J.

Matthew Andry, J y, MD
IU Health Bloomington MDWeightWoRx BeWell Grant Grant-Centerstone Centerstone

1. 2. 3 3. 4.

Nutrition/Diet Physical Activity Behavior Management Medical Treatment

1 1. 2. 3.

Evaluate and optimize current meds Endocrine/Hormone management Psychiatric y treatment

Why don dont t programs always work?

Compliance Readiness Medications Saboteurs Discipline Evolution???

The Body resists weight loss. Why???

We have the SAME genetics as those whose genes were selected for in a calorie poor environment. It believes there will be a famine tomorrow No Weight Set Point. The heavier the better Energy Savings Account

Not about Anti Anti-Aging Aging Not about Body Building Its It s about: HOMEOSTASIS Not about maximizing hormone levels Its It s about balancing hormone levels and rere approximating normal/optimal function in disordered body y systems y Too much can be just as bad as not enough

$$$
TIME!!
CALORIES IN

Social

Metabolic
(Hormones)

y Psych

Metabolic/Hormonal Influences

Insulin Leptin p NPY Ghrelin Glucagon Amylin Et Etc

Calories Out
10% DIGESTION

70%
20% PHYSICAL ACTIVITY

RESTING METABOLIC RATE

CALORIES OUT

Obesity y is a result of energy gy imbalance. Loss of Homeostasis. Hormones are substances released from specific ifi places l i in the h b body d to cause specific ifi effects in different tissues Hormones are the currency currency of homeostasis Innumerable hormones involved with weight management. g Improper hormone balance can be a major cause of weight gain and hinder weight loss. P bl Problems arise i f from too much h and d too li little. l

Insulin/Glucose Metabolism Thyroid Estrogen/Progesterone Testosterone

1 in 3 Americans have insulin resistance Require high levels of insulin to control g glucose. This causes a reflexive hypoglycemia and leads to overeating, g especially p y of carbohydrates y

Glucose & Insulin Levels in Insulin Resistance

Glucose

Insulin

Hyperinsulinemia leads to:

Hypoglycemia Hyperphagia/carbohydrate yp p g y cravings g Cortisol release Increased Fat Storage (incr. lipoprotein lipase) Fatigue Disrupts other hormone systems

High Protein Intake

Delayed rise in glucose due to prolonged digestion Gives insulin more time to work at lower levels Pushes glucose into cells Increased muscle mass improves Insulin Sensitivity Metformin, Januvia, Vytorin, Byetta

Exercise

Medications

Biguanide. g Used for over 50 y years Can treat AND prevent Diabetes

Decreases diabetes risk by one third!!!

Mechanism: Drives glucose into cells and inhibits glucagon conversion on glycogen to glucose in the liver. liver Have to have healthy kidneys Watch Liver Enzymes closely (NASH???) Treatment of choice in Insulin Resistance Syndromes y

J Januvia, , Onglyza, g y , Tradjenta, j , et al. DPP4 inhibitors

DPP4 is an enzyme that breaks down GLP-1

They increase GLP-1 Activity GLP-1: an incretin: released from the gut after f di food intake t k t to assist i t appropriate i t i insulin li release, inhibits glucagon, and SLOWS GASTRIC EMPTYING. Low risk for hypoglycemia Safe, , but subtle and expensive! p

Byetta ( (lizard lizard spit), spit ), Vytorin These are ANALOGUES of GLP-1. Stronger More effective Stronger, effective, Studied for weight loss, Expensive SQ Injections Can cause lots of Nausea and vomitting if client overeats Low risk for hypoglycemia

Active in all body cells, many functions:

Energy/Glucose Utilization, Body Temperature, Catecholamine sensitivity, Heart Rate, Fat utilization, Growth, Memory and Concentration

Produces T4 (which the body converts to T3) Production d controlled ll d by b the h pituitary gland l d and its release of Thyroid Stimulating Hormone (TSH)

Low Thyroid y can be a major j barrier to weight g loss. Low Thyroid Symptoms:

Cold Intolerance, Low BBT Goiter (from TSH overstimulation) Weight Gain Menorrhagia Edema Brain Fog Heart arrythmias D Depression i

AutoImmune, Surgical, Secondary, Idiopathic

Hashimotos is Most Common

Assessed by y levels of TSH ( (longer g half-life than T4 and T3) Problem: What is a normal TSH?? Major debate in Endocrinology currently Normal values 0.34 mIU/L N / to 5.6 mIU/L / What is an Optimal TSH?

Probably y less than 2.0 ( (Some say y less than 1.0) )

Treat with:

Iodine Supplementation Synthetic y T4 ( (Synthroid) y ) Synthetic T3 (Cytomel) Natural Thyroid (Armour) Compounded Formulations (specific ratios, individualized per patient)

Overtreatment, not good either:

Osteoporosis and Osteopenia

Dexa Scans, NTx Ratio

Cardiac problems, arrhythmias, cardiomyopathy Wasting of lean tissue Anxiety Tremors

Menopause and Perimenopause Imbalances in E and P are common during this p period. Estrogen Dominance very common

New Name? Insulin Related Sex Hormone Dysfunction Extremely y common 4-12% of the p population. p (much higher for sub-acute forms) Leading hormonal cause of infertility High insulin increases GnRH pulse frequency, raising LH, lowering FSH. Leads to high androgens and low SHBG
Waldstreicher et al. 1988, , Morales et al. 1996 MacArthur et al. 1958, Yen et al. 1970

Clinical Features:

Weight Gain Anovulation Acne Hirsutism Insulin Resistance/Hyperinsulinemia Edema I Irregular/painful l / i f l periods i d Infertility Ovarian Cysts

Inability to lose weight PMS-type symptoms Headaches Edema Anxiety/Depression Insomnia Nausea/Bloating

Estrogen and Progesterone levels fall as approach menopause. Often P falls farther faster than E. ( (Especially p y if excess adipose tissue, which produces E) Occurs despite p monthly y cycling. y g

Is it safe? Womens Health Initiative Recent Reversal At least safe, at best, effective for breast cancer prevention

( (Think PMS) ) Headaches (migraine) Fluid Retention Breast Tenderness Weight Gain (hips) F ti Fatigue Anxiety Insomnia Dysmenorrhea Decreased Libido

( (More Serious Risks) ) Endometrial/Breast Hyper plasia O i C Ovarian Cysts Insulin Resistance Fibroids Endometriosis Fibrocystic y Breasts Infertility Blood Clots

Treat by methods to reduce Estrogen

Weight Loss High g Fiber Diet Reduce insulin resistance Avoid extrinsic Estrogens: soy, chemicals, pesticides

Replace/Augment Progesterone itself

Can use progestins (but have significant risks) Natural progesterone

Topical or Oral or injectable

Males lose about 3% Free T p per y year after 40.1 Functions pertaining to weight:

Increase lean mass, decrease body fat Increases insulin sensitivity Deficiencies lead to fat accumulation, insulin resistance and diabetes Can increase appetite Debate on what are normal levels

1 Feldman 1. Feldman, et al , J Clin Endocrinol Metab 2002; 87:8998. 87:8998

HRT. Is it safe? WHI: 2002. Stopped early due to 0.3%/yr risk increase in breast cancer for women taking g Premarin and Provera. Millions of women told to stop p hormones Instructed smallest dose for shortest time Results were extrapolated p to all hormones Why??? Not evidence based to do so.

HRT is it safe?

April 2011 JAMA2011;305(13):1305-1314.

Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy
Andrea Z. LaCroix, PhD; Rowan T. Chlebowski, MD, PhD; JoAnn E. Manson, MD, DrPH; Aaron K. Aragaki, MS; Karen C.

J Johnson,MD,MPH; , , ; Lisa Martin, , MD; ; Karen L. Margolis, g , MD, , MPH; ; Marcia L. Stefanick, , PhD; Robert Brzyski, MD, PhD; J. David Curb, MD, MPH; Barbara V. Howard, PhD; Cora E. Lewis, MD, MSPH; Jean Wactawski-Wende, PhD for the WHI Investigators

HRT is it safe?

April 2011 JAMA2011;305(13):1305-1314.

Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy
Johnson,MD,MPH; J , , ; Lisa Martin, , MD; ; Karen L. Margolis, g , MD, , MPH; ; Marcia L. Stefanick, , PhD; ; Robert Brzyski, MD, PhD; J. David Curb, MD, MPH; Barbara V. Howard, PhD; Cora E. Lewis, MD, MSPH; Jean Wactawski-Wende, PhD for the WHI Investigators
Andrea Z. LaCroix, PhD; Rowan T. Chlebowski, MD, PhD; JoAnn E. Manson, MD, DrPH; Aaron K. Aragaki, MS; Karen C.

25% DECREASE in BRCA in women on Premarin only over placebo

N New G Guidelines???? id li ????

Topical versus Injectable Multiple New Agents Again too much not great either Again, Risks: irritability, erythrocytosis, elevated cholesterol, hair loss, BPH No evidence it causes Prostate Cancer. Some that it decreases it. Can make an active cancer grow faster Will raise E2 levels as well, close monitoring g

In y younger g males ( <45-50), ), can use agents g to increase endogenous Testosterone production Cl id/A i d Clomid/Arimadex

Clomid a SERM. Raises LH and FSH Arimadex Aromatase inhibitor, , raises LH

HCG (Human Chorionic Gonadotropin)

Functions like LH in the male Increases T production, partial estrogen reducer Tends e ds to cause weight e g t loss oss ( (hypothalamic ypot a a c moa??) oa??)

Cycloset y .

New medication for diabetes. Increases DA activity in the hypothalamus Moves glucose into cells Improves pp glucose w/o increasing insulin! Seems to increase glucose utilization Helps with dysmetabolism and dysglycemia, may be particularly helpful in circadian misalignment (night shift workers).

Scranton, et al, BMC endocrine disorders 2007 Jun 25;7:3