Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 32 Diabetes Mellitus and the Metabolic Syndrome

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Anabolism and Catabolism Anabolism insulin, anabolic steroids Catabolism glucagon, epinephrine, cortisol available foodstuffs (in blood) glucose amino acids free fatty acids stored foodstuffs (in cells) glycogen proteins triglycerides liver can convert amino acids and free fatty acids into ketones

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Insulin and Glucagon Are the Main Controls Anabolism insulin, anabolic steroids Catabolism glucagon, epinephrine, cortisol available foodstuffs (in blood) glucose amino acids free fatty acids stored foodstuffs (in cells) glycogen proteins triglycerides liver can convert amino acids and free fatty acids into ketones

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Tell whether the following statement is true or false. Anabolic reactions release energy.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer False Rationale: Anabolic reactions use energy to build/produce/synthesize (like building proteins from amino acids). Catabolic reactions break down substances, releasing energy in the process (like digestion).

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Scenario Two women have benign pancreatic tumors. In one, the tumor is an insulinoma that secretes insulin In the other, the tumor is a glucagonoma that secretes glucagon Questions: What differences do you expect to see between these two women? Why? Both of the women have arthritis, but only one is being treated with corticosteroids. Which one? Why is the other not receiving corticosteroids?

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins The Pancreas pancreas exocrine pancreas releases digestive juices through a duct to the duodenum endocrine pancreas releases hormones into the blood

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins endocrine pancreas: islets of Langerhans alpha cells beta cells delta cellsPP cells pancreatic polypeptide glucagon insulin and amylin somatostatin

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Functions of Pancreatic Hormones Glucagon: causes cells to release stored food into the blood Insulin: allows cells to take up glucose from the blood Amylin: slows glucose absorption in small intestine; suppresses glucagon secretion Somatostatin: decreases GI activity; suppresses glucagon and insulin secretion

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Question Which pancreatic hormone decreases blood glucose levels? a.Glucagon b.Insulin c.Amylin d.Somatostatin

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer b.Insulin Rationale: Insulin allows cells to take glucose from the blood and use it for energy/to make ATP. Because it stimulates movement of glucose out of the blood and into the cells, blood glucose levels decrease when insulin is released.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Discussion Think back on your day so far. When do you think you had your highest insulin levels? When do you think you had your lowest insulin levels? When did you have your highest glucagon levels?

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Discussion Review the figure on insulin’s actions. If someone lacks insulin, what happens to his: –Blood glucose levels? –Blood amino acid levels? –Blood pH? –Intracellular fat levels? –Intracellular protein levels? –Cell growth?

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Discussion Review the following diagrams on anabolism/catabolism and insulin’s mechanism of action. Questions: Identify five things that could go wrong to cause increased blood glucose Which of the cases you identified would be least likely to respond to insulin?

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Anabolism and Catabolism Anabolism insulin, anabolic steroids Catabolism glucagon, epinephrine, cortisol available foodstuffs (in blood) glucose amino acids free fatty acids stored foodstuffs (in cells) glycogen proteins triglycerides liver can convert amino acids and free fatty acids into ketones

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Types of Diabetes Mellitus Type 1: pancreatic beta cell destruction predominantly by an autoimmune process Type 2: a combination of beta cell dysfunction and insulin resistance Other –Genetic defects in insulin production –Genetic defects in insulin action –Diabetes secondary to other diseases –Drug interactions Gestational diabetes mellitus

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Pathogenesis of Type 2 Diabetes

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Tell whether the following statement is true or false. Type 2 DM is more common than type 1 DM.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer True Rationale: Type 1 DM is autoimmune (juvenile diabetes is type 1), and affects only 5–10% of the diabetic population. Type 2 DM is associated with risk factors like obesity, poor diet, and sedentary lifestyle; 90–95% of diabetics suffer from this type.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Metabolic Syndrome Abdominal obesity Increased blood triglyceride levels Decreased HDL levels Increased blood pressure Increased fasting plasma glucose

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Treatments for Type 2 diabetes

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Acute Complications of Diabetes Diabetic ketoacidosis Hyperglycemic hyperosmolar nonketotic coma Hypoglycemia Somogyi effect Dawn phenomenon

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Discussion How would hyperglycemia with ketoacidosis cause: –Heavy breathing? –Polyuria? –Dehydration? Which of these would you not see in hyperglycemia without ketoacidosis? Acute Complications of Diabetes (cont.)

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Scenario You find a man collapsed on the sidewalk. He is wearing a diabetic alert bracelet and has an insulin syringe in his briefcase Questions: Does he need insulin? Why or why not? What signs might help you tell whether he has a hyperglycemic or hypoglycemic problem?

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Chronic Complications of Diabetes Mellitus Increased glucose levels allow glucose to bind to proteins in: –Hemoglobin  Hb A1C has higher O 2 affinity –Basement membranes of blood vessels ºNephropathy ºRetinopathy ºMay cause increased risk of atherosclerosis –Lens  cataracts (Porth, C. M. [2005]. Pathophysiology [7th ed.]. Lippincott Williams & Wilkins and Greenspan, F. & Gardner, D. G. [2004]. Basic and clinical endocrinology [7th ed.]. McGraw-Hill.)

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Osmolarity in Diabetes Mellitus When blood glucose is high, increased blood osmolarity can cause cells to shrink Nerve cells produce intracellular osmoles to keep their osmolarity balanced with the blood A B Hypotonic cell A shrinks Cell B is in osmotic balance (Porth, C. M. [2005]. Pathophysiology [7th ed.]. Lippincott Williams & Wilkins.)

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Osmolarity in Diabetes Mellitus (cont.) When the client brings blood glucose back to normal, the nerve cells are hyperosmolar to the blood and gain water, swelling Nerve damage may be caused by swelling, demyelination, and lack of O 2 secondary to vascular disease A B Cell A is in osmotic balance Hypertonic cell B swells (Porth, C. M. [2005]. Pathophysiology [7th ed.]. Lippincott Williams & Wilkins.)

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Diabetic Neuropathy Somatic neuropathy –Diminished perception of vibration, pain, and temperature –Hypersensitivity to light touch; occasionally, severe “burning” pain Autonomic neuropathy –Defects in vasomotor and cardiac responses –Impaired motility of the gastrointestinal tract –Inability to empty the bladder –Sexual dysfunction

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Which of the following is not a complication of diabetes mellitus? a.Nephropathy b.Retinopathy c.Neuropathy d.All of the above are complications of DM.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer d.All of the above are complications of DM. Rationale: Nephropathy and retinopathy are caused by increased blood glucose levels that cause binding of excess glucose to the basement membranes of the blood vessels of the kidneys and eyes. Neuropathy is due to swelling and demyelination of nervous tissue.