Hypoglycemia and DM: Report of the ADA and Endocrine Society
Hypoglycemia and DM: Report of the ADA and Endocrine Society
Recurrent hypoglycemia increases the risk of severe hypoglycemia and the development of hypoglycemia unawareness and HAAF. Effective approaches known to decrease the risk of iatrogenic hypoglycemia include patient education, dietary and exercise modifications, medication adjustment, careful glucose monitoring by the patient, and conscientious surveillance by the clinician.
There is limited research related to the influence of self-management education on the incidence or prevention of hypoglycemia. However, there is clear evidence that diabetes education improves patient outcomes. As part of the educational plan, the individual with diabetes and his or her domestic companions need to recognize the symptoms of hypoglycemia and be able to treat a hypoglycemic episode properly with oral carbohydrates or glucagon. Hypoglycemia, including its risk factors and remediation, should be discussed routinely with patients receiving treatment with insulin or sulfonylurea/glinide drugs, especially those with a history of recurrent hypoglycemia or impaired awareness of hypoglycemia. In addition, patients must understand how their medications work so they can minimize the risk of hypoglycemia. Care should be taken to educate patients on the typical pharmacokinetics of these medications. When evaluating a patient's report of hypoglycemia, it is important to adopt interviewing approaches that guide the patient to a correct identification of the precipitating factors of the episodes of hypoglycemia. Such a heuristic review of likely factors (skipped or inadequate meal, unusual exertion, alcohol ingestion, insulin dosage mishaps, etc.) in the period prior to the event can deepen the patient's appreciation of the behavioral factors that predispose to hypoglycemia.
There is convincing evidence that formal training programs that teach patients to replace insulin "physiologically" by giving background and mealtime/correction doses of insulin can reduce the risk of severe hypoglycemia. The Insulin Treatment and Training programs developed by Mühlhauser and Berger have reported improved glycemic control comparable with DCCT while reducing the rates of severe hypoglycemia. These programs have been successfully delivered in other settings with comparable reductions in hypoglycemic risk. Patients with frequent hypoglycemia may also benefit from enrollment in a blood glucose awareness training program. In such a program, patients and their relatives are trained to recognize subtle cues and early neuroglycopenic indicators of evolving hypoglycemia and respond to them before the occurrence of disabling hypoglycemia.
Patients with diabetes need to recognize which foods contain carbohydrates and understand how the carbohydrates in their diet affect blood glucose. To avoid hypoglycemia, patients on long-acting secretagogues and fixed insulin regimens must be encouraged to follow a predictable meal plan. Patients on more flexible insulin regimens must know that prandial insulin injections should be coupled to meal times. Dissociated meal and insulin injection patterns lead to wide fluctuations in plasma glucose levels. Patients on any hypoglycemia-inducing medication should also be instructed to carry carbohydrates with them at all times to treat hypoglycemia.
The best bedtime snack to prevent overnight hypoglycemia in patients with type 1 diabetes has been investigated without clear consensus. These conflicting reports suggest that the administration of bedtime snacks may need to be individualized and be part of a comprehensive strategy (balanced diet, patient education, optimized drug regimens, and physical activity counseling) for the prevention of nocturnal hypoglycemia.
Physical activity increases glucose utilization, which increases the risk of hypoglycemia. The risk factors for exertional hypoglycemia include prolonged exercise duration, unaccustomed exercise intensity, and inadequate energy supply in relation to ambient insulinemia. Postexertional hypoglycemia can be prevented or minimized by careful glucose monitoring before and after exercise and taking appropriate preemptive actions. Preexercise snacks should be ingested if blood glucose values indicate falling glucose levels. Patients with diabetes should carry readily absorbable carbohydrates when embarking on exercise, including sporadic house or yard work. Because of the kinetics of rapid-acting and intermediate-acting insulin, it may be prudent to empirically adjust insulin doses on the days of planned exercise, especially in patients with well-controlled diabetes with a history of exercise-related hypoglycemia.
Hypoglycemic episodes that are not readily explained by conventional factors (skipped or irregular meals, unaccustomed exercise, alcohol ingestion, etc.) may be due to excessive doses of drugs used to treat diabetes. A thorough review of blood glucose patterns may suggest vulnerable periods of the day that mandate adjustments to the current antidiabetes regimen. Such adjustments may include substitution of rapid-acting insulin (lispro, aspart, glulisine) for regular insulin, or basal insulin glargine or detemir for NPH, to decrease the risk of hypoglycemia. Continuous subcutaneous insulin infusion offers great flexibility for adjusting the doses and administration pattern of insulin to counteract iatrogenic hypoglycemia. For patients with type 2 diabetes, sulfonylureas are the oral agents that pose the greatest risk for iatrogenic hypoglycemia and substitution with other classes of oral agents or even glucagon-like peptide 1 analogs should be considered in the event of troublesome hypoglycemia. Interestingly, successful transplantation of whole pancreata or isolated pancreatic islet cells in patients with type 1 diabetes results in marked improvements in glycemic control and near abolition of iatrogenic hypoglycemia.
Patients who develop hypoglycemia unawareness do so because of frequent and recurrent hypoglycemia. To avoid such frequent hypoglycemia, adjustments in the treatment regimen that scrupulously avoid hypoglycemia are necessary ( Table 1 ). In published studies, this has required frequent (almost daily) contact between clinician and patient, and adjustments to caloric intake and insulin regimen based on blood glucose values. With this approach, restoration of autonomic symptoms of hypoglycemia occurred within 2 weeks, and complete reversal of hypoglycemia unawareness was achieved by 3 months. In some but not all reports, the recovery of symptoms is accompanied by the improvement in epinephrine secretion. The return of hypoglycemic symptom awareness was associated with a modest increase (~0.5%) in HbAlc values, but others have reported no loss of glycemic control.
Glucose monitoring is essential in managing patients at risk for hypoglycemia. Patients treated with insulin, sulfonylureas, or glinides should check their blood glucose whenever they develop the symptoms of hypoglycemia in order to confirm that they must ingest carbohydrates to treat the symptoms and collect information that can be used by the clinician to adjust the therapeutic regimen to avoid future hypoglycemia. Patients on basal-bolus insulin therapy should check their blood glucose before each meal and figure this value into the calculation of the dose of rapid-acting insulin to take at that time. Such care in dosing will likely reduce the risk of hypoglycemia.
Recent technological developments have provided patients with new tools for glucose monitoring. Real-time CGM, by virtue of its ability to display the direction and rate of change, provides helpful information to the wearer leading to proactive measures to avoid hypoglycemia, e.g., when to think about having a snack or suspending insulin delivery on a pump. The CGM's audible and/or vibratory alarms may be particularly helpful in avoiding severe hypoglycemia at night and restoring hypoglycemic awareness. With the low-glucose alarms set at 108 mg/dL, 4 weeks of real-time CGM use restored the epinephrine response and improved adrenergic symptoms during a hyperinsulinemic hypoglycemic clamp in a small group of adolescents with type 1 diabetes and hypoglycemic unawareness.
The artificial pancreas, which couples a CGM to an insulin pump through sophisticated predictive algorithms, holds out the promise of completely eliminating hypoglycemia. Several internationally collaborative groups are working on various approaches to the artificial pancreas. The first step in this direction is the low-glucose suspend pump that is available in Europe and currently in clinical trials in the U.S. This device shuts off insulin delivery for up to 2 h once the interstitial glucose concentration reaches a preset threshold and reduces the duration of nocturnal hypoglycemia.
Clinicians and educators must assess the risk of hypoglycemia at every visit with patients treated with insulin and insulin secretagogues. An efficient way to begin this assessment might be to have the patient complete the questionnaire shown in Table 2 while in the waiting room. Review of the completed questionnaire will help the clinician learn how often the patient is experiencing symptomatic and asymptomatic hypoglycemia, ensure the patient is aware of how to appropriately treat hypoglycemia, and remind both parties of the risks associated with driving while hypoglycemic. To ensure that hypoglycemia has been adequately addressed during a visit, providers may want to use the
A careful review of the glucose log collected by the patient should also be done at each visit. The date, approximate time, and circumstances surrounding recent episodes of hypoglycemia should be noted, together with information regarding the awareness of the warning symptoms of hypoglycemia. A reliable history of impaired autonomic responses (tremulousness, sweating, palpitations, and hunger) during hypoglycemia may be the most practical approach to making the diagnosis of hypoglycemia unawareness. If symptoms are absent or if frequent episodes of recurrent hypoglycemia occur within hours to days of each other, it is likely that the patient has HAAF. Other historical clues such as experiencing more than one episode of severe hypoglycemia that required the assistance of another over the preceding year or a family report that they are recognizing more frequent episodes of hypoglycemia may also provide clues that the patient has developed hypoglycemia unawareness. A self-reported history of impaired or absent perception of autonomic symptoms during hypoglycemia correlates strongly with laboratory confirmation of hypoglycemia unawareness.
What Strategies Are Known to Prevent Hypoglycemia, and What Are the Clinical Recommendations for Those at Risk for Hypoglycemia?
Recurrent hypoglycemia increases the risk of severe hypoglycemia and the development of hypoglycemia unawareness and HAAF. Effective approaches known to decrease the risk of iatrogenic hypoglycemia include patient education, dietary and exercise modifications, medication adjustment, careful glucose monitoring by the patient, and conscientious surveillance by the clinician.
Patient Education
There is limited research related to the influence of self-management education on the incidence or prevention of hypoglycemia. However, there is clear evidence that diabetes education improves patient outcomes. As part of the educational plan, the individual with diabetes and his or her domestic companions need to recognize the symptoms of hypoglycemia and be able to treat a hypoglycemic episode properly with oral carbohydrates or glucagon. Hypoglycemia, including its risk factors and remediation, should be discussed routinely with patients receiving treatment with insulin or sulfonylurea/glinide drugs, especially those with a history of recurrent hypoglycemia or impaired awareness of hypoglycemia. In addition, patients must understand how their medications work so they can minimize the risk of hypoglycemia. Care should be taken to educate patients on the typical pharmacokinetics of these medications. When evaluating a patient's report of hypoglycemia, it is important to adopt interviewing approaches that guide the patient to a correct identification of the precipitating factors of the episodes of hypoglycemia. Such a heuristic review of likely factors (skipped or inadequate meal, unusual exertion, alcohol ingestion, insulin dosage mishaps, etc.) in the period prior to the event can deepen the patient's appreciation of the behavioral factors that predispose to hypoglycemia.
There is convincing evidence that formal training programs that teach patients to replace insulin "physiologically" by giving background and mealtime/correction doses of insulin can reduce the risk of severe hypoglycemia. The Insulin Treatment and Training programs developed by Mühlhauser and Berger have reported improved glycemic control comparable with DCCT while reducing the rates of severe hypoglycemia. These programs have been successfully delivered in other settings with comparable reductions in hypoglycemic risk. Patients with frequent hypoglycemia may also benefit from enrollment in a blood glucose awareness training program. In such a program, patients and their relatives are trained to recognize subtle cues and early neuroglycopenic indicators of evolving hypoglycemia and respond to them before the occurrence of disabling hypoglycemia.
Dietary Intervention
Patients with diabetes need to recognize which foods contain carbohydrates and understand how the carbohydrates in their diet affect blood glucose. To avoid hypoglycemia, patients on long-acting secretagogues and fixed insulin regimens must be encouraged to follow a predictable meal plan. Patients on more flexible insulin regimens must know that prandial insulin injections should be coupled to meal times. Dissociated meal and insulin injection patterns lead to wide fluctuations in plasma glucose levels. Patients on any hypoglycemia-inducing medication should also be instructed to carry carbohydrates with them at all times to treat hypoglycemia.
The best bedtime snack to prevent overnight hypoglycemia in patients with type 1 diabetes has been investigated without clear consensus. These conflicting reports suggest that the administration of bedtime snacks may need to be individualized and be part of a comprehensive strategy (balanced diet, patient education, optimized drug regimens, and physical activity counseling) for the prevention of nocturnal hypoglycemia.
Exercise Management
Physical activity increases glucose utilization, which increases the risk of hypoglycemia. The risk factors for exertional hypoglycemia include prolonged exercise duration, unaccustomed exercise intensity, and inadequate energy supply in relation to ambient insulinemia. Postexertional hypoglycemia can be prevented or minimized by careful glucose monitoring before and after exercise and taking appropriate preemptive actions. Preexercise snacks should be ingested if blood glucose values indicate falling glucose levels. Patients with diabetes should carry readily absorbable carbohydrates when embarking on exercise, including sporadic house or yard work. Because of the kinetics of rapid-acting and intermediate-acting insulin, it may be prudent to empirically adjust insulin doses on the days of planned exercise, especially in patients with well-controlled diabetes with a history of exercise-related hypoglycemia.
Medication Adjustment
Hypoglycemic episodes that are not readily explained by conventional factors (skipped or irregular meals, unaccustomed exercise, alcohol ingestion, etc.) may be due to excessive doses of drugs used to treat diabetes. A thorough review of blood glucose patterns may suggest vulnerable periods of the day that mandate adjustments to the current antidiabetes regimen. Such adjustments may include substitution of rapid-acting insulin (lispro, aspart, glulisine) for regular insulin, or basal insulin glargine or detemir for NPH, to decrease the risk of hypoglycemia. Continuous subcutaneous insulin infusion offers great flexibility for adjusting the doses and administration pattern of insulin to counteract iatrogenic hypoglycemia. For patients with type 2 diabetes, sulfonylureas are the oral agents that pose the greatest risk for iatrogenic hypoglycemia and substitution with other classes of oral agents or even glucagon-like peptide 1 analogs should be considered in the event of troublesome hypoglycemia. Interestingly, successful transplantation of whole pancreata or isolated pancreatic islet cells in patients with type 1 diabetes results in marked improvements in glycemic control and near abolition of iatrogenic hypoglycemia.
Patients who develop hypoglycemia unawareness do so because of frequent and recurrent hypoglycemia. To avoid such frequent hypoglycemia, adjustments in the treatment regimen that scrupulously avoid hypoglycemia are necessary ( Table 1 ). In published studies, this has required frequent (almost daily) contact between clinician and patient, and adjustments to caloric intake and insulin regimen based on blood glucose values. With this approach, restoration of autonomic symptoms of hypoglycemia occurred within 2 weeks, and complete reversal of hypoglycemia unawareness was achieved by 3 months. In some but not all reports, the recovery of symptoms is accompanied by the improvement in epinephrine secretion. The return of hypoglycemic symptom awareness was associated with a modest increase (~0.5%) in HbAlc values, but others have reported no loss of glycemic control.
Glucose Monitoring
Glucose monitoring is essential in managing patients at risk for hypoglycemia. Patients treated with insulin, sulfonylureas, or glinides should check their blood glucose whenever they develop the symptoms of hypoglycemia in order to confirm that they must ingest carbohydrates to treat the symptoms and collect information that can be used by the clinician to adjust the therapeutic regimen to avoid future hypoglycemia. Patients on basal-bolus insulin therapy should check their blood glucose before each meal and figure this value into the calculation of the dose of rapid-acting insulin to take at that time. Such care in dosing will likely reduce the risk of hypoglycemia.
Recent technological developments have provided patients with new tools for glucose monitoring. Real-time CGM, by virtue of its ability to display the direction and rate of change, provides helpful information to the wearer leading to proactive measures to avoid hypoglycemia, e.g., when to think about having a snack or suspending insulin delivery on a pump. The CGM's audible and/or vibratory alarms may be particularly helpful in avoiding severe hypoglycemia at night and restoring hypoglycemic awareness. With the low-glucose alarms set at 108 mg/dL, 4 weeks of real-time CGM use restored the epinephrine response and improved adrenergic symptoms during a hyperinsulinemic hypoglycemic clamp in a small group of adolescents with type 1 diabetes and hypoglycemic unawareness.
The artificial pancreas, which couples a CGM to an insulin pump through sophisticated predictive algorithms, holds out the promise of completely eliminating hypoglycemia. Several internationally collaborative groups are working on various approaches to the artificial pancreas. The first step in this direction is the low-glucose suspend pump that is available in Europe and currently in clinical trials in the U.S. This device shuts off insulin delivery for up to 2 h once the interstitial glucose concentration reaches a preset threshold and reduces the duration of nocturnal hypoglycemia.
Clinical Surveillance
Clinicians and educators must assess the risk of hypoglycemia at every visit with patients treated with insulin and insulin secretagogues. An efficient way to begin this assessment might be to have the patient complete the questionnaire shown in Table 2 while in the waiting room. Review of the completed questionnaire will help the clinician learn how often the patient is experiencing symptomatic and asymptomatic hypoglycemia, ensure the patient is aware of how to appropriately treat hypoglycemia, and remind both parties of the risks associated with driving while hypoglycemic. To ensure that hypoglycemia has been adequately addressed during a visit, providers may want to use the
A careful review of the glucose log collected by the patient should also be done at each visit. The date, approximate time, and circumstances surrounding recent episodes of hypoglycemia should be noted, together with information regarding the awareness of the warning symptoms of hypoglycemia. A reliable history of impaired autonomic responses (tremulousness, sweating, palpitations, and hunger) during hypoglycemia may be the most practical approach to making the diagnosis of hypoglycemia unawareness. If symptoms are absent or if frequent episodes of recurrent hypoglycemia occur within hours to days of each other, it is likely that the patient has HAAF. Other historical clues such as experiencing more than one episode of severe hypoglycemia that required the assistance of another over the preceding year or a family report that they are recognizing more frequent episodes of hypoglycemia may also provide clues that the patient has developed hypoglycemia unawareness. A self-reported history of impaired or absent perception of autonomic symptoms during hypoglycemia correlates strongly with laboratory confirmation of hypoglycemia unawareness.