Prevalence of Diabetes in United States DIABETES MELLITUS  24 million people (8% of populaJon)  Another 57 million pre-­‐diabeJc from a lecture by C.L. Stanfield, HAPS June, 2010
Diabetes the Disease Diabetes: Projected Cases Worldwide I.
ClassificaJon of Diabetes Mellitus II.
Risk Factors III.
Diagnosing Diabetes Mellitus IV.
Acute Effects of Diabetes Mellitus V.
Chronic ComplicaJons of Diabetes Mellitus: Early Stages VI.
Chronic ComplicaJons of Diabetes Mellitus: Advanced Stages VII.  Progression of Diabetes Mellitus to CriJcal States VIII.  Treatment and Management of Diabetes Mellitus IX.
Current Research on Diabetes Mellitus Figure 1.9
I. Classifica=on • Diabetes mellitus type 1 –  (Insulin-­‐dependent) –  (Juvenile-­‐onset) • Diabetes mellitus type 2 –  (Non-­‐insulin dependent) –  (Adult-­‐onset) –  By far, most prevalent (>90%) Type 1 Diabetes Mellitus –  Autoimmune disease of endocrine pancreas •  Damage to beta cells that produce insulin •  Insufficient amounts of insulin produced •  Progressive unJl disease state –  Percent cases: 5–10 % in US –  Other names •  IDDM = insulin-­‐dependent diabetes mellitus •  Juvenile-­‐onset diabetes mellitus 1
Type 2 Diabetes Mellitus –  Target cells: decreased response to insulin –  Percent cases: 90–95% in US –  Other names •  IIDM = insulin-­‐independent diabetes mellitus •  NIDDM = non-­‐insulin-­‐dependent diabetes mellitus •  Adult-­‐onset diabetes mellitus Diabetes: by Age and Gender Obesity and Diabetes II. Risk Factors • Who gets diabetes? • Increases with: –  Age –  Obesity • Varies with ethnicity Diabetes: by Ethnicity/Ancestry BMI and Diabetes • Obesity measured on the Body Mass Index or BMI scale, which measures the weight relaJve to the height BMI = Body Weight (kilograms) Height (meters)2 2
The Diabetes Epidemic –  Diabetes is a metabolic disease •  Blood glucose levels are affected •  Plasma volumes are affected –  Diabetes results in •  Excessive thirst •  Massive fluid loss –  Diabetes affects every system Diagnosing Diabetes –  Oral glucose tolerance test –  Procedure •
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III. Diagnosing Diabetes –  FasJng plasma glucose test •  Measurement of blood glucose levels while fasJng •  60–100 mg/dL: normal •  100–125 mg/dL: pre-­‐diabetes •  >125 mg/dL: indicates diabetes –  Hemoglobin A1c (HbA1c) •  Minor component of hemoglobin which glucose is bound •  Referred to as glycosylated hemoglobin •  Measure levels of HbA1c > 7% indicates diabetes Graphical Analysis of Data Oral Glucose Tolerance Test Baseline blood sample is drawn PaJent given a measured dose of glucose soluJon to drink within a 5 minutes 1.75 grams of glucose per kilogram of body weight Maximum dose 75 grams –  Results •  <139 mg/dl: normal •  140–199 mg/dl: pre-­‐diabetes •  200 and greater: diabetes http://www.rajeun.net/assess.html
IV. Acute Effects of Diabetes Mellitus –  DiabeJc ketoacidosis –  Hyperosmolar nonketoJc coma –  Hypoglycemic coma Diabe=c Ketoacidosis –  More common complicaJon of Type 1 –  Glucose is unavailable to cells and epinephrine levels are elevated (due to low blood volume and baroreceptor reflex) •  Lipolysis occurs: Increase fajy acids in blood •  Beta oxidaJon in liver results in ketones (acids) –  ResulJng acidosis = ketoacidosis •  Ketones in urine •  More dehydraJon (thus more epinephrine) •  Electrolyte imbalance 3
How will body compensate? •  Metabolic acidosis •  Respiratory and renal compensaJon –  RespiraJon: Tachypnea –  Renal: Increased hydrogen ion secreJon and bicarbonate reabsorpJon and synthesis Diabe=c Ketoacidosis Treatment –  Treatment •  Insulin •  RehydraJon with fluids and electrolytes •  Bicarbonate (severe cases) –  Failure to treat can result in •  Cardiovascular failure •  Coma •  Death Hyperosmo=c Nonketo=c Coma –  Common in elderly with diabetes –  Glucose levels: 600–2400 mg/dL –  OsmoJc pull of water into urine •  Severe dehydraJon •  Coma likely: blood = 325 mOsm Hyperosmo=c Nonketo=c Coma –  Treatment •  Insulin injecJons •  Replace fluids and electrolytes –  Primary danger—blood clots –  Weakened baroreceptor reflex in elderly, so fajy acids and ketones are not as elevated Hypoglycemic Coma –  Caused by insulin overdose •  Lowers blood glucose •  Blood glucose <50 mg/dL = hypoglycemia –  Can result in seizures and coma –  Treatment: Consume simple carbohydrates Chronic Complica=ons of Diabetes Mellitus –  Early stages –  Advanced stages •  Fruit juice •  Soda •  Hard candy 4
Chronic Complica=ons: Early V. Chronic Complica=ons: Early Stages –  Three polys •  Polyuria •  Polydipsia •  Polyphagia Chronic Complica=ons: Early –  Polydipsia •  Increased thirst •  Caused by dehydraJon VI. Chronic Complica=ons: Advanced Stages –  Effects of hyperglycemia –  Effects on microvasculature –  Polyuria •  Increased urine producJon •  Direct result of hyperglycemia Chronic Complica=ons: Early –  Polyphagia •  Increased hunger •  No saJety because of low insulin Effects of Hyperglycemia –  LimitaJon of cell acJvity –  GlycosylaJon •  Hemoglobin (HbA1c): marker of Diabetes Mellitus •  FibronecJn: compromises wound healing •  Increases capillary permeability •  Elevated LDLs, decreased HDLs –  Increased free radicals and oxidaJve stress 5
Hyperglycemia and Microvascular Disease Effects on Microcircula=on –  ReJnopathy –  Nephropathy –  Neuropathy –  Delayed wound healing Re=nopathy Nephropathy •  Approximately 30% of people with diabetes will develop some level of nephropathy •  DiabeJc nephropathy is the number one cause of end-­‐stage renal disease in the United States Non-­‐proliferaJve stage: starts with microaneurysms, followed by blockage of blood vessel ProliferaJve stage: many new blood vessels form (angiogenesis) to compensate for the decrease in blood flow due to blockage of blood vessels, but these new blood vessels are weak and leaky, causing blurred vision and possibly blindness.
Neuropathy Neuropathies of Sensory Systems •  DiabeJc neuropathy occurs in the peripheral nervous system, affecJng afferents and efferents of both the somaJc and autonomic nervous systems •  Parasthesia (abnormal sensaJon of the skin such as Jngling, pricking, or numbness) •  Dysthesia (unpleasant sensaJon produced by normally innocuous sJmuli) •  Pain •  Altered sensaJon to feet contributes to diabeJc foot ailments, as a person may be unaware of a sore on the foot. The sore can become infected, gangrene can set in, and amputaJon may be required 6
Delayed Wound Healing Autonomic Diabe=c Neuropathies –  Wound healing is impaired in diabetes mellitus –  DiabeJc foot ulcers common in diabeJcs •  May lead to loss of limb •  Can progress and require leg amputaJon •  84% of amputaJons started with foot ulcer Diabetes: Delayed Wound Healing VII. Progression of Diabetes Mellitus –  Lifelong progression •  Macrovasculature effects •  DiabeJc cardiomyopathy –  ComplicaJons can cause death Progression of Diabetes Mellitus –  Macrovasculature disease complicaJons •  Increased lipid transport to cells (High LDLs, low HDLs) •  ProducJon of reacJve oxygen species •  FormaJon of free radicals VIII. Treatment and Management of Diabetes –  Currently there is no cure for diabetes mellitus –  Disease is managed –  Primary focus: Maintain normal blood glucose –  Atherosclerosis •  May progress to heart ajack or stroke •  May lead to cardiomyopathy 7
Type 1: Treatment and Management –  Carbohydrate intake regulated –  Insulin injecJons •  Subcutaneous •  Insulin is digested, cannot be taken orally –  Insulin pump Type 2: Treatment and Management –  Obesity is open an issue •  Carbohydrate intake regulated •  Diet important to maintain proper weight –  Oral hypoglycemics •  Sulfonylureas – sJmulate insulin release •  Biguanides – decrease liver producJon of glucose •  α-­‐glucosidase inhibitors – decrease carbohydrate absorpJon •  Thiazolidinediones – sensiJze Jssue to insulin –  Insulin injecJons IX. Research on Insulin Administra=on –  Insulin is a protein •  Digested if taken orally •  InjecJons become choice of insulin delivery –  AlternaJve routes of insulin administraJon •  Rectal •  Ocular •  Nasal •  Oral in encapsulated form Research: Nonpharmaceu=cal Therapies Research: Non-­‐pharmaceu=cal Therapies –  Treatment of Type 1 diabetes mellitus •  Replicate β cells •  Stem cell transplant •  Gene therapy •  PrevenJon of β cell loss Bariatric Surgery –  Gastric banding –  Treatment of Type 2 diabetes mellitus •  Gene therapy •  Weight loss – Diet and lifestyle changes – Bariatric surgery •  Exercise 8
Bariatric Surgery –  Gastric stapling Bariatric Surgery –  Gastric bypass 9