Fructosamines are compounds that result from glycation reactions between glucose and a primary amine, followed by isomerization via the Amadori rearrangement. Biologically, fructosamines are recognized by fructosamine-3-kinase, which may trigger the degradation of advanced glycation end-products (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 in 1886.[ citation needed ]
Most commonly, fructosamine refers to a laboratory test for diabetes management that is rarely used in human clinical practice (simple blood glucose monitoring or hemoglobin A1c testing are preferred). In small animal veterinary practice however it is part of the diabetic cat or dog diagnosis and monitoring [1] giving an indication of blood glucose levels over the previous week. [2] Many direct-to-consumer lab testing companies sell fructosamine tests.
In diabetes, maintaining a normal blood glucose is essential to preventing many medical complications, including heart attacks, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy eventually leading to blindness. Most commonly, blood sugars are measured by either blood glucose monitoring which measures the current blood glucose level, or by glycated hemoglobin (HbA1c) which measures average glucose levels over approximately 3 months. In a similar way to hemoglobin A1c testing (which measures the glycation 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 of approximately 20 days, the plasma fructosamine concentration reflects relatively recent (1–2 week) changes in blood glucose.[ citation needed ]
In patients with diseases that reduce red blood cell lifespan, such as hemolytic anaemia or hemoglobinopathies such as sickle-cell disease, 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 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.[ citation needed ]
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. 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 [3] 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, and capillary electrophoresis) can more accurately assay A1c levels during complex hemoglobinopathies and other conditions. [4] However this does not overcome the effect of shortened red blood cell lifespan on A1c results.[ citation needed ]
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 and peritoneal dialysis 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. [5]
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. [6] 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, [7] which has been used in official advice for Quality and Outcomes Framework guidance in the UK [8] and summarized by the United States' National Quality Measures Clearinghouse, [9] gives the following formula and resulting values:
Fructosamine (μmol) | HbA1c % | HbA1c IFCC (mmol/mol) |
---|---|---|
200 | 5 | 31 |
258 | 6 | 42 |
288 | 6.5 | 48 |
317 | 7 | 53 |
346 | 7.5 | 58 |
375 | 8 | 64 |
435 | 9 | 75 |
494 | 10 | 86 |
552 | 11 | 97 |
611 | 12 | 108 |
Hemoglobin is a protein containing iron that facilitates the transport of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the exception of the fish family Channichthyidae. Hemoglobin in the blood carries oxygen from the respiratory organs to the other tissues of the body, where it releases the oxygen to enable aerobic respiration which powers the animal's metabolism. A healthy human has 12 to 20 grams of hemoglobin in every 100 mL of blood. Hemoglobin is a metalloprotein, a chromoprotein, and globulin.
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 to draw blood, then applying the blood to a chemically active disposable 'test-strip'. The other main option is continuous glucose monitoring (CGM). Different manufacturers use different technology, but most systems measure an electrical characteristic and use this to determine the glucose level in the blood. Skin-prick methods measure capillary blood glucose, whereas CGM correlates interstitial fluid glucose level to blood glucose level. Measurements may occur after fasting or at random nonfasting intervals, each of which informs diagnosis or monitoring in different ways.
Clinical chemistry is a division in medical laboratory sciences focusing on qualitative tests of important compounds, referred to as analytes or markers, in bodily fluids and tissues using analytical techniques and specialized instruments. This interdisciplinary field includes knowledge from medicine, biology, chemistry, biomedical engineering, informatics, and an applied form of biochemistry.
Drugs used in diabetes treat diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.
The blood sugar level, blood sugar concentration, blood glucose level, or glycemia is the measure of glucose concentrated in the blood. The body tightly regulates blood glucose levels as a part of metabolic homeostasis.
Acarbose (INN) is an anti-diabetic drug used to treat diabetes mellitus type 2 and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay, in North America as Precose, and in Canada as Prandase.
Glycated hemoglobin, also known as HbA1c, glycohemoglobin, glycosylated hemoglobin, or simply A1c, is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose, and fructose, spontaneously bond with hemoglobin when present in the bloodstream. However, glucose is only 21% as likely to do so as galactose and 13% as likely to do so as fructose, which may explain why glucose is used as the primary metabolic fuel in humans.
Glycation is the covalent attachment of a sugar to a protein, lipid or nucleic acid molecule. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic process responsible for many complications in diabetes mellitus and is implicated in some diseases and in aging. Glycation end products are believed to play a causative role in the vascular complications of diabetes mellitus.
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, atherosclerosis, chronic kidney disease, and Alzheimer's disease.
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 (ESRD) globally. The triad of protein leaking into the urine, rising blood pressure with hypertension and then falling renal function is common to many forms of CKD. Protein loss in the urine due to damage of the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) so called nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage renal disease. It usually is slowly progressive over years.
The term diabetes includes several different metabolic disorders that all, if left untreated, result in abnormally high concentrations of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces significant amounts of the hormone insulin, usually owing to the autoimmune destruction of the insulin-producing beta cells of the pancreas. Diabetes mellitus type 2, in contrast, is now thought to result from autoimmune attacks on the pancreas and/or insulin resistance. The pancreas of a person with type 2 diabetes may be producing normal or even abnormally large amounts of insulin. Other forms of diabetes mellitus, such as the various forms of maturity-onset diabetes of the young, may represent some combination of insufficient insulin production and insulin resistance. Some degree of insulin resistance may also be present in a person with type 1 diabetes.
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.
The polyol pathway is a two-step process that converts glucose to fructose. In this pathway glucose is reduced to sorbitol, which is subsequently oxidized to fructose. It is also called the sorbitol-aldose reductase pathway.
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 important in carbohydrate chemistry, specifically the glycation of hemoglobin.
Prediabetes is a component of metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesity, dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension. It is also associated with increased risk for cardiovascular disease (CVD). Prediabetes is more accurately considered an early stage of diabetes as health complications associated with type 2 diabetes often occur before the diagnosis of diabetes.
A postprandial glucose (PPG) test is a blood glucose test that determines the amount of glucose in the plasma after a meal. The diagnosis is typically restricted to postprandial hyperglycemia due to lack of strong evidence of co-relation with a diagnosis of diabetes.
Remogliflozin etabonate (INN/USAN) is a drug of the gliflozin class for the treatment of non-alcoholic steatohepatitis ("NASH") and type 2 diabetes. Remogliflozin was discovered by the Japanese company Kissei Pharmaceutical and is currently being developed by BHV Pharma, a wholly owned subsidiary of North Carolina, US-based Avolynt, and Glenmark Pharmaceuticals through a collaboration with BHV. In 2002, GlaxoSmithKline (GSK) received a license to use it. From 2002 to 2009, GSK carried out a significant clinical development program for the treatment of type-2 diabetes mellitus in various nations across the world and obesity in the UK. Remogliflozin etabonate's pharmacokinetics, pharmacodynamics, and clinical dose regimens were characterized in 18 Phase I and 2 Phase II investigations. Due to financial concerns, GSK stopped working on remogliflozin and sergliflozin, two further SGLT2 inhibitors that were licensed to the company, in 2009. Remogliflozin was commercially launched first in India by Glenmark in May 2019.
Canagliflozin, sold under the brand name Invokana among others, is a medication used to treat type 2 diabetes. It is used together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth.
1,5-Anhydroglucitol, also known as 1,5-AG, is a naturally occurring monosaccharide found in nearly all foods. Blood concentrations of 1,5-anhydroglucitol decrease during times of hyperglycemia above 180 mg/dL, and return to normal levels after approximately 2 weeks in the absence of hyperglycemia. As a result, it can be used for people with either type-1 or type-2 diabetes mellitus to identify glycemic variability or a history of high blood glucose even if current glycemic measurements such as hemoglobin A1c (HbA1c) and blood glucose monitoring have near normal values. Despite this possible use and its approval by the FDA, 1,5-AG tests are rarely ordered. There is some data suggesting that 1,5-AG values are useful to fill the gap and offer complementary information to HbA1c and fructosamine tests.
Gemigliptin (rINN), sold under the brand name Zemiglo, is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 inhibitor class of drugs. Glucose lowering effects of DPP-4 inhibitors are mainly mediated by GLP-1 and gastric inhibitory polypeptide (GIP) incretin hormones which are inactivated by DPP-4.