Hypoglycemia

Causes by drugs used to treat diabetes mellitus or by

exposure to other drugs, including alcohol, critical organ
failure, sepsis and inanition, hormone deficiencies, non–
beta-cell tumors, insulinoma, and prior gastric surgery
DX of Hypoglycemia by Whipple's triad:
(1) Symptoms consistent with hypoglycemia,
(2) A low plasma glucose concentration and(less
than55mg/dl)
(3) Relief of those symptoms after the plasma glucose
level is raised.
The lower limit of the fasting plasma glucose
concentration is normally approximately 70 mg/dL.
It should be considered in any patient with episodes of
confusion, an altered level of consciousness, or a
seizure.
Systemic Glucose Balance and Glucose
Counterregulation
Plasma glucose concentrations are normally maintained
within a relatively narrow range, roughly 70–110 mg/dL.
Between meals and during fasting, plasma glucose levels
are maintained by endogenous glucose production,
hepatic glycogenolysis, and hepatic (and renal)
gluconeogenesis
hepatic glycogen stores are usually sufficient to maintain
plasma glucose levels for approximately 8 h

A decrease in insulin secretion is the first defense

against hypoglycemia.
Physiologic Responses to Decreasing Plasma Glucose
Concentrations
Insulin dec- Primary glucose regulatory factor/first
defense against hypoglycemia
Glucagon inc- Primary glucose counterregulatory
factor/second defense against hypoglycemia
Epinephrine de- Third defense against hypoglycemia,
critical when glucagon is deficient
Symptoms (50–55) -Recognition of hypoglycemia
-Prompt behavioral defense against hypoglycemia (food
ingestion)
Cognition -(<50) — (Compromises behavioral defense
against hypoglycemia)

When hypoglycemia is prolonged beyond 4 hours,

cortisol and growth hormone also support glucose
production and limit glucose utilization, albeit only 20%
of that of epinephrine.
Clinical Manifestations

Neuroglycopenic symptoms of hypoglycemia are the

direct result of central nervous system (CNS) glucose
deprivation. They include behavioral changes, confusion,
fatigue, seizure, loss of consciousness, and, if
hypoglycemia is severe and prolonged, death.
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.
They include adrenergic symptoms such as palpitations,
tremor, and anxiety.
They also include cholinergic symptoms such as
sweating, hunger, and paresthesias.
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.
Neuroglycopenic manifestations are often observable.
Transient focal neurologic deficits occur occasionally.
Permanent neurologic deficits are rare.

Etiology and Pathophysiology

Hypoglycemia is most commonly a result of the

treatment of diabetes.
Hypoglycemia in Diabetes

Impact and Frequency

Hypoglycemia is a fact of life for people with T1DM. They
suffer an average of two episodes of symptomatic
hypoglycemia per week and at least one episode of
severe, hypoglycemia each year.
An estimated 6–10% of people with T1DM die as a result
of hypoglycemia.
Metformin, thiazolidinediones, -glucosidase inhibitors,
glucagon-like peptide-1 (GLP-1) receptor agonists, and
dipeptidyl peptidase-IV (DPP-IV) inhibitors should not
cause hypoglycemia.
Conventional Risk Factors
Relative or absolute insulin excess occurs when:
(1) insulin doses are excessive, ill-timed, or of the wrong
type;
(2) the influx of exogenous glucose is reduced
(3) insulin-independent glucose utilization is increased
(4) sensitivity to insulin is increased
(5) endogenous glucose production is reduced
(6) insulin clearance is reduced (e.g., in renal failure).

Hypoglycemia-Associated Autonomic Failure

Defective glucose counterregulation compromises
physiologic defense, and hypoglycemia unawareness
compromises behavioral defense.
Defective Glucose Counterregulation
The first defense against hypoglycemia is lost.
Glucagon levels do not increase as plasma glucose levels
fall further; the second defense against hypoglycemia is
lost.

Hypoglycemia Unawareness

The attenuated sympathoadrenal response (largely the

reduced sympathetic neural response) to hypoglycemia
causes the clinical syndrome of hypoglycemia
unawareness, i.e., loss of the warning adrenergic and
cholinergic symptoms that previously allowed the patient
to recognize developing hypoglycemia and therefore
abort the episode by ingesting carbohydrates.
Affected patients are at a sixfold increased risk of severe
iatrogenic hypoglycemia during aggressive glycemic
therapy of their diabetes.

Hypoglycemia Risk Factor Reduction

The glycemic maintenance goals have been modified to
fall between 140 and 180 mg/dL.
Intensive glucose control can reduce the prevalence of
microvascular disease in both T1DM and T2DM.
Hypoglycemia Without Diabetes
It is reasonable to conclude that a hypoglycemic disorder
is present only in patients in whom Whipple's triad can
be demonstrated.
Focus should on medications, and then critical illnesses,
hormone deficiency, or nonislet cell tumor hypoglycemia.
In the absence of any of these and in a seemingly well
individual, the focus should shift to the possibilities of
endogenous hyperinsulinism
Drugs
Insulin and insulin secretagogues suppress glucose
production and stimulate glucose utilization.
Ethanol blocks gluconeogenesis but not glycogenolysis.
Critical Illness
Among hospitalized patients, serious illnesses such as
renal, hepatic, or cardiac failure, sepsis, and inanition are
second only to drugs as causes of hypoglycemia.
Rapid and extensive hepatic destruction (e.g., toxic
hepatitis) causes fasting hypoglycemia because the liver
is the major site of endogenous glucose production.
mechanism of hypoglycemia
cardiac failure is unknown. It may involve hepatic
congestion and hypoxia.
kidneys are a source of glucose production,
hypoglycemia in patients with renal failure is also caused
by the reduced clearance of insulin and reduced
mobilization of gluconeogenic precursors in renal failure.
Sepsis is a relatively common cause of hypoglycemia.
Increased glucose utilization is induced by cytokine
production
Hypoglycemia can be seen with starvation

Approach to the Patient: Hypoglycemia

Recognition and documentation, and often urgent
treatment, diagnosis of the hypoglycemic mechanism is
critical for choosing a treatment that prevents, or at least
minimizes, recurrent hypoglycemia.
Recognition and Documentation
Typical symptoms; in the presence of confusion, an
altered level of consciousness, or a seizure; or in a
clinical setting in which hypoglycemia is known to occur.
Blood should be drawn
Convincing documentation of hypoglycemia requires the
fulfillment of Whipple's triad. Thus, the ideal time to
measure the plasma glucose level is during a
symptomatic episode.
A normal glucose level excludes hypoglycemia as the
cause of the symptoms. A low glucose level confirms that
hypoglycemia is the cause of the symptoms, provided the
latter resolve after the glucose level is raised.

When the history suggests prior hypoglycemia, and a

potential mechanism is not apparent, the diagnostic
strategy is to measure these values, and assess for
Whipple's triad, during and after an episode of
hypoglycemia.

Urgent Treatment
Oral treatment with glucose tablets or glucose-
containing fluids, candy, or food is appropriate if the
patient is able and willing to take these. A reasonable
initial dose is 20 g of glucose
Intravenous glucose (25 g) should be given and followed
by a glucose infusion guided by serial plasma glucose
measurements. If intravenous therapy is not practical,
subcutaneous or intramuscular glucagon (1.0 mg in
adults) can be used, particularly in patients with T1DM.
Glucagon is ineffective in glycogen-depleted individuals
(e.g., those with alcohol-induced hypoglycemia).
Prevention of Recurrent Hypoglycemia
Prevention of recurrent hypoglycemia requires an
understanding of the hypoglycemic mechanism.
Offending drugs can be discontinued or their doses
reduced.
Underlying critical illnesses can often be treated.
Miesso(MD)