The revision of this chapter was prepared by Karen Gorecki, RN, MN, CDE
Hypoglycemia is a common medical adverse effect of treatment in persons with insulin treated diabetes. It can also occur in people taking antihyperglycemic agents. It may often be prevented or minimized through appropriate self-management decisions and an appropriate medical prescription, in which available insulin levels match the person's needs and lifestyle in the most physiological way possible. Prevention of hypoglycemic episodes is crucial to avoid emotional and social costs to the patient, as well to prevent the cycle of impaired counter-regulation and severe hypoglycemia.
Clinical Hypoglycemia is defined as a state in which there is:
- Autonomic (activation of the sympathetic nervous system) or neuroglycopenic (by lack of glucose to the brain) symptoms
- Biochemical determination of a low blood glucose (usually < 3. 5 mmol/L). For those on insulin or insulin secretagogues, < 4.0 mmol/L is often considered hypoglycemia.
- Relief with administration of carbohydrate
Hypoglycemia can be further described by its degree of severity:
- Mild Hypoglycemia: Autonomic mediated symptoms, able to treat self.
- Moderate Hypoglycemia: Autonomic & neuroglycopenic mediated symptoms. Able to treat self.
- Severe Hypoglycemia: Unable to treat self. Requires assistance. May be unconscious. Plasma glucose usually < 2.8 mmol/L
When the individual is accustomed to a higher blood glucose level and plasma glucose levels fall rapidly, hypoglycemic symptoms may be felt at levels higher than 3.5- 4 mmol/L. Normalization of perception is anticipated when blood glucose levels are stabilized.
The threshold for autonomic warning symptoms becomes lower than the threshold for neuroglycopenic symptoms. Often the first sign is confusion or loss of consciousness. This is thought to be due to impaired compensatory responses (frequent lows in past, inadequate release of counter-regulatory hormones, the use of beta- blockers or the presence of autonomic neuropathy).
A relative excess of insulin is the inevitable cause of low blood glucose, but surrounding circumstances vary widely.
- A major cause is iatrogenic, through excess insulin administration, compromised glucose counterregulation and/or insufficient self-management education
- Intensive diabetes therapy has been associated with an increased risk of hypoglycemia. However, with adequate self-management education, appropriate BG targets, SMBG and professional support, intensive therapy may result in less hypoglycemia than previously reported. The benefits of intensive therapy must be balanced against the risks of increased severe hypoglycemia in a particular individual. Rapid acting insulin analogues are associated with less nocturnal hypoglycemia.
- Inappropriate sulfonylurea doses or decreasing renal function in patients on sulfonylureas may result in hypoglycemia.
- It has been demonstrated that 85.6% of hypoglycemic episodes are associated with self-care actions of less food, more insulin and more activity. However, making decision to prevent hypoglycemia is not necessarily easy. The Biopsychosocial Model of hypoglycemia summarizes the complex interplay of variables that lead to severe hypoglycemia (see Figure 12.1). Treatment and self- management education may be described in relation to this model.
If appropriate self-management education is feasible, a person can typically recognize and respond to early symptoms with appropriate treatment. Identify high risk patients to allow special self-management education. Persons at high risk for severe hypoglycemia are those with:
- A history of severe lows
- Pre-existing autonomic dysfunction
- Frequent mild-moderate lows (low mean BG)
- Lower HbA1c (< 6%)
- Longer duration of diabetes
- Hypoglycemia unawareness
Improve/Maintain Hypoglycemia Awareness
- Improve self-management education to aim for meticulous avoidance of lows.
- Blood glucose awareness training as part of intensive diabetes therapy education may have a positive effect on increasing accurate detection and treatment of lows.
- Avoidance of hypoglycemia from 2 to 90 days has been associated with improved hypoglycemia recognition. Restoration of hypoglycemia awareness can reduce severe lows.
Insulin Regimens (or any medication plan)
- Design to mimic physiological insulin replacement as closely as possible, with appropriate target glucose goals for the individual.
- Set BG targets/goals for high risk individuals, appropriate to their individual needs and goals.
- Higher glycemic targets (e.g. 6 - 12 mmol/Lt) are prudent for those at risk for severe hypoglycemia.
- Assessment of overnight BG should be done at the time when overnight insulin is considered to be peaking
- Targets for children may need to be age adjusted (see Chapter 6).
- When fixed dose medication regimens are used, care should be taken to develop an individualized meal and activity plan that the person can and will follow.
- Prandial (bolus) insulins: lispro, aspart, and glulisine have been demonstrated to cause less postprandial hypoglycemia when dose is adjusted to carbohydrate content and activity plans.
- Use of the basal analogues, lantus or determir instead of intermediate-acting insulin has decreased the incidence of hypoglycemia, including nocturnal hypoglycemia.
- Education should include guidelines for insulin dose adjustment for exercise, alcohol use, meal/snack choices.
- Patients should be informed how to alter meals and snacks with appropriate adjustments and of the risk of low BG associated with omission of meals.
- Bedtime snacks may be needed to avoid nocturnal hypoglycemia. The evidence that addition of protein to complex CHO at bedtime reduces the frequency of nocturnal hypoglycemia is not definitive. Prepared snack bars with cornstarch have demonstrated some effectiveness in reducing lows overnight. A snack of 15 g carbohydrate and a protein choice when an HS BG is 4--7.0mmol/L for those taking premixed insulin or intermediate-acting insulin as the basal insulin or those at high risk of severe hypoglycemia (regardless of insulin type) may reduce the risk of nocturnal hypoglycemia. However this may result in an elevated FBS. Improved basal insulin delivery is the preferred solution.
- Guidelines for eating extra food or decreasing insulin prior to strenuous activity are important. Blood glucose monitoring before, during and after exercise is required to evaluate proper treatment.
- The use of alcohol (which may lead to impaired hepatic gluconeogenesis) should be discussed.
- Prevention of nocturnal hypoglycemia is a priority and should include use of insulin which does not "peak" between 2100 and 0300 (pump or HS basal dose or long acting analogue insulin preparations) and the addition of a bedtime snack if HS BG level warrants (eg. < 7 mmol/L, see above) or if there has been sustained exercise that day.
- Approximately 50% of lows are reported to occur at night and are often asymptomatic, with episodes reported at frequencies varying from 36% to 67%. Symptoms may present as nightmares or morning headaches.
- Counterregulatory impairment may be a part of general reduction in sympathetic activity with stage 3 & 4 non REM sleep and may increase risk of hypoglycemia at night
- Dawn Phenomenon: Refers to a rise in blood glucose occurring during the early morning between 0600 and 0800 hours in the absence of hypoglycemia. It is thought to be due to a rise in the counter-regulatory hormones, particularly growth hormone, that increase hepatic glucose output and therefore insulin requirements. Increasing basal insulin doses may result in nocturnal lows but insufficient insulin to counteract the Dawn effect. The problem may be dealt with more effectively with Continuous Subcutaneous Insulin Infusion (insulin pump).
- Somoygi Effect: Refers to post-hypoglycemia hyperglycemia, traditionally thought to be a potential cause of morning hyperglycemia. It is difficult to determine whether morning hyperglycemia is associated with preceding hypoglycemia or is just the consequences of the waning effect of insulin or the Dawn phenomenon. Establishing the patterns of night blood glucose levels over a period of a few days by testing at bedtime, again at 0300-0400 and at 0700-0800 hours is essential for proper diagnosis and treatment (same as for Dawn phenomenon).
- Continuous Glucose Monitoring (CGM) may be useful in assessing nocturnal control.
- Management of individuals with gastropathy may be enhanced with the use of an insulin analogue, taken after meals or when the BG level begins its rise.
Goals of Hypoglycemia Treatment
- To detect and treat a low blood glucose level promptly.
- To increase the blood glucose quickly to remove the risk of injury.
- To relieve symptoms quickly to avoid over-treatment and rebound hyperglycemia.
- To avoid over treatment of hypoglycemia which can lead to weight gain.
For Mild to Moderate Hypoglycemia
- 15 g glucose, preferably as glucose tablets or sucrose tablets. This should produce a rise in BG of approximately 2.1 mmol/L in 20 minutes.
- Patients taking an α-glucosidase inhibitor must use glucose (dextrose) tablets or if unavailable, milk or honey to treat hypoglycemia.
- Patients should be encouraged to wait 15 minutes, retest BG and retreat with another 15 g glucose if BG remains < 4.0 mmol/L.
- If the next meal is > 1 hour, a snack containing 15g carbohydrate and a protein source is recommended to prevent repeated hypoglycemia
For Severe Hypoglycemia Occurring Outside of a Hospital Setting
If Conscious and Able to Take Oral Treatment
- 20 g glucose in tablet form.
- Patients should wait 15 minutes retest BG and retreat with another 15 g glucose if BG remains < 4.0 mmol/L.
- If the next meal is > 1 hour, a snack containing 15g carbohydrate and a protein source is recommended to prevent repeated hypoglycemia
Unconscious or Unable to Take Oral Treatment
- Support person may administer 0.5 to 1.0 mg glucagon subcutaneously or intramuscularly. This should produce a significant BG rise (from 3.0 to 12 mmol/L) within 60 minutes.
- In children < 5 years (weighing less than 44 lbs or 20 kg), 0.5 mg glucagon should be given. Use of mini-doses of glucagons is an option in the management of hypoglycemia associate with refusal of oral carbohydrate. A dose of 20 ug per year of age up to a maximum of 150 ug can treat and prevent hypoglycemia. An additional doubled dose can be given if BG has not increased in 20 minutes.
- Glucagon may cause people to vomit. Unconscious persons should be on his/her side (recovery position) to reduce the risk of aspiration.
- Hospitalization is probably not required once consciousness and the ability to take oral food have been restored.
- The patient should be advised of the need for follow up carbohydrate, the risk of recurrence and the need to prevent future episodes.
- Glucose gel should not be administered buccally since absorption through the mucosa is minimal. Glucose gel is quite slow to react (< 1 mmol/L rise at 20 minutes) and must be swallowed to have a significant effect.
- Other forms of oral glucose, such as fruit juice and honey are absorbed more slowly and provide less rapid relief of symptoms. Regular soft drinks (not diet drinks) may be used also.
- If the episode of hypoglycemia will not be followed by a snack or meal within one hour, then a carbohydrate snack should be taken in addition to the glucose used to treat the hypoglycemia.
- For severe low BG with unconsciousness in an institutional setting, IV Glucose 10 to 25 g dose (20-50 cc D50W), for adults and dextrose 0.5 to 1g/kg for children given over 1 -3 minutes is the standard treatment.
Hypoglycemia in People on Sulfonylurea Agents:
- Necessitates an adjustment in management. Some sulfonylureas may have a prolonged hypoglycemia effect, particularly in the elderly.
- If severe hypoglycemia with loss of consciousness occurs, hospitalization for several hours to days may be required to prevent recurrent severe hypoglycemia.
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