Chapter 24 Diabetes Mellitus

Transcription

1 Chapter 24 Diabetes Mellitus Classification of Diabetes Mellitus Acute Effects of Diabetes Mellitus Chronic Complications of Diabetes Mellitus: Early Stages Chronic Complications of Diabetes Mellitus: Advanced Stages Progression of Diabetes Mellitus to Critical States Delayed Wound Healing Treatment and Management of Diabetes Mellitus Current Research on Diabetes Mellitus Figure 1.9 Prevalence of diabetes in the world Figure 24.1 Effects of diabetes on organs throughout the body 24.1 Classification of Diabetes Mellitus (Table 23.1) a. Type 1 DM b. Type 2 DM Which type is an autoimmune disease of pancreatic beta cells? Which type is more prevalent? Which type is insulin dependent? Which type is insulin independent? Which one shows the presence of antibodies to beta-cell components? Which form dependents more on a familial history? 24.2 Acute Effects of Diabetes Mellitus Acute hyperglycemia Diabetic ketoacidosis Hyperosmolar nonketotic coma Hypoglycemic coma Acute Hyperglycemia o Is short term, when blood glucose is above 240 mg/ml o Mild symptoms: dry mouth, thirst and increased urination o Severe symptoms: hypotension, headache and blurred vision Lead to ketoacidosis Diabetic Ketoacidosis o More common complication of Type 1 o Causes (Figure 24.2) Hormone- induced metabolic pathway alterations Low level causes hyperglycemia, however glucose is unavailable to cells Increased lipolysis due to increased secretion of,, and results in more (acids) production Resulting acidosis = ketoacidosis o Symptoms Mild: Dehydration, electrolyte imbalance and tachypnea (rapid breathing) Severe: Coma and death 1

2 o Treatment Insulin Rehydration with fluids and electrolytes Bicarbonate (severe cases) o Failure to treat can result in Cardiovascular failure Coma Death Hyperosmotic Nonketotic Coma o Common in elderly with diabetes o Cause Glucose levels: Osmotic pull of water into urine triggers Decreased blood volume and blood pressure level causes cells to switch to glycolysis and cause acidosis Coma likely: blood = 325 mosm o Primary danger blood clots (Many elderly patients have increased thrombus formation) o Treatment is similar to that of ketoacidosis Hypoglycemic Coma o Caused by insulin overdose Lowers blood glucose Blood glucose <50 mg/dl = hypoglycemia o Hypoglycemic symptoms: Nausea, trembling, hunger; Blurred vision, dizziness, confusion and lethargy Seizures and coma o Treatment: Consume simple carbohydrates such as fruit juice, soda and hard candy 23.3 Chronic Complications: Early Three polys (Figure 24.3) o Polyuria: Excessive o Polydipsia: Excessive o Polyphagia: Excessive Polyuria o Direct result of o Glucose in renal tubules increase the osmotic force for water to move into lumen Polyphagia o No satiety because of low and low (CCK) Polydipsia o Dehydration: Decreased MAP elevates angiotensin II (vasoconstrictor) in blood o Increased thirst due to the elevated level of 2

3 24.4 Chronic Complications: Advanced Stages Adverse Effects of Hyperglycemia (Figure 24.4) o due to decreased ability to extract energy from glucose. It promotes arthrosclerosis. o Glycosylation is the addition of to protein to form AGE = advanced glycosylation endproducts. o Glycosylation activities. Glycosylation of hemoglobin (HbA1c): marker of DM Glycosylation of fibronectin: compromises wound healing o Generation of Promotion of glucose conversion to sorbitol and generate oxidative stress Causes tissue damages (cataract formation) Increase protein kinesis C that activates the production of vasodilators and cause All of these promote damage o Metabolic Handling of Glucose (Figure 24. 5) o Production of Superoxide: O2 - (Figure 24.6) o Hyperglycemia and Microvascular Disease (Figure 24.7) Adverse Effects of Diabetes Mellitus on the Microcirculation (Table 24.2) o Retinopathy o Nephropathy o Neuropathy o Delayed wound healing 24.5 Progression of Diabetes Mellitus Lifelong progression o Macrovasculature effects o Diabetic cardiomyopathy Complications can cause death Progression of Diabetes Mellitus o Macrovasculature disease complications affect large blood vessels Increased lipid transport to cells Production of reactive oxygen species Formation of free radicals Is secondary to Increase LDLs and decrease HDLs; therefore increase atherosclerosis Atherosclerosis may progress to heart attack or stroke May lead to cardiomyopathy Cause macrovasculature damage 24.6 Diabetes: Delayed Wound Healing Phases of normal wound healing (24.9) o Phase 1: o Phase 2: o Phase 3: 3

4 Functions 1) Macrophages These cells start the proliferative phase by laying down new extracellular matrix and they also secrete chemicals that stimulate keratinocyte proliferation. 2) Neutrophils These cells are first recruited to the wounding site and they initiate the inflammatory phase. 3) Fibroblasts These cells arrive 10 hours later. They attack the foreign invaders by phagocytosis. They also secrete chemicals to attract fibroblast to the wounding area. Diabetes: Delayed Wound Healing o Glycosylation Decreases activity of neutrophils and macrophages to phagocytize bacteria Slows the inflammation phase o Loss of erythrocyte flexibility Decreases oxygen delivery Prolongs remodeling phase and decrease healing o Decreased secretion of messengers Less cytokines and growth factors Decreased collagen production by fibroblasts o Diabetes delay wounding healing by slowing o Diabetic foot ulcers (Figure 24.10) Can progress Require leg amputation Due to delayed wound healing and infection. Neuropathy may suppress the sensation. Both can lead to gangrene (the death of tissues) 84% of amputations started with foot ulcer 24.7 Treatment and Management of Diabetes Currently there is no cure for diabetes mellitus Disease is managed Primary focus: Maintain normal blood glucose Type 1: Treatment and Management o o o Insulin is a protein and is digested, cannot be taken orally Insulin pump Type 2: Treatment and Management o Life style change: exercise and diet important to maintain proper weight o Oral hypoglycemics o Sulfonylureas (most common) stimulate insulin release o Biguanides reduce glucose production and increase cells sensitivity to insulin 4

5 o α-glucosidase inhibitors decrease the ability to form glucose after a meal. o Thiazolidinediones increase cells sensitivity to insulin. New Medicine for DM Treatment o Aldose reductase inhibitors o Sorbitol dehydrogenase inhibitors o Glucagon-like peptide-1 (GLP-1) o Autoimmune response against β in type 1 DM 24.8 Current Research on Diabetes Mellitus New techniques for insulin administration o Rectal o Ocular o Nasal o Oral in encapsulated form Research: Nonpharmaceutical Therapies o Treatment of Type 1 diabetes mellitus Replicate β cells Stem cell transplant Gene therapy Prevention of β cell loss o Treatment of Type 2 diabetes mellitus Gene therapy Weight loss Diet and lifestyle changes Bariatric surgery (Clinical Connections 24.1 Surgical gastric banding options). Exercise More information: Diabetes Health Topic 5