Type 1 Diabetes Flashcards
What is type 1 diabetes?
An autoimmune condition in which insulin-producing beta-cells in the pancreas are attacked and destroyed by the immune system
The result is a partial or complete deficiency of insulin production, which results in hyperglycaemia
The resultant hyperglycaemia requires life-long insulin treatment
What causes type 1 vs type 2 diabetes
Type1 : Environmental trigger and genetic risk
Leads to autoimmune destruction of islets
Absolute insulin deficiency
Type 2: Genetic risk and Obesity
Insulin resistance
Relative insulin deficiency
Why do we measure c peptide instead of insulin
As c peptide has a longer half life
And insulin can be given so when measured won’t know if it due to what has been given or it is being produced
What are the stages of development of type 1 diabetes?
Genetic predisposition
Potential precipitating event
Overt immunological abnormalities; normal insulin release
Progressive loss of insulin release; glucose normal
Overt diabetes; c-peptide present
No C-peptide present
Genetic risk
Immune activation
Immune response - development of single autoantibody
Why is the immune basis important
Increased prevalence of other autoimmune disease
Risk of autoimmunity in relatives
More complete destruction of B-cells
Auto antibodies can be useful clinically
Immune modulation offers the possibility of novel treatments
Not there yet
Explain a brief overview of immunology in type 1 diabetes
Defect in innate and adaptive immune system
Primary step is the presentation of auto-antigen to autoreactive CD4+ T lymphocytes
CD4+ cells activate CD8+ T lymphocytes
CD8+ cells travel to islets and lyse beta-cells expressing auto-antigen
Exacerbated by release of pro-inflammatory cytokines
Underpinned also, by defects in regulatory T-cells that fail to supress autoimmunity
Why is it a positive that some Beta cells are not destroyed in type 1 diabetes
Shows that some are avoiding the immune system
When you have a low blood sugar and too much insulin is given and heading towards a hypo, pancreas can switch of insulin production
Less likely to develop microvascular complications later on
What allele does the biggest genetic susceptibility come from?
HLA -DR allele
(Human leukocyte antigen)
DR3 +4
What are environmental factors for type 1 diabetes
Dip during Summer
Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota
What are pancreatic auto-antibodies detectable in the sera of people with type 1 diabetes at diagnosis
Insulin antibodies (IAA)
Glutamic acid decarboxylase (GADA) – widespread neurotransmitter
Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc-transporter 8 (ZnT8)
What are the presenting symptoms of type 1 diabetes
Excessive urination (polyuria)
Nocturia
Excessive thirst (polydipsia)
Blurring of vision
Recurrent infections eg thrush
Weight loss
Fatigue
What are the presenting signs of type 1 diabetes
dehydration
cachexia
hyperventilation
smell of ketones
glycosuria
ketonuria
What is the diagnosis of type 1 diabetes based on
DIAGNOSIS IS BASED ON CLINICAL FEATURES and presence of ketones (in some cases pancreatic autoantibodies / C-peptide may be measured)
What happens with an insulin deficiency
Protienolysis into amino acids
Hepatic glucose output increases (counter-intuitive)
Lipolysis increases so more glycerol and NEFA
What happens when NEFA is taken up by the liver
More Beta oxidation and ketone bodies made
Can cause ketoacidosis
What are the aims of treatment in type 1 diabetes
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 complications of hyperglycaemia
Acute
Diabetic ketoacidosis
Chronic
Microvascular
Retinopathy
Neuropathy
Nephropathy
Macrovascular
Ischaemic heart disease
Cerebrovascular disease
Peripheral vascular disease
What are the effects of treatment itself?
Hypoglycaemia
How to manage type 1 diabetes
Insulin Treatment
Dietary support / structured educations
Technology
Transplantation
Describe an insulin profile
Second phase insulin release half an hour after meal
Insulin never 0, just at basal insulin level
What are examples of short/quick-acting insulin
Human insulin – exact molecular replicate of human insulin (actrapid)
Insulin analogue (Lispro, Aspart, Glulisine)
What are background - long acting/basal - types of insulin
Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH)
Insulin analogue (Glargine, Determir, Degludec)
How does insulin pump therapy work
Continuous delivery of short-acting insulin analogue e.g. novorapid via pump
Delivery of insulin into subcutaneous space
Programme the device to deliver fixed units / hour throughout the day (basal)
Actively bolus for meals
What is the dietary advice offered for those with type 1 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)
NICE Guidelines [NG17] for type 1 diabetes
All people with type 1 diabetes should be offered a Structured Education Programme
e.g. DAFNE but many others
5 day course on skills and training in self-management
How does closed loop / artificial pancreas work?
Algorithm to use glucose value to calculate insulin requirement
Insulin pump delivers calculated insulin
Real-time continuous glucose sensor
How does islet cell transplant work
Isolate human islets from pancreas of deceased donor
Transplant into hepatic portal vein
Requires life-long immunosuppression
Is it better to transplant both pancreas and kidney
Better survival of pancreas graft when transplanted with kidneys
Requires life-long immunosuppression
How do we monitor glucose levels
Capillary (finger prick) blood glucose monitoring
Continuous glucose monitoring (restricted availability, NICE guidelines)
What is glycated haemoglobin (HbA1c)
Reflect last 3 months (red blood cell lifespan) of glycaemia
Biased to the 30 days preceding measurement
Glycated (no enzyme involved) NOT glycosylated (enzymatic)
Therefore linear relationship
Irreversible reaction
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 acute complications from type 1
Diabetic ketoacidosis
Uncontrolled hyperglycaemia
Hypoglycaemia
What is diabetic ketoacidosis
Can be a presenting feature of new-onset type 1 diabetes
Occurs in those with established type 1 diabetes
-Acute illness
-Missed insulin doses
-Inadequate insulin doses
Life-threatening complication
Can occur in any type of diabetes
How to diagnose diabetic ketoacidosis
pH <7.3, ketones increased (urine or capillary blood), HCO3- <15 mmol/L and glucose >11 mmol/L
What are symptoms of hypoglycaemia
Adrenergic:
-Tremors
-Palpitations
-Sweating
-Hunger
Neuroglycopenic:
Somnolence
Confusion
Incoordination
Seizures, coma
What is severe hypoglycaemia
Any event requiring 3rd part assistance
When does hypoglycaemia become a problem?
Excessive frequency
Impaired awareness (unable to detect low blood glucose)
Nocturnal hypoglycaemia
Recurrent severe hypoglycaemia
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
Who is at risk of hypoglycaemia
All people with type 1 diabetes
Risk factors:
Exercise
Missed meals
Inappropriate insulin regime
Alcohol intake
Lower HbA1c
Lack of training around dose-adjustment for meals
What are 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
Describe the acute management of hypoglycaemia
Alert & Orientated:
Oral Carbohydrates
Rapid acting;
juice / sweets
Longer acting;
sandwich
Drowsy / confused but swallow intact:
Buccal glucose
e.g. Hypostop / glucogel
Complex carbohydrate
Unconscious or concerned about swallow:
IV access
20% glucose IV
Deteriorating / refractory /insulin induced /difficult IV access: consider IM /SC 1mg Glucagon
