Acute Complications of DM by Dr. Md. Wasiul Alam Taufique.pptx

Acute complications of DM

1. Acute Complications in DM Prepared By: Dr. Md. Wasiul alam Taufique Intern Doctor Dept. of medicine (Blue Unit) East West Medical College & Hospital

2. What Is Diabetes Mellitus? Diabetes mellitus, commonly known as diabetes, is a chronic medical condition characterized by high levels of sugar (glucose) in the blood. This happens because the body either doesn’t produce enough insulin or can’t effectively use the insulin it produces. 

3. what is the Acute Complications of DM? Diabetic Ketoacidosis Hyperglycemic Hyperosmolar State Hypoglycemia Associated Autonomic Failure (HAAF) Hypoglycemia in DM

4. DIABETIC KETOACIDOSIS Described by Dr. Julius Dreschfeld in 1886. Diabetic Ketoacidosis is an acute, major, life-threatening complication of Diabetes mellitus It mainly occurs in patients with Type 1 Diabetes but it is not uncommon in some patients with Type 2 diabetes.

5. Definition: DKA is defined as an complex acute metabolic state characterized by hyperglycemia, ketoacidosis and ketonuria. It is associated with absolute or relative insulin deficiency, volume depletion and acid base abnormalities that results in potentially serious complication if not promptly treated.

6. Epidemiology: The incidence of DKA in developing countries is higher. It is far more common in young patients. DKA is frequently observed in diagnosis of type 1 diabetes and often indicates this diagnosis (3%). DKA accounts for 14% of all hospital admissions of patients with diabetes and 16% of all diabetes-related fatalities. The overall mortality rate for DKA is 0.2-2%, being at the highest in developing countries.

7. Diagnosis Triad of hyperglycemia, high anion gap metabolic acidosis and ketonemia . Glucose >13.9 mmol/L (250 mg/dl). Bicarbonate <15 mmol/L; pH< 7.3. Ketonemia (>3mmol/L) and ketonuria.

8. Pathophysiology It usually occurs as a consequence of absolute or relative insulin deficiency that is accompanied by an increase in counter-regulatory hormones ( i.e , glucagon, cortisol, growth hormone, epinephrine). Both insulin deficiency and glucagon excess are necessary for DKA to develop.

9. Cont …….. Decreased ratio of insulin to glucagon promotes gluconeogenesis, glycogenolysis and ketone body formation in liver, as well as increase in substrate delivery from fat and muscle (free fatty acids, amino acids) to the liver. Insulin deficiency also reduces the levels of GLUT4 glucose transporter, which impairs glucose uptake into skeletal muscle and fat and reduces intracellular glucose metabolism.

10. Insulin deficiency and hyperglycemia reduces the activity of F2,6BP increase the activity of PEPCK. Glucagon excess decrease the activity of pyruvate kinase. This changes shift the handling of pyruvate toward glucose synthesis and away from glycolysis. Increased levels of glucagon and catecholamines promote glycogenolysis and proteolysis. Increased levels of catecholamines and growth hormones activate hormone sensitive lipase that leads to lipolysis. Increased FFA and decreased activity of insulin sensitive lipoprotein lipase increases VLDL-triglyceride production and decreases VLDL removal.

11. Clinical Presentations (Symptoms) DKA usually evolves rapidly, over a 24 hour period. Earliest symptoms are polyuria, polydipsia, weight loss. Nausea, vomiting and abdominal pain are usually present. Malaise, generalized weakness, fatigability and shortness of breath. As the duration of hyperglycemia progresses, neurologic symptoms, including lethargy, focal signs, and obtundation can develop. Frank coma is uncommon in DKA.

12. ClinicAl presentations : (Signs) Dehydration - Dry mucous membranes, dry skin and decreased skin turgor Tachycardia/Hypotension Tachypnea Kussmauls respiration/ ketotic odor of breath- characteristic Abdominal tenderness Hypothermia/ Fever (if infection is present) Decreased reflexes Confusion Coma

13. Lab Investigations : Blood test for glucose every 1-2 hour. ABG/ VBG. Serum electrolytes (includes phosphate and magnesium) Renal function test. Urine dipstick test (acetoacetate). Serum ketones (3-hydroxybetabutyrate). CBC. Anion gap. Osmolarity. Cultures. Amylase. Note: Repeat lab investigations are key!

14. Management : Correction of fluid loss with intravenous fluids. Correction of hyperglycemia with insulin. Correction of electrolyte disturbances, particularly potassium. Correction of acidosis. Treatment of concurrent infection, if present.

15. Correction of Fluid Loss It is a critical part of treating patients with DKA. Recommended fluid - isotonic saline. 0.45% saline once euvolumic or serum Na+ >150 mEq /l to prevent overhydration and hyperchloremia acidosis. Replete circulating volume 2- 3 L of isotonic saline over first 1 - 3 hrs (10-20mL/kg/hour) After initial bolus of normal saline, replacement of the sodium and free water deficit is carried out over the next 12 - 24 h. Total water deficit - 10% of body weight. Replenish total body water deficit - 0.45% saline over 150-500ml/ hr

16. Insulin Therapy : Insulin therapy to be initiated only if potassium levels are above 3.3 mEq /L then Intravenous regular insulin preferred. Initiated with IV bolus of regular insulin (0.1 units/kg) followed by continuous infusion of regular insulin of 0.1 units/kg/hour. SC route may be taken in uncomplicated DKA (0.3 U/kg then 0.2 U/kg one hour later) Target decrease in blood glucose - 50 -100mg/dL Note: Most rapid correction of serum glucose can precipitate cerebral edema

17. Cont ….. When serum glucose reaches 200 mg/dl, reduce insulin infusion to 0.02-0.05U/kg/hour and switch the IV saline solution to dextrose in 0.45% saline. Acidosis and ketosis resolves slowly than hyperglycemia. So insulin infusion should be maintained at lower rate to inhibit ketogenesis. Revert to SC insulin, after patient begins to eat (continue IV infusion simultaneously for 1 to 2 hours).

18. Potassium Replacement: If the initial serum potassium is below 3.3 mEq /L, IV potassium chloride is started with saline (20 to 40 mEq /hour). If the initial serum potassium is between 3.3 and 5.3 mEq /L, IV KCl (20 to 40 mEq ) is added to each liter of IV replacement fluid and continued to maintain serum potassium between 4.0 to 5.0 mEq /L range. If the serum potassium is initially greater than 5.3 mEq /L, then potassium replacement should be delayed.

19. Correction of Acidosis Bicarbonate therapy still remains a controversial subject, as clear evidence of benefit is lacking. Indications ○ pH < 6.9 ○ Bicarbonate < 5mEq/L ○ Shock/coma ○ Severe hyperkalemia 50 mEq of sodium bicarbonate in 200 mL sterile water isadministered over 2 hours with potassium supplements. Repeat doses until pH rises above 7.0.

20. Complications : Lactic acidosis Arterial thrombosis - stroke, MI, peripheral limb ischemia Venous thrombosis - DVT, CVT Cerebral edema (rare in adults) Rebound ketoacidosis Late hypoglycemia Gastric dilatation (vomiting of bloody and dark material) Respiratory distress syndrome Infections (pneumonia, cystitis)

21. HYPERGLYCEMIC HYPEROSMOLAR STATE HHS is an subacute metabolic complication with high morbidity and mortality occurring in middle aged and elderly diabetics. Precipitating factors Infection - Sepsis, Pnemonia, UTI, MI, Prior stroke Drugs - Diazoxide, Diuretics , Phenytoin , Chlorpromazine

22. Pathophysiology: Relative insulin deficiency and inadequate fluid intake are the underlying causes of HHS Insulin deficiency - increase glycogenolysis, gluconeogenesis and impairs peripheral glucose utilization. Less severe insulin deficiency and lower level of counter regulatory hormones and FFA compared to DKA are responsible for absence of ketosis in HHS

23. Clinical Manifestations Earliest symptoms are polyuria, polydipsia, weight loss, malaise, generalized weakness, fatigability , dehydration, hypotension, tachycardia and shock As the duration of hyperglycemia progresses, neurologic symptoms including lethargy, focal signs, seizures, obtundation and frank coma can develop. Nausea, vomiting and abdominal pain are usually absent. Kussmaul respiration and fruity odor of breath are absent.

24. Diagnosis: Marked Hyperglycemia >600mg/dl Hyperosmolality >330 mosm /L Absence of acidosis and ketonemia (Small anion gap metabolic acidosis and moderate ketonuria may be present secondary to lactic acidosis and starvation respectively)

25. Management : Correction of fluid loss with intravenous fluids. Correction of hyperglycemia with insulin. Correction of electrolyte disturbances, particularly potassium. Correction of precipitating causes.

26. Correction of Fluid : Fluid loss and dehydration are more pronounced in HHS. Recommended fluid - isotonic saline. 0.45% saline once euvolumic or serum Na+ >150 mEq/l Replete circulating volume - 1- 3 L of isotonic saline over first 2 - 3 hrs. After initial bolus of normal saline, replacement of the sodium and free water deficit is carried out over the next 1 - 2days Total water deficit - 25% of body weight Replenish total body water deficit - 0.45% saline over 200-300ml/ hr

27. Insulin Therapy Insulin therapy to be initiated only if potassium levels are above 3.3 mEq /L then intravenous regular insulin preferred. Initiated with IV bolus of regular insulin (0.1 units/kg) followed by continuous infusion of regular insulin of 0.1 units/kg/hour. Target decrease in blood glucose - 50-100mg/dL

28. A low dose heparin may be advantageous to prevent vascular thrombosis and intramuscular coagulation. Seizure in HHS should not be treated with phenytoin as it worsens hyperglycemia by impairing insulin release.

29. Hypoglycemia in DM Hypoglycemia is a reversible condition associated with severe morbidity and if severe can be fatal. It is a limiting factor in the glycemic management of diabetes mellitus and requires more complex treatment. T he incidence of hypoglycemia is higher in T1DM but the prevalence of hypoglycemia is higher in T2DM. A person with T1DM suffer an average of 2 episodes per week of symptomatic hypoglycemia and atleast 1 episode per year of severe disabling hypoglycemia

30. Hypoglycemia Associated Autonomic Failure (HAAF) HAAF occurs as a result of interplay between relative or absolute therapeutic excess and and compromised physiologic and behavioral defenses against falling plasma glucose concentrations. Defective glucose counter regulation - loss of physiologic defense Hypoglycemia Unawareness - loss of behavioral defense It causes a vicious cycle of recurrent iatrogenic hypoglycemia.

31. Treatmment : Concious - Oral Glucose tablets or glucose containing food Unconscious - IV Glucose (25 g) or Glucagon 1mg IM/SC (Glucagon is ineffective in alcohol induced hypoglycemia and T2DM) Sulfonylurea induced hypoglycemia - somatostatin analogies (Octreotide)