Diabetic Ketoacidosis (DKA)

Insulin is the body's master 'fed-state' signal — it tells tissues to take up glucose and tells fat cells to store, not release, free fatty acids. Without insulin, hormone-sensitive lipase in adipocytes is uninhibited and lipolysis floods the bloodstream with free fatty acids. The liver, also flooded with counterregulatory glucagon, takes those fatty acids into mitochondria via CPT-1 (which is suppressed by malonyl-CoA in the fed state, but rises when insulin/glucagon ratio plummets). Beta-oxidation produces massive acetyl-CoA — more than the TCA cycle can handle (oxaloacetate is being diverted into gluconeogenesis). The excess acetyl-CoA is shunted into ketogenesis: acetoacetate, β-hydroxybutyrate, and a small amount of acetone (the source of fruity breath). These ketoacids dissociate in blood, generating H+ that overwhelms buffering.

Three biochemical features required: (1) Hyperglycemia: glucose >250 mg/dL (note: euglycemic DKA with glucose <250 occurs in pregnancy, prolonged fasting, severe vomiting, and SGLT2 inhibitor use). (2) Acidosis: arterial pH <7.3 and serum bicarbonate <18 mEq/L. (3) Ketonemia: serum β-hydroxybutyrate >3 mmol/L (preferred over urine ketones, which detect acetoacetate and underestimate severity early). Anion gap >12 confirms high-gap metabolic acidosis. Severity: mild (pH 7.25-7.30, HCO3 15-18), moderate (pH 7.0-7.24, HCO3 10-14), severe (pH <7.0, HCO3 <10). Additional findings: leukocytosis, elevated BUN/Cr from dehydration, hyperkalemia by lab (total body K is severely depleted), low sodium (or 'normal' after correction).

Five priorities, simultaneous: (1) Fluids: 0.9% NaCl 1-1.5 L over first hour, then 250-500 mL/h; switch to 0.45% NaCl once intravascularly replete and to D5/0.45% NaCl once glucose <250. Patients are often 6-8 L down. (2) Insulin: regular insulin 0.1 U/kg/h IV infusion (no bolus needed) — aim for glucose drop of 50-75 mg/dL/h; continue until anion gap closes, NOT until glucose normalizes. (3) Potassium: K+ <5.3 → add 20-30 mEq/L to fluids; K+ <3.3 → HOLD insulin until K+ replaced (insulin will drive K+ intracellularly and cause arrhythmia). (4) Bicarbonate: only for pH <6.9. (5) Treat the trigger: infection, missed insulin, MI, pancreatitis, drugs. Transition to subcutaneous insulin only after anion gap closes, patient eating, and overlap by 1-2 hours.

Five 'I's: Insulin deficiency (missed doses, pump failure, new diagnosis), Infection (UTI, pneumonia, viral illness — ~30% of cases), Infarction (MI, stroke, mesenteric), Inflammation (pancreatitis, cholecystitis), and Intoxication (alcohol, cocaine, certain drugs). The common pathway: any acute stress raises counterregulatory hormones (cortisol, catecholamines, glucagon, growth hormone) that override basal insulin needs. New-onset type 1 diabetes presenting as DKA happens in ~25% of pediatric cases — pancreatic autoimmune destruction has been silently progressing for months and finally crosses the threshold. Always investigate the trigger; failure to identify one explains why ~10% of patients return with another episode.

Euglycemic DKA is DKA with glucose <250 mg/dL — the metabolic acidosis and ketonemia are present but hyperglycemia is masked. Most commonly seen in: SGLT2 inhibitor users (the drug class — empagliflozin, dapagliflozin, canagliflozin — promotes glucosuria, lowering serum glucose while still allowing ketogenesis if insulin is low or counterregulation high); pregnancy (especially T1DM in third trimester); prolonged fasting or severe vomiting reducing carb intake; alcohol-related ketoacidosis. The danger is missed diagnosis — clinicians may dismiss DKA because glucose looks fine. Always check pH, bicarbonate, and ketones in any insulin-dependent diabetic with acidosis or new GI symptoms. SGLT2 inhibitors should be held perioperatively and during acute illness.

Hypokalemia: insulin drives K+ into cells; if K+ drops below 3.3 cardiac arrhythmias can be fatal. Hypoglycemia: from continuing insulin while glucose has normalized — add dextrose to fluids once glucose <250. Cerebral edema: rare (~1%) but devastating, mostly in pediatric DKA, especially with rapid correction of hyperosmolarity, excessive fluids, or bicarbonate use. Aspiration: from gastroparesis and altered mental status — NG tube if obtunded. Thromboembolism: profound dehydration + hyperosmolar state + inflammation; DVT prophylaxis. Rebound DKA: insulin drip stopped before subcutaneous insulin overlap leaves a gap that lets ketogenesis restart. Hyperchloremic non-gap acidosis: from large-volume normal saline, resolves spontaneously.

DKA is a type 1 diabetes disease of insulin deficiency; HHS is a type 2 disease of relative insulin sufficiency. In HHS, residual insulin is enough to suppress ketogenesis but not enough to handle massive glucose loads in the face of severe dehydration and counterregulation. Result: extreme hyperglycemia (often >600 mg/dL), severe dehydration, hyperosmolarity (>320 mOsm/kg), profound mental status change, minimal or no ketonemia/acidosis. Patients are usually older with comorbidities. Mortality is ~10-20%, much higher than DKA's <2%, mostly from underlying illness and complications. Treatment overlaps with DKA (fluids, insulin, electrolytes) but fluid replacement is even more central, insulin doses lower, and goal glucose drop slower to avoid cerebral edema.