1b T1DM Flashcards
What is T1DM?
an autoimmune condition in which insulin producing beta-cells in the pancreas are
attacked and destroyed by the immune system
What are the triggers of type 1 diabetes which can lead to an autoimmune destruction of islets?
Environmental triggers
Genetic risk
How does T1DM lead to hyperglycaemia?
Absolute insulin deficiency
What is MODY?
Maturity Onset Diabetes of the Young
What is pro insulin cleaved into?
Insulin and C peptide
What happens in the stages A and B of the diabetes onset graph?
Normal B cell Mass results in normal insulin production
What happens at stage C in the diabetes onset graph?
Genetic predisposition
What happens after the C stage in the diabetes onset graph?
Progressive loss of insulin release, glucose levels normal and then eventually Overt diabetes
What happens in the G stage of diabetes in the graph?
Overt diabetes, C peptide Present
What happens in the H stage of diabetes in the graph?
No C peptide and no insulin present
What are the pancreatic Beta cells attacked with?
Pancreatic autoantibodies = immune activation
Why is the immune basis of T1DM important?
- Increased risk of other autoimmune conditions
- Risk of autoimmunity on relatives
- More destruction of Beta Cells
Are all the beta cells destroyed in T1DM?
No = some people with type 1 diabetes continue to produce insulin but not enough to negate the need for insulin therapy
Which HLA-DR genes pose a significant risk to the genetic susceptibility of Diabetes?
DR3 and DR4
What are four environmental factors which might contribute to the implications of T1DM?
- Enteroviral infections
- Cow’s milk protein exposure
- Seasonal variation
- Changes in microbiota
Where are pancreatic autoantibodies detectable?
Detectable in the sera of people with Type 1 diabetes at
diagnosis.
What are three examples of pancreatic autoantibodies which are detectable?
- Insulin antibodies (IAA)
- Glutamic acid decarboxylase (GADA) – widespread
neurotransmitter - Insulinoma-associated-2 autoantibodies (IA-2A)-Zinctransporter 8 (ZnT8)
What are the symptoms of T1DM?
Excessive urination (polyuria)
Nocturia
Excessive thirst (polydipsia)
Blurring of vision
Recurrent infections eg thrush
Weight loss
Fatigue
What are the signs of T1DM?
dehydration
cachexia
hyperventilation
smell of ketones
glycosuria
ketonuria
What is the diagnosis of T1DM based on?
CLINICAL FEATURES and presence of ketones
What are the effects of insulin deficiency on the muscle?
Proteinolysis resulting in more Amino acid
What are the effects of lack of insulin on the liver?
Hepatic glucose output increases resulting in more glucose
what are the effects of lack of insulin on the fat cells?
Lipolysis increases resulting in more NEFA
Describe how ketone bodies are produced?
NEFA taken into the liver
Beta Oxidation - Fatty Acyl CoA is converted into Acetyl CoA which is then made into Acetoacetate, Acetone and 3 Hydroxybutyrate (ketone bodies)
What are ketone bodies?
Fuel source in times of starvation
Why can ketone bodies become problematic?
they are acidic, therefore too many results in the blood becoming more acidic and an accumulation of H+
what is the effect of insulin on beta oxidation?
insulin inhibits it, stimulated by glucagon
What are the treatment aims for someone with T1DM?
Maintain glucose levels without excessive
hypoglycaemia
* Restore a close to physiological insulin profile
* Prevent acute metabolic decompensation
* Prevent microvascular and macrovascular
complications
What are the acute complications of hyperglycaemia?
Diabetic ketoacidosis
What are the macrovascular complications of T1DM?
Ischaemic heart disease
* Cerebrovascular disease
* Peripheral vascular disease
What are the microvascular complications of T1DM?
Retinopathy
* Neuropathy
* Nephropathy
What word id used to describe T1DM treatment?
Self - Management
What are the compensatory mechanisms for Hypoglycaemia?
Glucagon
Catecholamines
Cortisol
growth hormones
How many phases does the prandial peak have?
2 Phases - first and second phase insulin release
What are the key characteristics of the physiological insulin profile?
- Basal insulin has a flat profile
- Prandial peak has 2 phases
- Insulin is never completely suppressed
What is the basal Bolus Regime?
Treatment for T1DM
- Short / quick acting insulin with meals = Bolus
- Background long lasting insulin = Basal
What are the two types of basal insulin?
- Human insulin - exact molecular replicate of human insulin
- Insulin Analogue
What are the types of short acting human insulin?
actrapid
What are the types of short acting insulin analogues?
Lispro
Aspart
Glulisine
What is an insulin analogue?
Recombinant = one or two amino acids have been changed in order to increase absorption
Why is c peptide measured rather than insulin?
C peptide has a longer half life
What are the two types of background insulin?
- Bound to zinc or protamine
- Insulin analogues
What is the name of the insulins which are bound to zinc or protamine?
Neutral Protamine Hagedorn, NPH
What is the typical basal Bolus regime?
TDS (three times/day) short-acting
Once daily long-acting
What is insulin pump therapy?
Continuous delivery of short-acting insulin analogue - delivery of insulin into the subcutaneous space
What are the benefits of insulin pump therapy?
Programme the device to deliver fixed units / hour
throughout the day (basal)
What are the characteristics of a insulin from a pump?
Variable basal rates
Extended boluses
Greater flexibility
What is the dietary advice which should be given to patients with diabetes?
- Dose adjustment for carbohydrate content of food.
- All people with type 1 diabetes should receive training for carbohydrate counting
- Where possible, substitute refined carbohydrate
containing foods (sugary / high glycaemic index) with complex carbohydrates (starchy / low glycaemic index)
What course are all people with a diagnosis of diabetes given?
Structured Education programme on how to administer their insulin
What is the closed loop system?
Artificial insulin delivery:
- Algorithm to use glucose value to calculate insulin requirement
- Pump delivers insulin
- Results in a change in glucose
- real time continuous glucose sensor
What are the side effects of a islet cell transplantation?
Requires life-long immunosuppression
Why are pancreas transplants often done with kidney?
Better survival of pancreas graft when
transplanted with kidneys
what are the limitations of transplantation?
availability of donors, complications of lifelong immunosuppression
How are glucose levels monitored?
Capillary (finger prick) blood glucose monitoring
Continuous glucose monitoring
What is HbA1c a measurement of?
Glycated haemaglobin -
Why is HbA1c useful?
Reflect last 3 months (red blood cell lifespan) of glycaemia
what is the relationship between glucose levels and HbA1c levels?
linear relationship
What four things can affect HbA1c levels?
- Erythropoesis
- Altered Haemaglobin
- Glycation
- Erythrocyte production
What is used to guide insulin doses?
Using self monitoring of blood glucose results at home and HbA1c results every 3-4 months
Based on results - increase or decrease insulin doses
What are the three acute complications of T1DM?
- Diabetic ketoacidosis
- Uncontrolled hyperglycaemia
- Hypoglycaemia
What are the criteria needed for DKA diagnosis?
pH <7.3, ketones increased (urine or
capillary blood), HCO3
- <15 mmol/L and
glucose >11 mmol/L
Which types of diabetes can ketoacidosis occur in?
both
what is the numerical definition of hypoglycaemia?
<3.6 mmol/L
What is severe hypoglycaemia?
any event requiring 3rd party assistance
What are the adrenergic symptoms of hypoglycaemia?
*Tremors
*Palpitations
*Sweating
*Hunger
What are the neuroglycopaenic symptoms of hypoglycaemia?
*Somnolence
*Confusion
*Incoordination
*Seizures, coma
When does hypoglycaemia become a problem?
- Excessive frequency
- Impaired awareness (unable to detect low
blood glucose) - Nocturnal hypoglycaemia
- Recurrent severe hypoglycaemia
What are the risks of hypoglycaemia?
Seizure / coma/ death (dead in bed)
* Impacts on emotional well-being
* Impacts on driving
* Impacts on day to day function
* Impacts on cognition
What are risk factors for hypoglycaemia?
Exercise
Missed meals
Inappropriate insulin regime
Alcohol intake
Lower HbA1c
Lack of training around dose-adjustment for meals
What are the strategies to support problematic hypoglycaemia?
- Indication for insulin-pump therapy (CSII)
- May try different insulin analogues
- Revisit carbohydrate counting / structured
education - Behavioral psychology support
- Transplantation
What is the acute management plan for someone with a hypo who is alert and orientated?
Oral Carbohydrates
Rapid acting;
juice / sweets
What is the acute management plan for someone with a hypo who is drowsy / confused but swallowing is intact?
Buccal Glucose
Glucogel
Complex Carbohydrates
Describe the development of type 1 diabetes?
- starts with genetic predisposition
- precipitating event - virus, stressful event
- triggers autoimmune process
- loss of beta cells
- insulin production decreases rapidly
- become hyperglycaemic
- however not all beta cells are destroyed
Describe the reversible reaction in the process of making HbA1c and how long does it take?
N-terminal valine residue Beta chain + Glucose → Schiff base
This is fast
Describe the irreversible reaction that makes HbA1c and how long does it take?
Schiff Base -> Amadori Product (HbA1c) (Slow)
