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

Lecture 10 - Managing and Preventing Metabolic Syndrome Flashcards

1
Q

Describe the weight loss trial for MS

A

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

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

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2
Q

Can genetics account for the epidemic of obesity?

A

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

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3
Q

Describe Levin’s study in mice of epigenetics in obesity

A

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

  1. 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)

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4
Q

Describe the VLCD

A

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)

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5
Q

Describe the efficacy of diets in achieving and sustaining weight loss

A

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

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6
Q

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

A

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'
  1. Weight was regained after intervention
  2. 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

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7
Q

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

A

Weigh gained:
• Increased energy expenditure

Weight lost:
• Decreased energy expenditure

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

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8
Q

Describe pharmacotherapy for weight loss

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

Diabetes:

  1. Exenatide
  2. Liraglutide
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9
Q

What are off-label drugs?

A

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

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10
Q

Describe the effects of the drug Topiramate

A

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

However, has nasty adverse effects

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11
Q

Describe the efficacy of Ph/T combination therapy

A

Lead to more profound weigh loss than Phentermine on its own

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12
Q

Describe the side effects of Phentermine and Topiramate

A 
Phentermine:
 • Increased HR and BP
 • Dry mouth
 • Sleep disturbances
 • Interactions with SSRIs
Topiramate:
 • Parasthesiae
 • Depression
 • Memory loss
 • etc.
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13
Q

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

A

103 patients

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

Those that remained on the drug had sustained weight loss

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14
Q

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

A
  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
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15
Q

Describe how the individual components of MS can be managed

A
  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

  1. Lipids
    a. Pharmacological
    • TAGs: Fenofibrinate
    • LDL: Statins
    b. Non-pharmacological:
    • Diet
    • Exercise
  2. Hyperuricaemia
    • Allopurinol
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16
Q

Describe the hormonal axis for body mass control

A
  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

  1. Brain stem
    • Receive signals from hypothalamus
    • Influences behaviour (conscious, subconscious)
17
Q 
Compare the effect of the following:
 • Ghrelin
 • MSH
 • Leptin
 • NPY
 • CCK
 • Amylin
 • PYY
 • AGRP
 • CART

Where do they all come from?

A

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
Q

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

A

Leptin levels are proportional to the size of adipocytes

Hence, when weight is lost, leptin levels decrease

When weight is gained, leptin levels increase

BIOM30001 - Frontiers in Biomedicine (35 decks)

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