Hyperglycemia

Question 1

Diabetes mellitus

Answer 1

Etiopatho
- Chronic metabolic disease characterized by
hyperglycemia as a cardinal biochemical feature

Question 2

Pathophysiology of DM

Answer 2

Pathophysio
- Insulin inhibits glycogenolysis, gluconeogenesis,
lipolysis and ketogenesis.
- Hunger in the midst of plenty: hyperglycemia without
cellular uptake of glu because of receptor resistance or
hyposensitivity.
- Reactivation of counterregulatory hormones (in order
of activation): glucagon –> epinephrine –> cortisol –>
GH
- Patient remains hyperglycemic despite poor oral intake
and increased losses because of counterregulatory
hormone effect, causing lipolysis and ketogenesis = net
effect is hyperglycemia, ketoacidosis, and
hyperthyroidisemia
- Kidney max glu 180mg/dL, beyond that result to
glucosuria resulting to polyuria and hypotension,
ketonuria

Question 3

Clinical manifestations of DM

Answer 3

CM
Mnemonic: 3P’s+weight loss/ 4T’s: Toilet, Thirsty, Tired, Thinner
1. Polydipsia, polyuria, nocturia
2. Unexplained weight loss
3. Glucosuria, ketonuria
4. Monilial vaginitis – among F with chronic glucosuria
5. Polyphagia/ Hyperphagia
6. BOV, mood changes, skin infections, oral thrush,
abdominal pain
7. Ketoacidosis

Question 4

Diagnostics

Answer 4

Impaired fasting glucose Tolerance
Fasting glucose: 100-125 mg/dl (5.6-7.0 mmol/L)
2-hr Plasma glucose (OGTT):
≥140mg/dL but <200 (≥7.8 mmol/L)
HBA1C: 5.7-6.4%

Diabetes Mellitus
≥126 mg/dL (7.0mmol/L)
2hr Plasma glucose (OGTT): ≥200 mg/dL (≥11.1mmol/L)
HBA1C: ≥6.5%
others: symptoms of DM + random blood glucose ≥200mg/dL (≥11mmol/L)

Question 5

Management

Answer 5

Mgt
1. Glycemic control – gycohemoglobin (HbA1c)
monitoring
- Reliable index of long-term glycemic control
- Reflects the ave blood glu concentration of the
preceding 2-3 months
- For known diabetics:
o 6-7.5%: good diabetic control
o 7.6-9.9%: fair
o >10%: poor

Question 6

Rapid acting

Answer 6

Aspart
Glulisine
Lispro

Question 7

Short acting

Answer 7

regular Humulin R

Question 8

Intermediate

Answer 8

NPH

Question 9

Long-acting

Answer 9

Detemir

Question 10

What is the “honeymoon period”?

Answer 10

reduced exogenous insulin needs shortly
after starting tx due to residual B-cell function. Usually fades
within a few months reflected as steady increase in insulin
requirements and wider glu excursions.

Question 11

What is the usual regimen?

Answer 11

Usual regimen:
- 4 injection regimen: basal bolus regimen at night that
is slow-onset, long duration for between mean glucose
control (glargine/detemir) (40-50% of total dose) +
rapid-onset insulin at each meal (Lispro/aspart) (50-
60% of total dose div by 3)
- 3 injection regimen: NPH + rapid analog bolus at
breakfast à rapid-acting bolus analog at supper à
glargine at bedtime
- Insulin pump therapy/ continuous SC insulin infusion
(CSII)

Question 12

Other medications for DM?

Answer 12

Metformin – insulin sensitizer; usual starting dose 500mg OD, may
be inc to 1500-2500mg/d BID-TID
- AE: GI disturbance, lactic acidosis. Avoid in hepatic or
renal impairment
Sulfonylureas – occasionally used when metformin monotx
unsuccessful or contraindicated
- 1st gen: Acetohexamide, Chlorpropamide, Tolbutamide
- 2nd gen: Glipizide, Glyburide, Glimepiride
2. To ensure N growth (height and weight)
- CHO counting: allows patients to adjust insulin dosage
to their mealtime CHO intake
- Exercise. WOF hypoglycemia post workout
3. To prevent acute complications – DKA, cerebral edema
4. To prevent long-term vascular complications –
retinopathy, nephropathy, CAD, CV ds, neuropathies
- Diabetic retinopathy: leading cause of blindness
- Diabetic nephropathy: leading known cause of ESRD
5. Refer to endo/multidisciplinary specialists (ophtha,
nephro, cardio, neuro)

Question 13

What is dawn phenomenon?

Answer 13

Elevated blood glu early morning before breakfast:
Dawn phenomenon – due to overnight GH secretion à inc insulin
clearance

Question 14

What is Somogyi phenomenon?

Answer 14

Somogyi phenomenon – theoretical rebound from late-night or
early-morning hypoglycemia (exaggerated counterregulatory
response)

Question 15

What is etiopathogenesis of DKA?

Answer 15

Etiopatho
- End result of metabolic abN due to severe deficiency of
insulin or severe insulin ineffectiveness
- Effects of insulin deficiency:
o Glu utilization by muscle and fat decreases
o Excess glu production via glycogenolysis and
gluconeogenesis –> leading to
hyperglycemia
o Resultant osmotic diuresis produces
polyuria, urinary losses of e’ and
dehydration
o Combination of insulin deficiency + elevated
counterregulatory hormones = accelerated
lipolysis and impaired lipid synthesis
o Increased plasma cholesterol and FFA –>
leads to ketone body formation
(acetoacetate & beta-hydroxybutyrate) à
resulting in metabolic acidosis

Question 16

What are the clinical manifestations of DKA?

Answer 16

CM
1. Abdominal discomfort or pain, nausea, emesis
2. Tachypnea, tachycardia
3. Fruity breath odor – from acetone
4. Kussmaul respiration – deep, heavy, nonlabored rapid
breathing
5. Dehydration with continuing polyuria
6. Diminished neurocognitive function, confusion,
drowsiness, possible coma
7. Progression of sx may be accelerated during
illness/trauma

Question 17

Diagnostics

Answer 17

Dx
Biochemical Criteria for DKA
a. Hyperglycemia blood glu >200 mg/dL or >11
mmol/L
b. Venous pH <7.3
c. serum bicarbonate <15mmol/L
d. Ketonemia (blood beta-hydroxybutyrate) >3
mmol/L or moderate/large ketonuria (>2+)
- All 4 criteria should be met
- Metabolic acidosis

Question 18

Classification of DKA

Answer 18

MILD
oriented, alert or fatigued
venous pH: 7.25-7.35
serum HCo3: 16-20 mEq/L

MODERATE
Kussmaul respiration, fruity breath odor, oriented by sleepy, arousable
venous pH: 7.15-7.25
serum HCO3: 10-15 mEq/L

SEVERE
Kussmaul or depressed respiration, sleepy to depressed sensorium, comatose
venous pH: <7.15
serum HCO3: <10 mEq/L

Question 19

Other diagnostics

Answer 19

1. Serum Hgt
2. VBG/ABG (pH, HCO3, PCO2) – metabolic acidosis
3. Serum Na, K, ketones
4. ECG/cardiac monitor – WOF peaked T waves, ST
   depression, widening QRS (hyperK), flattened T waves,
   arrhythmia, u waves (hypoK)
5. BUN, Crea, Osm
6. CBC – an elev WBC count in response to stress is
   characteristic of DKA and is not indicative of infection
7. HbA1c
8. Urine ketones

Question 20

Management

Answer 20

Mgt
1. Refer to Endo/PICU
2. Fluids
- 1st hr = Resuscitation fluids:
o If volume depleted but not in shock:
10mL/kg IV 0.9% PNSS over 30-60min (more
rapidly if with poor tissue perfusion)
o Shock: 20mL/kg isotonic saline boluses.
Additional bolus of 10ml/kg may be needed
to be administered cautiously 1-2x
o Shock must be adequately treated before
proceeding due to volume depletion
- Subsequent fluid mgt:
o 0.45% NaCl, 0.9% NaCl, or LR (depends on
hydration status, serum Na, and Osm)
o Give M fluid requirement + replace
estimated fluid deficit over 24-48h
§ 5-7% deficit in moderate DKA
§ 7-10% deficit in severe DKA
o Dehydration should be slowly corrected over 48h
3. 2nd hr = Mgt of hyperglycemia – insulin infusion
(human regular insulin 0.05-0.1 U/k/h) at least 1 h
after fluid replacement tx
- Addition of glucose to avoid hypoglycemia:
o 5% solution when blood glucose <300 mg/dl
o 10% solution when blood glu <200mg/dL
- When CBG <250mg/dL. May add 5% glu: change IVF to
D5NSS
- 100 mg/dl/h = target rate of insulin decrese
4. K replacement – if hypokalemic: start K replacement
before insulin tx
- If hyperkalemic: defer K replacement until UO
documented
- If N: start K replacement tx after initial volume
expansion, concurrent with insulin Tx
- 20-40 mmol K/L IVF
5. Bicarbonate Tx – rarely needed
- May increase risk of hypokalemia and cerebral edema
- Administer 1-2 mmol/kg over 60 min only if with:
o Life-threatening hyperkalemia
o Severe acidosis (venous pH <6.9)
6. Supportive Tx
- Mannitol: for cerebral edema
- Secure airway and continuous NGT suction to
decompress stomach
- Oxygen support for patients with circulatory
impairment or shock
- Hook to cardiac monitor: r/o hyper/hypokalemia
- Urinary catheterization prn
7. Monitoring – VS, neuro status, fluid I&O, CBG q1h or
more frequently prn
- E’ and ABG q2-4h or more frequently prn
- Q1 blood glu
- Q1 I&O
- Repeat e’s after start of IVF
8. Transition care – transition to oral intake and SC insulin
upon resolution of DKA:
a. HCO3 > 15 mEq/L
b. pH > 7.30
c. Na 135-145 mEq/L
d. No emesis

Question 21

What are the complications?

Answer 21

Complications
1. Cerebral edema – most dreaded complication of DKA
- Warning signs: headache and slowing of HR, change in
neurological status (restlessness, irritability, inc
drowsiness, incontinence), specific neurological signs
(CN palsy), rising BP, dec O2 sat
- Mgt: treat urgently
o Reduce rate of IVF by 1/3
o Mannitol 0.5-1 g/kg IV over 20 mins, repeat
if there is no initial response in 30min to 2h
o Hypertonic saline (3%) 5ml/kg over 30 min
as alternative tx
o Elevate head of bed by 30-45 degrees
o Intubation – impending respiratory distress
o Cranial CT scan – r/o other intracerebral causes of neuro deterioration: thrombosis, hemorrhages)
2. Hypoglycemia – due to overaggressive tx, or poor
monitoring
- Sweating, trembling, dizziness, mood changes, hunger,
headache, BOV, extreme tiredness, paleness, sz
- Mgt:
o Uncomplicated: immediate source of glu= juice/ milk
o Glucagon (n/a)
o Dextrose infusion (D50-50)