Differentiating Diabetic ketoacidosis from other diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Overview

Diabetic ketoacidosis (DKA) must be differentiated from other conditions presenting with hyperglycemia, ketosis and metabolic acidosis. The differentials include diabetes mellitus, non-ketotic hyperosmolar state, impaired glucose tolerance, ketotic hypoglycemia, alcoholic ketosis, starvation ketosis, lactic acidosis, salicylic acid ingestion, uremic acidosis and drug-induced acidosis. All these conditions may be differentiated on the basis of history findings, clinical features and laboratory abnormalities.

Differentiating Diabetic Ketoacidosis From Other Diseases

Diabetic ketoacidosis must be differentiated from other diseases causing the following conditions:^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]

Hyperglycemia
Ketosis
- Ketotic hypoglycemia
- Alcoholic ketosis
- Starvation ketosis
Metabolic acidosis
- Lactic acidosis
- Salicylic acid ingestion
- Uremic acidosis
- Drug-induced acidosis

**Schematic showing DKA as a confluence of hyperglycemia, ketosis and acidosis**

Characteristic Common to DKA	Condition	History Findings	Clinical Features	Lab abnormalities
Hyperglycemia	Diabetes mellitus	Family history of diabetes Obesity (BMI >25 kg/m2) Stress Sedentary lifestyle History of gestational diabetes Polycystic ovarian syndrome Acanthosis nigricans Hypertension (Blood pressure >140/90 mmHg)	Polyuria Polydipsia Polyphagia Weight loss Central obesity Autonomic and peripheral neuropathy Vascular occlusion secondary to atherosclerosis (Stroke, myocardial infarction) Renal impairment (microalbuminuria leading to renal failure) Decreased visual acuity (diabetic retinopathy) Increased susceptibility to infections Charcot's joints	Hyperglycemia: Fasting blood glucose level: >126 mg/dl Random blood glucose level: >200 mg/dl HbA1C: >6.5 % Urinanalysis may show: Proteinuria Glucosuria Positive antibodies:(Type 1 diabetes) Anti-glutamic acid decarboxylase Anti-islet cell Anti-insulin
	Non-ketotic hyperosmolar state	Elderly with type 2 diabetes mellitus Undiagnosed type 2 diabetes Prolonged hyperglycemia	May have all clinical features of diabetes mellitus plus: Hypotension Dehydration Tachycardia Decreased mentation Focal neurological abnormalities	Hyperglycemia (600-2000 mg/dl) Increased serum osmolarity (330-380 mOsm/kg) Arterial pH >7.3 Anion gap normal No ketosis
	Impaired glucose tolerance	Family history of diabetes Obesity (BMI >25 kg/m2) Stress Sedentary lifestyle History of gestational diabetes Acanthosis nigricans	May have all clinical features of diabetes mellitus	Hyperglycemia: Fasting blood glucose level: 100-125 mg/dl Oral glucose tolerance test: 140-200 mg/dl
Ketosis	Alcoholic ketosis	Non-diabetic chronic alcohol user Binge drinking history Fasting for 1-2 days after binge drinking	Nausea Vomiting Diffuse abdominal pain Dehydration Stress Anorexia	Serum glucose normal (only 10% with serum glucose >250 mg/dl) Serum bicarbonate < 18 mEq/L Arterial pH may show acidosis or may be alkalotic due to respiratory alkalosis Increased anion gap Acetoacetate and beta hydroxybutyrate elevated
Ketosis	Starvation ketosis	Several weeks of low caloric intake Malnourishment	Halitosis Dehydration Dry coated tongue Confusion Drowsiness Cold extremities Hypotension (postural or supine) Leg cramps	Serum glucose normal or hypoglycemia Serum bicarbonate > 18 mEq/L Arterial pH may show acidosis Increased anion gap
Metabolic acidosis	Lactic acidosis	Hypermetabolic states: Trauma Burns Sepsis Hypoxia Short bowel syndrome Jejuno-ileal bypass surgery Chronic pancreatic insufficiency Chronic renal insufficiency Large carbohydrate intake Carbon monoxide poisoning Drug intake: Cyanide Salicylates Biaguanides INH Anti-retroviral agents Valproic acid COPD Asthma Mesenteric ischemia	Neurological: Confusion Stupor Slurred speech Nausea Vomiting Warm extremities Dyspnea Cough Tachycardia Weakness Fatigue	Arterial pH <7.3 Increased anion gap Increased blood lactate
	Salicylic acid ingestion	Acute overdose: Young individuals or infants Intentional Suicidal Rapid progression of signs and symptoms Chronic overdose: Therapeutic misadventures Chronic pain disorders Acute lung injury	Early symptoms: Nausea Vomiting Anorexia Diaphoresis Tinnitus Hyperventilation Tachycardia Late symptoms: Drowsiness Fatigue Dizziness Confusion Delirium Hallucinations Seizures Hyperthermia	Mixed respiratory alkalosis and metabolic acidosis Increased anion gap Hyperkalemia Increased bleeding time, normal prothrombin time (PT) and activated partial thromboplastin time (aPTT)
	Uremic acidosis	Renal failure Pre-renal: Dehydration due to gastroenteritis, diarrhea, hemorrhage, hypovolemia, cardiac failure Renal: Hemolytic uremic syndrome, acute glomerulonephritis, renal necrosis, drugs, sepsis, shock Post-renal: Renal stones, renal tumors, posterior ureteric valves, renal trauma, renal vein thrombosis	Neurological: Delayed tendon reflexes Confusion Headache Seizures Peripheral neuropathy Uremic frost Uremic fetor Hypertension Osteomalacia Muscular weakness Cardiac arrythmias Gout (podagra) Kussmaul breathing Nausea Vomiting	Arterial pH < 7.3 Increased anion gap Hyperkalemia Hypocalcemia Hyperphosphatemia Secondary hyperparathyroidism Hyperuricemia Hypermagnesemia
	Drug-induced acidosis	Drug intake: Potassium sparing diuretics (amiloride, triamterene, spironolactone Trimethoprim Pentamidine ACE inhibitors ARBs NSAIDs Cyclosporine Tacrolimus Aspirin Amphotericin B Opiates Anaesthetics Phenobarbital	Neurological: Confusion Seizures Nausea Vomiting Chest discomfort Cardiac arrythmias Abdominal pain	Arterial pH < 7.3 Normal anion gap Increased hepatic transaminases (aspartate aminotrasnferase, alanine aminotransferase) Hyperkalemia (ACE inhibitors, ARBs, NSAIDs, trimethoprim, potassium sparing diuretics) Increased BUN, creatinine

Differentiating Diabetic Ketoacidosis from Hyperosmolar Hyperglycemia state


Parameters	Diabetic ketoacidosis (DKA)	Hyperosmolar hyperglycemic state (HHS)
Plasma glucose	> 250 mg/dl	> 600 mg/dl
Serum osmolality	Variable	> 320 mOsm/kg
Plasma and urine ketones	Positive	None or trace
Serum bicarbonate	< 18 mEq/L	> 15 mEq/ L
Arterial ph	< 7.30	> 7.30
Anion gap	> 12	< 12

Differential diagnosis of increased anion gap metabolic acidosis

Causes of increased anion gap metabolic acidosis can be differetiated from each other with the help of following alogrhythm:^[9]^[10]^[11]^[12]^[13]

↑ anion gap metabolic acidosis

↑ Lactate

Yes

No

Lactic acidosis

Check for hyperglycemia and ketonuria

Present

Not Present

Diabetic ketoacidosis

↑ BUN, ↑ creatinine and history of hemodyalysis

Yes

No

Uremic acidosis

Physical findings include odor of alcohol

Yes

No

↑ Ethanol level in serum or expired air

Auditory symptoms present

Ethanol overdose

Salicylic acid overdose

References

↑ "Diabetic Ketoacidosis: Evaluation and Treatment - American Family Physician".
↑ Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN (2009). "Hyperglycemic crises in adult patients with diabetes". Diabetes Care. 32 (7): 1335–43. doi:10.2337/dc09-9032. PMC 2699725. PMID 19564476.
↑ Chiasson JL, Aris-Jilwan N, Bélanger R, Bertrand S, Beauregard H, Ekoé JM, Fournier H, Havrankova J (2003). "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state". CMAJ. 168 (7): 859–66. PMC 151994. PMID 12668546.
↑ Joseph F, Anderson L, Goenka N, Vora J (2009). "Starvation-induced true diabetic euglycemic ketoacidosis in severe depression". J Gen Intern Med. 24 (1): 129–31. doi:10.1007/s11606-008-0829-0. PMC 2607495. PMID 18975036.
↑ Williams HE (1984). "Alcoholic hypoglycemia and ketoacidosis". Med. Clin. North Am. 68 (1): 33–8. PMID 6361416.
↑ Durnas C, Cusack BJ (1992). "Salicylate intoxication in the elderly. Recognition and recommendations on how to prevent it". Drugs Aging. 2 (1): 20–34. PMID 1554971.
↑ Gokel Y, Paydas S, Koseoglu Z, Alparslan N, Seydaoglu G (2000). "Comparison of blood gas and acid-base measurements in arterial and venous blood samples in patients with uremic acidosis and diabetic ketoacidosis in the emergency room". Am. J. Nephrol. 20 (4): 319–23. doi:10.1159/000013607. PMID 10970986.
↑ Brinkmann B, Fechner G, Karger B, DuChesne A (1998). "Ketoacidosis and lactic acidosis--frequent causes of death in chronic alcoholics?". Int. J. Legal Med. 111 (3): 115–9. PMID 9587792.
↑ Lim S (2007). "Metabolic acidosis". Acta Med Indones. 39 (3): 145–50. PMID 17936961.
↑ Kraut JA, Nagami GT (2013). "The serum anion gap in the evaluation of acid-base disorders: what are its limitations and can its effectiveness be improved?". Clin J Am Soc Nephrol. 8 (11): 2018–24. doi:10.2215/CJN.04040413. PMC 3817910. PMID 23833313.
↑ Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW (2013). "Etiology and therapeutic approach to elevated lactate levels". Mayo Clin. Proc. 88 (10): 1127–40. doi:10.1016/j.mayocp.2013.06.012. PMC 3975915. PMID 24079682.
↑ Abuelo JG, Shemin D, Chazan JA (1992). "Serum creatinine concentration at the onset of uremia: higher levels in black males". Clin. Nephrol. 37 (6): 303–7. PMID 1638782.
↑ Warnock DG (1988). "Uremic acidosis". Kidney Int. 34 (2): 278–87. PMID 3054224.

Template:WH Template:WS

[urlDiabetic_Ketoacidosis:_Evaluation_and_Treatment_-_American_Family_Physician-1] "Diabetic Ketoacidosis: Evaluation and Treatment - American Family Physician".

[pmid19564476-2] Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN (2009). "Hyperglycemic crises in adult patients with diabetes". Diabetes Care. 32 (7): 1335–43. doi:10.2337/dc09-9032. PMC 2699725. PMID 19564476.

[pmid12668546-3] Chiasson JL, Aris-Jilwan N, Bélanger R, Bertrand S, Beauregard H, Ekoé JM, Fournier H, Havrankova J (2003). "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state". CMAJ. 168 (7): 859–66. PMC 151994. PMID 12668546.

[pmid18975036-4] Joseph F, Anderson L, Goenka N, Vora J (2009). "Starvation-induced true diabetic euglycemic ketoacidosis in severe depression". J Gen Intern Med. 24 (1): 129–31. doi:10.1007/s11606-008-0829-0. PMC 2607495. PMID 18975036.

[pmid6361416-5] Williams HE (1984). "Alcoholic hypoglycemia and ketoacidosis". Med. Clin. North Am. 68 (1): 33–8. PMID 6361416.

[pmid1554971-6] Durnas C, Cusack BJ (1992). "Salicylate intoxication in the elderly. Recognition and recommendations on how to prevent it". Drugs Aging. 2 (1): 20–34. PMID 1554971.

[pmid10970986-7] Gokel Y, Paydas S, Koseoglu Z, Alparslan N, Seydaoglu G (2000). "Comparison of blood gas and acid-base measurements in arterial and venous blood samples in patients with uremic acidosis and diabetic ketoacidosis in the emergency room". Am. J. Nephrol. 20 (4): 319–23. doi:10.1159/000013607. PMID 10970986.

[pmid9587792-8] Brinkmann B, Fechner G, Karger B, DuChesne A (1998). "Ketoacidosis and lactic acidosis--frequent causes of death in chronic alcoholics?". Int. J. Legal Med. 111 (3): 115–9. PMID 9587792.

[pmid17936961-9] Lim S (2007). "Metabolic acidosis". Acta Med Indones. 39 (3): 145–50. PMID 17936961.

[pmid23833313-10] Kraut JA, Nagami GT (2013). "The serum anion gap in the evaluation of acid-base disorders: what are its limitations and can its effectiveness be improved?". Clin J Am Soc Nephrol. 8 (11): 2018–24. doi:10.2215/CJN.04040413. PMC 3817910. PMID 23833313.

[pmid24079682-11] Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW (2013). "Etiology and therapeutic approach to elevated lactate levels". Mayo Clin. Proc. 88 (10): 1127–40. doi:10.1016/j.mayocp.2013.06.012. PMC 3975915. PMID 24079682.

[pmid1638782-12] Abuelo JG, Shemin D, Chazan JA (1992). "Serum creatinine concentration at the onset of uremia: higher levels in black males". Clin. Nephrol. 37 (6): 303–7. PMID 1638782.

[pmid3054224-13] Warnock DG (1988). "Uremic acidosis". Kidney Int. 34 (2): 278–87. PMID 3054224.

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