(PM3B) Diabetes Flashcards
What is diabetes mellitus?
Metabolic disorder characterised by chronic hyperglycaemia
Name different sources of glucose.
(1) Diet
(2) Glycogenolysis
(3) Gluconeogenesis
Which hormones regulate glucose?
- Insulin
- Glucagon
What is the normal glucose range?
3-8 mM
Does DM affect life expectancy? If so, by how much?
Yes
Approx. 1/3
What is the greatest risk factor for DM?
(1) Renal failure - 100x risk
(2) Cardiovascular disease incidence - 3-5x
What co-morbidities does DM increase risk of?
(1) Increased risk of blindness
(2) Amputation
What are the major diabetes mellitus complications?
(1) Retinopathy
(2) Cerebrovascular disease
(3) Coronary heart disease
(4) Nephropathy
(5) Peripheral vascular disease
(6) Neuropathy
(7) Diabetic foot - ulceration/ amputation
How is low glucose detected? What is the response?
(1) Pancreas detects it
(2) Glucagon is secreted:
ø Glucose is freed from muscle, fat + liver
ø Storage of glycogen is stopped
How is high glucose detected? What is the response?
(1) Pancreas detects it
(2) Insulin is secreted
ø Removes glucose from the bloodstream
ø Glucose stored in fat and muscle
ø Glucose converted to glycogen in the liver
ø Glucose production by liver is stopped
If someone has DM, and therefore cannot use glucose for energy, what sources do they use? What are these pathways called?
(1) Lipids + Proteins
(2) Catabolic pathways
What do effects do catabolic pathways have?
(1) Ketotic breath
(2) Acidosis
(3) Increased lipolysis - produces more FFAs (hyperlipidaemia)
What are the types of primary DM?
Type 1: Insulin-dependent
Type 2: Non-insulin dependent
Describe Type 1 DM.
- Polygenic autoimmune disorder
- Specific destruction of pancreatic beta-cells
- Leads to complete insulin deficiency
Describe Type 2 DM.
- Polygenic disorder
- Decrease in beta-cell mass
- Decreased secretion by beta-cells
- Leads to increased peripheral insulin resistance
What types of risk factors for diabetes mellitus are there?
Modifiable and non-modifiable
What are examples of non-modifiable risk factors for DM?
(1) Family history
(2) Ethnicity
(3) Age - Type 2
(4) Gestational diabetes/ polycystic ovary syndrome
What are examples of modifiable risk factors for DM?
(1) Weight - Type 2
(2) Waist circumference - Type 2
(3) Sedentary lifestyle - Type 2
(4) Social deprivation/ low income
ø 2.5x more likely to develop DM
How could the symptoms of DM Type 1 be described?
Acute symptoms
How could the symptoms of DM Type 2 be described?
Sub-acute symptoms
What are the common symptoms of Type 1 DM?
(1) 2-4 history of thirst
(2) Polyuria
(3) Weight-loss
(4) Lethargy
What are the common symptoms of Type 2 DM?
(1) History of thirst
(2) Polyuria
(3) Lethargy
(4) Visual disturbances
(5) Infections
How long is the duration of symptoms for Type 1 DM? How does this compare with Type 2?
(1) 2-4 weeks
(2) Several months
What are the clinical signs of DM?
(1) Glucosuria - excretion of glucose in urine
(2) Hyperglycaemia
(3) Impaired glucose tolerance
(4) Complications of diabetes
ø Retinopathy
ø Nephropathy
ø Peripheral neuropathy
ø Foot ulceration
How is the symptom of polyuria caused in patients with DM?
(1) Blood glucose levels are increased
(2) Blood osmolarity is decreased - Water is drawn into blood from interstitial spaces
(3) Blood volume is increased
(4) Increased urination frequency reduces blood volume
How is the symptom of increased thirst caused in patients with DM?
(1) Loss of fluids + electrolytes
(2) Stimulation of thirst
How is weight loss caused in patients with DM?
(1) Loss of fluids (dehydration)
(2) Breakdown of fat + muscle energy stores
What happens when fats are broken down for energy supply?
(1) Leads to production of ketone bodies
(2) Ketone bodies increase the acidity of the blood (ketoacidosis)
(3) Ketoacidosis leads to a hyperglycaemic coma if untreated
When are 2 tests to confirm DM required?
When the patient is asymptomatic
What are the tests used to diagnose diabetes mellitus?
(1) Detection of glucose in urine (glucosuria)
(2) Random venous plasma glucose test
(3) Fasting venous plasma glucose test
(4) Oral glucose tolerance test
(5) Glycated haemoglobulin levels
When is the oral glucose tolerance test used?
(1) Testing for Type 1 DM
(2) Testing for Type 2 DM
(3) Screening for gestational diabetes
What is the middle ground between ‘normal’ and ‘diabetes’ called?
Impaired fasting glycaemia
What is the oral glucose tolerance test?
The gold standard test for diagnosing diabetes
What is the normal venous plasma glucose for fasting and 2 hour post-prandial range ?
(1) <6mmol/L
(2) <7.8mmol/L
What is the diabetic venous plasma glucose for fasting and 2 hour post-prandial range?
(1) ≥7mmol/L
(2) ≥11.1mmol/L
What is the impaired glucose tolerance venous plasma glucose for fasting and 2 hour post-prandial range?
(1) <7mmol/L
(2) 7.8-11mmol/L
What is the impaired fasting glycaemia venous plasma glucose range?
6-6.9mmol/L
What happens when haemoglobin (RBCs) is exposed to glucose?
They become irreversibly glycated
What is the acronym for glycated haemoglobin?
HbA1c
What is HbA1c?
Glycated haemoglobin
What can the amount of HbA1c be used for?
Determining the average glucose levels that RBCs have been exposed to for last 1-3 months
What does FPG stand for?
Fasting plasma glucose
What is Type 1 diabetes mellitus?
Auto-immune destruction of pancreatic beta cells
Meaning no insulin can be produced
Where is insulin produced in the body?
Pancreatic beta cells
What are the main risk factors for Type 1 diabetes?
(1) Family history
(2) Ethnicity - Northern European descent
What initiates the autoimmune beta cell destruction?
Not fully understood
But TRIGGERED by something
Define ‘iatrogenic’.
Illness following treatment or medical intervention
What is the first line treatment for T1DM?
Injected insulin replacement - lifelong
What dietary modification is required for management of T1DM?
(1) Low fat
(2) High fibre
(3) Healthy diet - to spread nutrients across the day
What monitoring requirements are there for T1DM?
(1) Insulin dose adjustment
(2) Glycaemic control
(3) Complications - retinopathy, diabetic foot, CVD risk
What management options are there for T1DM?
(1) Injected insulin replacement
(2) Diet modification
(3) Monitoring
(4) Exercise
(5) Education on the importance of adherence
What is the purpose of insulin replacement therapy?
To be administered in a way that mimics the normal insulin secretion pattern
Describe the concentration of insulin secretion in a healthy patient.
(1) Secreted at a slow basal rate
(2) Secreted rapidly in response to a meal
(3) Secretion returns to basal rate after 2 hours following meal
Why would it be beneficial to genetically modify a human insulin?
To achieve rapid/ short/ intermediate/ long lasting onset/ duration of effect
Name example(s) of rapid onset insulin.
- Lispro
- Aspart
- Glulisine
Name example(s) of short onset insulin.
- Normal insulin
Name example(s) of intermediate insulin.
- NPH
Name example(s) of long-acting insulin.
- Detemir
- Glargine
What is commonly experienced by newly diagnosed T1DM patients when starting treatment?
Patients can experience a partial remission phase
Only low levels of insulin are required to maintain good glycaemic control
What is hypoglycaemia, and how is it caused?
(1) Abnormally low blood sugar
(2) Most common side effect of insulin therapy
What is lipohypertrophy? Where does it occur and what causes it?
Accumulation of fat at injection sites
Due to local effects of insulin
What is the purpose of rotating injection sites?
To avoid lipohypertrophy
How can lipohypertrophy be avoided?
Rotation of injection sites
Is insulin allergy common?
No, insulin is highly purified
If a patient were allergic to injected insulin, what would be the anticipated effect?
- Atrophy of fat
- Altered effect of insulin
Why is monitoring glucose levels important in T1DM?
Allows insulin doses to be adjusted accordingly
What is retinopathy?
Disease of the retina, impairs/ loses vision
How prevalent is T2DM?
90% of all DM cases
How is T2DM characterised?
(1) Reduced insulin secretion
(2) Increased insulin resistance
What change is present in patients with T2DM, that affects their insulin secretion?
A 50% reduction in pancreatic beta-cell mass
How is hypoglycaemia caused in patients with T2DM?
Impaired insulin secretion in early phase (first meal)
Increased second phase response
Exaggerated second phase can lead to hypoglycaemia after 3-4 hours
What are the common symptoms of T2DM?
(1) Increased thirst/ hunger
(2) Polyuria - increased urination - especially at night
(3) Fatigue
(4) Blurred vision
(5) Infection
What is HHS?
Hyperosmolar Hyperglycaemic State
Hyperglycaemia, dehydrated, uraemia
What is uraemia?
Raised level of urea and other nitrogenous waste in the blood - which would normally be eliminated by the kidneys
What condition is characterised by a raised level of urea and other nitrogenous waste in the blood?
Uraemia
How can incidence of T2DM be reduced?
Lifestyle interventions
(1) Reduce weight
(2) Reduce fat intake
(3) Increase dietary fibre
(4) Exercise
How long can T2DM be asymptomatic for?
Up to 10 years
Why are diabetes screening programmes used?
To prevent T2DM
To detect T2DM in asymptomatic patients
Universal screening tests are not practical. Who is target by the screening programs?
Patients at risk
What tests do diabetes screening programs include?
(1) Oral glucose tolerance test - random glucose levels
(2) Fasting blood glucose tests
(3) HbA1c levels - glycated haemoglobin
What is the first line treatment for T2DM?
Lifestyle interventions, e.g. diet + weight loss + exercise
What drug treatment options are there for T2DM?
(1) Hypoglycaemic agents
(2) Insulins
What categories of oral hypoglycaemic agents are there?
(1) Insulin sensitisers
(2) Insulin secretagogues
(3) Inhibitor of glucose absorption from GIT
(4) Inhibitor renal glucose reuptake
What is an ‘insulin sensitiser’?
- Enhances the effect of endogenous insulin
- Increases target cell sensitivity to insulin
- Decreases glucose production in liver
What does metformin do?
- First line treatment for T2DM
- Suppresses appetite
- Cardio-protective effect
When can metformin not be given? Why?
When the patient has renal impairment, cardiac failure, or liver failure
Because metformin is associated with lactic acidosis
What comorbidity are the glitazones linked to?
Cardiovascular disease
What comorbidities does pioglitazone increase risk of?
(1) Heart failure
(2) Bladder cancer
What does an insulin secretagogue do?
Stimulates insulin release from the pancreas
What is the purpose of an insulin secretagogue?
- To restore early phase insulin release
- To return plasma levels to pre-prandial levels
What does post-prandial mean?
Following dinner/ lunch/ a meal
What does pre-prandial mean?
Prior to dinner/ lunch/ a meal
What are 2 types of insulin secretagogues?
(1) Sulphonylureas
(2) Meglitinides
How do sulphonylureas affect a patient’s weight?
Cause patients to gain weight
Not first choice for overweight patients
What is the mechanism of action of sulphonylureas and meglitinides? How does it differ?
Bind to receptors that close a K+ ATP channel
Causes a rise in intracellular calcium and insulin release
How do the side effects of meglitinides compare to other insulin secretagogues?
Fewer side-effects/ shorter duration
Because it is shorter acting
Which insulin secretagogue has reduced side-effects? Why?
(1) Meglitinides
(2) Because they are short-acting
Give an example of an inhibitor of glucose absorption in the GIT.
Acarbose
What is the mechanism of action of an inhibitor of glucose absorption in the GIT?
It binds to alpha-glucosidase with higher affinity than dietary carbohydrates
Reduces post-prandial peak in blood glucose by slowing the digestion and absorption of glucose
What is more effective in reducing HbA1c plasma concentration, metformin or inhibitors of glucose absorption in the GIT?
Metformin is more effective
What side-effects are associated with inhibitors of glucose absorption in the GIT, such as acarbose?
(1) Flatuence
(2) Bloating
(3) Diarrhoea
What is GLP-1?
Glucagon-like peptide-1
- Stimulates insulin release from pancreatic beta-cells
- Suppresses glucagon release from pancreatic alpha-cells
- Decreases gastric emptying
What are incretins? Give 2 examples
- Molecules which reduce glucagon production and increase insulin
- GLP-1 or GIP
How are GLP-1 analogues (mimetics) delivered?
Subcutaneous injection
What is SGLT2? Where is it located?
(1) Responsible for 90% of glucose reabsorption
(2) Proximal tubule of nephron
What is gestational diabetes?
Diabetes occurring for the first time during pregnancy
What are the side effects of gestational diabetes?
(1) Increases risk of miscarriage
(2) Congenital malformations
(3) Increased risk of still birth
(4) Premature baby death (first year of life)
How can the side-effects of gestational diabetes be reduced/ managed?
Effective glycaemic control
What are the risk factors for gestational diabetes?
Same as Type 2 diabetes mellitus
- Family history
- Age
- Weight
- Ethnicity
When are pregnant women screened for gestational diabetes?
If they are at risk
What is the treatment for gestational diabetes?
(1) Lifestyle modification
(2) Insulin therapy if lifestyle modification is insufficient
