Diet and Metabolic Syndrome: Practical Approaches to Lowering Risks of Heart Disease and Diabetes
Health Risks and Comorbid Conditions. Outline Overview of the Metabolic Syndrome Risks of Obesity...
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Health Risks and Comorbid Conditions
Outline
• Overview of the Metabolic Syndrome
• Risks of Obesity and the Metabolic Syndrome
• Specific Health Risks
• Answers to Questions & Summary
Question # 1
Which of the following is not part of the Metabolic Syndrome?
1. High HDL-cholesterol (> 50 mg/dL)
2. High blood pressure (> 130/85)
3. High Triglyceride (> 150 mg/dL)
4. Impaired fasting glucose (100-126 mg/dL)
5. Increased waist circumference [> 88cm (F) 102cm (M)]
Development of the Concept
• 1904 - Life insurance data
• 1947 - Vague introduces adipomuscular ratio
• 1967 - Crepaldi insulin resistance and disease
• 1970 - Feldman Epidemiological relation
• 1982 - Ratio of waist to hip circumference related to morbidity and mortality in 2 separate laboratories
• 1988 - Reaven describes Syndrome X
Abdominal Obesity
Abdominal Adiposity
Courtesy of Steven Smith, M.D.
Visceral Subcutaneous
Body Fat Distribution and Glucose Tolerance
Kissebah JCEM 1982;54:254-260.
Time (min)
Insu
lin
(μ
U/m
L
0 30 60 90 120 150 1800
50
100
150
200
250
Upper Body Lower Body Control
Time (min)
Glu
cose
(m
g/d
L)
0 30 60 90 120 150 1800
50
100
150
200
250
Visceral Obesity and Risk of Dyslipidemia
Despres JP, et al. Arteriosclerosis. 1990;10:497-511.
Obese: Level of deep abdominal fat
VariableNonobese
(n = 25)Low
(n = 10)High
(n = 10)
% Body fat 28.0 ± 5.6 47.0 ± 6.4 49.8 ± 3.2
Deep abdominal fat area (cm2) 50.3 ± 16.8 107.0 ± 33.4 186.7 ± 36.8
TG (mmol/L) 0.79 ± 0.35 1.47 ± 0.79 2.57 ± 2.41
CHOL (mmol/L) 4.59 ± 0.88 5.18 ± 0.93 5.65 ± 1.23
LDL CHOL (mmol/L) 3.00 ± 0.87 3.56 ± 0.92 3.81 ± 1.10
HDL CHOL (mmol/L) 1.36 ± 0.24 1.25 ± 0.18 0.96 ± 0.12
Fasting insulin (pmol/L) 39.0 ± 12.4 91.5 ± 59.9 150.3 ± 57.3
Glucose area ([mmol/L/180 min] x 103)
10.7 ± 0.19 1.14 ± 0.22 1.40 ± 0.19
Insulin area ([pmol/L/180] x 103) 46.6 ± 19.4 82.1 ± 48.3 121.0 ± 39.5
Metabolic Syndrome: NCEP ATP III
JAMA 2001;285:2486-2497.
Risk Factor Cut-PointsCentral Adiposity
M (waist) > 40 in > 102 cm F > 35 in > 88 cmTriglycerides ≥ 150 mg/dL ≥ 7.1 mmol/LHDL-C M < 40 mg/dL < 0.9 mmol/L F < 50 mg/dL < 1.0 mmol/LBlood Pressure ≥ 130/≥ 85 mm Hg
Fasting Glucose ≥ 110 (100) mg/dL ≥ 6.1 mmol/L
Age-Adjusted Prevalence of the Metabolic Syndrome
Ford. JAMA 2002;287:356-9.
Among 8814 Adults Age > 20
Characteristics of the Metabolic Syndrome
• Abdominal obesity• Glucose intolerance• High triglycerides• Low HDL-cholesterol• High blood pressure• Insulin resistance
• Microalbuminuria• Small dense LDL• Inflammatory markers• Thrombotic factors• Endothelial
dysfunction• Hyperuricemia
Full members Wannabes
Central Fat and Lifestyle Health Risk
1st quintile
5th quintile
0 1 2 3 4 5 6 7 8 9 10 11 12
1.0
0.95
1.0
0.95
Years of follow-up
Waist to hip ratio
Pro
babi
lity
of r
emai
ning
fr
ee o
f myo
card
ial
infa
rctio
nP
roba
bilit
y of
su
rviv
al
Lapidus. BMJ 1984;289:1257-61.
Outline
• Overview of the Metabolic Syndrome
• Risks of Obesity and the Metabolic Syndrome
• Specific Health Risks
• Answers to questions & Summary
Excess fat stores
GenesEnvironment
Activity Food Intake
Diseases due to increased fat cellsize & visceral fat
Stigma
Sleep apnea
OsteoarthritisDiabetes
GB Disease
NAFLD CVD
Cancer
Diseases due to increased fat
mass
Pathogenesis of Health Problems Associated with Obesity
AngiotensinogenAngiotensinogen
Fat CellFat Cell
Free Fatty Acids Free Fatty Acids
LactateLactate
LeptinLeptin
Adipsin (ASP) (complement (3a;D)Adipsin (ASP) (complement (3a;D)Lipoprotein
Lipase (LPL)LipoproteinLipase (LPL)
IL-6IL-6
Cholesterolester Transfer Protein (CETP)
Cholesterolester Transfer Protein (CETP)
Prostacyclin Prostacyclin
Plasminogen Activator Inhibitor (PAI-1)Plasminogen Activator Inhibitor (PAI-1)
TNF-TNF-
Phospholipid Transfer Protein (PLTP)
Phospholipid Transfer Protein (PLTP)
AdiponectinAdiponectin
ProstaglandinProstaglandin
Monobutyrin Monobutyrin
Galectin-12Galectin-12
The Fat Cell is an Endocrine Cell
Pulmonary diseaseabnormal functionobstructive sleep apneahypoventilation syndrome
Nonalcoholic fatty liver diseasesteatosissteatohepatitiscirrhosis
Coronary heart disease Diabetes Dyslipidemia Hypertension
Gynecologic abnormalitiesabnormal mensesinfertilitypolycystic ovarian syndrome
Osteoarthritis
Skin
Gall bladder disease
Cancerbreast, uterus, cervixcolon, esophagus, pancreaskidney, prostate
Phlebitisvenous stasis
Gout
Medical Complications of ObesityIdiopathic intracranial hypertension
Stroke
Cataracts
Severe pancreatitisSevere pancreatitis
Outline
• Overview of the Metabolic Syndrome
• Risks of Obesity and the Metabolic Syndrome
– Mortality
– Morbidity
• Specific Health Risks
• Answers to questions & Summary
Question # 2
Which of the following is NOT an estimate of excess deaths from obesity?
1. 450,000
2. 365,000
3. 325,000
4. 275,000
5. 112,000
0
0.5
1
1.5
2
2.5
3
< 1
8.5
18.5
- 2
0.4
20.5
- 2
1.9
22.0
- 2
3.4
23.5
- 2
4.9
25.0
- 2
6.4
26.5
- 2
7.9
28.0
- 2
9.9
30.0
- 3
1.9
32.0
- 3
4.9
35.0
- 3
9.9
> 4
0.0
Body Mass Index Interval
Rela
tive
Ris
k o
f D
eath
White Men
White Women
BMI and Mortality by Ethnic Group The American Cancer Society Study
Calle NEJM 1999;341:1097.
Relative Risk of Death by BMI Levels from the NHANES I, II, & III Surveys
BMI Level Relative Risk by Age Category
25-59 60-69 ≥ 70
< 18.5 1.38 2.30 1.69
18.5 to < 25 1.00 1.00 1.00
25 to < 30 0.83 0.95 0.91
30 to < 35 1.20 1.13 1.03
≥ 35 1.83 1.63 1.17
Flegal et al JAMA. 2005;1861.
Range of Estimates of Mortality Associated with Overweight
Author YearEstimated excess
deaths
Foege & McGinnis 1993 300,000
Fontaine et al 1999275,000 to
325,000
Mokdad et al 2004 365,000
Flegal et al NHANES I
2005 112,000
Overweight*(BMI 25 - 29.9)
Obese*(BMI > 30)
Female (non-smoker, 40 years of age) 3.29 y 7.08 y
Male (non-smoker, 40 year of age) 3.05 y 5.82 y
Obesity Decreases Life Expectancy:The Framingham Study
Peeters Ann Int Med 2003;138:24-32.
* Compared to a BMI 18.5-24.9 kg/m2
Question # 3
Which disease has the highest risk in association with obesity?
1. Breast cancer
2. Diabetes
3. Cardiovascular disease
4. Osteoarthritis
5. Kidney stones
Outline
• Overview of the Metabolic Syndrome
• Risks from Obesity and Metabolic Syndrome– Increased mortality
– Increased morbidity
• Specific Health Risks
• Answers to Questions & Summary
Relationship Between BMI and Comorbidities Is Positive,
Even in the “Normal” Range
Willett WC, et al. N Engl J Med. 1999;341:427-434.
Body Mass Index(kg/m2)
Rel
ativ
e R
isk
Women Men
4
6
5
3
2
1
0
< 21 22 23 24 25 26 27 28 29 30
Body Mass Index(kg/m2)
4
6
5
3
2
1
0
< 21 22 23 24 25 26 27 28 29 30
Rel
ativ
e R
isk
Type 2 diabetes
Cholelithiasis
Hypertension
Coronary heart disease
Prevalence (%) by BMI Categories
< 21.9 22 to 23.9
24 to 24.9
25 to 27.9
28 to 29.9
30 to 34.9
35 to 39.9
> 40
High BP 18.7 21.8 25.3 31.6 39.2 46.6 55.8 62
High Chol
33.5 38.4 40.9 44.1 46.1 46.7 44.1 38.9
Diabetes 1.9 2.2 2.7 3.7 5.6 8.7 12.8 15.2
Arthritis 31 33.8 36.3 38.6 42.3 45.1 48.7 54.9
Coakley et al IJO 1998;22:958.
BMI and Chronic Disease Prevalence in the Nurses Health Study
Proportion of Disease Prevalence Attributable to Obesity
Type 2 Diabetes 57%
Gall bladder disease 30%
Hypertension 17%
Cardiovascular disease 17%
Osteoarthritis 14%
Breast Cancer 11%
Uterine Cancer 11%
Colon Cancer 11%
Age- and Sex-Adjusted Prevalence of Risk Factors for BMI > 30 kg/m2
Variable
NHES
1960-62
NHANES
1971-75
NHANES
1976-80
NHANES
1988-94
NHANES
1999-00
High cholesterol (>6.2 mM)
38.9 33.1 31.5 23.0 17.9
High BP
>140/>90
41.6 46.5 35.6 22.3 23.7
Diagnosed Diabetes
2.9 5.9 6.3 9.0 10.1
Gregg et al JAMA 2005;293:1868.
Outline
• Overview of the Metabolic Syndrome
• Specific Health Risks– Increased risk of diabetes
– Increased risk of heart disease
– Increased risk of hypertension
– Increased risk of cancer
– Other increased risks
• Answers to Questions & Summary
Relationship Between BMI and Risk of Type 2 Diabetes Mellitus
Chan J et al. Diabetes Care 1994;17:961.Colditz G et al. Ann Intern Med 1995;122:481.
Age
-Adj
uste
d R
elat
ive
Ris
k
Body Mass Index (kg/m2)
< 23 24 - 24.9
25 - 26.9
27 -28.9
33 -34.9
0
25
50
75
100
1.02.9 4.3 5.0
8.1 15.8
27.6
40.3
54.0
93.2
< 22 23 - 23.9
29 -30.9
31 -32.9
35 +
1.0 1.52.2
4.46.7
11.6
21.3
42.1
1.0
Men
Women
Waist Circumference Relative Risk of Type 2 DM
< 28 inches 1.0
28 - 29 1.2
30 - 31 2.8
32 - 33 4.0
34 - 35 4.8
36 - 37 5.5
> 38 6.2
*Controlled for age, family history of diabetes, exercise, smoking, saturated fat intake, calcium, potassium, magnesium, and glycemic index.
Nurses’ Health Study: Waist Circumference Directly Related to Risk for Type 2 Diabetes
Carey et al. Am J Epidemiol. 1997;145:614.
Prevalence
Caucasian/African-American (N = 1057) 17%
Caucasian/Hispanic(N = 560) 18%
Hispanic (N = 31) 45%
African-American(N = 97) 47%
Prevalence of Type 2 Diabetes Among Diabetic Children in 4 Studies
Fagot-Campagna et al. J Pediatr 2000;136:664.
Group Relative Risk
Non-diabetic throughout 1.0
MI/stroke before diabetes 2.8
MI/stroke after diabetes 3.7
Diabetes at baseline 5.0
Nurses Health Study: Diabetes & MI/Stroke
Hu Diab Care 2002;25:1129.
Outline
• Overview of the Metabolic Syndrome
• Specific Health Risks– Increased risk of diabetes
– Increased risk of heart disease
– Increased risk of hypertension
– Increased risk of cancer
– Other increased risks
• Answers to Questions & Summary
BMI Multivariate Relative Risk< 21 1.0
21 to < 23 1.2
23 to < 25 1.3*
25 to < 29 1.8*
> 29 3.3*
BMI and Risk of Coronary Heart Disease in the Nurses Health Study
Manson et al NEJM 1995;333:677-85.
* = p < 0.05
0
0.5
1
1.5
2
2.5
Folsom et al. Arch Intern Med 2000;160:2117.
Body Mass Index Tertile3 2
3
11
2
Re
lativ
e R
isk
Waist
-Hip R
atio
Tertile
Abdominal Fat Distribution Increases the Risk of Coronary Heart Disease
The Iowa Women’s Health Study
0
1
2
3
4
5
6
7
< 19.1 19.1 -20.3
20.4 -21.5
21.6 -23.2
> 23.3
-5 or more-4.9 to +4.9
+5 to 10.9+11 to 19.9
+20 or more
WeightChange, kg
Body Mass Index (kg/m2) at 18 Years of Age
RelativeRisk
BMI Weight Gain and Cardiovascular Risk
Willett et al JAMA. 1995;273:461-5.
Body Weight and Weight Gain During Adult Life and Risk of CHD
Weight Change Category Relative Risk of CHD
Loss of 4% 1.89
Stable 1.00
Gain 4 - 10% 1.48
Gain 10 - 15% 1.65
Gain 15 - 25% 1.48
Gain 25 - 35% 1.95
Gain more than 35% 2.62
Rosengren et al Europ H J 1999;20:269-277.
The Interheart Study: Risk of MI
FactorOdds Ratio
Population Attributable Risk
Abdominal Obesity (WHR)+ 2.24 33.7
Diabetes+ 3.08 12.3
Hypertension+ 2.48 23.4
ApoB/ApoA1+ 3.87 54.2
Smoking* 2.27 36.4
Psychosocial+ 2.51 28.8
* Adj for Age, Sex & Geography+ Adj Age, Sex & Smoking
Yusuf et al Lancet 2004;364-352.
Incidence per 1000 person years
Group Men Women
Normal Weight 5.1 9.7
Overweight 8.6 10.7
Obese 9.9 14.3
Obesity and the Risk of New Onset Atrial Fibrillation
Wang et al JAMA 2004;292:2471-77.
Incidence (%)
Group Men Women
Normal Weight 5.0 3.5
Overweight 6.0 3.8
Obese 10.0 6.8
10-Year Cumulative Incidence of Heart Failure in the Framingham Study
Kenchaiah et al NEJM 2002;347:305-313.
Outline
• Overview of the Metabolic Syndrome
• Specific Health Risks– Increased risk of diabetes
– Increased risk of heart disease
– Increased risk of hypertension
– Increased risk of cancer
– Other increased risks
• Answers to Questions & Summary
Prevalence of Elevated Blood Pressure by BMI Category
BMI Ranges Men Women
< 25 18.2 16.6
25 - 26 22.5 21.9
27 - 29 25.2 24.0
> 30 38.4 32.2
NHLBI Evidence Report 1988.
Outline
• Overview of the Metabolic Syndrome
• Specific Health Risks– Increased risk of diabetes
– Increased risk of heart disease
– Increased risk of hypertension
– Increased risk of cancer
– Other increased risks
• Answers to Questions & Summary
Mortality from Cancer in American Men and Women
Calle NEJM 2003;348:1625.
Men Women
• Liver• Pancreas• Stomach/Esophagus• Colon/Rectum• Gallbladder• Multiple Myeloma• Kidney• Non-Hodgkin’s• Prostate
• Uterus• Kidney• Cervix• Pancreas/Esophagus• Gallbladder• Breast• Non-Hodgkin’s• Liver• Ovary• Colon/Rectum
Outline• Overview of the Metabolic Syndrome
• Overview of Risks
• Specific Health Risks– Increased risk of diabetes
– Increased risk of heart disease
– Increased risk of hypertension
– Increased risk of cancer
– Other increased risks
• Answers to Questions and Summary
Other Increased Risks
• Kidney stones• Complications of pregnancy• Sleep disorders• Osteoarthritis• Stigmatization
Relative Risk
BMI Categories Men Women
< 21 0.73 1.15
21 - 22.9 1.00 1.00
23 - 24.9 0.94 1.26
25 - 27.4 1.20 1.34
27.5 - 29.9 1.24 1.75
> 30 1.33 1.90
Taylor et al JAMA 2005;293:455-462.
Body Mass Index and the Relative Risk of Symptomatic Kidney Stones
Pregnancy Complications in Obese and Overweight Nulliparous Women
BMI Categories
Complications < 2020 to 24.9
25 to 29.9 >30
Gestational Diabetes 1.0 1.3 2.4 5.2
Preeclampsia 1.0 1.3 2.0 3.3
Eclampsia 1.0 1.4 2.0 3.0
Caesarean 1.0 1.3 1.8 2.7
Baeten et al Am J Pub Health 2001;91:436-440.
Moderate Weight Change and Sleep Disordered Breathing
Weight Change (%)Apnea-Hypopnea Index
(Events/hour)
- 20 kg - 48
10 kg - 26
- 5 kg - 14
5 kg 15
10 kg 32
20 kg 70
Peppard et al JAMA 2000;284:3015-3021.
Adjusted Odds Ratio for Osteoarthritis by Tertiles of BMI
Tertiles of BMI Hand Hip Knee
1 1 1 1
2 5.4 3.4 3.8
3 8.3 1.4 9.3
Oliveria et al Epidemiology 1999;10:161.
BMI and Physical Functioning (SF-36)The Nurses Health Study
BMI Categories Relative Risk
< 21.9 0.94
22 - 23.9 1.00
24 - 24.9 1.05
25 - 27.9 1.23
28 - 29.9 1.49
30 - 34.9 1.66
35 - 39.9 2.08
> 40 3.08
Coakley et al IJO 1998;22:958-963.
Outline
• Overview of the Metabolic Syndrome
• Risks of Obesity and the Metabolic Syndrome
• Specific Health Risks
• Answers to Questions & Summary
Question # 1
Which of the following is not part of the Metabolic Syndrome?
1. High HDL-cholesterol (> 50 mg/dL)
2. High blood pressure (> 130/85)
3. High Triglyceride (> 150 mg/dL)
4. Impaired fasting glucose (100-126 mg/dL)
5. Increased waist circumference [> 88cm (F) 102cm (M)]
Question # 1
Which of the following is not part of the Metabolic Syndrome?
1. High HDL-cholesterol (> 50 mg/dL)
2. High blood pressure (> 130/85)
3. High Triglyceride (> 150 mg/dL)
4. Impaired fasting glucose (100-126 mg/dL)
5. Increased waist circumference [> 88cm (F) 102cm (M)]
Question # 2
Which of the following is NOT an estimate of excess deaths from obesity?
1. 450,000
2. 365,000
3. 325,000
4. 275,000
5. 112,000
Question # 2
Which of the following is NOT an estimate of excess deaths from obesity?
1. 450,000
2. 365,000
3. 325,000
4. 275,000
5. 112,000
Question # 3
Which disease has the highest risk in association with obesity?
1. Breast cancer
2. Diabetes
3. Cardiovascular disease
4. Osteoarthritis
5. Kidney stones
Question # 3
Which disease has the highest risk in association with obesity?
1. Breast cancer
2. Diabetes
3. Cardiovascular disease
4. Osteoarthritis
5. Kidney stones
Summary
• The metabolic syndrome defined as central adiposity, hypertension, impaired fasting glucose and dyslipidemia is a major risk factor for heart disease and diabetes
• Obesity shortens life and increases the number of excess deaths
• Diabetes, heart disease, osteoarthritis, cancer, kidney stones, complications of pregnancy, sleep apnea and impaired physical functioning are all associated with obesity