INTERNAL MEDICINE II

CARBOHYDRATE METABOLISM 3: ACUTE COMPLICATIONS OF DIABETES EVALS 17

Hyperglycemia Crises & Hypoglycemia TRANS 18
Dr. Danica C. Francisco

B. SEVERE HYPERGLYCEMIA/HYPERGLYCEMIC CRISIS

TOPIC OUTLINE
● Diabetic Ketoacidosis (DKA) and the Hyperglycemic
I. Hyperglycemic Crises Hyperosmolar State (HHS) are the two most serious acute
A. Acute Complications: DM Type 1 and 2 metabolic complications of diabetes
B. Severe Hyperglycemia / Hyperglycemic Crisis ● DKA can be distinguished by the presence of
C. Clinical Features of DKA and HHS → METABOLIC ACIDOSIS
D. Precipitating Factors → INCREASED TOTAL BODY KETONE CONCENTRATIONS
E. Diabetic Ketoacidosis ● HHS is characterized by
F. Hyperglycemic Hyperosmolar State → HYPEROSMOLALITY
G. Laboratory Profile → DEHYDRATION IN THE ABSENCE OF SIGNIFICANT
H. Approach to Diagnosis KETOACIDOSIS.
I. Management ▪ The absence of significant keto acids does not always
J. Case equate to no keto acid at all. These patients may have
II. Hypoglycemia keto acids present but they are not considered significant.
A. Acute Complications: DM Type 1 and 2
C. CLINICAL FEATURES OF DKA AND HHS
B. Causes and Risk Factors
C. Levels of Hypoglycemia
Table 1. 🚩 Clinical Features of DKA and HHS.
DKA HHS
D. Mechanisms
Occurs in Type 1 and 2 DM Primarily in Type 2 DM
E. Clinical Presentation
F. Hypoglycemia-associated Autonomic Failure Usually develops in 24 hrs Usually symptomatic for
G. Approach and Management weeks
H. Prevention Nausea, vomiting, shortness Polyuria, poor oral intake,
of breath, abdominal pain weight loss →
📢 - Lecturer’s notes/Audio Inputs
LEGEND
resembling acute pancreatitis or confusion/lethargy/coma
📖 - From Book (cite sources)
IMPORTANT TERMINOLOGIES
ruptured viscus
📝 - From Old Transes 📌
Disclaimers/Transer’s notes
Tachycardia, dehydration, Tachycardia, profound
🚩 - Important 💡
- Undiscussed Sections
- Nice to Know fruity/acetone breath, dehydration, hypotension,
Kussmaul breathing, hyperosmolality, altered
The transcription follows the video lecture of Dr. Francisco
abdominal tenderness mental status.

I. HYPERGLYCEMIC CRISES ● DKA was formerly considered a hallmark of type 1 Diabetes, but
A. ACUTE COMPLICATIONS: DM TYPE 1 AND 2 now we know that this is wrong. Although this may be the initial
● As diabetes is fundamentally a play of sugar levels, there’s presentation of type 1, DKA can also occur in long standing
basically only two ways this can acutely go wrong, whether it’s type 2.
from TYPE 1 OR TYPE 2 DIABETES. Either glucose goes ● HHS, on the other hand, is primarily seen in individuals with
abnormally high or abnormally low. But it’s only in those TYPE 2 DM.
severely high and low glucose that we encounter life threatening ● Symptoms of DKA usually develop over 24 hours and these
complications such as: prominently include nausea, vomiting, shortness of breath,
● DIABETIC KETOACIDOSIS (DKA), as well as severe abdominal pain that may resemble acute
● HYPERGLYCEMIC HYPEROSMOLAR STATES (HHS), and pancreatitis or a surgical abdomen.
● SEVERE HYPOGLYCEMIA ASSOCIATED WITH ● While HHS usually presents with several days to weeks of
SIGNIFICANT COGNITIVE IMPAIRMENT among many other polyuria, weight loss, diminished oral intake that culminates
things. in mental confusion, lethargy or coma.
● As hyperglycemia leads to glucosuria and volume depletion,
both conditions exhibit different degrees of DEHYDRATION
TACHYCARDIA AND HYPOTENSION but these are MORE
PROMINENT WITH HHS.
● more distinguishing characteristics of DKA
→ FRUITY OR ACETONE BREATH
→ KUSSMAUL’S BREATHING,
▪ a deep and rapid type of breathing as seen in the video
(Timestamp: 2:48- 3:02).
● Triggering events for DKA and HHS are practically similar.

Figure 1. Acute Complications of Diabetes Type 1 and 2

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INTERNAL MEDICINE II CARBOHYDRATE METABOLISM 3: ACUTE COMPLICATIONS OF DIABETES - Hyperglycemia Crises & Hypoglycemia

● The body responds to metabolic starvation by INCREASING the

levels of these counterregulatory hormones:
→ GLUCAGON
→ EPINEPHRINE
→ CORTISOL
→ GROWTH HORMONES
● They work to produce more glucose in an attempt to supply
more energy to starving cells
● Both INSULIN DEFICIENCY AND GLUCAGON EXCESS, in
particular, are necessary for DKA to develop.
● The combination of insulin deficiency in hyperglycemia reduces
the hepatic level of Fructose-2,6-bisphosphate which alters the
activity of Phosphofructokinase and inhibits glycolysis.
● Glucagon excess on the other hand, decreases the activity
of pyruvate kinase, whereas insulin deficiency increases
the activity of phosphoenolpyruvate carboxykinase,
Figure 2. Kussmaul Breathing promoting gluconeogenesis.
D. PRECIPITATING FACTORS ● On top of this, insulin deficiency also reduces levels of the
Table 2. 🚩Precipitating factors for DKA and HHS GLUT4 glucose transporter which impairs glucose uptake into
skeletal muscle and fat.
DKA HHS
Infections (Pneumonia, UTI, AGE, ✓ ✓
sepsis)
Vascular disease/ event (MI, stroke, ✓ ✓
mesenteric infarction, peripheral
vascular disease)
Drugs (cocaine, corticosteroids, ✓ ✓
diuretics)
Pregnancy ✓ ✓
Relative insulin deficiency/ inadequate ✓ ✓
treatment
Absolute insulin deficiency ✓ X
● Any severe physiologic stress may precipitate either event.
These frequently include
● INFECTIONS,
● ISCHEMIC VASCULAR EVENTS
● DRUGS
● PREGNANCY
Figure 4. Mechanism of Diabetic Ketoacidosis
● INADEQUATE/ABSENT DIABETIC TREATMENT
● So these counterregulatory hormones increase glucose by
→ And here is one of the differences of DKA and HHS, both
breaking down glycogen and using non-carbohydrate
events may be triggered by inadequate insulin levels but
substrates such as proteins and lipids.
absolute or complete insulin deficiency can only lead to
● But since cells cannot use the glucose, this only results in
DKA.
MORE SUGAR IN THE BLOOD.
E. MECHANISM OF DIABETIC KETOACIDOSIS ● As blood sugar levels exceed the ability of the kidney to
reabsorb, it overflows into the urine, taking water and
electrolytes along with it in a process known as OSMOTIC
DIURESIS.
→ This results in large volumes of urine (polyuria),
dehydration, and excessive thirst (polydipsia).

Figure 3. Mechanism of Diabetic Ketoacidosis

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F. HYPERGLYCEMIC HYPEROSMOLAR STATE

Figure 5. Mechanism of Diabetic Ketoacidosis.

Figure 6. Hyperglycemic Hyperosmolar State
● Another action of counterregulatory hormones is the activation
● The main difference between Diabetic Ketoacidosis (DKA)
of lipolysis and fatty acid metabolism.
and Hyperglycemic Hyperosmolar State (HHS) is the
● Normally, these free fatty acids are converted to very low
ABSENCE OF ACIDOSIS IN HHS.
density lipoprotein (VLDL) in the liver.
→ Similar to DKA, the rise in counterregulatory hormones
● However, in DKA, high glucagon levels favor ketone body
further increases glucose into the blood. But this time, the
formation as an alternative energy source through activation of
level of insulin in HHS is high enough to suppress
Carnitine palmitoyltransferase 1.
lipolysis and ketogenesis.
→ Among these ketone bodies, ACETONE is the volatile
● This explains why HHS occurs more often in patients with
substance that gives the patient’s breath a
type 2 Diabetes because they still have varying levels of
CHARACTERISTIC SWEET SMELL.
circulating insulin.
→ As for ACETOACETATE, this is the one being detected in
→ So here, RELATIVE INSULIN DEFICIENCY and
the urine by a commonly used detection reagent,
INADEQUATE FLUID INTAKE are the underlying causes.
NITROPRUSSIDE.
→ And because of the absence of acidotic symptoms, its
▪ However, certain medications such as Captopril or
DEVELOPMENT MAY GO UNNOTICED until blood glucose
Penicillamine may cause false positive reactions.
levels become extremely high, even higher in those with
● On the other hand, Β-HYDROXYBUTYRATE is synthesized
DKA.
three times greater than acetoacetate and more accurately
● Because of this, concentration of solutes in the blood
reflects the true ketone body level. And so, serum or plasma
significantly raises its osmolality, promoting further osmotic
assay detection is much more preferred.
diuresis.
● KETONE BODIES, unlike fatty acids, can cross the blood
→ As a result, there is MORE SEVERE DEHYDRATION,
brain barrier and therefore, can serve as fuel for the brain
enough to cause hypotension and altered consciousness
during starvation.
due to cellular dysfunction of the brain tissues. This can
→ They are, however acidic and in large amounts, can
range from confusion to coma.
overwhelm the buffering capacity of the blood, resulting
in METABOLIC ACIDOSIS (pH<7.3). G. LABORATORY PROFILE
▪ As the body tries to reduce blood acidity by exhaling Table 3. Laboratory Profile of DKA and HHS
more carbon dioxide, a deep and labored breathing
known as KUSSMAUL BREATHING may result.
▪ Another compensation mechanism for high acidity moves
hydrogen ions into cells in exchange for potassium
which leads to HYPERKALEMIA. But as potassium is
excreted in the urine during osmotic diuresis, the overall
potassium in the body is eventually depleted.
− A blood test may show hyperkalemia, but once insulin
treatment starts, potassium moves back into cells and
hypokalemia may result instead.
− For this reason, BLOOD POTASSIUM LEVEL is
monitored throughout treatment.

● Now we know the mechanism, we can better understand the

laboratory profile of both conditions.

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● As mentioned, GLUCOSE in HHS patients tends to be much

higher than DKA.
● But in general, assessment of these acute complications
should already start once SEVERE HYPERGLYCEMIA > 250
mg/dL is noted.
→ There is only one exception to this: occasionally, DKA may
occur in minimally elevated or even normal glucose in a
condition called EUGLYCEMIC DKA and this has been
noted in patients treated with SGLT2 inhibitors.
● Among the electrolytes, SERUM SODIUM is notably reduced
in DKA as a consequence of hyperglycemia.
→ Please take note that FOR EVERY 100 mg/dL RISE IN
GLUCOSE, there is a 1.6 mEq/L REDUCTION OF SERUM
SODIUM.
→ So we always compute the CORRECTED SODIUM for
these patients using the following formula:
▪ Corrected Sodium = (RBS - 100) 0.016 + actual Na
− RBS is random blood sugar. Figure 7. Summary of Classic Features of DKA and HHS
→ A normal sodium in this setting indicates more ● As a summary of classic features, GLUCOSE is typically much
concentrated serum solutes due to profound water deficit, higher in HHS while SODIUM is usually lower in DKA.
as seen in HHS. ● AZOTEMIA may be worse in HHS because of more profound
● As we previously discussed, serum potassium at dehydration as exhibited by the very high osmolality
presentation may be elevated in DKA brought by the ● signs of significant KETONEMIA AND ACIDEMIA are more
extracellular shift induced by acidosis. prominent in DKA.
→ Nevertheless, TOTAL BODY STORES OF ALL THESE
H. APPROACH TO DIAGNOSIS
ELECTROLYTES ARE ACTUALLY REDUCED in both
● Further assess unstable patients with diabetes on SGLT2i or
conditions but are not accurately reflected because of
with plasma glucose of > 250 mg/dL.
dehydration and hyperglycemia.
● Determine:
● BUN, CREATININE, AND OSMOLALITY are all ELEVATED,
→ Electrolytes (K+, Na+, Mg+, Cl-, P)
reflecting the severity of intravascular volume depletion.
→ Acid-base status (pH, HCO3-, PCO2, serum ketones)
→ The serum osmolality counts as a vital information we
→ Assess renal function (creatinine, urine output)
compute for in these patients since it’s one of the major
● Compute:
distinguishing characteristics of HHS.
→ Corrected Na
▪ Serum Osmolality =
𝑔𝑙𝑢𝑐𝑜𝑠𝑒 (𝑚𝑔/𝑑𝐿) 𝐵𝑈𝑁
→ Serum osmolality
2 × (𝑁𝑎 + 𝐾) + 18
+ 2.8 → Anion gap
▪ Normal Serum Osmolality: 280 - 295 mmol/kg
I. MANAGEMENT
● ABUNDANT KETONES distinguish DKA from HHS, as well
● ADMIT TO INTENSIVE CARE
as ACIDOSIS WITH VERY LOW SODIUM BICARBONATE
● Replace fluids (HYDRATE)
LEVELS, and low arterial PCO2 as compensation for the
→ Due to patients having large water deficits, it is just as
acidosis.
important as insulin administration.
● When acid anions accumulate, such as acetoacetate and
● Administer SHORT-ACTING INSULIN through IV drip
lactate, the ANION GAP INCREASES and this explains why it
→ May be done simultaneously with fluid resuscitation.
is significantly higher in DKA than in HHS.
● Monitor glucose every 1-2 hours while on insulin drip
→ A COMPUTED ANION GAP (AG) OF MORE THAN 10-12
→ because the dose should be titrated frequently in order to
mEq/L indicates the presence of increased anion gap
achieve a stable decrease in sugar without
metabolic acidosis supporting a diagnosis of DKA.
hypoglycemia
→ Anion Gap = Na+ - Cl- + HCO3-
→ Monitor vital signs 1-4 hours depending on stability.
→ Increased AG if > 10-12 mEq/L
● Replace and regularly check SERUM K+ while on intensive
insulin therapy
● Do not give bicarbonate unless pH is < 6.9
● Investigate underlying cause/precipitating event and treat
appropriately

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J. CASE osmolality can be diagnosed with DIABETIC KETOACIDOSIS

● A 68-year-old Filipino male came in due to difficulty breathing.
He is a known diabetic with no regular check-up with his
doctor. He developed a cough and fever 2 days prior to
admission which was accompanied by decreased appetite and
generalized body weakness. Symptoms progressed to
drowsiness and difficulty breathing, hence he was brought to
the emergency room.
→ Physical exam: he was drowsy but arousable with
.
(DKA).
→ RBS 600 mg/dL, plasma ketones +1, HCO3 10 mEq/L, high
anion gap, and mildly elevated serum osmolality
→ HHS will not present with very low bicarbonate level and a
high anion gap.
→ Endocrine diagnosis: DIABETIC KETOACIDOSIS, TYPE 2
DIABETES MELLITUS, UNCONTROLLED
II. HYPOGLYCEMIA

kussmaul breathing A. ACUTE COMPLICATIONS: DM TYPE 1 AND 2

→ Vital signs: BP 160/90 mmHg, HR 110 bpm, RR 27 cpm, ● Hypoglycemia leads to severe cognitive impairment.
Temp 36.8 0C ● It is defined as PLASMA GLUCOSE LEVEL <70mg/dl (<3.9
→ Initial labs: mmol/l)
HbA1c = 12.5% Cl = 102 mEq/L ● It can be documented with the WHIPPLE’S TRIAD.
RBS = 600 mg/dL BUN = 16 mg/dL → (+) HYPOGLYCEMIC SYMPTOMS
Plasma ketones = +1 Crea = 163 umol/L → DOCUMENTED LOW PLASMA GLUCOSE
Na = 133 mmol/L HCO3 = 10 mEq/L → RESOLUTION OF SYMPTOMS AFTER PLASMA
K = 4.5 mmol/L
GLUCOSE IS RAISED
● 📢 The patient appears to be in distress with dyspnea and a ● Limiting factor in managing diabetes
decrease in sensorium. In the background of being known → We cannot give as many hypoglycemic agents as we
diabetic, we should ALWAYS RULE OUT ANY want even if sugar is very high due to the risk of causing
HYPERGLYCEMIC CRISIS. Note not only the symptoms, but repeated hypoglycemia.
also the time they appear. ● Take Note: HYPOGLYCEMIC EVENTS may also apply to
→ For this patient, it is very acute with only 2 days of patients with or without DM
development. B. CAUSES AND RISK FACTORS
● 📢 SEVERAL FEATURES OF DKA AND HHS MAY OVERLAP
in one patient. He has kussmaul breathing but is also
drowsy. He has extremely high sugars and positive plasma
ketones which both conditions may have.
● 📢 Without any pH given, the objective way of making a
complete diagnosis is to compute the missing data that we
need.
→ Compute for corrected Na, serum osmolality, anion gap.
● Initial sodium is low, but adjusted for hyperglycemia, we
now know that it is within the normal range and no additional
sodium correction should be given to the patient.
→ Corrected Na = actual Na + 0.016 (RBS - 100)
→ Corrected Na = 133 + 0.016 (600 - 100)
→ Corrected Na = 133 + 8
→ CORRECTED Na = 141 mmol/L
▪ Interpretation: normal
● Anion gap showed to be 21 mEq/L, which is very high in this
patient.
→ Anion Gap = actual Na - (Cl + HCO3)
→ Anion Gap = 133 - (102 + 10)
→ Anion Gap = 133 - 112
→ ANION GAP = 21 mEq/L Figure 8. Causes of Hypoglycemia
▪ Interpretation: high ● Drugs are by far the most common cause of hypoglycemia,
● In serum osmolality, the 305 mmol/kg is only slightly above and the most notorious of them are INSULINS,
normal. SULFONYLUREAS, AND GLINIDES. Other classes of drugs
→ Serum Osmolality = 2 Na + (RBS/18) + (BUN/2.8) don’t normally cause hypoglycemia, but they may, if combined
→ Serum Osmolality = 2 (133) + (600/18) + (16/2.8) with these.
→ Serum Osmolality = 266 + 33.3 + 5.7 ● Imbalances in homeostasis may also occur either by
→ SERUM OSMOLALITY = 305 mmol/kg significantly increasing glucose utilization such as in critical
▪ Interpretation: slightly high illness or decreasing glucose production with counter-regulatory
● This patient presenting with kussmaul breathing, high sugars, hormone deficiencies.
low bicarbonate level, high anion gap, and a slightly high ● Numbers 4 to 8 are rare including tumors and autoimmunity
which may or may not be seen in diabetics.

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Conventional Risk Factors (Patients with Diabetes)
● Insulin / insulin secretagogues are excessive, ill-timed or wrong
type
→ any errors in insulin administration (amount, time, type)
● Increased sensitivity to insulin (ie. increased fitness/glucose
control, weight loss)
→ augmented insulin action or duration
● Reduced insulin clearance (ie. renal failure)
→ augmented insulin action or duration
● Increased glucose utilization (ie. exercise, critical illness)
→ conditions of increased demand
● Reduced exogenous glucose (ie. fasting/missed meals)
→ with decreased oral intake
● Reduced endogenous glucose production (ie. alcohol ingestion)
C. LEVELS OF HYPOGLYCEMIA
● The BRAIN is incapable of synthesizing and storing energy
of more than a few minutes supply so it REQUIRES A
CONTINUOUS STREAM OF GLUCOSE to survive.
● Once glucose starts dropping, peripheral and central nervous
system sensors in the hypothalamus detect and activate a
sequence of responses to maintain the brain's energy supply
under stress or starvation.
● For any reason that the blood sugars go down there are two
clinically significant values to be aware of:
→ SUGARS < 70 mg/dL is termed LEVEL 1 HYPOGLYCEMIA
(alert level),
▪ which triggers the physiologic responses from
pancreas, adrenal gland, and pituitary gland including the
INCREASE IN THE COUNTERREGULATORY
HORMONES (glucagon, epinephrine, norepinephrine,
cortisol, growth hormone).
→ The NEUROGENIC/AUTONOMIC SIGNS AND SYMPTOMS
that may appear at this point are alerts to allow protection
against further decline in glucose.
Figure 9. Level 1 Hypoglycemia
→ LEVEL 2 HYPOGLYCEMIA (clinically significant) which is
<54 mg/dL is the threshold at which NEUROGLYCOPENIC
SYMPTOMS begin to appear as a direct result of CNS
glucose deprivation.
▪ This requires immediate action to resolve.
Figure 10. Level 2 Hypoglycemia
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● But at any level, where there is ALTERED MENTAL OR
PHYSICAL STATUS requiring assistance from others would
already be considered LEVEL 3 HYPOGLYCEMIA.
→ This level is strongly associated with risk of physical injury,
cardiovascular events, and death.
→ Therefore, level 3 severe events are markers of risk and
cover both more conservative glycemic management and
review of other aspects of care.
Figure 11. Level 3 Hypoglycemia
D. MECHANISMS
● Three main effects that will all end up to increase glucose
levels:
→ INCREASE IN GLYCOGENOLYSIS
→ INCREASE IN GLUCONEOGENESIS
→ DECREASE IN GLUCOSE UTILIZATION
● (1) As decrease in plasma level glucose reaches 80-85
mg/dL, the body responds first by decreasing insulin
secretion from pancreatic beta-cells, thereby INCREASING
HEPATIC GLYCOGENOLYSIS AND GLUCONEOGENESIS.
Figure 12. Hypoglycemia Mechanism (1)
● (2) As glucose levels decline just below the physiologic
range (65-70 mg/dL), counter-regulatory hormones are
released particularly pancreatic alpha-cell GLUCAGON and (3)
adrenal medullary EPINEPHRINE. Both stimulate hepatic
glycogenolysis and gluconeogenesis. But epinephrine has
additional actions of limiting peripheral glucose uptake and
stimulating lipolysis to produce glycerol and fatty acids for
gluconeogenesis.
→ Epinephrine becomes critical when glucagon is
deficient.
Figure 13. Hypoglycemia Mechanism (2) and (3)
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Figure 14. Hypoglycemia Mechanism (3)

● (4) When hypoglycemia is prolonged beyond 4 hours, Figure 17. Hypoglycemia Mechanism
cortisol and growth hormone also stimulate glucose
E. CLINICAL PRESENTATION
production and restrict glucose utilization but only by 20%
● Patients typically complain of HUNGER, WEAKNESS,
compared to epinephrine.
TREMORS, AND DIAPHORESIS.
→ So these play no role in defense against acute
● These sympathoadrenal manifestations serve as warnings and
hypoglycemia.
urge the person to intervene by ingesting food.
● More severe glucose deprivation now affecting the brain
would present with CONFUSION, BEHAVIORAL CHANGES,
SEIZURES, and may lead to DEATH.

Figure 15. Hypoglycemia Mechanism (4)

● (5) As glucose goes further down to LESS THAN 56 mg/dL,
more apparent symptoms and behavioral change is
triggered in order to stimulate intake of food or exogenous
Figure 18. Hypoglycemia Manifestations
glucose.
F. HYPOGLYCEMIA-ASSOCIATED AUTONOMIC FAILURE
● Although we know obvious excess of insulin and hypoglycemic
agents can cause hypoglycemia, it is also a consequence of the
interplay of therapy and physiologic defenses.
● Defective counterregulation and hypoglycemia
unawareness - both contribute to the development of
HYPOGLYCEMIA-ASSOCIATED AUTONOMIC FAILURE.

Figure 16. Hypoglycemia Mechanism (5)

● During these compensatory mechanisms, we note the
appearance of different signs and symptoms of
hypoglycemia, primarily mediated by EPINEPHRINE,
NOREPINEPHRINE, AND ACETYLCHOLINE.
Figure 19. Hypoglycemia-associated Autonomic Failure
● DEFECTIVE COUNTERREGULATION may occur in cases with
absolute endogenous insulin deficiency, such as type I DM.
→ The body’s first line of defense which is decreasing
insulin levels can no longer occur since there is no more
insulin to decrease. As a consequence, the trigger for
glucagon increase is lost as well.

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→ In long standing type 2 DM, although pancreatic alpha-cells
are still functioning, there is a signaling defect which
impairs the rising glucagon and the glycemic threshold
for neurogenic manifestations is lowered.
→ So, SYMPTOMS DO NOT OCCUR UNTIL BLOOD
SUGARS ARE ALREADY SEVERELY LOW.
● As for HYPOGLYCEMIC UNAWARENESS, repeated
hypoglycemic episodes eventually attenuates the
sympathoadrenal response. Therefore blunting the warning
signs for hypoglycemia and impairing behavioral defenses,
such as the urge to eat.
● Losing all these layers of defenses increases the risk of
patients for SEVERE IATROGENIC HYPOGLYCEMIA by 6x to
25x and creates a vicious cycle.
Figure 20. Defective Glucose Counterregulation and Hypoglycemia
Unawareness
form of carbohydrate that contains glucose can raise
blood sugars.
▪ A reasonable initial dose is 15-20g of glucose or
approximately equivalent to 1 tablespoon of sugar.
→ If incapacitated: IV GLUCOSE (25g) with serial infusion
and monitoring (guided by serial plasma glucose
measurements)
▪ 📢 If the patient is unable to drink or eat due to
neuroglycopenia of severe hypoglycemia, parenteral
therapy is necessary.
→ Other options:
▪ If IV therapy is not practical, GLUCAGON 1 mg SC OR
IM can be used, particularly in patients with T1DM
− But because it acts by stimulating glycogenolysis, this
is ineffective in glycogen-depleted individuals, like
those with alcohol-induced hypoglycemia.
▪ OCTREOTIDE (somatostatin analogue) – for suppression
of insulin secretion in Sulfonylurea-induced
hypoglycemia (SU-induced).
→ Afterwards, patients should be URGED TO EAT AS SOON
AS THEY ARE ABLE to prevent recurrent hypoglycemia →
CARBOHYDRATES WITH GLUCOSE is ideal food since
fats and proteins will not aid in the acute glycemic response.
▪ Fats may retard and prolong glycemic response
▪ Protein increases insulin response without lowering blood
glucose
H. PREVENTION

G. APPROACH AND MANAGEMENT

● 📢Management should not end there. Steps to prevent these
events must be taken.
● RECOGNITION AND DOCUMENTATION:
● EDUCATION
→ Fulfillment of Whipple’s triad -- convincing documentation
→ One of the most important is educating patients about their
requires the fulfillment of this triad.
disease and making sure they understand the common
→ Measure glucose
mechanisms of how hypoglycemia may occur in diabetes
▪ The ideal time to measure glucose levels is during a
▪ REGULAR SUGAR MONITORING – important for high
SYMPTOMATIC EPISODE
risk patients
▪ Hypoglycemia may still be diagnosed in the absence
▪ Proper time of medication and food intake
of symptoms, but must be put into context in relation to
▪ Effects of fasting, exercise and alcohol
the patient’s history and medical condition.
● RE-EVALUATION OF THERAPY
● INVESTIGATION OF CAUSE/MECHANISM:
→ For us physicians it is important to tailor the treatment for
→ Critical in selection of therapy to prevent or minimize
diabetes for each patient because no patients are exactly
recurrent hypoglycemia
alike
→ DRUGS, ALCOHOL, HYPOGLYCEMIC AGENTS
→ Appropriate type, dose and frequency
▪ Should be the first consideration even in the absence
● TREATMENT OF UNDERLYING OR CONCOMITANT
of known use of any drug, even the possibility of
ILLNESS
surreptitious, accidental, or malicious drug administration
→ Once other causes of hypoglycemia are identified, these
→ Others: evidence of a relevant critical Illness, hormone
must be resolved simultaneously with hypoglycemia
deficiencies, or tumors
treatment so as to avoid recurrence
→ When the cause of the hypoglycemic episode is obscure,
→ Hormone deficiencies
additional testing should include:
→ Acute infections or other disease stressors
▪ plasma insulin, C-peptide, proinsulin, B-hydroxybutyrate
● DIET MODIFICATION
levels and screening for circulating hypoglycemic agents
→ Ensuring a BALANCED DIET can definitely lower the risk for
● TREATMENT
hypoglycemia. Patients may be referred to nutritionists for
→ GLUCOSE-TABLETS/CANDIES/GLUCOSE-CONTAINING
more comprehensive guidance with their diet
FLUIDS/FOOD (15-20g glucose)
▪ 📢
For initial treatment, if the patient is able, then oral
→ Balance amount and composition of food

glucose in the form of candies, juices, or even table sugar

may be given. PURE GLUCOSE is preferred, but any

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INTERNAL MEDICINE II CARBOHYDRATE METABOLISM 3: ACUTE COMPLICATIONS OF DIABETES - Hyperglycemia Crises & Hypoglycemia

III. SUMMARY Case for #3-5: A 45-year old diabetic female was brought to
● HYPERGLYCEMIA results to diabetic ketoacidosis (DKA) and the ER due to dyspnea and abdominal pain. She is compliant
hyperglycemic hyperosmolar state (HHS). with her medications and has been doing intermittent fasting
● Clinical features of DKA: occur in type 1 and 2 DM, develop in for some time now in order to lose weight and help lower her
24 hrs, nausea, vomiting, shortness of breath, abdominal pain, blood sugars. She started complaining of epigastric pain the
tachycardia, dehydration, fruity breath, and kussmaul breathing. night before the consult. In the morning, the abdominal pain
● Clinical features of HHS: primarily type 2 DM, symptomatic for is now accompanied by vomiting and she started complaining
weeks, polyuria, poor oral intake, weight loss, confusion, of difficulty breathing.
lethargy, tachycardia, dehydration, hyperosmolality, and altered 3. Which of the following would be the most likely expected
mental status. finding in this patient?
● Laboratory profile of DKA: 125-135 mEq/L sodium, positive a. Low potassium
plasma ketones, < 15 mEq/L serum bicarbonate, 6.8-7.3 pH, b. Low CO2
20-30 mmHg arterial pCO2, and high anion gap. c. High sodium
● Laboratory profile of HHS: high glucose, high creatinine, and d. High HCO3-
high osmolality.
● Approach to diagnosis for hyperglycemic patients 4. If the patient was noted to have the following laboratory
→ Assess diabetic patients results, which among these medications could be the
→ Determine electrolytes, acid-base, renal function MOST likely to cause the patient’s symptoms?
→ Compute corrected sodium, serum osmolality anion gap
pH 6.8 K+: 3.2 mEq/L
● Management for hyperglycemic patients HCO3-: 7 Cl-: 105 mEq/L
→ Admit to intensive care serum ketones +3 Na+: 135 mEq/L
→ Rehydration blood sugar: 199 mg/dL BUN: 22 mg/dL
→ Administer short-acting insulin through IV drip
a. Gliclazide
→ Monitor glucose (1-2 hrs) and vital signs (1-4 hrs)
b. Dapagliflozin
→ Replace and check serum potassium
c. Metformin
→ Don’t give bicarbonate unless pH is < 6.9
d. Sitagliptin
→ Treat underlying cause
● HYPOGLYCEMIA results in severe cognitive impairment.
5. Given the case above, which of the following should not be
Defined as plasma glucose level of < 70 mg/dL.
given yet at this point on initial management?
● Levels of Hypoglycemia
a. Potassium
→ Level 1, Alert Level: < 70 mg/dL glucose
b. Insulin
→ Level 2, Clinically Significant: < 54 mg/dL glucose
c. Sodium bicarbonate
→ Level 3, Severe Hypoglycemia: severe altered mental status
d. IV fluids
● Clinical presentation of Hypoglycemia
→ Hunger, weakness, tremors, diaphoresis Answers: d, a, b, b, b
→ Confusion, behavioral changes, seizures
● Approach and management of hypoglycemia REFERENCES
→ Recognition and documentation ● Francisco, D. (2022). Carbohydrate Metabolism 3: Acute
→ Investigation of cause/mechanism Complications of Diabetes. Online Video Lecture.
→ Treatment
● Prevention
→ Education
→ Treatment of underlying or concomitant illness
→ Diet modification
REVIEW QUESTIONS (PAST-E 2022)
1. The processes that contribute to the formation of
hyperglycemic crises include:
a. Increased glycolysis
b. Decreased gluconeogenesis
c. Decreased glycogenolysis
d. Increased lipolysis

2. Which among these features would best point to a

hyperglycemic hyperosmolar state?
a. pH of 7.35
b. Serum bicarbonate level of 10 mEq/L
c. Plasma glucose of 250 mg/dL
d. Anion gap of 15 mEq/L

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