Diabetes/ Lipoproteins


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Diabetes/ Lipoproteins

  1. 1. PEP532: Diabetes, Blood Lipids, and Exercise
  2. 2. What is diabetes? <ul><li>A condition where the body cannot produce or properly use insulin </li></ul><ul><ul><li>Problematic because insulin is needed to get glucose into cells </li></ul></ul><ul><li>Type I :Body does not produce insulin </li></ul><ul><li>Type II : Insulin is produced, but does not function </li></ul><ul><li>Gestational Diabetes : 5-10% of women develop diabetes (Type II) during pregnancy </li></ul><ul><li>Pre-diabetes : glucose levels are high, but not high enough to be diagnosed as diabetic </li></ul><ul><li>http://www.diabetes.org/about-diabetes.jsp </li></ul>
  3. 3. What is diabetes? <ul><li>Detected using fasting blood glucose test, or an oral glucose tolerance test (fasting test is preferable) </li></ul><ul><li>Pre-diabetes was formerly referred to as &quot;glucose intolerance&quot;, or an inability to regulate glucose well </li></ul><ul><ul><li>Blood glucose is elevated, but not high enough to be considered diabetic </li></ul></ul>Fasting Blood Glucose Category [mg/dL] Normal 70-100 Pre-diabetes 100-125 Diabetes >125
  4. 4. What is diabetes? <ul><li>The pancreas is the organ that produces insulin and glucagon (Islets of Langerhans) </li></ul><ul><ul><li>Beta cells of the pancreas produce insulin and monitor blood glucose </li></ul></ul>
  5. 5. Type I <ul><li>Sometimes referred to as Insulin-dependent diabetes mellitus (IDDM) </li></ul><ul><li>Immune system attacks the pancreatic beta cells, so insulin cannot be produced </li></ul><ul><ul><li>These patients must rely on an exogenous supply of insulin </li></ul></ul><ul><li>Accounts for only 5-10% of diagnosed cases of diabetes </li></ul><ul><ul><li>Generally children or young adults </li></ul></ul><ul><ul><li>Autoimmune, genetic, and/or environmental causes </li></ul></ul><ul><ul><li>No known way to prevent it </li></ul></ul>
  6. 6. Type II <ul><li>Sometimes referred to as non-insulin dependent diabetes mellitus (NIDDM) </li></ul><ul><li>Usually begins as insulin resistance, then progresses to the point that the pancreas loses the ability to produce it </li></ul><ul><li>Accounts for about 90-95% of the cases of diagnosed diabetes </li></ul><ul><li>Factors are: age, obesity, family history, impaired glucose metabolism, physical inactivity, and ethnicity </li></ul>
  7. 7. Ethnicity is a strong predictor
  8. 8. Insulin resistance (IR) <ul><li>Refers to the body's inability to respond to and use the insulin it produces </li></ul><ul><li>Type II diabetics produce insulin, but doses that are adequate in non-diabetics are not sufficient </li></ul><ul><ul><li>Type II diabetics have to produce increasingly greater amounts of insulin to produce &quot;the same effect&quot; </li></ul></ul>
  9. 9. Why is it a problem? <ul><li>If diabetes progresses without treatment: </li></ul><ul><ul><li>Blindness </li></ul></ul><ul><ul><li>Kidney damage </li></ul></ul><ul><ul><li>Cardiovascular disease </li></ul></ul><ul><ul><li>Poor wound healing </li></ul></ul><ul><ul><ul><li>71,000 amputations in 2004 alone </li></ul></ul></ul><ul><li>Typically, other diseases tend to be prevalent in Type II </li></ul><ul><ul><li>High cholesterol and blood pressure, and obesity </li></ul></ul><ul><li>Costs the USA $174 billion in 2007 alone </li></ul><ul><ul><li>$116 billion on direct medical costs </li></ul></ul><ul><ul><li>$50 billion due to disability, work loss, mortality </li></ul></ul>
  10. 10. How prevalent? <ul><li>Approximately 7.8% of (24 million!) Americans are diabetic </li></ul><ul><ul><li>6.8% are diagnosed, 1.9% are not diagnosed </li></ul></ul>Prevalence goes up a great deal with age
  11. 11. How prevalent? <ul><li>There were 1.6 million NEW cases of diagnosed diabetes in 2007 alone! </li></ul>
  12. 12. How prevalent? <ul><li>Type II diabetes in children <10 yrs is rare </li></ul><ul><li>But… notice how the trends change in the 10-19 yrs age group </li></ul>
  13. 13. Treatment of diabetes <ul><li>Type I: </li></ul><ul><li>Must have exogenous insulin </li></ul><ul><li>Type II: </li></ul><ul><li>Recommended to implement dietary and physical activity changes </li></ul><ul><li>Weight loss </li></ul><ul><li>Medications </li></ul>
  14. 14. What role does exercise play? <ul><li>The problem with Type II diabetes is inability to dispose of dietary glucose </li></ul><ul><ul><li>Fortunately, exercise can play acute and chronic roles in improving glucose uptake </li></ul></ul>
  15. 15. There are 2 ways glucose is taken up by a cell <ul><li>Insulin </li></ul><ul><li>Insulin interacts with a specific receptor </li></ul><ul><li>Muscle Contraction </li></ul><ul><li>Changes in AMP:ATP, intracellular Ca 2+ , and other mechanisms are signals </li></ul>Rockl,SK.S.C.ignaling Mechanisms in Skeletal Muscle: Acute Responses and Chronic Adaptations to Exercise IUBMBLife, 60(3): 145–153, March 2008
  16. 16. Glucose uptake <ul><li>GLUT4 receives the signal to bring glucose into the cell via 2 mechanisms: </li></ul><ul><ul><li>Insulin signal </li></ul></ul><ul><ul><li>Muscle contraction </li></ul></ul><ul><ul><li>These 2 processes operate independently of each other </li></ul></ul><ul><ul><li>There are additive effects of both mechanisms; maximal glucose uptake occurs with insulin and muscle contraction </li></ul></ul>
  17. 17. Benefits of exercise <ul><li>Given that skeletal muscle is a huge site of glucose disposal, exercise can have a beneficial effect by: </li></ul><ul><ul><li>Up-regulation of GLUT4 </li></ul></ul><ul><ul><li>Facilitation of the insulin signaling process </li></ul></ul><ul><li>Following exercise, the improvement in glucose uptake stays elevated </li></ul><ul><ul><li>Insulin sensitivity is enhanced 16 to 48 hours after exercise </li></ul></ul><ul><ul><li>This effect occurs even in un-fit people </li></ul></ul>
  18. 18. What have we learned from training studies? <ul><li>A number of clinical studies indicate that lifestyle interventions (of which physical activity is a part) indicate that the development of type 2 diabetes can be prevented or delayed </li></ul><ul><ul><li>Physical activity is a beneficial part due to  insulin sensitivity and/or weight/body fat loss </li></ul></ul><ul><li>However, is it the weight loss or the physical activity that was the causes the improvements? </li></ul><ul><li>There is good evidence, however, that insulin sensitivity can improve due to exercise alone </li></ul>Hayes, C. Role of Physical Activity in Diabetes Management and Prevention. J Am Diet Assoc. 2008;108:S19-S23.
  19. 19. What about Type I? <ul><li>Since exercise improves insulin sensitivity, type I diabetics have to be very careful </li></ul><ul><ul><li>Type I diabetics are susceptible to becoming hypoglycemic </li></ul></ul><ul><ul><li>Exogenous insulin is more effective… may work too well, can cause hypoglycemia! </li></ul></ul><ul><li>Type I diabetics can exercise, but: </li></ul><ul><ul><li>Careful with pre-exercise insulin levels </li></ul></ul><ul><ul><li>Adjust carbohydrate intake before, during, and after exercise </li></ul></ul><ul><ul><li>Monitor blood glucose carefully </li></ul></ul>
  20. 20. American Diabetes Association (2006) <ul><li>Lifestyle measures for prevention of type 2 diabetes </li></ul><ul><ul><li>In people with impaired glucose tolerance: </li></ul></ul><ul><ul><li>program of weight control is recommended, including at least 150 min/week of moderate to vigorous physical activity and a healthful diet with modest energy restriction. </li></ul></ul><ul><ul><li>At least 3 days/wk and no more than 2 consecutive days without </li></ul></ul>
  21. 21. Hyperlipidemia <ul><li>The elevation of lipids (fats) in the bloodstream. </li></ul><ul><ul><li>These include cholesterol, cholesterol esters (compounds), phospholipids, and triglycerides </li></ul></ul><ul><li>There are the five major types of lipoproteins: </li></ul><ul><ul><li>Chylomicrons </li></ul></ul><ul><ul><li>Very low-density lipoproteins (VLDL) </li></ul></ul><ul><ul><li>Intermediate-density lipoproteins (IDL) </li></ul></ul><ul><ul><li>Low-density lipoproteins (LDL) </li></ul></ul><ul><ul><li>High-density lipoproteins (HDL) </li></ul></ul>
  22. 22. Review of lipoprotein metabolism Williams, K.J. Molecular processes that handle —and mishandle — dietary lipids. J Clin Invest. Volume 118 (10):2008 Energy storage Uptake and oxidation Chylomicron remnant (loss of TG)
  23. 23.
  24. 24. Types of lipoproteins <ul><li>Apolipoproteins interact with cell membranes of different tissues </li></ul>Cholesterol Apolipoprotein B Apolipoprotein A
  25. 25. What is cholesterol? <ul><li>It is a soft, fat-like, waxy substance found in the bloodstream and in all cells </li></ul><ul><ul><li>It is an important part of the production of cell membranes and some hormones </li></ul></ul><ul><ul><li>Must travel through the bloodstream bound to lipoproteins </li></ul></ul><ul><li>However, too much cholesterol in the blood is a major risk for coronary heart disease and stroke </li></ul>
  26. 26. Good vs. bad cholesterol? <ul><li>Cholesterol has to be transported to and from the cells by lipoproteins </li></ul><ul><ul><li>Low-density lipoprotein, or LDL, is known as “bad” cholesterol </li></ul></ul><ul><ul><li>High-density lipoprotein, or HDL, is known as “good” cholesterol </li></ul></ul><ul><li>Total Cholesterol (TC)= LDL + HDL + (TG/5) </li></ul>
  27. 27. LDL <ul><li>LDL carry most of the cholesterol in the blood </li></ul><ul><ul><li>The main source of damaging buildup and blockage in the arteries </li></ul></ul><ul><li>Elevated LDL in the blood can slowly build up in the inner walls of the arteries that feed the heart and brain (atherosclerosis) </li></ul><ul><ul><li>If a clot forms and blocks a narrowed artery, heart attack or stroke can result </li></ul></ul><ul><li>Overall, the higher the LDL the higher the risk of CHD </li></ul>
  28. 28. LDL <ul><li>The amount of LDL in the blood is controlled in two places: the liver and the intestines </li></ul><ul><ul><li>The liver produces cholesterol and removes it from the blood </li></ul></ul><ul><ul><li>The intestines absorb cholesterol, which comes from food and from bile </li></ul></ul><ul><ul><li>Dietary cholesterol has a large influence on blood values </li></ul></ul><ul><li>Smaller the LDL particle, the larger the risk </li></ul>
  29. 29. HDL <ul><li>Synthesized in liver and intestines </li></ul><ul><li>HDL carry cholesterol in the blood from other parts of the body back to the liver </li></ul><ul><li>Referred to as “good” cholesterol because high levels of HDL seem to protect against heart attack </li></ul><ul><ul><li>HDL tends to carry cholesterol away from the arteries and back to the liver, where it's removed from the body </li></ul></ul><ul><ul><li>Possible that HDL removes excess cholesterol from arterial plaque </li></ul></ul>
  30. 30. Triglycerides (TG) <ul><li>High blood TG concentrations alone do not necessarily cause atherosclerosis </li></ul><ul><ul><li>Some people with  TG are often also demonstrate other problems (such as low HDL or a tendency toward diabetes) that raise heart disease risk </li></ul></ul><ul><ul><li>So  TG may be a sign of a lipoprotein problem that contributes to heart disease </li></ul></ul>
  31. 31. What can cholesterol do? <ul><li>High total cholesterol (TC) is one of the major controllable risk factors for coronary heart disease, heart attack and stroke </li></ul><ul><li>The presence of other risk factors (such as high blood pressure or diabetes) as well as high cholesterol increases the risk even more </li></ul><ul><ul><li>The greater the number of risk factors, the greater the chance of developing heart disease </li></ul></ul>
  32. 32. What is atherosclerosis? <ul><li>Arteriosclerosis is a general term for the thickening and hardening of arteries </li></ul><ul><ul><li>Atherosclerosis is a type of arteriosclerosis </li></ul></ul><ul><li>Atherosclerosis is the term for the process of fatty substances, cholesterol, cellular waste products, calcium and fibrin (a clotting material in the blood) building up in the inner lining of an artery </li></ul><ul><ul><li>The buildup that results is called plaque </li></ul></ul><ul><ul><li>Plaque may partially or totally block the blood's flow through an artery </li></ul></ul><ul><ul><li>LDL accumulation is a common observation </li></ul></ul>
  33. 33. What is atherosclerosis? <ul><li>Two things that can happen where plaque occurs: </li></ul><ul><ul><li>Bleeding (hemorrhage) into the plaque </li></ul></ul><ul><ul><li>A blood clot (thrombus) may form on the plaque's surface </li></ul></ul><ul><li>If either of these occurs and blocks the whole artery, a heart attack or stroke may result </li></ul><ul><li>Atherosclerosis is a slow, progressive disease that may start in childhood </li></ul><ul><ul><li>In some people this disease progresses rapidly in their third decade. In others it doesn't become threatening until they're in their 50s or 60s. </li></ul></ul>
  34. 34. Atherosclerosis <ul><li>Accumulation of LDL, monocytes, macrophages and other inflammatory cells </li></ul><ul><li>Results in build up cholesterol in the arterial wall </li></ul>
  35. 35. How does atherosclerosis start? <ul><li>Possible that atherosclerosis starts because the innermost layer of the artery becomes damaged </li></ul><ul><li>Three possible causes of damage to the arterial wall are: </li></ul><ul><ul><li> cholesterol and triglyceride in the blood </li></ul></ul><ul><ul><li> blood pressure </li></ul></ul><ul><ul><li>Smoking </li></ul></ul><ul><ul><li>Smoking aggravates and speeds up the growth of atherosclerosis in the coronary arteries, the aorta and the arteries of the legs </li></ul></ul><ul><li>Often a blood clot forms and blocks the artery, stopping the flow of blood. If the oxygen supply to the heart muscle is reduced, a heart attack can occur. If the oxygen supply to the brain is cut off, a stroke can occur. And if the oxygen supply to the extremities occurs, gangrene can result. </li></ul>
  36. 36. Arterial atherosclerosis
  37. 37. What is too high? <ul><li>American Heart Association </li></ul>TC (mg/dL)   High >240 Borderline high 200-239 Desirable <200 LDL (mg/dL)   Very High >190 High 160-189 Borderline High 130-159 Near Optimal 100-129 Optimal <100 HDL (mg/dL)* Women Men Higher Risk <40 <50 Average 40-50 50-60 Lower Risk >60 >60 *Higher is better TG (mg/dL)   Very High 500 High 200-499 Borderline High 150-199 Normal <150
  38. 38. How to reduce risk of CVD via lipoproteins? <ul><li>Reductions in LDL from dietary studies </li></ul><ul><ul><li> fat intake (particularly saturated) </li></ul></ul><ul><ul><li> cholesterol intake to <200 mg/day </li></ul></ul><ul><li>Weight loss </li></ul><ul><ul><li>Associated with  LDL and TG;  HDL </li></ul></ul><ul><li>Increase physical activity </li></ul><ul><ul><li>American Heart Association/ACSM </li></ul></ul><ul><ul><li>30 min mod intensity 5 or more days of the week </li></ul></ul>
  39. 39. How to reduce risk of CVD via lipoproteins (AHA)? American Heart Association. Managing Abnormal Blood Lipids: A Collaborative Approach. Circulation. 2005;112:3184-3209
  40. 40. What is the role of aerobic exercise? NC*=no change unless the exercise is prolonged NC †=no change if body weight and diet do not change Lipid/Lipoprotein Acute Chronic TG  20%  24% Total cholesterol NC* NC† LDL‡ NC* NC† HDL  %  8% Chylomicron/VLDL  
  41. 41. Resistance training <ul><li>Not enough information to come to a conclusion </li></ul><ul><li>May be some beneficial changes if  body fat and  lean body mass </li></ul>
  42. 42. Overall <ul><li>A combination of lifestyle and pharmacological interventions is generally recommended (depending on how high TC and LDL are) </li></ul><ul><ul><li>Diet=  TC and LDL </li></ul></ul><ul><ul><li>Exercise=  HDL and  TG </li></ul></ul><ul><ul><li>Can potentially reduce the dose of drug if lifestyle interventions are effective </li></ul></ul><ul><li>For our purposes, can communities be designed differently to promote physical activity and/or diet? </li></ul>