® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

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BiomarkersofWellness Slide 2 What Gets Measured- Gets Managed Gets Managed Peter Drucker Slide 3 Slide 4 Body Mass Index (BMI) BMI = Weight (in kg) Height 2 (in meters) BMI = Weight (in kg) Height 2 (in meters) Lbs/ inches 2 x 703 Lbs/ inches 2 x 703 A BMI of A BMI of 30 = obese Slide 5 Slide 6 Relationship of BMI to Excess Mortality 20-40yoa 300 Age at Issue Bray GA. Overweight is risking fate. Definition, classification, prevalence and risks. Ann NY Acad Sci 1987;499:14-28. 20-29 250 Mortality Ratio Body Mass Index (kg/[m 2 ]) 200 150 100 50 15 0 30-39 202530 Low Risk 4035 High Risk Moderate Risk Slide 7 BMI & Obesity Sample size and weight status NHE S I 1960 - 1962 NHANE S I 1971- 1974 NHANE S II 1976- 1980 NHANE S III 1988- 1994 NHANE S 1999- 2000 NHANE S 2001- 2002 NHANE S 2003- 2004 NHANE S 2005- 2006 NHANE S 2007- 2008 Sample (n)6,12612,91111,76514,4683,6033,9163,7563,8354,881 Overweight (25 BMI < 30) 31.532.332.132.733.634.433.432.233.6 Obese (BMI 30) 13.414.515.023.230.931.332.935.134.3 Extremely obese (BMI 40) 0.91.31.43.05.05.45.16.26.0 The 773 morbidly obese female members had used a mean of $11,145 in medical insurance expenses in the year 2003 versus a mean of $8,096 for the other 106,908 adult women (27% higher). Similar values for the men were $16,720 for the 138 morbidly obese men versus $5,943 for the other 82,490 men. (64% higher) Slide 8 While BMI certainly tells us how unhealthy a person is, it doesnt tell us how healthy a person is. Example, a skinny fat person aka sarcopenic obesity Slide 9 #1 Biomarker of Aging... no decline with age is as dramatic or potentially more significant than the decline in lean body mass. J Nutr 127:990S-991S (1997) Slide 10 Over a lifetime 30% of muscle mass is lost Over a lifetime 30% of muscle mass is lost From age 20, women lost 5 7 lbs of muscle @ decade From age 20, women lost 5 7 lbs of muscle @ decade 25% weight loss on a typical diet is muscle 25% weight loss on a typical diet is muscle One lb of muscle burns at least 3Xs the calories as one lb of fat One lb of muscle burns at least 3Xs the calories as one lb of fat Body Fat Slide 11 Biochemistry of Vitamin D Slide 12 What is a vitamin? Organic compound Required to support life Generally a co-factor for enzyme activation (most B vitamins) or antioxidant (E and C) Must be obtained from the diet Cannot be synthesized in adequate quantities Slide 13 Vitamin D, on the other hand Can be synthesized in the body Has receptors and target tissues More accurately characterized as a pro-hormone Since it is synthesized by the body from cholesterol, it is not necessarily essential that it be supplied by diet. Slide 14 Historical understanding of vitamin D Fundamental to calcium and phosphorus metabolism Deficiencies/insufficiencies related to: Rickets Osteomalacia Osteoporosis 400 IU/day is currently the RDI The amount shown to prevent rickets Slide 15 Vitamin D is called the sunshine vitamin It is manufactured in the skin from cholesterol upon exposure to UV radiation. Healthy (RDI) levels of vitamin D production can be achieved by: 10-15 minutes of sun exposure Hands, forearms and face 3-5 times per week Spring, summer fall months only Slide 16 Dietary vitamin D is found in two forms: Vegetable Ergocalciferol/D 2 Manufactured from the plant sterol ergosterol Synthetic form of the vitamin Animal Cholecalciferol/D 3 Manufactured from cholesterol Both can be converted to active hormone 1,25-(OH) 2 D 3, (also called calcitriol) via a two-step hydroxylation first in the liver, then in the kidneys. May also be hydroxylated in the colon, breast, lungs and prostate. Slide 17 Look a bit closer and vitamin D gets more interesting Vitamin D regulates uptake of calcium from the gut through stimulation of gene expression Activating the production of calcium-binding proteins such as calbindin that increase calcium absorption. Upwards of 200 genes are believed to be regulated by Vitamin D, most of which are not involved in mineral metabolism. Essentially every tissue and cell in the body has a vitamin D receptor. Slide 18 Blood levels of vitamin D below 20 ng/mL led to 30-50% increased risk of developing and dying from various cancers (colorectal, breast, prostate etc.) Low 25(OH)D levels are associated with all-cause mortality and even more pronounced with cardiovascular mortality Women with blood vitamin D levelSlide 19 Theres more Low sun exposure for the first 10 years of life doubles the risk to multiple sclerosis development. Children receiving ~2000 IU of vitamin D daily had 78% reduced risk to development of type I diabetes. Vitamin D lowered BP to normal levels Low blood vitamin D level is associated with depression, autoimmune disease, osteoarthritis, increased susceptibility to infection, even postulated as a cause of seasonal cold and flu. Slide 20 Today, a number of factors have contributed to what one researcher calls a deficiency pandemic of vitamin D Aggressive campaign to use sunscreen has led to a significant segment of the population with vitamin D deficiency Use of sunscreen results in a 99% reduction of vitamin D production Fewer people get out in the sun regularly Fear of skin cancer Work location/habits (garage to car to office to car to garage) Changing perceptions of beauty Aging and skin tone reduce the efficiency of vitamin D synthesis People of color require 5-10 times longer sun exposure compared to Caucasians to make the same amount of vitamin D Slide 21 Vitamin D levels in our society An estimated 1 billion people worldwide are thus considered deficient Adults >65 52% of postmenopausal women 36% of young adults 18-29 had vit D levelsSlide 22 Current requirements: 30 ng/mL:adequate >30 ng/mL:adequate If insufficient or deficient, it may take >10,000 IU/day to attain adequate levels. If insufficient or deficient, it may take >10,000 IU/day to attain adequate levels. Slide 23 To sum up Vitamin D has evolved into a hormone that is active throughout the body, not only to regulate calcium and bone metabolism, but to control cellular growth, regulate immune function, and control production of insulin and renin among other hormones. All healthcare professionals should be alert to the vitamin D deficiency pandemic. Michael Holick, University of Boston Slide 24 Waist/Hip Ratio Waist/Hip Ratio Waist/Hip Ratio Ideal:.7050 37/hr for diuretics; $715/yr Norvasc (2002) Slide 28 2006 Top 10 Drugs Drug Name Sales in Billions Drug Use 1Lipitor14,385Cholesterol 2 Advair, Seretide 6,129Asthma 3Plavix, Iscover6,057Thrombotic events 4Nexium5,182Gastrointestinal disorders 5Norvasc4,866Hypertension 6Remicade4,428 Crohn's disease, Rheumatoid arthritis 7Enbrel4,379Rheumatoid arthritis 8Zyprexa4,364Psychosis 9Diovan4,223Hypertension 10Risperdal4,183Psychosis Slide 29 In case you were wondering 9 billion dollars will buy 3,409,090 8 Weeks to Wellness Programs in our office 2,141,051 8 Weeks to Wellness Programs in Dr. Prakashs office Slide 30 Sugar Biomarkers Diabetes is the seventh leading cause of death listed on U.S. death certificates. Diabetes is the seventh leading cause of death listed on U.S. death certificates. Cardiovascular disease is the leading cause of death among people with diabetes about 68 percent die of heart disease or stroke. Cardiovascular disease is the leading cause of death among people with diabetes about 68 percent die of heart disease or stroke. Total health care and related costs for the treatment of diabetes run about $174 billion annually. Total health care and related costs for the treatment of diabetes run about $174 billion annually. Actos world wide drug sales are $2.5 Billion, the 9 th best selling drug in America. Actos world wide drug sales are $2.5 Billion, the 9 th best selling drug in America. In 1967, 3000 tons of HCFS were produced and 2007 over 9,000,000 tons of HCFS were produced In 1967, 3000 tons of HCFS were produced and 2007 over 9,000,000 tons of HCFS were produced Slide 31 How much sugar is in your body 100mgx 10 dl X 5 liters X 1 grams = 5 grams = 1 teaspoon dl liter 1000 mg Normal Fasting Glucose: 80-100 mg/dl Slide 32 A BMJ investigation into the top-selling diabetes drug rosiglitazone (Avandia) raises concerns about its safety and the whole system by which drugs are evaluated, regulated, and promoted around the world. Sept. 7, 2010 Slide 33 HbA1C Equal to % of RBCs that are glycated Equal to % of RBCs that are glycated You can run but you cant hide from HbA1C because once a RBC is glycated, it stays that way. You can run but you cant hide from HbA1C because once a RBC is glycated, it stays that way. The predictive value of HbA1C for total mortality was stronger than that documented for cholesterol concentration, body mass index and blood pressure. BMJ 2001 The predictive value of HbA1C for total mortality was stronger than that documented for cholesterol concentration, body mass index and blood pressure. BMJ 2001 Slide 34 HbA1C (%)(mg/dL) 5 97 (76 120) 6 126 (100 152) 7 154 (123 185) 8 183 (147 217) 9 212 (170 249) 10 240 (193 282) 11 269 (217 314) 12 298 (240 347) Slide 35 Insulin Fasting Insulin Fasting Insulin Increased insulin production causes insulin resistance Hyperinsulinemia is associatd with inflammastion in the brain and triggers increase in plaques that are hallmark of Alzheimers (JAMA 2006) Hyperinsulinemia is associatd with inflammastion in the brain and triggers increase in plaques that are hallmark of Alzheimers (JAMA 2006) The neurodengeration that occurs in AD is linked with abnormal insulin signaling (J Alzheimers Disease 2005) The neurodengeration that occurs in AD is linked with abnormal insulin signaling (J Alzheimers Disease 2005) Insulin resistance also linked to depression, bipolar disease, autism, and schizophrenia. Insulin resistance also linked to depression, bipolar disease, autism, and schizophrenia. Slide 36 Lipid Bi