Obesity & Metabolic Syndrome Flashcards
BMI Categories
Underweight: < 18.5 Normal: 18.5-24.9 Overweight: 25 - 29.9 Obese: 30-39.9 Severely Obese: 40+
Weight circumference measurements indicative of high metabolic risk
> 40” in men
> 35” in women
*Measured at the top of the iliac crest
Metabolic Syndrome - Diagnostic Critiera
Waist circumference > 40” (for men) or > 35” (for women), plus 3 or more of the following:
Elevated triglycerides (>150) - or on TG lowering meds Low HDL (130/85) - or on anti-hypertensives Impaired fasting glucose (>100) - or on hypoglycemic
Steps in clinical evaluation of obese patients
- Measure degree of adiposity
- Assess other existing risk factors for cardiovascular disease
- Screen for complications of obesity
- Rule out medical causes of obesity
- Assess readiness for treatment
Diet Guidelines for weight loss
Reduce daily calories by 500-1,000 (20-40% of calorie requirement)
Target calorie goal: 1,200-1,500 (< 250 lbs) or 1,500-1,800 (> 250 lbs)
Reduce portion sizes by 1/4 to 1/3
Low fat (55%)
Exercise Guidelines
Minimum 30 minutes moderate activity/day; ideally 60 minutes
Weight loss maintenance requires physical activity at a threshold level of 328 calories/day; equivalent to 35 minutes vigorous or 70 minutes moderate activity/day
Weight loss maintenance lessons
Low calorie intake: 1,300-1,400/day Low fat (20-20%) high carbohydrate 1 hour/day of moderate activity Regular self monitoring Eat breakfast 11,000 steps/day
Lateral hypothalamus
“Hunger center” of the brain; stimulation produces voracious eating, lesions produce aphagia
Mediated by melanin concentrating hormone (MCH) and orexins (hypocretins)
Glucose is inhibitory
Which centrally released hormones mediate hunger?
Melanin concentrating hormone (MCH) and orexins (hypocretins) from the lateral hypothalamus
Ventromedial nucleus
“Satiety center”
Stimulation results in cessation of eating, even in hungry animals; animals with lesions eat excessively and become obese due to re-setting of weight to a higher level
Glucose is excitatory
Arcuate nucleus
Contains populations of neurons which respond to peripherally generated hormones to either increase hunger or satiety
NPY/AgRP neurons activate feeding
POMC/CART neurons activate satiety
a-MSH
a-MSH is a precursor of the proopiomelanocortin (POMC) precursor molecule
Released by cells of the POMC/CART population of the arcuate nucleus in response to leptin and insulin
Interacts with the MCR in the LH/PVN to produce satiety
Ghrelin
Gut peptide secreted from the stomach; blood concentration peaks prior to a meal to induce feeding
Receptors located in the arcuate nucleus; ghrelin activates the NPY/AgRP population of arcuate neurons
CCK
Released from the duodenum in response to the presence of nutrients from the stomach
CCK activates vagal afferents which project to the hypothalamus, signaling satiety
PPY
Released from L cells of the distal ileum in response to nutrients
Inhibits hypothalamic NPY/AgRP system, inducing satiety
GLP-1
Released by L-cells of the distal ileum in response to the arrival of nutrients
Potentiates insulin release and acts via the NST to induce satiety
Insulin
Circulates at levels that parallel body fat mass; insulin concentrations are well correlated with body fat content
Insulin receptors are located in the glucose-sensitive regions of the hypothalamus, i.e.:
In the LH (‘hunger center’) where glucose is inhibitory
In the VMN (‘satiety center’) where glucose is excitatory
Leptin
Peptide hormone produced from adipose tissue; acts on the brain to decrease appetite and increase metabolic rate via activation of POMC/CART and inhibition of NPY/AgRP in the arcuate nucleus
Phentermine
Chemically related to amphetamine; increases brain NE without risk of abuse, acts centrally to increase satiety and decrease food intake
Adverse effects: Nervousness, insomnia, headache, xerostomia, hypertension
FDA approved for 3 months; achieves ~5% baseline weight loss
Orlistat (Xenica, Alli)
Pancreatic lipase inhibitor; inhibits absorption of dietary fat from GI tract
No systemic side effects (not systemically absorbed); may cause fatty stools, diarrhea, fat soluble vitamin deficiency
DDIs: Warfarin (increased INR), cyclosporine
Achieves ~5% baseline weight loss; may prevent development of diabetes in high risk individuals; improves blood lipids and lowers HbA1C in people with diabetes
Lorcarsin
Serotonin 2C receptor agonist; serotonin 2C receptors are found only in the brain (no cardiotoxicity)
Achieves ~5% baseline weight loss
Phentermine/Topiramate
Significantly greater weight loss efficacy (10-12% of baseline weight)
Side effects: Paresthesias, insomnia, irritability, anxiety; topiramate is teratogenic and requires monthly pregnancy monitoring
Naltrexone / Buproprion
Opioid antagonist / NDRI
Achieves ~5% baseline weight loss
Side effects: Black box warning for suicidal ideation, reduced seizure threshold, hypertension, tachycardia, elevated LFTs, glaucoma
Atypical antipsychotics least associated with weight gain
Ziprasidone (Geodon)
Aripriprazole (Abilify)
