METABOLIC SYNDROME

Nature, Nurture, Nutrition

Genomics, Proteomics,
Metabolomics
 Janice Werbinski, M.D., FACOG

Gynecologist -Borgess Women’s Health

Former Medical Director -BMH Women’s Center
Associate Clinical Professor - MSU / CHM
Author, Curriculum, Women’s Health Track,
Internal Medicine Residency, MSU/KCMS
Founding President, ACWHP
Consultant/Metabolic Syndrome Program –
Borgess Integrative Medicine
 CLASSIC DEFINITION
Syndrome X (Dr. G. Reaven)

High Blood Pressure (>130/85)

High Blood Fats (Triglyceride) (>150)
Low HDL (Good) Cholesterol (<50 mg/dl)
Borderline Diabetes (FBS>110 mg/dl)
Increased Waist to Hip Ratio (>35” waist)
Central Obesity-Inability to Lose Weight
Family History of DM, HTN, CVD,Obesity
 FUNCTIONAL MEDICINE
DEFINITION
Metabolic Syndrome
“An age-related functional disorder of
glucose metabolism, mediated by
altered genetic expression at the cell
membrane level, and manifested under
particular environmental conditions.”

-Dan Lukaczer, ND
Institute for Functional Medicine
 Alternative Labels

Syndrome “X”
Metabolic Syndrome
Insulin Resistance
Pre-Diabetes
Glucose Intolerance
 INCIDENCE
Up to 25% of Americans (47,000,000 in US)
50% May not be Obese
Increasing in Children and Adolescents
Increasing in Industrialized Nations
Very Close Association with:
-Diabetes
-Cardiovascular Disease
-PCOS
-Preeclampsia / Eclampsia
 LABORATORY
PARAMETERS

Fasting Glucose & Insulin

2 hour Glucose & Insulin after 75gm glucola
Lipid panel
Homocysteine
Thyroid panel
CRP
Euglycemic Clamp Studies (Research)
 CAUSES
1. GENETIC PREDISPOSITION (Genomics)
2. STANDARD AMERICAN DIET (SAD)
– Processed Foods, Preservatives, Additives
– Low-and No-Fat Foods (High Carb)
– The Food Pyramid (High Carb)
– Trans- and Saturated Fats
– Low in Essential Nutrients and Fiber
– High Fructose Corn Syrup and Soda
3. SEDENTARY LIFESTYLE
4. GLUTEN AND DAIRY INTOLERANCE common
Does Nutrigenomics Play a Role?
 RESULTING SYNDROMES
Classic presentation
CAD
CVA
Hyperlipidemia
Hypertension
DM
Obesity
Cancer
PCOS
CLASSIC APPROACH
(KNEE-JERK)

Missing the Forest for the

Trees
Traditional Allopathic Approach
Abnormal Parameter, Symptom, or Laboratory
Blood Values:
– GTT, or 2 hr Postprandial Glucose
– LDL Cholesterol
– Blood Pressure
– High BMI
– Mood Disorders
– GERD
– Fibromyalgia/ Chronic Fatigue Syndrome
– Signs of PCOS
– IBS
 Knee-Jerk Reaction
Diabetic Meds
Antihypertensives
Statins
Analgesics
OC’s/Progestins
Antidepressants
Proton pump inhibitors
Anorexics
Bariatric Surgery
 WHY TRADITIONAL
APPROACH FAILS
Patient has intense CHO cravings – diet &
medications alone do not lessen the cravings
Patients worry about the multiple symptoms, thinking
their body is becoming alien - need emotional support
& education of this multidimensional condition
Medications are prescribed to treat a prevalent
symptom or disease, not the global assimilation of
symptoms
Poly-pharmacy increases drug interaction, cost, side
effects, & non-compliance
Patients ask for a holistic model due to multiple
symptoms
Patients want to be FUNCTIONAL again
NUTRITIONAL APPROACH

Kalamazoo Heart Center of

Excellence:
Metabolic Syndrome
Program
 THE CASE FOR NUTRITIONAL
THERAPIES
This disorder does not result from a lack of
prescription drugs
There is no “magic bullet”
Many end up taking 4 or more drugs then
dealing with an array of side effects
Drugs merely treat a symptom or lab value
while allowing the underlying disease
process to continue
 TREATMENT PLAN
Once diagnosis is made:
Assess any medical problems
Psychophysiological assessment: meet the patient in
their moment with all of their symptoms
Set up Primary and Secondary goals together with
the patient
Nutritional Supplement Recommendations
40-30-30 Macronutrient Plan
Lifestyle Modification Discussion
F/U at 3 wks, 8 wks, 3 mos, 6 mos, 9 mos, 12 mos
Group Classes for Health Education
 PROGRAM GOALS
Appropriate Calories to Ideal Weight
Increase Omega-3 Oils
Increase MonoUnsaturated (Mediterranean) Fat
Low Saturated and Trans Fatty Acids
Low Glycemic Index Foods
High Fiber
Low simple CHO (increase complex CHO)
Moderate Protein
 NUTRICEUTICAL
TREATMENT
DIET IN GENERAL:
“Mediterranean”
30% Protein
30% Good Fats (monounsaturated)
40% Low Glycemic Index Carbs
Soy
High in Soluble Fiber
Micronutrients
 NUTRICEUTICAL
MODE OF ACTION
OMEGA - 3 FATS (EPA/DHA)-Cell Wall and
Receptor Function
a LIPOIC ACID -Mimics Insulin
MG -Needed for release of Insulin
CHROMIUM -Increases function of insulin
VANADIUM -Mimics insulin (>100mg toxic)
gamma LINOLEIC ACID-Restores insulin
function. Restores nerve function
FIBER -Slows Glu absorption in GI Tract
 MODE OF ACTION
Pharmaceutical vs. Nutriceutical
ENHANCED SLOWED REDUCED PERIPHERAL IMPROVED
INSULIN GLUCOSE GLUCOSE GLUCOSE RECEPTOR
SECRETION ABSORPTION PRODUCTION DISPOSAL FUNCTION

Sulfonylurea Biguanides
(Micronase) (Metformin)
Alpha-
Glycosidase Thiazolidine-
PHARMA
Inhibitors Thiazolidine- diones
CEUTICAL Meglitinides
diones (Actos)
(Prandin) (Acarbose)
(Actos)

SolubleFiber Complex
PUFA PUFA
NUTRI Magnesium Complex Carbs
Lipoic Acid Omega-3
CEUTICAL Vanadium Carbs Protein
Linoleic Acid Vanadium
Protein Fiber
 Recommended Nutrients
EPA 1500-4000 MG
DHA 1000-2000MG
Mg 200-400 mg
Cr 400-1000 ug
Vd 15-50 mg
CLA 1000-3000 mg
Vit E 400-800 U
Vit C 2-6 gm
aLA 50-200 mg
Arg 2 gm
 GOOD CARBS
GLYCEMIC INDEX
Volunteers’ blood sugar response to a test food
containing 50 gm carbohydrate, as compared to
50 gm pure glucose (3 Tbs)

HIGH >70%
MODERATE 55-66%
LOW 40-54%
VERY LOW <39%
 Glycemic Load of Various
Foods
White bread 70
Potato 85
Carrots 71
Rice 88
Oat Grain Bread 47
Pasta 45
All-Bran 42
Corn Flakes 84
Corn Chips 73
Pretzels 80
Peanuts 14
 Foods that Lower I.R.
Rice (esp. high amylose starch)
Soluble Fiber (slows glucose absorption)
Vegetable Protein (modulate GLUT-4
transport)
Complex CHO (slowly digested, prevents
rapid change in glucose and insulin)
 Foods to Avoid
Refined CHO (Glycemic Index)
Simple Sugars -High Fructose Corn Syrup
White bread and flour
Juices
Sugar-containing Soda
Processed Foods
Trans Fats
Saturated Fats
 GOOD FATS

Monounsaturated, “Mediterranean” (olive)

Omega-3 Fatty Acids (Fish Oils, Flaxseed)
Conjugated Linoleic Acid (PPAR agonist,
acts like TZD’s)
Alpha Lipoic Acid (Antioxidant)
FATS AND HEART DISEASE

Saturated Fat Diet

– Finland
– US
Monounsaturated Fat
– Italy
– Greece
Low Total Fat
– Japan
 Shopping Tips
AVOID THE CENTER AISLES AT THE
SUPERMARKET
SHOP MAINLY IN THE PERIMETER
AREAS:
– Fresh Produce
– Fruits and Vegetables
– Meats and Eggs
– +/- Frozen Foods
 UNHEALTHY DIET
Refined CHO is absorbed rapidly and
triggers release of excess insulin
Diminished insulin signal impedes fusion of
transport channel vesicles with cell
membrane
Insulin signal is diminished by
Phosphotyrosine, TNF alpha, cytokines,
NF-kappa, inflammatory substances
 HEALTHY DIET AND
MICRONUTRIENTS
Complex CHO more slowly absorbed in
intestine – appropriate insulin released
(Soy, Amylose Starch, fiber)
Insulin signal supported by: Vn, Cr, CLA,
Lipoate, Inositol, Mg, Vit E
Strong insulin signal directs sugar transport
vesicle to fuse with cell wall
CLA binds to nucleus to support gene
expression
 GOALS

Work closely with PCP

Approach chronic“diseases” by addressing
underlying functional problems
Formulate a viable program for the
prevention of disease
 CONCLUSION
Correction of lab values does not
constitute wellness
Lifestyle intervention REQUIRES
immediate positive effects & education
for optimal change and management.
The healing process needs: support,
love, hope & humor
END
CASE PRESENTATIONS

Metabolic Syndrome
Insulin Resistance
Syndrome X
 Case Study - PCOS
(Rebecca)
31 y.o. Woman with:
Anxiety
PMS and Moodiness
Fatigue
Amenorrhea
Sleep Disorder
 PCOS (Rebecca)
October 31 December 21
Glucose Glucose
– FBS 93 – FBS 91
– 2 hr 112 – 2 hr 83
Insulin Insulin
– Fasting 12 – Fasting 9
– 2 hr 108 – 2 hr 17
Cholesterol 271 Cholesterol 200
HDL 39 HDL 45
LDL 178 LDL 141
Triglyceride 269 Triglyceride 71
Weight 165 Weight 153
Menses absent Menses regular
 Case Study – PMS, Fatigue
(Martha)
54 y.o. Woman with:
Anxiety
Irritable Bowel Symptoms
Adrenal Fatigue
Fibromyalgia
No weight loss with low fat diet, exercise
 Fatigue, FMA (Martha)
November 8 February 21
Glucose Glucose
– FBS 114 – FBS 104
– 2 hr 209 – 2 hr 92
Insulin Insulin
– Fasting 9 – Fasting 7
– 2 hr 87 – 2 hr 25
Cholesterol 204 Cholesterol
HDL 77 HDL 70
LDL 111 LDL 97
Triglyceride 78 Triglyceride 84
Weight 189 Weight 169
TSH 3.94 (2/13/02)
 PHARMACEUTICAL
SIDE EFFECTS
SU - hypoglycemia, weight gain,
hyperinsulinemia
Non-SU Secretagogues - same, plus
3/day dosing
Biguanides - GI upset, lactic acidosis
a-Glucosidase Inhib - GI upset, 3/day
dose
Thiazolidinediones - LFT, weight gain,
edema, slow onset of action
 METABOLIC SYMPTOMS
AND SYNDROMES
Symptoms: Syndromes:
Weakness/Fatigue
Chronic Fatigue
Muscle Pain
Diarrhea/Constipation Fibromyalgia
Stomach Irritation Irritable Bowel
Sleep Problems Syndrome
Allergy Symptoms Somatization
Inability to Lose Wt
Immune Problems PMS/PCOS
Hypoglycemia Mood Disorders
Chronic Yeast