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Management of hypoglycemia during treatment of diabetes mellitus Author Philip E Cryer, MD Section Editor David M Nathan, MD Deputy Editor

Jean E Mulder, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2012. | This topic last updated: ago 28, 2012. INTRODUCTION Hypoglycemia is an important problem in type 1 diabetes, especially in patients receiving intensive therapy in whom the risk of severe hypoglycemia is increased more than threefold (figure 1) [1-4]. Less commonly, hypoglycemia may also affect patients with type 2 diabetes who take a sulfonylurea or a meglitinide or who use insulin. Identification of patients at risk for hypoglycemia and the prevention and management of hypoglycemia are reviewed here. The clinical manifestations of hypoglycemia and the physiologic response to hypoglycemia are discussed elsewhere. (See "Hypoglycemia in adults: Clinical manifestations, definition, and causes" and "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus".) BIOCHEMICAL AND CLINICAL CRITERIA In 2005, The American Diabetes Association (ADA) published criteria for the definition and clinical classification of hypoglycemia in patients with diabetes mellitus [1]. Definition In patients with diabetes, hypoglycemia is defined as all episodes of an abnormally low plasma glucose concentration (with or without symptoms) that expose the individual to harm [1]. The workgroup recommended that people with diabetes become concerned about the possibility of hypoglycemia at a self-monitored blood glucose (SMBG) level 70 mg/dL (3.9 mmol/L). While that value is higher than the value used to diagnose hypoglycemia in people without diabetes, it approximates the lower limit of the physiological fasting nondiabetic range, the normal glycemic threshold for glucose counterregulatory hormone secretion, and the highest antecedent low glucose level reported to reduce sympathoadrenal responses to subsequent hypoglycemia [2]. This cut-off value has been debated, with some favoring a value of <63 mg/dL (3.5 mmol/L) to avoid overclassification of hypoglycemia in asymptomatic patients [5-8]. However, when an SMBG value is 70 mg/dL, it does not mean that patients should always self-treat. Defensive options include repeating the measurement in the near term, avoiding critical tasks, such as driving, adjusting the subsequent treatment regimen, or ingesting carbohydrates. (See 'Treatment of hypoglycemia' below.) Clinical classification The American Diabetes Association Workgroup on Hypoglycemia recommends the following classification of hypoglycemia in diabetes [1]: Severe hypoglycemia An event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions is classified as a severe hypoglycemic event. Plasma glucose measurements may not be available during such an event, but neurological recovery attributable to restoration of plasma glucose to normal is

considered sufficient evidence that the event was induced by a low plasma glucose concentration. Documented symptomatic hypoglycemia An event during which typical symptoms of hypoglycemia are accompanied by a measured (typically with a monitor or with a validated glucose sensor) plasma glucose concentration 70 mg/dL (3.9 mmol/L) is classified as a documented symptomatic hypoglycemic event. Asymptomatic hypoglycemia Asymptomatic hypoglycemia is classified as an event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration of 70 mg/dL (3.9 mmol/L). Probable symptomatic hypoglycemia Probable symptomatic hypoglycemia is classified as an event during which typical symptoms of hypoglycemia are not accompanied by a plasma glucose determination (but that was presumably caused by a plasma glucose concentration 70 mg/dL [3.9 mmol/L]). Relative hypoglycemia Relative hypoglycemia is classified as an event during which the person with diabetes reports typical symptoms of hypoglycemia, and interprets those as indicative of hypoglycemia, but with a measured plasma glucose concentration >70 mg/dL (3.9 mmol/L). This category reflects the fact that patients with chronically poor glycemic control can experience symptoms of hypoglycemia at plasma glucose levels >70 mg/dL (3.9 mmol/L) as glucose levels decline into the physiological range.

MAGNITUDE OF THE PROBLEM Frequency Type 1 diabetes Hypoglycemia occurs frequently in patients with type 1 diabetes [3,4,9]. The average patient suffers countless numbers of episodes of asymptomatic hypoglycemia (which are not benign because they impair defenses against subsequent falling plasma glucose concentrations), two episodes of symptomatic hypoglycemia per week, and one episode of temporarily disabling hypoglycemia per year [3,4]. Severe hypoglycemia events, the most reliable values albeit representing only a small fraction of the total hypoglycemic experience, have been reported to range from 62 to 170 episodes per 100 patient years in type 1 diabetes [2,3]. In the Diabetes Control and Complications Trial (DCCT), a greater proportion of patients in the intensively treated group had at least one episode of severe hypoglycemia (65 versus 35 percent of patients in the control group), with overall rates of 61 and 19 per 100 patient-years, respectively (figure 1) [10]. Type 2 diabetes Hypoglycemia is less common in type 2 diabetes [2-4,9,11]. Population-based data indicate that the overall event rate for severe hypoglycemia (requiring the assistance of another individual) in insulin-treated type 2 diabetes is approximately 30 percent of that in type 1 diabetes (35 versus 115 episodes per 100 patient-years) [11] and that event rates for hypoglycemia requiring professional emergency medical treatment range from 40 to 100 percent of those in type 1 diabetes [12,13]. However, because there are a greater number of individuals with type 2 than type 1 diabetes, and because most people with type 2 diabetes ultimately require treatment with insulin, most episodes of iatrogenic hypoglycemia occur in people with type 2 diabetes. Among the commonly used insulin secretagogues (sulfonylureas, meglitinides), hypoglycemia is most often reported in patients taking long-acting drugs, such asglyburide (glibenclamide) [14]. Hypoglycemia is relatively uncommon during treatment with insulin early in the course of type 2 diabetes [3,4,9]. However, its frequency increases, approaching type 1 diabetes, as patients approach the insulin deficient end of the spectrum of type 2 diabetes. The prevalence of mild

hypoglycemic symptoms has been reported as 16 to 20 percent in patients using sulfonylurea agents, and 30 to 50 percent in patients treated with insulin [15]. (See "Sulfonylureas and meglitinides in the treatment of diabetes mellitus" and "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus", section on 'Type 1 versus type 2'.) In contrast to insulin and insulin secretagogues, agents that do not cause unregulated hyperinsulinemia, such as metformin, alpha glucosidase inhibitors (acarbose, miglitol, voglibose), thiazolidinediones (pioglitazone, rosiglitazone), GLP-1 receptor agonists (exenatide, liraglutide), and DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin) probably do not cause hypoglycemia [16]. However, they increase the risk if used with insulin or an insulin secretagogue [3,4]. Better glycemic control is associated with an increased incidence of symptomatic hypoglycemia in patients with type 2 diabetes. In three large randomized trials (ACCORD, ADVANCE, VADT) of intensive glucose control in patients with type 2 diabetes, hypoglycemia occurred more frequently in the intensively treatment groups (A1C 6.4 to 6.9 percent), and in one trial (ACCORD), there were more deaths in the intensive treatment arm. Although the cause of excess mortality could not be ascribed to recognized hypoglycemia, unrecognized iatrogenic hypoglycemia may have resulted in arrhythmias and been a possible contributor. These trials are discussed in detail elsewhere. (See"Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'Macrovascular disease'.) Nocturnal hypoglycemia A particular problem is nocturnal hypoglycemia, which can lead to disruption of sleep and delays in correction of the hypoglycemia [3,4,10]. Nighttime is typically the longest period between self-monitoring of plasma glucose, between food ingestion, and the time of maximum sensitivity to insulin. Nocturnal hypoglycemia is less common in individuals using rapid acting insulin analogs (lispro, aspart, glulisine) rather than regular insulin before meals and in individuals using long-acting insulin analogs (glargine, detemir) rather than NPH as the basal insulin. (See "General principles of insulin therapy in diabetes mellitus".) In one report of patients undergoing continuous glucose monitoring, patients with type 1 diabetes had hypoglycemic values (glucose <70 mg/dL [<3.9 mmol/liter]) an average of 2.3 hours/day and type 2 patients 1 hour/day; most of the hypoglycemic values occurred at night [17]. In another study with continuous glucose monitoring at night in type 1 patients, nocturnal hypoglycemia occurred on more than half the nights studied, with an average duration over 2.5 hours [18]. Consequences Hypoglycemia is an important problem in type 1 diabetes and in many with advanced (absolutely endogenous insulin deficient) type 2 diabetes [2-4,19,20]. It can cause a vicious cycle of recurrent hypoglycemia, resulting in morbidity and preventing the maintenance of euglycemia over a lifetime [2-4]. In addition, hypoglycemia can be fatal, with hypoglycemia mortality estimates in patients with type 1 diabetes ranging from 6 to 10 percent [21-23]. Hypoglycemia mortality rates in type 2 diabetes are currently unknown, but fatal hypoglycemia has been documented in type 2 diabetes [3,4,24]. The extent to which recurrent hypoglycemia causes cognitive impairment is uncertain. The results from the DCCT are reassuring. Although the frequency of severe hypoglycemia in the DCCT was over three times higher in the intensive treatment group as compared with the conventional treatment group, there were no differences between the two groups in multiple psychosocial and neurobehavioral parameters measured at two, five, seven, and eighteen years; furthermore, patients with repeated episodes of hypoglycemia did not perform differently from those who rarely had hypoglycemia [21,25]. However, those data did not include young children or elderly persons

with diabetes; recurrent severe hypoglycemia has been associated with cognitive impairment in both groups. (See "Complications and screening in children and adolescents with type 1 diabetes mellitus", section on 'Hypoglycemia' and "Treatment of type 2 diabetes mellitus in the elderly patient", section on 'Avoiding hypoglycemia'.) Elderly The risk of hypoglycemia is related to the duration of diabetes [3,4] and appears to be increased in the elderly [15]. Older adults may have more neuroglycopenic manifestations of hypoglycemia (dizziness, weakness, delirium, confusion) compared with adrenergic manifestations (tremors, sweating). Severe hypoglycemia requiring hospitalization has been associated with an increased risk of dementia. In addition, even mild episodes of hypoglycemia may lead to adverse outcomes in frail elderly; episodes of dizziness or weakness increase the risk of falls and fracture leading to nursing home placement. (See "Treatment of type 2 diabetes mellitus in the elderly patient", section on 'Avoiding hypoglycemia'.) RISK FACTORS FOR HYPOGLYCEMIA Hypoglycemia is typically the result of the interplay of absolute or relative therapeutic insulin excess and compromised physiological and behavioral defenses against falling plasma glucose concentrations (defective glucose counterregulation and hypoglycemia unawareness). (See"Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus".) In clinical practice, insulin excess alone explains only a minority of episodes of hypoglycemia. Impaired counterregulatory defenses resulting in hypoglycemia is the primary risk factor for subsequent hypoglycemia. Impaired counterregulatory responses The first and second physiological defenses against hypoglycemia, decrements in insulin and increments in glucagon as glucose levels fall in response to therapeutic hyperglycemia, are lost in parallel with beta-cell failure in diabetes [2-4]. This occurs rapidly in type 1 diabetes and more gradually in type 2 diabetes. The third physiological defense, an increment in epinephrine, is typically attenuated in such patients. In the setting of absent insulin and glucagon responses, the attenuated epinephrine response causes defective glucose counterregulation. In addition, an attenuated epinephrine response is a marker of an attenuated sympathoadrenal, including sympathetic neural, response that causes hypoglycemia unawareness. These are the components of hypoglycemia-associated autonomic failure (HAAF) in diabetes. [2-4]. HAAF can be caused by recent antecedent hypoglycemia, prior exercise, or sleep, but the precise mechanisms are unknown. (See "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus", section on 'Hypoglycemia-associated autonomic failure'.) Risk factors for HAAF include the following: Absolute endogenous insulin deficiency A past history of severe hypoglycemia, hypoglycemia unawareness, recent antecedent hypoglycemia, prior exercise, or sleep Intensive glycemic therapy, ie, lower A1C level levels, stricter glycemic goals, or both

Insulin excess Absolute or relative insulin excess occurs in the following settings: Insulin (or insulin secretagogue) doses are excessive, ill-timed or of the wrong type

Exogenous glucose influx is reduced (eg, during an overnight fast or following missed meals) Insulin-independent glucose utilization is increased (eg, during and shortly after exercise) Sensitivity to insulin is increased (eg, hours after exercise, in the middle of the night, following improved glycemic control or weight loss) Endogenous glucose production is reduced (eg, following alcohol ingestion) Insulin clearance is reduced (eg, with renal failure)

Intensive therapy Hypoglycemia is the most common adverse effect of intensive insulin therapy in both the outpatient and inpatient setting. (See "Glycemic control and intensive insulin therapy in critical illness", section on 'Hypoglycemia' and "Insulin therapy in adults with type 1 diabetes mellitus", section on 'Hypoglycemia' and "Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'Intensive therapy'.) Other risks Although insulin secretagogues and insulin are the most common drugs associated with hypoglycemia, other drugs that are often prescribed for people with diabetes and that possibly increase the risk of hypoglycemia are angiotensin-converting enzyme (ACE) inhibitors, angiotensin II antagonists, and non-selective beta2-adrenergic antagonists [26]. (See "Treatment of hypertension in patients with diabetes mellitus".) Alcohol is an additional drug that can potentially cause hypoglycemia. Prediction of risk from blood glucose monitoring Measuring symptomatic and counterregulatory hormone response to hypoglycemia, although accurate in determining the risk of severe hypoglycemia, is too cumbersome for routine use. A simpler and more practical approach during intensive insulin therapy is to evaluate the frequency and severity of low blood glucose readings from blood glucose monitoring records kept by the patient [27]. (See "Blood glucose selfmonitoring in management of adults with diabetes mellitus".) STRATEGIES TO PREVENT HYPOGLYCEMIA In 2009, The Endocrine Society published evidence-based guidelines for the evaluation and management of hypoglycemic disorders in adults [2]. Our approach to the management of hypoglycemia outlined here is consistent with the guidelines. The prevention of hypoglycemia involves assessing for risk factors and tailoring treatment regimens to reduce risk. Reducing the risk of hypoglycemia while maintaining or improving glycemic control involves application of the principles of aggressive glycemic therapy in people with diabetes [24,28]. These principles include patient education and empowerment, frequent self-monitoring of blood glucose (SMBG), flexible and rational insulin (and other drug) regimens, individualized glycemic goals, and ongoing professional guidance and support. Regular SMBG is critical to the glycemic management of intensively treated (basal/bolus insulin) type 2 diabetes as well as that of type 1 diabetes. Continuous glucose monitoring may further facilitate glycemic control as accurate and reliable continuous sensors become available. (See "Blood glucose self-monitoring in management of adults with diabetes mellitus".) Glycemic targets Glycemic control can minimize risks for retinopathy, nephropathy, and neuropathy in both type 1 and type 2 diabetes and may decrease the risk for cardiovascular disease. Target A1C levels in patients with type 1 and 2 diabetes should be tailored to the individual, balancing the improvement in microvascular complications with the risk of hypoglycemia [29-31]. Less stringent treatment goals may be appropriate for patients with a history of severe

hypoglycemia, patients with limited life expectancies, very young children or older adults, and individuals with comorbid conditions. Glycemic goals are reviewed in detail elsewhere. (See "Glycemic control and vascular complications in type 1 diabetes mellitus", section on 'Glycemic targets' and"Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'Glycemic targets'.) Insulin regimens In patients with type 1 or type 2 diabetes, the use of long-acting insulin analogs (eg, glargine, detemir) as the basal insulin and rapid-acting insulin analogs (eg, lispro, aspart, glulisine) as the pre-meal bolus insulin reduces the risk of hypoglycemia, particularly nocturnal hypoglycemia. Although many clinicians believe continuous subcutaneous insulin infusion (CSII) is better, at comparable A1C levels CSII has not been found to consistently result in less hypoglycemia than a basal-bolus regimen with insulin analogs. However, sensor-augmented CSII has been reported to achieve lower A1C levels without an increase in hypoglycemia. Continuous glucose monitoring is reviewed in detail elsewhere. (See "Blood glucose self-monitoring in management of adults with diabetes mellitus", section on 'Continuous glucose monitoring' and "Management of type 1 diabetes mellitus in children and adolescents", section on 'Continuous glucose monitoring' and "Insulin therapy in type 2 diabetes mellitus" and "Insulin therapy in adults with type 1 diabetes mellitus".) Behavioral approaches Avoidance of severe hypoglycemia requires the recognition of early symptoms and signs by the patient (and by those around them). Autonomic symptoms include sweating, tremor, hunger, and anxiety, while neuroglycopenic symptoms include difficulty concentrating, incoordination, weakness, lethargy, blurred vision, and confusion. (See "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus", section on 'Response to hypoglycemia in normal subjects'.) However, the exact set of symptoms perceived varies between patients, and also within the same patient on different occasions [32]. Factors such as alcohol, fatigue, and beta-blockers can affect which symptoms occur and how well they are recognized. Beta-blockers, for example, can mask the early warning symptoms of hypoglycemia [33]; detection of symptoms is also less likely if the person is asleep, tired, or distracted by other events. Using a variety of well-validated behavioral approaches, people can be trained to improve their ability to recognize hypoglycemia [34]. Furthermore, this increase in recognition may be associated with long-term improvement in A1C values and a reduction in the number of severe hypoglycemic events. Blood glucose awareness training involves techniques in which patients are asked to guess their blood glucose concentration, record their symptoms, and then verify the blood glucose values with a glucose meter. Patients also can be taken through hypoglycemic thresholds in a controlled hospital setting, while recording the symptoms they notice at different times. Using these techniques, the most frequently helpful symptoms were, in rank order, difficulty concentrating, trembling, feeling uncoordinated, pounding heart, slowed thinking, feeling nervous and tense, and sweating [32]. Hypoglycemia unawareness If there is a history of hypoglycemia unawareness, a two- to threeweek period of scrupulous avoidance of hypoglycemia is advisable since that often restores awareness [35-41]. That can be accomplished by more intensive professional involvement (eg, by telephone); in practice, it may require higher glycemic goals in the short-term. Prevention of nocturnal hypoglycemia Bedtime snacks are the traditional strategy for preventing nocturnal hypoglycemia. Snacks containing protein have not been shown to be more

effective than carbohydrate alone [42]. A study of 21 patients with type 1 diabetes managed with intensive insulin regimens found that terbutaline 5 mg, a beta2-adrenergic agonist, decreased nocturnal hypoglycemic episodes but caused morning hyperglycemia; a usual bedtime snack, snack plus acarbose, or cornstarch snack were not more effective than no intervention in preventing nocturnal hypoglycemia [18]. A lower dose of terbutaline produced intermediate nocturnal plasma glucose levels [43]. Other experimental approaches include overnight infusions of glucagon and reduction of insulin doses [31]. None of these approaches have been shown to be safe and effective in suitably powered randomized clinical trials. Prevention of exercise-induced hypoglycemia Exercise increases glucose utilization by muscle and, therefore, can cause hypoglycemia in patients with insulin deficient diabetes who have near normal or moderately elevated plasma glucose levels at the start of exercise [2-4,28]. In addition, exercise, like hypoglycemia, can shift the glycemic threshold for the sympathoadrenal response to subsequent hypoglycemia to a lower plasma glucose concentration hours later. This shift causes defective glucose counterregulation by reducing epinephrine responses in the setting of absent insulin and glucagon responses. It also causes hypoglycemia unawareness by reducing autonomic symptom responses. (See "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus", section on 'Exercise'.) Hypoglycemia during or shortly after exercise can be prevented by frequent SMBG and, when indicated, reduced insulin doses, carbohydrate ingestion, or both prior to exercise. Because post exercise hypoglycemia can occur many hours after exercise, patients should remain vigilant for its occurrence and consider action (eg, bedtime snack) to prevent nocturnal hypoglycemia (see 'Prevention of nocturnal hypoglycemia' above). Fear of hypoglycemia Hypoglycemia can be a frightening, unpleasant, and potentially lethal complication of diabetes and, therefore, fear of hypoglycemia is understandable. At its best, this concern should prompt diabetic patients to be aware of early symptoms and to ingest carbohydrate before symptoms progress. In some cases, however, fear of hypoglycemia can become a major barrier to lowering blood glucose concentrations substantially. In one survey, patients who had a frightening episode of severe hypoglycemia in the previous year often became so fearful that they kept their blood glucose excessively high for several months afterwards [44]. As a result, it is important to explore the patient's past experience with hypoglycemia before embarking on an intensified insulin regimen. TREATMENT OF HYPOGLYCEMIA Asymptomatic When SMBG reveals a blood glucose of 70 mg/dL (3.9 mmol/L), it is reasonable for a person with drug-treated diabetes to consider defensive actions. The options include repeating the measurement in the near term, avoiding critical tasks such as driving, ingesting carbohydrates, and adjusting the treatment regimen [8]. Symptomatic In order to treat early symptoms of hypoglycemia, patients should be certain that fast-acting carbohydrate (such as glucose tablets, hard candy, or sweetened fruit juice) is available at all times. Fifteen to 20 grams is usually sufficient to raise the blood glucose into a safe range without inducing hyperglycemia. This can be followed by long-acting carbohydrate to prevent recurrent symptoms.

In patients taking insulin or an insulin secretagogue in combination with an alpha-glucosidase inhibitor (acarbose, miglitol, voglibose), only pure glucose (dextrose) should be used to treat symptomatic hypoglycemia. Other forms of carbohydrates, such as table sugar (sucrose), will be less effective in raising blood sugar as alpha-glucosidase inhibitors slow digestion of other carbohydrates. Severe Treatment of severe hypoglycemia, when the patient is unconscious or unable to ingest carbohydrate, requires that close friends or relatives be trained to recognize and treat this complication. Dealing with a loved one who is pale, sweaty, acting in a bizarre fashion, or unconscious and convulsing is often a terrifying situation, yet one that can be reversed with an injection of glucagon. Successful glucagon therapy requires that the glucagon kit can be located and that the relative or friend is able to remain calm, mix the glucagon powder with the diluent, draw it up, and give the injection. The glucagon kit should be checked regularly and replaced when it is beyond its expiration date. A subcutaneous or intramuscular injection of 0.5 to 1.0 mg of glucagon will usually lead to recovery of consciousness within 10 to 15 minutes, although it may be followed by marked nausea or even vomiting. Patients brought to the hospital can be treated more quickly by giving 25 g of 50 percent glucose (dextrose) intravenously. A subsequent glucose infusion (or food, if patient is able to eat) is often needed, depending upon the cause of the hypoglycemia. There are no efficacy or safety data to guide the management of severe hypoglycemia (while awaiting emergency personnel) in patients with impaired consciousness and no immediate access to glucagon or intravenous dextrose. In a study of normoglycemic volunteers, the buccal absorption of glucose was minimal [45]. However, in the absence of other options for such patients, some experts, including some UpToDate authors and editors, suggest that while awaiting emergency personnel, family members squeeze a glucose gel (eg, InstaGlucose) or cake frosting in the space between the teeth and buccal mucosa, keeping the patient's head tilted slightly to the side. If a glucose gel or cake frosting is unavailable, some advocate sprinkling table sugar under the tongue, as table sugar has been reported to raise plasma glucose concentrations to some extent in ill children with malaria [46,47]. However, other experts, including the author of this topic review, would not administer buccal or sublingual preparations or foods, given the lack of supporting evidence and concerns about aspiration. Although a comatose diabetic patient may have marked hyperglycemia (with or without ketoacidosis) rather than hypoglycemia, these disorders can be distinguished by estimating blood glucose with a glucose stick. If this is not available, then glucose should be given empirically. This will correct hypoglycemia and will not be particularly deleterious if the blood glucose concentration is high. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, th th at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,

more sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient information: Type 1 diabetes (The Basics)" and "Patient information: Type 2 diabetes (The Basics)" and "Patient information: Low blood sugar in people with diabetes (The Basics)") Beyond the Basics topics (see "Patient information: Diabetes mellitus type 1: Overview (Beyond the Basics)" and "Patient information: Diabetes mellitus type 2: Overview (Beyond the Basics)" and "Patient information: Hypoglycemia (low blood sugar) in diabetes mellitus (Beyond the Basics)")

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SUMMARY AND RECOMMENDATIONS Our approach to the management of insulin secretagogue or insulin-treated patients is as follows: Risk factor assessment Ask about hypoglycemia at every patient contact, particularly details about previous major episodes of hypoglycemia, accompanying symptoms, the frequency of minor episodes, the timing of meals, exercise, and diabetes medications preceding hypoglycemia, and how hypoglycemic episodes are usually treated. (See 'Risk factors for hypoglycemia' above.) Review the self-monitoring of blood glucose record to estimate the frequency of hypoglycemia and the adequacy of counterregulation, particularly before starting intensive insulin therapy or if there is a previous history of hypoglycemic episodes. Review any continuous glucose sensing data obtained. (See 'Prediction of risk from blood glucose monitoring' above.)

Prevention Hypoglycemia can occur at any level of glycemia, but the risk increases with more intensive therapy. The goal is to achieve the best degree of mean glycemia (A1C) that can be accomplished safely. We consider more modest goals for A1C values in patients with one or more previous episodes of severe hypoglycemia, with significant impairment in recovery from hypoglycemia, or in those with little expected benefit from glycemic control. We continually reevaluate with the patient whether the benefits of improved blood glucose control are worth the number of hypoglycemic episodes that are occurring. (See 'Glycemic targets' above.) Provide education for the patient on the recognition and treatment of hypoglycemia. Patients should be told to be especially vigilant following an episode of hypoglycemia, since both recognition of hypoglycemia and the counterregulatory response to it will be impaired during this time. (See "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus", section on 'Hypoglycemia-associated autonomic failure'.) For patients who have hypoglycemia unawareness, avoidance of hypoglycemia for two to three weeks may restore awareness. (See 'Hypoglycemia unawareness' above.)

Treatment For a person with drug-treated diabetes, we suggest defensive actions when selfmonitoring reveals a glucose level 70 mg/dL (3.9 mmol/L) (Grade 2C). (See'Definition' above.) Defensive actions include repeating the measurement in the near term, avoiding critical tasks such as driving, ingesting carbohydrates, and adjusting the treatment regimen. Patients with asymptomatic or symptomatic hypoglycemia should ingest carbohydrates. Fifteen to 20 grams of oral glucose is typically sufficient. Glucose may be ingested in the form of tablets, juice, milk, other snacks, or a meal. (See 'Symptomatic' above.) For the treatment of hypoglycemia in a person with impaired consciousness and no established intravenous (IV) access, we suggest the immediate administration ofglucagon, rather than waiting to establish IV access (Grade 2B). The usual dose is 0.5 to 1.0 mg given as a subcutaneous or intramuscular injection. Education and training for clinicians, friends, and family on the recognition and treatment of severe hypoglycemia, including the use of glucagon kits, is necessary. (See'Severe' above.) Intravenous dextrose (25 g of 50 percent glucose [dextrose]) can be administered to treat hypoglycemia in patients with impaired consciousness and established IV access (typically in a hospital). (See 'Severe' above.) In the latter settings, a subsequent glucose infusion (or food, if patient is able to eat) is often needed, depending upon the cause of the hypoglycemia, to prevent recurrence of symptoms. We routinely check that the patient's blood glucose monitoring equipment is accurately calibrated, that fast-acting carbohydrate is being kept available, that the patient is staying vigilant, and that glucagon kits are not out of date.

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