Chapter 33 Diabetes Mellitus and the Metabolic Syndrome Essentials of Pathophysiology Chapter 33 Diabetes Mellitus and the Metabolic Syndrome

Pre lecture Quiz Type 2 diabetes is more common than type 1. F Type 2 diabetes is more common than type 1. All cells can use fatty acids interchangeably with glucose for energy. Insulin is produced by the pancreatic beta cells in the islets of Langerhans. Hyperglycemia is characterized by headache, difficulty in problem solving, disturbed or altered behavior, coma, and seizures. Chronic complications of diabetes mellitus refer only to type 1 diabetes mellitus.

Pre lecture Quiz Alpha Insulin ketoacidosis Metabolic one ______________ lowers the blood glucose concentration by facilitating the movement of glucose into body tissues. Glucagon, a polypeptide molecule produced by the _____________ cells of the islets of Langerhans, maintains blood glucose between meals and during periods of fasting. Type __________ diabetes mellitus is characterized by destruction of the pancreatic beta cells and is characterized by an absolute lack of insulin, an elevation in blood glucose, and a breakdown of body fats and protein. The ________________ syndrome is a condition of abnormalities that are identified through specific criteria such as abdominal obesity, elevated triglycerides, elevated blood pressure, elevated fasting plasma glucose, and decreased high-density lipoprotein cholesterol (HDL). Diabetic ____________________ occurs when ketone production by the liver exceeds cellular use and renal excretion. Alpha Insulin ketoacidosis Metabolic one

Anabolism and Catabolism available foodstuffs Anabolism stored foodstuffs (in blood) insulin, (in cells) anabolic steroids glucose glycogen Catabolism amino acids proteins glucagon, epinephrine, free fatty acids cortisol triglycerides liver can convert amino acids and free fatty acids into ketones

Insulin and Glucagon Are the Main Controls available foodstuffs Anabolism stored foodstuffs (in blood) insulin , (in cells) anabolic steroids glucose glycogen Catabolism amino acids proteins glucagon , epinephrine, free fatty acids triglycerides cortisol liver can convert amino acids and free fatty acids into ketones

Question Tell whether the following statement is true or false. Anabolic reactions release energy.

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).

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?

The Pancreas pancreas exocrine endocrine pancreas pancreas releases digestive releases hormones juices through a into the blood duct to the duodenum

endocrine pancreas: islets of Langerhans alpha beta cells delta cells PP cells cells insulin pancreatic glucagon somatostatin and amylin polypeptide

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

Question Which pancreatic hormone decreases blood glucose levels? Glucagon Insulin Amylin Somatostatin

Answer 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.

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?

Review the figure on insulin’s actions. 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?

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?

Anabolism and Catabolism available foodstuffs Anabolism stored foodstuffs (in blood) insulin, (in cells) anabolic steroids glucose glycogen Catabolism amino acids proteins glucagon, epinephrine, free fatty acids cortisol triglycerides liver can convert amino acids and free fatty acids into ketones

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

Pathogenesis of Type 2 Diabetes

Question Tell whether the following statement is true or false. Type 2 DM is more common than type 1 DM.

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.

Metabolic Syndrome Abdominal obesity Increased blood triglyceride levels Decreased HDL levels Increased blood pressure Increased fasting plasma glucose

Treatments for Type 2 diabetes

Acute Complications of Diabetes Diabetic ketoacidosis Hyperglycemic hyperosmolar nonketotic coma Hypoglycemia Somogyi effect Dawn phenomenon

Acute Complications of Diabetes (cont.) Discussion How would hyperglycemia with ketoacidosis cause: Heavy breathing? Polyuria? Dehydration? Which of these would you not see in hyperglycemia without ketoacidosis?

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?

Chronic Complications of Diabetes Mellitus Increased glucose levels allow glucose to bind to proteins in: Hemoglobin  Hb A1C has higher O2 affinity Basement membranes of blood vessels Nephropathy Retinopathy May 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.)

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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 Hypotonic cell A shrinks A B Cell B is in osmotic balance (Porth, C. M. [2005]. Pathophysiology [7th ed.]. 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 O2 secondary to vascular disease A Cell A is in osmotic balance B Hypertoniccell B swells (Porth, C. M. [2005]. Pathophysiology [7th ed.]. Lippincott Williams & Wilkins.)

Diabetic Neuropathy Somatic neuropathy Autonomic 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

Question Which of the following is not a complication of diabetes mellitus? Nephropathy Retinopathy Neuropathy All of the above are complications of DM.

Answer 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.

Advanced Diabetic Foot Ulcer Typical Diabetic Foot Ulcer Advanced Diabetic Foot Ulcer