(as house staff)
Matt Bouchonville
Endocrinology Division
Thursday School
July 25, 2013

+
=

↓ insulin
↓ glucose utilization
Hyperglycemia
↑ glucagon
↑ gluconeogenesis
↑ lipolysis
↑ ketone bodies
Ketosis
DKA
Acidosis

↓ insulin
↑ lipase
↑ glycerol ↑ FFA
↑ glucagon
↑ GH
↑ cortisol
↑ catecholamines
Adipocytes
Liver gluconeogenesis ketoacids
(acetoacetic acid, betahydroxy butyrate)

Absolute Insulin
Deficiency
↑ Counterregulatory
Hormones
Relative Insulin
Deficiency
↑ Ketoacidosis
DKA
HHS
Absent or minimal ketogenesis

2009: 140,000 admissions for DKA http://www.cdc.gov/diabetes
~10% of all diabetes-related admissions
Year

Year http://www.cdc.gov/diabetes
Year

• Mortality:
– Precipitating event-related
– DKA-related
• Hyperglycemia  osmotic diuresis  dehydration  shock
2006 – Overall mortality
• Acidosis  electrolyte imbalance  arrhythmias
 rate for DKA: 0.41% impaired cardiac contractility  shock
 vasodilation  shock http://www.cdc.gov/diabetes
Mortality (%)

• Diagnosis
• Management
• Common “Pitfalls”
• Clinical cases

Diabetes Care, Vol 32 (7)1335-1343, 2009

• Clinical presentation
• Polydipsia/polyuria
• Constitutional symptoms
• Nausea/vomiting
• Abdominal pain (40-75%)
• Altered sensorium
• Physical Exam
• Tachycardia
• Postural hypotension
• Kussmaul respirations
• Fruity breath
• Altered sensorium
• Abdominal tenderness

Diagnostic criteria
Laboratory Parameters
Serum glucose, mg/dL
Arterial pH
Bicarbonate, mEq/L
Ketones (urine, serum)
> 250
< 7.3
<18
+

Mild Moderate Severe
Laboratory Parameters
Serum glucose, mg/dL
Arterial pH
Bicarbonate, mEq/L
Ketones (urine, serum)
Anion gap
> 250 >250 >250
7.25-7.30
7.00-7.24
<7.00
15-18
+
↑
10-14
+
↑
<10
+
↑

Total Water, L
Serum n/a
Total body deficit
5-8
Laboratory Parameters
Na, mEq/kg
Cl, mEq/kg
K, mEq/kg
Phos, mEq/kg
Mg, mEq/kg
↓
(↑↔)
↑
(↓↔)
7-10
3-5
3-5
5-7
1-2
Ca, mEq/kg 1-2

Factors Precipitating DKA
Most Common
Infection (UTI, PNA)
Noncompliance
New-onset diabetes
Other
Myocardial infarction
Stroke
Trauma
Pregnancy
Pancreatitis
EtOH abuse
Medications

• Diagnosis
• Management
• Common “Pitfalls”
• Clinical cases

Assess need for
?
bicarbonate

Severe dehydration
IV Fluids
0.9% NaCl 1L/hr
Mild dehydration
Insulin corrected Na
Shock
Na high
0.45% NaCl
250-500 cc/hr
Na normal
Assess need for bicarbonate
Change to D5 0.45% NaCl
150-250 cc/hr when glucose reaches 200 mg/dL
Na low
0.9% NaCl 250-
500 cc/hr

If serum glucose does not fall by
50-70 mg/dL in first hour, double IV rate
Insulin
+/-
IV Bolus: 0.1
U/kg regular
IV Continuous infusion: 0.1
U/kg/hr
Target glucose: 150-200 mg/dL until DKA resolved
Serum glucose
↓ to 200 mg/dL: decrease IV rate to 0.05-0.1
U/kg/hr

Potassium
Establish adequate renal function (UOP
~50 cc/hr)
Serum K+ ≤ 3.3 mEq/L: Hold insulin
& give 20-30 mEq/hr
K+ until serum K+ >
3.3 mEq/L
Serum K+ 3.4-
5.2 mEq/L: Give
20-30 mEq K+ in each liter of
IV fluid to maintain serum
K+ 4-5 mEq/L
Serum K+ ≥ 5.3 mEq/L: Do not give K+ but check serum K+ every 2 hrs

Assess need for bicarbonate pH < 6.9
pH 6.9 - 7
Dilute NaHCO
3
(100 mmol) in 400 ml water with 20 mEq KCl.
Infuse 2 hr
Dilute NaHCO
3
(50 mmol) in 200 ml water with 10 mEq KCl.
Infuse 1 hr
Repeat NaHCO
3 infusion every 2 hr until pH > 7.0. Monitor K+ pH > 7.0
No HCO
3

• Serum glucose < 200 mg/dL
• pH < 7.3
• Anion gap < 14
• Serum bicarbonate ≥ 18 mEq/L
• Ready for transition to SQ insulin?
• Eating >50% meal?

• Total daily dose:
• Resume previous outpatient dose
• Insulin naïve (new diagnosis of T1D)
• Weight based or infusion rate derived ?
½ basal
• 0.5-0.8 units/kg/day
½ bolus
• Timing of SQ insulin dose?
1-2 hours before stopping IV insulin

• Diagnosis
• Management
• Common “Pitfalls”
• Clinical cases

• Hypoglycemia (10-25%)
• Hypokalemia
• Hyperchloremic (nongap) acidosis
• NaCl treatment
• Loss of substrate for bicarbonate regeneration
• Recurrent DKA
• Failure to overlap SQ insulin with IV insulin

• Cerebral edema
• Associated with rapid correction of serum osmolality
• 1% of children with DKA
• Reported in young adults
• Mortality 40-90%
• Clinical manifestations:
• Lethargy
• Seizures
• Bradycardia
• Respiratory arrest

• Diagnosis
• Management
• Common “Pitfalls”
• Clinical cases

• 34 yo F with T1D treated with glargine and humalog presents to ER in DKA. Which of the following antihypertensive medications may be precipitating her current presentation?
A) Lisinopril
B) HCTZ
C) Amlodipine
D) Losartan

• Medications which may precipitate DKA:
• HCTZ
• Beta blockers
• Steroids
• Phenytoin

• 56 yo obese M with T2D treated with metformin,
HTN treated with HCTZ, lisinopril brought in by
EMS. Obtunded and found to have the following labs:
• Gluc 286 mg/dL
• Creat 3.5 mg/dL
• Bicarb 8 mEq/L
• Anion gap 20
• Serum ketones neg

• What is the most likely cause of this patient’s presentation?
A) DKA
B) HCTZ use
C) Metformin use
D) Vitamin D deficiency

• Starvation ketosis
• Generally not hyperglycemic
• Alcoholic ketoacidosis
• Bicarb rarely < 18; generally not hyperglycemic
• Anion gap acidosis
• Lactic acidosis , salicylates, toxic alcohols

• 29 yo M presents to ER with abdominal pain, nausea, vomiting, weight loss, and polyuria. Found to be in DKA with likely new dx T1D. Hemodynamically stable.
Exam remarkable for abdominal tenderness, no peritoneal signs. Labs remarkable for an elevated serum amylase. What next step would be most appropriate to determine whether the patient has acute pancreatitis?
A) CT abdomen
B) Abdominal ultrasound
C) Serum lipase
D) Whipple procedure

• Serum amylase levels commonly elevated in patients with DKA (up to 80% cases)
• Lipase much less commonly elevated

• 17 yo F with T1D, poor compliance, admitted with
DKA. Treated with aggressive IV fluids, IV insulin.
Receives supplemental potassium, phosphate, and magnesium overnight. Presents with tetany in the morning. Which laboratory abnormality could explain this finding?
A) Serum potassium
B) Serum phosphate
C) Serum magnesium
D) Serum calcium

• Phosphate replacement:
• Prospective randomized studies have failed to show benefit in DKA outcomes
• Risk of severe hypocalcemia (younger patients)
• Not routinely recommended
• ADA: “Careful phosphate replacement may sometimes be indicated in patients with cardiac dysfunction, anemia, or respiratory depression and in those with a serum phosphate concentration of < 1.0 mg/dL ”

• 28 yo M with unknown medical history is brought in by EMS after being found down. The patient is obtunded and found to be in DKA. Serum glucose is 400 mg/dL, serum bicarbonate is 10 mEq/L, anion gap is 20, serum osmolality is 298, serum ketones are positive. Which answer most accurately describes his mental status?
A) It is likely related to the DKA and should improve with treatment
B) It is unlikely to be related to the DKA
C) Both, A & B are correct
D) Answer A

• ADA
:
• “The occurrence of stupor or coma in diabetic patients in the absence of definitive elevation of effective osmolality (320 mOsm/kg) demands immediate consideration of other causes of mental status change.”

• Diagnosis
• Management
• Common “Pitfalls”
• Clinical cases