Nyenwe - Obesity Flashcards
(34 cards)
1
Q
Obesity basics
A
- Excessive adipose tissue
- Chronic, relapsing condition
- Genetics, environment, and behavior contribute to etiology
- Driver of multiple risk factors that INC morbidity and mortality
2
Q
What are the BMI categories? How do these correlate with risk of disease?
A
- Underweight: <18.5 -> INC risk of disease
- Normal: 18.5-24.9
- Overweight: 25-29.9 -> INC risk of disease
- Obese I: 30-34.9 -> high risk of disease
- Obese II: 35-39.9 -> very high risk of disease
- Extreme obesity (III): >= 40 -> extremely high risk of disease
- GRAPH: multivariate RR of death from CV disease, cancer, and all other causes
3
Q
Why is waist circumference important? What measurements yield high risk of disease?
A
- Indirect measure of central adiposity, correlated with visceral fat
- Excess fat in the abdomen is an INDEPENDENT PREDICTOR of risk factors and morbidity
- High risk: >40 inches for men, and >35 for women
4
Q
How has obesity trended in the past 25 years?
A
UP
5
Q
What are the basic contributing factors to obesity?
A
- About 50% genetic predisposition
- Chronic disequilibrium between intake and output
6
Q
What are the monogenic causes of obesity? How common are they?
A
- RARE: <5% of cases
- Melanocortin-4 receptor mutations (attached)
- Leptin deficiency/leptin receptor deficiency
- POMC (proopiomelanocortin) gene mutations
- Prohormone convertase-1 mutations
- PPAR (peroxisome proliferator-activated receptor)-gamma-2 mutations
- Thyroid hormone receptor-beta mutations
7
Q
How does genetics contribute to obesity?
A
- POLYGENIC
- Can only explain about 50%, even all added together
8
Q
What substances promote positive energy balance (weight gain)?
A
- Neuropeptide Y
- Melanin-concentrating hormone
- Agouti-related peptide
- Ghrelin
- Galanin, Dynorphin, beta-endorphin
- Orexin A and B
- NE, epinephrine
- Opioids
- GHRH, Somatostatin
- Androgen, progesterone
- Endocannabinoids
9
Q
What substances promote negative energy balance (weight loss)?
A
- Leptin: produces anorexia and weight loss
- Peptide YY
- Ciliary neutrotrophic factor, Insulin (promotes satiety)
- Alpha-melanocyte-stimulating hormone
- Glucagon-like peptide-1
- Urocortin, Neurotensin
- CRH, Bombesin
- Cocaine-amphetamine-regulated peptide (CART)
- Serotonin
- Cholecystokinin, Enterostatin
- Dopamine
10
Q
Why can leptin therapy be useful?
A
- Leptin produces anorexia and weight loss
11
Q
What is leptin? What does it do?
A
- Leptin is made by fat cells
- The more adipose you have, the more leptin you make -> body sees this as there being plenty of resources, so you don’t need more
-
INH agouti-related protein and neuropeptide Y
1. MCH and orexin orexigenic effectors - Also stimulates alpha-MSH, which has an appetite suppressant effect (from POMC) —> acts through MC4R
1. CRH and TRH anorexigenic effectors - Produces ANOREXIA and WEIGHT LOSS: reduces food intake and INC energy expenditure
12
Q
What 3 factors contribute to energy expenditure? Why is this important in obesity?
A
- 70% expenditure from basal metabolic rate (this diminishes as we grow older
1. Can INC this by exercising - 10% from thermic effect of food
- One way to tip the balance is to INC our physical activity, which is 20% of expenditure
- Balance between energy intake and energy expenditure -> the difference is stored as fat
13
Q
Fecal matter and obesity?
A
- New area of research in obesity
- Fecal matter transplant resulted in weight gain (from obese to lean mice)
- It is possible that the microbiota/flora play a role in obesity
14
Q
What is the endocannabinoid system?
A
- Endogenous signaling system discovered in 1990s via research into psychoactive props of THC
- 2 types of receptors: CB1 and CB2, and several endogenous compounds, incl anandamide
- Generally silent, but becomes activated to:
1. Reduce pain and anxiety
2. Modulate body temp, hormone release, and smooth muscle tone
3. Inhibit motor behavior
4. Extinguish aversive memories
5. Induce appetite, contributing to obesity
15
Q
What happens in endocannabinoid system overactivity?
A
- Brain:
1. Hypothalamus: INC hunger
2. Nucleus accumbens: INC motivation to eat
3. INC food intake + INC fat storage - Peripheral tissues (adipose, liver, GI, muscle):
1. INC insulin resistance, DEC glucose uptake
2. DEC HDL-C, INC TG
3. DEC adiponectin (synergistic effects with leptin)
16
Q
What are some of the comorbidities of obesity?
A
- NAFLD: non-alcoholic fatty liver disease
- DJD: degenerative joint disease
17
Q
How can obesity lead to DM, HTN, CAD, and CHF? Describe the “flow chart.”
A
- Residual fat becomes a reservoir of fatty acids that can be delivered to the liver to make cholesterol; body can only get rid of this cholesterol via bile, pre-exposing you to gallstones
- High FA in the blood can be toxic to beta cells of the pancreas too (lipotoxicity) —> can contribute to diabetes
- Hyperinsulinemia is also a known risk factor for some types of cancer
- INC SYM tone leads to HTN via effects on blood vessels, heart, and kidneys
- Obesity directly related to some diseases, like T2D (i.e., controlling weight can relieve disease) -> for others, cause and effect is not as well established
18
Q
What are the treatment categories for obesity?
A
-
Lifestyle modification
1. Diet: Atkins, South Beach, Mediterranean, DASH, etc.
2. Physical activity
3. Behavior modification - Pharmacotherapy: phentermine, topiramate, rimonabant, liraglutide, orlistat, etc.
- Surgery: lapband, vertical banded gastroplasty, gastric bypass, biliopancreatic diversion w/duodenal switch
19
Q
How does most obesity pharmacotherapy work? What is the exception?
A
- Most work through central mechanism
- Orlistat: only one that works through the gut, INH breakdown of fat, and producing malabsorption
20
Q
Phentermine
A
- CNS
- Stimulates NE release
- (+) anti-convulsant: Topiramate (anorexigenic effect)
21
Q
What obesity drugs are serotonergic?
A
- Dexfenfluramine, Fenfluramine: INC release of serotonin and DEC reuptake of serotonin
- Lorcaserin: 5HT2c (serotonin) receptor agonist
22
Q
Sibutramine
A
- Blocks NE, serotonin, and dopamine reuptake
23
Q
Rimonabant
A
- Cannabinoid receptor antagonist
- Depression is the major side effect (not approved by the FDA because of this)
24
Q
Liraglutide
A
- GLP-1
- Anti-diabetes drug that can produce significant weight loss at higher dose
25
Orlistat
- INH of lipase in the gut
- Only obesity drug that doesn't work in the CNS
26
Is behavior modification of pharmacotherapy more beneficial for weight loss?
- Behavior modification, but the COMBO is most effective
- He said pharmacotherapy alone is NOT effective
27
What are the bariatric surgeries? Most effective? Mortality benefit?
- _Procedures_ (restriction to malabsorption): lapband, vertical banded gastroplasty, gastric bypass, biliopancreatic diversion with duodenal switch (BPD)
- BPD most effective at initial weight loss, then bypass, then gastroplasty
1. All sxs: 29.7kg weight loss, 14.2 BMI DEC, 32.6% initial weight loss
- Very small mortality from the procedures, and **reduction in overall morbidity/mortality** in most studies
1. 30/40% risk reduction in 2 studies; no change in another
28
What are the health benefits of modest weight loss?
- Weight loss of 5%–10% in obese ppl with type 2 diabetes, hypertension or dyslipidemia resulted in:
1. Improved diabetes control (remission ~16%)
2. Improved blood pressure control
3. Improved lipid profile
4. Need for fewer medications
29
What are the predictors of T2D remission in obese patients who lose weight (LOOK AHEAD)?
- \<2-yr history of diabetes (21%)
- \>6.5% weight loss (16%)
- Fitness improvements (15%)
- Low initial HbA1c values (17%)
- No BP meds (15%)
30
Describe the obesity tx pyramid (image).
31
What is obesity? Highest risk?
- BMI measurement of 30 and above considered obese
- Highest risk at BMI of 40 or more
32
Describe the regulation of body weight. What are some things that cause weight gain/loss?
- Energy intake vs. output
- GLP-1 inhibits appetite
- Agouti-related peptide stimulates appetite
- Ghrelin comes from the stomach, and stimulates appetite
33
What effect does insulin have on appetitie?
Insulin is an appetite suppressant
34
Name some factors that have an orexigenic effect.
- Neuropeptide Y
- Agouti-related peptide
- Ghrelin
- Endocannabinoid system
