Diabetic Ketoacidosis (DKA)

• Acute complications from diabetes include diabetic comas and infections. Complications can also stem from specific systems like ARF, AMI, or acute neuropathy.

Diabetic Coma

• Can manifest as Diabetic Ketoacidosis (DKA), Hyperglycemic Hyperosmolar State (HHS), Lactic Acid coma, or Hypoglycemic coma.

Diabetic Ketoacidosis (DKA)

• Defined as an acute metabolic complication of diabetes that may be fatal without swift medical intervention.
• Characterized by absolute or relative insulin deficiency. It is the most common acute hyperglycemic complication for those with type 1 diabetes mellitus.
• Occurs in type 1 or type 2 diabetes mellitus patients with high levels of anti-insulin due to concurrent illness.
• The triad of DKA is hyperglycemia, ketosis, and acidosis.

Causes of DKA

• Missed insulin doses.
• Relative insulin deficiency due to stress, steroid use, or infection.
• Tissue damage from trauma, operations, burns, shock, stroke, or myocardial infarction.
• Pregnancy, labor, and lactation.
• Drug use, including corticosteroids, thiazides, pentamidine, sympathomimetics, second-generation antipsychotics, cocaine, immune checkpoint inhibitors, or SGLT2 inhibitors.

Pathogenesis of DKA

• Reduced insulin levels paired with increased levels of counter-regulatory hormones lead to hyperglycemia, volume depletion, and electrolyte imbalances.
• Inability for glucose to enter cells causes hyperglycemia and glycosuria.
• Fat is mobilized for energy (lipolysis), resulting in excess ketone body production.
• Excess production of KB includes acetone, acetoacetic acid, and β-hydroxybutyric acids.
• Ketonemia occurs, with ketones excreted in urine, leading to ketonuria and polyuria, and in breath detectable as acetone odor.
• Patients may exhibit Kussmaul respiration and experience a shift of potassium outside cells, which is then lost in urine.

Clinical Picture of DKA

• DKA can be the initial presentation in up to 25% of patients who are newly diagnosed with diabetes.
• Symptoms of uncontrolled diabetes mellitus lasts for 2–3 days.
• Patients will have Kussmaul respiration and acetone breath.
• Patients will exhibit shock, peripheral vasodilation, and dysrhythmias.
• Patients will experience dehydration and hypothermia.
• GI symptoms include acute abdomen with epigastric pain, nausea, vomiting, constipation, and hematemesis.
• Kidney-related symptoms that include ketonuria and glucosuria which results in severe polyuria, polydipsia and dehydration, and dry inelastic skin, sunken eyes, thirst, low blood pressure, and low temperature.
• In its end stage, DKA can lead to coma, acidosis, ketosis, dehydration, and electrolyte imbalance.

Investigations in DKA

• DKA is diagnosed if blood glucose is ≥250 mg%.
• With DKA, blood ketone levels are >3.0 mmol/L or ketonuria is present (2+ or more on standard urine sticks).
• Acidosis - bicarbonate (HCO3 is <15.0 mmol/L, and/or venous pH is <7.3.
• Venous blood gas should be ordered.
• Metabolic acidosis with a raised anion gap will be observed. A high anion gap (>16) indicates severe DKA.
• pH is used to determine the severity of DKA, with pH ≥7.0 indicating mild to moderate DKA and pH <7.0 indicating severe DKA.
• Order urinalysis if near-patient testing for ketones is unavailable or if a urinary tract infection is suspected.
• Urinalysis shows ketonuria (2+ or more on standard urine sticks) and may be positive for glucose.
• ECG is used to look for cardiac precipitants of DKA like myocardial infarction. Findings may include abnormal T or Q waves or ST segment changes.
• Evidence of hypokalemia (U waves) or hyperkalemia (tall 'peaked' T waves) may be present.
• The potassium level on venous blood gas is used to replace potassium if ≤5.5 mmol/L.
• Plasma osmolality is high (>320 mmol/kg) in DKA and is an indication of dehydration.
• Leukocytosis is common in DKA and correlates with blood ketone levels. Leukocytosis more than 25 × 10^9/L (25,000/microlitre) may indicate infection and further investigation.
• With suspected DKA, patients may have a pH ≤7.3, bicarbonate ≤15 mmol/L, and an anion gap >12 mmol/L.
• Positive serum or urine ketones, plasma glucose ≥250 mg% and a precipitating factor is to be expected.

Summary of Investigation

• In blood, hyperglycemia and ketonemia occurs.
• Acidosis is typically observed (plasma HCO3), dehydration leading to increased serum creatinine.
• Serum potassium is normal or high despite depletion of body potassium due to extracellular shift.
• Leukocytosis and elevated serum amylase are typical as well.
• In urine, glycosuria, ketonuria, and polyuria are common findings.

Conditions that can make DKA Diagnosis Difficult:

• Increased β-hydroxybutyrate, pregnancy, SGLT2 inhibitor use, significant osmotic diuresis, and conditions increasing bicarbonate (e.g. vomiting).
• Negative serum ketones, normal (euglycemic DKA), and mixed acid-base conditions where pH is not as low as expected.
• Testing for serum levels of β-hydroxybutyrate should be ordered where appropriate, with an awareness of normal anion gaps.

Management of DKA

• Confirm diagnosis of DKA.
• Search for and treat any precipitating cause.
• Assess hydration and give fluid.
• Give insulin.
• Monitor clinical signs and biochemistry.
• Hospitalization is often better in the ICU.
• Fluid replacement is the first line of management.
• The amount of fluid should be guided by CVP (10cm H2O) 1 L / hour until HR & BP return normal.
• For fluid type, begin with isotonic saline. Switch to Glucose 5% when blood glucose drops < 250mg to avoid hypoglycemia. Use hypotonic saline for hypernatremia or if patient is taking NaHCO3 for acidosis.
• Administer insulin, using a short-acting insulin analogue.
• Use a low-dose regimen of 0.1 U / kg / h. as a continuous infusion or deep IM.
• Follow up by checking blood sugar every hour and administer further insulin accordingly.
• Treat metabolic acidosis with NaHCO3 in severe cases.
• Indication for NaHCO3 in severe cases where clinical manifestations inclue Kussmaul respiration and lab values reflect pH < 6.9 & HCO3 < 5 mEq.
• Correct plasma K+ level by administering K from the start.
• Hypokalemia occurs with insulin treatment due to intracellular shift.
• Add 10 mL KCL (20 mEq) to each 1L of fluid given.
• Oral K+ given after recovery.
• Monitoring includes state of hydration, urine output, conscious level, plasma glucose, potassium, and ABG.
• insert a nasogastric tube to aspirate gastric content.
• Administer Heparin IV in old and dehydrated patients to guard against DIC.
• After control DKA, use insulin therapy.
• Prevent recurrence by avoiding reduction of insulin dose during intercurrent illness.

Hyperosmolar Hyperglycemic State (HHS)

• Defined by low levels of insulin sufficient to prevent lipolysis but insufficient to lower blood glucose. More common in type 2 diabetes (NIDDM).
• It occurs in elderly patients developing an infection, in the insensate patient and/or living alone. Decreased thirst fluid intake results in dehydration, placing patients at risk of thrombosis in cerebral vessels.

Clinical Picture of HHS

• Severe polyuria, polydipsia, and dehydration are the main symptoms.
• Little or no ketosis.
• Pre-renal uremia due to dehydration.
• Neurologic symptoms include convulsions, coma, hemiparesis, and stupor.

HHS vs DKA

• HHS will have marked Hyperglycemia compared to normal to high glucose
• HHS ECFV has the same contraction as DKA.
• HHS will have marked increased Level of consciousness, DKA will just have Increased Level of consciousness.
• HHS and DKA patients are to be careful with hypokalemia and may need Insulin

Investigations in HHS

• Severe hyperglycemia, often >1000mg is expected
• Increased positive Na, increased positive plasma osmolality are expected to show in blood.
• Glucose without ketone bodies in urine.

Management of HHS

• Treatment mirrors that of DKA, but excludes bicarbonate.
• Fluids: 1/2 normal saline (1/2 molar).
• Amount to manage 1L / hour, not faster, to avoid cerebral edema.
• Amount of Insulin is less compared to Ketonemia
• Heparin is given in order to prevent the high chance of DIC.

Diabetic Lactic Acidosis

• Caused by tissue hypoxia from pneumonia or myocardial infarction or by taking biguanides.
• Clinical presentation is of acidosis, involving Kussmaul respiration and late CNS/CVS inhibition.
• Investigations: Low positives in pH and bicarbonate, increased positive in plasma lactate.
• Treatment: correct hypoxia, administer with NaHCO3 and Insulin-glucose combination.

Hypoglycemia

• The normal lower limit of fasting plasma glucose is typically 70 mg/dL (3.9 mmol/L) in diabetic patients.
• A clinical syndrome of diverse causes, where low serum glucose levels can eventually lead to neuroglycopenia.
• Individuals whom are eldery with compromised cerebral blood supply and the manifestations of neuroglycopenia is provoked at slightly higher plasma glucose.
• Patients that are chronic hyperglycemia for example , those with poorly controlled controlled, insulin-treated diabetes mellitus may experience symptoms of neuroglycopenia at considerably higher plasma glucose concentrations than people WITHOUT diabetes.
• Glucose <70 mg/dL (3.9 mmol/L) and ≥54 mg/dL (3.0 mmol/L), Glucose <54 mg/dL is consider level 2, Level 3 is charactered by altered menta and/or physical stats requiring assistance of hypoglycemia
• Reduction of exogenous glucose, taking to much insulin or increased insulin sensitivities.

Clinical Picture of Hypoglycemia

• Has Neurogenic symptoms which are autonomic and has Adrenergic symptoms where the symptoms are palpitations, tremor, and anxiety
• Could have Hypertension and cardiac ischemia or arrhythmias in patients with underlying cardiac disease.
• Chollinergic symptoms happen but are mediated by acethcholine released from sympathetic postganglionic neurons.
• The symptoms are sweating, hunger, and paresthesias.
• Then they has Neuroglycopenic symptoms of hypoglycemia, which are central nervous system glucose deprivation.
• These include behavioral changes, confusion, fatigue, seizure, loss of consciousness.
• Prolonged, severe hypoglycemia can cause irreversible brain damage and death.

Treatments of Hypoglycemia

• If the patient is conscious and able to drink and swallow administer a rapidly-absorbed oral carbohydrate with 3 teaspoons of sugar.
• Then 1-2 tablespoons of honey
• Then 3 or 4 glucose tablets
• Then 4-6 small hard candies
• Then 6 oz. regular (not diet) soda (about half a can)
• Lastly 4 oz. Fruit juice
• Fast acting carbs are to be ( 15g ) Check blood glucose 10-15 minutes after treatment and Rechecking every 15 minutes
• If blood glucose remains <70 mg/dl after 45min or three cycles, consider 1mg of glucagon IM or 10% glucose IV infusion at 100mL/h and Once blood glucose is above 70mg/dl and the patient has recovered, give 20g of long-acting carbohydrate for example, Two biscuits or One slice of bread or 200-300mL glass of milk or Normal Meal
• Patietn who are conscious but confused but able to swallw need to be able to take  Glucagon 1mg IM or If IV access available, give 75mL of 20% glucose or 150mL of 10% glucose over 12– 15min

DKA vs Hyoglycemia Chart

• Hypoglycemia has excess TTT ( Treatment ,Missed meal and DKA has Infection
• Hypoglycemia has a rapid with irritated Onset and DKA is slow and silent,
• Respiration is Normal with Hypoglycemia and Kuassmal in DKA
• Pulse is strong with Hypoglycemia and weak/Rapid in DKA. Skin is wet with Hypoglycemia and Dry and Cold with DKA,Tongue is moist for Hypoglycemia and Dry for DKA and Eyes are normal for Hypoglycemiia and Sunken for DKA
• Urine is Normal or sugar with DKA and sugar is more prominent.