Diabetic hypoglycemia 1763662 224238408 2008-07-07T23:03:32Z 166.107.76.4 /* Intravenous glucose */ {{DiseaseDisorder infobox | Name = Diabetic hypoglycemia | ICD10 = | ICD9 = {{ICD9|250.8}} | }} '''Diabetic hypoglycemia''' describes a [[hypoglycemia|low blood glucose level]] occurring in a person with [[diabetes mellitus]]. It is one of the most common types of hypoglycemia seen in [[emergency department]]s and [[hospital]]s. According to the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP), and based on a sample examined between 2004 and 2005, an estimated 55,819 cases (8.0% of total admissions) involved insulin, and severe hypoglycemia is likely the single most common event.[http://jama.ama-assn.org/cgi/content/abstract/296/15/1858 <ref>Budnitz Daniel S; Pollock Daniel A, et al.: National Surveillance of Emergency Department Visits for Outpatient Adverse Drug Events. JAMA. 2006;296(15):1858-1866.</ref>] In general, hypoglycemia occurs when a treatment to lower the elevated blood glucose of diabetes inaccurately matches the body's physiological need, and therefore causes the glucose to fall to a below-normal level. {{Diabetes}} ==Etiology== Diabetic hypoglycemia can occur in any person with diabetes who takes any medicine to lower his blood glucose, but severe hypoglycemia occurs most often in people with [[type 1 diabetes]] who must take insulin for survival. In type 1 diabetes, iatrogenic [caused by medicine] hypoglycemia is more appropriately viewed as the result of the interplay of insulin excess and compromised glucose counterregulation rather than as absolute or relative insulin excess alone.<ref>Cryer PE: Hypoglycemia, Pathophysiology, Diagnosis and Treatment, New York, Oxford Univ Press, 1997.</ref> Hypoglycemia can also be caused by [[sulfonylurea]]s in people with [[type 2 diabetes]], although it is far less common because glucose counterregulation generally remains intact in people with type 2 diabetes. Severe hypoglycemia rarely, if ever, occurs in people with diabetes treated only with diet, exercise, or insulin sensitizers. For people with insulin-requiring diabetes, hypoglycemia is one of the recurrent hazards of treatment. It limits the achievability of normal glucoses with current treatment methods. Hypoglycemia is a true medical emergency, which requires prompt recognition and treatment to prevent organ and brain damage. ==Definition, manifestations and recognition== A commonly used "number" to define the lower limit of normal glucose is 70 mg/dl (3.9 mmol/l), though in someone with diabetes, hypoglycemic symptoms can sometimes occur at higher glucose levels, or may fail to occur at lower. Some textbooks for nursing and pre-hospital care use the range 80 mg/dl to 120 mg/dl. This variability is further compounded by the imprecision of [[glucose meter]] measurements at low levels, or the ability of glucose levels to change rapidly. Diabetic hypoglycemia can be mild, recognized easily by the patient, and reversed with a small amount of [[carbohydrate]]s eaten or drunk, or it may be severe enough to cause unconsciousness requiring intravenous [[dextrose]] or an injection of [[glucagon]]. Severe hypoglycemic unconsciousness is one form of [[diabetic coma]]. A common medical definition of severe hypoglycemia is "hypoglycemia severe enough that the person needs assistance in dealing with it." A co-morbidity is the issue of hypoglycemia unawareness. [[Symptom]]s of diabetic hypoglycemia, when they occur, are those of [[hypoglycemia]]: [[neuroglycopenia|neuroglycopenic]], [[adrenergic]], and abdominal. Symptoms and effects can be mild, moderate or severe, depending on how low the glucose falls and a variety of other factors. It is rare but possible for diabetic hypoglycemia to result in brain damage or death. Indeed, an estimated 2-4% of deaths of people with type 1 diabetes mellitus have been attributed to hypoglycemia.<ref>Cryer PE: Hypoglycemia, Pathophysiology, Diagnosis and Treatment, New York, Oxford Univ Press, 1997.</ref><ref>Lang Sp, Swerdlow AJ, Slater SD, et al: The British Diabetic Association Cohort Study.II: Cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabet Med 16:466-471, 1999.</ref> In North America a mild episode of diabetic hypoglycemia is sometimes termed a "low" or an "insulin reaction," and in Europe a "hypo", although all of these terms are occasionally used interchangeably in North America, Europe, Australia and New Zealand. A severe episode is sometimes also referred to as "insulin shock". In a counter-intuitive manifestation, hypoglycemia can trigger a [[Chronic Somogyi rebound|Somogyi effect]], resulting in a rebounding high [[blood sugar]] or [[hyperglycemia]]. == Treatment == === Oral intake of glucose === The blood glucose can usually be raised to normal within minutes with 15-20 grams of [[carbohydrate]], although overtreatment should be avoided if at all possible. It can be taken as food or drink if the person is conscious and able to swallow. This amount of carbohydrate is contained in about 3-4 ounces (100-120 ml) of orange, apple, or grape juice, about 4-5 ounces (120-150 ml) of regular (non-diet) soda, about one slice of bread, about 4 crackers, or about 1 serving of most starchy foods. [[Starch]] is quickly digested to glucose, but adding fat or protein retards digestion. Composition of the treatment should be considered, as fruit juice is typically higher in fructose which takes the body longer to metabolize than simple dextrose alone. Following treatment, symptoms should begin to improve within 5 to 10 minutes, although full recovery may take 10-20 minutes. It should be noted that over treatment does not speed recovery, and will simply produce hyperglycemia afterwards, which ultimately will need to be corrected. === Intravenous glucose === If a person cannot receive oral glucose gel or tablets, such as the case with unconsciousness, seizures, or altered mental status, then emergency personal (EMTs/Paramedics and in-hospital personnel) can establish a peripheral or central IV line and administer a solution containing dextrose and saline. These are normally referred to as Dextrose (Concentration) Water, and come in 5%, 10%, 25% and 50%. Dextrose 5% and 10% come in IV bag and syringe form, and are mainly used in infants and to provide a fluid medium for medications. D10W is given at a 2cc/kg rate for Neonates and Infants. Dextrose 25% is given in children under the age of 8, and Dextrose 50% is given in adults. The Dosage for D50W is one half of the ampule, with verification of IV patency after the half of the amp is given, and a recheck of blood glucose levels before administering the other half. Dextrose 25% and 50% are heavily necrotic due to their hyperosmolarity, and should only be given through a patent IV line - Any infiltration can cause massive tissue necrosis. ===Glucagon=== [[Glucagon]] is a hormone that rapidly counters the metabolic effects of insulin in the liver, causing [[glycogenolysis]] and release of glucose into the blood. It can raise the glucose by 30-100 mg/dl within minutes in any form of hypoglycemia caused by insulin excess (including all types of diabetic hypoglycemia). It comes in a [[glucagon rescue|glucagon emergency rescue kit]] which includes tiny vials containing 1 mg, which is a standard adult dose. The glucagon in the vial is a lyophilized pellet, which must be reconstituted with 1 ml of sterile water, included in the "kit". In the widely used [[Eli Lilly and Company|Lilly]] Emergency Kit, the water is contained in a syringe with a large needle for intramuscular injection and must be injected into the vial with the pellet of glucagon before being injected. Glucagon works if given subcutaneously, but absorption and recovery are faster if it is injected deep into a muscle (usually the middle of the outside of the thigh). It has an even more rapid effect when given intravenously but this is rarely practicable. Side effects of glucagon can include nausea and headache, but these can also occur after severe hypoglycemia even when glucagon is not used. Risks of glucagon use are far lower than risks of severe hypoglycemia, and it can usually produce a faster recovery than calling for paramedics and waiting for them to start an intravenous line to give dextrose. If someone uses this kit, they should be seen in an emergency room, as glucagon depletes [[glycogen]] stores, and can lead to a deadly rebound hypoglycemia. In the United States, normal use of this kit in the out-of-hospital setting is restricted to EMS units carrying Paramedics (EMTs in some states can use Glucagon, but most require very specific training to do so). These are usually 1 to 2 mg dry power vials with 1 to 2 ml of sterile water used to reconstitute the drug. 1 to 2 milligrams of the drug is usually administered via the IM route. Most treatment protocols only allow Glucagon to be given after attempts to establish a peripheral IV for dextrose have failed. Despite the fact that this drug causes a rapid recovery, the patient must be transported to a hospital for evaluation due to the depletion of glycogen stores and the potential for catastrophic hypoglycemia to reoccur is the paitent is not treated properly. ==Hypoglycemic unawareness== Although one expects hypoglycemic episodes to be accompanied by the typical symptoms (e.g., tremor, sweating, palpitations, etc.), this is not always the case. When hypoglycemia occurs in the absence of such symptoms it is called ''hypoglycemic unawareness''. Especially in people with long-standing type 1 diabetes and those who attempt to maintain glucose levels which are closer to normal, hypoglycemic unawareness is common. In patients with type 1 diabetes mellitus, as plasma glucose levels fall, insulin levels do not decrease - they are simply a passive reflection of the absorption of exogenous insulin. Also, glucagon levels do not increase. Therefore, the first and second defenses against hypoglycemia are already lost in established type 1 diabetes mellitus.<ref>[Cryer PE: Hypoglycemia, Pathophysiology, Diagnosis and Treatment, New York, Oxford Univ Press, 1997.]</ref> Further, the epinephrine response is typically attenuated, i.e., the glycemic threshold for the epinephrine response is shifted to lower plasma glucose concentrations, which can be aggravated by previous incidents of hypoglycemia. To further complicate matters, there may also be other contributing factors which contribute to hypoglycemic unawareness: a) there may be [[autonomic neuropathy]] b) the brain may have become desensitized to hypoglycemia c) the person may be using medicines which mask the hypoglycemic symptoms d) unexpected pharmacokinetics of the insulin being dosed a) '''[[Autonomic neuropathy]]:''' During hypoglycemia, the body normally releases epinephrine [more commonly known as adrenalin] and related substances. This serves two purposes: The β-effect of epinephrine is responsible for the palpitations and tremors, giving the patient warning that hypoglycemia is present. The β-effect of epinephrine also stimulates the liver to release glucose ([[gluconeogenesis]] and [[glycogenolysis]]). The epinephrine warns the patient that hypoglycemia is present and signals the liver to release glucose to reverse it. In the absence of epinephrine release, or when it is attenuated (reduced) during hypoglycemia, then patient may not be aware that his/her glucose level is low, therefore, the usual responses of glycogenolysis and gluconeogenesis may also lost or blunted. Since epinephrine release is a function of the [[autonomic nervous system]], the presence of autonomic neuropathy (i.e., a damaged autonomic nervous system) will cause the epinephrine release in response to hypoglycemia to be lost or blunted. Unfortunately, damage to the autonomic nervous system in the form of autonomic neuropathy is a common complication of long-standing diabetes (especially type 1 diabetes), so the presence of hypoglycemic unawareness may be a sign of autonomic neuropathy, although the autonomic response to hypoglycemia is already impaired in patients with type 1 diabetes mellitus even in the absence of autonomic neuropathy. Because the autonomic response is, in effect, the body's backup system for responding to hypoglycemia, patients with type 1 diabetes are forced to rely almost exclusively on a backup system for protection, which can unfortunately, deteriorate over time. The reduced autonomic response (including the sympathetic neural norepinephrine and acetylcholine as well as the adrenomedullary epinephrine response) causes the clinical syndrome of hypoglycemia unawareness — loss of the largely neurogenic warning symptoms of developing hypoglycemia. b) '''Brain desensitization to hypoglycemia:''' If a person has frequent episodes of hypoglycemia (even mild ones), the brain becomes "used to" the low glucose and no longer signals for adrenalin to be released during such times. More specifically, there are [[glucose transporter]]s located in the brain cells ([[neurons]]). These transporters increase in number in response to repeated hypoglycemia (this permits the brain to receive a steady supply of glucose even during hypoglycemia). As a result, what was once the hypoglycemic threshold for the brain to signal adrenalin release becomes lower. Epinephrine is not released, if at all, until the blood glucose level has dropped to even lower levels. Clinically, the result is hypoglycemic unawareness. Since repeated hypoglycemia is common in people with diabetes who strive to keep their glucose levels near normal, and they have impaired glucose counterregulation, the incidence of hypoglycemic unawareness becomes more prevalent in patients who follow prescribed treatment protocols. The most common treatment for this condition is to liberalize the patient's target glucose levels, in an attempt to decrease the frequency of hypoglycemic episodes. Hypoglycemic unawareness will sometimes disappear when the frequency of hypoglycemic episodes has declined, but this is not always the case. '''Blood Glucose Awareness Training (BGAT)''' Researchers at University of Virginia Health Sciences Center have developed a psychoeducational program that helps patients identify their blood glucose symptoms more accurately, better predict when hypoglycemia is more likely to occur, and then treat hypoglycemia earlier than they might if they were relying exclusively on blunted autonomic symptoms alone. The program, called [http://care.diabetesjournals.org/cgi/content/full/24/4/637 Blood glucose awareness training (BGAT)], is designed to improve the accuracy of patients' detection and interpretation of relevant BG symptoms and other cues. Unfortunately, awareness of these treatments among certified diabetes educators is surprisingly low, and awareness of the program is not even required to attain certification. The reasons for this are multi-faceted, but a frequent criticism is the fact that a disproportionate share of the certification training is dedicated to issues related to the more common type 2 diabetes. Also, BGAT is training is more complex, and requires considerable effort on the part of educators, and many may not view it as justified given the proportion of the patients who have type 1 diabetes. An online version of BGAT has been developed and was being tested, but is expected to be functional in the not-too-distant future. It is called [http://www.healthsystem.virginia.edu/bmc/bgathome/flash/index2.htm BGAThome], and may bring this useful training program to more people in the future. c) '''[[Beta blocker]] drugs:''' These medicines are designed to blunt the β-effect of adrenalin and related substances. Hence, if hypoglycemia occurs in someone who is using this type of drug, he/she may not experience the typical adrenergic warning symptoms such as tremor and palpitations. Again, the result is hypoglycemic unawareness. As noted above, beta blockers will also prevent adrenalin from stimulating the liver to make glucose. Although this phenomenon does not contribute to hypoglycemic awareness, it will make the hypoglycemia more severe and/or more protracted. d) unexpected pharmacokinetics of the insulin being dosed. Unlike endogenously produced insulin which is secreted directly into the bloodstream, insulin given as a medication is typically dosed subcutaneously. The time-activity profile of insulin administered this way can vary widely depending on the site the injection given, the angle of the injection and and the relative size of the dosage. Thus, while clinical trials may provide ranges, the reality is that the time-activity profiles of artificially dosed insulin often vary considerably and may not be absorbed, distributed into the bloodstream, metabolized or excreted the same way regardless of how consistent the other variables may be, which may lead to unexpected incidents of hypoglycemia. == See also == * [[Diabetic coma]] * [[Glucagon]] * [[Glucagon rescue]] * [[Hypoglycemia]] * [[Chronic Somogyi rebound]] == References == {{reflist}} [[Category:Diabetes]] [[fr:Hypoglycémie diabétique]] [[pt:Hipoglicemia diabética]]