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Dr. Hammad Hasan Medical Unit 2 Holy Family Hospital



Define diagnostic criteria for diabetic ketoacidosis Define diagnostic criteria for hyperosmolar hyperglyemia Understand the five key components to the treatment algorithm


Š . He understood that the disease drained more fluid than a person could consume. . 250 BC. Apollonius of Memphis coined the name "diabetesµ meaning "to go through" or siphon.Š Earliest known record of diabetes mentioned on 3rd Dynasty Egyptian papyrus by physician Hesy-Ra: mentions polyuria as a symptom.

" was added to diabetes because it made the urine sweet. as it was sweet-tasting. "mellitus. Š Up to 11th century diabetes was commonly diagnosed by ´water tastersµ who drank the urine of those suspected of having diabetes. . .Š Gradually the Latin word for honey.

a German medical student announced in a dissertation. Paul Langerhans.Š In the 1869. that the pancreas contains two systems of cells. removed the pancreas from a dog to determine the effect of an absent pancreas on digestion Š . 1889 Oskar Minkowski and Joseph von Mering in France.

then on: 7 . and give it to diabetic dogs.Š Š Š Š Boss leaves on vacation May 1921 Banting and his assistant Best isolate insulin from dogs. Boss returns and is skeptical that insulin works Try extract on themselves.

Charles Best·s extract. a complication of his diabetes 8 . Two weeks later he used the purified extract of Dr.The first patient to receive injections of pancreatic extract on January 11.B. He died at the age of 27 due to pneumonia. Thompson lived another 13 years with the insulin. Collip and Thompson's symptoms began to disappear. At first he received Dr. J. 1922. F. He weighed only 65 pounds and was about to slip into a coma and die. Banting·s and Dr. The young Toronto resident had been diabetic since 1919. his blood sugar returned to normal and he was brighter and stronger. He was 14.

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Insulin Released in Response to Elevated Plasma Glucose Glucose Production Muscle Adipose Tissue Decreased Glucose Output Normal Physiologic Plasma Insulin Increased Glucose Transport Euglycemia 10 .Normal F-Cell Function Pancreas Liver Normal Insulin Sensitivity Decreased ipolysis Decreased Plasma FFA Glucose Uptake Islet F-Cell Degranulation.

Features of type 1 diabetes ‡ Onset in childhood/ dolescence ‡ Le n body h bitus ‡ Acute onset of osmotic sym toms ‡ Ketosis. though ketosis can occur Š Immune markers in only 10% Š Family history is often positive with almost 100% concordance in identical twins .rone ‡ High levels of islet uto ntibodies ‡ High rev lence of genetic susce tibility Features of type 2 diabetes Š Usually presents in over-30s (but also seen increasingly in younger people) Š Associated with overweight/obesity Š Onset is gradual and diagnosis often missed (up to 50% of cases) Š Not associated with ketoacidosis.

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Schematic of the pathogenesis of diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) .

Islets of F-cell destruction Insulin Deficiency Langerhans Decreased Glucose tilization & Increased Production Stress Adi ocytes Amino Increased Acids Protein Muscle Liver Glucagon Catabolism Increased ipolysis Polyuria Volume Depletion Ketonuria FattyAcids Increased Ketogenesis Gluconeogenesis. Glycogenolysis Threshold 180 mg/dl Hyperglycemia Ketoacidosis HyperTG .

Reduced Insulin Content Muscle Increased Glucose Output Reduced Plasma Insulin Adipose Tissue Hyperglycemia 15 Decreased Glucose Transport & Activity (expression) of GLUT4 .F-Cell Dysfunction Insulin Resistance Increased ipolysis Pancreas Li er Glucose Production Elevated Plasma FFA Glucose Uptake Islet F-Cell Degranulation.

Autoimmune destruction Honeymoon ³Diabetes threshold´ 100% Islet loss .

Insulin Glucagon E ine hrine Cortisol Growth Hormone .

Insulin Glucagon E ine hrine Cortisol Growth Hormone Dec Glucose tilization Li olysis .

randial and Stress-Induced hy erglycemia .Decreased tilization Š Relative Insulin Deficiency Glycogenolysis & gluconeogenesis restrained Peripheral glucose uptake Elevates blood glucose ost.

Insulin Glucagon Epinephrine Cortisol Growth Hormone Gluconeogenesis Glycogenolysis Li olysis Ketogenesis .

Increased Production & Decreased tilization Š Insulin Deficiency Glycogenolysis Gluconeogenesis Hepatic glucose output Peripheral glucose uptake Elevates blood glucose Lipolysis Release FFA -> liver VLDL & ketones Ketonemia and hyperTG Acidosis & Diuresis Fasting hy erglycemia .

Š Glucose > 250 Arterial pH 7. 22 2005. Diabetic Ketoacidosis.high Anion gap >10 Patient is alert Š Š Š Š Š Š Trachtenbarg David.71:1705-1714 .25-7. American Family Physician.30 Serum bicarb 15-18 mEq Urine and Serum ketones B-hydroxybutyrate.

Š Glucose > 250 Arterial pH 7. Diabetic Ketoacidosis.high Anion gap >12 Patient is alert/drowsy Š Š Š Š Š Š Trachtenbarg David.00-7. 23 2005.71:1705-1714 .24 Serum bicarb 10 to <15 mEq Urine and Serum ketones B-hydroxybutyrate. American Family Physician.

Diabetic Ketoacidosis.00 Serum bicarb <10 mEq Urine and Serum ketones B-hydroxybutyrate.high Anion gap >12 Patient is stupor/coma Š Š Š Š Š Š Trachtenbarg David. 24 2005. American Family Physician.Š Glucose > 250 Arterial pH <7.71:1705-1714 .

paraldehyde. salicylates) .Š Š Š Š Š Š Anion gap acidosis DKA Lactic acidosis Alcoholic ketoacidosis Renal failure Certain poisonings (ethylene glycol. methanol. methyl alcohol.

26 2005.small B-hydroxybutyrate.Š Glucose > 600 Arterial pH <7. Diabetic Ketoacidosis.30 Serum bicarb <15 mEq Urine and Serum ketones.n or elevated Anion gap-variable Patient is stupor/coma Š Š Š Š Š Š Trachtenbarg David. American Family Physician.71:1705-1714 .

renal failure). Mortality as high as 12% to 46%. pancreatitis) OR complications of treatment. abdominal pain Short (hours to days) new diabetes OR existing diabetes AND: med noncompliance. seizures. polydipsia.000 personyears. trauma. GI bleed. MI. PE. sepsis. weakness. polyuria.Comparison of DKA vs. meds (thiazides. pancreatitis. Mortality 1-2% (usually NOT from DKA itself but rather the precipitant. AMS (mild confusion to lethargy). Increasing age and higher S/Sx correspond with increased mortality. 2% to 8% of all diabetic hospital admissions. burns.3 < 15 <25 <320 5-7 L 27 . e. acute illness (infection. 1 in 1000 diabetic hospital admissions. substance abuse (EtOH. beta-blockers. cocaine). steroids..6 ± 8 per 1000 diabetic patients.g. fatigue. lethargy. CVA. coma Insidious (days to weeks) DKA 4. Precipitant not always clear but try to identify one whenever possible. cisplatinum).5 cases per 100. HHNS HHNS Epidemiology 17. thirst. phenytoin. poor glycemic control. MI. polyuria. Presentation Onset Precipitants vomiting.3 > 20 >30 >330 8-10 L > 250 < 7. altered. Blood Glucose Arterial pH Serum bicarbonate BUN Osmolality TBW Deficit > 600 > 7.

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Symptoms ‡ Nausea and vomiting ‡ Abdominal pain ‡ Thirst and polyuria ‡ Visual disturbances ‡ Weakness and/or anorexia ‡ Somnolence .

Signs ‡ Tachycardia ‡ Weight loss ‡ Hypotension ‡ Warm. respiration and/or coma ‡ ´Fruityµ breath (odor of ketones) ‡ Dehydration 30 . dry skin ‡ Hyperpnea or Kussmaul·s ‡ Impaired consciousness.

Non-respiratory Acidosis 4. Hyperkalemia 7.Hyperglycemia 2. . Hemoconcentration 1. Hypertriglyceridemia 8. Ketonemia 5. Uremia 6.‡ Glycosuria 3.

Im aired gluconeogenesis Liver disease Acute alcohol ingestion Prolonged fasting Insulin-inde endent glucose is high ( regnancy) 6. 3. 5. 4. 2.DKA can be resent with BS <300. 32 . Chronic oor control but taking insulin 1.

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Manage symptoms Prevent acute and late complications Improve quality of life Avoid premature diabetes-associated death An individualized approach
Glycemic control BP Li ids Management Patient education Eye care Foot care

Lifestyle (e.g. diet & exercise) Microalbuminuria & kidneys



Treatment involves 5 key components: Monitoring Fluid resuscitation Insulin and dextrose infusion Electrolyte repletion Treating underlying cause

1. 2. 3. 4. 5.


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pulse ox Foley to monitor I &O Initially blood work every 1-2 hours If pH is less that 6. Oxygen.ƒ ƒ ƒ ƒ ƒ ICU 2 IV·s. cardiac monitor. continuous vitals.9 be frightened 38 .

calculate GFR Beta-hydroxybutyrate or serum ketones UA CBC EKG Infection-cultures. Mag Bun & creatinine.Š Š Š Š Š Š Glucose.chest xray Cardiac status-cardiac enzymes 39 Š Š . lytes with calculated anion gap.


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If severely hyperosmolar (>330) begin with hypotonic fluids (1/2 NS). Replace at a rate of 1 ² 2 L/hr for first 1 to 2 hours followed by 1 L/hr for 3 to 4 hour.  · If initial corrected serum sodium is > 150 or when calculated serum Osm >320 may begin with hy otonic saline. Goal is to replace half of TBW deficit over first 12 hours and remainder in the next 24 hours. 42 Resuscitate with isotonic saline (NS) initially followed by hypotonic saline (1/2NS). then correct total body water deficit in the following 24 to 48 hours with hy otonic saline (1/2NS or D5-1/2NS).    . In HHNS water losses usually exceed sodium losses resulting in hypertonic dehydration.  · Begin initial re lacement with NS at 1-2 L/hr for first 1-2 hours followed by 250/hr.HHNS  DKA  Initial goal is to correct intravascular volume beginning with isotonic saline (NS).

Š Š Š Š Sodium Potassium Ketones WBC .

6 meq/L x (glucose-100)/100)) Example: ƒ Na+ = 123 meq/L and Glucose = 1.5 x 1.250 mg/dl ƒ 1.150 / 100 = 11.6 = 18 meq/L ƒ Corrected Na+ = 123 + 18 = 141 meq/L .Š Š Š Na+ depressed 1.6 mEq/L per 100 mg% glucose Corrected Na+ = measured Na + 1.250 ² 100 = 1.

Š Triglycerides also artificially lower Na Li id Na Na Na Na Na Na Na Na Na Serum Li id Na Na Gluc Na Na Gluc .

Š Š Acidosis leads to flux of K+ out of cells as H+ enters cells to buffer Dehydration and volume depletion ƒ Aldosterone K+ wasting Na reabsorption and Serum K+ usually normal or high. but total body K+ is low .

long PR.Š With insulin therapy ƒ K+ moves into cells (1 meq/L / 0. Prom U-wave ƒ Cardiac dysrythmia .1 unit pH ) Š Even with K+ you must ƒ Give large doses (40 meq/L) K+ ƒ Monitor K+ levels and EKG High K . wide QRS Low K .tall peaked T.depressed ST. diphasic T.

Š Š In the absence of insulin. FFA go to the liver. and into mitochondria via carnitine ß-oxidation excess acetylCoA Nitro russide reaction ‡ Acetyl-CoA condenses to acetoacetate ‡ Insulin revents utilization of acetoacetate ‡ so levels and shunt to ß-hydroxybutyrate and acetone .

Urine Dip stick vs. anion gap/serum bicarb Specificity Sensitivity DKA 99 % 69 % Š Diabetic with minor signs and symptoms and negative urine ketone dip stick is unlikely to have acidosis = high negative predictive value for excluding DKA Am J Emer Med 34: 1999 .

9.more common in children < 3 years of age ƒ All need to be evaluated and re-evaluated if ersistent acidosis Am J Emer Med 19: 270-3.9% bacterial infection . 2001 .519/mm3 (+/.8% presumed viral infection ƒ 12.582) ƒ 69% without infection ƒ 17.Š N = 247 DKA admissions over 6 years Mean WBC = 17.

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15 units/kg Š Insulin drip.1 units/kg/hr Š Patient to ICU Š Stop insulin drip when sugar is less than 250 Š 52 . . . most protocols 5-7 units per hour.Initially 10 units R Insulin IV.

Because the primary problem is one of dehydration.1 to 0.  53 . Follow blood glucose hourly x 4 ² 8 hours. Insulin drip may be used but remember that hydration comes first in HHNS. CHANGE IVF TO D5-1/2NS when plasma glucose reaches 250 (to avoid hypoglycemia and excessive decline in Sosm that might precipitate cerebral edema) with the goal of continuing the insulin infusion and resolving the acidosis (close anion gap). Š LOADING DOSE OF INSULIN: 0.Š  HHNS Š DKA Begin with hydration alone ² glucose concentration may fall by 80 to 200 per hour with hydration alone. Frequent assessment of the patients· clinical status and labs followed by judicious use of insulin is preferable to simply using an insulin sliding scale. Subcutaneous insulin is usually sufficient and is not accompanied by the risks of hypoglycemia that one has with insulin drips. mainstay of therapy should be rehydration. Manage HHNS using drip or SQ insulin.2 U/kg IV INITIATE INSULIN DRIP (5-10 U/hr) to restore euglycemia and correct acidosis while limiting rapid changes in serum osmolality. Decrease insulin drip to Regular Insulin 1u per hour for every 100cc hr of D5-1/2NS in IVFs. Goal of decrease of 75 ² 100 of serum glucose/hr.

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and then start insulin when K above 3.3 mmol replete.Whole body potassium deficits exist.3 mmol/L Š 57 . (3-5 mmol/kg) Š Acidosis increases K Š Glucose + Insulin lowers K Š Start K with K less than 5 mmol and adequate urine output Š If initial K less than 3.

Š Commonly under repleted Resident mistakenly uses the replacement of potassium protocol. which vastly under repletes potassium Watch like a hawk!!!! Replace/repete/replace/repete Š Š Š 58 .

Š A serum deficit usually exists of .5-1 mmol per L Consider repleting if less than 1.8 mg/dL Š 59 .

5 give >40meq/L. and acidosis can cause shift of K out of the intracellular space which in the setting of diuresis causes significant urinary loss of K. there is often total body phosphate deficit in both Magnesium: Caution in renal failure. K=4. K reenters the cell causing further decrease of serum K. If patient has normal renal function. K 3. for the first 3 to 4 hours.0-5. Actual repletion of phosphate is rarely required unless it is severe (i. replace only if severe (<1. As rehydration and correction of hyperglycemia occurs. add K to IVFs as follows: K < 3. Š Phosphate: Like K.0 give at 20/L. Always follow serum calcium because rapid phosphate repletion can cause hypocalcemia. 60 .e.54. If initial measured K is normal or low there is severe K deficit. Hypertonicity.0-4. less than 1.Š Potassium: regardless of measured K.5 give at 30/L. Follow K closely! Š DKA and HHNS.3 give at 10/L. K=5.5-5. there is always total body K depletion (3 to 5 in DKA and 5 to 10 in HHNS)..6) or in refractory hypokalemia.0 give 40/L.0). K=4. insulin deficiency.

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loss of consciousness and convulsions can occur with severe hypoglycemia. Sweating. and palpitations may occur with mild hypoglycemia.Š 1. Hypoglycemia: Severe hypoglycemia can be a life-threatening complication. Patients should receive hourly monitoring of plasma glucose initially and after adjustments in intravenous insulin or administered carbohydrates to detect a rapidly decreasing blood glucose level and to prevent the development of hypoglycemia Š Š 62 . tremors.

Hypokalemia usually occurs after the initiation of insulin therapy. Hypokalemia Potentially life-threatening if potassium replacement is delayed or inadequate. secondary to the intracellular movement of potassium Š Š 63 .Š 2.

is present in ~10% of patients admitted with DKA and is common in patients recovering from DKA.24 It is usually caused by an excessive use of saline for fluid and electrolyte replacement during treatment. Hyperchloremia: Hyperchloremic normal anion gap metabolic acidosis. 64 .3.

Prolonged stasis.19 Antithrombotic therapy in the form of external compression devices or subcutaneous heparin is warranted in more severe or prolonged cases. and hemoconcentrationare major precipitating factors of a thromboembolic event. immobility.4. Thromboembolic events: May cause death in adults with DKA. 65 .

Congestive heart failure Can develop with fluid replacement therapy.Š 5. especially if an acute myocardial infarction or an underlying diabetic cardiomyopathy is missed 66 .

It is more common in children. or unconsciousness. Frequent ongoing neurologic assessments of the patient are critical during fluid replacement and insulin therapy. seizures. bradycardia. 67 . There are no established warning signs or clinical predictors. Cerebral edema: It is a rare. papilledema.6. behavioral changes. especially those younger than 4 to 5 years of age with DKA and new-onset diabetes. Signs and symptoms may include headache. lethargy. often fatal complication that usually occurs within the first 4 to 24 hours after the initiation of therapy. abnormal pupil response.

Š 68 .Cerebral edema is an extremely serious. complication Š of DKA and occurs more often in children than adults. although rare.

Sepsis is the predominant risk factor. and pneumonia. 69 . drug overdose. severe nonthoracic trauma. Respiratory distress syndrome: Š It is a form of acute lung injury that may occur as a result of various insults.7. Caution in the rate of replacement of intravenous fluids should be exercised in patients with hypoxia and with suspected intrapulmonary or systemic infection. multiple fractures.Other predisposing conditions include multiple transfusions. aspiration of gastric contents. This may lead to decreased intravascular osmotic pressure and fluid shifts resulting in pulmonary edema. pulmonary contusion.

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insulin can be tapered and s/c insulin can be started in patients who meet the following diagnostic criteria: 1. suggests that i. 3.Venous pH >7.A.v.3 (The last three criteria apply only to DKA) 71 .Serum glucose <200mg/dl in DKA and between 250-300 mg/dl in HHNS 2. 4.The A.D.Serum anion gap <12mEq/L.Serum bicarbonate >18mEq/L.

5 to 1.5-1 U/kg/d and divide dose into 2/3 in AM (1/3 to be regular or humalog. Check QAC. d. give less when not eating full meal (i. Can give 0. QHS and 0200 dsticks to optimize dose. Lantus (glargine) or Detemir and Novlog or Humalog ² give 0.0 units/kg/day total with 50% long-acting and 50% short acting (split between 3 meals). the remainder NPH) and 1/3 before dinner (1/3 to 1/2 regular or humalog.3 U/kg regular insulin AC or Q 4-6 hours. bedtime. give 0. the remainder NPH) Š OR Š c. Š OR Š b.Š In newly diagnosed diabetic. NOTE: **Small children may only need long-acting insulin** 72 Š . or still nauseous. 3 hour post-prandial.15-0.e.) BE SURE TO STOP GLUCOSE INFUSION WHEN STOPPING INSULIN DRIP.

Protocols.but use Common sense which is not common 73 .

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