Hypoglycaemia(Causes, types and Management)

Joy Shu’aibu

Outline

• Introduction
• Epidemiology of hypoglycaemia.
• Physiologic response to hypoglycaemia in normal subjects and in patients with diabetes
• Diagnosis of Hypoglycaemia
• Classification of Hypoglycaemia
• Symptoms and signs of Hypoglycaemia
• Management of Hypoglycaemia
• Complications/differential diagnosis of Hypoglycaemia
• Prevention of Hypoglycaemia
• Case Studies

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Introduction

• Hypoglycaemia is a clinical syndrome characterised by low plasma glucose levels resulting in signs and symptoms which are reversible when the plasma glucose concentration is corrected.
• 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.
• Hypoglycemia is possibly the most common metabolic emergency.

Epidemiology

• Hypoglycemia is common in type 1 diabetes, especially in patients receiving intensive therapy, in whom the risk of severe hypoglycemia is increased more than threefold.
• They suffer an average of two episodes of symptomatic hypoglycemia per week, thousands of such episodes over a lifetime of diabetes, and one episode of severe, at least temporarily disabling hypoglycemia per year.

Epidemiology

• Hypoglycemia is less frequent in type 2 diabetes than it is in type1.
• Hypoglycemia was reported in 38% of patients with T2DM who added a sulfonylurea or meglitinide to metformin therapy.
• The frequency of hypoglycemia in patients with type 2 diabetes approaches that in type 1 diabetes as patients with type 2 diabetes approach the insulin deficient end of the spectrum of the disease and require aggressive treatment with insulin.

Physiologic response to Hypoglycaemia

• Discussion questions
• In normal subjects
• Among Diabetics

Diagnosis of Hypoglycaemia

• The diagnosis of hypoglycemia is not based on an absolute blood glucose level; it requires fulfilment of the Whipple triad:

I) Signs and symptoms consistent with hypoglycemia

2) Associated low glucose level

3) Relief of symptoms with supplemental glucose

Classifications of Hypoglycemia

• In the context of diabetes mellitus, hypoglycemia is classified as:

1) Severe hypoglycemia

2) Documented symptomatic hypoglycemia (patient feels typical hyperadrenergic hypoglycemic symptoms and verifies the blood glucose level is less than 70 mg/dL (3.9 mmol/L)

3) Probable symptomatic hypoglycemia (Typical hypoglycemia symptoms not accompanied by plasma glucose determination)

Classifications of Hypoglycemia

• In the context of diabetes mellitus, hypoglycemia is classified as:

4) Asymptomatic hypoglycemia(or hypoglycemic Unawareness) patient does not develop typical hyperadrenergic symptoms but has a measured plasma glucose level of less than 70 mg/dL (3.9mmol/L).

5) Relative hypoglycemia (patient experiences hyperadrenergic hypoglycemic symptoms but has a measured plasma glucose level greater than 70 mg/dL (3.9 mmol/L).

Classifications of Hypoglycemia

Outside the context of diabetes mellitus, hypoglycemia is classified as:

1) Reactive(sometimes called "postprandial"): develops in response to a nutrient challenge. Post-GI surgical patients, when gastric contents get dumped into the small intestine too quickly

2) Nonreactive(sometimes called "fasting").

1. iatrogenic (most common overall cause)
2. Fasting/factitious: the patient is unable to maintain glucose levels with fasting (alcohol abuse, drugs , sepsis, and renal failure.

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CAUSES OF HYPOGLYCEMIA

• Drugs are the most common cause of hypoglycemia , Hypoglycemia is common in type 1 diabetes, especially in patients receiving intensive therapy in whom the risk of severe hypoglycemia is increased more than threefold.
• Less commonly, hypoglycemia may also affect patients with type 2 diabetes who take insulin.

CAUSES OF HYPOGLYCEMIA

• Alcohol
• Common critical illnesses such as hepatic, renal, or cardiac failure, sepsis.
• Adrenal insufficiency, an insulinoma, or an IGF-secreting tumor.

SYMPTOMS OF HYPOGLYCEMIA

• Symptoms of hypoglycemia have been classified into two major groups:
• Autonomic Symptoms (Adrenergic And Cholinergic) : recognized at a threshold of approximately 60 mg/dL: occurs at a threshold of approximately 50 mg/dL.

SYMPTOMS HYPOGLYCEMIA

• Autonomic or Neurogenic (or autonomic) symptoms of hypoglycemia are the result of the perception of physiologic changes caused by the CNS-mediated sympathoadrenal discharge triggered by hypoglycemia.
• Adrenergic symptoms (mediated largely by norepinephrine released from sympathetic postganglionic neurons but perhaps also by epinephrine released from the adrenal medullae)
• palpitations, tremor, and anxiety are usually experienced first.

SYMPTOMS HYPOGLYCEMIA

• 2. Cholinergic symptoms (mediated by acetylcholine released from sympathetic postganglionic neurons) such as
• sweating, hunger, and paresthesias.

SYMPTOMS OF HYPOGLYCEMIA

• Neuroglycopenic symptoms of hypoglycemia are the direct result of central nervous system (CNS) glucose deprivation.
• They include;
• Behavioral changes, Confusion,
• Fatigue, loss of consciousness , cognitive impairment, somnolence, dizziness, slurred speech .

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SYMPTOMS OF HYPOGLYCEMIA

• If these signs and symptoms are not recognized and treated and the plasma glucose level continues to decrease , the patient may develop focal neurologic signs such as hemiparesis, or have seizures and death results.

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SIGNS OF HYPOGLYCEMIA

• Common signs of hypoglycemia include:
• Diaphoresis and pallor.
• Heart rate and systolic blood pressure are typically increased but may not be raised in an individual who has experienced repeated, recent episodes of hypoglycemia.

3. Transient focal neurologic deficits occur occasionally.

4. Permanent neurologic deficits are rare.

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SIGNS OF HYPOGLYCEMIA

• Physical-Exam

1) General : confusion, lethargy

2) HEENT: diplopia

3) CVS: tachycardia

4) Neurologic: tremulousness, weakness, paresthesias, stupor, seizure, or coma

5) Mental status: irritability, inability to concentrate, or short-term memory loss

6) Skin: pale, diaphoresis

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Management of Hypoglycaemia

Who should be evaluated?

• Only those patients in whom Whipple's triad is documented require evaluation and management of hypoglycemia.
• In patients with symptoms of hypoglycemia but normal plasma glucose concentrations at the same time, no further evaluation is needed.

Management of Hypoglycaemia

Clinical Evaluation

• The first step is to review the patient's history in detail, including the nature and timing of symptoms (particularly in relationship to meals), existence of underlying illnesses or conditions, surgical history ,medications taken by the individual and by family members, and social history.

Management of Hypoglycaemia

Clinical Evaluation

• In a patient with documented hypoglycemia, the cause may be apparent from the history and physical examination.
• In a seemingly well individual, the cause is less apparent and may be due to hyperinsulinism or factitious hypoglycemia.

Management of Hypoglycaemia

Laboratory Evaluation

1) Complete blood count

2) Glucose

3) Electrolytes and BUN/Cr

4) liver function tests, cortisol and thyroid levels , growth hormone level

5) Other tests: ECHO, ECG, CXR , CT and MRI

6)Important but not readily available to us: C-peptide, Beta-hydroxybutyrate, insulin, Proinsulin, Antibodies for insulin and its receptors .

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Management of Hypoglycaemia

Treatment approach

1. Acute intervention to prevent and minimize neurological damage.
2. Maintenance therapy to prevent recurrence of hypoglycemia.
3. Subsequent measures to search for and treat the underlying cause.

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Acute intervention to prevent and minimize neurological damage

• The treatment for all hypoglycaemia events is the administration of glucose.
• The route and amount of administration will depend on the glucose level as well as the patient’s level of consciousness and available access.

Acute intervention to prevent and minimize neurological damage

• Where possible an oral carbohydrate load should be administered urgently, followed by careful blood glucose monitoring.
• Consider the ‘rule of 15s’ during therapy (i.e. 15 g of carbohydrate will raise the glucose level about 15 mg/dl in about 15 minutes.

Acute intervention to prevent and minimize neurological damage

• In cases of impaired consciousness or an uncooperative patient, IV glucose infusion is used; 25-50 ml (i.e.12.5-25 g) 50% dextrose (D50) to be administered and is adequate in most circumstances.
• D50 is highly irritating and should be administered through a large gauge needle into a large vein if possible and followed by a saline flush.

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Acute intervention to prevent and minimize neurological damage

• Larger volumes of less concentrated dextrose in IV infusions (e.g. 250 ml of 10% dextrose [D10]) or 500mls of 5% dextrose may be used to minimize irritation.
• For inpatients with hypoglycaemia, D50 mixed with equal parts of water can also be given through a feeding tube if available.

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Acute intervention to prevent and minimize neurological damage

• If the patient has a history of malnutrition or chronic alcohol abuse, intravenous (IV) thiamine at a bolus dose of 12 mg/kg should be given before initiation of glucose treatment, to avoid precipitating Wernicke’s encephalopathy.

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Maintenance therapy

• The clinical response of hypoglycaemia to IV glucose administration is rapid and dramatic.
• Patients with hypoglycaemic coma are expected to regain consciousness and become coherent within 5-10 minutes.

Maintenance therapy

• However, complete cognitive recovery may be delayed for 30-60 minutes after restoration of normoglycaemia. If there is no obvious improvement in symptoms or consciousness within 10-15 minutes, alternative diagnoses (e.g. stroke or drug overdose) should be reconsidered.

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Subsequent Measures

• After initial stabilization, subsequent management should be directed at searching for the underlying etiology of hypoglycemia and preventing further attacks .
• Once the underlying cause is established, definitive therapy should be offered.
• Repeated hypoglycemia in an otherwise stable diabetic patient should alert the healthcare provider of the onset of nephropathy, concomitant Addison’s disease, hypothyroidism, hypopituitarism or interfering medications.

Treatment of Non-Diabetes Related Hypoglycemia

• Non diabetic hypoglycemia definitive management depends on the underlying etiology.
• Hypoglycemia induced by medications improves promptly once the medication is removed.
• Correction of sepsis and improvement in hepatic and renal function improves hypoglycemia of the critical illness.

Treatment of Non-Diabetes Related Hypoglycemia

• Deficiencies of counter regulatory hormones can be corrected with replacement of relevant hormone.
• Dietary changes are importance in the context of hyperinsulinaemic hypoglycemia, and the frequency and severity of episodes can be significantly reduced with frequent smaller volume meals.

PATIENT-CONSIDERATIONS

• Admission-Criteria

1) Any doubt of cause

2) Expectation of prolonged hypoglycemia (e.g., caused by sulfonylurea drug)

3) Inability to drink or eat

4) Treatment has not resulted in prompt sensory recovery.

5) Seizures, coma, or altered behavior (e.g., ataxia, disorientation, unstable motor coordination, dysphasia) secondary to documented or suspected hypoglycemia

6) Recurrent hypoglycemia during observation

• Discharge-Criteria

1. Normoglycemia and negligible risk of severe hypoglycemia

Complications/Differential Diagnosis of Hypoglycaemia

• Differential diagnosis
• Neurologic: CVA/TIA, seizure disorder
• Drug/alcohol intoxication
• Psychosis, depression
• Complications
• Recurrent/persistent psychosocial morbidity(Emotional liability , irritability, depression).
• Fear of hypoglycemia-barrier for diabetic control.
• Seizure
• Permanent neurologic deficit (including cognitive impairment)
• Coma and ultimately Death

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Algorithm for the management of Hypoglycaemia

Prevention of Hypoglycaemia

• Patient Education is Key: Patient to always have a fast-acting carbohydrate with you, such as juice or glucose tablets so that you can treat a falling blood sugar before it dips dangerously low.
• A continuous glucose monitor (CGM) is an option for some people, particularly those with hypoglycemia unawareness. These devices insert a tiny wire under the skin that can send blood glucose readings to a receiver. When blood sugar levels are dropping too low, some models of CGM will alert patients with an alarm.

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Prevention of Hypoglycaemia

• Some insulin pumps are now integrated with CGMs and can shut off insulin delivery when blood sugar levels are dropping too quickly to help prevent hypoglycemia.
• Eating frequent small meals throughout the day is a stop gap measure to help prevent blood sugar levels from getting too low in patients that are not diabetic.

Case study

• A. S., 28 year old Youth Corper, arrived in the accident and emergency room semiconscious. Her friends explained they had all been drinking alcohol at a party since early afternoon and that  30 minutes  ago A.S. had suddenly become very irritable and angry, just before she passed out.  One of her friends knew she was  a diabetic  and thought  she might need some medical  attention  A.S.  has  been on 22IU  Mixtard insulin daily for the last two years.

DISCUSSION QUESTIONS�

1.  Briefly explain the pathophysiology of hypoglycemia in A.S

2. What are the clinical manifestations  of hypoglycemia? Which did her friends  observe?

3.  What were the precipitating factors in this case?

4.  What effect does alcohol have on the blood glucose?

5.  What educational needs must be met for A.S. prior to her discharge?

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Conclusion……