Obesity

Question 1

What is the following BMI cut-off points for:

• underweight
• normal weight
• overweight
• obese
• morbidly obese

Answer 1

• underweight <18.5
• normal weight 18.5-24.9
• overweight 25-29.9
• obese >30
• morbidly obese >40

Question 2

What is the association between insulin and obesity?

Answer 2

insulin:

• decreases the rate of lipolysis in adipose tissue (and lowers plasma fatty acid level)
• -> increases the uptake of triglycerides from blood into adipose tissue
• stimulates fatty acids and triglyceride synthesis in tissues
• decreases rate of fatty acid oxidation in muscle and liver

Question 3

Which T2D drugs have the following impact on insulin levels:

• increase
• stable
• decrease

Answer 3

• increase: insulin injections, sulfonylureas, TZD
• stable: metformin, DPP-4 inhibitors
• decrease: SGLT2 inhibitors

Question 4

Describe the thrift gene hypothesis.

Answer 4

Genes that predispose people to obesity could have a selective advantage to populations that experience frequent starvation

Question 5

What are the characteristics of syndromic monogenic obesity? Give examples of syndromic monogenic obesity.

Answer 5

Characteristics:

• mental retardation
• dysmorphic features
• organ specific abnormalities

Examples:

1. Prader-Willi syndrome
2. Bardet-Biedl + Alström Syndrome
   - primary cilium has a key role in differentiation of adipocytes
   - the cilia mediate leptin receptor signalling

Question 6

What pathway is involved in non-syndromic monogenic obesity?

Answer 6

Leptin-melanocortin pathway

Question 7

What is polygenic obesity?

Answer 7

227 genetic variants involved in different biologic pathways have been identified

• involves CNS, food sensing + digestion, insulin signalling, lipid metabolism, muscle and liver biology, gut microbiotica
• also involved in adipocyte differentiation (ciliopathies and mutations in PPAR gamma 2 )

Question 8

What conditions/disease does obesity increase the risk of?

Answer 8

• cardiovascular disease
• pulmonary disease
• metabolic disease
• osteoarticular disease
• cancer
• psychiatric illnesses

Question 9

How can obesity cause T2D/what is the association between the two?

Answer 9

Obesity causes:

• chronic inflammation of the fat tissue
• altered adipokine levels
• -> especially leptin = this causes tissues to become leptin resistant
• breakdown of fat metabolism
• -> accumulation of lipids in tissue
• breakdown of glucose metabolism

Question 10

What are the main treatment options for obesity (non pharmacological/pharmacological)?

Answer 10

1. PREVENTION/LIFESTYLE CHANGES!!
2. Orlistat: gastric and pancreatic lipase inhibitor (reduced absorption of dietary fat)
3. Phentermine: noradrenaline transporter inhibitor - appetite suppression
4. Liraglutide: GLP1 agonist - reduced appetite
5. Lorcaserin: Selective 5-HT agonist - increased satiety

Question 11

When is surgery indicated in obesity?

Answer 11

When BMI >40 or >35 with obesity-related complications

- must go through weight management course first

Question 12

What is the difference between restrictive and malabsorption procedures in the treatment of obesity?

Answer 12

1. restrictive: restrict ability to eat
   - e.g. = adjustable gastric band
2. malabsorptive: reduce ability to absorb nutrients
   - e.g. = gastric bypass