Diabetes/ Lipoproteins
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Transcript of Diabetes/ Lipoproteins
1
PEP532: Diabetes, Blood Lipids, and Exercise
What is diabetes?
• A condition where the body cannot produce or properly use insulin– Problematic because insulin is needed to
get glucose into cellsType I:Body does not produce insulinType II: Insulin is produced, but does not
functionGestational Diabetes: 5-10% of women
develop diabetes (Type II) during pregnancyPre-diabetes: glucose levels are high, but not
high enough to be diagnosed as diabetic
• http://www.diabetes.org/about-diabetes.jsp
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What is diabetes?
• Detected using fasting blood glucose test, or an oral glucose tolerance test (fasting test is preferable)
• Pre-diabetes was formerly referred to as "glucose intolerance", or an inability to regulate glucose well– Blood glucose is elevated, but not high enough to be considered diabetic
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Fasting Blood GlucoseCategory [mg/dL]Normal 70-100Pre-diabetes 100-125Diabetes >125
What is diabetes?
• The pancreas is the organ that produces insulin and glucagon (Islets of Langerhans)– Beta cells of the pancreas produce insulin
and monitor blood glucose
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Type I
Sometimes referred to as Insulin-dependent diabetes mellitus (IDDM)• Immune system attacks the pancreatic beta cells, so insulin cannot be produced
–These patients must rely on an exogenous supply of insulin
• Accounts for only 5-10% of diagnosed cases of diabetes
–Generally children or young adults–Autoimmune, genetic, and/or environmental causesNo known way to prevent it
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Type II
• Sometimes referred to as non-insulin dependent diabetes mellitus (NIDDM)
• Usually begins as insulin resistance, then progresses to the point that the pancreas loses the ability to produce it
• Accounts for about 90-95% of the cases of diagnosed diabetes
• Factors are: age, obesity, family history, impaired glucose metabolism, physical inactivity, and ethnicity
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7Ethnicity is a strong predictor
Insulin resistance (IR)
• Refers to the body's inability to respond to and use the insulin it produces
• Type II diabetics produce insulin, but doses that are adequate in non-diabetics are not sufficient– Type II diabetics have to produce
increasingly greater amounts of insulin to produce "the same effect"
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Why is it a problem?
• If diabetes progresses without treatment:– Blindness– Kidney damage– Cardiovascular disease– Poor wound healing
•71,000 amputations in 2004 alone• Typically, other diseases tend to be prevalent in
Type II– High cholesterol and blood pressure, and
obesity• Costs the USA $174 billion in 2007 alone
– $116 billion on direct medical costs– $50 billion due to disability, work loss, mortality
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How prevalent?• Approximately 7.8% of (24 million!)
Americans are diabetic– 6.8% are diagnosed, 1.9% are not
diagnosed
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Prevalence goes up a great deal with age
How prevalent?
• There were 1.6 million NEW cases of diagnosed diabetes in 2007 alone!
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How prevalent?
• Type II diabetes in children <10 yrs is rare• But… notice how the trends change in the 10-
19 yrs age group
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13Treatment of diabetes
Type I:• Must have
exogenous insulin
Type II:• Recommended
to implement dietary and physical activity changes
• Weight loss• Medications
What role does exercise play?
• The problem with Type II diabetes is inability to dispose of dietary glucose– Fortunately, exercise can play acute and
chronic roles in improving glucose uptake
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There are 2 ways glucose is taken up by a cell
Insulin• Insulin interacts with a
specific receptor
Muscle Contraction• Changes in AMP:ATP,
intracellular Ca2+, and other mechanisms are signals
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Rockl,SK.S.C.ignaling Mechanisms in Skeletal Muscle: Acute Responses and Chronic Adaptations to Exercise IUBMBLife, 60(3): 145–153, March 2008
Glucose uptake
• GLUT4 receives the signal to bring glucose into the cell via 2 mechanisms:– Insulin signal– Muscle contraction– These 2 processes operate independently of
each other– There are additive effects of both
mechanisms; maximal glucose uptake occurs with insulin and muscle contraction
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Benefits of exercise
• Given that skeletal muscle is a huge site of glucose disposal, exercise can have a beneficial effect by:– Up-regulation of GLUT4– Facilitation of the insulin signaling process
• Following exercise, the improvement in glucose uptake stays elevated– Insulin sensitivity is enhanced 16 to 48
hours after exercise– This effect occurs even in un-fit people
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What have we learned from training studies?
• 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– Physical activity is a beneficial part due to
insulin sensitivity and/or weight/body fat loss
• However, is it the weight loss or the physical activity that was the causes the improvements?
There is good evidence, however, that insulin sensitivity can improve due to exercise alone
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Hayes, C. Role of Physical Activity in Diabetes Management and Prevention. J Am Diet Assoc. 2008;108:S19-S23.
What about Type I?
• Since exercise improves insulin sensitivity, type I diabetics have to be very careful– Type I diabetics are susceptible to becoming
hypoglycemic– Exogenous insulin is more effective… may
work too well, can cause hypoglycemia!• Type I diabetics can exercise, but:
– Careful with pre-exercise insulin levels– Adjust carbohydrate intake before, during,
and after exercise– Monitor blood glucose carefully
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American Diabetes Association (2006)
• Lifestyle measures for prevention of type 2 diabetesIn people with impaired glucose tolerance:– 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.
– At least 3 days/wk and no more than 2 consecutive days without
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2121Hyperlipidemia
• The elevation of lipids (fats) in the bloodstream.– These include cholesterol, cholesterol
esters (compounds), phospholipids, and triglycerides
• There are the five major types of lipoproteins:– Chylomicrons– Very low-density lipoproteins (VLDL)– Intermediate-density lipoproteins (IDL)– Low-density lipoproteins (LDL)– High-density lipoproteins (HDL)
Review of lipoprotein metabolism
Williams, K.J. Molecular processes that handle —and mishandle — dietary lipids. J Clin Invest. Volume 118 (10):2008
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Energy storage Uptake and oxidation
Chylomicron remnant (loss of TG)
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24Types of lipoproteins
• Apolipoproteins interact with cell membranes of different tissues
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Cholesterol
Apolipoprotein B
Apolipoprotein A
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What is cholesterol?
• It is a soft, fat-like, waxy substance found in the bloodstream and in all cells– It is an important part of the production of
cell membranes and some hormones– Must travel through the bloodstream bound
to lipoproteins• However, too much cholesterol in the blood is
a major risk for coronary heart disease and stroke
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Good vs. bad cholesterol?
• Cholesterol has to be transported to and from the cells by lipoproteins– Low-density lipoprotein, or LDL, is known as
“bad” cholesterol– High-density lipoprotein, or HDL, is known
as “good” cholesterol• Total Cholesterol (TC)= LDL + HDL + (TG/5)
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LDL• LDL carry most of the cholesterol in the blood
– The main source of damaging buildup and blockage in the arteries
• Elevated LDL in the blood can slowly build up in the inner walls of the arteries that feed the heart and brain (atherosclerosis) – If a clot forms and blocks a narrowed artery,
heart attack or stroke can result• Overall, the higher the LDL the higher the risk
of CHD
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LDL
• The amount of LDL in the blood is controlled in two places: the liver and the intestines– The liver produces cholesterol and removes
it from the blood – The intestines absorb cholesterol, which
comes from food and from bile Dietary cholesterol has a large influence on
blood values• Smaller the LDL particle, the larger the risk
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HDL
• Synthesized in liver and intestines• HDL carry cholesterol in the blood from other
parts of the body back to the liver• Referred to as “good” cholesterol because
high levels of HDL seem to protect against heart attack– HDL tends to carry cholesterol away from
the arteries and back to the liver, where it's removed from the body
– Possible that HDL removes excess cholesterol from arterial plaque
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Triglycerides (TG)
• High blood TG concentrations alone do not necessarily cause atherosclerosis– Some people with TG are often also
demonstrate other problems (such as low HDL or a tendency toward diabetes) that raise heart disease risk
– So TG may be a sign of a lipoprotein problem that contributes to heart disease
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What can cholesterol do?
• High total cholesterol (TC) is one of the major controllable risk factors for coronary heart disease, heart attack and stroke
• The presence of other risk factors (such as high blood pressure or diabetes) as well as high cholesterol increases the risk even more– The greater the number of risk factors, the
greater the chance of developing heart disease
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What is atherosclerosis?
• Arteriosclerosis is a general term for the thickening and hardening of arteries– Atherosclerosis is a type of arteriosclerosis
• 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– The buildup that results is called plaque– Plaque may partially or totally block the
blood's flow through an artery– LDL accumulation is a common observation
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What is atherosclerosis?
Two things that can happen where plaque occurs:1. Bleeding (hemorrhage) into the plaque2. A blood clot (thrombus) may form on the
plaque's surface
• If either of these occurs and blocks the whole artery, a heart attack or stroke may result
• Atherosclerosis is a slow, progressive disease that may start in childhood– 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.
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Atherosclerosis
• Accumulation of LDL, monocytes, macrophages and other inflammatory cells
• Results in build up cholesterol in the arterial wall
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How does atherosclerosis start?
• Possible that atherosclerosis starts because the innermost layer of the artery becomes damaged
• Three possible causes of damage to the arterial wall are:1. cholesterol and triglyceride in the blood2. blood pressure3. Smoking– Smoking aggravates and speeds up the
growth of atherosclerosis in the coronary arteries, the aorta and the arteries of the legs
• 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.
36Arterial atherosclerosis
37What is too high?
• American Heart Association
TC (mg/dL) High >240Borderline high 200-239Desirable <200
LDL (mg/dL) Very High >190High 160-189Borderline High 130-159Near Optimal 100-129Optimal <100
HDL (mg/dL)* Women MenHigher Risk <40 <50Average 40-50 50-60Lower Risk >60 >60*Higher is better
TG (mg/dL) Very High 500High 200-499Borderline High 150-199Normal <150
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How to reduce risk of CVD via lipoproteins?
• Reductions in LDL from dietary studies fat intake (particularly saturated) cholesterol intake to <200 mg/day
• Weight loss– Associated with LDL and TG; HDL
• Increase physical activity– American Heart Association/ACSM– 30 min mod intensity 5 or more days of the
week
39How to reduce risk of CVD via lipoproteins
(AHA)?
American Heart Association. Managing Abnormal Blood Lipids: A Collaborative Approach. Circulation. 2005;112:3184-3209
40What 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 ChronicTG 20% 24%Total cholesterol NC* NC†LDL‡ NC* NC†HDL 1% 8%Chylomicron/VLDL
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Resistance training
• Not enough information to come to a conclusion
• May be some beneficial changes if body fat and lean body mass
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Overall
• A combination of lifestyle and pharmacological interventions is generally recommended (depending on how high TC and LDL are)– Diet= TC and LDL– Exercise= HDL and TGCan potentially reduce the dose of drug if
lifestyle interventions are effective
For our purposes, can communities be designed differently to promote physical activity and/or diet?