Lecture 10 - Managing and Preventing Metabolic Syndrome Flashcards Preview

BIOM30001 - Frontiers in Biomedicine > Lecture 10 - Managing and Preventing Metabolic Syndrome > Flashcards

Flashcards in Lecture 10 - Managing and Preventing Metabolic Syndrome Deck (18):
1

Describe the weight loss trial for MS

Individuals:
• BMI 30-35
• 38% Metabolic syndrome in both groups

Two groups:
1. Medical therapy
• VLCD
• Optifast
• Orlistat (inhibits lipase)
• Behavioural therapy

2. Surgical intervention
• LAP-BAND placement

Results:
• 0-6 mths: both groups showed same rates of weight loss
• >6 mths: medical group had weigh regain; surgical group had continued and sustained weight loss

Effects on MS:
• Medical group: 24% of individuals had MS at end
• Surgical group: 3% of individuals had MS at end

Conclusions:
• Surgical intervention with placement of LAP-BAND leads to superior weight loss and resolution of metabolic syndrome in comparison to medical therapy

2

Can genetics account for the epidemic of obesity?

No

Rates of obesity have increased from 7% to 18.4% in the last 30 years

Genetic drift does not occur at a rate to account for this

3

Describe Levin's study in mice of epigenetics in obesity

Two groups of mice:
1. CHOW diet
• 'Control'
• Normal weight gain over course of life

2. High energy diet
• Had increased weight gain over the course of life in comparison to CHOW

• HE mice were then placed on CHOW
• Mice lost weight
• These mice were then allowed to consume food at will
• These mice ate amounts such that they regained the weight lost and rebounded to their previous weight

Conclusion:
• Greater body mass is 'defended'

(What is the driver to this?
Hormones)

4

Describe the VLCD

Very low calorie diet

• Energy intake limited to 1.88-3.35 MJ daily

• >50g protein

• Essential fatty acids

• Trace elements, vitamins, minerals

• Fibre (to lessen hunger & constipation)

• Lasts 8-16 weeks

Only recommended in BMI > 30 (or 27 if there are one or more co-morbidities)

5

Describe the efficacy of diets in achieving and sustaining weight loss

Diets invariably fail

Weight may be lost initially, but the weight is then regained

This is the same whether it be VLCD alone, or in conjunction with exercise and/or behavioural therapy

6

Describe Proietto's 2011 paper that investigated long term persistence of hormonal adaptations to weight loss

Was looking at why diets fail to sustain weight loss

1. Group of overweight individuals in study

2. Baseline post-prandial hormone levels were measured (Ghrelin, PYY, CCK, Amylin)

3. Intervention: VLCD

4. Post-prandial hormone levels were re-tested

Results; after weight loss:
• Increased Ghrelin post-prandially
• Decreased CCK
• Decreased amylin
• Decreased PYY
• Decreased leptin
• Increased 'Hunger'
• Increased 'Desire to eat'

5. Weight was regained after intervention

6. Post-prandial hormone levels were retested
• Hunger suppressive hormones were still lower, and Ghrelin levels were still elevated

Implication:
• When weight is lost, the body alters hormone levels that have the net effect of increasing hunger
• These hormonal changes persist even after weight is regained

7

Describe the changes in energy expenditure when weight is lost or gained

Weigh gained:
• Increased energy expenditure

Weight lost:
• Decreased energy expenditure

This decreased energy expenditure persists for a long time after the weight is lost

8

Describe pharmacotherapy for weight loss

1. Phentermine
2. Topiramate (off-label)
3. Combination of the two

Diabetes:
1. Exenatide
2. Liraglutide

9

What are off-label drugs?

Use of the drug when it has not been approved for that use

10

Describe the effects of the drug Topiramate

Results in sustained weight loss after VLCD intervention, in comparison to placebo

However, has nasty adverse effects

11

Describe the efficacy of Ph/T combination therapy

Lead to more profound weigh loss than Phentermine on its own

12

Describe the side effects of Phentermine and Topiramate

Phentermine:
• Increased HR and BP
• Dry mouth
• Sleep disturbances
• Interactions with SSRIs

Topiramate:
• Parasthesiae
• Depression
• Memory loss
• etc.

13

Describe Proietto's recent paper looking at Ph/T combination therapy for weight loss

103 patients

The majority did not complete the trial due to the adverse effects

Those that remained on the drug had sustained weight loss

14

Describe the various options for bariatric surgery, and how each works

1. Adjustable gastric banding
• Band placed around the cardia of the stomach
• Size of stomach greatly restricted

2. Sleeve gastrectomy
• Large portion of stomach removed
• Lose cells that produce Ghrelin (-> reduced hunger)

3. Roux-en-Y bypass
• Bypass from cardia of stomach directly to intestine
• Undigested food in the small intestine stimulates the release of hunger suppressing hormones

15

Describe how the individual components of MS can be managed

1. Diabetes
a. Pharmacological
• Metformin
• Insulin therapy
• GLP-1 enhancing drugs
• Acarbose
• Sulphonylureas
b. Non-pharmacological
• Diet
• Exercise

2. BP
a. Pharmacological
• Beta blockers
• ACE inhibitors
• Thiazide diuretics
• Angiotensin II receptor blockers
• Ca2+ channel blockers

b. Non-pharmacological:
• Reduced salt intake

3. Lipids
a. Pharmacological
• TAGs: Fenofibrinate
• LDL: Statins
b. Non-pharmacological:
• Diet
• Exercise

4. Hyperuricaemia
• Allopurinol

16

Describe the hormonal axis for body mass control

1. Peripheral signals
a. Hunger inducing:
• Ghrelin (from stomach)
b. Hunger suppressing:
• CCK
• Amylin
• Leptin (from adipocytes)
etc.

2. Hypothalamus
a. Arcuate nucleus:
• NPY
• AGRP
• Both decrease energy expenditure; increase hunger

b. POMC neurons:
• MSH
• CART
• Both increase energy expenditure and decrease hunger

3. Brain stem
• Receive signals from hypothalamus
• Influences behaviour (conscious, subconscious)

17

Compare the effect of the following:
• Ghrelin
• MSH
• Leptin
• NPY
• CCK
• Amylin
• PYY
• AGRP
• CART

Where do they all come from?

Ghrelin:
• Increase hunger
• From stomach

MSH
• Decreases hunger and increases energy expenditure
• POMC neurons in hypothalamus

Leptin:
• From adipocytes
• Decreases hunger

NPY:
• From arcuate nucleus in hypothalamus
• Increases hunger and decreases energy expenditure

CCK:
• From small intestine
• Terminates meal

Amylin:
• From beta cells of pancreas
• Promotes satiety

PYY:
• From small intestine
• Reduces appetite

AGRP:
• From arcuate nucleus
• Increases hunger and decreases energy expenditure

CART:
• From POMC neurons in hypothalamus
• Increases energy expenditure and decreases hunger

18

Describe what happens to leptin levels when weight is lost and regained

Leptin levels are proportional to the size of adipocytes

Hence, when weight is lost, leptin levels decrease

When weight is gained, leptin levels increase