The Skinny About Fat
Adam S. Nally, D.O.
Board Certified Family Physician
Board Certified Medical Bariatrician
American Society of Bariatric Physicians Advanced Curriculum Fellow
American Osteopathic Association Health Policy Fellow
Disclosures
•
None
“Change starts
when someone
sees the next
step.”
Colonel William Drayton
Agricultural Adjustment Act of 1933
Food, Conservation & Energy Act 2002, 2012
Agricultural Act of 2014




“Farm Bill” making us fatter?
Omnibus Bill
 $300 billion/year
 Signed into law Feb 7,
2014
80% -> Nutrition Program
Funding (based on USDA
guidelines)
CBO estimates $973 billion to
be spent over next 10 years
 Legislating Our Waistlines?
Kasperowicz P, Wasson E, www.thehill.com,Sept 20,2013
www.USDA.gov, Agricultural Act of 2014, May 17, 2014
“Farm Bill” Making Us Fatter
USDA


Dietary Guidelines
Unchanged since 1977
“…people who are the most
successful at achieving and
maintaining a healthy
weight do so through . . .
consuming only enough
calories from foods and
beverages to meet their
needs and by being
physically active”
Mirror subsidy funding
trends (SNAP & NSLP)
http://www.cnpp.usda.gov/dietaryguidelines.htm
Am J Public Health. 2005 September; 95(9): 1602–1606

Three Massive Studies

The Women’s Health Initiative (WHI)
 1991 - 48,835 postmenopausal women followed for 8 years
 Low Fat Group vs Control Group
 Only 0.4 kg of weight loss!
 (JAMA. 2006 Jan 4;295(1):39-49.)

Multiple Risk Factor Intervention Trial (MRFIT)
 1972 - 12,866 men at a high risk for CAD followed for 7 years
 All Placed on Low Fat Diets
 100% failure to reduce weight or CAD
 (JAMA. 1982;248(12):1465-1477.)

Action For Health in Diabetes (The Look AHEAD Study)
 2001 - Intensive Lifestyle Intervention in DM Type II – 5,145
patients
 Supposed to last 13.5 yrs – stopped at 9.6 yrs (wasn’t working)
 Intense Calorie restriction 1200-1800 cal /day
 Did loose weight (~6% of body weight lost)
 Didn’t live longer – Didn’t reduce CAD
 (N Engl J Med 2013; 369:145-154)

Grossly unsuccessful in decreasing obesity
 MRFIT - 1972
 WHI - 1991
 Look AHEAD - 2001
What Is A Low Carbohydrate Diet?
Low

<100 grams / day
Very

Carbohydrate
Low Carb
< 50 grams /day
Ketogenic

Diet
<20 grams / day
o
Primary Fuel of Ketogenic
Diet
Acetoacetic acid - initial ketone
o reduced to beta-hydroxybutyric
acid
o nonenzymatically decarboxylated
to acetone
o Serum Ketones
o
o 0.4
– 4 mmol/L
Glucose <110
o pH ~7.4 (7.35-7.45)
o
o
Diabetic Ketoacidosis
Serum Ketones > 25 mmol/L
o pH <7.3
o Glucose >500
o
Kitabchi, 2014
Definition of Obesity
Waist Circumference
Men . . . . .>40”
Women . . .
> 35”
BMI
Men / Women
>24 . . . Overweight
>29 . . . Obese
Body Fat %
>25% in Men
>30% in Women
Body Mass Index

Estimated weight of 240
lbs. and 6’2”
= BMI of 30.8 kg/m2


What?!
The Terminator Obese?!
http://www.health.com/health/gallery/0,,20460621_4,00.html
Cause of Obesity?
Cause of Obesity?
80-85% due to Insulin
Resistance
•
Defect in regulation of
fat metabolism
Defect causes imbalance
of energy distribution
• Insulin plays a primary
role
•
10-15% Due to Sedentary
Lifestyle
5-10% other Metabolic
Deficiencies
Impaired Insulin Secretion
1.
Diet high in sugar &
fat
• Impairs
GLUT-2 transport
• Reduces Insulin
Secretion
2.
High Cholesterol
•
•
Impaired Abca1
transport (not shown)
Lacking Abca1 in βcells shown to cause
insulin resistance
Thorens B, 2006; McGillicuddy F et al., 2009
↑ Carbs
Obesity
Insulin
Resistance
Hyperinsulinemia
Impaired
Glucose
Tolerance
-Cell Defect
(↓ insulin secretion)
Early
Diabetes
 -Cell Failure
Late
Diabetes
Xu H. J Clin Invest. 2003
ADA, 2013
Are You Insulin Resistant?
•
Signs of Insulin Resistance
•
•
•
•
•
•
Fasting Insulin >5
Insulin Resistance Score > 45
Trig/HDL-C > 3.0
Skin Tags
Acanthosis Nigricans
Waist Circumfrence
•
•
>40 inches (men)
>35 inches (women)
Insulin Resistance

Adipocyte Functions:
 Provide
cushion
 Provide Insulation
 Unlimited Ability to Store
Energy
 Regulate Energy Use, Appetite,
Metabolism & Inflammation by
releasing:
 Leptin,
adiponectin, plasminogen
activator inhibitor-1 (PAI-1),
resistin, TNF-alpha, Interleukin-6,
estradiol (E2)
Bays HE, 2011
Insulin Resistance
Neary et al., 2004
Inhibits appetite
Increases appetite
Insulin Resistance
•
Leptin resistance
•
•
•
Associated with
insulin resistance
Increased Leptin
resistance worsens
insulin resistance
Leading to
“Adiposopathy” or
“Sick Fat Cells”
Bays HE, 2011
Havel P, Diabetes, 2004
Physiology of Insulin Resistance
Proteins
Amino Acids
Carbohydrates
Fats
Glycogen
Triglycerides
Glucose Insulin
Pyruvate
Free Fatty Acids (FFA)
Acetyl CoA
Kreb Cycle
(TCA)
&
Electron
Transport
System
CO2, H2O, ATP
Lipoprotein Lipase
is regulated by insulin
Kahn BB. J Clin Invest. 2000
5Inflammation
6Testosterone (men)
5Testosterone (women)
5Estrogen (men)
6Estrogen (women)
5Weight Gain
Insulin
5Blood Pressure
5Uric Acid
5Free Radicals
5Cholesterol
5Triglycerides
The Fat Regulator
Insulin
“Let food be thy
medicine,
thy medicine be
thy food.”
Hippocrates
 20% of
glucose is
metabolized
in liver
 Most is
converted to
Glycogen
 Increased
Insulin and
Leptin
decrease
hunger
Lustig R. J Am Diet Assoc. 2010.
 80% is
metabolized
in liver
 Notable
inactivation of
IRS-1
increasing
insulin
resistance and
insulin
production
 Most of the
ethanol is
converted to
TG leading to
obesity
Lustig R. J Am Diet Assoc. 2010.
 100% of fructose
metabolized by
liver. 20% of
glucose.
 Increases uric
acid leading to
HTN
 Induction of
fructose increases
glucose and
further insulin
resistance/ Leptin
resistance in
some.
 De novo
lipogenesis is
induced
 TG formation,
obesity, increased
Dopamine in NA
Lustig R. J Am Diet Assoc. 2010.
Hormones Effecting Insulin Resistance
Hormone
Location
Cell
Type
Action
Hormone
Location
Cell
Type
Action
CCK
Duodenum
Jejunum
I-Cells
Anorexigenic
PP
Pancreas
F-Cells
Anorexigenic
GIP
Duodenum
Jejunum
K-Cells
Anorexigenic
Pancreas β-Cells
Anorexigenic
PYY
Ileum
Colon
L-Cells
Anorexigenic
Adiponectin
Adipose
Anorexigenic
Enterostatin
Pancreas
GLP-1
Ileum
Colon
L-Cells
Anoxrexigenic
Amylin
Pancreas β-Cells
Anorexigenic
OXM
Ileum
Colon
L-Cells
Anorexigenic
Somatostatin
Pancreas δ-Cells
Anorexigenic
Apo A-IV
Intestine
Glucagon
Pancreas
α-Cells
Ghrelin
Stomach
Pancreas
P/D 1 Cells
ε-Cells
Leptin
White Adipose
Anorexgenic
Orexigenic
Anorexigneic
Insulin
ParaVentricular Nucleus
Neurotensin
Neurotrophic Factor
CRH
TRH
Second Order
Neurons
Y1 R
MC4 R
α-MSH
Hypothalamus MCH
Arcuate Nucleus
POMC
First Order
NPY
CART MC3 R
Neurons
MC3 R
AgRP
Y4 R
GABA
Stimulate Hunger
Decrease Hunger
Lateral
Hypothalamus
MCH
Orexin/Hypocretin
Ghrelin
CCK
GIP
GLP-1
PYY
OXM
Lenard NR, Obesity, 2008
Apo A-IV
Serotonin
Insulin
Somatostatin
Glucagon
Amylin
PP
Leptin
Adiponectin
Adipose Cells
Vagal Afferents
ParaVentricular Nucleus
Neurotensin
Neurotrophic Factor
CRH
TRH
Second Order
Neurons
Y1 R
MC4 R
α-MSH
Hypothalamus MCH
Arcuate Nucleus
POMC
First Order
NPY
CART MC3 R
Neurons
MC3 R
AgRP
Y4 R
GABA
Ghrelin
CCK
GIP
GLP-1
PYY
OXM
Lenard NR, Obesity, 2008
Apo A-IV
Stimulate Hunger
Decrease Hunger
Lateral
Hypothalamus
MCH
Orexin/Hypocretin
Serotonin
Insulin
Somatostatin
Glucagon
Amylin
PP
Leptin
Adiponectin
Adipose Cells
Vagal Afferents
ParaVentricular Nucleus
Neurotensin
Neurotrophic Factor
CRH
TRH
Second Order
Neurons
Y1 R
MC4 R
α-MSH
Hypothalamus MCH
Arcuate Nucleus
POMC
First Order
NPY
CART MC3 R
Neurons
MC3 R
AgRP
Y4 R
GABA
Stimulate Hunger
Decrease Hunger
Lateral
Hypothalamus
MCH
Orexin/Hypocretin
Ghrelin
CCK
GIP
GLP-1
PYY
OXM
Lenard NR, Obesity, 2008
Apo A-IV
Serotonin
Insulin
Somatostatin
Glucagon
Amylin
PP
Leptin
Adiponectin
Adipose Cells
Vagal Afferents
ParaVentricular Nucleus
Neurotensin
Neurotrophic Factor
CRH
TRH
Second Order
Neurons
Y1 R
MC4 R
α-MSH
Hypothalamus MCH
Arcuate Nucleus
POMC
First Order
NPY
CART MC3 R
Neurons
MC3 R
AgRP
Y4 R
GABA
Ghrelin
CCK
GIP
GLP-1
PYY
OXM
Lenard NR, Obesity, 2008
Apo A-IV
Stimulate Hunger
Decrease Hunger
Lateral
Hypothalamus
MCH
Orexin/Hypocretin
Serotonin
Insulin
Somatostatin
Glucagon
Amylin
PP
Leptin
Adiponectin
Adipose Cells
Vagal Afferents
ParaVentricular Nucleus
Neurotensin
Neurotrophic Factor
CRH
TRH
Second Order
Neurons
Y1 R
MC4 R
α-MSH
Hypothalamus MCH
Arcuate Nucleus
POMC
First Order
NPY
CART MC3 R
Neurons
MC3 R
AgRP
Y4 R
GABA
Ghrelin
CCK
GIP
GLP-1
PYY
OXM
Lenard NR, Obesity, 2008
Apo A-IV
Stimulate Hunger
Decrease Hunger
Lateral
Hypothalamus
MCH
Orexin/Hypocretin
Serotonin
Insulin
Somatostatin
Glucagon
Amylin
PP
Leptin
Adiponectin
Adipose Cells
Vagal Afferents
ParaVentricular Nucleus
Neurotensin
Neurotrophic Factor
CRH
TRH
Second Order
Neurons
Y1 R
MC4 R
α-MSH
Hypothalamus MCH
Arcuate Nucleus
POMC
First Order
NPY
CART MC3 R
Neurons
MC3 R
AgRP
Y4 R
GABA
Decrease Hunger
Lateral
Hypothalamus
MCH
Orexin/Hypocretin
Serotonin
Insulin
Somatostatin
Glucagon
Amylin
Ghrelin
CCK
GIP
GLP-1
PYY
OXM
Lenard NR, Obesity, 2008
Stimulate Hunger
Apo A-IV
PP
Leptin
Adiponectin
Adipose Cells
Vagal Afferents
Weight Changes during 2 Years According to Diet Group.
Shai I et al. N Engl J Med 2008;359:229-241.
How Do I Use A Low Carb
Diet?
•Realistic Expectations
• 10-15% body weight
reduction in 3-6
months
•Goal Setting & Accountability
•Dietary Change is the Key
•Exercise
•Medication
•Supplementation
How Do I Use A Low Carb
Diet?
“Everything should be
made as simple as
possible, but no
simpler.”
Albert Einstein
Low Carbohydrate Diet
•Keep
carbohydrate intake very low
• < 20g per day for weight loss
• < 10-20g per meal for cholesterol reduction
• Closely monitored by your physician!
•High fat foods for hunger/appetite suppression
•High Fat sources:
• Meat, fish, poultry & eggs
• Legumes
• Cheese
• Nuts & Seeds
Low Carbohydrate Diet
•High
•
•
•
•
•
•
•
•
•
Fat Foods/Rescue Foods:
Bacon
Eggs
Hard Cheeses (Velveeta is not real cheese!)
Avocado
Grass Fed Red Meats / Pork
Fatty Fish
Butter
Heavy Cream
Almonds/Walnuts
Ketosis Killers
•
Anything that raises insulin levels …
•
•
•
Complex Carbohydrates
Simple Carbohydrates
Sweeteners
•
•
Artificial Sweeteners
•
•
Sugar, High Fructose Corn Syrup, Agave, Honey, etc
Xylitol, Maltitol, Acesulfame Potassium, Dextrose,
Maltodextrin etc.
Excessive Protein Intake
Nally, AS, 2011, “The Skinny About Sweeteners,”
http://www.sensiblemedicalsolutions.com/abi_sweetener.html
45 y/o male on Metformin for diabetes type II and
started on Low Carbohydrate diet.
Date Weight BMI Chol HDL LDL HbA1C
Trig Prot/
Ur
4/10
466
58
155
29
95
5.5
154
7.6
6/10
445
55
184
27
120
5.0
184
19.7
4/11
404
50
203
5.3
145
9.2
71 y/o male on Januvia, Lisinopril & Zocor for diabetes type II
and started on Low Carbohydrate diet.
Date
Weight
BMI
Chol
HDL
LDL
HbA1C
Trig
Prot/
Ur
8/10
267.2
40
161
29
91
6.4%
259
2264
10/10
1/11
240
228.9
36
33
132
146
29
36
79
89
5.2%
5.8%
142
104
1274
1198
11/13
250.0
36.4
163
41
103
6.2%
94
1119
2/14
254.4
37.0
146
31
78
6.8%
184
399
28y/o female started on Low Carbohydrate diet.
Date Weight BMI Chol HDL LDL
Abd
Circ
10/10
170.5
27
38.5
2/11
147
23.7
35.5
5/11
144.4
23
34.5
160
70
77
Trig Prot/
Ur
65
36y/o female started on Low Carbohydrate diet.
Date Weight BMI Chol HDL LDL
3/10
184.4
29.4
9/10
157
25
12/10
147.8
24
1/11
144.9
23
151
56
82
Abd
Circ
39
Trig HbA1C
78
5.6
45
5.6
30.5
140
62
71
31
29.5
39y/o female started on Low Carbohydrate diet.
Date Weight BMI Chol HDL LDL
Abd
Circ
Trig HbA1C
3/10
170
29.2
171
40
94
38
224
7/10
165.5
29
171
40
102
36
175
10/10
144.1
25
33
12/10
139.7
24
33.5
"If it were not for the
great variability
among individuals,
medicine might as
well be a science and
not an art.“
Sir William Ostler, 1892
60y/o female previously on Metformin & Zocor for
Diabetes Type II, started on Low Carbohydrate diet.
Date Weight Fat Chol HDL LDL LDL-P Trig HbA1C
%
5/10
172.6
37.2 210
60
119
9/10
171.2
158
53
70
5/11
171.7
37.3 148
68
66
189
6.4
1369
212
6.1
742
70
6.0
40y/o male with Insulin Resistance and Clotting
Disorder started on Low Carbohydrate diet.
Date Weight BMI Chol HDL LDL
12/10
437.2
5/11
414
Abd
Circ
Trig HbA1C
62.7 172
40
108
38
143
5.9
59.4
41
111
36
94
5.9
171
56 y/o female with hypothyroidism, hypertension &
insulin resistance
Date
Weight
BMI
Chol
HDL
LDL
sd LDL-P
Abd Circ
Trig
HbA1C
4/11
248.
46
195
55
125
665
50.5
75
6.0
6/13
160
29
184
67
109
149
35.5
40
5.3
51 y/o female with dyslipidemia, migraines, insomnia &
insulin resistance started low carb diet before labs
Date
Weight
BMI
Chol
HDL
LDL
sd LDL-P
Abd Circ
Trig
HbA1C
11/11
216
38
253
72
172
147
41
46
5.4
7/13
166
29
212
107
96
103
36
47
5.4
Low Carbohydrate Diet
Diet high in fat has
significant
improved effect on
heart failure.
ajpheart.physiology.org/content/early/2010/05/28/ajpheart.00270.2010
Low Carbohydrate Diet
Multiple studies
reveal patient’s with
insulin resistance
have twice risk for
contracting
Alzheimer’s disease
Studies in large populations: Ott et al. 1999 (Rotterdam: “direct or indirect”)
Low Carbohydrate Diet
Ketones have notable
effect on reduction of free
radicals & slow the aging
process
Veech RL, 2004, "The therapeutic implications of ketone bodies...,”
Prostaglandins Leukot Essent Fatty Acids, 2004 Mar;70(3):309-19. 70
Figure 1. Changes in biomarkers according to diet groups during the maximum weight loss
phase (1 to 6 months) and the weight loss maintenance phase (7 to 24 months) of the 2-year
intervention.
Copyright © American Heart Association
Shai I et al. Circulation 2010;121:1200-1208
Figure 2. A, Examples of
Vessel Wall Volume (VWV)
measurements at baseline
and follow-up.
Shai I et al. Circulation
2010;121:1200-1208
Copyright © American Heart Association
Increased sdLDL particle
number
correlates with
increased CIMT
Fig. 2 Common carotid IMT mean max by LDL diameter values. Error bars indicate
S.E., N=228.
(Italian study of 228 post menopausal women)
Gentile M, Panico S, et al., Clinica Chimica Acta, 2013, Association between small dense LDL and early
atherosclerosis in a sample of menopausal women, Department of Clinical Medicine and Surgery,
University “Federico II” Medical School, Naples, Italy Division of Cardiology, Moscati Hospital, Aversa, Italy
A. Cardarelli Hospital, Naples, Italy
Prevalence of LDL subclass pattern B as a function of dietary carbohydrate content for each
experimental diet before and after weight loss and stabilization with the diets.
©2006 by American Society for Nutrition
Krauss R M et al. Am J Clin Nutr 2006;83:1025-1031
Questions
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The End