Blood sugar
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2008-07-16T10:14:38Z
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{{ For|the 2007 [[Pendulum (band)|Pendulum]] single|Blood Sugar/Axle Grinder }}
[[Image:Suckale08 fig3 glucose insulin day.jpg|thumbnail|400px|The idealised diagram shows the fluctuation of [[blood sugar]] (red) and the sugar-lowering hormone [[insulin]] (blue) in humans during the course of a day containing three meals. In addition, the effect of a [[sucrose|sugar]]-rich versus a [[starch]]-rich meal is highlighted.]]
'''Blood sugar''' is [[glucose]] in the blood. Glucose, transported via the bloodstream from the intestines to body cells, is the primary source of energy for the body's cells.
Blood sugar concentration, or glucose level, is tightly [[blood sugar regulation|regulated]] in the human body. Normally, the blood glucose level is maintained between about 4 and 6 mM per litre. Normal blood glucose level (homoeostasis) is about 90mg/100ml, which works out to 5mM/L, as the molecular weight is of glucose, C<sub>6</sub>H<sub>12</sub>O<sub>6</sub>, is about 180 g/mol. The normal total amount of glucose in circulating blood is therefore about 3.3 to 7g (assuming an ordinary adult blood volume of 5 liters, plausible for an average adult male). Glucose levels rise after meals for an hour or two and are usually lowest in the morning, before the first meal of the day.
Failure to maintain blood glucose in the normal range leads to conditions of persistently high ([[hyperglycemia]]) or low ([[hypoglycemia]]) blood sugar. [[Diabetes mellitus]], characterized by persistent hyperglycemia from any of several causes, is the most prominent disease related to failure of blood sugar regulation.
Although it is called "blood sugar," other simple sugars aside from glucose are found
in the blood, such as [[fructose]] and [[galactose]]. But only glucose levels are used as metabolic regulation signals (via [[insulin]] and [[glucagon]]).
==Normal values==
Despite long intervals between meals or the occasional consumption of meals with a substantial [[carbohydrate]] load, human blood glucose levels normally remain within a remarkably narrow range. In most humans this varies from about 80 mg/dl to perhaps 120 mg/dl (3.9 to 6.0 [[mmol]]/litre) except shortly after eating when the blood glucose level rises temporarily (up to 140 mg/dl in a non-diabetic).
It is usually a surprise to realize how little glucose is actually maintained in the blood and body fluids. The control mechanism works on very small quantities. In a healthy adult male of 75 [[kilogram|kg]] (165.35 [[Pound (mass)|lb]]) with a [[blood]] volume of 5 [[litre]]s (1.32 [[Gallon|gal]]), a blood glucose level of 100 mg/dl or 5.5 mmol/l corresponds to about 5 g (0.2 [[Fluid ounce|oz]] or 0.002 [[Gallon|gal]], 1/500 of the total) of glucose in the blood and approximately 45 g (1½ [[Fluid ounce|ounces]]){{Fact|date=April 2008}} in the total [[body water]] (which obviously includes more than merely blood and will be usually about 60% of the total [[body weight]] in men). A more familiar comparison may help – 5 grams of glucose is about equivalent to a commercial sugar packet (as provided in many restaurants with [[coffee]] or [[tea]]).
==Regulation== <!--Blood sugar regulation redirects here-->
The [[homeostasis|homeostatic]] effect that keeps the blood value of glucose in a remarkably narrow range is the result of many factors, of which hormone regulation is the most important.
There are two types of mutually antagonistic metabolic hormones affecting blood glucose levels:
* [[catabolic]] hormones (such as [[glucagon]], [[growth hormone]], and [[catecholamines]]thyroxine, somatostatin), which increase blood glucose
* and one [[anabolic]] hormone ([[insulin]]), which decreases blood glucose.
==Glucose measurement==
===Sample type===
Glucose can be measured in whole blood, [[blood serum|serum]], or [[blood plasma|plasma]]. Historically, blood glucose values were given in terms of whole blood, but most laboratories now measure and report the [[serum]] glucose levels. Because [[RBC]] ([[erythrocytes]]) have a higher concentration of protein (i.e. hemoglobin) than serum, serum has a higher water content and consequently more dissolved glucose than does whole blood. To convert from whole-blood glucose, multiply the value by 1.15 to give the serum/plasma level.
Collection of blood in clot ([[Serum-separating tube|red-top]]) tubes for serum chemistry analysis permits the metabolism of glucose in the sample by blood cells until separated by [[centrifugation]]. Higher than normal amounts of [[White blood cell|white]] or [[RBC|red]] blood cell counts can lead to excessive [[glycolysis]] in the sample with substantial reduction of glucose level if the sample is not processed quickly. Ambient temperature at which the blood sample is kept prior to centrifugation and separation of Plasma/Serum also affects glucose levels. At refrigerator temperatures, glucose remains relatively stable for several hours in the blood sample. At room temperature (25 °C), a loss of 1 to 2% of glucose per hour should be expected. The loss of glucose levels in aforementioned conditions can be prevented by using Fluoride top (gray-top) as the anticoagulant of choice upon blood collection, as Fluoride inhibits glycolysis. However, this should only be used when blood will be transported from one hospital laboratory to another for glucose measurement. Red-top serum separator tubes also preserve glucose in samples once they have been centrifugated to isolate the serum from cells, this tube would be the most efficient. Particular care should be given to drawing blood samples from the arm opposite the one in which an intravenous line is inserted, to prevent contamination of the sample with [[intravenous fluids]] (IV). Alternatively, blood can be drawn from the same arm with an IV line after the IV was turned off for at least 5 minutes and the arm is elevated to drain the infused fluids away from the vein. As little as 10% contamination with 5% [[dextrose]] (D5W) will elevate glucose in a sample by 500 mg/dl or more. Arterial, capillary and venous blood have comparable glucose levels in a fasting individual, whereas after meals venous levels are lower than capillary or arterial blood.
===Methodology===
There are two different major methods that have been used to measure glucose. The older one is a chemical method that exploits the ''nonspecific reducing property of glucose'' in a reaction with an indicator substance that acquires or changes color on its reduction. Since other blood compounds also have reducing properties (e.g., urea, which can build up in uremic patients), this method can have erroneous measurements up to 5 to 15 mg/dl. This is solved by the Enzymatic methods that are highly specific for glucose. The two most common employed enzymes are [[glucose oxidase]] and [[hexokinase]].
{| class="wikitable" border="2" cellpadding="5" cellspacing="0" align="center"
|-
| align="center" colspan="3" bgcolor="orange"| '''I. CHEMICAL METHODS'''
|-
| align="center" colspan="3" bgcolor="lightblue"| '''A. Oxidation-Reduction Reaction'''
|-
| align="center" colspan="3" bgcolor="white"|<math>Glucose + Alkaline Copper Tartarate\xrightarrow{Reduction} Cuprous Oxide </math>
|-
| width="900pt" align="center" colspan="3"|'''1. Alkaline Copper Reduction'''
|-
| width="200pt" align="center"| '''Folin Wu Method'''
| width="600pt" align="center" bgcolor="white"| <math>Cu^{++} + Phosphomolybdic Acid\xrightarrow{Oxidation} Phosphomolybdenum Oxide</math>
| width="100pt" align="center"| Blue end-product
|-
| width="200pt" align="center"| '''Benedict's method'''
| bgcolor="white" colspan="2"|
* Modification of Folin wu for Qualitative Urine Glucose
|-
| width="200pt" align="center"| '''Nelson Somoygi Method'''
| width="600pt" align="center" bgcolor="white"| <math>Cu^{++} + Arsenomolybdic Acid\xrightarrow{Oxidation} Arsenomolybdenum Oxide</math>
| width="100pt" align="center"| Blue end-product
|-
| width="200pt" align="center"| '''Neocuproine Method'''
| width="600pt" align="center" bgcolor="white"| <math>Cu^{++} + Neocuproine\xrightarrow{Oxidation} Cu^{++} Neocuproine Complex </math>*
| width="100pt" align="center"| Yellow-orange color [http://www.jtbaker.com/msds/englishhtml/d6824.htm Neocuproine]
|-
| width="200pt" align="center"| '''Shaeffer Hartmann Somygi'''
| bgcolor="white" colspan="2"|
* Utilizes the principle of [[Iodine]] reaction with Cuprous byproduct.
* Excess I<sub>2</sub> is then titrated with [[thiosulfate]].
|-
| width="900pt" align="center" colspan="3"|'''2. Alkaline Ferricyanide Reduction'''
|-
| width="200pt" align="center"| '''Hagedorn Jensen'''
| width="600pt" align="center" bgcolor="white"| <math>Glucose + Alk. Ferricyanide Yellow\longrightarrow Ferrocyanide</math>
| width="100pt" align="center"| Colorless end product; other reducing substances interfere with reaction
|-
| align="center" colspan="3" bgcolor="lightblue"| '''B. Condensation'''
|-
| width="200pt" align="center"| '''Ortho-toluidine Method'''
| width="600pt" bgcolor="white" colspan="2"|
* Utilizes [[aromatic amines]] and hot [[acetic acid]]
* Forms [[Glycosylamine]] and Schiff's base which is emerald green in color
* This is the most specific method, but the reagent used is toxic
|-
| width="200pt" align="center"| '''Anthrone (Phenols) Method'''
| bgcolor="white" colspan="2"|
* Forms hydroxymethyl furfural in hot acetic acid
|-
| align="center" colspan="3" bgcolor="orange"| '''II. ENZYMATIC METHODS'''
|-
| align="center" colspan="3" bgcolor="lightblue"|'''A. Glucose Oxidase'''
|-
| align="center" bgcolor="white" colspan="3"|<math>Glucose + O^{2}\xrightarrow[Oxidation] {glucose oxidase}Cuprous Oxide </math>
|-
| width="200pt" align="center"| '''Saifer Gernstenfield Method'''
| width="600pt" align="center" bgcolor="white"| <math>H_{2}O_2 + O-dianisidine\xrightarrow[Oxidation] {peroxidase} H_2O + oxidized chromogen</math>
| width="100pt" align="center"| Inhibited by reducing substances like BUA, [[Bilirubin]], [[Glutathione]], [[Ascorbic Acid]]
|-
| width="200pt" align="center"| '''Trinder Method'''
| bgcolor="white" colspan="2"|
* uses [http://www.online-medical-dictionary.org/4-Aminophenazone.asp?q=4-Aminophenazone 4-aminophenazone] oxidatively coupled with Phenol
* Subject to less interference by increases serum levels of [[Creatinine]], [[Uric Acid]] or [[Hemoglobin]]
* Inhibited by [[Catalase]]
|-
| width="200pt" align="center"| '''Kodak Ektachem'''
| bgcolor="white" colspan="2"|
* A Dry Chemistry Method
* Uses [[Reflectance Spectrophotometry]] to measure the intensity of color through a lower transparent film
|-
| width="200pt" align="center"| '''Glucometer'''
| bgcolor="white" colspan="2"|
* Home monitoring blood glucose assay method
* Uses a strip impregnated with a Glucose Oxidase reagent
|-
| align="center" colspan="3" bgcolor="lightblue"|'''B. Hexokinase'''
|-
| align="center" bgcolor="white" colspan="3"|
<math>
\begin{alignat}{2}
& Glucose + ATP\xrightarrow[Phosphorylation] {Hexokinase + Mg^{++}} G-6PO_4 + ADP \\
& G-6PO_4 + NADP\xrightarrow[Oxidation] {G-6PD} G-Phosphogluconate + NADPH + H^{+} \\
\end{alignat}
</math>
|-
| bgcolor="white" colspan="3"|
* [[NADP]] as cofactor
* NADPH (reduced product) is measured in 340 nm
* More specific than Glucose Oxidase method due to G-6PO_4, which inhibits interfering substances except when sample is hemolyzed
|-
|}
===Laboratory tests===
# Fasting Blood Sugar or Glucose test (FBS)
# Urine Glucose test
# Two-hr Postprandial Blood Sugar Test (2-h PPBS)
# Oral [[glucose tolerance test|Glucose Tolerance test]] (OGTT)
# Intravenous Glucose Tolerance test (IVGTT)
# Glycosylated Hemoglobin (HbA<sub>1C</sub>)
# Self-monitoring of Glucose level via Home Kits
===Clinical correlation===
The fasting blood glucose (FBG) level is the most commonly used indication of overall glucose homeostasis. Conditions that affect glucose levels are shown in the table below. They reflect abnormalities in the multiple control mechanism of glucose regulation.
The metabolic response to a carbohydrate challenge is conveniently assessed by the postprandial glucose level drawn 2 hours after a meal or a glucose load. In addition, the glucose tolerance test, consisting of serial timed measurements after a standardized amount of oral glucose intake, is used to aid in the diagnosis of [[diabetes]].
{| class="wikitable"
|+ '''Causes of Abnormal Glucose Levels'''
! style="background:#ffdfae;" | '''Persistent Hyperglycemia'''
! style="background:#ffdfae;" | '''Transient Hyperglycemia'''
! style="background:#ffdfae;" | '''Persistent Hypoglycemia'''
! style="background:#ffdfae;" | '''Transient Hypoglycemia'''
|-
| colspan="4" align="center" bgcolor="lightblue"| '''Reference Range, FBG: 70-110 mg/dl'''
|-
| width="200pt" align="center"|Diabetes Mellitus
| width="200pt" align="center"|[[Pheochromocytoma]]
| width="200pt" align="center"|[[Insulinoma]]
| width="200pt" align="center"|Acute Alcohol Ingestion
|-
| width="200pt" align="center"|Adrenal cortical hyperactivity [[Cushing's Syndrome]]
| width="200pt" align="center"|Severe [[Liver Disease]]
| width="200pt" align="center"|Adrenal cortical insufficiency [[Addison's Disease]]
| width="200pt" align="center"|Drugs: [[salicylates]], antituberculosis agents
|-
| width="200pt" align="center"|[[Hyperthyroidism]]
| width="200pt" align="center"|Acute stress reaction
| width="200pt" align="center"|[[Hypopituitarism]]
| width="200pt" align="center"|Severe Liver disease
|-
| width="200pt" align="center"|[[Acromegaly]]
| width="200pt" align="center"|[[Shock (medical)|Shock]]
| width="200pt" align="center"|[[Galactosemia]]
| width="200pt" align="center"|Several [[Glycogen storage diseases]]
|-
| width="200pt" align="center"|[[Obesity]]
| width="200pt" align="center"|[[Convulsions]]
| width="200pt" align="center"|Ectopic Insulin production from tumors
| width="200pt" align="center"|Hereditary fructose intolerance
|-
|}
==Health effects==
If blood sugar levels drop too low, a potentially fatal condition called [[hypoglycemia]] develops. Symptoms may include [[lethargy]], impaired mental functioning, [[irritability]], and [[Unconsciousness|loss of consciousness]].
If levels remain too high, appetite is suppressed over the short term. Long-term [[hyperglycemia]] causes many of the long-term health problems associated with [[diabetes]], including eye, kidney, and nerve damage.
==Low blood sugar==
Some people report drowsiness or impaired cognitive function several hours after meals, which they believe is related to a drop in blood sugar, or "low blood sugar". For more information, see:
*[[idiopathic postprandial syndrome]]
*[[hypoglycemia]]
Mechanisms which restore satisfactory blood glucose levels after [[hypoglycemia]] must be quick and effective, because of the immediate serious consequences of insufficient glucose (in the extreme, coma, less immediately dangerous, confusion or unsteadiness, amongst many other effects). This is because, at least in the short term, it is far more dangerous to have too little glucose in the blood than too much. In healthy individuals these mechanisms are indeed generally efficient, and symptomatic hypoglycemia is generally only found in diabetics using insulin or other pharmacological treatment. Such hypoglycemic episodes vary greatly between persons and from time to time, both in severity and swiftness of onset. In severe cases prompt medical assistance is essential, as damage (to brain and other tissues) and even death will result from sufficiently low blood glucose levels.
==Converting glucose units==
The standard unit for measuring blood glucose is mmol/L (same as millimolar, mM). The U.S. is the only country in the world to use mg/dL. {{Fact|date=April 2008}}
To convert blood glucose readings:
* Divide the mg/dL figure by 18 (or multiply by 0.055) to get mmol/L.
* Multiply the mmol/L figure by 18 (or divide by 0.055) to get mg/dL.
==References==
* John Bernard Henry, M.D.: Clinical diagnosis and Management by Laboratory Methods 20th edition, Saunders, Philadelphia, PA, 2001.
* Ronald A. Sacher and Richard A. McPherson: Widmann's Clinical Interpretation of Laboratory Tests 11th edition, F.A. Davis Company, 2001.
==See also==
* Current research - [[Boronic_acid#Boronic_acids_in_supramolecular_chemistry|Boronic acids in supramolecular chemistry: Saccharide recognition]]
* [[Blood glucose monitoring]]
[[Category:Blood tests]]
[[Category:Diabetes]]
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