Lecture 16 - Insulin and Diabetes Flashcards
When was diabetes mellitus first described?
c1500 BCE as too great emptying of urine
when was the term diabetes introduced?
250 BCE, meaning “siphone”
When was mellitus introduced?
1600s, meaning from honey
What did the introduction of diabetes mellitus allow?
the distinction from diabetes insipidus
What is the most common endocrine disorder?
Diabetes
what is diabetes?
an insufficiency in the production or action of the pancreatic hormone insulin on target cells
Who identified insulin
Banting and Best in the McLeod lab
who and when was the first person to receive insulin?
Leonard Thompson, 1922
What is diabetes characterised by?
abnormal fuel metabolism, which results most notably in hyperglycaemia and dyslipidaemia due to defects in insulin production/secretion, insulin action or both
What causes hyperglycaemia?
loss of insulin stimulated glucose uptake and loss of insulin repression of gluconeogenesis and glycogen breakdown
What causes dyslipidemia?
loss of insulin repression of lipolysis
What is type 1 diabetes?
loss of insulin production
What is type 2 diabetes?
insulin resistance; insufficient secretion of insulin
What is T1D sometimes referred to as?
insulin dependent diabetes
What % have T1D?
5-10%
When does T1D typically develop?
in children and young adults
What is the peak age for diagnosis of T1D?
10-14 years
Insulin secretion in T1D?
pancreas produces little or no insulin
What causes T1D?
it is an autoimmune disorder
What do T1D patients need as treatment?
insulin injections
When does type 2 diabetes occur?
when the body is in an insulin resistant state and pancreatic beta cells cannot release sufficient insulin to compensate for the resistance
What % have type 2?
90-95% of diabetic people
When is type 2 typically diagnosed?
Later in life, but disease onset is getting earlier
What is type 2 largely a result of?
lifestyle - obesity, lack of exercise, diet
genetic factors are also important
what % of patients with type 2 are overweight?
International Diabetes Federation - 80% of people with type 2 are overweight or obese at the time of diagnosis
How is type 2 picked up?
can develop without the person knowing and is usually picked up during routine medical screening
How is type 2 managed?
by oral medications or insulin injections, with diet and exercise contrl
How many people does gestational diabetes affect?
18 in every 100 women during pregnancy
When does gestational diabetes develop?
in the 2nd trimester and disappears after the child is born
What causes gestational diabetes?
not clear but thought to be due to various hormonal changes that occur during pregnancy, many of which can block the action of insulin
In 2018, how many people in the UK were diagnosed with diabetes?
6% (~3.8 million people)
this figure has more than doubled since 1996
How many people in the UK have undiagnosed diabetes?
~1 million
What % of NHS budget is spent on diabetes?
~10% (£10 billion = £192 million per week)
How many hospital beds are occupied by someone with diabetes?
1 in 7 beds
How many prescription items dispensed for diabetes?
52 million items in England, 3.6 million in Scotland
What are most cases of diabetes?
type 2 - due to ageing population and increasing numbers of overweight and obese people
What are the 3 main tests for diagnosis of diabetes?
Fasting glucose test/random glucose test
glucose tolerance test
HbA1c
What is the fasting glucose test?
no food or drinks (except water) for 8-10 hours
values for fasting plasma glucose taken
what is a normal fasting plasma glucose level?
below 6.1mmol/L (110mg/dL)
What fasting glucose level is impaired?
6.1-6.9mmol/l
111-125mg/dL
What fasting glucose levels indicates diabetes?
> 7.0 mmol/l (126mg/dL and above)
What is the random glucose test?
Regardless of when a person last ate, a random plasma glucose value of 11.1mmol/l (100mg/dL) indicates diabetes
What is the oral glucose tolerance test?
Subject fasts for at least 8 hours, plasma glucose is measure immediately before and 2 hours after drinking 75g of glucose dissolved in water
What plasma glucose 2 hours after glucose indicates diabetes?
> 11.1mmol
What plasma glucose level 2 hours after glucose indicates impaired glucose tolerance?
7.9-11mmol/l
What is haemoglobin A (HbA)?
the major form of haemoglobin
What does HbA1c form as?
a result of slow and irreversible reaction between HbA and glucose
What is the amount of HbA1c formed proportional to?
the amount of glucose present
What do HbA1c levels give a measure of?
the average blood glucose levels over the previous 3 months (the average life-time of red blood cells)
What do HbA1c levels indicate?
how well blood glucose is being controlled (long term trend)
What can HbA1c levels be used as?
a diagnostic test for type 2 diabetes
HbA1c results…?
> 48mmol/mol (6.5%) indicates type 2 diabetes
42-47 mmol/mol (6-6.4%) indicates a risk of developing diabetes
For most adults with diabetes, what is the HbA1c target?
48mmol/mol (6.5%)
Why can HbA1c not be used to diagnose type 1 diabetes?
these symptoms can develop very rapidly, a rapid increase of blood glucose levels over a short period of time would not be picked up by HbA1c because it is a long term trend
Diagnosis of diabetes?
Made by classic acute symptoms of hyperglycaemia (excess urination, thirst, fatigue) and an abnormal blood test
In patients without classic symptoms, how is a diagnosis made?
by two abnormal blood tests on separate days
How are type 2 asymptomatic patients diagnosed?
through opportunistic screening of high risk groups during routine medical visits
Why is early diagnosis important?
diabetes will get progressively worse if not treated correctly
What is diabetes associated with?
significant morbidity and mortality due to both acute and chronic effects
What are the acute complications due to?
hyperglycaemia
What do chronic complications arise due to?
damage to various organs (eyes, kidneys, nerves, heart, brain)… the main reason is vascular damage
What are some of the chronic complications of diabetes?
blindness, stroke, kidney disease, nerve damage, amputation, heart attack, loss of circulation in arms and legs
What are the acute symptoms of diabetes?
frequent urination (polyuria)
increased thirst (polydipsia)
tiredness
unexplained weight loss
extreme hunger
blurred vision
cuts or wounds that heal slowly
genital itching/frequent episodes of thrush
Why do patients have polyuria?
amount of glucose filtered by the kidney exceeds the maximal capacity for reabsorption, resulting in glucose entering the urine (glycosuria) and drawing water with it by osmotic diuresis
Why do patients have increased thirst?
as a result of urinating more
Why are diabetic patients tired?
the cells do not get the energy they need as the glucose is not taken up
cells cannot use glucose as a metabolic fuel to make ATP
Why is there unexplained weight loss?
the fat stores are broken down and used to supply energy
Why is there extreme hunger?
glucose is not utilised for energy
Why is there blurred vision?
lens of eye becomes dry due to dehydration and glucose build up
Why do cuts or wounds heal slowly in diabetic patients?
damage to blood vessels limits the flow of oxygen and nutrients needed for repair
Why do patients get genital itching/frequent episodes of thrush?
yeast infections caused by high glucose in blood/urine (supports yeast growth)
How do acute symptoms of type 1 develop?
rapidly
How do acute symptoms of type 2 develop?
over a number of years
What is diabetic ketoacidosis?
a potentially life threatening complication of type 1 diabetes
What does absence of insulin enhance?
free fatty acid (FFA) release from adipocytes
What are FFAs converted to?
ketone bodies by the liver, which serve as an energy source
Give examples of ketone bodies
acetoacetate and beta-hydroxybutyrate
What do ketones cause?
the pH of the blood to become acidic
What does the liver do in diabetic ketoacidosis?
continue to synthesise glucose so the blood glucose rises
What does high glucose in the urine cause?
takes water and solutes such as sodium and potassium with it, causes dehydration
What does a lack of insulin limit?
the use of glucose as an energy source
Early signs of diabetic ketoacidosis?
feeling very thirsty, urinating often, high blood glucose levels, high ketone levels in the urine
Later, extreme signs of DKA?
feeling weak and constantly sleepy, dry/flushed skin, nausea, vomiting and abdominal pain, difficulty breathing, fruity smelling breath
Treatment of DKA?
fluid replacement, insulin, mineral replacement
When does DKA usually develop?
at the time of diagnosis of diabetes, during illness, during growth spurt/puberty, when insulin has not been taken correctly
Why does DKA not occur in type 2?
the metabolic changes are not usually severe enough
When do chronic complications of diabetes develop?
gradually, over decades
What are chronic complications due to?
due to vascular damage
What can the vascular damage be?
either microvascular or macrovascular
What is microvascular damage?
damage to small blood vessels (capillaries)
What is macrovascular damage?
damage to larger blood vessels (arteries and veins)
What is hyperglycaemia associated with?
damage to blood vessels and atherosclerosis
What do diabetics have an increased risk of?
developing high blood pressure
What is diabetic retinopathy?
leading cause of blindness in adults
caused by damage to vessels in the eye
What is diabetic nephropathy?
leading cause of end-stage renal disease
caused by damage to small blood vessels in the kidney
What is diabetic neuropathy?
leading cause of non-traumatic lower extremity amputation, causes sensory loss and impotence
caused by hyperglycaemia and damage to blood vessels
What increased risk of stroke to diabetics have?
2-4 fold increase in CV mortality and stroke
How many diabetics die from CV events?
8 out of 10
what % of mortality does diabetes account for globally?
14.5% in the age group of 20-79
What is diabetic foot?
nerve damage or poor blood flow to feet increases risk of various complications
What can happen to cuts/blisters of diabetic patients?
they become serious infections, which often heal poorly and may ultimately need toe, foot or leg amputation
What is the most common cause of lower limb amputations?
diabetes
~7,400 leg, toe and foot amputations happen each year in England alone
Diabetes and dementia?
people with diabetes are at a 1/5-2/5 fold increase of dementia
Pregnancy complications to child?
increased risk of miscarriage, still birth and birth defects when diabetes is not well treated
Pregnancy complications for mother?
increased risk of DKA, retinopathy, pregnancy induced high blood pressure and pre-eclampsia
What is the key to preventing acute and chronic diabetes complications?
good control of blood glucose
patient education is key
What is the estimated diabetes prevalence?
for adults ages 20-70 is 422 million
How many people is diabetes expected to affect?
1 in 10 people by 2040 (642 million)
How many adults with type 2 are undiagnosed?
1 in 2
10 countries with highest diabetes prevalence?
Tokelau, Nauru, Mauritius, Cook Islands, Marshall Islands, Palau, Kuwait, Saudi Arabia, Qatar, New Caledonia
WHO Fact 6?
people with diabetes can lead a long and healthy life when their condition is detected and well managed
WHO Fact 7?
early diagnosis and intervention is the starting point for living well with diabetes
WHO Fact 10?
type 2 diabetes can be prevented and cured by lifestyle changes
