Acute complications of diabetes mellitus

a short take on acute complications of diabetes mellitus in a practical approach

1. ACUTE COMPLICATIONS OF DIABETES MELLITUS

2. Questions A 39 year old Male patient presented to you in emergency department for Acute Abdomen with H/O vomiting,Restlessness,Lethargy,dehydration.On palpation of abdomen diffuse tenderness+,no guarding/ rigidity.On Auscultation Bowel sounds heard. On eliciting History you detect the patient is a known diabetic and is on insulin and because of frequent travelling he is poorly complaint with insulin.Your first probable diagnosis a)Acute cholecystitis b) Perforative peritonitis c)Diabetic Ketoacidosis d)Intestinal Obstruction

3. Questions A 62 yr old Diabetic Male presented to the Emergency with H/O fever,Right Hypochondrial Pain,tachycardia for 2 days.CT abdomen done image is shown below The possible diagnosis a)Emphysematous nephritis b)Emphysematous cholecystitis c) Perforative peritonitis d)Alcoholic pancreatitis

4. Questions A 42 yr old Male known Diabetic for past 11 years with HbA1C 10.0 referred from an ENT surgeon to you the physician as a case of chronic otorrhea,otalgia with hearing loss and now p resenting with facial asymmetry a provisional diagnosis of Rt. Facial N. palsy is made. You suspect an infective pathology.The Probable organism could be a)Streptococcus pneumonia b) Hemophilus influenza c)Pseudomonas aeruginosa d)Clostridium perfringens

5. Questions A 54 yr old lady who is a diabetic for 12 years brought with h/o orbital cellulitis,6 th Nerve palsy and anosmia presenting with the following clinical picture the Drug of choice for this patient? a) Piperacillin Tazobactem b)Amphotericin B c) Mitomycin C d) Actinomycin D

6. Diabetic ketoacidosis Non ketotic hyperglycemic hyperosmolar coma Hypoglycaemia & Hypoglycaemic coma Infections

7. Hyperglycemia Ketosis Acidosis * Definition of Diabetic Ketoacidosis 7 DKA is defined as the presence of all three of the following: Hyperglycemia (glucose >250 mg/ dL ) Ketosis, Acidemia (pH <7.3). Williams textbook of endocrinology 10 th edition

8. Role of Insulin Required for transport of glucose into: Muscle Adipose Liver Inhibits lipolysis Absence of insulin Glucose accumulates in the blood. Uses amino acids for gluconeogenesis Converts fatty acids into ketone bodies : Acetone, Acetoacetate, β - hydroxybutyrate .

9. Electrolyte Losses Renal Failure Shock CV Collapse Insulin Deficiency 9 Hyperglycemia Hyper- osmolality Lipolysis  FFAs Acidosis Ketones CV Collapse Glycosuria Dehydration

10. Diabetic Ketoacidosis: Pathophysiology Unchecked gluconeogenesis  Hyperglycemia Osmotic diuresis  Dehydration Unchecked ketogenesis  Ketosis Dissociation of ketone bodies into hydrogen ion and anions  Anion-gap metabolic acidosis Often a precipitating event is identified (infection, lack of insulin administration)

11. Clinical Presentation of Diabetic Ketoacidosis History Physical Exam Thirst Polyuria Abdominal pain Nausea and/or vomiting Profound weakness Kussmaul respirations Fruity breath Tachycardia Dry mucous membranes Poor skin turgor Abdominal tenderness(may resemble acute pancreatitis or surgical abdomen)

12. Diabetic Ketoacidosis PRECIPITATING EVENTS Infection(Pneumonia / UTI / Gastroenteritis / Sepsis) Inadequate insulin administration Infarction(cerebral, coronary, mesenteric, peripheral) Drugs (cocaine) Pregnancy. Harrison’s Principle of internal medicine 18 th edition p2977

13. DIAGNOSIS LAB INVESTIGATIONS Complete blood count Serum ketones/ Urine ketones and sugar Calculate serum osmolality and anion gap Urinalysis and urine culture Consider blood culture Consider chest radiograph Acid-base assessment Williams textbook of endocrinology 10 th edition

14. TREATMENT OF DKA Initial hospital management Replace fluid and electrolytes IV Insulin therapy Watch for complications Treat causes Once resolved Convert to home insulin regimen Prevent recurrence TYPICAL BODY DEFICIT OF WATER AND ELECTROLYTES

15. FLUIDS FLUID RESUSCITATION IS A CRITICAL PART OF TREATING PATIENTS WITH DKA . Intravenous solutions replace extravascular and intravascular fluids and electrolyte losses. They also dilute both the glucose level and the levels of circulating counterregulatory hormones. Fluid it self leads to correction of acidosis to some extent Insulin is needed to help switch from a catabolic state to an anabolic state, with uptake of glucose in tissues and the reduction of gluconeogenesis as well as free fatty acid and ketone production

16. FLUID REPLACEMENT Administer NS as indicated to maintain hemodynamic status, then follow general guidelines: NS for first 4 hr. Consider half NS thereafter. Change to D5 half NS when blood glucose ≤250 mg/ dL . Williams textbook of endocrinology 10 th edition Hours Volume 1st half-hour to 1 hour 1 L 2nd hr 1 L 3rd hr 500 mL– 1 L 4th hr 500 mL– 1 L 5th hr 500 mL– 1 L Total 1st 5 hr 3.5 - 5 L 6th–12th hr 250– 500 mL/ hr May need to adjust type and rate of fluid administration in the elderly and in patients with congestive heart failure or renal failure.

17. INSULIN MANAGEMENT Regular insulin 10 U i.v. stat (for adults) or 0.15 U/kg i.v. stat. Start regular insulin infusion 0.1 U/kg per hour or 5 U per hour. Increase insulin by 1 U per hour every 1–2 hr if less than 10% decrease in glucose or no improvement in acid-base status. Decrease insulin by 1–2 U per hour (0.05–0.1 U/kg per hour) when glucose ≤250 mg/dL and/or progressive improvement in clinical status with decrease in glucose of >75 mg/dL per hour. Do not decrease insulin infusion to <1 U per hour . Williams textbook of endocrinology 10 th edition

18. INSULIN MANAGEMENT CONTD… Maintain glucose between 140 and 180 mg/dL. If blood sugar decreases to <80 mg/dL, stop insulin infusion for no more than 1 hr and restart infusion. If glucose drops consistently to <100 mg/dL, change i.v. fluids to D10 to maintain blood glucose between 140 and 180 mg/dL. Once patient is able to eat, consider change to s.c. insulin: Overlap short-acting insulin s.c. and continue i.v. infusion for 1–2 hr. For patients with previous insulin dose: return to prior dose of insulin. For patients with newly diagnosed diabetes: full-dose s.c. insulin based on 0.6 U/kg per day. Williams textbook of endocrinology 10 th edition

19. POTASSIUM REPLACEMENT Do not administer potassium if serum potassium >5.5 mEq /L or patient is anuric . Use KCl but alternate with KPO4 if there is severe phosphate depletion and patient is unable to take phosphate by mouth. Add i.v. potassium to each liter of fluid administered unless contraindicated. Williams textbook of endocrinology 10 th edition p 454 Serum K ( mEq /L) Additional K required 3.5 - 4.0 - 40mEq/L 3.5–4.5 - 20mEq/L 4.5–5.5 - 10mEq/L >5.5 - Stop K infusion

20. -Williams textbook of endocrinology 10 th edition

21. BICARBONATE Clinical trials do not support the routine use of bicarbonate replacement HCO3 replacement and rapid reversal of acidosis can impair cardiac function, reduce tissue oxygenation and promote hypokalemia and hypocalcemia . However in presence of severe acidosis p H<6.9,in hemodynamic instability with pH<7.1 and hyperkaemia with ecg finding bicarbonate therapy considered In the presence of severe acidosis (arterial pH <6.9), the ADA advises bicarbonate [50 mmol /L ( meq /L) of sodium bicarbonate in 200 mL of sterile water with 10 meq /L KCl per hour for 2 h until the pH is >7.0]. Williams textbook of endocrinology 10 th edition p456

22. TREATMENT OF DKA GLUCOSE ADMINISTRATION Plasma glucose reaches 250 mg/dl in DKA or 300 mg/dl in HHS, D ecrease the insulin infusion rate to 0.05–0.1 unit/kg/h (3–6 units/h), Add dextrose (5–10%) to the intravenous fluids. Maintain the above glucose values until acidosis in DKA or mental obtundation and hyperosmolarity in HHS are resolved Williams textbook of endocrinology 10 th edition p 455

23. Criteria for resolution of DKA glucose <200 mg/dl, serum bicarbonate ≥18 mEq /l, and venous pH of >7.3. Once DKA is resolved, if the patient is NPO, continue intravenous insulin and fluid replacement and supplement with subcutaneous regular insulin as needed every 4 h.

24. ONCE DKA RESOLVED… Most patients require 0.5-0.6 units/kg/day highly insulin resistant patients 0.8-1.0 units/kg/day Give subcutaneous insulin at least 2 hours prior to weaning insulin infusion . Williams textbook of endocrinology 10 th edition p455

25. CLINICAL ERRORS Fluid shift and shock Giving insulin without sufficient fluids Using hypertonic glucose solutions Hyperkalemia Premature potassium administration before insulin has begun to act Hypokalemia Failure to administer potassium once levels falling Recurrent ketoacidosis Premature discontinuation of insulin and fluid when ketones still present Hypoglycemia Insufficient glucose administration .

26. Hyperglycemic-Hyperosmolar State (HHS) HNC is a syndrome characterized by impaired consciousness, sometimes accompanied by seizures, extreme dehydration, , and extreme hyperglycemia that is not accompanied by ketoacidosis.

27. DKA HHS Ketonemia / Ketonuria + Ketonemia / Ketonuria - Serum Osmolality N Serum Osmolality >320mosm pH<7.3 pH>7.3 S.Glucose >250mg/ dL S.Glucose >600mg/ dL

28. Physical examination Severe dehydration is invariably present. Various neurologic deficits (such as coma, transient hemiparesis, hyperreflexia, and generalized areflexia) are commonly present. Altered states of consciousness from lethargy to coma are observed. Findings associated with coexisting medical problems (e.g., renal disease, cardiovascular disease) may be evident.

29. Laboratory findings Extreme hyperglycemia (blood glucose levels from 30 mmoll /l and over are common. A markedly elevated serum osmolality is present, usually in excess of 350 mOsm /l. (Normal = 290 mOsm ) Serum ketones are usually not detectable, and patients are not acidic. Serum sodium may be high (if severe degree of dehydration is present), normal, or high Serum potassium levels may be high (secondary to the effects of hyperosmolality ) Low or normal

30. Treatment This condition is a medical emergency and the patient should be placed in an intensive care unit. Many of the management techniques recommended for a patient with DKA are applicable here as well. The goals of therapy include: rehydration; reduction of hyperglycemia; electrolytes replacement; investigation of precipitating factors, treatment of complications.

31. Hypoglycemia It is a syndrome characterized by symptoms of sympathetic nervous system stimulation or central nervous system dysfunction that are provoked by an abnormally low plasma glucose level and it can occur at any time.

32. Precipitating factors irregular ingestion of food; extreme activity; alcohol ingestion; drug interaction; liver or renal disease; hypopituitarism and adrenal insufficiency.

33. HYPOGLYCEMIA

34. Pathophysiology of hypoglycaemia Inhibition of endogenous insulin secretion Counter-regulatory hormone release Glucagon Adrenaline Onset of symptoms Autonomic Neuroglycopaenic Neurophysiological dysfunction Evoked responses Widespread EEG changes Cognitive dysfunction Inability to perform complex tasks Severe neuroglycopaenia Reduced level of consciosness Convulsions Coma 83 mg/ dL 58–50 mg/ dL 68 mg/ dL 54–43 mg/ dL 54 mg/ dL 50 mg/ dL <27 mg/ dL Arterialised venous blood glucose concentration (mmol/L) 2.0 3 .0 4 .0 1 .0 5.0 Cryer et al. Diabetes Care 2003;26:1902–12 EEG , electroencephalogram

35. Physical examination The skin is cold, moist. Hyperreflexia can be elicited. Hypoglycemic coma is commonly associated with abnormally low body temperature Patient may be unconscious.

36. Treatment The most effective treatment of an insulin reaction is the immediate ingestion of a concentrated carbohydrate source, such as sugar, honey, candy, or orange juice. Alternative methods for increasing blood glucose may be required when the person having the reaction is unconscious or unable to swallow: Glucagon may be given intramuscularly or subcutaneously. In situations of severe or life-threatening hypoglycemia, it may be necessary to administer glucose intravenously.

37. Hypoglycaemia Protoco l If BG < 70mg% : 25% dextrose as per calculation. Check BG q15 mins If BG > 70mg% : Check BG q30 mins till BG > 90mg% If BG > 90mg% : Check BG q1hrly, Hold Infusion If BG > 140mg%: Restart infusion at 50% of previous rate BG ≤70 – Suspend Insulin, Give 25% Dextrose (100-BG) X 0.8**

38. Infections Complement: some studies have detected a deficiency of the C4 component in DM,this reduction of C4 is probably associated with polymorphonuclear dysfunction and reduced cytokine response Polymorphonuclear and mononuclear leukocytes: Decreased mobilization of polymorphonuclear leukocytes, chemotaxis, and phagocytic activity may occur during hyperglycemia. hyperglycemic environment inhibits glucose-6-phosphate dehydrogenase (G6PD), increasing apoptosis of polymorphonuclear leukocytes, and reducing polymorphonuclear leukocyte transmigration In tissues that do not need insulin for glucose transport, the increased intracellular glucose levels are then metabolized, using NADPH as a cofactor and the low NADPH prevents the regeneration of molecules that play a key role in antioxidant mechanisms of the cell, thereby increasing the susceptibility to oxidative stress. the glycated hemoglobin (HbA1c) is <8.0 %, to maintain the proliferative function of CD4 T lymphocytes and their response to antigens.

39. Infections Respiratory infections Streptococcus pneumoniae and influenza virus Tuberculosis Urinary infections Bacterial pyelonephritis E.Coli & Proteus Emphysematous pyelonephritis E.Coli & Proteus followed by enterobacter . Emphysematous cystitis The most frequent pathogen is E. coli , followed by Enterobacter , Proteus, Klebsiella , and Candida Perinephric abscess gram-negative bacilli (predominantly E. coli ) or polymicrobial infection Emphysematous cholecystitis The emphysematous cholecystitis is more frequent in males with DM.The main pathogens are Salmonella enteritidis and Campylobacter Invasive external otitis Invasive external otitis is an infection of the external auditory canal that can extend to the skull base and adjacent regions.It often affects elderly diabetic individuals and the etiologic agent is usually Pseudomonas aeruginosa

40. Questions A 39 year old Male patient presented to you in emergency department for Acute Abdomen with H/O vomiting,Restlessness,Lethargy,dehydration.On palpation of abdomen diffuse tenderness+,no guarding/ rigidity.On Auscultation Bowel sounds heard. On eliciting History you detect the patient is a known diabetic and is on insulin and because of frequent travelling he is poorly complaint with insulin.Your first probable diagnosis a)Acute cholecystitis b) Perforative peritonitis c)Diabetic Ketoacidosis d)Intestinal Obstruction

41. Questions A 62 yr old Diabetic Male presented to the Emergency with H/O fever,Right Hypochondrial Pain,tachycardia for 2 days.CT abdomen done image is shown below The possible diagnosis a)Emphysematous nephritis b)Emphysematous cholecystitis c) Perforative peritonitis d)Alcoholic pancreatitis

42. Questions A 42 yr old Male known Diabetic for past 11 years with HbA1C 10.0 referred from an ENT surgeon to you the physician as a case of chronic otorrhea,otalgia with hearing loss and now p resenting with facial asymmetry a provisional diagnosis of Rt. Facial N. palsy is made. You suspect an infective pathology.The Probable organism could be a)Streptococcus pneumonia b) Hemophilus influenza c)Pseudomonas aeruginosa d)Clostridium perfringens

43. Questions A 54 yr old lady who is a diabetic for 12 years brought with h/o orbital cellulitis,6 th Nerve palsy and anosmia presenting with the following clinical picture the Drug of choice for this patient? a) Piperacillin Tazobactem b)Amphotericin B c) Mitomycin C d) Actinomycin D