Unified Field Theory of Diseases of

Civilization
 Credentials
Private Practice, Family Medicine and Bariatric Medicine in Northeast Kansas
Medical Director, University of Kansas Weight Control Program (VLCD-very low
calorie liquid diet)
Consultant, Duke Diet and Fitness Center
Consultant, Atkins Nutritionals, Inc.
Consultant, Veronica Atkins
Clinical Faculty, University of Kansas Medical School
Diplomate of the American Society of Bariatric Physicians
Past President, American Society of Bariatric Physicians
Fellow, American Society of Bariatric Physician
Co-author, lay press diet book
Co-author, “Dietary Treatment of the Obese Individual” and “Medical Treatment of
Pediatric Obesity” in Handbook of Obesity Treatment.
Partner: Innovative Metabolic Solutions
 Credentials
Behavioral

40 + years training animals including cats, dogs, horses, and one

chicken.
I have participated in the training of 10 nationally ranked agility dogs
including the #2 beagle (2 years) and #1 Norfolk Terrier (8 years)
Currently employed by Joan Meyer (Triune Training) AKC World
Agility Team member 2001, 2003, 2008.

I specialize in behavior problems as well as the biomechanics of the

working animal.
 Metabolic Health
Its not the weight, it’s the fuel source.
 Metabolic Syndrome
• Vernon, M.
• Retrospective chart review
• Outpatient clinical setting
• 124 patients-64 rx’d low CHO
57 rx’d low fat + anorectic
Vernon, M. C., B. Kueser, et al. (2004). "Clinical Experience of a Carbohydrate-Restricted Diet for
the Metabolic Syndrome." Metabolic Syndrome and Related Disorders 2(3): 180-186.
 Methods
Outpatient clinical setting
Low fat diet + phen/fen (n=64)
Carbohydrate restricted diet (n=57)
Diet prescription was written.
20 grams carbohydrate/day until weight loss goal
obtained or patient willing to slow weight loss.
Both groups routinely monitored with office
visits and blood work.
 Parameters Followed
Vital Signs; Blood Pressure, TPR, Weight.
Initially used caliper measurements of Body Fat
(Phen-fen). Low CHO patients followed with bio-
electric impedance body composition scale.
Obtained CBC, fasting lipids, thyroid studies,
chemistry panel, C-peptide and UA.
Now also obtain hs-CRP, 24 hr urine for creatinine
clearance and microalbumin followed on all
diabetic patients. Labs repeated at ~3 mon.
intervals until stable weight –then at least yearly.
  Demographics
LF Diet + Meds Carb Restriction
mean (SD) mean (SD)
n 56 66
Age, years 41.3 (8.7) 47.9 (12.7)
Gender female 80.4% 71.2%
Race Caucasian 94.6% 92.3%
Height, inches 66.2 (3.5) 65.9 (3.7)
Weight, kg 94.0 (21.1) 97.7 (28.8)
Body mass index, kg/m2 38.3 (7.4) 38.7 (11.1)
Family history of obesity 82.1% 65.2%
Hypertension therapy 21.4% 33.3%
Diabetes mellitus therapy 8.9% 22.7%
Lipid therapy 16.2% 27.6%
Psychiatric medical therapy 21.4% 21.2%
Thyroid therapy 19.6% 6.1%
 Results
  Low-Fat Diet + Medication Carbohydrate Restricted Diet
Variable Baseline Follow-up Change Baseline Follow-up Change P value*

Mean
Body weight, kilograms** 108.7 94.9 -12.7% 108.2 98.7 -8.8% 0.005*
 
Total cholesterol, mg/dl 219.9 194.8 -11.4% 213.9 203.1 -5.0% 0.39
Triglycerides, mg/dl 210.5 151.8 -27.9% 203.8 115.5 -43.3% 0.02*
LDL-C, mg/dl 134.9 121.2 -10.2% 123.0 128.0 +4.1% 0.52
HDL-C, mg/dl 40.2 40.8 +1.5% 44.7 48.9 +9.4% 0.003*
Total chol/HDL-C ratio 5.8 5.1 -12.1% 5.3 4.6 -13.2% 0.08
Trigycerides/HDL-C ratio 5.8 4.3 -25.9% 5.7 2.8 -50.9% 0.01*
 

** The mean follow-up was 20.2 wks for the LF Diet + Meds group and 15.0 wks for the Carb
Restriction group
How did these options compare?
• Weight loss almost as much with CHO
restriction as our best medication effort
using phen/fen.
• Lipid profile was markedly improved:
• 51% improvement in Trig/HDL ratio (an
emerging marker of cardiovascular
disease).1
1
Gaziano JM, Hennekens CH, O’Donnell CJ, Breslow JL, and Buring JE “Fasting Triglycerides, high-
density lipoproteins and risk of myocardial infarction.” Circulation 96: 2520-2525 (1996)
 Rate of Loss

250
B o d y W e ig h t, lb s (s e m )

240

230
Very Low Carbohydrate Diet
220

210

200

190
Phen/Fen and Low Calorie Diet

180

170
Wk 0 Wk 4 Wk 8 W k 12 W k 16 W k 20 W k 24
Duration of Intervention

* p = 0.04 comparing change from Week 0 to Week 24 between groups

 News Flash
Not all weight loss is the same in terms of
metabolic state.
Metabolic outcomes are different based on the
fuel source ( fat or carbohydrates)
 What Can You Impact?
• Any condition related to hyperinsulinemia:
• CAD, prediabetes, metabolic syndrome, Type 2 diabetes
mellitus, hypertension, hyperlipidemia, dyslipidemia
including high triglycerides and low HDL, proteinuria due to
metabolic syndrome, obesity, acanthosis nigricans
• Central nervous system irritability such as seizures and
migraines
• Ovarian dysfunction due to hyperinsulinemia manifested as
polycystic ovary syndrome, irregular menses, anovulation,
irregular ovulation, facial hirsuitism
• GERD
• Sleep apnea, Pickwician syndrome
• Gestational diabetes, pre-eclampsia
• Osteoarthritis
• Inflammation
• Some Psychiatric conditions
 Diseases of Civilization
Elevated carbohydrate intake (different
tolerance from one individual to another)
causes chronically high levels of insulin and
other inflammatory mediators.
These are the drivers of the diseases of
civilization-hypertension, metabolic
syndrome, prediabetes, diabetes and excess
fat mass gain.
Mitochondrial Energy Production
This is the key to life.
No mitochondrial energy production=death
No mechanic, no oil changes, only on-site
repair and oxidation must continue at all
times.
That’s a challenge-and nutrition is the key.
 Mitochondrial Fuel Source
Mitochondrial fuel source is linked to
oxidative stress
Oxidative stress is linked to tissue damage
Mitochondrial enzymes adjust to fuel source
Constant mitochondrial energy production
without oxidative damage is the goal.
 Is Adiposity the problem?
Sunburn is the best analogy
Genetic predisposition and environmental
exposure combine to cause damage.
Adiposity is a marker for hyperinsulinemia.
Excess adipose tissue is part of the pathologic
process of insulin resistance and
hyperinsulinemia
 Two Approaches to Understanding
Human Metabolism
Classic
• All calories have equal value,
regardless of source
• Importance of each
macronutrient tied to caloric
density
• Weight gain when energy intake
exceeds energy expenditure
• Lose weight by reducing caloric
intake and/or increasing caloric
expenditure
Hormonal
• Increased carbohydrate intake
increases insulin production and
decreases lypolysis (fat-burning)
• Macronutrients control metabolic
hormone production, which
controls storage metabolism.
• High carbohydrate consumption
leads to hyperinsulinemia, which
leads to obesity and Metabolic
Syndrome
 Hormones
Insulin
Glucagon
Incretins
Epinephrine
Norepinephrine
Cortisol
Sex Steroids
Branched chain amino acids
IL-6
Dietary Carbohydrates
 Visceral Adiposity
Dr. Eric Freedland proposed the concept of the “critical
visceral adipose threshold”-the amount of visceral fat storage that
an individual could gain after which metabolic obesity ensued.

This hypothesis, in conjunction with individual tissue levels of

insulin resistance, may explain why one person is obese to the eye
but has fewer metabolic abnormalities while an apparently thin
individual is metabolically at risk.

Freedland, E. S. (2004). "Role of a critical visceral adipose tissue threshold

(CVATT) in metabolic syndrome: implications for controlling dietary
carbohydrates: a review." Nutr Metab (Lond) 1(1): 12.
 Physiology of Obesity Treatment
Obesity is excessive adipose tissue (fat)

“Excess” is defined by metabolic and functional

parameters

The goal is to mobilize, or “burn fat”

To accomplish this goal, a change from “glucose

burning” to “fat burning” is needed
 Fat Metabolism and Insulin
The hormonal milieu needs to be appropriate for “fat
burning”
The effect of insulin to facilitate glucose uptake is
linked to fat synthesis
“Fat burning” is inhibited by insulin, so insulin levels
need to be around basal levels
Insulin levels can be lowered by:
Increasing energy expenditure
Reducing carbohydrate intake
 Insulin Promotes Fat Synthesis
Glucagon Promotes Fat Burning

citrate Fatty acid

synthase

TCA cycle Malonyl CoA Triglycerides

ACCb CPT I
mitochondria cytosol Intracellular and
intravascular

Glucose abundant-TCA Acetyl CoA carboxylase CPT I (Carnitine

producing citrate via (ACCb ) is activated by palmitoyltransferase I)
acetyl CoA and moves long chain fatty acyl
citrate and insulin, inhibited
oxaloacetate. Insulin CoA groups into the
by glucagon.
increases availability of mitochondria for oxidation.
TCA intermediates via Fatty acid synthase inhibited Inhibited by malonyl CoA.
enzyme regulation by glucagon
 Fuel Sources: Fatty acids, ketones, glucose

Fatty acids can be utilized by most tissues for energy.

Ketone bodies are generated by the liver from fatty acid

oxidation. Ketones can be utilized by all cells except
glucose obligate cells and liver.

Glucose is synthesized by the liver and renal medulla from

amino acid precursors (gluconeogenesis). Cells without
mitochondria (erythrocytes, cornea, lens, retina) and cells
in low oxygen tension conditions (renal medulla) are
obligate glucose users.
 Fatty Acids
Fatty acids are the main cellular fuel for all non-obligate
glucose using cells
Preferred fuel of the myocyte
A large pool of fatty acids are circulating on albumin at
any given time
There is nearly unlimited storage potential as
triglyceride in adipose tissue
 Ketone bodies

Ketone bodies are molecules that deliver energy

(acetoacetate, acetone, -hydroxybutyrate)

Ketone levels
Fed state 0.1 mmol/L
Overnight fast 0.3 mmol/L
Nutritional ketosis 1 - 2 mmol/L
> 20 days fasting 10 mmol/L
Diabetic ketoacidosis > 25 mmol/L

Meckling et al. Can J Physiol Pharmacol 2002;80:1095-1105.

Sharman et al. J Nutr 2002;132:1879-1885.
Yancy et al. Eur J Clin Nutr 2007;February 17:1-7.
 Glucose
Can come from diet, but also from internal sources
Excess is stored as glycogen in limited amounts, or as
triglyceride
Protein (amino acids) used by liver and kidney to produce
glucose (gluconeogenesis) and glycogen (glycogenesis)
Under mixed diet conditions, CNS use of glucose can be as high
as 120 grams/day
However, daily glucose use is only about 30 grams/day when
adapted to fat burning state (when fatty acids and ketones are
available for muscle and CNS use)
This 30 grams of glucose is easily supplied by endogenous
sources
 Caloric Content of Food
A Calorie (kcal) is the amount of heat required to raise the temperature of 1 kg
of water by 1 degree Celsius

Foods can be oxidized to release energy, and the estimated caloric values
using bomb calorimetry are:

Triglyceride: 9.461 kcal per gm…… 9 kcal

Protein: 4.442 kcal per gm………… 4 kcal
Carbohydrate: 4.183 kcal per gm... 4 kcal
Alcohol: 7 kcal per gram……………7 kcal
Ketones: 4.5 cal per gram………….4 kcal

The actual caloric value will depend upon what oxidation pathway is used,
whether the energy has been stored, etc.

Glycogen is stored with water 1:3, so 1 gram of glycogen leads to 4 gram of

weight gain
 Oh, Those Free Radicals
• The effect of burning glucose as fast as
possible overwhelms the mitochondrial
electron transport chain and generates
increased numbers of free radicals.
• Free radicals cause tissue damage.
• Control glucose/insulin metabolism=control
free radical formation=control tissue
destruction.
Salway JG, Metabolism at a Glance. Third edition. Blackwell Publishing Ltd, 2004.
Veech, R. L., B. Chance, et al. (2001). "Ketone bodies, potential therapeutic uses."
IUBMB Life 51(4): 241-7.
 Free Radical Management Plan
“Finally there are broad therapeutic implications from
the ability of ketone body metabolism to oxidize the
mitochondrial co-enzyme Q couple. The major source
of mitochondrial free radical generation is Q
semiquinone. The semiquinone of Q, the half-reduced
form, spontaneously reacts with O2 to form free
radicals. Oxidation of the Q couple reduces the
amount of the semiquinone form and thus would be
expected to decrease O2- production.” 1

Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological
conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism.
Prostaglandins Leukotrienes Essential Fatty Acids 2004;70:309-19.
 Mitochondrial Ketone Metabolism
Vacuums Free Radicals
In addition, the metabolism of ketones causes a reduction of the
cytosolic free {NAD+}/{NADH} couple which is in near
equilibrium with the glutathione couple. Reduced glutathione
is the final reductant responsible for the destruction of H2O2.

Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies
in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance,
and mitochondrial metabolism. Prostaglandins Leukotrienes Essential Fatty Acids
2004;70:309-19.
 Ketones Improve Myocardial
Function
“How ketone bodies could improve the hydraulic
efficiency of heart by 28% could not be explained by
the changes in the glycolytic pathway alone, but
rather by the changes that were induced in
mitochondrial ATP production by ketone body
metabolism.”

Veech RL. The therapeutic implications of ketone bodies: the effects of

ketone bodies in pathological conditions: ketosis, ketogenic diet, redox
states, insulin resistance, and mitochondrial metabolism. Prostaglandins
Leukotrienes Essential Fatty Acids 2004;70:309-19.
 Ketotic Benefits
Chronic adaptation to fat as primary energy
source may offer benefits such as improved
cerebral function (treatment of seizures),
improved mitochondrial ATP production,
decreased oxidative stress and protection of
glycogen stores during exercise.
Kossoff, E. H. (2004). "More fat and fewer seizures: dietary therapies for epilepsy."
Lancet Neurol 3(7): 415-20.
Phinney, S. D., B. R. Bistrian, et al. (1983). "The human metabolic response to chronic
ketosis without caloric restriction: preservation of submaximal exercise capability with
reduced carbohydrate oxidation." Metabolism 32(8): 769-76.
 Dietary CHO =Insulin Secretagogue

Boden, G., K. Sargrad, et al. (2005). "Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin
resistance in obese patients with type 2 diabetes." Ann Intern Med 142(6): 403-11.
 Carbohydrate Signal Effects on
Metabolic Hormones

Ludwig, D. S., J. A. Majzoub, et al. (1999). "High glycemic index foods, overeating, and obesity." Pediatrics 103(3): E26.
 Eat or Die

Ludwig, D. S., J. A. Majzoub, et al. (1999). "High glycemic index foods, overeating, and obesity." Pediatrics 103(3): E26.
Lack of Postprandial Rise in Serum Glucose
and Insulin After a Low Carbohydrate Meal

Glucose and insulin concentrations in response to a 300 kcal meal with low-
(closed circles), intermediate- (open circles), and high-carbohydrate
(triangles) content after 10 d on these respective diets (n=6).
Data are means (SE). Areas under the curve for insulin was different for each
diet (P 0.001). Glucose area under the curve was lower in response to the
low-carbohydrate diet (P 0.001 vs. other diets).
Bisschop et al. J Clin Endocrinol Metab;2003:88:3801–3805.
 Eating Fat Equals Fasting
The importance of either carbohydrate or energy restriction in initiating the
metabolic response to fasting was studied in five normal volunteers. The
subjects participated in two study protocols in a randomized crossover fashion.
In one study the subjects fasted for 84 h (control study), and in the other a
lipid emulsion was infused daily to meet resting energy requirements during
the 84-h oral fast (lipid study). Glycerol and palmitic acid rates of appearance
in plasma were determined by infusing [2H5]glycerol and [1-13C]palmitic
acid, respectively, after 12 and 84 h of oral fasting. Changes in plasma
glucose, free fatty acids, ketone bodies, insulin, and epinephrine
concentrations during fasting were the same in both the control and lipid
studies. Glycerol and palmitic acid rates of appearance increased by 1.63 +/-
0.42 and 1.41 +/- 0.46 mumol.kg-1.min-1, respectively, during fasting in the
control study and by 1.35 +/- 0.41 and 1.43 +/- 0.44 mumol.kg-1.min-1,
respectively, in the lipid study. These results demonstrate that restriction of
dietary carbohydrate, not the general absence of energy intake itself, is
responsible for initiating the metabolic response to short-term fasting.

Klein, S. and R. R. Wolfe (1992). "Carbohydrate restriction regulates the adaptive

response to fasting." Am J Physiol 262(5 Pt 1): E631-6.
 The New Paradigm
Food can exert hormonal type influence on
metabolic pathways
Fat is not the problem
The changes caused by excess dietary
carbohydrate intake result in a shift in
metabolic pathways (characterized by
elevated insulin levels) which increase
inflammation and tissue damage.
 Hyperinsulinemia and Reactive
Hypoglycemia
Time Glucose Insulin
50 yo red headed female
(mg/dl) (uIU) Weight=191.3 lbs
Hgt=63 inches
fasting 115 19
BMI=33.9

1 hr 261 72

2 hr 212 119

3 hr 41 34
 DM with elevated Insulin
54 yo wf . 269 lb. 5’6” tall. BMI=43.4
Multiple complaints: gluten enteropathy,
vegetarian, joint aches
Meds: Synthroid 62.5 mcg/day, Accupril 40
mg po daily, HCTZ 25 mg po daily
Referred by Dr. Phinney, Dr. Westman, and
Dr. Kolotkin
 Type 2 DM with elevated insulin levels

Time Glucose Insulin

54 yo Caucasian female
(mg/dl) (uIU) Weight=269 lbs
Hgt=66 inches
fasting 123 81
BMI=43.4
Stage 5 (DM) with
reactive hypoglycemia
1 hr 273 632
and hyperinsulinemia.

2 hr 200 777

3 hr 119 259
 Type 2 DM with Elevated Insulin levels
Treatment Outcomes
Test Wgt Gluc % change
(lbs)
Weight (lbs) 269 245 -9
Glucose (mg/dl) 123 99 -20
HgbA1C (%) 6.0 (<5.7) 5.1 -15
Cpeptide 8.9 (<4.5) 4.3 -52
T. Chol (mg/dl) 157(<200) 146 -7
Triglyceride(mg/dl) 222 (<150) 72 -68
HDL (mg/dl) 36 (>50) 37 +2
LDL (mg/dl) 76.6 (<100) 95 +24
T.chol/HDL 4.36 3.95 -9
Trig/HDL 6.16 1.9 -69
 Type 2 DM 3 hr GTT with Insulin
Levels
Time Glucose Insulin
56 yo Caucasian female
(mg/dl) (uIU) Weight=276 lbs
Hgt= 62 inches
fasting 131 14.9
BMI= 50.1
Stage 5 moving to Stage 6
Insulin levels don’t adequately
1 hr 278 50.9
suppress serum glucose response
to dietary carbohydrate. Insulin
2 hr 246 40.3 resistance present.
Reactive hypoglycemia present

3 hr 158 27
 Type 2 DM with Low Insulin levels
Treatment Outcomes
Test Baseline 3 months % change

Weight (lbs) 276 226 -18

Glucose (mg/dl) 109 90 -17
HgbA1C (%) 7.1 (<5.7) 5.4 -24
T. Chol (mg/dl) 249 (<200) 226 -9
Triglyceride(mg/dl) 125 (<150) 99 -21
HDL (mg/dl) 64 (>50) 54 -15
LDL (mg/dl) 160 (<100) 152 +5
T.chol/HDL 3.89 4.1 +5
Trig/HDL 1.95 1.83 -6
 Remission of Type II Diabetes
A 45 year old white female with Type II diabetes mellitus, obesity (BMI =
60.5), HTN on pioglitizone, glipizide, and metformin, lisinopril, sertraline, oral
contraceptives, itraconazole, rofecoxib.

Date Wt (lbs) Chol TrigLDL HDL HgbA1C Trig/HDL BMI

7/00 375 257 252 118 50 11.0 5 60.5
7/00 Initiation of Carbohydrate Restricted Diet
9/00 350 153 193 69 45 7.7 3
1/01 317 165 153 84 50 6.4 1.8
12/01 243 198 131 116 56 5.4 2 39.2
All hypoglycemic meds dc’d 7/00. Off all meds except setraline by 9/01
 Not Just For Weight
 Individuals with normal BMI may exhibit
the metabolic characteristics of obesity.
 This is not treatment of adiposity- it is
metabolic management of metabolic risk
through dietary treatment/lifestyle change.
 This works whether or not excess fat mass
is present.
 Metabolic Fitness
Improvement in Metabolic Fitness Without Weight
Change
A 48 year old WF requested dietary treatment for abnormal lipids.
Date Chol Trig HDL T/HDL Weight (lbs) % B F HgbA1c
9/99 256 2208 20 110 158
3/01 214 2407 ---- 158 36 5.8
3/01 Initiation of Carbohydrate Restricted Diet
11/01 162 147 31 4.7 157 29 6.0
7/02 145 127 37 3.4 153.5 31 ---
8/03 149 84 39 3.8 147 27.5 5.1
 What about other lipid problems?
Decrease in Lp(a) Without Weight Loss
A 28 year old white female with strong FH of premature CAD. Acne
rosacea and hypertrophic skin over elbows. (BMI=17.5)
Date Lp(a) Chol Trig LDL HDL Wt (lbs)
3/97 215 87 171 27 98
3/00 64 214 113 154 37 109
2/01 52 243 95 197 27 112
7/01 Initiation of Carbohydrate Restricted Diet 104
11/01 44 211 66 153 45 101
2/02 36 176 52 113 52 110
(normal Lp(a) < 32)
 Current Testing Misses the Problem
 Insulin resistance, hyperglycemia, hyperinsulinemia, hyperlipidemia
and oxidative stress are risk factors related to cardiovascular diseases
including congestive heart failure, myocardial infarction, ventricular
hypertrophy, endothelial nitric oxide impairment in systemic blood
vessels and the heart, atherosclerosis, and hypercoagulability of blood.
The traditional focus on insulin sensitivity and blood levels of markers
of risk determined in the fasted state is inconsistent with the large
volume of recent data that indicates that the metabolic defect in the
pre-diabetic and diabetic condition relates more strongly to
postprandial deficiency than to the fasting state. Risk factors for
adverse cardiovascular events can be detected in the pre-diabetic
insulin-resistant subject based upon the metabolic response to a test
meal even in the absence of altered fasting parameters.

Haffner, S. M., M. P. Stern, et al. (1990). "Cardiovascular risk factors in confirmed

prediabetic individuals. Does the clock for coronary heart disease start ticking before the
onset of clinical diabetes?" Jama 263(21): 2893-8.
 Patients who fall outside of the
existing paradigm

• Metabolically obese normal weight

patients share the CV risk factors of their
obese neighbors, without the external
marker of obesity to alert their physicians
that preventative treatment is needed.
 Looking for the Wrong Factors?

12% of patients with MI did not have

traditional risk factors.

Body, R., G. McDowell, et al. (2008). "Do risk factors for chronic coronary heart disease
help diagnose acute myocardial infarction in the Emergency Department?" Resuscitation
79(1): 41-5.
Risk is related to metabolic state
When subjects with impaired glucose tolerance at baseline (n
= 106) were eliminated, the more atherogenic pattern of
cardiovascular risk factors was still evident (and
statistically significant) among initially normoglycemic
prediabetic subjects. These results indicate that
prediabetic subjects have an atherogenic pattern of risk
factors (possibly caused by obesity, hyperglycemia, and
especially hyperinsulinemia), which may be present for
many years and may contribute to the risk of
macrovascular disease as much as the duration of
clinical diabetes itself.
Lautt, W. W. (2007). "Postprandial insulin resistance as an early predictor of
cardiovascular risk." Ther Clin Risk Manag 3(5): 761-70.
 Acetyl CoA
TCA Cycle
Ketone Bodies

Insulin &
HMGCoA
Reductase

Direction of
Cholesterol Synthesis
www.expasy.ch/cgi.bi
n/search-biochem-
index

Roche Biomedical
Pathways
 Hyperinsulinemia in MONW
Time Glucose Insulin
46 year old Caucasian female
(mg/dl) (uIU) Weight=118 lbs
BMI=18
fasting 94 2.2
Her orthopedist told her she needed
testing for diabetes.
1 hr 93 76
Her father has Type 2 DM.

2 hr 86 89 Hyperinsulinemia
Reactive hypoglycemia
3 hr 31 15
 MONW # 2
Date Gluc Chol TrigLDL HDL Wt (lbs) urine alb
1/96 74 177 120 101 52 107
4/00 72 191 44 110 72 113
2/02 87 2hr glucose tolerance 140.
37 week gestation 7# 14 oz infant male
3/03 70 171 92 92 60 104
10/05 110.4 35.2 mg
2/06 77 177 54 86 80 103 23 mg
8/06 69 162 65 71 78 97 Pat A
5/07 82 194 74 97 82 101
11/08 74 159 61 73 74 109 10 mg
 MONW

 44 yo Caucasian male-construction type

work
 Presented with Ca oxalate kidney stones.
 194#
 5’11”
 BMI 27.1
 13% BF
 Low Carbohydrate Diet Program and
Diabetes Mellitus
Before Diet After Low Carbohydrate
Pgm
Age Sex Duration Weight A1C Trig HDL Weight A1C Trig HDL
(lb) (lb)
56 M 2 mos 182 12 336 43 186 6.8 169 37

57 F 3 mos 135 16.8 179 46 153 5.3 47 62

35 F 3 mos 188 11.3 503 27 175 6.3 145 41

44 M 4 mos 301 8.7 297 33 260 4.8 112 40

69 F 5 mos 247 8.1 186 61 233 5.4 146 63

33 M 15 mos 289 10.9 342 46 279 4.8 183 54

50 M 26 mos 275 9.0 6500 - 215 5.3 329 37
36 F 18 mos 264 9.2 150 48 202 5.5 122 53
 Effect of Carbohydrate Restriction on Weight, Glycemic
Control and Fasting Lipid Profiles in Type 2 Diabetes
Mellitus (n=13)
 

Variable Baseline Follow-up Change P value*

Mean
Body weight, kilograms 123.2 110.8 -9.7% 0.003
Hemoglobin A1C, % 10.0 5.9 -41.0% <0.001
Total cholesterol, mg/dl 224.8 198.8 -14.3% 0.03
Triglycerides, mg/dl 327.5 165.4 -50.3% 0.003
LDL-C, mg/dl 131.1 125.0 -4.7% 0.94
HDL-C, mg/dl 44.5 48.2 +8.3% 0.07
Total chol/HDL-C ratio 5.3 4.2 -21.2% 0.01
Trigycerides/HDL-C ratio 8.3 3.8 -55.0% 0.004
 
*Signed rank test comparing baseline to follow-up value. P<0.05 was used for
statistical significance.

Vernon MC et al. Metabolic Syndrome and Related Disorders 2003;1:233-237.

 Low Carbohydrate Diet Program in Type 2
Diabetes Mellitus: Microalbuminuria

Before Diet After Low Carbohydrate Pgm

Age Sex Duration Weight A1C Trig UAlb Weight A1C Trig UAlb
(lb) (lb)

50 M 26 mos 273 7.0 6500 736 215 5.3 329 151

59 M 53 mos 182 12.0 336 300 181.8 6.1 386 12.5

49 F 12 mos 203 12.5 242 483 196 7.5 165 262

58 F 8 mos 252 6.4 121 50 197.6 5.5 68 13

49 M 12 mon 283 6.0 295 45.5 228.6 5.1 80 13

 Renal Failure
Carbohydrate restricted, low available iron, polyphenol
enriched diet (CR-LIPE)
191 Type 2 DM patients
Randomized to CR-LIPE or standard protein restriction
Mean follow up interval 3.9 years (+/- 1.8 years)
Serum creatinine doubled in CR-LIPE (19 pts/21%) and in 31
controls (31%).
Renal replacement or death=18 pts on CR-LIPE (20%) and
31 controls (39%)

Facchini, F. S. and K. L. Saylor (2003). "A low-iron-available, polyphenol-enriched,

carbohydrate-restricted diet to slow progression of diabetic nephropathy." Diabetes
52(5): 1204-9.
 Renal Failure

“ In conclusion, CR-LIPE was 40-50% more

effective than standard protein restriction in
improving renal and overall survival rates.”

Facchini, F. S. and K. L. Saylor (2003). "A low-iron-available, polyphenol-enriched,

carbohydrate-restricted diet to slow progression of diabetic nephropathy." Diabetes 52(5):
1204-9.
 Remove The Emotional “Hit”
We have told patients with Metabolic Syndrome to
eat a diet that increased their tendency to store and
which triggered rebound and stress hormones.
We have accused them of non-compliance when the
outcome was due to our recommedation.
Societal message is that to need to eat is to be weak.
We have contributed to “learned helplessness”.
 JUST STOP
No guilt for provider.
No guilt for patient.
Honor your body-eat to prevent hunger and
stress chemistry.
Exercise to enhance metabolic and body
chemistry function.
Empower control.
 Long Term Data
Medical monitoring was provided to taper diabetic
and anti-hypertensive medication
Inclusion criteria: baseline and greater than 12
months weight and laboratory studies
106 patients identified
Mean duration of treatment and follow up was 765
days (365 days to 3777 days )
For the 17 Type 2 diabetics with initial HgbA1C
greater than 6.5 mg%, the mean HgbA1c
improved from 9.2% to 5.8% (p=0.001)

Long-term Effects of Carbohydrate-restriction on Obesity in Clinical Practice

Mary Vernon, Eric Westman The Obesity Society 10/2008.
 Long Term Data
365-3777 days of follow up in outpatient clinical practice
TABLE 2
Effect of Carbohydrate Restriction on Metabolic Parameters
Variable Baseline Follow-up Change P value*
n=106 mean mean
Body mass index, kg/m2 38.2 32.4 -13.9% <0.0001
Body weight, kg 105.8 89.9 -14.0% 0.003
Hemoglobin A1c, pct (n=75) 6.4 5.5 -7.9% 0.0002
Hemoglobin A1c, pct (n=17) 9.2 5.8 -38.0% 0.0002
Total cholesterol, mg/dL 204.4 200.6 0% 0.03
Triglycerides, mg/dL 196.5 101.5 -37.6% <0.001
LDL-C, mg/dL 131.1 125.0 +6.0% 0.64
HDL-C, mg/dL 46.8 58.8 +31.9% <0.001
Total chol/HDL-C ratio 5.3 4.2 -11.8% <0.001
Trigycerides/HDL-C ratio 5.6 2.0 -49.7% <0.001
Systolic blood pressure, mmHg** 130.9 121.7 -4.7% 0.0007
Diastolic blood pressure, mmHg 78.2 74.3 -2.5% 0.008
*p<0.05 was used for statistical significance
**n=94 for systolic blood pressure and diastolic blood pressure
 Remove The Emotional “Hit”
We have told patients with Metabolic Syndrome to
eat a diet that increased their tendency to store and
which triggered rebound and stress hormones.
We have accused them of non-compliance when the
outcome was due to our recommedation.
Societal message is that to need to eat is to be weak.
We have contributed to “learned helplessness”.
 JUST STOP
No guilt for provider.
No guilt for patient.
Honor your body-eat to prevent hunger and
stress chemistry.
Exercise to enhance metabolic and body
chemistry function.
Empower control.
 More Information?
info@myimsonline.com

Amber Wiley
VP Public Relations
amber@myimsonline.com
1-888-880-1858 ext:503