Obesity Diabetes and Complications

Obesity, Diabetes & Complications COPE #7999-GO
Stuart Richer, OD, PhD, FAAO DVA Medical Center Chief, Optometry Section Associate Professor, Family & Preventive Medicine, RFUMS, North Chicago, IL 9 November 2008 Jackson , MI
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. a balanced, healthy diet and moderate exercise taken on a regular basis can cut a person's risk of developing diabetes by 58 percent.
Will All Americans Become Overweight or Obese? Estimating the Progression and Cost of the US Obesity Epidemic July 24, 2008
If current trends continue, 86% of the US adult population will be overweight or obese by 2030 At this rate, 100% of the population will be affected by 2048
What overweight and obese patients most want from their primary care providers is dietary advice, help setting weight loss goals, and exercise recommendations
J Fam Pract. 2001 Jun;50(6): 513-18
A mere 1 in 5 are having this need met..
Course Considerations
Why is obesity associated with ocular (and systemic) disease? Clinical Entities Epidemiology & Definitions Biological Rationale for Specific Macronutrients Rationale for Specific Micronutrients & Nutraceuticals
Course Considerations
Specific Patient Recommendations
Exercise Diet Supplements
Effective Communication
Conclusion
keeping the overflowing bath from ruining the bathroom floor
Battling the systemic & ocular complications of obesity is analogous to keeping an overflowing bathtub from ruining the bathroom floor
Turn Off the Faucet
Bail the Tub
Pull the Plug
Mop Up the Floor
Why is Obesity Associated With Ocular & Systemic Disease?

An Unholy Triumvirate Inflammation Hypertension Hypoxia
Inflammation
Fat cells (adipocytes) are endocrine cells, secreting hormones regulating insulin sensitivity & satiety, and are associated with elevated markers of inflammation
Resistan Adiponectin Leptin PAI-1 CRP Factor VII ICAMs iNOS IL-6 Fibrinogen TNF-
Subcutaneous vs. Visceral Fat

Reactive Oxygen Species & Inflammation
Fat Cells Are Endocrine Cells!!
Inflammation & Oxidative Stress

Visceral fat (VAT) secretes hormones causing insulin resistance (IR) & increased mitochondrial production of reactive oxygen species (ROS) in insulin independent tissues (liver, kidney, aorta, retina) VAT mobilizes free fatty acids which are oxidized by vascular endothelium to generate ROS Increased oxidative stress causes inflammation & endothelial dysfunction
Diabetes. 2005 Jun;54(6): 1615-25 Circulation. 2007 Sep;116(11): 1234-41
Oxidative Stress
an imbalance between tissue oxidants (free radicals or reactive oxygen species) and antioxidants may be a unifying mechanism in the development of major-obesityrelated co morbidities such as cardiovascular disease and diabetes
HK Vincent and AG Taylor, Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans, International Journal of Obesity, 30 p400-18, 2006
Oxidative Stress
Endothelial Dysfunction
Hypercoaguability Vasoconstriction Inflammation
Disease
Inflammation iron metabolism

Iron (Fe2+) overload also promotes inflammation & ROS
Metabolic (common in T2DM and the metabolic syndrome)* Genetic (haptoglobin genotype)** Dietary
2002;51: 2348-54 **Arterioscler Thromb Vasc Biol. 2007, Nov 21 JAMA 2000 Sep 13;284(10):1244-5
*Diabetes
Inflammatory Cytokines
TNF- PAI-1 ICAMs CRP FFAs Adipokines
Iron Overload
Metabolic Hp Genotype Diet
Obesity
VAT
Insulin Resistance
Skeletal Muscle Liver Hypothalamus
Increased Oxidative Stress
Hunger & Increased Caloric Intake
Blunted Satiety Receptors
Disease
Hypertension
Obesity & BMI are clear and continuous risk factors for HTN
IR activates the renin-angiotensin system
Weight loss results in reduced BP in large clinical trials HTN is a definitive risk factor for CVD and myriad ocular diseases (RVOs, AION, DR)
Blood Press. 2007;16(1): 13-19 Am J Hyperten. 2006 Nov;19(11): 1103-9
Hypoxia
Obesity is THE major risk factor for obstructive sleep apnea syndrome (OSAS) OSAS causes hypoxic stress and elevates blood pressure OSAS is associated with endothelial dysfunction and several eye diseases
J Clin Sleep Med. 2007 Jun 15;3(4): 409-15 Exp Physiol. 2007 Jan;92(1): 51-65
OBSTRUCTIVE SLEEP APNEA

ROS Endothelial Dysfunction
Inflammation
Hypertension
Hypoxia
Clinical Entities: Eye Disease Associated with Obesity

Cataract AMD Glaucoma Diabetic Retinopathy NAION Floppy Eyelid Syndrome (FES) Pseudotumor cerebri (PTC) Venous Occlusive Disease
Cataract
BMI > 30 increased risk of PSC and cortical cataract (Blue Mountains Eye Study.
Ophthalmic Epidemiol. 2003;10(4):227-40)
Metabolic Syndrome increases risk of cataract by 30-40% (Eur J Ophthal.

2007;17(4): 605-14)
Risk of PSC 2.5X higher for women with waist circumference > 89cm
(Am J Clin Nutr 2003;78:400-5)
Did you know all of these are associated with Obstructive Sleep Apnea (OSAS)?
Glaucoma prevalence estimated -27% (Eye.
2007, May 4)
Floppy Eyelid Syndrome prevalence - 25%

(Ophthalmology. 2006;113(9):1669-74)
Pseudotumor Cerebri (15-40%)

2001 21(3):235)
J Neuroophthal
OSAS is the most frequent disorder in patients with NAION (BJO. 2006;90(7):879-82)
Higher IOP also associated with obesity

(Diab Metab Res Rev. 2005;21(5): 434-40)
AMD
Increased risk with increasing BMI & waist size (Arch Ophthalmol. 2003;121(6): 785-92) 5% increased risk of advanced AMD with every 1 kg/m2 increase in BMI
(Am J Ophthalmol. 2007;143(3): 473-83)
In AREDS, BMI > 30 doubled the risk of SRNV (Ophthalmology. 2005;112(4):533-9) Greater waist circumference and DM related to lower MPOD in the Womens Health Initiative (n=1698)
(Am J Clin Nutr. 2006;84(5): 1107-22)
Diabetic Retinopathy
Obesity & weight gain are the primary risk factors for T2DM (Ann
Intern Med. 1997;122:481-6)
Marked obesity increases the risk of DR (Diabetes Care. 1986;9(4): 961-9)
Venous Occlusive Disease

Risk of RVO and arterial emboli is 3.8 fold higher for BMI > 30
(Ophthalmology. 2005;112(4): 540-7)
Highest risk of CRVO if patient has HTN, DM or OHTN High risk of BRVO reported when BMI > 25 kg/m2 at 25 years of age (Ophthalmology. 1996;114(5): 545-54)
Epidemiology and Definitions

In 2006, 60.5% of Americans were overweight, 23% were obese, and 3% were morbidly obese
1990
No Data <10% 10%14%
1998
15%19% 20%24%
2006
25%29% 30%
BMI > 30
1 in 3 Children Born in 2000 will develop Diabetes

Ben Szirth, PhD New Jersey Medical College
Classic Definition
BMI BMI BMI BMI > 25 > 30 > 35 > 40 overweight obese severely obese morbidly obese
BMI = Weight (kg)/Height (m)2

or Weight (pounds)/Height (inches)2 x 703
Children & Teens

Overweight BMI > 85% percentile Obese BMI > 95% percentile
Girls
Boys
Other measures of obesity

Abdominal Adiposity
Waist Circumference > 102 cm (40 inches) in men Waist Circumference > 88 cm (35 inches) in women Waist:Hip Ratio >1.0 for men > 0.8 for women
My doctor told me to stop having intimate dinners for four. Unless there are three other people -Orson Welles
Nutritional Management
There is a charm about the forbidden that makes it unspeakably desirable -Mark Twain
Biologic Rationale For Specific Macronutrients

Dietary Macronutrients are nutrients needed in relatively large quantities
Fats (glycerin + 3 fatty acids) Carbohydrates (sugars) Proteins (amino acids joined by peptide bonds)
Dietary Fat
Saturated Fat:
High intake unquestionably linked to increased CV risk & inflammation (J Lipid Res.
2006;47: 1661-7)
Intake > 10% of calories worsens insulin sensitivity and LDL-C (Hepatology. 2003;37: 909-16) But intake < 7% of calories has little effect on LDL-C and significantly lowers protective HDL-C, especially in patients with insulin resistance (Obes Surg. 2005;15: 502-5)
Dietary Fat
Trans Fat
Multiple isomers with varying metabolic effects trans-10,cis-12 conjugated linoleic acid from partially hydrogenated oils (corn oil & vegetable oil) significantly increases inflammation and CV risk (N Engl J Med. 1997;337: 1491-99) and induces endothelial dysfunction (Atheroscler Supp.
2006;7: 29-32) Note: trans fats < 0.5 g are reported as 0 on food labels
Monounsaturated Fats - MUFA

Decrease triglycerides, LDL-C and oxidized LDL-C without decreasing HDL-C (J Nutr Biochem.
2006;17: 645-58)
Decrease ICAMs & improve endothelial dysfunction (Ann Intern

Med. 2001;134: 1115-19)
High levels of MUFA in macadamia & olive oil, nuts and avocadoes
Polyunsaturated Fats - PUFA

n-3 and n-6 subtypes n-3 PUFA (e.g. -linolenic acid) tend to decrease inflammation The high arginine content of tree nuts (esp. walnuts) also decreases CRP (Nutrition.
2005;21:125-130)
n-6 PUFA (linoleic acid) tend to increase inflammation Debate: does the ratio of n-6:n-3 PUFA determine the inflammatory effect? A 2:1 to 6:1 ratio is recommended to maximize CV benefit Typical US Diet has an inflammatory 20:1 ratio
Benefits of PUFA
Rates of heart disease decline when PUFA are substituted for saturated fat
(Arch Intern Med. 2005;165: 193-7)
The n-3 PUFA, -linolenic acid (flax, canola, walnut, linseed oils) is a precursor to the long chain, omega-3 fatty acids DHA & EPA TGs, FFAs, blood glucose & insulin levels, visceral fat mass and many inflammatory markers decrease with intake of DHA/EPA (J Nutr Biochem.
2006;17: 1-13)
High DHA and EPA in cold water, oily fish (salmon, sardines, herring)
Take Home on Fats

Keep SFA between 7% and 9% of calories Eliminate all trans fats Increase consumption of MUFA Substitute PUFA for SFA Increase consumption of n-3 PUFA as well as DHA & EPA
The Dangers of Refined Carbs & Low Fiber

High intake of simple sugars (glucose, fructose & sucrose) increases serum FFAs and oxidative stress (Am J Clin Nutr.
2001;74: 737-46)
Refined carbs elevate blood glucose & insulin, reduce NO and impair vasodilatation By a mass effect, post-prandial hyperglycemia increases cellular glucose uptake, production of ROS and pro-inflammatory cytokines (Nature.
2001;414:813-20; Circulation. 2002;106: 2067-72)
Production of reactive oxygen species (Superoxide) by mitochondria exposed to any glucose

Intracellular Glucose & FFAs
ATP + Superoxide (O2-) Mitochondrian

Inflammatory Cytokines
HFCS and Obesity?

HFCS and Obesity?

Fructose is metabolized by hepatocytes to produce triacylglycerol and uric acid Uric acid reduces NO levels NO is requisite for insulin receptor function HFCS elevates triglycerides and fosters hyperuricemia-induced insulin resistance HFCS contributes to the Metabolic Syndrome (Am J Physiol Renal Physiol 2006;
290(3):f625-31)
Uric Acid & Metabolic Syndrome

Metabolism. 2008 Jun;57(6):845-52
FPG > 110 HDL < 40 (male) or < 50 (female) BP > 130/85 TG > 150 Waist > 40 inches (male) or 36 inches (female)
100
Prevalence 80 of Metabolic 60 Syndrome
%
Per NCEP ATP-III Criteria
40 20 0
10
Serum Uric Acid (mg/dl)
The Case for Fruits & Vegetables

Diets with high intake of fruits & vegetables are consistently associated with lower CV risk (JAMA
2002;288: 2569-78)
Rich in antioxidants High in fiber
Fiber increases insulin sensitivity (Diabetes

Care 2005;28: 1022-28) 2006;29(2): 207-21)
Fiber reduces CRP and TNF- (Diabetes Care 25 gm fiber reduces BP 6mm/4mm in hypertensive patients (J Hyperten. 2005;23(3):
475-81)
The Case for Pomegranates??

Juice, seeds and extract all reduce biomarkers of oxidative stress (J Agric Food
Chem. 2007;55(24): 10050-4)
PJ reduced systolic BP 21% and oxidized LDL-C by 90% in patients with CAS PJ decreased carotid intima media thickness by an average of 30% at one year (Clin Nutr. 2004;23(3): 423-33)
Carotid IMT before and after 1 year of daily PJ consumption (50 ml) in a patient with carotid artery stenosis (CAS)
30% mean decrease at 12 months
Control subjects on 80 mg simvistatin had a mean carotid IMT increase of 9%
Fermentable Carbs: The Case for Alcohol

Moderate intake of all alcoholic beverages lowers CRP and is associated with lower rates of fatal & non-fatal CV disease (Am J
Cardiol. 2005;96(1): 83-88) Cardiol. 83-
drink per day confers protection by increasing insulin sensitivity and HDL-C (J
Am Coll Cardiol. 2007;50(11): 1009-14)
Resveratrol, a polyphenolic component of red wine, enhances insulin sensitivity by activating the enzyme SIRT-1
SIRT1 extends lifespan in mammals (Nature.
2006;444(71): 337-42) 337-
SIRT activators prevent neurodegeneration in animal models of MS & optic neuritis (Invest
Opthalmol Vis Sci. 2007;48(8): 3602-9)
CAN WE TRICK OUR GENES ?

Mass. Institute of Technology
David Sinclair, PhD Harvard Medical School
Candidate SIRTUIN1 Gene Activators

Slide courtesy Mr. Bill Sardi; www.Longevinex.com
The Case For Dark Chocolate

6.5 grams of dark chocolate 3x/wk reduced C-reactive protein by 17% in a prospective study of 11,000 healthy Italians
J Nutr. 2008 Oct;138(10):1939-45
Polyphenols
Equivalent to a 25% CV risk reduction in men and 33% in women A square Q2-3 days
Good Carb: Bad Carb
Do particular dietary sources of carbohydrate influence glucose homeostasis and inflammation?
Glycemic Index (GI) & Glycemic Load (GL)

GI is the incremental area under the blood glucose response curve of a 50g portion of test food compared to a standard (white bread or glucose)
GL = GI x portion size (gms) 100
Criticisms: Many
GI and GL are Useful

Low GI food delay hunger, reduce caloric intake (Lipids. 2003;38(2): 117-21) High dietary glycemic load (dGL) triglycerides and CRP and HDL-C
(Arch Intern Med. 2001;161(4): 572-6)
low dGL diets result in much more weight loss than high dGL diets in the short term (Am J Clin Nutr 1994;60(1): 48-53)
Are GI & GL useful?

Low dGI/dGL diets reduce fasting blood glucose, glycated protein and insulin resistance (Am J Clin Nutr. 2008 Jan;87(1):258S-268S) dGL specifically influences CV risk in obese patients (Am J Clin Nutr. 2007;85(3): 724-34) High dGI increases the risk of developing T2DM (Diab Technol Ther 2006;8(1): 45-54) & AMD (large drusen, GA, CNVM) (Am J Clin
Nutr. 2007;86(1): 180-8)
GL x Carbohydrate Content more useful according to Loren Cordaine, PhD
48 % of US Food can cause insulin resistance and an increased glycemic load

Loren Cordaine, PhD The Paleo Diet
Association between dietary glycemic index and age-related macular degeneration in nondiabetic participants in AREDS 4099 patients 55-80 yo
49% increased risk of advanced AMD (GA + SRNV) if dGI is above the sex median 20% of prevalent AMD cases would have been eliminated if dGI was < sex median
100,000 cases of AMD would have been prevented if dGI had been < sex median
(Am J Clin Nutr. 2007;86(1): 180-8) Slide courtesy of Jeffrey Anshel, O.D.
Take Home on Carbs & Fiber

Decrease or eliminate intake of refined carbs (avoid white food) Reduce & diffuse the glycemic load (smaller, more frequent meals) Eat a variety of lower GI/GL fruits & vegetables; increase intake of dietary fiber to > 25g/day Consider moderate alcohol consumption (1 drink QOD), preferably red wine, 3 oz. pomegranate juice daily and a small square of dark chocolate twice/week
Eat Drink & Be Healthy, Walter Willett
Dietary Protein
Increased protein intake results in heightened satiety and weight loss
(J Nutr. 2004;134:975S-979S; Cell Metab. 2006;4:223-33)
Triggers release of gut hormones (adiponectin, GLP-1) that appetite Increases thermogenesis 2-3X (body heat) BUT
Appears to worsen insulin sensitivity and may contribute to kidney disease

(Annu Rev Nutr. 2007;27:293-310; Clin J Am Soc Nephrol. 2006;1(6): 1293-9)
IGF which may shorten lifespan

(Aging Cell. 2008;7(5): 681-7)
Iron Its Whats For Dinner

Strong association between T2DM & consumption of iron-rich red meat as well as serum levels of nontransferrin-bound iron (NTBI)(Diabetes
Care. 2007;30: 1926-33)
Suggests Fe2+ overload & abnormal iron metabolism in diabetes Hp genotype may exacerbate the risk of retinopathy
Iron overload also has been implicated in the pathogenesis of AMD (Retina. 2007;27(8):997-1003)
Benefits of Soy Protein

An increasing body of literature suggests benefits in obesity
Reduces TC, LDL and TGs by cholesterol absorption & synthesis

Reduces FFAs and improves insulin sensitivity (Br J Nutr. 2006;96: 469-75) Improves endothelial function and inflammatory markers (Am J Clin Nutr. 2003
Jul;78(1):123-30; Diabetes Care. 2007 Apr;30(4):967-73)
Take Home on Protein

Increased protein consumption decreases appetite and assists in weight loss These benefits must be weighed against the possible risk of kidney dysfunction & worsened insulin resistance (but see Skov AR 1999; 528-36 International J of Diabetes) Increased consumption of cold water, fatty fish, and some fermented soy protein may be is preferable
Dietary Recommendations for Overweight & Obese Patients

Eat an anti-inflammatory, calorie restricted diet consisting of a variety of low GL fruits & vegetables, nuts, whole grains and plentiful fiber, favoring cold water, fatty fish, lean grass fed meat and some soy protein, with minimal, regular alcohol consumption (1/2 glass of red wine daily)
Modify based on clinical history
The Mediterranean Diet

Nurses Health Study showed reduced biomarkers of inflammation & endothelial dysfunction (Am J Clin Nutr. 2005;82: 163-73) Lyon Heart Study showed a 70% reduction in MI and unstable angina EPIC showed an inverse correlation between adherence to a Med style diet and death (N Engl J Med. 2003;348: 2599-2608) The NIH-AARP study (n= 380,000) showed a 20+% reduction in CVD & Cancer mortality (Arch Intern Med. 2007 Dec
10;167(22):2461-8 )
83% reduced risk of T2DM over 4 years

(BMJ 2008, May 29 EPub June 1)
Little proof of ocular benefit but good probability
Killer Containers?
Bisphenol A (BPA): a polymer additive commonly lining bottles, cans and food containers of BPA in the US is found in polycarbonate Higher urinary BPA concentartions associated with a 39% increased risk of both CV dx and diabetes Early BPA exposure may trigger fat cell growth (Diabesity)
JAMA. 2008 Sep 17;300(11):1303-10. Epub 2008 Sep 16
USA Dietary Patterns (1890-2008)

High simple carbohydrate consumption Soda -3.5 cans/day (only 25 % diet) - started in 1890 85% is White Flour Baked goods - started in 1890 Potatoes - French Fries as #1 vegetable Low Fruit & Vegetable (micronutrient/fiber) consumption 3 servings per day is average 20:1 imbalance W6:W3 fatty acids 5-10 % calories from trans fats Grain-fed & fattened cows, pigs, chickens -and stable, (perhaps slightly lower %) saturated fat consumption Progressive increase in calories to 3700/capita in 1990s (fast food , meal super-sizing & nocturnal 24/7 eating) Lack of Variety in Food Supply
Modern Nutrition and Ocular Disease

Excess Carbohydrates & Low Micronutrients Obesity and increased risk of CVD, HTN and +/- CANCER Obesity and increased risk of AMD & CATARACT Obesity, Diabetes and increased risk of RETINOPATHY Obesity and increased inflammation Insufficient Nutrition induced by average plant food consumption of only 3 servings/day induced by individual pharmaceuticals & polypharmacy induced by an RDA for ascorbic acid that is too low induced by recommendations to avoid fish omega III induced by recommendations to avoid sunlight vitamin D Induced by mixed message nutri phobia Mal-nutrition -- TRANS fats from soy oils -- high fructose corn syrup -- aspartame
US Public Health & Primary Prevention

90 % of Americans will develop HTN 80 % of CVD in western culture is a direct consequence of diet & lifestyle. 70 % of Americans are overweight or obese. 36 % of Americans have diabetes or pre-diabetes. CVD disease kills almost half of us.
Alzheimer's in America
72.8 years average age of onset (1 study). Alzheimers affects 1 in 10 people over age 65, the rate is closer to 50 % for Americans over age 85. 6-8 % develop symptoms before age 65 (~300,000 people). Few people experience symptoms between ages 30 and 40.
Is ALZ Type 3 Diabetes ?

Wei-Quin Zhao et al, Amyloid beta oligomers induce impairment of neuronal insulin receptors, FASEB, 24 Aug 2007.
1.
2.
3.
Amyloid beta diffusible ligand (ADDL) initiates deterioration of dendrite synapse function, composition & structure Insulin resistance in the AD brain exists. May be reversible and some DM meds likely helpful.
abdominal fat in mid-life risk for dementia, study suggests.

Being overweight / obese nearly doubles one's risk of dementia in old age "abdominal fat is a bigger risk factor than even family history Highest amount of abdominal fat between ages 40 and 45 are 3X more likely to develop dementia than those with the lowest amount of abdominal fat whereas having a parent or sibling w ALZ only doubles the risk"
R Whitmer et al, Neurology, 3-26-2008
in 2008,
Only 2% of Medical Students are Entering Primary Care Family and Preventive Medicine
Primary Care OD INTERVENTION Promote Exercise Promote Dietary Knowledge

2005 USDA Food Triangle
Rx Comprehensive Multivitamins
Omega fatty Acids
Rx Targeted antioxidants
3 EXERCISE GOALS
1.
MAINTAIN MUSCLE MASS (Resistance) JOINT FLEXIBILITY & Bone Health CARDIOVASULAR STATUS & Weight Maintenance
2.
3.
Overweight Children PDF Created with deskPDF PDF Writer - Trial :: http://www.docudesk.com
10 % between age 2 to 5 15 % between age 6 and19

20 hours of TV/Computer/week (LESS EXERCISE) Fast Food Consumption and Toys Drink soda (Liquid Candy Bars) Fat and sugary snacks (ice cream, donuts, muffins, candy) Sugary cereals for breakfast (make triglycerides & cholesterol) Effect on Family depression? ; hostility?, ADD? ; $40 per week extra on food bill.
American College of Cardiology Study, 3/20/2002

575 females with normal BP average age = 20 years; from parochial &
public schools in Cincinnati, Ohio
20 % of students with left ventricular hypertrophy (precursor to congestive heart failure)

1. 2. 3. 4. Premature sudden death - 4x the MI risk Irregular heart beats Failure to nourish heart Difficulty with BP and cholesterol control
Cafeteria Food Fight

7-eleven with books ?
Vending machines 43 % of elementary schools 74 % of middle schools * nearly all high schools
National School Lunch Program 27 million meals/day $ 2.09 meal subsidy (break even) Fast Food higher profit margins of 50% 20 % of schools serve branded foods
Physical Activity
Get 30 minutes of moderate exercise most days of the week

Exercise with or without weight loss reduces abdominal fat (Obes Res.
2004;12(5): 789-98)
Reduces insulin secretion 40%, BP 15%, and mortality by 27% (Arch Intern Med. 2007
Dec 10;167(22):2461-8)
Both the Finnish Diabetes Study and the Diabetes Prevention Program showed a 60% reduction in T2DM Dx in at-risk patients (N Engl J Med. 2004;346:393-403; Diabetes.
2005;54(1):158-65) 2007)
Exercise promotes SIRT1 (Rejuvenation Res.
CALORIC RESTRICTION
& EXERCISE
2005 ADA Scientific Session
Courtesy of Steven Freed, RPh, CDE
ADA
Okinawa Centenarian Study NIH/ Japan Ministry of Health

M Sukuki, MD, PhD Principal Investigator B Wilcox, MD, MSc Co-PI D Wilcox, PhD, MHSc Co-PI
Key Findings of this 28 year diet study 1) Lifestyle trumps genes 2) Energy Balance is crucial for healthy weight 3) Macronutrient balance is key to healthy weight maintenance and loss 4) Biomarkers show health benefits 5) Fights stress and inflammation
The Diabetes Prevention Program

A Randomized Clinical Trial to Prevent Type 2 Diabetes in Persons at High Risk
Northwestern Univ School of Medicine Massachusetts General Hospital Univ of California, San Diego St Lukes-Rossevelt Hospital Indiana Univ School of Medicine Medstar Clinical Research Center Washington Univ Scool of Medicine John Hopkins University University of New Mexico School of Medicine
NEJM 346:393-403, 2002
Mean Weight Change

Weight Change (kg)
0 -2 -4 -6 -8 0 1 2
Years from Randomization
Placebo Metformin Lifestyle
The DPP Research Group, NEJM 346:393-403, 2002
Percent developing diabetes Incidence of Diabetes

All Placebo (n=1082)

40
participants
Cumulative incidence (%)
Metformin (n=1073, p<0.001 vs. Placebo) Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac ) Lifestyle (n=1079, p<0.001 vs. Metformin , Metformin (n=1073, p<0.001 vs. Plac) Placebo (n=1082) p<0.001 vs. Placebo)
30
Risk reduction 31% by metformin 58% by lifestyle
20
10
0 0 1 2 3 4
Years from randomization

Mean Change in Fasting Plasma Glucose

115
FPG (mg/dl)
Placebo
110 Lifestyle Metformin 105
100 0 1 2 Years from Randomization

Mean Change in HbA1c

Placebo
6.1
HbA1c (%)
6.0 5.9 5.8 0 1 2 Years from Randomization 3 4
Metformin Lifestyle
Loren Cordaine, PhD

1. 2.
3.
4.
5.
6.
7.
Glycemic load Fatty acid composition Macronutrient composition Micronutrient density Acid-base balance Sodiumpotassium ratio Fiber content
Chronic pancreatic Hyper-insulinemia (The last 180 years)

Increased Stature Decreased age of Menarche Acne Polyscystic Ovary Syndrome Epithelial Cancers (breast, colon, lung, prostate) via hepatic IGF-1 & hepatic IGFBP-1 Skin tags Acanthosis Nigricans Male Vertex Balding
START WITH A GOOD DIET

AGING
Foods Deficient in the Standard American Diet (SAD)

Percentage of Individuals Not Consuming the Recommended number of Pyramid Servings Per Day
90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
35% 48% 40% 37% 63% 58% 55% 59% 73% 72% 72% 84% 73% 73%
72%
Grain
Vegetables Female 20+
Fruit Males 20+
Dairy All Individuals 2+
Meat
Fruits Vegetables Fish Whole Grains Legumes Nuts & Seeds
Anatomy of www.MyPyramid.gov
2005 for Americans (over age 2) One Size Doesnt Fit All
Activity Moderation Personalization Proportionality Variety Gradual Improvement

Age ; Gender ; Activity; 12 tailored diet plans
USDA /HHS Key Recommendations

EAT FEWER CALORIES BE MORE ACTIVE WISER FOOD CHOICES * compatible with DASH (Dietary Approaches to Stop Hypertension)
Doctors: Think about reading this important book, from the Chairman, Harvard School of Public Health
But only 3% of Americans follow 4 basic health practices

MJ Reeves, AP Rafferty, Healthy lifestyle characteristics among adults in the US, 2000, Arch Intern Med 2005;165:854-7. 4 HLCs (Healthy Lifestyle Characteristics) 153,000 adults, random household telephone surveys
1. 2. 3. 4.
Nonsmoking (76 %) BMI 18.5 25 (40%) 5 or more F &V daily (23%) > 30 minutes physical activity 5 times per week (22%)
What are Nutraceuticals?

Nutraceutical can be defined as, "a food (or part of a food) that provides medical or health benefits, including the prevention and/or treatment of a disease. However, the term nutraceutical as commonly used in marketing has no regulatory definition. * Prescription drugs are approved through the rigorous new drug application process (NDA). In contrast, dietary supplements are regulated as foods and the FDA must determine that a dietary supplement ingredient poses a "significant or unreasonable risk of illness or injury"
RDA = Recommended Daily Allowance-prevent 97% of deficiencies Allowancedeficiencies RDI = Recommended Dietary Intake
* J Pharmacol Exp Ther. 2005 Apr 15; [Epub ahead of print]
What are Functional Foods ?

ORAC SCORES
14 SuperFoods Handout
Spinach Sardines Turkey Breast Broccoli Walnuts Tomato Soy Blueberries Citrus Pumpkin Yogurt Oats Legumes Green Tea
Daily sunlight and/or 1000 IU vitamin D twice per day daily also is very important for general health www.mypyramid.gov
Pro-Oxidants vs. Anti-oxidants in Obesity & Diabetes
Figure 1 : HK Vincent and AG Taylor, Biomarkers and potential mechanisms of obesityinduced oxidant stress in humans, International Journal of Obesity, 30 p 400-18, 2006
A plethora of helpful supplements

Vitamin E (natural d-alpha & mixed isomers) BV & nerve sheath health Vitamin C 500 mg to as much as 2500 mg but serially dosed BV health & insulin resistance, cataract & cancer Flavonoids @70% of vitamin C dose Quercetin prevents sorbitol BV damage Bilberry (160-320 mg 25% stnd xtract) Genistein multiple MOA Ginkgo Biloba BV health Carotenoids i.e. Lutein (6-20 mg) Protects Eye & Cardiovascular BVs
Additional Supplements
B Vitamin Complex B1 Thiamin better carbohydrate metabolism B3 Niacin improves HDL status B6 Pyridoxine(s) better protein metabolism Folic acid healing; homocysteine B12 Methylcarbolamine for nerve cell function Biotin better fatty acid metabolism Zn/Cu & manganese better immune system & healing response Vanadyl Sulfate better glucose tolerance Selenium insulin mimic
Andrew Weil, MD top 4

GTF (glucose tolerance factor) chromium (picolinate) 200 mcg 1000mcg / day Helps insulin transport glucose into cells Alpha Lipoic Acid 600 1200 mg Helps insulin transport glucose into cells Inhibits glycosylated attachment of sugar to protein Maintains eye and nerve health (peripheral neuropathy) Also Acetyl-L-Carnosine (2 recent studies)- 500 & 1000mg Magnesium (citrate or taurate) 400mg Insulin production COQ10- 100 mg Maintains cardiac function Protects against high dose statins, AMD & Parkinsons Dz 31% drop in blood sugar in 1 study
Diabetes and CVDz

CVDz 2 - 5X over general population 55 % prevalence rate among adults Compared with 2 -4% of the general population 75 % of all deaths from DM I and DM II 35 % die from CVDz before age 55 Hyperglycemia is a necessary but not sufficient condition for the development of diabetic vascular disease
R Asieh, AP Levy, In vivo & in vitro studies establishing haptoglobin as a major susceptibility gene for diabetic vascular disease, Vasc Health & Risk Management, 2005:1(1) 19-28.
A plethora of nutrients for better blood Vessels

Vitamin C/E and lysine Bioflavanoids 4 ounces frozen berries / day 2 ounces pomegranate juice / day B Vitamins Magnesium Omega III and FlaxSeed (omega III & IP6) Rice Bran: IP6 CA++ & Fe++ chelating agents Vitamin D and K Arginine Condrointin Sulfate Resveratrol
Vitamins C & E together Protective Synergy against Atherosclerosis

Supportive Synergy of Vitamin C & E Randomized Control Trials

The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study
Vits. C & E: 500 mg; 182 mg
Harvard Intravascular Ultrasonography (IVUS) Study

Vits. C & E: 1000 mg; 536 mg
HDL-Atherosclerosis Treatment Study (HATS)

Vits. C & E: 1000 mg; 536 mg
*Multi-Vitamins and Probucol (MVP) Study

Restenosis s/p balloon angioplasty; Vit C, E, & -carotene- 500 mg, 700 IU (637 mg), 30000 IU
*Heart Protection Study

Mortality; Vit C, E & -carotene- 250 mg, 600 mg, 20 mg
1 kg guinea pig
Veterinarians know Cavies should receive between 2550mg of vitamin C daily Fresh fruits and vegetables high in vitamin C are a great source
70 kg human equivalent is 1,750 mg to 3,500 mg / day
Maybe thats why we need those 13 portions of fruits and vegetables per day, The average American consumes only 3 portions.
Simplify thru Rx of Comprehensive Multivitamin / (Ocular) Multi-Mineral Supplements

www.PurityProducts.com Perfect MultiGreens Formula 1-800-281-7781 www. MedOp.com Whole Body Formula 1-800-358-7797 www. Lef.com Two per day superior to Centrum 1-800-544-4440 www.drwhitaker.com ForwardPlus 1-800-722-8008
Multi-betic males & females

DO YOU ASK YOUR PATIENTS IF THEY CONSUME FISH / FISH OIL ???
HDL triglycerides Blood pressure Heart Beat rate arrhythmias (studies show as effective as a pacemaker) sudden death heart attack Violent Behavior; Mood Cognitive function MI, CVA, CA & AMD Fish (sardines, herring, salmon, tuna) 3x per week or 1000mg cod liver oil BID daily
Reversing Diabetes, Revised and Updated, by Julian Whitaker, M.D.

THINK ABOUT THE DOSE OF OTC SUPPLEMENTS
Image from AARP
Comprehensive Multivitamin Dose w Age (or extent of health challenge)

4 3.5 3 2.5 2 1.5 1 0.5 0 Age 20 Age 40 Age 60 Age 80 # Capsules
SERIAL INTAKE IF POSSIBLE
KNOW YOUR MEDICATIONS
A9093
Fiscal & Nutritional Cost of Pharmaceuticals

DRUGS 2001: $120 Billion 2006: $200 Billion 2008 $300 Billion estimate AVERAGE age 65 y/o 4 medications Growing % of healthcare budget with political aspects
Even OTC Pharmaceuticals can induce nutritional deficiencies which are often treated with additional pharmaceuticals
Examples of Additional Targeted Supplementation in Obesity / Diabetes

Fiber Resveratrol/Quercetin
red wine
Benfotiamine Lipoic acid
Oxidative Stress & Diabetes

Causes Hyperglycemia Hyperleptinemia tissue lipids AGEs protein kinase C antioxidant defenses free radical formation Chronic inflammation
Effects 1. Cellular Insulin Resistance 2. Pancreatic Beta Cell Dysfunction 3. Accelerated arteriosclerosis & arteriolarsclerosis 4. Neuropathy 5. Retinopathy
HK Vincent and AG Taylor, Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans, International Journal of Obesity, 30 p400-18, 2006
Controlling the Glucose Flash Flood -upon Blood Vessels

Obesity creates the oxidant conditions of a breeding ground for diseases such as diabetes, heart disease, HTN and CVDz
Image from Life Enhancement Inc, Petaluma, CA
Hyperglycemia & Vascular Complications from blood sugar
Professor Thomas C Washer, Karl-Franzens University of Graz, Austria, Understanding Diabetes, Oxidative Stress and Vascular Complications in type 2 diabetes
Lowers Insulin Resistance by 40% when taken before meals

Proprietary Fiber blend of koniac root, Na alginate & xanthum gum 3-5X better effect on cholesterol than oats or psyllium (total & LDL-C by 19/29%) May lessen need for insulin or other diabetic medications
University of Toronto & Canadian Center for Functional Medicine
Talk with your doctor
Fiber Supplement Benefits:

Controls & balances blood sugar levels Lowers glycemic index of meals by up to 50% Supports healthy weight loss Promotes satiety & food cravings total and LDL cholesteraol
Stevia for diabetics ? Better than aspartame

A no calorie herbal natural sweetener
Oral Medications to Treat Type 2 Diabetes

Combination Therapy for Type 2 Diabetes

Sulfonylureas Biguanides Alpha-glucosidase Inhibitors
Meglitinide
Thiazolidinediones
Insulin
Diabetes Defeated 7 Herbal Formula (Glucator v.2 to sugar metabolism)

HSI.COM Panelist Jon Barron Reviewed 44 herbs used in 2500 y/o Ayurvedic Medicine
1. 2.
3. 4. 5. 6. 7.
Fenugreek pancreatic fn & 54% urine BS Gymnema Sylvesta BS craving and increase pancreatic regeneration. Konjac Mannin 52% BS Nopal Cactus (prickly pear) 15% BS Banaba Leaf Extract: BS by 30% Bitter Melon: 3 components acting on BS Cinnulin PF: insulin receptivity
Phase 1 Clinical Trial of 7 Herbal Formula in patients with T2DM

BS by 54.4 pts 52% in BS utilization & optimization carbohydrate metabolism 5.5 pounds average weight loss
www.HSIBaltimore.com www.baselinenutritionals.com 800-695-5995
Oxidative Stress is implicated in both the etiology & long term complications of diabetes
Increasing Insulin Sensitivity

Pharmacologic
TZD (Actos, Avandia) AKA glitizones
Environmental
Decreasing Decreasing Decreasing iron overload HFCS visceral fat (i.e. FFA)
Exercise to decrease VAT Polyphenols
Decreasing glucose storm
Insulin Resistance
courtesy Bill Sardi
Iron overload = > increased ferritin = > inflammation = insulin resistance = > hunger = >caloric intake = obesity
IP6 phytate* Resveratrol Quercetin Taurine

*Rice bran, chia seed powder or flaxseed meal all contain phytate
Tart Cherry Extract for
VAT
Dahl rats were fed whole tart cherry or isocoloric placebo. After 90 days, the cherry-enriched diet was associated with reduced FBS, hyperlipidemia, hyperinsulinemia, and fatty liver.. Physiologically relevant tart cherry consumption reduced several phenotypic risk factors that are associated with risk for metabolic syndrome and Type 2 diabetes. Tart cherries may represent a whole food research model of the health effects of anthocyanin-rich foods and may possess nutraceutical value against risk factors for metabolic syndrome and its clinical sequelae.
Altered hyperlipidemia, hepatic steatosis, and hepatic peroxisome proliferator-activated receptors in rats with intake of tart cherry.Seymour EM et al Department of Food Science and Human Nutrition, Michigan State University
The FDA against the USDA & 29 Cherry Marketers (Oct 2006)
Eat 9 13 portions of Fruits & Vegetables per day
Warning letter threatening regulatory action if scientific drug like claims are not removed from the web.
20 cherries reduces inflammation in a similar manner as aspirin or Cox-2 inhibiting drugs without the lethal side effects of gastric bleeding or vitamin depletion associated with these drugs The molecules in cherries, called anthocyanins, work to reduce inflammation at ten times less dosage than aspirin. [Journal Natural Products 1999 Feb; 62(2): 2946]
Figure 2: HK Vincent and AG Taylor, Biomarkers and potential mechanisms of obesityinduced oxidant stress in humans, International Journal of Obesity, 30 p400-18, 2006
Benfotiamine
(natural lipid form of Vitamin B1) that prevents age-related cellular damage
1.
2.
Blocks formation of harmful sugar products Prevents and protect tissue structure and function
i.e. i.e. i.e. retinal damage nerve function damage nephropathy
www.diabetesincontrol.com
benfotiamine was shown to block at least 3 pathways of hyperglycemia mediated vascular damage
1. hexosamine pathway (increased PAI 1 & clotting) 2. protein kinase C and vasc leakage and VEGF 3. AGEs & crosslinking 4. Polyol (sorbitol)
Diabetes: A Systemic Disease

Leading cause of blindness in working age adults Diabetic Retinopathy 2- to 4- fold increase in cardiovascular mortality and stroke
Stroke
Diabetic Nephropathy Leading cause of end-stage renal disease
Cardiovascular Disease
Diabetic Neuropathy
Leading cause of non-traumatic lower extremity amputations
National Diabetes Information Clearinghouse. Diabetes StatisticsComplications of Diabetes. (website) Statistics http://www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm#comp. http://www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm#comp.
Lipoic Acid
Helps insulin transport glucose into cells Inhibits glycosylated attachment of sugar to protein Maintains eye and nerve health ( peripheral neuropathy) Also Acetyl-L-Carnosine (2 recent studies)- 500 & 1000mg
Nutrients against VEGF & neovascularization (in DM & AMD)

Genistein Curcumin EGCG Bioflavanoids Vitamin D
Learn To Love Indian Cuisine!
Tertiary (Add-On) Treatment for very High Risk & Active AMD Retinal Patients in place of Fish Oil Capsules (contains fish oil)
Oxidation Neovascularization
Inflammation Soy (genistein), Tumeric and & Vitamin D against neovascularization (wet AMD)
Inflammation promotes oxidative stress
Figure 5: HK Vincent and AG Taylor, Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans, International Journal of Obesity, 30 p400-18, 2006
16 Ways to Decrease Inflammation: Steve Pratt, MD

1. 2. 3.
4. 5. 6.
7. 8.
Ave 7-8 quality hrs sleep/night 10% weight if BMI over 25 Min 30 min/d moderate exercise most days Better = 60-90 min/d exercise most days Weight training 2-3x /wk Adequate quantities dietary fiber Eat high n-3 fatty acid fish 4x/wk, 3.5 oz/serving, (i.e. Wild Salmon best, then sardines, herring, tuna) & take 1-3 g fish oil capsules daily. 2 Tbsp ground flaxseed meal most days 1 - 1 oz walnuts 5x/wk
16 Ways to Decrease Inflammation

9.
1 c berries, cherries or purple grapes, or 4-8 oz 100% pomegranate juice (or purple grape juice) daily--better yet, bathe each meal with berries, cherries, grapes, pomegranate juice Fasting blood sugar 75 mg/dL 2 Tbsp extra-virgin cold pressed olive oil most days High carotenoid diet Spice it up Prebiotics / probiotics Fruits & veggies unlimited Dark chocolate
10. 11.
12. 13. 14. 15. 16.
Communication
Physicians face numerous barriers when counseling patients on weight loss and risks, including how, when and with whom to have discussions Obese patients find the terms fat and obese highly derogatory, preferring excess weight or high BMI (Obes Res.
2003;11(9): 1140-6)
The vast majority of overweight (84%) and obese patients (97%) believe they need to lose weight, but fewer than 25% had discussed weight loss with their PCPs
(J Fam Pract. 2001;50(6): 513-18)
Effective Patient Communication

Ask for permission to discuss weight status
Be careful to distinguish between the weight problem and the person Focus on specific health risks (AMD, DR, cataract, CHD and cancer)
Assess motivation, current dietary and exercise status Build a partnership by helping patients set a few realistic goals
Walk 5,000 steps daily, lose 7% of weight, reduce BP by 10/5, increase MPOD, etc.
Conclusion
Battling ocular & systemic complications of obesity is analogous to keeping an overflowing bathtub from ruining the bathroom floor Turn off the faucet: reduce calories,
increase exercise, control blood glucose & blood pressure, treat any OSAS Bail the water and pull the plug: lose weight, especially VAT that drives IR, HTN, ROS and inflammation Mop up the floor: eat an antiinflammatory diet, use synergistic antioxidants & micronutrients to target the metabolic abnormalities of obesity
Caloric restriction Increase energy expenditure BG and BP control CPAP for OSAS
TURN OFF the FAUCET
BAIL the BATH/Pull the Plug

Caloric restriction Exercise Pharmacotherapy
Sibutramine, Orlistat, rimonabant
Targeted Antioxidants Targeted micronutrients Anti-inflammatory Diet
Bariatric Surgery
MOP UP the FLOOR
THANK YOU !
A Society Whose Time Has Come www.optometricnutritionsociety .org

Obesity Diabetes and Complications

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Obesity, Diabetes & Complications COPE #7999-GO

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A mere 1 in 5 are having this need met..

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Turn Off the Faucet

Bail the Tub

Pull the Plug

Mop Up the Floor

Why is Obesity Associated With Ocular & Systemic Disease?

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Subcutaneous vs. Visceral Fat

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Fat Cells Are Endocrine Cells!!

Inflammation & Oxidative Stress

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Hypercoaguability Vasoconstriction Inflammation

Inflammation iron metabolism

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Increased Oxidative Stress

Hunger & Increased Caloric Intake

Blunted Satiety Receptors

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OBSTRUCTIVE SLEEP APNEA

ROS Endothelial Dysfunction

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Clinical Entities: Eye Disease Associated with Obesity

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Metabolic Syndrome increases risk of cataract by 30-40% (Eur J Ophthal.

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Floppy Eyelid Syndrome prevalence - 25%

Pseudotumor Cerebri (15-40%)

Higher IOP also associated with obesity

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Marked obesity increases the risk of DR (Diabetes Care. 1986;9(4): 961-9)

Venous Occlusive Disease

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Epidemiology and Definitions

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1 in 3 Children Born in 2000 will develop Diabetes

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BMI = Weight (kg)/Height (m)2

Children & Teens

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Other measures of obesity

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Biologic Rationale For Specific Macronutrients

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