CSI 5 Flashcards
What are microvascular complications of diabetes?
complications due to damage to the small blood vessels:
- damage to eye(retinopathy) leading to blindness
- Kidney damage(nephropathy) leading to renal failure
- nerve damage(neuropathy) leading to impotence and diabetic foot disorders which can include severe infections leading to amputation
What are macrovascular complications of diabetes?
Damage due to larger blood vessels:
-Includes cardiovascular diseases such as heart attacks, strokes and insufficiency in blood flow to legs
How can you delay the onset of diabetes complications?
Good metabolic control
What is diabetic retinopathy caused by?
small blood vessel damage to the back of the eye, the retina, leading to eventual blindness
-It is the leading cause of blindness and visual disability
What are the symptoms of diabetic retinopathy?
blurred vision
How can you treat diabetic retinopathy?
- Good metabolic control can delay onset and progression
- early detection and treatnment can prevent/delay blindness
- regular eye examinations and timely intervention helps early diagnosis
What is diabetic nephropathy caused by?
damage to the small blood vessels in the kidneys leading to kidney failure and eventual death
-In developed countries this is the leading cause of dialysis and kidney transplant
What are the symptoms of nephropathy?
- No early symptoms
- become tired and anaemic
- not thinking clearly
- dangerous electrolyte imbalances
How can you diagnose nephropathy?
- urine test for protein
- blood test for kidney function
How can you treat someone with nephropathy?
If diagnosed at an early stage, several measures can retard the progression to kidney failure. These include control of high blood glucose, control of high blood pressure, intervention with medication in the early stage of kidney damage, and restriction of dietary protein.
What is the cause of diabetic neuropathy?
nerve damage through different mechanisms:
- direct damage by the hyperglycemia
- decreased blood flow to nerves by damaging small blood vessels.
This nerve damage can lead to sensory loss, damage to limbs, and impotence in diabetic men. It is the most common complication of diabetes.
What are the symptoms of neuropathy?
depends which nerves are effected:
- numbness
- pain
- impotence
- decresased feet sensation can lead to patients not recognising cuts and thus developing foot infection (if not treated early can lead to foot amputations)
How can you diagnose neuropathy?
- early recognition of symptoms
- examinations at regular intervals
How can you treat neuropathy?
bring blood glucose under control if detected early
What causes cardiovascular disease?
Hyperglycaemia damages blood vessels through a process called ATHEROSCLEROSIS (clogging of the arteries)
Narrowing of the arteries can lead to decreases blood flow to the heart muscle(heart attack), or to the brain(stroke) or to extremities(leading to pain and decreases healing of infections)
How can we treat cardiovascular complications?
Early detection and control of risk factors such as smoking, high blood pressure, high serum cholesterol and obesity
What is the most common type of diabetes?
T2DM (more than 90% of case)
What is the most important risk factor of T2DM and what is the exception?
BMI over 25
However T2DM has increased in china and India despite low obesity rates
Probably due to the different fat:muscle ratios, different fat distribution, and greater severity of beta cell dysfunction
Who should be screened for T2DM?
adults over 45 who are obeses, have a family hisory
What is shown to be effective at controlling T2DM?
intensive lifestyle interventions sometimes combined with medication(not approved in most countries)
How can you have successful glycaemic control?
- Lifestyle
- Metaformin- promotes insulin secretion, increases, insulin sensitivity, acts on the incretin axis or target intestinal and renal glucose absorption
How do you diagnose T2DM?
- difficult as clinicalpresentation and pathology can vary a lot between individuals
- Mainly depends on serum glucose levels-fasting glucos elevels of more than 100mg/dl are considered pre diabets and more than 126 is T2DM
- Also Glycerated haemoglobin HbA1c levels of more than 6.5% is now a diagnosis criteria
What causes T2DM?
- Impaired insulin secretion due to pancreatic beta cell dysfunction e.g. lipotoxicity, glucotoxicity and resistance to incretins(intestinal hormones that stimulate insulin secretion)
- `Peripheral organs e.g. liver, muscle and kidney become insulin resistant+reduced blood glucose uptake, increased glucose reabsorption by the kidney and increased gluconeogenesis=HYPERGLYCAEMIA
What is a cause of insulin resistance?
Genetic abnormalities ectopic lipid accumulation mitochondrial dysfunction inflammation -endoplasmic reticulum stress
What is glut 4?
insulin regulated glucose transporter found in adipose and muscle cells
Describe how glucose enters the cell and is converted into ATP?
1-Insulin binds to insulin receptor on muscle cells causing a SIGNALLING CASCADE
2-This causes GLUT 4 to one via exocytosis into the cell membrane
3-Glucose enters and is converted to pyruvate via glycolysis
4-Pyruvate-> ACETYL CoA via PYRUVATE OXIDATION
5- Acetyl CoA enters the KREB/citric acid cycle
6-Reduced coenzymes enter the oxidative phosphoryltion to generate 30ATP
What is the hallmark of T2DM?
hyperglycaemia
What are the 2 main reasons for T2DM?
- Body becomes resistant to insulin (to do with insulin receptors) this means glucose cant enter the cell as GLUT 4 is insulin dependent
- pancreas unable to produce enough insulin due to impaired beta cell function
What is the effect of insulin on the liver, fat cells and muscle?
Liver:
- increased Glucose uptake
- increased glycogenesis
- decreases glycogenolysis
- decreased gluconeogenesis
- decreased lipolysis
Fat:
- increased glucose uptake
- increased lipogenesis
- decreases lipolysis
Muscle:
- increased glucose uptake
- increased Glycogenesis
- Increased protein synthesis
- decreased protein catabolism(breakdown)
What is the effect of T2DM on liver, fat cells and muscle?
Opposite of the normal insulin effect on liver, fat cell and muscle
Overall there is :
- increased blood glucose- because less glucose uptake
- increased free fatty acids-due to increased lipolysis to release energy
What are the causes of T2DM?
- Diabetes susceptibilty genes
- Adipokines-cytokines secreted by adipose tissue as some are associated with beta cell failure and death
- Inflammation-excess body fat =abnormal inflammation=can alter insulin action
In order what are the stages to T2DM ?
1-Normoglycaemia
2-Impaired fasting glucose
3-impaired glucose tolerance
4-T2DM
What is the Fasting glucose, Post prandial glucose, Random glucose and Urine dip test for Normoglycaemia?
Fasting Glucose: less than 5.5mmol/L
Post Prandial glucose:less than 7.8mmol/L
Random Glucose: Less than 11.1mmol/L
Urine:-ve
What is the Fasting glucose, Post prandial glucose, Random glucose and Urine dip test for Impaired fasting glucose?
Fasting Glucose: 5.5mmol/L-6.9mmol/L
Post Prandial glucose:less than 7.8mmol/L
Random Glucose: Less than 11.1mmol/L
Urine:-ve
What is the Fasting glucose, Post prandial glucose, Random glucose and Urine dip test for Impaired glucose tolerance?
Fasting Glucose: less than 7mmol/L
Post Prandial glucose:less than 7.8mmol/L-11.1
Random Glucose: Less than 11.1mmol/L
Urine:+ve
What is the Fasting glucose, Post prandial glucose, Random glucose and Urine dip test for T2DM?
Fasting Glucose: more than/equal to 7mmol/L
Post Prandial glucose:more than/equal to 11.1mmol/L
Random Glucose:more than/equal to 11.1mmol/L
Urine:++
What is post prandial glucose?
Tested using oral glucose test: blood glucose taken 2 hours after been given 75g oral glucose load (not as practical as it takes a while)
What is impaired fasting glucose?
Predominantly hepatic insulin resistance leads to continuous glucose output from the liver
What is impaired glucose tolerance?
Predominantly Muscle insulin resistance + impaired post pradial insulin release results in poor cellular glucose uptake
What is the least useful test for diagnosing T2DM?
Urine dip test=- because people have different RENAL GLUCOSE THRESHOLDS depending on this people may/may not have glucose in their urine
What does the urine dip test measure?
Glucose-shows less glucose absorption
Ketones-if lipolysis happens for a long time fatty acids are used by the liver to make ketones -ketoacidosis
What are synonyms of prediabetes?
Imparied fasting glucose Impaired glucose tolerance Borderline diabetes Impaired glucose regulation Non-diabetic hyperglycaemia
What is HbA1c?
Haemoglobin that has become glycosylated- chemically linked to sugar(occurs non enzuymatically with glucose least easily and fructose and galactose)
Why would you measure HbA1c levels to diagnose and monitor diabetes?
because as Hb1Ac levels rise PLASMA GLUCOSE LEVELS rise proportionately
What are the risk factors for T2DM?
-overweight
-45+
-family history
-African american , american Indian, hispanic
-High blood pressure
-Low HDL (good cholesterol)
-Not physically active
-history of heart disease/stroke
-depression
-PCOS
-Alcohol/smoking
Disturbed sleep
What is prediabetes?
Means blood sugar is higher than normal but not high enough to be counted as diabetes but high enough to be developing it
What are the symptoms of prediabetes?
No symptoms as if you have the symptoms of T2DM it means you already have it
What are the 3 main ways to prevent T2DM?
1-Manage weight
2-Eat healthy balanced diet
3-Be more active
What is the NHS diabetes prevention programme?
Programme to deliver evidence based BEHAVIOURAL INTERVENTIONS for individuals identified as being at high risk of developing T2DM
Why implement a diabetes prevention programme?
Many T2DM cases are preventable and their is STRONG evidence that behavioural interventions can significally reduce the risk
What are the aims of the programme?
- reduce incidence of T2DM
- Reduce incidence of complications associated with incidence diabetes
- Over the long term to reduce health inequalities associated with diabetes
Who is eligible for the programme?
people who have non diabetic hyperglycaemia (HbA1c= 42-47mmol/mol or pasting plasma glucose of 5.5-6.9mmol/L)
Blood result must be from the last 12 months and only the most recent bllod result can be used
18+ years old
What does the diabetes prevention programme focus on?
BEHAVIORAL INSIGHT:
-an approach that uses knowledge of the HOW +WHY people behave the way they do-this is used to encourage positive behaviour change
- considers all aspects of behaviour e.g psychology, social, behavioral, economic
- acknowledges the importance of the fast autonomic system in driving behaviour change
- insight helps people change habits when they struggle to
How can we increase the UPTAKE of people to the programme?
Uptake -people are often put off by complicated recruitment processes
Make it easy- simple invitation letters, taster session
Make it attractive-offer other incentives, highlight benefit
Make it social -normalise attendence, testomonies,
How can you increase RETENETION to the programme?
Retention-people are likely to forget to attend sessions
- send daily text reminders a day or 2 before the session
- sessions at convenient times
- Add an element of competition
- Make sessions a game
How can you encourage long term BEHAVIOR CHANGE from the programme?
Behaviour-people may have different motivations and beliefs
-Tailor session content to members of the group and make messages more relevant to their beliefs
-Challenging but realistic goals
-Tell people ‘how’ rather than ‘what’ to do
emphasise immediate benefits that matches their motivations
-time orientated goals
What is metaformin?
- used as a first line drug to help treat T2DM
- lowers fasting plasma insulin instead of increasing it and instead increase INSULIN SENSITIVITY=increases glucose uptake +decreases hepatic glucose output=lowers blood glucose and insulin with minimal risk of HYPOGLYCAEMIA
-When used as a monotherapy it can lower Hb1Ac by around 1.5%
What are the advantages and disadvantages of using Hb1Ac to monitor and diagnose T2DM?
Advantages:
-No fasting necessary
-Sample may be obtained at any time of the day
-
Reflects long-term BGC (blood glucose curve)
-Not altered by acute factors
Disadvantages:
- Delay in diagnosis- later than with blood glucose assessment
- Poor indicator of what happens post-prandial
- Will miss acute hyperglycaemia (only captures chronic)
What incretin contributes to failure of beta cells?
Glucagon like petide
What contributes to the excessive glucose production by the liver?
Increase glucagon levels
-enhanced hepatic sensitivity to glucagon
What does insulin resistance of adipocytes cause?
-Increases lipolysis
-Increased plasma free fatty acids
both aggravate insulin resistance in muscle and liver and contribute to beta cell failure
What contributes to the maintainence of hyperglycaemia?
- increased renal glucose reabsorption by the sodium glucose transporter
- increased threshold for glucose spillage in the urine
What exacerbates insulin resistance?
- resistance to appetite supressing hormones
- low brain dopamine
- increased brain serotonin levels
all these=weight gain=exacerbates resistance
Where are the different Glut transporters distributed?
1-endothelium, erythrocytes
2-kidney, small intestine, liver, pancreatic beta cells
3-Neurons, placenta
4-skeletal muscle, adipose
What is the function the different GLUT transporters?
1-Basal transport
2-low affinity transport
3-high affinity transport
4-Insulin regulated glucose transport
all are insulin independent apart from 4
What are incretins?
Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells