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
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Disclosures None
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Change starts when someone sees the next step. Colonel William
Drayton
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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? Agricultural
Adjustment Act of 1933 Food, Conservation & Energy Act 2002,
2012 Agricultural Act of 2014 Kasperowicz P, Wasson E,
www.thehill.com,Sept 20,2013 www.USDA.gov, Agricultural Act of
2014, May 17, 2014
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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) Farm Bill Making Us Fatter
http://www.cnpp.usda.gov/dietaryguidelines.htm Am J Public Health.
2005 September; 95(9): 16021606
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Three Massive Studies The Womens 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 (wasnt
working) Intense Calorie restriction 1200-1800 cal /day Did loose
weight (~6% of body weight lost) Didnt live longer Didnt reduce CAD
(N Engl J Med 2013; 369:145-154)
o Primary Fuel of Ketogenic Diet o Acetoacetic acid - initial
ketone o reduced to beta-hydroxybutyric acid o nonenzymatically
decarboxylated to acetone o Serum Ketones o 0.4 4 mmol/L o Glucose
25 mmol/L o pH 500 Kitabchi, 2014
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Waist Circumference Men.....>40 Women...> 35 BMI Men /
Women >24... Overweight >29... Obese Body Fat % >25% in
Men >30% in Women
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Estimated weight of 240 lbs. and 62 = BMI of 30.8 kg/m2 What?!
The Terminator Obese?!
http://www.health.com/health/gallery/0,,20460621_4,00.html
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80-85% due to Insulin Resistance Defect in regulation of fat
metabolism Defect in regulation of fat metabolism Defect causes
imbalance of energy distribution Defect causes imbalance of energy
distribution Insulin plays a primary role Insulin plays a primary
role 10-15% Due to Sedentary Lifestyle 5-10% other Metabolic
Deficiencies
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1. Diet high in sugar & fat Impairs GLUT-2 transport
Impairs GLUT-2 transport Reduces Insulin Secretion Reduces Insulin
Secretion 2. High Cholesterol Impaired Abca1 transport (not shown)
Impaired Abca1 transport (not shown) Lacking Abca1 in - cells shown
to cause insulin resistance Lacking Abca1 in - cells shown to cause
insulin resistance Impaired Insulin Secretion Thorens B, 2006;
McGillicuddy F et al., 2009
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Impaired Glucose Tolerance Insulin Resistance Late Diabetes
Hyperinsulinemia -Cell Defect ( insulin secretion) Early Diabetes
-Cell Failure Obesity Carbs Xu H. J Clin Invest. 2003 ADA,
2013
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
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Insulin Resistance Neary et al., 2004 Inhibits appetite
Increases appetite
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Leptin resistance Leptin resistance Associated with insulin
resistance Associated with insulin resistance Increased Leptin
resistance worsens insulin resistance Increased Leptin resistance
worsens insulin resistance Leading to Adiposopathy or Sick Fat
Cells Leading to Adiposopathy or Sick Fat Cells Bays HE, 2011 Havel
P, Diabetes, 2004 Insulin Resistance
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ProteinsCarbohydratesFats Amino Acids Glycogen Triglycerides
Glucose Pyruvate Acetyl CoA Kreb Cycle (TCA) & Electron
Transport System Free Fatty Acids (FFA) CO2, H2O, CO2, H2O, ATP
Physiology of Insulin Resistance Insulin
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Kahn BB. J Clin Invest. 2000 Lipoprotein Lipase is regulated by
insulin
Let food be thy medicine, thy medicine be thy food.
Hippocrates
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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.
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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.
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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.
NPYAgRPGABA GLP-1PYYOXM Ghrelin Insulin Leptin ParaVentricular
Nucleus Y1 R LateralHypothalamus Hypothalamus MCHOrexin/Hypocretin
Serotonin Stimulate Hunger Decrease Hunger Arcuate Nucleus Second
Order Neurons First Order Neurons POMCCART Adipose Cells -MSH
Neurotensin Neurotrophic Factor CRHTRH Y4 R PP Adiponectin MCH MC4
R MC3 R Amylin CCK Vagal Afferents Somatostatin Glucagon MC3 R GIP
Apo A-IV Lenard NR, Obesity, 2008
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NPYAgRPGABA GLP-1PYYOXM Ghrelin Insulin Leptin ParaVentricular
Nucleus Y1 R LateralHypothalamus Hypothalamus MCHOrexin/Hypocretin
Serotonin Stimulate Hunger Decrease Hunger Arcuate Nucleus Second
Order Neurons First Order Neurons POMCCART Adipose Cells -MSH
Neurotensin Neurotrophic Factor CRHTRH Y4 R PP Adiponectin MCH MC4
R MC3 R Amylin CCK Vagal Afferents Somatostatin Glucagon MC3 R GIP
Apo A-IV Lenard NR, Obesity, 2008
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NPYAgRPGABA GLP-1PYYOXM Ghrelin Insulin Leptin ParaVentricular
Nucleus Y1 R LateralHypothalamus Hypothalamus MCHOrexin/Hypocretin
Serotonin Stimulate Hunger Decrease Hunger Arcuate Nucleus Second
Order Neurons First Order Neurons POMCCART Adipose Cells -MSH
Neurotensin Neurotrophic Factor CRHTRH Y4 R PP Adiponectin MCH MC4
R MC3 R Amylin CCK Vagal Afferents Somatostatin Glucagon MC3 R GIP
Apo A-IV Lenard NR, Obesity, 2008
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NPYAgRPGABA GLP-1PYYOXM Ghrelin Insulin Leptin ParaVentricular
Nucleus Y1 R LateralHypothalamus Hypothalamus MCHOrexin/Hypocretin
Serotonin Stimulate Hunger Decrease Hunger Arcuate Nucleus Second
Order Neurons First Order Neurons POMCCART Adipose Cells -MSH
Neurotensin Neurotrophic Factor CRHTRH Y4 R PP Adiponectin MCH MC4
R MC3 R Amylin CCK Vagal Afferents Somatostatin Glucagon MC3 R GIP
Apo A-IV Lenard NR, Obesity, 2008
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NPYAgRPGABA GLP-1PYYOXM Ghrelin Insulin Leptin ParaVentricular
Nucleus Y1 R LateralHypothalamus Hypothalamus MCHOrexin/Hypocretin
Serotonin Stimulate Hunger Decrease Hunger Arcuate Nucleus Second
Order Neurons First Order Neurons POMCCART Adipose Cells -MSH
Neurotensin Neurotrophic Factor CRHTRH Y4 R PP Adiponectin MCH MC4
R MC3 R Amylin CCK Vagal Afferents Somatostatin Glucagon MC3 R GIP
Apo A-IV Lenard NR, Obesity, 2008
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NPYAgRPGABA GLP-1PYYOXM Ghrelin Insulin Leptin ParaVentricular
Nucleus Y1 R LateralHypothalamus Hypothalamus MCHOrexin/Hypocretin
Serotonin Stimulate Hunger Decrease Hunger Arcuate Nucleus Second
Order Neurons First Order Neurons POMCCART Adipose Cells -MSH
Neurotensin Neurotrophic Factor CRHTRH Y4 R PP Adiponectin MCH MC4
R MC3 R Amylin CCK Vagal Afferents Somatostatin Glucagon MC3 R GIP
Apo A-IV Lenard NR, Obesity, 2008
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Weight Changes during 2 Years According to Diet Group. Shai I
et al. N Engl J Med 2008;359:229-241.
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Realistic Expectations 10-15% body weight reduction in 3-6
months Goal Setting & Accountability Dietary Change is the Key
Exercise Medication Supplementation
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Everything should be made as simple as possible, but no
simpler. Albert Einstein
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Keep carbohydrate intake very low Keep carbohydrate intake very
low < 20g per day for weight loss < 20g per day for weight
loss < 10-20g per meal for cholesterol reduction < 10-20g per
meal for cholesterol reduction Closely monitored by your physician!
Closely monitored by your physician! High fat foods for
hunger/appetite suppression High fat foods for hunger/appetite
suppression High Fat sources: High Fat sources: Meat, fish, poultry
& eggs Meat, fish, poultry & eggs Legumes Legumes Cheese
Cheese Nuts & Seeds Nuts & Seeds
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High Fat Foods/Rescue Foods: High Fat Foods/Rescue Foods: Bacon
Bacon Eggs Eggs Hard Cheeses (Velveeta is not real cheese!) Hard
Cheeses (Velveeta is not real cheese!) Avocado Avocado Grass Fed
Red Meats / Pork Grass Fed Red Meats / Pork Fatty Fish Fatty Fish
Butter Butter Heavy Cream Heavy Cream Almonds/Walnuts
Almonds/Walnuts
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Ketosis Killers Anything that raises insulin levels Complex
Carbohydrates Simple Carbohydrates Sweeteners Sugar, High Fructose
Corn Syrup, Agave, Honey, etc Artificial Sweeteners Xylitol,
Maltitol, Acesulfame Potassium, Dextrose, Maltodextrin etc.
Excessive Protein Intake Nally, AS, 2011, The Skinny About
Sweeteners,
http://www.sensiblemedicalsolutions.com/abi_sweetener.html
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DateWeightBMICholHDLLDLHbA1CTrig Prot/ Ur
4/104665815529955.51547.6 6/1044555184271205.018419.7 4/1140450203
5.31459.2 45 y/o male on Metformin for diabetes type II and started
on Low Carbohydrate diet.
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DateWeightBMICholHDLLDLHbA1CTrig Prot/ Ur
8/10267.24016129916.4%2592264 10/102403613229795.2%1421274
1/11228.93314636895.8%1041198 11/13250.036.4163411036.2%941119
2/14254.437.014631786.8%184399 71 y/o male on Januvia, Lisinopril
& Zocor for diabetes type II and started on Low Carbohydrate
diet.
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DateWeightBMICholHDLLDL Abd Circ Trig Prot/ Ur
10/10170.527160707738.565 2/1114723.7 35.5 5/11144.423 34.5 28y/o
female started on Low Carbohydrate diet.
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DateWeightBMICholHDLLDL Abd Circ TrigHbA1C
3/10184.429.4151568239785.6 9/1015725 30.5 12/10147.824140627131 45
455.6 1/11144.92329.5 36y/o female started on Low Carbohydrate
diet.
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DateWeightBMICholHDLLDL Abd Circ TrigHbA1C
3/1017029.2171409438224 7/10165.5291714010236175 10/10144.125 33
12/10139.72433.5 39y/o female started on Low Carbohydrate
diet.
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"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
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DateWeight Fat % CholHDLLDLLDL-PTrigHbA1C
5/10172.637.2210601191896.4 9/10171.2158537013692126.1
5/11171.737.31486866 742 74270 6.0 6.0 60y/o female previously on
Metformin & Zocor for Diabetes Type II, started on Low
Carbohydrate diet.
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DateWeightBMICholHDLLDL Abd Circ TrigHbA1C
12/10437.262.717240108381435.9 5/1141459.4171411113694 5.9 5.9
40y/o male with Insulin Resistance and Clotting Disorder started on
Low Carbohydrate diet.
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DateWeightBMICholHDLLDL sd LDL-P Abd Circ TrigHbA1C
4/11248.461955512566550.5756.0 6/13160291846710914935.540 5.3 5.3
56 y/o female with hypothyroidism, hypertension & insulin
resistance
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DateWeightBMICholHDLLDL sd LDL-P Abd Circ TrigHbA1C
11/11216382537217214741465.4 7/1316629212107961033647 5.4 5.4 51
y/o female with dyslipidemia, migraines, insomnia & insulin
resistance started low carb diet before labs
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Diet high in fat has significant improved effect on heart
failure.
ajpheart.physiology.org/content/early/2010/05/28/ajpheart.00270.2010
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Multiple studies reveal patients with insulin resistance have
twice risk for contracting Alzheimers disease Studies in large
populations: Ott et al. 1999 (Rotterdam: direct or indirect)
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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 70 Prostaglandins Leukot Essent Fatty Acids, 2004
Mar;70(3):309-19. 70
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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. Shai
I et al. Circulation 2010;121:1200-1208 Copyright American Heart
Association
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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
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Fig. 2 Common carotid IMT mean max by LDL diameter values.
Error bars indicate S.E., N=228. 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 Increased sd-
LDL particle number correlates with increased CIMT (Italian study
of 228 post menopausal women)
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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. Krauss R M et al. Am
J Clin Nutr 2006;83:1025-1031 2006 by American Society for
Nutrition
