Transcript Low-Grade Inflammation

Low-Grade Inflammation and
Exercise
Wren L. McLaughlin
Department of Physical Education, Health, and Recreation
Western Washington University
Overview
•
•
•
•
Definitions
Potential Causes
Detection
Exercise Effects
–
–
–
–
Overall Effects
Aging Population
Insulin-Resistant Population
Type of Exercise
• Exercise Recommendations
Low-grade Inflammation
• Inflammation is the
body's response to
infection, irritation or
injury.
• Substantial research
shows that chronic lowgrade inflammation plays
an important role in the
development of
atherosclerosis and
insulin resistance
Adapted from Barzilay & Freeland (2003)
Treat Endocrinol 2: 85-94.
Associated Diseases
• Low-grade inflammation is an independent risk
factor for:
–
–
–
–
Heart disease1
Stroke2
Diabetes3,4
All-cause mortality5
1 Hansson
(2005) N Engl J Med 352:1685-95.
2 Corrado et al. (2006) Stroke 37:482-6.
3 Pradhan et al. (2001) JAMA 286:327-34.
4 Spranger et al. (2003) Diabetes 52: 812-7
5 Ford (2005) Diabetes Care 28: 1769-78.
Summary of the phases of the
immune response
Immediate
0-4 hours
Early
4-96 hours
Late
>96 hours
Type
Innate
Innate (inducible)
Specific
Key Molecules and
Antibodies
Complement
Histamine etc.
Complement
IL-1,TNFalpha, IL-12
IFN-α/β
MBP, CRP
IgM and IgG
IL-2, IL-4, IL-12,
IFNgamma
Key Cells
Macrophages
Mast Cells
Neutrophils
Macrophages
Neutrophils
NK cells
T cells
B cells
Macrophages
What is Low-grade Inflammation?
• Innate (instinctive) immune system
– Release of various substances like interleukins &
TNF-α leads to production of acute phase
reactants
– When injurious stimuli persist, acute phase
reactant levels remain elevated
– Clinically, 2-4 fold increase in pro-inflammatory
markers indicates low-grade inflammation
Inflammation in the Arteries
Injury
(modified lipoproteins, hemodynamic insults, reactive oxygen species, infectious agents)

Migration of monocytes/leukocytes into arteries

Interleukins (released by macrophages) stimulate expression of adhesion
molecules

Endothelial activation

LDL oxidation
(CRP aids LDL binding to complement for macrophage uptake)

Foam cell production

Synthesis of growth factors and cytokines

Plug formation

Turbulence downstream
Feed-forward mechanism
Image Source: http://www.clevelandclinic.org/heartcenter/images/professionals/cardiacconsult/2001_Fall/crp2.JPG
Potential Causes
•
•
•
•
Activity Level
Diet
Obesity
Infection
A Sedentary Lifestyle
• Skeletal muscle may act as an endocrine organ
– Influencing metabolism (“IL-6 as energy sensor”)
– Modify immune system message production in other tissues
including endothelial and adipose tissues1
– Production and release anti-inflammatory substances into the
blood2
– Exercise training reduces skeletal muscle TNF-α, IL-1b, IL-6
expression in patients with heart failure3
• Exercise may improve endothelial function
– Exercise may limit leukocyte adhesion molecules and thus modify
monocyte-endothelial cell interaction
– Preserved NO availability
– Up-regulation of antioxidant enzymes therefore increasing
antioxidant effect in vessels (less LDL oxidization)
1 Bruungsgaard
(2005) J Leukoc Biol 78: 819-35.
& Pederson (2006) Exerc Sport Sci Rev 33:114-9.
3 Gielen et al. (2003) J Am Coll Cardiol 42:861-8.
2 Febbraio
Western Diet
• Refined foods may boost inflammation
• Necessary nutrients for optimal immune function and
prevention of cardiovascular disease and diabetes is
lacking1
• Glycemic load
– Predictor of type 2 diabetes independent of total calories
consumed
– Increase the risk of diabetes by 2.5 times in both men and
women2,3
– High glycemic load is related to high levels of C-reactive
protein independent of weight and total caloric intake in
healthy middle-aged women4
1 Calder
& Kew (2002) Br J Nutr 88: S165-77.
2 Salmeron et al. (1997) Diabetes Care 20: 545-50.
3 Salmeron et al. (1997) JAMA 277: 472-7.
4 Liu et al. (2002) Am J Clin Nutr 75: 492-8.
Western Diet
• Polyunsaturated fatty acids
– Cell membrane functioning
– Ratio Omega-6:Omega 3 1:1 to 15:1 1
– Associated with lower levels of proinflammatory markers
(IL-6, TNF-α, CRP) and higher levels of
anti-inflammatory markers2
– Mediterranean-inspired diet (one month) showed no significant
change in IL-6 or CRP3
1 Simpoulo
(2002) Biomed Pharmacother 56: 365-79.
2 Ferrucci et al. (2006) J Clin Endocrinol Metab 91: 439-46.
3 Ambring et al. (2006) Am J Clin Nutr 83: 575-81.
Image Source: http://www.ec.gc.ca/EnviroZine/images/Issue43/omega3source_l.jpg
Western Diet
• Vitamins and Minerals
– Insufficient consumption of B vitamins and folic acid can harm
the lining of blood vessels by increasing clotting, oxidative
stress, and interactions with white blood cells1
– Potential role of magnesium deficiency in chronic inflammation2,3
– High meat diet + low antioxidant vitamin (E &C) consumption
may increase free radical production in the blood vessels4,5
1Jonasson
et al. (2005) Clin Chem Lab Med 43: 628-34.
2 King et al. (2005) J Am Coll Nutr 24: 166-71.
3 Song et al. (2005) Diabetes Care 28: 1438-44.
4 Ford et al. (2005) Am J Kidney Dis 45: 248-55.
5 Accinni et al. (2006) Nutr Metab Cardiovasc Dis 16: 121-7.
Obesity
• Adipocytes may promote inflammation1
• Concentrations of IL-6, TNF-α, MMP-9 and CRP from
mononuclear cells were significantly higher in obese
subjects2
• In severely obese individuals treatment of caloric
reduction and exercise changed levels of inflammatory
markers in adipose tissue but not in skeletal muscle3
• Association established between inflammatory cytokines
and adipose tissue function4
• In centrally obese individuals, adipocytes produce more
IL-6 than subcutaneous adipocytes5
1 Bastard
et al. (2006) Eur Cytokine Netw 17: 4-12. .
et al. (2004) Circulation 110:1564-71.
3 Bruun et al. (2006) Am J Physiol Endocrinol Metab. 2006 May;290(5):E961-7
4 Trayhurn & Wood (2004) Br J Nutr. 2004 Sep;92(3):347-55.
5 Barzilay & Freedland (2003) Treat Endocrinol 2: 85-94.
2 Ghanim
Infection
• Chlamydia pneumoniae is
associated with inflammation
and lower limb
atherosclerosis1,2
• Helicobacter pylori, a
common bacteria that effects
the gastrointestinal system,
is suggested as potential
cause of low-grade
inflammation3
• Recent research indicates
that herpes simplex virus
may also play an important
role in chronic inflammation
and insulin resistance4
1
Image Source: http://herkules.oulu.fi/isbn9514269853/html/graphic55.png
Kaperonis et al. (2006) Eur J Vasc Endovasc Surg 31: 509-15.
Kuppuswamy & Gupta (2006) Timely Top Med Cardiovasc Dis 10: E2.
3 Corrado et al. (2006) Stroke 37: 482-6.
4 Fernadez-Real et al. (2006) Diabetes Care 29: 1058-64.
2
Detection Methods
• Clinical Blood Test for C-Reactive Protein
Global Risk Assessment
http://www.americanheart.org/presenter.jhtml?identifier=3003500
– provided by American Heart Association
– Low Risk = no test
– Moderate or High Risk = CRP testing warranted
Ridker (2001) Circulation 103: 1813-8.
C-Reactive Protein
• Acute phase reactant
• Risk of ischemic heart
disease and reported risk of
developing myocardial
infarction significantly
increases with elevated hsCRP levels
Ridker (2001) Circulation 103: 1813-8.
Image source: http://focus.hms.harvard.edu/2002/Nov22_2002/pathology.html
CRP- Physiologic Role
• Primary production in liver
• Stimulated by IL-6
(IL-1 and TNF-α also)
Roles:
–CRP enhances binding of LDL to
complement for easier uptake by
macrophages (form foam cells)
–Stimulates macrophages to activate complement
–Activate endothelial cells to express adhesion molecules (which
may decrease expression and bioavailability of endothelial nitric
oxide synthase)
–Plaque destabilization and rupture
Verma et al. (2002) Nat Clin Pract Cardiovasc Med 2: 29-36.
Image Source: http://www.medscape.com/viewarticle/440972_10
Interleukins
• Messengers
• Pro/anti-inflammatory
• Secreted by leukocytes
to stimulate immune
response to trauma
• IL-1, IL-4, 1L-6, 1L-10
etc.
Image source: http://www.rndsystems.com/DAM_public/5645.jpg
Other Important Inflammatory
Markers
• Adiponectin
– Adipokine with anti-inflammatory and insulin
sensitizing properties
• Tumor Necrosis Factor-α
– Adipose tissue is main source of circulating TNF-α
– Acts on other tissues to increase insulin resistance
– Leads to an increase in C-reactive protein and other
mediators
– May cause increased systemic levels of IL-6
Summary of Pro/Anti-inflammatory Markers
Pro-inflammatory
C-Reactive Protein
Serum Amyloid A
Fibrinogen
IL-1
IL-18
IL-6
TNF-α
Homocysteine
Leukocyte counts
Anti-inflammatory
Nitric Oxide
Adiponectin
IL-4
IL-10
TGF-β
IL-6
Note: This list is far from exhaustive
Exercise Effects
• Exercise has a positive effect on immune function
• In moderate doses, exercise induces an immune
response that may include protective effects against:
–
–
–
–
–
1
Cancer1
Immune senescence associated with the aging process2,3,4
Cardiovascular disease5
Diabetes6
All-cause mortality7
Woods (1998) Can J Physiol Pharmacol 76: 581-8.
Bruunsgaard & Pedersen (2000) Immunol Cell Biol 78: 523-31.
3 Drela et al. (2004) BMC Geriatrics 4:1-7.
4 Shinkai et al. 1998 Can J Physiol Pharmacol 76: 562-72.
5 Hansson (2005) NEJM 352: 1685-95.
6 Petersen (2006) Essays Biochem 42: 105-17.
7 Petersen & Petersen (2005) J Appl Physiol 98: 1154-62.
2
Over-training
• Overtraining can induce oxidative
stress and compromise resistance to
minor illnesses such as upper
respiratory track infections1,2
• “Open-window” time period in
athletes following physical exertion
during which they are more
susceptible to invasion by viruses
and bacteria3
1 MacKinnon
2
3
(2000) Med Sci Sports Exerc 32: S369-76.
Nieman (2000) Immunol Cell Biol 78: 496-501.
Nieman (2000) Med Sci Sports Exerc 32: S406-11.
Image Source: http://athleticssuperstars.tripod.com/paula_marathon.jpg
Cross-Sectional Studies
on the Effects of Regular Physical Activity on Baseline Serum CRP
Study
Participants
Dufaux et al. (1984) Int J Sports Med 5: 102-6
459 athletes/95 untrained
controls ♀ & ♂
King et al. (2003) Med Sci Sports Exerc 35: 575-81
Average CRP in Lowest
Physical Activity Levels*
Average CPR in Highest
Physical Activity Levels*
p value
♂: 0.502
♀: 0.396
♂: 0.102
♀: 0.110
<0.001
4,072 adult ♀ & ♂
286
69
<0.01
Ford (2002) Epidemiology 13: 561-8
13,748 adult ♀ & ♂
21%†
8%†
<0.001
Albert et al. (2004) Am J Cardiol 93: 221-5
2,833 adult ♀ & ♂
2.6
1.68
<0.001‡
Abramson et al. (2002) Arch Intern Med 162: 1286-92
3,638 adult ♀ & ♂
15.1%€
6.5%€
<0.001
Geffken et al. (2001) Am J Epidemiol 153: 242-50
5,888 elderly ♀ & ♂
2.24
1.82
<0.001
Taaffe et al. (2000) J Gerontol A Biol Sci Med Sci 55: M709-15
880 elderly ♀ & ♂
.74
.76₪
.44
.53₪
<0.001
0.11₪
Wannamethee et al. (2002) Circulation 105: 1785-90
3810 elderly ♂
2.29
1.43
<0.001
Tomaszewski et al. (2003) Arterioscler Thromb Vasc Biol
23: 1640-4
67 ♂ athletes/63
sedentary
.9
.4
0.0013
Koenig et al. (1999) Circulation 99: 237-42
936 adult ♂
1.82
1.23
0.001
Pitsavos et al. (2003) Am J Cardiol 91: 368-70
891 ♂ & 965 ♀
9.1
0.02
Rohde et al. (1999) Am J Cardiol 84: 1018-22
1172 adult ♂
1.4
1.2
<0.01
Verdaet et al. (2004) Atherosclerosis 176: 303-10
892 sedentary adult ♂
1.05
.88₪
.68
.81₪
0.02
.46
Aronson et al. (2004) Atherosclerosis 176: 173-9
892 adult ♀ & ♂
1.62
2.37
<0.0001
Church et al. (2002) Arterioscler Thromb Vasc Biol 22: 1869-76
722 adult ♂
2.29
.52
<0.001
LaMonte et al. (2002) Circulation 106: 403-6
135 adult ♀
4.3
2.3
.002**
Isasi et al. (2003) Pediatrics 111:332-8
205 ♀ & ♂ age 6-24
1.9
1.1
<0.01
*CRP reported in mg/l. Differences in assay technique explain wide variation of values between studies
† % participants with CRP > 85th percentile, ‡ Significant in ♂, but not ♀ after adjustment, €% participants with CRP > 7 mg/l
₪After adjustments for confounding factors **Significant in Native American and Caucasian but not in African-American ♀
Adapted from Kasapis & Thompson (2005) J Am Coll Cardiol 45: 1563-9.
Limitations of Cross-sectional Studies
• Self-reported
– Recall bias, reporting bias
– Ability to classify fitness level
• Cardiorespiratory fitness correlates to
CRP levels
– Must adjust for all potential confounders
Prospective Studies of Exercise
Effects on CRP Levels
CRP Before (mg/L)
CRP After (mg/L)
Study
Participants
Intervention
Duration
Exercise
Control
Exercise
Control
Tissi et al.
(1997)
39 ♀ & ♂*
Exercise/Observation
3 months
5.3
5.6
4.4
4.8
<0.05
Mattusch et al.
(2000)
22 ♂
Endurance training
(marathon)/control
9 months
1.19
0.77
0.82
1.15
<0.05
Smith et al.
(1999)
43 ♀ & ♂^
Supervised exercise
6 months
48.1
-
31.3
-
.12a
Rauramaa et
al. (2004)
125 ♂
Cardiovascular exercise
(5x/wk 40-60% VO2max)
6 years
1.0
1.0
.9
1.0
.20b
Lakka et al.
(2005)
652 ♀ & ♂#
Cardiovascular exercise
(3xwk 50 min)
5 months
Low 0.50
Med 1.66
High 5.60
-
Low 0.62
Med 1.79
High 4.56
-
High
only
<0.001
Kohut et al.
(2006)
87 ♀ & ♂$
Cardiovascular or
Flexibility/Strength
10
months
4.0
4.0
-
1.7
4.6
-
<0.05
NS
*Patients with intermittent claudication
^Patients with high risk of ischemic heart disease
# Sedentary
Older adults either <3 days aerobic exercise/week or below 75%tile for 6 min- walk test
Post-menopausal, overweight or obese
aMononuclear cell production of atherogenic cytokines fell by 58.3 % (P<.001) following the exercise program, where as the
production of atheroprotective cytokines rose by 35.9% (P<.001).
b Main study outcome intima-media thickness
$
@
Pvalue
Prospective Studies of
Exercise + Diet Effects
CRP Before
(mg/L)
Study
Participants
Duration
Nicklas et al.
(2004)
316 M & F^#
18
months
CRP After
(mg/L)
Intervention
P-value
•Control
•Dietary Weight Loss
•Exercise (3 days/wk walking/
resistance training)
•Dietary Weight Loss + Exercise
5.9
6.0
6.8
6.25
5.87
6.78
6.5
6.32
NS main
effect for
exercise
You et al.
(2004)
34 F@ #
6 months
Control: Hypocaloric diet
Experimental: Diet + exercise
Exercise (3x/wk 40-60 min @ 70%
VO2 max )
8.57
5.46
9.54
3.60
<0.01
Bruun et al.
(2006)
23 M & F+
15 weeks
Hypocaloric diet + exercise (2-3
hours “moderate-intensity” 5x/wk)
9.8
7.0
<0.05
Roberts et al.
(2006)
31 M*
3 weeks
Hypocaloric, high-fiber diet +
exercise (45-60 min daily 70-85%
max HR)
2.39
1.46
<0.01
Age >60, overweight or obese
# Sedentary
@Age 50-70, post-menopausal, overweight or obese
=Obese
*Age 46-76, overweight or obese, 50% w/metabolic syndrome
^
Type of exercise?
Intensity of exercise?
Study design?
Exercise Effects in Older Adults
• Three studies 8-12 weeks healthy older adults (65-84) resistance
training had no effect in immune function1,2,3
• Three studies 10-24 weeks older adults (65-87) endurance training
of moderate intensity showed minimal effect4,5,6
• 32 weeks nursing home, frail older adults (79-95) combination
endurance and resistance training showed no effect on lymphocyte
subpopulations, activation markers or cytokine products7
• Six weeks older adults (60-75) resistance training showed no
significant effect on cytokine products (trend only)8
• Most recently Kohut et al. (2006) provides first positive finding
1 Berman
et al. (1996) J Sports Med Phys Fitness 41: 196-202.
et al. (1999) J Appl Physiol 86: 1905-13.
3 Rall et al. (1996) Med Sci Sports Exerc 28: 1356-65.
4 Chin et al. (2000) Med Sci Sports Exerc 32: 2005-11.
5 Fahlman et al. (2000) Gerontology 46: 97-104.
6 Woods et al. (1999) Mech Ageing Dev 109: 1-19.
7 Kapasi et al. (2003) J Gerontol A Biol Sci Med Sci 58: 636-43.
8 Bautmans et al. (2005) Gerontology 51: 253-65.
2 Flynn
Exercise Effects in Older Adults
Adapted from Kohut et al. (2006) Brain Behav Immun 20: 201-9.
Insulin Resistance
• CRP and IL-6 predict the development of type-2 diabetes
in women1 and older adults2
• Possible relationship between inflammation and glucose
utilization and insulin sensitivity in overweight and obese
postmenopausal women
– Improvements in glucose metabolism associated w/ decreased
cytokine concentrations during weight loss program3
• Possible association between low cardio respiratory
fitness and C-reactive protein levels in women with type2 diabetes4
1 Prahhan
et al. (2001) JAMA 286: 327-34.
et al. (2001) Diabetes 50: 2384-9.
3 Ryan & Nicklas (2004) Diabetes Care 27: 1699-705
4 McGavock et al. (2004) Diabetes Care 27: 320-5.
2 Barzilay
Insulin Resistance
and Inflammatory Markers
• Middle-aged white M & F
• 4 week training
– 3x/week 60 minutes (20 min warm-up/cool down, 20 min run/bike,
20 min power training) + 1x/week 60 minutes swimming
– Significant reduction in adiponectin in impaired glucose tolerant
and type-2 diabetes participants
– Significant reduction in CRP levels in normal, impaired, and type2 diabetes groups, however reduction in normal glucose tolerant
participants did not change as much.
– NO significant change in IL-6 or IL-10
Oberbach et al. (2006) Eur J Endocrinol 154: 577-85.
Insulin Resistance, Endothelial Dysfunction
and Low-grade Inflammation
• Proposed mechanisms
– Liberation of fatty acids from adipose tissue leads to increased
production of free radicals which inhibits nitric oxide (important
for healthy arterial walls)
– IL-6 from skeletal muscle may be involved in mediation of
glucose uptake during exercise
– TNF-α involvement in increased insulin resistance
• Precise role of inflammation in insulin resistance and the
relationship to endothelial dysfunction remains unclear
Barzilay & Freeland (2003) Treat Endocrinol 2: 85-94.
Post-menopausal Women
• Special risk factors with Hormone Replacement Therapy
(HRT)
• HRT has a vascular inflammation effect and may lead to
increased risk of adverse cardiovascular events
• Women's Health Initiative1
– Elevated levels of CRP and IL-6 were associated with HRT use
– Use or nonuse of HRT is less important as a predictor of
cardiovascular risk than baseline levels of either CRP or IL-6
• Stauffer Study2
– CRP levels unchanged from normal values in women who
exercised while taking hormone replacement therapy (HRT)
– CRP levels were significantly higher in sedentary HRT users
– Exercise may be beneficial to counteract the negative impacts of
HRT
1 Pradhan
2
et al. (2002) JAMA 288: 980-7.
Stauffer et al. (2004) J Appl Physiol 96: 143-8.
What is the best type of exercise to
reduce inflammation?
– In athletes, effects of exercise training on
CRP varied by type of exercise low in
swimmers and rowers but not soccer
players1
– National Health and Nutrition Examination
Survey III found joggers and aerobic
dancers less likely to have elevated CRP
compared with cyclists, swimmers and
weightlifters2
CRP Levels
• Overall amount of leisure time activity was
found to be inversely associated with CRP
levels in 4072 adults
• Adjustments made for confounds such as
age, gender, ethnicity, education,
occupation, smoking, hypertension, BMI,
waist-to-hip ratio, HDL, aspirin use, insulin
levels etc.
– In older adults, cardiorespiratory group
significantly greater reductions in proinflammatory markers than
flexibility/strength group3
• Independent of b-blocker use, sex, BMI
OR
95% CI
Jogging
.33
0.14-0.78**
Swimming
.62
0.25-1.52
Cycling
1.30
0.76-2.22
Aerobic dancing
.31
0.13-0.78**
Other dancing
.76
0.33-1.73
Calisthenics
.77
0.48-1.23
Gardening
1.36
0.87-2.12
Weight lifting
.83
0.41-1.67
** P < 0.05
Adapted from King et al. (2003)
1
Dufaux et al. (1984) Int J Sports Med 5: 102-6.
King et al. (2003) Med Sci Sports Exerc 35: 575-81
3 Kohut et al. (2006) Brain Behav Immun 20: 201-9.
2
American College of Sports Medicine
Exercise Prescription Guidelines
• No specific section devoted to low-grade inflammation
• Section on metabolic syndrome (pg 219-220)
– Standard exercise prescription
– Hypertension, diabetes, obesity may be present and require
special exercise prescription
– Referral to Obesity section
• Exercise progression should include increased training
intensity (50-75% max VO2 or HR)
ACSM's Quidelines for Exercise Testing and Prescription (2006) 7 ed., Philadephia: Lippincott
Williams & Wilkins
Exercise Prescription
Recommendations
– Low-grade inflammation may be present in asymptomatic
individuals…
– Pre-exercise Testing
• Assess global risk factors; recommendation for follow-up with
physician
• History of work-related MSD
– Pathophysiology of disorder, wide-spread symptoms may be present
– Cardiorespiratory 3-5 days/wk
• Progressive up to 75% Maximum Oxygen consumption (VO2max) or
16 Rating of Perceived Exertion (RPE)
• Progress up to 30 minute minimum
– Strength training 2 days/wk
• Progressive up to 19-20 RPE
• 8-10 reps on all major muscle groups
Note: strength training important for sarcopenia prevention but likely
not as important in the reduction of chronic low-grade inflammation
Consumer Education Materials:
Exercise doesn’t make money, drugs and supplements DO!
Stop Inflammation NOW!
A Step-by-Step Plan to Prevent,
Treat, and Reverse Inflammationthe Leading Cause of Heart
Disease and Related Conditions
Richard M. Fleming, M.D.0
Approximately 25.7% of women,
representing approximately
26.8 million women,
did not report using hormone
replacement therapy and had a
CRP concentration >3.0 to 10
mg/L, a category considered to
indicate high risk for cardiovascular
disease1
1 Ford
et al. (2004) Clin Chem 50: 574-81.
C-Reactive Protein:
Everything You Need to Know
About CRP and Why It’s More
Important than Cholesterol to
You Health
What CRP is and why you need to be
concerned about it
What do to do if your CRP level is high
Lifestyle information on nutrition,
supplements, exercise and medication
Scott J. Deron, D.O., FACC
Resources on the Web
•
American Heart Association: Inflammation, Heart Disease and Stroke: The
Role of C-Reactive Protein
http://www.americanheart.org/presenter.jhtml?identifier=4648
•
Diabetes Drug Reduces Development of Heart Stent Blockage
http://www.diabetes.org/for-media/scientific-sessions/06-14-03-1.jsp
•
Vitamins C And E: Protection For Your Blood Vessels?
http://www.diabetes.org/diabetes-forecast/jun2005/research.jsp
•
Low-grade inflammation ready to move to the mainstream
http://www.theheart.org/viewArticle.do?simpleName=336538
•
Inflammation and the Metabolic Syndrome- A powerpoint presentation by
Dr. Jorge Plutzky
http://www.medscape.com/viewarticle/440972_8
•
Latest News and Resources on Metabolic Syndrome X from Medline
http://www.nlm.nih.gov/medlineplus/metabolicsyndromex.html