HYPOGLYCAEMIA

Block 1 Posting
Department of Chemical Pathology

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Meditation
Daniel 4
• Now I Nebuchadnezzar praise and extol and honour the King of heaven, all
whose works are truth, and his ways judgment: and those that walk in pride
he is able to abase.

• Nebuchadnezzar possibly suffered from a form of insanity in which a man

thinks that he is an animal. It could have been lycanthropy, which is the
wolf-man syndrome, or boanthropy, in which a person thinks he/she is an
ox. A Babylonian cuneiform text, published in 1975, may refer to
Nebuchadnezzar's madness. The text states that the king gave contradictory
orders, refused to accept counsel, showed love neither to son nor daughter,
neglected his family, and no longer performed his duties as head of state.
(3rd quarter 2004 Sabbath school study guide)
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Introduction/Definition
• Hypoglycemia is one of the common metabolic problems in contemporary
medicine.

• Normal glucose requirement: 4-10mg/kg/min

• When plasma glucose concentration is less than the lower limit of the reference
interval.

• Normal plasma glucose concentration is 70-110mg/dL (3.9-6.1mmol/L) –adult.

• In newborn infant, 2.0mmol/L or less.

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Introduction/Definition
• Rapid decline in value → symptoms.

• Clinically defined by Whipple’s triad ;

> hypoglycemia,
>neuroglycopenic symptoms, and
>recovery on raising the blood glucose.

• It is a disease manifestation, not a diagnosis.

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 Hypoglycaemia is clinically
defined by Whipple’s triad
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Causes of hypoglycemia
1. Drugs
- insulin or insulin secretagogue
- alcohol
- others (salicylates, quinine, sulphonamide, ACEIs, quinolones)

2. Critical illness
- Hepatic, renal or cardiac failure
- sepsis

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Causes
3. Hormone deficiency
- cortisol
- glucagon and epinephrine
- hypopituitarism
it’s rarely their presenting manifestation.

4. Non-islet cell tumor

- hepatoma & retroperitoneal sarcoma- IGF-2
- breast, lymphomas, leukaemias.

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Causes
5. Endogenous hyperinsulinism
- insulinoma
- functional beta-cell disorders (nesidioblastosis)
- insulin autoimmune hypoglycemia
antibody to insulin- (AIS)
antibody to insulin receptor
- maternal DM, Beckwith-Wiedemann syndrome

6. Accidental, surreptitious or malicious hypoglycemia.

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Brain
• Completely dependent on blood glucose for energy production.
• Consumes about 2/3rd of glucose use in resting adult.
• Very low concentration (20-30mg/dL)- severe CNS dysfunction
• Can use ketone during prolong fasting
• Neuroglycopenia

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At Risk Baby
• Premature
• SGA, LGA
• BW < 2500g
• Smaller of discordant twins (wt diff. >25%)
• Asphyxiated infant (5 min APGAR <5)
• Infant of diabetic mothers
• Infants of massively obese mother
• Infant with polycythemia, infection

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Clinical features
Autonomic
Trembling
Palpitation
Sweating
Anxiety
Hunger
Nausea
Tingling

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Clinical features
• Neuroglycopenic
Difficulty in concentrating
Confusion
Drowsiness
Vision changes
Difficulty in speaking
Headache
Dizziness.
Tiredness

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Severity of hypoglycaemia
Mild
• Autonomic symptoms are present
• Individual is able to self-treat
Moderate
Autonomic and neuroglycopenic symptoms
Individual is able to self-treat
Severe (usually < 2.8mmol/L)
individual requires assistance, unconsciousness

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Investigation
• Measurement: plasma glucose estimation
• Fingerstick glucometer- within 15% accuracy.
• Neonatal blood sugar level much lower than adult’s.

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Investigation
• Exclude pseudo-hypoglycaemia from in vitro glucose metabolism.
• Evidence from the medical and drug history, clinical exam.
• Plasma C-peptide and plasma insulin.
>↑insulin and ↓C-peptide →exogenous insulin
>↑insulin and ↑C-peptide→ endogenous insulin production, drugs especially
sulphonylureas

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Investigation
• Negative drug screen & insulin autoantibody, with ↑ plasma insulin and C-
peptide(ratio <1) → insulinoma.

• ↓ insulin & C-peptide → ketotic /non-ketotic.

• Hypoinsulinaemia hypoglycaemia non-ketotic conc <600µmol/L→ IGF-1 activity

e.g non-islet cell tumor, liver & renal disease.

• Ketotic – (conc >600µmol/L) e.g hypopituitarism (↓plasma GH conc), adrenal

↓ & high alcohol intake.

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Treatment
• Depends on the severity; conscious level.
• 20mg of glucose tablets or glucose containing fluid.
≠ 15mg of glucose→↑ blood glucose by 2.1mmol/L within 20minutes with
adequate symptom relief
≠ 20g will → ↑ blood glucose by 3.6mmol/L within 45mins.

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Treatment

• Intravenous glucose (25mg) followed by maintenance.

• If I.V therapy is not possible, subcut or I.M glucagon (10mg) especially in
T1DM, less important in alcoholics or T2DM.
• These raise plasma glucose transiently, hence need for oral intake .

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Treatment
• In severe hypoglycemia with unconsciousness in adults, when IV
access is available, glucose 10-25g (20-50cc of D50W) should be given
over 1 -3mins.
• The pediatric dose of glucose for IV treatment is 0.5-1g/kg.
• Following recovery, identify a cause and treat.

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Prevention
• Requires an understanding of the hypoglycaemic mechanism:
>Drug- discontinued or ↓ doses; sulfonylurea
>Hormone deficiency : replacement
>Reduction of a non-Islet cell tumor.
>Insulinoma- surgical resection-curative.
medical- diazoxide (hypertrichosis)
- somatostatin (expensive, IM/IV)

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Prevention
• Non-tumor β-cell disorder
> Medical-dioxide or octreotide
> Surgical- partial pancreatectomy
• Autoimmune hypoglycemia: immunosuppressive drugs, self limiting.
• Health education
• Frequent feeding & avoidance of fast

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Hypoglycaemia in DM
• Impact and frequency
-limiting factor in the glycemic mgt of diabetes

-two episodes/week & at least a severe one/yr

-killed about 6-10% of people with T1DM.

-sulfonylurea, glinides or insulin ↑ risk

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Cont.
• Conventional risk factors
- insulin
-↓ exogenous glucose
-↑ glucose utilization
-↑ sensitivity to insulin
-↓ endogenous glucose production
-↓ insulin clearance

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Hypoglycaemia in DM
• Overtreatment – insulin, oral agents (SU)
• Missed meal, Excessive exercise (post medication)
• Autoimmune- insulin/receptor autoAb
• Hepatic dysfunction -
• Renal insufficiency
• Hypocortisolism (↓ insulin requirement)
• Drugs – B blocker, Alcohol - ↓gluconeogenesis, ↓glycogen store
• Autonomic neuropathy – gastroparesis delays gastric emptying
• Infants of diabetic mothers - ↑insulin
• Hypo unawareness - lack glucagon and epinephrine responses
• Lab error – no flouride
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Hypoglycaemia in DM
• RPG (<70mg/dl)
• Drug assay – insulin, SU, B blockers, alcohol
• Autoantibodies
• Liver FT
• Renal FT – E/U, Cr
• Cortisol (plasma, 24hr urinary)
• Autonomic neuropathy dynamic tests

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