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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
. 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
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
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-
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
Disease
Inflammatory Cytokines
TNF- PAI-1 ICAMs CRP FFAs Adipokines
Iron Overload
Metabolic Hp Genotype Diet
Obesity
VAT
Insulin Resistance
Skeletal Muscle Liver Hypothalamus
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
Inflammation
Hypertension
Hypoxia
Cataract
BMI > 30 increased risk of PSC and cortical cataract (Blue Mountains Eye Study.
Ophthalmic Epidemiol. 2003;10(4):227-40)
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)
J Neuroophthal
OSAS is the most frequent disorder in patients with NAION (BJO. 2006;90(7):879-82)
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)
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)
1990
No Data <10% 10%14%
1998
15%19% 20%24%
2006
25%29% 30%
BMI > 30
Classic Definition
BMI BMI BMI BMI > 25 > 30 > 35 > 40 overweight obese severely obese morbidly obese
Girls
Boys
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
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
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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
Decrease triglycerides, LDL-C and oxidized LDL-C without decreasing HDL-C (J Nutr Biochem.
2006;17: 645-58)
High levels of MUFA in macadamia & olive oil, nuts and avocadoes
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
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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)
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)
100
%
Per NCEP ATP-III Criteria
40 20 0
10
Diets with high intake of fruits & vegetables are consistently associated with lower CV risk (JAMA
2002;288: 2569-78)
Fiber reduces CRP and TNF- (Diabetes Care 25 gm fiber reduces BP 6mm/4mm in hypertensive patients (J Hyperten. 2005;23(3):
475-81)
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)
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)
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
Criticisms: Many
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)
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.
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
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)
Killer Containers?
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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
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.
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.
in 2008,
Only 2% of Medical Students are Entering Primary Care Family and Preventive Medicine
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
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
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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)
CALORIC RESTRICTION
& EXERCISE
ADA
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
0 -2 -4 -6 -8 0 1 2
Years from Randomization
participants
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
20
10
0 0 1 2 3 4
Placebo
Metformin Lifestyle
3.
4.
5.
6.
7.
Glycemic load Fatty acid composition Macronutrient composition Micronutrient density Acid-base balance Sodiumpotassium ratio Fiber content
AGING
72%
Grain
Meat
Anatomy of www.MyPyramid.gov
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2005 for Americans (over age 2) One Size Doesnt Fit All
Nonsmoking (76 %) BMI 18.5 25 (40%) 5 or more F &V daily (23%) > 30 minutes physical activity 5 times per week (22%)
ORAC SCORES
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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
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
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
1 kg guinea pig
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Veterinarians know Cavies should receive between 2550mg of vitamin C daily Fresh fruits and vegetables high in vitamin C are a great source
Maybe thats why we need those 13 portions of fruits and vegetables per day, The average American consumes only 3 portions.
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
A9093
Even OTC Pharmaceuticals can induce nutritional deficiencies which are often treated with additional pharmaceuticals
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
Professor Thomas C Washer, Karl-Franzens University of Graz, Austria, Understanding Diabetes, Oxidative Stress and Vascular Complications in type 2 diabetes
Meglitinide
Thiazolidinediones
Insulin
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
Oxidative Stress is implicated in both the etiology & long term complications of diabetes
Environmental
Decreasing Decreasing Decreasing iron overload HFCS visceral fat (i.e. FFA)
Insulin Resistance
courtesy Bill Sardi
Iron overload = > increased ferritin = > inflammation = insulin resistance = > hunger = >caloric intake = obesity
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)
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
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(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)
Stroke
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
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)
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
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
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.
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)
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
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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
Bariatric Surgery
THANK YOU !