Michael E. Farkouh, MD, MSc Peter Munk Chair in Multinational Clinical Trials Director, Heart and Stroke Richard Lewar Centre Vice Chair Research and Professor Of Medicine University of Toronto The Four “Links” of Obesity: Diabetes, Fatty Liver, Cardiomyopathy and AF The Potential Benefit and Rapid Evolution of Bariatric Surgery
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Michael E. Farkouh, MD, MSc
Peter Munk Chair in Multinational Clinical Trials
Director, Heart and Stroke Richard Lewar Centre
Vice Chair Research and Professor Of Medicine
University of Toronto
The Four “Links” of Obesity:
Diabetes, Fatty Liver, Cardiomyopathy and AF
The Potential Benefit and Rapid
Evolution of Bariatric Surgery
o Research Grant: Amgen
Disclosures
Obesity is a public health issue, through common
pathways, that links:
o Diabetes
o Fatty Liver Disease
o Cardiomyopathy
o Atrial Fibrillation
Weight Loss including Bariatric Surgery is the cornerstone
of breaking these links and to restoring health
The Four Links of Obesity
For adults, overweight and obesity ranges are determined by using weight and
height to calculate a number called the "body mass index" (BMI). BMI is used
because, for most people, it correlates with their amount of body fat.
See the following table for an example:
Height Weight Range BMI Considered
5' 9"
124 lbs or less Below 18.5 Underweight
125 lbs to 168 lbs 18.5 to 24.9 Healthy weight
169 lbs to 202 lbs 25.0 to 29.9 Overweight
203 lbs or more 30 or higher Obese
Other methods of estimating body fat and body fat distribution include
measurements of skinfold thickness and waist circumference, calculation of waist-
to-hip circumference ratios, and techniques such as ultrasound, computed
tomography, and magnetic resonance imaging
BMI
Obesity (BMI ≥30 kg/m2)
Diabetes
1994
1994
2000
2000
No Data <14.0% 14.0%–17.9% 18.0%–21.9% 22.0%–25.9% > 26.0%
No Data <4.5% 4.5%–5.9% 6.0%–7.4% 7.5%–8.9% >9.0%
2014
2014
Age-adjusted Prevalence of Obesity
and Diagnosed Diabetes Among US Adults
http://www.cdc.gov/diabetes/data
Insulin secretion
0 5-10
-5 10 15
Pre-diabetes
Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789Nathan DM. N Engl J Med. 2002;347:1342-1349
Insulin resistance
Postprandial glucose
Fasting glucose
Type 2 diabetes
Years from diagnosis Onset Diagnosis
Oral combo therapy
Insulin
Macrovascular complications
Diet and exercise
Oral monotherapy
Microvascular complications
Natural History of Type 2 Diabetes
Typical Progression of Disease and Treatment
Adapted from Esser N, et al. Expert Opin Investig Drugs. 2015 Mar;24(3):283-307
Role of inflammation in the pathophysiology of
type 2 diabetes and the increased risk of CVD
Non‐Alcoholic Fatty Liver Disease (NAFLD):
an Epidemiological and Molecular Perspective
Abnormalities in fatty acid metabolism, along with adipose tissue, hepatic, and systemic
inflammation are implicated in the development of insulin resistance, dyslipidemia,
and cardiometabolic risk factors associated with NAFLD.
The prevalence of NAFLD
is 80-90% in obese adults.
Adapted from: Bellentani S et al. Dig Dis 2010;28(1):155-61Bekaert M, et al. Obes Rev. 2016 Jan;17(1):68-80.
Adapted from Esser N, et al. Expert Opin Investig Drugs. 2015 Mar;24(3):283-307
Potential targets for pharmacotherapy in type 2 diabetes
and related metabolic abnormalities and CVD
o HFpEF is associated with substantial morbidity and mortality
o HFpEF is characterized by impaired diastolic function caused by impaired collagen metabolism and increased myocardial fibrosis
o Obesity is an independent predictor of advanced NYHA class and an independent predictor of a future event of hospitalizationfor HF or CV death
o Pathophysiology:
• Adipose tissue is metabolically active and elaborates inflammatory
cytokines;
• Associated with Hypertension
Dalos D, et al. JACC. 2016 Jul 12;68(2):189-99
Kitzman DW, et al. JACC. 2016 Jul 12;68(2):200-03
The Elephant in the Room: 1.8 million Americans with the Obesity and Heart Failure with
Preserved Left Ventricular Function (HFpEF) Phenotype
Vermond, RA, et al. JACC. 2015, 66(9):1000–1007
Figure Legend:
AF in a Community-Based Cohort in the Netherlands: Multivariate Determinants of Incident AF
Bars represent the hazard ratio for incident atrial fibrillation (AF) of each individual risk factor in the
multivariate model. The 95% confidence intervals (CIs) are shown under each bar. BMI = body mass
index; HT = antihypertensive; MI = myocardial infarction.
Incidence of Atrial Fibrillation and Relationship With
Cardiovascular Events, Heart Failure, and Mortality:
A Community-Based Study From the Netherlands
Mahajan R et al, JACC. 2015 Jul 7;66(1):1-11
Electrophysiological, Electroanatomical, and Structural
Remodeling of the Atria as Consequences of Sustained Obesity
Obesity requires long-term treatment
Weight loss of 0.5-9 kg associated with:
o 53% reduction in cancer deaths
o 44% reduction in diabetes associated mortality
o 20% reduction in total mortality
Survival increased 3-4 months for every kg of weight loss