H YPO G LYC E M IA

Divisi Endokrin-Metabolik
Departemen Ilmu Penyakit Dalam FK USU/
RSUP H Adam Malik Medan.

What is Hypoglycemia?
Hypoglycemia is an abnormally low
plasma glucose level that leads to symptoms
of sympathetic NS stimulation or of CNS
dysfunction.

The Merck Manual of Diagnosis and Therapy

Seventeenth Edition (1999)

Review of Blood Glucose control

Normal BG 60-100 mg/dL
Hypoglycemia: BG <50 mg/dL in men; <45
mg/dL in women
Important hormones:
Insulin, glucagon, epinephrine, cortisol, growth
hormone

PHYSIOLOGY OF GLUCOSE
COUNTERREGULATION
Characteristic sequence:
insulin secretion as glucose concentrations decline within the
physiological range (72108 mg/dl /4.06.0 mmol/l).
glucagon and epinephrine secretion, glucose concentrations fall
just below the physiological range (6570 mg/dl (3.63.9 mmol/l).
3. Neurogenic and neuroglycopenic symptoms, and cognitive
impairments in range (5055 mg/dl (2.8 3.0 mmol/l).

Liver glucose output responds to multiple hormonal signals

AntonioVidalPuig&StephenO'rahilly(2001)Nature413,125126.

Hypoglycemia Risk Factors

Missed or delayed meal

Eating less food at a meal than planned
Vigorous exercise without carbohydrate compensation
Taking too much diabetes medicine (e.g., insulin,
insulin secretagogues, and meglitinides)
Drinking alcohol

Causes
Fasting hypoglycemia
Result of a serious medical condition
Insulinomas (most are benign)*
Pancreatic tumors-secrete insulin
Other tumors (breast, cervix, adrenal glands)*
Secrete insulin-like growth factors (IGF)
Glucose production by liver inhibited; increased uptake in
peripheral tissues

Extensive liver disease

*Le Roith, Derek. (1999). Tumor-induced hypoglycemia. The New England Journal of Medicine,
341, 10.

Causes
Postprandial (reactive)
2-5 hrs after eating
Early insulin release with excess secretion in response to the
hyperglycemia

Alimentary
In patients w/GI procedures (gastrectomy, pyloroplasty,
gastrojejunostomy)

Idiopathic alimentary
RARE; over-diagnosed
Healthy young-adults
2-4 hrs after meal or after a missed meal

Various Causes
Alcoholic hypoglycemia
Ingestion of alcohol after a long fast

Factitious hypoglycemia
Insulin & sulfonylureas
Primarily in health care worker and relatives of
diabetics
Distribution of incorrect drugs to patients*
*Robinson, Irving, et. Al.
Family Practice, 38, 1.

(1994) Closet Hypoglycemia. Journal of

Hormones in the response to hypoglycemia:

(counterregulatory hormone)
1.
2.
3.

Glucagon (glycogenolysis and gluconeogenesis).

Epinephrine (glycogenolysis and gluconeogenesis and limits
glucose utilization)
growth hormone (reduce glucose utilization and support its
production).
Cortisol (reduce glucose utilization and support its production)

4.

play less important roles in the control of glucose flux during

normal physiologic circumstances, except in critically ill

Counter Regulation Respons to Hypoglycemia

Symptoms
BG level at which symptoms develop varies from person to person

Adrenergic
Sweating, trembling, anxiety, nausea, pallor, faintness,
palpitations, hunger
Neuroglycopenic (CNS manifestations)
Confusion, fatigue, difficulty speaking, headache, dizziness,
inability to concentrate, inappropriate behavior, stupor, coma

SYMPTOMS OF HYPOGLYCEMIA
Neurogenic (autonomic)
Neuroglycopenic
trembling
difficulty concentrating
palpitations
confusion
sweating
weakness
anxiety
drowsiness
hunger
vision changes
nausea
difficulty speaking
tingling
headache
dizziness
tiredness

Requirements for Diagnosis

Whipples Triad
Symptoms of hypoglycemia
Blood glucose levels <50 mg/dL in men or <45
mg/dL in women
Alleviation of symptoms after correction of the
low BG levels (ingestion of sugar)

Management of Hypoglycemia
Lifestyle:

5-6 small meals/day (CHO, PRO, FAT)

Spread out intake of CHO evenly (2-4/meal)
Avoid foods w/large amounts of CHO
Restrict/avoid coffee & alcohol
Decrease fat intake (moderate intake <30% of total kcal)
Moderate (upper range) PRO intake

Treatment
Two components:
Relief of symptoms by restoring blood glucose levels
within normal ranges
Correcting the underlying cause

Immediate:
Eat foods/beverages containing CHO
IV glucose may be required

TREATMENT
GOALS:
To detect and treat a low blood glucose level and provides a
rapid rise is blood glucose to a safe level
eliminating the risk of injury, and relieving symptoms
quickly.
15 g of glucose will usually increase blood glucose by
2.1 mmol/L within 20 minutes with adequate symptom
relief for most people.
20 g will usually increase blood glucose by 3.6 mmol/L
within 45 minutes.

TREATMENT
Mild to moderate hypoglycemia
15 g of oral carbohydrate (CHO), preferably as glucose or
sucrose tablets or solution. Retest blood glucose in 15 minutes;
repeat treatment if BG still < 4.0 mmol/L
Severe hypoglycemia, conscious
20 g of oral CHO (glucose tablets or equivalent); retest in 15
minutes, repeat treatment if BG still < 4.0 mmol/L
Severe hypoglycemia, unconscious adult
1 mg glucagon subcutaneously or intramuscularly or 10 to 25 g
of glucose intravenously (20 50 cc of D50W)

Preventing Hypoglycemia
If blood glucose is < 70 mg/dl, give 1520 g of quick-acting
carbohydrate (12 teaspoons of sugar or honey, 1/2 cup of regular
soda, 56 pieces of hard candy, glucose gel or tablets as directed,
or 1 cup of milk).
Test blood glucose 15 minutes after treatment. If it is still < 70
mg/dl, re-treat with 15 g of additional carbohydrate.
If blood glucose is not < 70 mg/dl but it is > 1 hour until the next
meal, have a snack with starch and protein (crackers and peanut
butter, crackers and cheese, half of a sandwich, or crackers and a
cup of milk).

HYPOGLYCEMIA
- RECOMMENDATIONS
In hospitalized patients, efforts must be made to ensure that
patients using insulin have ready access to an appropriate form
of glucose at all times, particularly when NPO or during
diagnostic procedures [Grade D, Consensus].
In adults, mild to moderate hypoglycemia should be treated by
the oral ingestion of 15 g of carbohydrate, preferably as
glucose or sucrose tablets or solution. These are preferable to
orange juice and glucose gels [Grade B, Level 2].
To wait 15 minutes, retest BG and retreat with another 15 g of
carbohydrate if BG level remains < 4.0 mmol/L. In smaller
children (< 5 years of age or < 20 kg), 10 g of carbohydrate
may be used initially [Grade D, Consensus].

HYPOGLYCEMIA
- RECOMMENDATIONS
Severe hypoglycemia in a conscious adult, should be treated by
the oral ingestion of 20 g of carbohydrate, preferably as glucose
tablets or equivalent. Patients should be encourage to wait 15
minutes, retest BG and retreat with another 15 g of glucose if the
BG level remains < 4.0 mmol/L [Grade D, Consensus].
Severe hypoglycemia in an unconscious individual 5 years of
age, in the home situation, should be treated with 1 mg of
glucagon subcutaneously or intramuscularly. In children < 5
years of age, a dose of 0.5 mg of glucagon should be given.
Caregivers or support persons should call for emergency services
and the episode should be discussed with the diabetes healthcare
team as soon as possible [Grade D, Consensus].

HYPOGLYCEMIA
- RECOMMENDATIONS
In the home situation, support persons should be taught
how to administer glucagon by injection [Grade D,
Consensus].
For severe hypoglycemia with unconsciousness in adults,
when intravenous (IV) access is available, glucose 10 to
25 g (20 to 50 cc of D50W) should be given over 1 to 3
minutes. The pediatric dose of glucose for IV treatment is
0.5 to 1 g/kg [Grade D, Consensus].

HYPOGLYCEMIA
- RECOMMENDATIONS
In hospitalized patients, a PRN order for glucagon should be
considered for any patient at risk for severe hypoglycemia (i.e.
requiring insulin and hospitalized for concurrent illness) when
IV access is not readily available [Grade D, Consensus].
To prevent repeated hypoglycemia, once the hypoglycemia has
been reversed, the person should have the usual meal or snack
that is due at that time of day. If a meal is > 1 hour away, a
snack (including 15 g of carbohydrate and a protein source) is
recommended in the absence of complicating factors [Grade
D, Consensus].

Conclusions
Hypoglycemia is rareshould not automatically
suspect it on basis of reported symptoms
Due to past over-diagnosis, Whipples Triad most
important determinant of hypoglycemia
In those with diagnosed hypoglycemia, serious
underlying medical conditions must be considered
Testing for medications in blood important in
ruling out insulinomas

HYPOGLYCEMIA IN DIABETES

CLINICAL RISK FACTORS FOR HYPOGLYCEMIA

IN DIABETES
Absolute or relative insulin excess occurs when
1. doses Insulin (or insulin secretagogue or sensitizer)
2. Exogenous glucose delivery.
3. Endogenous glucose production
4. Glucose utilization
5. Sensitivity to insulin
6. Insulin clearance

Sulfonylureas : hypoglycemic risk

RR
Tolbutamide

Gliclazide

1 - 2(2)

Repaglinide

1-2

Glipizide

2(1)

Glimepiride

3 - 4(3)

Glibenclamide

5(1)

1) Ferner 1988
(2) Teisse, Diab Med,1994
(3) Dills, Horm Metab Res,1996

Hypoglycemic risk

Glibenclamide has greatest risk for hypoglycemia (less so when

given 2-3 times a day in smaller portions)
Repaglinide (3 times a day) seems to have smallest risk, but needs
more confirmation on its efficacy in severe DM.
Although different receptor-binding explains this difference, the
small doses used is crucial.

HYPOGLYCEMIA-ASSOCIATED AUTONOMIC FAILURE

(1) counterregulatory hormone responses (type 1 diabetes)
- insulin levels do not decline as glucose levels fall (first
defense lost)
- glucagon response diminishes (the second defense lost)
- the epinephrine response reduced (third defense lost)
(2) hypoglycemia unawareness.
() a loss of the warning symptoms
() the first manifestation of hypoglycemia

Interventions
Mild
carbohydrate 10-15 gram
Moderate
20-30 gram of carbs
Glucagon, 1 mg SC or IM
Severe
50% dextrose 25 g IV
Glucagon 1 mg IM or IV

Somogyi Effect
Rebound hyperglycemia
Counterregulatory hormones activate
gluconeogenesis and glycogenolysis
Hormones supress insulin 12-48 hours
Also influenced by excessive carb intake

Somogyi Effect