Ketosis-Prone Type 2 Diabetes Differential Diagnoses

Updated: Jan 20, 2023
  • Author: Richard S Krause, MD; Chief Editor: George T Griffing, MD  more...
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Diagnostic Considerations

The main differential diagnostic consideration when diabetic ketoacidosis (DKA) is considered is a hyperosmolar hyperglycemic state (HHS). The primary metabolic differences between HHS and DKA are the extreme elevations of glucose seen in HHS and the lack of significant ketoacidosis. Although overlap is observed in these conditions, glucose levels tend to be higher in HHS than in DKA: Levels of more than 1000 mg/dL are not uncommon in HHS, and they are almost always more than 600 mg/dL. In DKA, glucose levels are typically between 500 amd 800 mg/dL, and they seldom exceed 900 mg/dL.

Of greater differentiating values are acidosis and ketonemia. Metabolic acidosis is absent or mild with HHS and, if present, ketonemia is mild. Anion gap is normal or minimally elevated in HHS. In contrast, the triad of hyperglycemia, elevated anion gap acidosis, and ketonemia is expected in DKA.

Clinically, patients with HHS are much more likely to have altered mental status than patients with DKA. Altered mental status in HHS is related to the degree of effective plasma osmolality elevation. Effective plasma osmolality can be calculated using the formula below. Values of more than approximately 320 mOsm/kg are usually seen in HHS. Both DKA and HHS are known stroke mimics because they may be associated with focal neurologic findings. The formula is as follows:

  • Effective plasma osmolality (in mOsm/kg) = [2 × Na (mmol/L)] + glucose (mmol/L)

Another cause of ketoacidosis is alcoholic ketoacidosis: Ketoacidosis in an individual with alcohol use disorder who does not have significant hyperglycemia is diagnostic of this state, and it is seen in chronic alcoholism with malnutrition. In the right setting, toxic alcohol (eg, methanol, ethylene glycol) ingestion may be considered. Poisoning with toxic alcohols also causes an elevated anion gap metabolic acidosis with altered mental status. For additional discussion of toxic alcohol poisoning see Methanol Toxicity, Ethylene Glycol Toxicity.

Many other causes of metabolic acidosis are noted besides DKA and the other diagnoses discussed above. For a detailed discussion, see the Medscape Drugs & Diseases articles Metabolic Acidosis in Emergency Medicine, Metabolic Acidosis, and Pediatric Metabolic Acidosis.

The signs and symptoms of DKA can overlap with other illnesses. In the case of known diabetes, DKA should always be considered when the patient presents with a systemic illness. Patients not known to have diabetes can be more of a diagnostic challenge, especially when they present early before metabolic derangements are severe.

Hints that a presentation may represent new-onset DKA in type 2 diabetes include obesity and a strong family history of diabetes. If no other reason to obtain laboratory tests is suggested, a finger stick blood sugar can be used as a screening test.

Although euglycemic DKA occurs, it is unusual. It has been described in type 1 diabetes and also in patients with diabetes who are pregnant or who are experiencing starvation. For practical purposes, a normal or near-normal random blood sugar level rules out DKA. The renal threshold for glucose in healthy people is approximately 180 mg/dL. This varies, but new-onset DKA in ketosis-prone type 2 diabetes should show elevated levels of glucose and ketones on a urine dipstick test. Thus, a urine dipstick test can also be used at the bedside to rule out most cases of DKA.

Typical patients with DKA appear significantly ill, leading to suspicion of the diagnosis or at least a less directed laboratory investigation, which reveals the characteristic hyperglycemia with an elevated anion gap acidosis (see the Anion Gap calculator). In such a setting, DKA is confirmed by the finding of significant ketonemia.