Epidemiology of Metabolic Disease: Diabetes and Insulin Resistance

Question 1

What is type 1 diabetes?

Answer 1

Insulin not produced by pancreas - need insulin injections
Autoimmune
Sudden onset in youth

Question 2

What is type 2 diabetes?

Answer 2

Cell does not recognise insulin signal - in insulin-resistant state
Treat with diet, insulin, drugs
Gradual adult onset

Question 3

What is gestational diabetes?

Answer 3

Diabetes during pregnancy - resolves after

Increased later life risk of type 2 diabetes

Question 4

What is glycated haemoglobin?

Answer 4

Glucose attached to haemoglobin in RBCs

Question 5

What does glycated haemoglobin indicate and why?

Answer 5

Gives 3 month average of glucose circulating - as RBCs have life of 3 months

Question 6

Which methods can be used to establish a cut off point for diabetes diagnosis?

Answer 6

Glycated haemoglobin
Fasting glucose
Glucose tolerance test - glucose 2 hours after glucose load
Glycaemic level where risk of diabetic retinopathy increases

Question 7

What is the largest cause of diabetes?

Answer 7

Obesity

Question 8

What are the relative contributions of genetics and environment to diabetes?

Answer 8

Genetic role

Mainly due to lifestyle

Question 9

What is the effect of living, working, and commuting closer to a takeaway food outlet?

Answer 9

Increased average BMI

Question 10

How are men affected by living in more walkable environments?

Answer 10

Decreased diabetes risk

Question 11

What is the relationship between birthweight and adult type 2 diabetes risk (decreased adult glucose tolerance)?

Answer 11

U-shaped

Question 12

What is higher maternal fasting glucose associated with?

Answer 12

Increased chance of offspring obesity

Question 13

Why might higher maternal fasting glucose be associated with an increased chance of offspring obesity?

Answer 13

Genotype - weak evidence
Shared familial lifestyles - weak evidence
Pedersen hypothesis

Question 14

What is the Pedersen hypothesis?

Answer 14

Gestational diabetes causes early obesity
Maternal high glucose causes foetal hyperinsulinaemia
Foetal insulin acts as growth hormone - via IGF-1 - causes rapid early growth
Interuterine programming of metabolic syndrome affects multiple foetal tissues - changes combine to impair glucose tolerance - insulin resistance

Question 15

What are the main complications of diabetes?

Answer 15

CV disease - main diabetes-related cause of death
Cataracts
Nephropathy
Neuropathy
Foot ulcers
Cognitive decline
Cancer

Question 16

What is the evidence that diabetes accelerates ageing?

Answer 16

Diabetes increases frequency of dementia, mild cognitive impairment, poor physical function (increased fractures)

Question 17

What are the vascular complications of diabetes?

Answer 17

Blood vessel stiffening, leaking, cell death, thrombus formation

Question 18

How does diabetes lead to vascular complications?

Answer 18

Metabolic disease - causes inflammation, DNA damage, apoptosis, O2 stress
Causes structural damage - impacts microcirculation - causes complications (e.g. retinopathy)
Causes fibrosis of perivascular space, vessel stiffening, fewer arteries - impairs blood delivery to organs
Causes macrovascular complications (e.g. CVD, stroke)

Question 19

What is the ‘metabolic memory’ of tissues and what is the implication of this?

Answer 19

Tissues retain memory of previous high glucose - damage develops even when glucose returns to normal levels
Must treat diabetes early to avoid CV complications

Question 20

Which diabetes complications are CVD risk factors?

Answer 20

High triglycerides
High LDL
Low HDL

Question 21

When do CVD risk factors appear in diabetes?

Answer 21

Cluster with diabetes onset - ~10yrs before diagnosis

Question 22

For individuals at high risk of diabetes which treatments had the lowest progression rates?

Answer 22

Diet and exercise plan - then metformin - then placebo

Question 23

What is a problem with a diet and exercise plan for individuals at high risk of diabetes?

Answer 23

Not appropriate for LMICs

Question 24

What are potential problems with long-term diabetes and CVD prevention interventions?

Answer 24

Lifestyle and metformin improve CVD risk factors - but no evidence for decreased CVD rates
Enthusiasm for diet and exercise plan likely to decline
Must consider generalisability to other countries
Age of intervention - midlife often targeted - but early life also affects diabetes development

Question 25

What are the 2 main approaches to diabetes prevention?

Answer 25

Individual approach

Population-based approach

Question 26

Give an example of an individual approach to diabetes prevention

Answer 26

Screen high risk individuals - refer to diet and exercise support

Question 27

Give an example of a population-based approach to diabetes prevention

Answer 27

Government restrictions on food fat and salt content

Question 28

What do programmes against smoking suggest is the best preventative approach?

Answer 28

Population-based

Question 29

What is the effect of drugs to lower blood glucose in diabetics?

Answer 29

Slightly decreased CV events

No effect on death rate

Question 30

What is the effect of statins and blood pressure lowering drugs in diabetics and what does this suggest?

Answer 30

Decreased CV events
Decreased death rate
Diabetes treatments should target lipids and BP - more than blood glucose levels - to decrease CV risk