Chapter 24 Diabetes Mellitus
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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)
24.2 Acute Effects of Diabetes Mellitus
• Acute hyperglycemia
• Diabetic ketoacidosis
• Hyperosmolar nonketotic coma
• Hypoglycemic coma
Acute Hyperglycemia
• Blood glucose is above 240 mg/ml
• Mild symptoms: dry mouth, thirst and increased urination
• Severe symptoms: hypotension, headache and blurred vision
o Lead to ketoacidosis
Diabetic Ketoacidosis
• More common complication of Type 1
• Causes (Figure 24.2)
o Glucose is unavailable to cells
o Increased lipolysis occurs
o Beta oxidation results in more ketones (acids) production
o Resulting acidosis = ketoacidosis
• Symptoms
o Mild:
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Dehydration
Electrolyte imbalance
Tachypnea (rapid breathing)
o Severe
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 Coma
 Death
Treatment
o Insulin
o Rehydration with fluids and electrolytes
o Bicarbonate (severe cases)
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Failure to treat can result in
o Cardiovascular failure
o Coma
o Death
Hyperosmotic Nonketotic Coma
• Common in elderly with diabetes
• Glucose levels: 600–2400 mg/dL
• Cause
o Osmotic pull of water into urine
o Severe dehydration
o Coma likely: blood = 325 mOsm
• Primary danger—blood clots (Many elderly patients have increased thrombus formation)
• Treatment is similar to that of ketoacidosis
Hypoglycemic Coma
• Caused by insulin overdose
o Lowers blood glucose
o Blood glucose <50 mg/dL = hypoglycemia
• Hypoglycemic symptoms:
o Nausea, trembling, hunger;
o Blurred vision, dizziness, confusion and lethargy
o Seizures and coma
• Treatment:
o Consume simple carbohydrates
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Fruit juice
Soda
Hard candy
23.3 Chronic Complications: Early
• Three polys (Figure 24.3)
o Polyuria: Excessive urination:
o Polydipsia: Excessive thirst
o Polyphagia: Excessive eating
• Polyuria
o Direct result of hyperglycemia
o Glucose in renal tubules increase the osmotic force for water to move into lumen
• Polyphagia
o No satiety because of low
o Insulin
o Cholecystokinin (CCK)
• Polydipsia
o Dehydration
o Decreased blood pressure elevates angiotensin II (vasoconstrictor) in blood
o Increased thirst due to the elevated level of angiotensin II
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24.4 Chronic Complications: Advanced Stages
• Adverse effects of hyperglycemia
• Adverse effects on the microvasculature
Adverse Effects of Hyperglycemia (Figure 24.4)
• Glycosylation
o Addition of glucose to protein to form AGE = advanced glycosylation end-products
o Impair protein activities
o Glycosylation of
o Hemoglobin (HbA1c): marker of DM
o Fibronectin: compromises wound healing
• Limitation of cell activity
• Promotion of glucose conversion to sorbitol
o Causes tissue damages (cataract formation)
o Generate oxidative stress
• Generation of free radicals and oxidative stress (include protein kinesis C that activates the
production of vasodilators)
• All of these promotion of microvasculature damage
Metabolic Handling of Glucose (Figure 24. 5)
Production of Superoxide: O2- (Figure 24.6)
Hyperglycemia and Microvascular Disease (Figure 24.7)
Adverse Effects of Diabetes Mellitus on the Microcirculation (Table 24.2)
• Retinopathy
• Nephropathy
• Neuropathy
• 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
• Macrovasculature disease complications
o Increased lipid transport to cells
o Production of reactive oxygen species
o Formation of free radicals
• Atherosclerosis
o May progress to heart attack or stroke
o May lead to cardiomyopathy
Normal Wound Healing (Figure 24.9)
• Phases of normal wound healing
o Phase 1: Inflammation
o Phase 2: Proliferation
o Phase 3: Remodeling
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24.6 Diabetes: Delayed Wound Healing
• Glycosylation
o Decreases activity of neutrophils and macrophages
o Slows the inflammation phase
• Loss of erythrocyte flexibility
o Decreases oxygen delivery
o Prolongs remodeling phase
Diabetes: Delayed Wound Healing
• Decreased secretion of messengers
o Less cytokines and growth factors
o Decreased collagen production by fibroblasts
• Diabetes delay wounding healing by slowing all three phases
o Glycosylation decreases the ability of macrophages and neutrophils to phagocytize
bacteria
o Decreased oxygen supply and nutrients to the healing processes
o Decreased secretion of collagen
• Diabetic foot ulcers (Figure 24.10)
o Can progress
o Require leg amputation
o Due to delayed wound healing and infection.
o Neuropathy may suppress the sensation.
o Both can lead to gangrene (the death of tissues)
o 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
• Carbohydrate intake regulated
• Insulin injections
o Subcutaneous
o Insulin is digested, cannot be taken orally
• Insulin pump
Type 2: Treatment and Management
• Obesity is an issue
o Carbohydrate intake regulated
o Diet important to maintain proper weight
• Oral hypoglycemics
o Sulfonylureas (most common)
o Biguanides
o α-glucosidase inhibitors
o Thiazolidinediones
Current Research on Diabetes Mellitus
• New medicines for the treatment of diabetes mellitus
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Aldose reductase inhibitors
Sorbitol dehydrogenase inhibitors
Glucagon-like peptide-1 (GLP-1)
Autoimmune response against β in type 1 DM
24.8 Current Research on Diabetes Mellitus
• New techniques for insulin administration
o Insulin is a protein
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Digested if taken orally
Injections become choice of insulin delivery
o Alternative routes of insulin administration
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Rectal
Ocular
Nasal
Oral in encapsulated form
Research: Nonpharmaceutical Therapies
• Treatment of Type 1 diabetes mellitus
o Replicate β cells
o Stem cell transplant
o Gene therapy
o Prevention of β cell loss
Research: Nonpharmaceutical Therapies
• Treatment of Type 2 diabetes mellitus
o Gene therapy
o Weight loss
o Diet and lifestyle changes
o Bariatric surgery
o Exercise
Clinical Connections 24.1 Surgical gastric banding options.
More information:
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www.diabetes.org
http://www.niddk.nih.gov/health-information/health-topics/diabetes/Pages/default.aspx
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