Blood sugar level

The blood sugar level, blood sugar concentration, or blood glucose level is the amount of glucose present in the blood of humans and other animals. Glucose is a simple sugar and approximately 4 grams of glucose are present in the blood of a 70-kilogram (150 lb) human at all times.[2] The body tightly regulates blood glucose levels as a part of metabolic homeostasis.[2] Glucose is stored in skeletal muscle and liver cells in the form of glycogen;[2] in fasted individuals, blood glucose is maintained at a constant level at the expense of glycogen stores in the liver and skeletal muscle.[2]

In humans, a blood glucose level of four grams, or about a teaspoon, is critical for normal function in a number of tissues, and the human brain consumes approximately 60% of blood glucose in fasted, sedentary individuals.[2] A persistent elevation in blood glucose leads to glucose toxicity, which contributes to cell dysfunction and the pathology grouped together as complications of diabetes.[2] Glucose can be transported from the intestines or liver to other tissues in the body via the bloodstream.[2] Cellular glucose uptake is primarily regulated by insulin, a hormone produced in the pancreas.[2]

Glucose levels are usually lowest in the morning, before the first meal of the day, and rise after meals for an hour or two by a few millimoles. Blood sugar levels outside the normal range may be an indicator of a medical condition. A persistently high level is referred to as hyperglycemia; low levels are referred to as hypoglycemia. Diabetes mellitus is characterized by persistent hyperglycemia from any of several causes, and is the most prominent disease related to failure of blood sugar regulation. There are different methods of testing and measuring blood sugar levels.

The intake of alcohol causes an initial surge in blood sugar, and later tends to cause levels to fall. Also, certain drugs can increase or decrease glucose levels.[3]

Suckale08 fig3 glucose insulin day
The fluctuation of blood sugar (red) and the sugar-lowering hormone insulin (blue) in humans during the course of a day with three meals. One of the effects of a sugar-rich vs a starch-rich meal is highlighted.[1]

Units

The international standard way of measuring blood glucose levels is in terms of a molar concentration, measured in mmol/L (millimoles per litre; or millimolar, abbreviated mM). In the United States, Germany and other countries mass concentration is measured in mg/dL (milligrams per decilitre).[4]

Since the molecular weight of glucose C6H12O6 is 180, the difference between the two units is a factor of 18, so that 1 mmol/L of glucose is equivalent to 18 mg/dL.[5]

Normal values

Humans

Normal value ranges may vary slightly among different laboratories. Many factors affect a person's blood sugar level. The body's homeostatic mechanism of blood sugar regulation (known as glucose homeostasis), when operating normally, restores the blood sugar level to a narrow range of about 4.4 to 6.1 mmol/L (79 to 110 mg/dL) (as measured by a fasting blood glucose test).[6]

The normal blood glucose level (tested while fasting) for non-diabetics, should be between 3.9 and 7.1 mmol/L (70 to 130 mg/dL). The global mean fasting plasma blood glucose level in humans is about 5.5 mmol/L (100 mg/dL);[7][5] however, this level fluctuates throughout the day. Blood sugar levels for those without diabetes and who are not fasting should be below 6.9 mmol/L (125 mg/dL).[8] The blood glucose target range for diabetics, according to the American Diabetes Association, should be 5.0–7.2 mmol/l (90–130 mg/dL) before meals, and less than 10 mmol/L (180 mg/dL) after meals (as measured by a blood glucose monitor).[9]

Despite widely variable intervals between meals or the occasional consumption of meals with a substantial carbohydrate load, human blood glucose levels tend to remain within the normal range. However, shortly after eating, the blood glucose level may rise, in non-diabetics, temporarily up to 7.8 mmol/L (140 mg/dL) or slightly more. For people with diabetes maintaining 'tight diabetes control', the American Diabetes Association recommends a post-meal glucose level of less than 10 mmol/L (180 mg/dL) and a fasting plasma glucose of 3.9 to 7.2 mmol/L (70–130 mg/dL).[10]

The actual amount of glucose in the blood and body fluids is very small. In a healthy adult male of 75 kg with a blood volume of 5 liters, a blood glucose level of 5.5 mmol/L (100 mg/dL) amounts to 5g, equivalent to about a teaspoonful of sugar.[11] Part of the reason why this amount is so small is that, to maintain an influx of glucose into cells, enzymes modify glucose by adding phosphate or other groups to it.

Other animals

In general, ranges of blood sugar in common domestic ruminants are lower than in many monogastric mammals.[12] However this generalization does not extend to wild ruminants or camelids. For serum glucose in mg/dL, reference ranges of 42 to 75 for cows, 44 to 81 for sheep, and 48 to 76 for goats, but 61 to 124 for cats; 62 to 108 for dogs, 62 to 114 for horses, 66 to 116 for pigs, 75 to 155 for rabbits, and 90 to 140 for llamas have been reported.[13] A 90 percent reference interval for serum glucose of 26 to 181 mg/dL has been reported for captured mountain goats (Oreamnos americanus), where no effects of the pursuit and capture on measured levels were evident.[14] For beluga whales, the 25–75 percent range for serum glucose has been estimated to be 94 to 115 mg/dL.[15] For the white rhinoceros, one study has indicated that the 95 percent range is 28 to 140 mg/dL.[16] For harp seals, a serum glucose range of 4.9 to 12.1 mmol/L [i.e. 88 to 218 mg/dL] has been reported; for hooded seals, a range of 7.5 to 15.7 mmol/L [i.e. about 135 to 283 mg/dL] has been reported.[17]

Regulation

The body's homeostatic mechanism keeps blood glucose levels within a narrow range. It is composed of several interacting systems, of which hormone regulation is the most important.

There are two types of mutually antagonistic metabolic hormones affecting blood glucose levels:

These hormones are secreted from pancreatic islets which are bundles of endocrine tissues. There are four types of pancreatic islets, alpha (A) cells, beta (B) cells, Delta (D) cells and F cells. Glucagon is secreted from alpha cells, while insulin is secreted by beta cells. Together they regulate the blood-glucose levels through negative feedback, a process where the end product of one reaction stimulates the beginning of another reaction. In blood-glucose levels, insulin lowers the concentration of glucose in the blood. The lower blood-glucose level (a product of the insulin secretion) triggers glucagon to be secreted, and repeats the cycle.[19]

In order for blood glucose to be kept stable, modifications to insulin, glucagon, epinephrine and cortisol are made. Each of these hormones has a different responsibility to keep blood glucose regulated; when blood sugar is too high, insulin tells muscles to take up excess glucose for storage. Glucagon responds to too low of a blood glucose level; it informs the tissue to produce more glucose. Epinephrine prepares the muscles and respiratory system for activity in the case of a "fight and flight" response. Lastly, cortisol supplies the body with fuel in times of heavy stress.[20]

Abnormalities

High blood sugar

If blood sugar levels remain too high the body suppresses appetite over the short term. Long-term hyperglycemia causes many health problems including heart disease, cancer,[21] eye, kidney, and nerve damage.[22]

Blood sugar levels above 300 can cause fatal reactions. Ketones will be very high (a magnitude higher than when eating a very low carbohydrate diet) initiating ketoacidosis. The Mayo Clinic recommends emergency room treatment above 300 mg/dL blood glucose.

The most common cause of hyperglycemia is diabetes. When diabetes is the cause, physicians typically recommend an anti-diabetic medication as treatment. From the perspective of the majority of patients, treatment with an old, well-understood diabetes drug such as metformin will be the safest, most effective, least expensive, most comfortable route to managing the condition.[23] Diet changes and exercise implementation may also be part of a treatment plan for diabetes.

Low blood sugar

If blood sugar levels drop too low, a potentially fatal condition called hypoglycemia develops. Symptoms may include lethargy, impaired mental functioning; irritability; shaking, twitching, weakness in arm and leg muscles; pale complexion; sweating; loss of consciousness.

Mechanisms that restore satisfactory blood glucose levels after extreme hypoglycemia (below 40 mg/dL) must be quick and effective to prevent extremely serious consequences of insufficient glucose: confusion or unsteadiness and, in the extreme (below 15 mg/dL) loss of consciousness and seizures. Without discounting the potentially quite serious conditions and risks due to or oftentimes accompanying hyperglycemia, especially in the long-term (diabetes or pre-diabetes, obesity or overweight, hyperlipidemia, hypertension, etc.), it is still generally more dangerous to have too little glucose – especially if levels are very low – in the blood than too much, at least temporarily, because glucose is so important for metabolism and nutrition and the proper functioning of the body's organs. This is especially the case for those organs that are metabolically active or that require a constant, regulated supply of blood sugar (the liver and brain are examples). In healthy individuals, blood glucose-regulating mechanisms are generally quite effective, and symptomatic hypoglycemia is generally found only in diabetics using insulin or other pharmacological treatment, and in starvation or severe malnutrition or malabsorption (of various causes), and conditions such as anorexia. Hypoglycemic episodes can vary greatly between persons and from time to time, both in severity and swiftness of onset. For 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.

Glucose measurement

Sample source

Glucose testing in a fasting individual, show comparable levels of glucose in arterial, venous, and capillary blood. But following meals, capillary and arterial blood glucose levels can be significantly higher than venous levels. Although these differences vary widely, one study found that following the consumption of 50 grams of glucose, "the mean capillary blood glucose concentration is higher than the mean venous blood glucose concentration by 35%."[24][25][26]

Sample type

Glucose is measured in whole blood, plasma or serum. Historically, blood glucose values were given in terms of whole blood, but most laboratories now measure and report plasma or serum glucose levels. Because red blood cells (erythrocytes) have a higher concentration of protein (e.g., hemoglobin) than serum, serum has a higher water content and consequently more dissolved glucose than does whole blood. To convert from whole-blood glucose, multiplication by 1.14[27] has been shown to generally give the serum/plasma level

To prevent contamination of the sample with intravenous fluids, particular care should be given to drawing blood samples from the arm opposite the one in which an intravenous line is inserted. Alternatively, blood can be drawn from the same arm with an IV line after the IV has been turned off for at least 5 minutes, and the arm has been elevated to drain infused fluids away from the vein. Inattention can lead to large errors, since as little as 10% contamination with a 5% glucose solution (D5W) will elevate glucose in a sample by 500 mg/dL or more. The actual concentration of glucose in blood is very low, even in the hyperglycemic.

Measurement techniques

Two major methods have been used to measure glucose. The first, still in use in some places, is a chemical method exploiting the nonspecific reducing property of glucose in a reaction with an indicator substance that changes color when reduced. Since other blood compounds also have reducing properties (e.g., urea, which can be abnormally high in uremic patients), this technique can produce erroneous readings in some situations (5–15 mg/dL has been reported). The more recent technique, using enzymes specific to glucose, is less susceptible to this kind of error. The two most common employed enzymes are glucose oxidase and hexokinase.[28] Average blood glucose concentrations can also be measured. This method measures the level of glycated hemoglobin, which is representative of the average blood glucose levels over the last, approximately, 120 days.[28]

In either case, the chemical system is commonly contained on a test strip which is inserted into a meter, and then has a blood sample applied. Test-strip shapes and their exact chemical composition vary between meter systems and cannot be interchanged. Formerly, some test strips were read (after timing and wiping away the blood sample) by visual comparison against a color chart printed on the vial label. Strips of this type are still used for urine glucose readings, but for blood glucose levels they are obsolete. Their error rates were, in any case, much higher. Errors when using test strips were often caused by the age of the strip or exposure to high temperatures or humidity.[29] More precise blood glucose measurements are performed in a medical laboratory, using hexokinase, glucose oxidase, or glucose dehydrogenase enzymes.

Urine glucose readings, however taken, are much less useful. In properly functioning kidneys, glucose does not appear in urine until the renal threshold for glucose has been exceeded. This is substantially above any normal glucose level, and is evidence of an existing severe hyperglycemic condition. However, as urine is stored in the bladder, any glucose in it might have been produced at any time since the last time the bladder was emptied. Since metabolic conditions change rapidly, as a result of any of several factors, this is delayed news and gives no warning of a developing condition. Blood glucose monitoring is far preferable, both clinically and for home monitoring by patients. Healthy urine glucose levels were first standardized and published in 1965[30] by Hans Renschler.

I. CHEMICAL METHODS
A. Oxidation-reduction reaction
1. Alkaline copper reduction
Folin-Wu method Blue end-product
Benedict's method
  • Modification of Folin–Wu method for qualitative urine glucose
Nelson–Somogyi method Blue end-product
Neocuproine method * Yellow-orange color neocuproine[31]
Shaeffer–Hartmann–Somogyi
  • Uses the principle of iodine reaction with cuprous byproduct.
  • Excess I2 is then titrated with thiosulfate.
2. Alkaline Ferricyanide Reduction
Hagedorn–Jensen Colorless end product; other reducing substances interfere with reaction
B. Condensation
Ortho-toluidine method
Anthrone (phenols) method
  • Forms hydroxymethyl furfural in hot acetic acid
II. ENZYMATIC METHODS
A. Glucose oxidase
Saifer–Gerstenfeld method Inhibited by reducing substances like BUA, bilirubin, glutathione, ascorbic acid
Trinder method
Kodak Ektachem
  • A dry chemistry method
  • Uses spectrophotometry to measure the intensity of color through a lower transparent film
Glucometer
  • Home monitoring blood glucose assay method
  • Uses a strip impregnated with a glucose oxidase reagent
B. Hexokinase

  • NADP as cofactor
  • NADPH (reduced product) is measured in 340 nm
  • More specific than glucose oxidase method due to G-6PO4, which inhibits interfering substances except when sample is hemolyzed

Clinical correlation

The fasting blood glucose level, which is measured after a fast of 8 hours, is the most commonly used indication of overall glucose homeostasis, largely because disturbing events such as food intake are avoided. Conditions affecting glucose levels are shown in the table below. Abnormalities in these test results are due to problems in the multiple control mechanism of glucose regulation.

The metabolic response to a carbohydrate challenge is conveniently assessed by a postprandial glucose level drawn 2 hours after a meal or a glucose load. In addition, the glucose tolerance test, consisting of several timed measurements after a standardized amount of oral glucose intake, is used to aid in the diagnosis of diabetes.

Error rates for blood glucose measurements systems vary, depending on laboratories, and on the methods used. Colorimetry techniques can be biased by color changes in test strips (from airborne or finger borne contamination, perhaps) or interference (e.g., tinting contaminants) with light source or the light sensor. Electrical techniques are less susceptible to these errors, though not to others. In home use, the most important issue is not accuracy, but trend. Thus if a meter / test strip system is consistently wrong by 10%, there will be little consequence, as long as changes (e.g., due to exercise or medication adjustments) are properly tracked. In the US, home use blood test meters must be approved by the federal Food and Drug Administration before they can be sold.

Finally, there are several influences on blood glucose level aside from food intake. Infection, for instance, tends to change blood glucose levels, as does stress either physical or psychological. Exercise, especially if prolonged or long after the most recent meal, will have an effect as well. In the typical person, maintenance of blood glucose at near constant levels will nevertheless be quite effective.

Causes of abnormal glucose levels
Persistent hyperglycemia Transient hyperglycemia Persistent hypoglycemia Transient hypoglycemia
Reference range, FBG: 70–110 mg/dL
Diabetes mellitus Pheochromocytoma Insulinoma Acute alcohol ingestion
Adrenal cortical hyperactivity Cushing's syndrome Severe liver disease Adrenal cortical insufficiency Addison's disease Drugs: salicylates, antituberculosis agents
Hyperthyroidism Acute stress reaction Hypopituitarism Severe liver disease
Acromegaly Shock Galactosemia Several glycogen storage diseases
Obesity Convulsions Ectopic insulin production from tumors Hereditary fructose intolerance

See also

References

  1. ^ Daly ME, Vale C, Walker M, Littlefield A, Alberti KG, Mathers JC (June 1998). "Acute effects on insulin sensitivity and diurnal metabolic profiles of a high-sucrose compared with a high-starch diet" (PDF). The American Journal of Clinical Nutrition. 67 (6): 1186–96. doi:10.1093/ajcn/67.6.1186. PMID 9625092.
  2. ^ a b c d e f g h Wasserman DH (January 2009). "Four grams of glucose". American Journal of Physiology. Endocrinology and Metabolism. 296 (1): E11–21. doi:10.1152/ajpendo.90563.2008. PMC 2636990. PMID 18840763.
  3. ^ Walker, Rosemary and Rodgers, Jill (2006) Type 2 Diabetes – Your Questions Answered. Dorling Kindersley. ISBN 1-74033-550-3.
  4. ^ Diabetes FAQs – Blood Glucose Measurement Units – Abbott Diabetes Care
  5. ^ a b What are mg/dl and mmol/l? How to convert? Glucose? Cholesterol? Advameg, Inc.
  6. ^ "Screening for Type 2 Diabetes". Clinical Diabetes. 18 (2). 2000.
  7. ^ Danaei, G (2 July 2011). "National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants". The Lancet. 378 (9785): 31–40. doi:10.1016/S0140-6736(11)60679-X. PMID 21705069.
  8. ^ Glucose test – blood. NIH – National Institutes of Health.
  9. ^ Davidson NK, Moreland P (26 July 2011). "Living with diabetes blog". Mayo Clinic. Archived from the original on 14 May 2013.
  10. ^ American Diabetes Association (January 2006). "Standards of medical care in diabetes--2006". Diabetes Care. 29 Suppl 1 (Supplement 1): S4–42. PMID 16373931. Standards of Medical Care – Table 6 and Table 7, Correlation between A1C level and Mean Plasma Glucose Levels on Multiple Testing over 2–3 months
  11. ^ USDA National Nutrient Database for Standard Reference, Release 22 (2009)
  12. ^ Eiler H (2004). "Endocrine glands". In Reese WO. Dukes' Physiology of Domestic Animals (12th ed.). Ithaca, NY: Comstock. pp. 621–69. ISBN 978-0801442384.
  13. ^ Kahn CM, ed. (2005). Merck Veterinary Manual (9th ed.). Whitehouse Station: Merck & Co. ISBN 978-0911910506.
  14. ^ Rice, C. G.; Hall, B. (2007). "Hematologic and biochemical reference intervals for mountain goats (Oreamnos americanus): effects of capture conditions". Northwest Science. 81 (3): 206. doi:10.3955/0029-344X-81.3.206.
  15. ^ Cornell LH, Duffield DS, Joseph BE, Stark B (April 1988). "Hematology and serum chemistry values in the beluga (Delphinapterus leucas)". Journal of Wildlife Diseases. 24 (2): 220–4. doi:10.7589/0090-3558-24.2.220. PMID 3373628.
  16. ^ Seal, U. S.; Barton, R.; Mather, L.; Gray, C. W. (1976). "Baseline Laboratory Data for the White Rhinoceros (Ceratotherium simum simum)" (PDF). The Journal of Zoo Animal Medicine. 7 (1): 11–17. JSTOR 20094341.
  17. ^ Boily F, Beaudoin S, Measures LN (January 2006). "Hematology and serum chemistry of harp (Phoca groenlandica) and hooded seals (Cystophora cristata) during the breeding season, in the Gulf of St. Lawrence, Canada". Journal of Wildlife Diseases. 42 (1): 115–32. doi:10.7589/0090-3558-42.1.115. PMID 16699154.
  18. ^ Lehninger A, Nelson D, Cox M (2017). Lehininger Principles of Biochemistry. New York: W.H. Freedom. p. 934. ISBN 9781319117689.
  19. ^ Tortora G (December 2016). Principles Anatomy and Physiology (15 ed.). New York: John Wiley & Sons, Inc. pp. Chapter 18. ISBN 9781119343738.
  20. ^ Lehninger A, Nelson D, Cox M (2017). Lehninger Principles of Biochemistry (7th ed.). New York: W.H.Freeman. p. 930. ISBN 9781319117689.
  21. ^ "Excess sugar linked to cancer". Science Daily.
  22. ^ "Diabetic ketoacidosis - Symptoms and causes". Mayo Clinic. Retrieved 2018-01-30.
  23. ^ Consumer Reports Health Best Buy Drugs. "The Oral Diabetes Drugs: Treating Type 2 Diabetes" (PDF). Best Buy Drugs: 2. Retrieved 18 September 2012.
  24. ^ Yang C (2012). "A Comparison between Venous and Finger-Prick Blood Sampling on Values of Blood Glucose" (PDF). International Proceedings of Chemical, Biological and Environmental Engineering. 39: 236.
  25. ^ Somogyi M (May 1948). "Studies of arteriovenous differences in blood sugar; effect of alimentary hyperglycemia on the rate of extrahepatic glucose assimilation" (PDF). The Journal of Biological Chemistry. 174 (1): 189–200. PMID 18914074.
  26. ^ Roe J. "Glucose Concentration Difference Between Arterial, Capillary, and Venous Blood". Best Thinking. Archived from the original on 4 December 2014.
  27. ^ Cox DL, Nelson MM (2013). Lehninger principles of biochemistry (6th ed.). New York: W.H. Freeman. p. 950. ISBN 9781429234146.
  28. ^ a b Cox MM, Lehninger AL, Nelson DL (2017). Lehninger Principles of Biochemistry. New York: W.H. Freeman. pp. 248–49. ISBN 9781319117689.
  29. ^ Ginsberg BH (July 2009). "Factors affecting blood glucose monitoring: sources of errors in measurement". Journal of Diabetes Science and Technology. 3 (4): 903–13. doi:10.1177/193229680900300438. PMC 2769960. PMID 20144340.
  30. ^ Renschler HE, Weicker H, von Baeyer H (December 1965). "[The upper limit of glucose concentration in the urine of healthy subjects]". Deutsche Medizinische Wochenschrift. 90 (53): 2349–53. PMID 5851934.
  31. ^ Neocuproine MSDS. hazard.com

Further reading

External links

Adrenaline

Adrenaline, also known as epinephrine, is a hormone, neurotransmitter, and medication. Adrenaline is normally produced by both the adrenal glands and certain neurons. It plays an important role in the fight-or-flight response by increasing blood flow to muscles, output of the heart, pupil dilation response, and blood sugar level. It does this by binding to alpha and beta receptors. It is found in many animals and some single cell organisms. Napoleon Cybulski first isolated adrenaline in 1895.

Carol Yager

Carol Ann Yager (January 26, 1960 – July 18, 1994) was an American woman who was the heaviest woman ever recorded and one of the most severely obese people in history.

Chronic Somogyi rebound

Chronic Somogyi rebound is a contested explanation of phenomena of elevated blood sugars in the morning. Also called the Somogyi effect and posthypoglycemic hyperglycemia, it is a rebounding high blood sugar that is a response to low blood sugar. When managing the blood glucose level with insulin injections, this effect is counter-intuitive to people who experience high blood sugar in the morning as a result of an overabundance of insulin at night.

This theoretical phenomenon was named after Michael Somogyi, a Hungarian-born professor of biochemistry at the Washington University and Jewish Hospital of St. Louis, who prepared the first insulin treatment given to a child with diabetes in the USA in October 1922. Somogyi showed that excessive insulin makes diabetes unstable and first published his findings in 1938.Compare with the dawn phenomenon, which is a morning rise in blood sugar in response to waning insulin and a growth hormone surge (that further antagonizes insulin).

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 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.

The main goal of diabetes management is, as far as possible, to restore carbohydrate metabolism to a normal state. To achieve this goal, individuals with an absolute deficiency of insulin require insulin replacement therapy, which is given through injections or an insulin pump. Insulin resistance, in contrast, can be corrected by dietary modifications and exercise. Other goals of diabetes management are to prevent or treat the many complications that can result from the disease itself and from its treatment.

Diabetes mellitus and pregnancy

For pregnant women with diabetes mellitus some particular challenges exist for both mother and child. If the woman has diabetes as an intercurrent disease in pregnancy, it can cause early labor, birth defects, and larger than average infants.

Planning in advance is emphasized if one wants to become pregnant and has type 1 diabetes mellitus or type 2 diabetes mellitus. Stringent blood glucose control is needed before pregnancy.

Diabetic coma

Diabetic coma is a reversible form of coma found in people with diabetes mellitus. It is a medical emergency.Three different types of diabetic coma are identified:

Severe low blood sugar in a diabetic person

Diabetic ketoacidosis (usually type 1) advanced enough to result in unconsciousness from a combination of a severely increased blood sugar level, dehydration and shock, and exhaustion

Hyperosmolar nonketotic coma (usually type 2) in which an extremely high blood sugar level and dehydration alone are sufficient to cause unconsciousness.In most medical contexts, the term diabetic coma refers to the diagnostical dilemma posed when a physician is confronted with an unconscious patient about whom nothing is known except that they have diabetes. An example might be a physician working in an emergency department who receives an unconscious patient wearing a medical identification tag saying DIABETIC. Paramedics may be called to rescue an unconscious person by friends who identify them as diabetic. Brief descriptions of the three major conditions are followed by a discussion of the diagnostic process used to distinguish among them, as well as a few other conditions which must be considered.

An estimated 2 to 15 percent of people with diabetes will suffer from at least one episode of diabetic coma in their lifetimes as a result of severe hypoglycemia.

Diabetic sock

People with diabetes have a greater chance of developing neuropathy, vascular disease, and infections, especially in the legs, so socks and footwear that reduce or eliminate pressures or hot spots is important. A diabetic sock is a non-restrictive, but close fitting sock which is designed to alleviate pressures on the foot or leg. Typically sufferers of diabetes are the most common users of this type of sock. Diabetes raises the blood sugar level, which can increase the risk of foot ulcers. Diabetic socks are made to be unrestrictive of circulation, but if inclusive of Medical Grade, FDA regulated gradient compression, may be include venous compression for enhanced circulation.Proper diabetic socks also help to manage moisture, a feature which can reduce the risk of infection. Another beneficial feature of diabetic socks is seamless toe-closures to avoid pressure, potential hot spots and blistering.

Glucagon-like peptide-1 receptor

The glucagon-like peptide-1 receptor (GLP1R) is a receptor protein found on beta cells of the pancreas. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of G protein-coupled receptors. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.

Glucose clamp technique

Glucose clamp technique is a method for quantifying insulin secretion and resistance. It is used to measure either how well an individual metabolizes glucose or how sensitive an individual is to insulin.Two types of clamps are quite commonly used. The hyperglycemic clamp, which requires maintaining a high blood sugar level by perfusion or infusion with glucose, is a way to quantify how fast beta-cells respond to glucose. The hyperinsulinemic clamp, which requires maintaining a high insulin level by perfusion or infusion with insulin, is a way to quantify how sensitive the tissue is to insulin. The hyperinsulinemic clamp is also called euglycemic clamp, meaning a normal blood sugar level is maintained.

Hyperglycemic clamp technique: The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a continuous infusion of glucose. This hyperglycemic plateau is maintained by adjustment of a variable glucose infusion, based on the rate of insulin secretion and glucose metabolism. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of insulin secretion and glucose metabolism. The hyperglycemic clamps are often used to assess insulin secretion capacity.

Hyperinsulinemic-euglycemic clamp technique: The plasma insulin concentration is acutely raised and maintained at 100 μU/ml by a continuous infusion of insulin. Meanwhile, the plasma glucose concentration is held constant at basal levels by a variable glucose infusion. When the steady-state is achieved, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue insulin sensitivity. The hyperinsulinemic clamps are often used to measure insulin resistance.

The glucose clamp technique was developed by UT School of Medicine Professors DeFronzo, Andres and Tobin in 1979. It has since been the gold standard for pharmacodynamic studies in diabetes drug development and diagnostics evaluation. In human clinical trials, manual glucose clamps as well as the more modern method of automated glucose clamp find common use.

Homeostasis

In biology, homeostasis is the state of steady internal physical and chemical conditions maintained by living systems. This dynamic state of equilibrium is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid balance, being kept within certain pre-set limits (homeostatic range). Other variables include the pH of extracellular fluid, the concentrations of sodium, potassium and calcium ions, as well as that of the blood sugar level, and these need to be regulated despite changes in the environment, diet, or level of activity. Each of these variables is controlled by one or more regulators or homeostatic mechanisms, which together maintain life.

Homeostasis is brought about by a natural resistance to change in the optimal conditions, and equilibrium is maintained by many regulatory mechanisms. All homeostatic control mechanisms have at least three interdependent components for the variable being regulated: a receptor, a control centre, and an effector. The receptor is the sensing component that monitors and responds to changes in the environment, either external or internal. Receptors include thermoreceptors, and mechanoreceptors. Control centres include the respiratory centre, and the renin–angiotensin system. An effector is the target acted on, to bring about the change back to the normal state. At the cellular level, receptors include nuclear receptors that bring about changes in gene expression through up-regulation or down-regulation, and act in negative feedback mechanisms. An example of this is in the control of bile acids in the liver.Some centers, such as the renin–angiotensin system, control more than one variable. When the receptor senses a stimulus, it reacts by sending action potentials to a control center. The control center sets the maintenance range—the acceptable upper and lower limits—for the particular variable, such as temperature. The control center responds to the signal by determining an appropriate response and sending signals to an effector, which can be one or more muscles, an organ, or a gland. When the signal is received and acted on, negative feedback is provided to the receptor that stops the need for further signaling.

Hyperglycemia

Hyperglycemia (also spelled hyperglycaemia or hyperglycæmia), is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/l (200 mg/dl), but symptoms may not start to become noticeable until even higher values such as 15–20 mmol/l (~250–300 mg/dl). A subject with a consistent range between ~5.6 and ~7 mmol/l (100–126 mg/dl) (American Diabetes Association guidelines) is considered slightly hyperglycemic, while above 7 mmol/l (126 mg/dl) is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average however, chronic levels above 10–12 mmol/L (180–216 mg/dl) can produce noticeable organ damage over time.

Insulin degludec

Insulin degludec (INN/USAN) is an ultralong-acting basal insulin analogue that was developed by Novo Nordisk under the brand name Tresiba. It is administered via subcutaneous injection once daily to help control the blood sugar level of those with diabetes. It has a duration of action that lasts up to 42 hours (compared to 18 to 26 hours provided by other marketed long-acting insulins such as insulin glargine and insulin detemir), making it a once-daily basal insulin, that is one that provides a base insulin level, as opposed to the fast and short acting bolus insulins.

Insulin degludec is a modified insulin that has one single amino acid deleted in comparison to human insulin, and is conjugated to hexadecanedioic acid via gamma-L-glutamyl spacer at the amino acid lysine at position B29.

Insulin pump

An insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin therapy.

The device configuration may vary depending on design. A traditional pump includes:

the pump (including controls, processing module, and batteries)

a disposable reservoir for insulin (inside the pump)

a disposable infusion set, including a cannula for subcutaneous insertion (under the skin) and a tubing system to connect the insulin reservoir to the cannula.Other configurations are possible. More recent models may include disposable or semi-disposable designs for the pumping mechanism and may eliminate tubing from the infusion set.

An insulin pump is an alternative to multiple daily injections of insulin by insulin syringes or an insulin pen and allows for flexible insulin therapy when used in conjunction with blood glucose monitoring and carbohydrate counting.

Jungle juice

Jungle juice is the name given to an improvised mix of liquor that is usually served for group consumption. There are countless recipes and even websites devoted solely to jungle juice. The term has also been used for similar less-than-reputable alcoholic concoctions.

MODY 2

MODY 2 is a form of maturity onset diabetes of the young.

MODY 2 is due to any of several mutations in the GCK gene on chromosome 7 for glucokinase. Glucokinase serves as the glucose sensor for the pancreatic beta cell. Normal glucokinase triggers insulin secretion as the glucose exceeds about 90 mg/dl (5 mM). These loss-of-function mutations result in a glucokinase molecule that is less sensitive or less responsive to rising levels of glucose. The beta cells in MODY 2 have a normal ability to make and secrete insulin, but do so only above an abnormally high threshold (e.g., 126–144 mg/dl, or 7-8 mM). This produces a chronic, mild increase in blood sugar, which is usually asymptomatic. It is usually detected by accidental discovery of mildly elevated blood sugar (e.g., during pregnancy screening). An oral glucose tolerance test is much less abnormal than would be expected from the impaired (elevated) fasting blood sugar, since insulin secretion is usually normal once the glucose has exceeded the threshold for that specific variant of the glucokinase enzyme.

The degree of blood sugar elevation does not worsen rapidly with age, and long-term diabetic complications are rare. In healthy children and adults, a high blood sugar level can be avoided by a healthy diet and exercise, primarily avoiding large amounts of carbohydrates. However, as people who have MODY2 enter their 50's and 60's, even though they continue to eat a healthy diet and exercise, they sometimes are unable to control a high blood sugar level with these measures. In these cases, many medicines for type II diabetes mellitus are not effective, because MODY2 does not cause insulin resistance. Repaglinide (Prandin) can help the body regulate the amount of glucose in the blood by stimulating the pancreas to release insulin before meals. In some cases, the baseline glucose levels are too high as well and insulin is required.

MODY2 is an autosomal dominant condition. Autosomal dominance refers to a single, abnormal gene on one of the first 22 nonsex chromosomes from either parent which can cause an autosomal disorder. Dominant inheritance means an abnormal gene from one parent is capable of causing disease, even though the matching gene from the other parent is normal. The abnormal gene "dominates" the pair of genes. If just one parent has a dominant gene defect, each child has a 50% chance of inheriting the disorder.

This type of MODY demonstrates the common circulation but complex interplay between maternal and fetal metabolism and hormone signals in the determination of fetal size. A small number of infants will have a new mutation not present in their mothers. If the mother is affected and the fetus is not, the maternal glucose will be somewhat high and the normal pancreas of the fetus will generate more insulin to compensate, resulting in a large infant. If the fetus is affected but mother is not, glucoses will be normal and fetal insulin production will be low, resulting in intrauterine growth retardation. Finally, if both mother and fetus have the disease, the two defects will offset each other and fetal size will be unaffected.

When both GCK genes are affected the diabetes appears earlier and the hyperglycemia is more severe. A form of permanent neonatal diabetes has been caused by homozygous mutations in the GCK gene.

Reactive hypoglycemia

Reactive hypoglycemia, postprandial hypoglycemia, or sugar crash is a term describing recurrent episodes of symptomatic hypoglycemia occurring within four hours after a high carbohydrate meal in people both with and without diabetes. The term is not necessarily a diagnosis since it requires an evaluation to determine the cause of the hypoglycemia.The condition is related to homeostatic systems utilised by the body to control the blood sugar level. It is described as a sense of tiredness, lethargy, irritation, or hangover, although the effects can be lessened if a lot of physical activity is undertaken in the first few hours after food consumption.

The alleged mechanism for the feeling of a crash is correlated with an abnormally rapid rise in blood glucose after eating. This normally leads to insulin secretion (known as an insulin spike), which in turn initiates rapid glucose uptake by tissues, either storing it as glycogen or utilizing it for energy production. The consequent fall in blood glucose is indicated as the reason for the "sugar crash". Another cause might be hysteresis effect of insulin action, i.e., the effect of insulin is still prominent even if both plasma glucose and insulin levels were already low, causing a plasma glucose level eventually much lower than the baseline level.Sugar crashes are not to be confused with the after-effects of consuming large amounts of protein, which produces fatigue akin to a sugar crash, but are instead the result of the body prioritising the digestion of ingested food.The prevalence of this condition is difficult to ascertain because a number of stricter or looser definitions have been used. It is recommended that the term reactive hypoglycemia be reserved for the pattern of postprandial hypoglycemia which meets the Whipple criteria (symptoms correspond to measurably low glucose and are relieved by raising the glucose), and that the term idiopathic postprandial syndrome be used for similar patterns of symptoms where abnormally low glucose levels at the time of symptoms cannot be documented.

To assist in diagnosis, a doctor may order an HbA1c test, which measures the blood sugar average over the two or three months before the test. The more specific 6-hour glucose tolerance test can be used to chart changes in the patient's blood sugar levels before ingestion of a special glucose drink and at regular intervals during the six hours following to see if an unusual rise or drop in blood glucose levels occurs.

According to the U.S. National Institutes of Health (NIH), a blood glucose level below 70 mg/dL (3.9 mmol/L) at the time of symptoms followed by relief after eating confirms a diagnosis for reactive hypoglycemia.

Reye syndrome

Reye syndrome is a rapidly progressive encephalopathy. Symptoms may include vomiting, personality changes, confusion, seizures, and loss of consciousness. Even though liver toxicity typically occurs, jaundice usually does not. Death occurs in 20–40% of those affected and about a third of those who survive are left with a significant degree of brain damage.The cause of Reye syndrome is unknown. It usually begins shortly after recovery from a viral infection, such as influenza or chickenpox. About 90% of cases in children are associated with aspirin (salicylate) use. Inborn errors of metabolism are also a risk factor. Changes on blood tests may include a high blood ammonia level, low blood sugar level, and prolonged prothrombin time. Often the liver is enlarged.Prevention is typically by avoiding the use of aspirin in children. When aspirin was withdrawn for use in children a decrease of more than 90% in rates of Reye syndrome was seen. Early diagnosis improves outcomes. Treatment is supportive. Mannitol may be used to help with the brain swelling.The first detailed description of Reye syndrome was in 1963 by Douglas Reye, an Australian pathologist. Children are most commonly affected. It affects fewer than one in a million children a year. The general recommendation to use aspirin in children was withdrawn because of Reye syndrome, with use of aspirin only recommended in Kawasaki disease.

Blood composition
Other
Common for blood tests (CPT 82000–84999)
Electrolytes
Acid-base
Iron tests
Hormones
Metabolism
Cardiovascular
Liver function tests
Pancreas

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