less often than blood sugar testing. An average blood glucose level of 155–160 mg/dL could be matched to a GA value of 18–19% in patients with ESRD. The ratio of GA/HbA1c is 3.0 approximately.


Interpretation of results

There is no standard reference range available for this test. The reference values depend upon the factors of patient age, gender, sample population, and test method. Hence, each laboratory report will include the patient's specific reference range for the test. An increase in fructosamine in lab testing results usually means an increase in glucose in the blood. On average, each change of 3.3 mmol (60 mg/dl) in average blood sugar levels will give rise to changes of 2% HbA1c and 75 µmol fructosamine values. However, this overemphasizes the upper limit of many laboratories' reference ranges of 285 μmol/L as equivalent to HbA1c 7.5% rather than 6.5%. A comparative study, which has been used in official advice for
Quality and Outcomes Framework The Quality and Outcomes Framework (QOF) is a system for the performance management and payment of general practitioners (GPs) in the National Health Service (NHS) in England, Wales, Scotland and Northern Ireland. It was introduced as part of a n ...
guidance in the UK and summarized by the United States' National Quality Measures Clearinghouse, gives the following formula and resulting values: : = \times + :Hence: : = ( - 1.61) \times


See also

* Fructosamine kinase family *
Diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
* Blood sugar regulation *
Human serum albumin Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric. Albumin ...
*
End Stage Renal Disease Program In 1972 the United States Congress passed legislation authorizing the End Stage Renal Disease Program (ESRD) under Medicare. Section 299I of Public Law 92-603, passed on October 30, 1972, extended Medicare coverage to Americans if they had stage ...
*
ECRI Institute ECRI (originally founded as Emergency Care Research Institute) is an independent nonprofit organization tasked with "improving the safety, quality, and cost-effectiveness of care across all healthcare settings worldwide." History In the early 19 ...


Footnotes


External links

* Fructosamine a
Lab Tests Online

Fructosamine: analyte monograph
– The Association for Clinical Biochemistry and Laboratory Medicine {{Blood tests Blood tests Diabetes Diabetes-related tests Hexosamines Veterinary diagnosis