Severe hyperglycemia with profound hyperosmolarity and dehydration but minimal ketoacidosis.
Also known as: HHS, hyperosmolar hyperglycemic state, HHNK, hyperosmolar nonketotic coma, HONK
Overview
Acute decompensation of diabetes characterized by severe hyperglycemia (≥600 mg/dL), hyperosmolality (calculated effective osmolality >300 mOsm/kg or total serum osmolality >320 mOsm/kg), and profound dehydration, without significant ketoacidosis (beta-hydroxybutyrate <3.0 mmol/L, pH ≥7.30, bicarbonate ≥15). Altered mental status is typical but is not required for the diagnosis.
Epidemiology
Less common than DKA (~1% of diabetes-related admissions) but mortality is higher (about 5% in hospital series vs about 1-3% for DKA, and about 8% in mixed DKA/HHS), reflecting older age and comorbidities. Most patients are >65 with T2DM, often with cognitive impairment or limited access to fluids.
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Question 1EndocrineMedium
A 68-year-old male with type 2 diabetes (HbA1c 11.2%) presents with polyuria, polydipsia, and confusion. Glucose is 892 mg/dL. Serum osmolality is 348 mOsm/kg. Sodium is 132 mEq/L (corrected 144). pH is 7.36, bicarbonate 22. Ketones are trace. Which of the following is the most likely diagnosis?
ASevere dehydration with stress hyperglycemia
BMetformin-associated lactic acidosis
CMixed diabetic ketoacidosis and hyperosmolar state
DDiabetic ketoacidosis
EHyperosmolar hyperglycemic state
Reveal answer & full explanation
Correct answer: E — Hyperosmolar hyperglycemic state
ASevere dehydration with stress hyperglycemia
BMetformin-associated lactic acidosis
CMixed diabetic ketoacidosis and hyperosmolar state
DDiabetic ketoacidosis
EHyperosmolar hyperglycemic state✓
Why Hyperosmolar hyperglycemic state is correct
Hyperosmolar hyperglycemic state (HHS) occurs predominantly in elderly patients with type 2 diabetes mellitus (T2DM).
Diagnostic features: glucose above 600 mg/dL (often 800-1000+), total serum osmolality above 320 mOsm/kg (or calculated effective osmolality above 300 mOsm/kg), minimal ketosis (residual endogenous insulin prevents lipolysis, distinguishing HHS from diabetic ketoacidosis (DKA)), and altered mental status proportional to osmolality.
This patient has glucose 892 mg/dL, osmolality 348 mOsm/kg, pH 7.36, bicarbonate 22, and only trace ketones — all consistent with HHS rather than DKA.
Corrected sodium = measured sodium + 1.6 per 100 mg/dL glucose above 100 (corrected sodium here is 144).
Why the others are wrong
Mixed diabetic ketoacidosis and hyperosmolar state — An overlap presentation still requires the ketoacidotic component (pH below 7.3, bicarbonate 18 mEq/L or less, significant ketonemia); this patient's pH of 7.36, bicarbonate of 22, and trace ketones exclude any acidotic component (confused-with overlap syndrome).
Diabetic ketoacidosis — Defined by significant ketonemia/ketonuria, anion-gap metabolic acidosis, and pH below 7.3; this patient's pH is 7.36, bicarbonate is 22, and ketones are only trace (anchoring).
Severe dehydration with stress hyperglycemia — Does not account for glucose this extreme or an osmolality of 348 mOsm/kg in a known diabetic (premature closure).
Metformin-associated lactic acidosis — an older patient with poorly controlled type 2 diabetes is often taking metformin, and volume depletion from osmotic diuresis can impair its renal clearance, but this complication is a high-anion-gap metabolic acidosis, whereas his pH is 7.36 and bicarbonate is 22; metformin also lowers rather than raises glucose, so it cannot account for a glucose of 892 mg/dL and an osmolality of 348 mOsm/kg (confused-with drug-induced acidosis)
Additional high-yield points
Treatment: (1) IV fluids first — isotonic saline or a balanced crystalloid at 500-1000 mL/h for the first 2-4 h, then titrated to hemodynamics; 0.45% saline only if osmolality is not falling despite adequate fluids and insulin; total fluid deficit is 8-10 L. (2) Insulin 0.05 U/kg/h (0.1 U/kg/h if mixed DKA/HHS) ONLY after fluids are under way and potassium is above 3.5 mEq/L — starting insulin first worsens hypovolemia and hypokalemia. (3) Replace potassium if below 5.0. (4) Identify the precipitant: infection (most common), myocardial infarction (MI), stroke, nonadherence.
Question 2EndocrineMedium
A 71-year-old woman is being treated in the intensive care unit for hyperosmolar hyperglycemic state precipitated by pneumonia. Over 9 hours she has received 6 L of intravenous fluid, starting with 0.9% saline and changing to 0.45% saline when her effective osmolality stopped falling despite adequate fluid balance and insulin, and she is now on 0.45% saline at 500 mL/h with 20 mEq/L of potassium chloride and a regular insulin infusion at 0.1 units/kg per hour. Blood pressure is 122/76 mm Hg and urine output is adequate. Potassium is 4.2 mEq/L, sodium is 153 mEq/L, glucose has fallen from 880 mg/dL to 238 mg/dL, and effective serum osmolality is 319 mOsm/kg. She remains drowsy and oriented only to person, unchanged from admission. Which of the following is the most appropriate next step in management?
AGive intravenous mannitol for suspected cerebral edema
BContinue the current orders until the glucose is below 200 mg/dL
CDouble the intravenous fluid rate to bring the osmolality down faster
DAdd dextrose to the fluids now and reduce the insulin infusion rate
EStop the insulin infusion and start subcutaneous basal-bolus dosing
Reveal answer & full explanation
Correct answer: D — Add dextrose to the fluids now and reduce the insulin infusion rate
AGive intravenous mannitol for suspected cerebral edema
BContinue the current orders until the glucose is below 200 mg/dL
CDouble the intravenous fluid rate to bring the osmolality down faster
DAdd dextrose to the fluids now and reduce the insulin infusion rate✓
EStop the insulin infusion and start subcutaneous basal-bolus dosing
Why Add dextrose to the fluids now and reduce the insulin infusion rate is correct
In hyperosmolar hyperglycemic state (HHS) the insulin drip is not titrated toward a normal glucose; once glucose falls below 250 mg/dL you add 5-10% dextrose to the intravenous fluid and reduce insulin to 0.05 units/kg per hour, holding glucose at 200-250 mg/dL until the hyperosmolar state resolves (2024 ADA/EASD hyperglycemic-crises consensus).
Her glucose is 238 mg/dL, so she has crossed that threshold, and the dextrose is what makes continued insulin safe: it prevents hypoglycemia while low-dose insulin keeps suppressing hepatic glucose output and lipolysis as the osmolality is brought down slowly.
The crisis itself has not resolved - effective osmolality is still 319 mOsm/kg (2(153) + 238/18) and she is drowsy and unchanged from admission - so low-dose insulin must continue rather than stop.
The prerequisites for that decision are already satisfied: 6 L of fluid is in, blood pressure and urine output are adequate, and potassium is 4.2 mEq/L with 20 mEq/L of potassium chloride running, so the only remaining question is how to run the insulin.
Her glucose fell about 71 mg/dL per hour, inside the 90-120 mg/dL per hour ceiling the 2024 consensus sets for HHS, and effective osmolality should fall no faster than 3-8 mOsm/kg per hour; nothing about the speed of the fall forces a change in orders, the 250 mg/dL dextrose threshold does.
Why the others are wrong
Continue the current orders until the glucose is below 200 mg/dL - she has already reached the 250 mg/dL trigger at which the 2024 consensus says to add 5-10% dextrose and cut insulin to 0.05 units/kg per hour, and 200 mg/dL sits below the 200-250 mg/dL range HHS glucose should be held in until the hyperosmolality clears; running 0.1 units/kg per hour with no dextrose down to 200 mg/dL courts hypoglycemia and pulls effective osmolality down faster than the brain has adapted to, long before the sensorium clears (the trap is carrying the old DKA number into HHS, when the 2024 consensus uses one dextrose threshold for both).
Double the intravenous fluid rate to bring the osmolality down faster - the intravascular deficit is already repaired (blood pressure 122/76 mm Hg, adequate urine output), and speed is not the goal: effective osmolality should fall no faster than 3-8 mOsm/kg per hour and sodium by no more than 10 mEq/L in 24 hours, so doubling the free water risks pushing the correction past those limits and shifting water into brain cells, while doing nothing about the glucose that has already crossed the dextrose threshold (the trap is chasing the osmolality number instead of following the insulin rule).
Stop the insulin infusion and start subcutaneous basal-bolus dosing - the transition waits until HHS has resolved and the patient is eating and drinking, and the first subcutaneous dose must overlap the drip by 1-2 hours; with effective osmolality 319 mOsm/kg and persistent drowsiness she has not resolved, and switching now produces rebound hyperglycemia (the trap is reading a normalizing glucose as a resolved crisis).
Give intravenous mannitol for suspected cerebral edema - her persistent drowsiness invites treating the brain, but it is unchanged from admission and fits a hyperosmolar state that has not yet cleared, with effective osmolality still 319 mOsm/kg; cerebral edema is rare in adults with HHS and shows itself as a new decline in consciousness, headache, or bradycardia with rising blood pressure during treatment, none of which has happened, and mannitol does nothing about the glucose that has crossed the dextrose threshold (the trap is reading slow-to-clear obtundation as a complication of therapy).
Additional high-yield points
The 2024 consensus unified the dextrose trigger at a glucose below 250 mg/dL for both DKA and HHS, retiring the 2009 split of 200 mg/dL in DKA and 300 mg/dL in HHS; what still differs by crisis is the glucose to hold until resolution - 150-200 mg/dL in DKA versus 200-250 mg/dL in HHS.
HHS is resolved when effective (calculated) osmolality falls below 300 mOsm/kg, glucose is below 250 mg/dL, urine output is above 0.5 mL/kg per hour, and cognition has improved; the older criteria used an osmolality of about 315 mOsm/kg with a return to mental baseline. A falling glucose by itself is not resolution.
DKA resolution is instead judged by closure of the ketoacidosis: beta-hydroxybutyrate below 0.6 mmol/L with a venous pH of 7.30 or above or a bicarbonate of 18 mEq/L or above. The 2024 consensus dropped the anion gap as a resolution criterion, because the large volumes of saline given in treatment create a hyperchloremic normal-gap acidosis, and dropped urine ketones, because beta-hydroxybutyrate converts to acetoacetate as the acidosis clears; the older criteria were glucose below 200 mg/dL plus two of bicarbonate 15 mEq/L or above, pH above 7.30, and an anion gap of 12 mEq/L or less.
Total water deficit in HHS is 8-10 L; start isotonic saline or a balanced crystalloid at 500-1000 mL/h for the first 2-4 hours, then set the rate by blood pressure, heart rate, fluid balance and sodium, replacing about half the deficit in the first 8-12 hours and the rest over 24-48 hours. A rising sodium as glucose falls is expected (roughly 1.6 mEq/L for every 100 mg/dL the glucose drops) and is not by itself an indication for hypotonic fluid; the 2024 consensus reserves 0.45% saline for the case where osmolality is not falling despite adequate positive fluid balance and appropriate insulin.
The 2024 consensus starts the fixed-rate insulin infusion at 0.05 units/kg per hour in HHS without significant ketosis and at 0.1 units/kg per hour in DKA or in mixed DKA/HHS; this patient is running 0.1 units/kg per hour, so the reduction at the dextrose threshold takes her to 0.05 units/kg per hour.
Insulin is withheld entirely until potassium is above 3.5 mEq/L in the 2024 consensus (3.3 mEq/L in the older criteria), and 10-20 mEq of potassium chloride per liter of fluid then keeps potassium between 4 and 5 mEq/L; insulin drives potassium into cells and can otherwise precipitate fatal hypokalemia.
Treat the precipitant (pneumonia, urinary infection, myocardial infarction, stroke, nonadherence) and give prophylactic-dose low-molecular-weight heparin; inpatient mortality runs about 5% in HHS and 3% in DKA, and is highest in mixed DKA/HHS at about 8%.
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Medications: thiazides, glucocorticoids, atypical antipsychotics, total parenteral nutrition
Newly diagnosed T2DM, medication non-adherence
Restricted access to water (institutionalized, post-stroke, debilitated)
Pathophysiology
Relative insulin deficiency permits hyperglycemia and hepatic glucose output but is sufficient to suppress hepatic ketogenesis. Sustained osmotic diuresis produces profound water and electrolyte losses (free water deficit 8-12 L). Hyperosmolarity draws water from intracellular compartments, including neurons, producing altered mentation, seizures, and coma.
Clinical presentation
Symptoms
Insidious onset over days to weeks (vs hours in DKA)
Polyuria, polydipsia, then progressive lethargy as dehydration worsens
Weakness, weight loss, decreased oral intake
Altered mental status: confusion → stupor → coma
Focal neurologic deficits, seizures (10-15%) — can mimic stroke
Stroke or intracranial event — Focal neurologic deficits persisting after metabolic correction; obtain CT/MRI
Diabetes insipidus with hyperglycemia — Hypernatremia with dilute urine; rare overlap
Toxic ingestion — Salicylates, lithium toxicity can cause altered mentation and metabolic derangement
Diagnostic workup
Diagnostic criteria
2024 ADA/EASD consensus (all four required): glucose ≥600 mg/dL; calculated effective osmolality >300 mOsm/kg or total serum osmolality >320 mOsm/kg; beta-hydroxybutyrate <3.0 mmol/L (urine ketones <2+); pH ≥7.30 and bicarbonate ≥15. Altered mental status is common and tracks with osmolality but is not a criterion. A patient meeting both DKA and HHS criteria has mixed DKA/HHS.
CT head if focal deficits persist after fluid resuscitation or if seizure
CT abdomen/pelvis if abdominal source suspected
Diagnostic algorithm
flowchart TD
A["Suspected HHS<br/>glucose ≥600, high osm, BOHB <3"] --> B["0.9% NaCl or balanced crystalloid<br/>500-1000 mL/h for 2-4 h"]
B --> C["Check K, ECG<br/>treat precipitant"]
C --> D{"K >3.5?"}
D -->|No| E["Replace K<br/>hold insulin"]
D -->|Yes| F["Insulin 0.05 U/kg/h, no bolus<br/>(0.1 if mixed DKA/HHS)"]
E --> F
F --> G{"Osm falling with adequate<br/>fluids and insulin?"}
G -->|No| H["Switch to 0.45% NaCl"]
G -->|Yes| I["Continue isotonic fluid"]
H --> K{"Glucose <250?"}
I --> K
K -->|Yes| L["Add D5-D10<br/>insulin to 0.05 U/kg/h<br/>keep glucose 200-250"]
L --> M["Resolved: osm <300, UO >0.5 mL/kg/h,<br/>cognition improved"]
M --> N["SC basal insulin 1-2 h<br/>before stopping drip"]
Aggressive IV fluids — 0.9% NaCl or balanced crystalloid 500-1000 mL/hr for the first 2-4 hours, then titrated to hemodynamics and urine output; total deficit 8-12 L replaced over 24-48 hours
A rising serum Na as glucose falls is expected (about 1.6 mEq/L per 100 mg/dL) and is not a reason to switch to hypotonic fluid; use 0.45% NaCl only if osmolality is not falling despite adequate positive fluid balance and insulin. Lower osmolality gradually (3-8 mOsm/kg/hr; Na change no more than 10 mEq/L per 24 hours)
When glucose falls below 250 mg/dL, add 5-10% dextrose and reduce insulin to 0.05 unit/kg/hr; hold glucose around 200-250 mg/dL until HHS resolves (osmolality <300, urine output >0.5 mL/kg/hr, improved cognition)
Insulin — start ONLY after initial fluid resuscitation and K is >3.5 mEq/L; fixed-rate regular insulin 0.05 unit/kg/hr IV in HHS (0.1 unit/kg/hr if mixed DKA/HHS with significant ketonemia), no bolus; glucose should fall no faster than 90-120 mg/dL/hr
Potassium replacement — hold insulin and replace K if <3.5 mEq/L, add 10-20 mEq KCl per liter of fluid if 3.5-5.0, recheck without K if >5.0; HHS patients are markedly K-depleted despite normal serum levels
Treat underlying precipitant aggressively — culture and start empiric antibiotics if infection suspected
VTE prophylaxis (high thrombosis risk from dehydration and hyperviscosity)
Complications
Thromboembolism — DVT, PE, stroke from hyperviscosity and dehydration; give prophylactic-dose LMWH unless contraindicated; therapeutic anticoagulation only for suspected or confirmed thrombosis
Cerebral edema — rare in adults; risk increased with rapid osmolarity correction
Rhabdomyolysis from prolonged immobility and hyperosmolarity
Total water deficit is typically 100-200 mL/kg (8-12 L). If a free water deficit is calculated, use the glucose-corrected Na, not the measured Na (which is dilutionally low and falsely shrinks the deficit), and an age-appropriate total body water fraction (about 0.5 × weight in older adults).
References
ADA 2026 — American Diabetes Association Professional Practice Committee for Diabetes. 6. Glycemic Goals, Hypoglycemia, and Hyperglycemic Crises: Standards of Care in Diabetes—2026 (Diabetes Care 2026;49 Suppl 1:S132-S149)
ADA Consensus 2024 — Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycemic Crises in Adults With Diabetes: A Consensus Report (Diabetes Care 2024;47(8):1257-1275)
Endocrine Society — Management of Hyperglycemia in Hospitalized Adult Patients in Non-Critical Care Settings (J Clin Endocrinol Metab 2022)
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