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Colorado Center for Health Wellness National Press Foundation April 29, 2013
Robert H. Eckel, M.D. Professor of Medicine Professor of Physiology and Biophysics Charles A. Boettcher II Chair in Atherosclerosis University of Colorado Anschutz Medical Campus
robert.eckel@ucdenver.edu
Skin
Gout
Women
Endometrial Gallbladder Esophageal - adenoCa Renal
T47D Cancer Cells Stained with Oil Red O for Neutral Lipid
FDG PET Scans of Metastatic Prostate Cancer before and 24 Hours after Fatty Acid Oxidation is Blocked
Basal FDG-PET Scan Etomoxir 24 hours
Vascular Endothelium
70-79
60-69 50-59 40-49
64
IHD mortality (floating absolute risk and 95% CI) 32 16 8 4
60-69
50-59
40-49
2
1 0
Men
6
5
4
3 2 1 0 <21 22 23 24 25 26 27 28 29 30
4
3 2 1 0 <21 22 23 24 25 26 27 28 29 30
BMI (kg/m2)
Type 2 diabetes Cholelithiasis
BMI (kg/m2)
Hypertension Coronary heart 23 disease
2007
Overweight 34%
Obese 31%
Attained BMI
NHS. Ann Int Med 122:481,
Diabetes
IGT
-10
-5
10
15
20
25
Insulin resistance
-cell
-15
-10
-5
10
15
20
25
Years of Diabetes
b-Cell Failure
400
300
200
100
Insulin Resistance
Weyer C et al. J Clin Invest 104: 787, 1999
Placebo
Metformin Lifestyle 4.2%
7.2% N= 3051
2865
1500
385
12 18
24
30
36
42
48
Months
30
31% 58%
20
10
0 0
NEJM 346: 393, 2002
11
metformin
6
-10 -8 -6 -4 -2 0 2 Change from baseline weight (kg) 4 6
Weight Loss in T2DM and Less CVD: Did Look AHEAD Answer All the Questions?
Primary Objective To assess the long-term
(11.5 yr) effects of an intensive weight loss program over 4 years in overweight and obese subjects with type 2 diabetes.
n ~ 5000 men and women age: 45-74 yr BMI > 25 kg/m2 Primary outcome time to a major CVD event Secondary outcomes - many Controlled Clin Trials 24:610, 2003
Percentage of Participants in ILI and DSE Groups Who Met Different Weight Loss Criteria at Year 4
100 90 80 % of Participants 70 60 50 40
45% 55% 46% 35% 26% 18% 8% 25% 18% 23% 10% 9% 4% 74%
30
20 10 0 5% 0% >0% 5%
7%
10 %
15 %
Weight Gain
LDL-C Goal
<100
(<70)
Consider Drug Rx
100*
2+ RF
(10-20%/10 yr)
130*
160* 190*
2+ RF
(<10%/10 yr)
01 RFs
* Consider drug options if below goal, but above goal for next higher risk level
Metabolic Syndrome:
April 2008
Known CHD
On a statin
Residual Risk
June 2008
AMI at work
Resuscitation failed
Could this have been Grady D. A Search for Answers in Russerts Death. The New York avoided?
Times. June 17, 2008.
Abdominal circumference (1 of 5) men > 94 cm women > 84 cm adjusted locally around the world Triglycerides > 150 mg/dl HDL cholesterol men < 40 mg/dl women < 50 mg/dl Blood pressure > 130/85 Glucose > 100 mg/dl
Eckel RH et al, Lancet, 375:181, 2010
39
Pathogenesis of NAFLD
Pathogenesis of NAFLD
first hit
Pathogenesis of NAFLD
second hit
Prevalence of NAFLD
Steatosis
-Neuschwander-Tetri, Hepatology,
Prevalence of NAFLD
-Neuschwander-Tetri,
Diabetes mellitus (Type 2) HOMA > 1.64 (More insulin resistant) Family History Age > 50 yr Males > females Hispanic > White > Black Metabolic syndrome
Important Caveat
Standard blood tests for liver disease, may be completely normal in many patients with NAFLD: Even patients with NASH or advanced fibrosis due to NASH!!!!
Abrams G, et al. Hepatology 2004;40:475
1.0
0.6 <18.5 22 25 28 30 Body Mass Index (BMI) 35
Abdominal Obesity and Coronary Heart Disease in Women: The Nurses Health Study
Incidence rate per 100,000 person-years
128 110
140 120
Follow-up of 8 years
83
106 89 77 46 55
97
100
80 60 40
20
0 High (25.2 - <48.8) Middle (22.2 - <25.2) Low (12.2 - <22.2)
CRP by Number of Metabolic Disorders (Dyslipidemia, Upper Body Adiposity, Insulin Resistance, Hypertension)
Mean Value of Log CRP
1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 0 1 2 3 4 Number of Metabolic Disorders
Festa et al. Circulation 102:42, 2000
Hazard Ratio for the Risk of Diabetes Over 17 Years in Healthy Young Adults, According to BMI in Adolescence and in Adulthood
37,674 young men, Staff Periodic Exam, Israeli Army Medical Corps
Hazard Ratio for the Risk of Coronary Heart Disease Over 17 Years in Healthy Young Adults, According to BMI in Adolescence and in Adulthood
37,674 young men, Staff Periodic Exam, Israeli Army Medical Corps
Cancer risk Hypertension Diabetes Dyslipidemia Non-alcoholic fatty liver disease Obstructive sleep apnea-hypopnea Cardiovascular disease risk Symptom-based further evaluation prn
Thank You!