Yes, You Should Expect Ketones in Poorly Controlled Diabetes with Severe Hyperglycemia
In a patient with poorly controlled diabetes and severe hyperglycemia, you should expect positive ketones, as this presentation strongly suggests diabetic ketoacidosis (DKA), which is characterized by the triad of hyperglycemia (>250 mg/dL), metabolic acidosis, and elevated ketones. 1, 2
Why Ketones Are Expected
The pathophysiology directly explains ketone production in this scenario:
Insulin deficiency combined with elevated counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone) leads to unregulated lipolysis and release of free fatty acids, which are then converted to ketone bodies in the liver 1
Severe hyperglycemia itself indicates inadequate insulin action, creating the metabolic environment for ketogenesis 1
The combination of poor glycemic control and severe hyperglycemia represents the exact hormonal milieu that drives ketone production 1
Diagnostic Criteria Supporting Ketone Presence
According to American Diabetes Association guidelines, DKA diagnosis requires all three components 2, 3:
- Hyperglycemia: Plasma glucose >250 mg/dL (which your patient has)
- Metabolic acidosis: pH <7.3 AND bicarbonate <18 mEq/L
- Positive ketones: In blood or urine
Optimal Ketone Testing Method
Measure blood β-hydroxybutyrate (βOHB) specifically, NOT nitroprusside-based tests 1, 2:
- βOHB is the predominant ketone body in DKA and provides accurate diagnosis 1, 2
- Nitroprusside methods (urine dipsticks, serum tablets) only detect acetoacetate and acetone, missing βOHB entirely 1, 2
- During treatment, βOHB converts to acetoacetate, making nitroprusside tests falsely suggest worsening when the patient is actually improving 1, 2
Clinical Presentation to Anticipate
Beyond ketones, expect these findings in DKA 1, 3:
- Symptoms: Polyuria, polydipsia, weight loss, vomiting, abdominal pain, weakness
- Physical exam: Poor skin turgor, Kussmaul respirations (deep, labored breathing), tachycardia, hypotension, altered mental status
- Timeline: DKA typically evolves rapidly, usually within 24 hours 1, 3
Important Caveats
Euglycemic DKA Exception
Be aware that ketoacidosis can occur with normal glucose levels (<250 mg/dL), particularly with SGLT2 inhibitor use 2, 3:
- SGLT2 inhibitors significantly increase DKA risk and commonly cause euglycemic DKA 2
- Other causes include pregnancy, reduced food intake, alcohol use, and continued insulin with inadequate carbohydrate intake 3, 4
- In these cases, ketones are still present despite "normal" glucose 4
Differential Diagnosis
Distinguish DKA from other causes of ketosis 2, 5:
- Starvation ketosis: Less severe acidosis (bicarbonate usually not <18 mEq/L), normal to mildly elevated glucose 5
- Alcoholic ketoacidosis: Clinical history of alcohol use, glucose rarely >250 mg/dL or may be hypoglycemic 2, 3
- Both conditions will show positive ketones but lack the severe hyperglycemia typical of DKA 2, 5
Initial Laboratory Workup
When DKA is suspected based on poorly controlled diabetes and severe hyperglycemia, obtain 2, 3:
- Plasma glucose
- Arterial blood gas (pH, bicarbonate) or venous pH
- Serum electrolytes with calculated anion gap (expect >10-12 mEq/L)
- Blood βOHB (preferred) or serum/urine ketones
- Blood urea nitrogen/creatinine
- Complete blood count with differential
- Urinalysis
- Electrocardiogram
The bottom line: Severe hyperglycemia in poorly controlled diabetes creates the exact metabolic conditions for ketone production, making positive ketones highly expected and diagnostically significant for DKA. 1, 2, 3