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Diabetes Mellitus..an understanding

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Diabetes Mellitus

Diabetes Mellitus

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  • Extra note: Insulin resistance (IR) is a condition in which cells fail to respond to the normal actions of the hormone insulin. The body produces insulin, but the cells in the body become resistant to insulin and are unable to use it as effectively, leading to hyperglycemia.

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  • 1. Pratap sagar Tiwari, MD, Internal Medcine, Lecturer, NMCTH UNDERSTANDING DIABETES..PART 1
  • 2. CASE SUMMARY • A 30 yrs old M was brought in ERD in the state of unconsciousness. (Note: Coma is a symptom, not a diagnosis.) Pic taken from http://censorbugbear-reports.blogspot.com/2010/03/shocking-neglect-of-comatose-patient-at.html
  • 3. CAUSES OF COMA Metabolic Coma Structural Coma Hypoglycemia Stroke DKA/ HONK Head injury/trauma Toxins/poison/drugs Subarachnoid hemorrhage Uremic encephalopthy Subdural/epidural hematoma Hepatic encephalopathy Tumours Infectious/sepsis Hypoxia (anoxic brain injury)/hypercapnic Hypo/hyperthermia Electrolyte disturbances Seizures Myxedema coma/ Addisonian crisis
  • 4. DEFINITIONS • The normal state of consciousness comprises either the state of wakefulness, awareness, or alertness. • Clouding of consciousness is a very mild form of altered mental status in which the patient has inattention and reduced wakefulness. • Confusional state is a more profound deficit that includes disorientation, bewilderment, and difficulty following commands. • Lethargy consists of severe drowsiness in which the patient can be aroused by moderate stimuli and then drift back to sleep.
  • 5. DEFINITIONS • Obtundation is a state similar to lethargy in which the patient has a lessened interest in the environment, slowed responses to stimulation, and tends to sleep more than normal with drowsiness in between sleep states. • Stupor means that only vigorous and repeated stimuli will arouse the individual, and when left undisturbed, the patient will immediately lapse back to the unresponsive state. • Coma is a state of unarousable unresponsiveness.
  • 6. OTHERS • [Sudden] cardiac arrest is the sudden cessation of cardiac activity so that the victim becomes unresponsive, with no normal breathing and no signs of circulation. • Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that occurs in a short time period (generally within 1 hour of symptom onset) in a person with known or unknown cardiac disease. References: American College of Cardiology/American Heart Association Task Force on Clinical Data Standards , Buxton AE, Calkins H, et al. Circulation 2006; 114:2534.
  • 7. CASE SUMMARY • A 30 yrs old M was brought in ERD in the state of unconsciousness. Pic taken from http://censorbugbear-reports.blogspot.com/2010/03/shocking-neglect-of-comatose-patient-at.html 1. Hypoglycemia due to Insulin therapy /OHA 2. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults
  • 8. INSULIN SYNTHESIS AND SECRETION Taken from Harrison 18th edition
  • 9. INSULIN • Insulin is a peptide hormone composed of 51 amino acids that is synthesized, packaged, and secreted by pancreatic beta cells. • Insulin is synthesized as preproinsulin in the ribosomes of the rough endoplasmic reticulum. • Preproinsulin is then cleaved to proinsulin, which is transported to the Golgi apparatus where it is packaged into secretory granules located close to the cell membrane. • Proinsulin is cleaved into equimolar amounts of insulin and C- peptide in the secretory granules .
  • 10. REGULATION OF GLUCOSE HEMOSTASIS Insulin has a number of effects on glucose metabolism, including: • Inhibition of glycogenolysis and gluconeogenesis • Increased glucose transport into fat and muscle • Increased glycolysis in fat and muscle • Stimulation of glycogen synthesis • Glucagon acts on the liver, increasing glucose production by stimulating both glycogenolysis and gluconeogenesis from alanine, among other amino acids, and glycerol.
  • 11. RESPONSE TO HYPOGLYCEMIA IN NORMAL SUBJECTS • In the fasting state, when glucose cannot be obtained from the intestinal absorption of food, glucose counterregulatory mechanisms prevent or rapidly correct falling plasma glucose concentrations . 1. Counterregulatory defence 2. Behavioral defence
  • 12. COUNTERREGULATORY HORMONES • The 1st defense is a decrease in insulin secretion as plasma glucose concentrations decline within the physiological range (starting at an venous PG threshold of 80-85 mg/dL ) • The 2nd defense is an increase in glucagon secretion. (The glycemic threshold for glucagon is 65 to 70 mg/dL ) • The 3rd is an increase in epinephrine secretion. Acting via beta- 2-adrenergic receptors, epinephrine has similar hepatic effects as glucagon. (The threshold for epinephrine secretion is 65 to 70 mg/dL ) • Cortisol and growth hormone contribute only if the hypoglycemia persists for several hours. These hormones limit glucose utilization and enhance hepatic glucose production.
  • 13. BEHAVIORAL DEFENSES • The initial symptoms of sweating, anxiety, palpitations, hunger, and tremor occur as the plasma glucose concentration falls below 55-65 mg/dL. • These symptoms trigger the important behavioral defense, ie, the ingestion of food. • They are signaled largely by increased sympathetic neural activity. • Hypoglycemia can also cause cognitive dysfunction, which occurs in normal subjects at PG below 50 mg/dL. Cognitive dysfunction can impair behavioral defenses. More severe neurologic symptoms, including obtundation, seizures, and coma, occur with progressive hypoglycemia. Profound and prolonged hypoglycemia can cause brain death.
  • 14. RESPONSE TO HYPOGLYCEMIA IN DIABETES • Impairment of behavioral and counterregulatory responses. • The main defense against hypoglycemia is increased release of counterregulatory hormones (glucagon and epinephrine), which raise plasma glucose concentrations by stimulating glucose production and by antagonizing the insulin-induced increase in glucose utilization.
  • 15. HYPOGLYCEMIA • In patients without diabetes, hypoglycemia is a clinical syndrome with diverse causes in which low plasma glucose concentrations lead to symptoms and signs, and there is resolution of the symptoms/signs when the plasma glucose concentration is raised [1]. • In patients with diabetes, hypoglycemia is defined as all episodes of an abnormally low plasma glucose concentration (with or without symptoms) that expose the individual to harm. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2009; 94:709.
  • 16. SIGN/SYMPTOMS OF HYPOGLYCEMIA Autonomic response (tends to occur with blood glucose below 55-65 mg/dL) - Sweating , Tachycardia, palpitation - Weakness, Hunger, Paresthesias - Tremor, Nervousness • Neuroglycopenia below 50 mg/dL (2.8 mmol/L) - Irritability, Confusion - Seizure, Occasionally, transient focal neurologic deficits - Visual disturbance, Loss-of-consciousness
  • 17. DKA • DKA is an acute, major, life-threatening complication of diabetes that mainly occurs in patients with type 1 DM, but it is not uncommon in some patients with type 2 DM. • This condition is a complex disordered metabolic state characterized by hyperglycemia, ketoacidosis, and ketonuria. Hyperglycemia Ketoacidosis
  • 18. DKA Insulin def/ resistance Inhibition of “insulin inhibition of Glucagon” ↑ Glucagon ↑ fat/muscle breakdown ↑ Hepatic gluconeogenesis ↑ delivery of gluconeogenetic precursors to Liver ↑ Glycerol/ Alanine
  • 19. Glycosuria ↓ Glucose excretion ↓ GFR Osmotic Diuresis Volume Depletion ↑ Blood GLucose
  • 20. Action of Insulin: ↑ utilisation of peripheral glucose in skeletal muscle ↑ Blood Sugar X Insulin↓/ Resistance (Note: Insulin resistance is a condition in which cells fail to respond to the normal actions of the hormone insulin. The body produces insulin, but the cells in the body become resistant to insulin and are unable to use it as effectively, leading to hyperglycemia.)
  • 21. Insulin def/ resistance Glucose utilization is impaired Alternate source of Energy : KETONES ↑ Lipolysis TG FFA Normally Plus increased catecholamines
  • 22. DEVELOPMENT OF KETOACIDOSIS • The development of ketoacidosis requires a specific alteration in hepatic metabolism so that free fatty acyl CoA can enter the mitochondria, where conversion to ketones occurs. • Mitochondrial entry is regulated by the cytosolic enzyme carnitine palmitoyltransferase I (CPT I), the activity of which varies inversely with malonyl CoA [1]. • Glucagon decreases the production of malonyl CoA, thereby increasing CPT I activity and ketogenesis [2]. • Insulin does not appear to directly affect hepatic ketogenesis [3]. 1. McGarry JD, Woeltje KF, Kuwajima M, Foster DW. Regulation of ketogenesis and the renaissance of carnitine palmitoyltransferase. Diabetes Metab Rev 1989; 5:271. 2. Cook GA, Nielsen RC, Hawkins RA, et al. Effect of glucagon on hepatic malonyl coenzyme A concentration and on lipid synthesis. J Biol Chem 1977; 252:4421. 3. Miles JM, Haymond MW.. Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man. J Clin Invest 1983; 71:1554.
  • 23. NOTE • Moderate insulin deficiency, as seen in HHS, might be associated with sufficient insulin to block lipolysis (and therefore ketoacid formation) but not enough to promote glucose utilization and prevent the development of hyperglycemia [1]. 1. Hillman K. Fluid resuscitation in diabetic emergencies--a reappraisal. Intensive Care Med 1987; 13:4.
  • 24. BREATHING PATTERNS: CHEYNE-STOKE • characterized by periods of respirations during which the tidal volume starts shallow and gets progressively deeper, and then gets progressively shallower. • This shallow-deep-shallow pattern is followed by periods of significant apnea that can last up to 30 seconds or longer, then the cycle starts over.
  • 25. BIOT’S BREATHING (CLUSTER RESPIRATION) • A respiratory pattern characterized by periods or “clusters” of rapid respirations of near equal depth or followed by regular periods of apnea. • damage to the medulla oblongata by stroke (CVA) or trauma.
  • 26. ATAXIA RESPIRATIONS • Completely irregular breathing pattern with irregular pauses and increasing episodes of apnea. • caused by damage to the medulla oblongata secondary to trauma or stroke.
  • 27. KUSSMAUL’S RESPIRATIONS • A type of labored or hyperventilation characterized by a consistently deep and rapid respiratory pattern. • Most of the time a respiratory pattern secondary to a metabolic acidosis is rapid and shallow and a true kussmaul breathing pattern is rarely reached before the acidosis is corrected
  • 28. APNEUSTIC RESPIRATIONS • have a prolonged inspiratory phase followed by a prolonged expiratory phase commonly believed to be apneic phases. • damage to the upper part of the pons
  • 29. FEATURES OF HYPEROSMOLARITY • Excessive thirst despite frequently taking water / other liquids • Continued high level of blood sugar • Dry and/ or parched mouth • Frequency of urination increases • Pulse rate becomes rapid • Shortness of breath with exertion • Skin becomes dry and warm and there is no sweating • Sleepiness and/ or a condition of confusion http://www.mayoclinic.org/diseases-conditions/diabetic-hyperosmolar-syndrome/basics/definition/con-20026142
  • 30. DIABETES MELLITUS • Diabetes mellitus is a clinical syndrome characterised by hyperglycaemia caused by absolute or relative deficiency of insulin.
  • 31. END OF SLIDES References: 1. Harrison's Principles of Internal Medicine, 18th Edition 2. Davidson Practice of Medicine 3. Uptodate 20.3 4. Standards of Medical Care in Diabetesd 2014. American Diabetes Association. Diabetes Care Volume 37, Supplement 1, January 2014 5. Medscape.com 6. Mercksmanual