1Obesity - Introduction to Obesity and Diabetes

Question 1

What is the source of energy intake?

Answer 1

Feeding

Question 2

What is the source of energy expenditure?

Answer 2

Basal metabolism, adaptive thermogenesis and PHYSICAL ACTIVITY

Question 3

When does obesity develop?

Answer 3

Obesity only develops in energy intake chronically exceeds energy expenditure

Question 4

What is the global prevalence of obesity?

Answer 4

Incidence of obesity is increasing in:
Highest - North America, Western Europe, Eastern Europe, Australia, Japan
Transition economies - China, India
Lowest - Developing world

Question 5

What is the prevalence of obesity in the UK?

Answer 5

Now, approximately 25% of men and women have a BMI >30
30 years ago, 6% of men and 8% of women were obese
Increased prevalence in lower socioeconomic status groups, over 40s and ethnic minority groups
From 1970-2000, the prevalence of childhood obesity rose from around 10% to around 20%

Question 6

What are the causes of obesity?

Answer 6

Overeating with high fat, energy dense foods
Lack of physical activity - between 1950-2000 the average fat intake and energy intake actually decreased, however there has been a two-fold increase in obesity since 1980
Increasing obesity despite reduced energy intake means substantial decrease in physical activity - i.e. less activity, more sedentary behaviour
There is a correlation between the rise in obesity and an increase in household car ownership and number of hours per week spent watching television

Question 7

How is obesity associated to risk of mortality?

Answer 7

For BMIs between 20-30, the risk of mortality is very low (20-25) and low (25-30).
For BMIs above 30, the risk of mortality is moderate (30-35), high (35-40) and very high (40+)

Question 8

What are the implications of obesity on health?

Answer 8

For people who are obese, there is an increased incidence of:
Cardiovascular disease
Type 2 diabetes
Cancer (severe obesity, BMI >40)
Gallstones
Arthritis
Sick leave
Psychosocial problems
There is a clear and direct correlation between prevalence of obesity in set geographical areas/localities and the prevalence of diabetes

Question 9

How is diabetes defined?

Answer 9

Metabolic disorder leading blood glucose levels to become too high
It is due to abnormalities in insulin release and its action
Leads to a wide range of disturbances of function and metabolism in addition to alterations in blood glucose levels

Question 10

How is diabetes diagnosed?

Answer 10

Patients with diabetes mellitus present with a fasting blood glucose level of >7.00mmol/l and a random blood glucose level of >11.1 mmol/l
A glucose tolerance test can be used to test for diabetes mellitus:
75 g of oral glucose administered
Blood glucose level tested at baseline (fasting) and 2 hours after glucose administration

Normal:
Fasting = <5.5
2 hours = <7.8

Pre-diabetes/IGT:
Fasting = <7.0
2 hours = 7.8-11.0

Diabetes:
Fasting = >7.0
2 hours = >11.1

Diabetes mellitus is a consequence of inadequate insulin release and/or insulin resistance.

Question 11

What is the release of insulin stimulated by?

Answer 11

Release stimulated by:
Glucose and amino acids
Parasympathetic nervous system
Gut hormones - e.g. GIP, CCK

Question 12

What are the main actions of insulin?

Answer 12

Main insulin actions:
Stimulates glucose uptake in skeletal muscle and adipose tissue, glycogen storage in liver and muscle
Stimulates lipid synthesis and storage from triglycerides
Inhibits proteolysis and facilitates protein synthesis
Inhibits lipolysis and ketogenesis

Question 13

What are the consequences of reduced insulin action?

Answer 13

Reduced glucose uptake in skeletal muscle and adipose tissue
Reduced lipid synthesis and storage from triglycerides
Increased proteolysis (muscle breakdown)
Increased lipolysis and ketogenesis (adipose fat breakdown)
INCREASED GLUCOSE AND KETONES
WEIGHT LOSS?
Metabolic acidosis:
Nausea, vomiting
Breathlessness 
Abdominal pain
Osmotic diuresis:
Frequency passing urine
Thirst
Dehydration

Question 14

How are the different types of diabetes classified?

Answer 14

Type 1 (Insulin dependent)
Type 2 (Non-insulin dependent)
Other causes of diabetes mellitus:
Pancreatic disease - Pancreatitis, Pancreatectomy, Haemochromatosis
Endocrine disease - Acromegaly, Cushing’s syndrome
Drugs and chemicals - Steroids, Beta-Blockers, Diuretics
Inherited disease - MODY, DIDMOAD, Cystic Fibrosis

Question 15

What is type 1 diabetes?

Answer 15

Autoimmune disease
Immune cells infiltrate the Islets of Langerhans Beta-Cells
Inherited predisposition
HLA-DR3 or HLA-DR4
Unknown environmental trigger
Coxsackie virus, Other viruses - Rubella?, Cow’s milk
Autoantibodies
Islet cell antibodies
Destruction of the beta cells
Insulin deficiency and rising blood glucose - symptoms

Question 16

What is the timescale in the development of type 1 diabetes?

Answer 16

Genetic predisposition to Type 1 Diabetes
Usually at around age 5 - Onset of autoimmune disease - Autoantibodies present
Reduction in beta cells - gradual rising of fasting blood glucose, correlated with increased likelihood of symptoms
Ultimately leading to severe insulin deficiency

Question 17

What is the treatment for type 1 diabetes?

Answer 17

Treatment = INSULIN
Injection - 2-4 times a day subcutaneous injections, or Infusion
Combinations of:
Short acting, medium acting and long acting
Inhalation? - in place of the short acting
Transplantation - Islet cells (Need protection against Islet cell autoantibodies)

Question 18

What is type 2 diabetes?

Answer 18

90% of all cases of diabetes are Type 2
Increases with obesity, inactivity and aging
Increased susceptibility in some ethnic groups
Asians
Afro-caribbeans
Disease of middle-aged and elderly 
70% of cases over 55 years of age
In the UK, current treatment:
15% diet alone
65% diet and tablets
20% insulin treated

Question 19

What is the natural history for type 2 diabetes?

Answer 19

HbA1c (glycated haemoglobin) is often measured in patients with diabetes.
HbA1c normal range = 4-6%
In women, gestational diabetes may be an indicator of future diabetes.
Diagnosis is typically made at around middle age (although can be younger) and HbA1c may be above 8% at diagnosis.
A target for good control of diabetes is an HbA1c level of below 7%

Question 20

What is the aetiology of type 2 diabetes?

Answer 20

Insulin resistance - reduced ability of tissues to respond to the glucose-lowering action and other actions of insulin
(Relative) Insulin deficiency - gradual failure of beta cells to produce insulin

Question 21

What is the interplay between insulin resistance and progressive beta cell failure in type 2 diabetes mellitus?

Answer 21

Insulin resistance is linked to hyperinsulinaemia
Hyperinsulinaemia is linked to increasing insulin resistance
Increased insulin resistance is linked to beta cell failure
Beta cell failure is linked to hypoinsulinaemia
Genetics appear to play a role in insulin resistance and beta cell failure
Environmental factors, drugs and endocrine disease can all play a role in insulin resistance and increasing insulin resistance
Increased insulin resistance and beta cell failure lead to impaired glucose tolerance
Impaired glucose tolerance leads to hyperglycaemia/Type 2 Diabetes

Question 22

What are some of the chronic complications that occur in type 2 diabetes?

Answer 22

Retinopathy - Most common cause of blindness in people of working age
Macrovascular and Cerebrovascular disease - 2-3 fold increased risk of coronary heart disease and stroke
Foot problems - 15% of diabetes patients develop foot ulcers; 5-15% of diabetes patients with foot ulcers need amputations
Erectile dysfunction - May affect up to 50% of men with long-standing diabetes
Nephropathy - 16% of all new patients requiring renal replacement therapy have diabetes

Question 23

What types of complications do type 2 diabetes often present with at diagnosis?

Answer 23

50% of newly presenting patients with Type 2 diabetes already have one or more complications at diagnosis
Ischaemic skin changes to feet - 6%
Hypertension - 35%
Retinopathy - 21%
Erectile dysfunction - 20%
Abnormal ECG - 18%
Absent foot pulses - 13%
Myocardial infarction - 1%
Stroke or transient ischaemic attack - 1%
Plasma creatinine (impaired kidney function)>120µmol/l - 3%
Intermittent claudication (cramping caused by arterial obstruction) - 3%

Question 24

How does type 2 diabetes affect a patient’s life expectancy?

Answer 24

Adults with diabetes have an annual mortality rate of 5.4% - this is double that of non-diabetics.
Life expectancy is reduced by 5-10 years.

Question 25

How is type 2 diabetes linked to macrovascular disease?

Answer 25

Atherosclerotic disease accounts for most of the excess mortality in patients with diabetes
There is a 2-3 fold increased risk of coronary heart disease and stroke

Question 26

How are patients with diabetes affected by peripheral vascular disease?

Answer 26

Diabetes accounts for 50% of all non-traumatic amputations

Amputation risk is 15 fold greater in patients with diabetes than non-diabetic subjects

Question 27

What is the prevalence of diagnosed diabetes in the USA since 1950 and what is the projection for the future?

Answer 27

In 1960, there were 2 million Americans with diabetes.
This rose to around 6 million by 1980.
By 2000, this figure was closer to 8 million.
By 2020, the number of Americans with diabetes is projected to be over 12 million.

Question 28

What is the distribution of causes of death in patients with diabetes?

Answer 28

Cardiovascular disease is the main cause of death in diabetes patients - accounting for 65% of deaths.
Other causes include diabetes itself, malignant neoplasms and pneumonia/influenza.

Question 29

What are the benefits of weight loss for patients with diabetes?

Answer 29

Even 10% weight loss can:
improve insulin resistance
reduce plasma lipids
decrease blood pressure

Question 30

How is obesity a disorder of energy balance?

Answer 30

Historically, leanness was a greater threat to survival than obesity
Evolution favoured energy storage and avoidance of starvation
This is no longer the case

Question 31

Who discovered a mutation in mice which made them obese?

Answer 31

Ingalls

Question 32

What did the obesity mutation in mice cause?

Answer 32

The mutation caused:
Early onset obesity
Hyperphagia
Decreased energy expenditure
Hyperglycaemia
Hyperinsulinaemia 
Increased fat stores result from adipocyte hyperplasia (rare)