1Obesity - Introduction to Obesity and Diabetes Flashcards
What is the source of energy intake?
Feeding
What is the source of energy expenditure?
Basal metabolism, adaptive thermogenesis and PHYSICAL ACTIVITY
When does obesity develop?
Obesity only develops in energy intake chronically exceeds energy expenditure
What is the global prevalence of obesity?
Incidence of obesity is increasing in:
Highest - North America, Western Europe, Eastern Europe, Australia, Japan
Transition economies - China, India
Lowest - Developing world
What is the prevalence of obesity in the UK?
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%
What are the causes of obesity?
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
How is obesity associated to risk of mortality?
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+)
What are the implications of obesity on health?
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
How is diabetes defined?
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
How is diabetes diagnosed?
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.
What is the release of insulin stimulated by?
Release stimulated by:
Glucose and amino acids
Parasympathetic nervous system
Gut hormones - e.g. GIP, CCK
What are the main actions of insulin?
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
What are the consequences of reduced insulin action?
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
How are the different types of diabetes classified?
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
What is type 1 diabetes?
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
What is the timescale in the development of type 1 diabetes?
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
What is the treatment for type 1 diabetes?
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)
What is type 2 diabetes?
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
What is the natural history for type 2 diabetes?
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%
What is the aetiology of type 2 diabetes?
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
What is the interplay between insulin resistance and progressive beta cell failure in type 2 diabetes mellitus?
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
What are some of the chronic complications that occur in type 2 diabetes?
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
What types of complications do type 2 diabetes often present with at diagnosis?
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%
How does type 2 diabetes affect a patient’s life expectancy?
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.
How is type 2 diabetes linked to macrovascular disease?
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
How are patients with diabetes affected by peripheral vascular disease?
Diabetes accounts for 50% of all non-traumatic amputations
Amputation risk is 15 fold greater in patients with diabetes than non-diabetic subjects
What is the prevalence of diagnosed diabetes in the USA since 1950 and what is the projection for the future?
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.
What is the distribution of causes of death in patients with diabetes?
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.
What are the benefits of weight loss for patients with diabetes?
Even 10% weight loss can:
improve insulin resistance
reduce plasma lipids
decrease blood pressure
How is obesity a disorder of energy balance?
Historically, leanness was a greater threat to survival than obesity
Evolution favoured energy storage and avoidance of starvation
This is no longer the case
Who discovered a mutation in mice which made them obese?
Ingalls
What did the obesity mutation in mice cause?
The mutation caused: Early onset obesity Hyperphagia Decreased energy expenditure Hyperglycaemia Hyperinsulinaemia Increased fat stores result from adipocyte hyperplasia (rare)
