Type 1 Diabetes Mellitus Flashcards
What is type 1 diabetes?
Autoimmune condition - beta cells in pancreas are attacked and destroyed by immune system
Partial or complete deficiency of insulin production leading to hyperglycaemia
Requires long-life insulin treatment
Is age a good classifier of diabetes type?
No, type 1 diabetes can present later in life -> latent autoimmune diabetes in adults (LADA)
Type 2 diabetes mellitus can present in childhood
Is diabetic ketoacidosis strictly a feature of T1D?
No - can be a feature of T2DM
Aside from autoimmunity and obesity, what are some other causes of diabetes?
Monogenic diabetes (can present at Type 1 or 2), e.g. Maturity-onset diabetes of the young (MODY) and mitochondrial diabetes
Diabetes following pancreatic damage or other endocrine disease
Is Type 1 diabetes a condition of childhood/early adulthood alone?
No, evidence suggests it can occur throughout every decade of life
Clinicians faced with a challenge to differentiate adult-onset type 1 diabetes from large number of cases of type 2
Describe the stages of development of Type 1 diabetes
Describe the stages of development of type 1 diabetes with regards to the immune response
Why is the immune basis of type 1 important?
Increased prevalence of other autoimmune disease, e.g. hyperthyroidism
Risk of autoimmunity in relatives
More complete B-cell destruction
Autoantibodies can be useful clinically
Immune modulation offers possibility of novel treatments
What allele may make people genetically susceptible to type 1 diabetes?
HLA-DR allele
Particularly DR3 and DR4
Is susceptibility to diabetes controlled by a single gene?
No it is polygenic, however the HLA allele has the biggest odds ratio of predicting type 1 diabetes
What factors are implicated in the development of type 1 diabetes?
Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota
However, causality has not been established
List the pancreatic autoantibodies measured for type 1 diabetes
Insulin antibodies
Glutamic acid decarboxylase antibodies
Insulinoma-associated-2-autoantibodies (IA-2A)
Zinc-transporter 8 (ZnT8) antibodies
What are the symptoms of type 1 diabetes?
Polyuria
Nocturia
Polydypsia
Blurring of vision
Recurrent infections, e.g. thrush
Weight loss
Fatigue
What are the signs of type 1 diabetes?
Dehydration
Cachexia
Hyperventilation
Smell of ketones
Glycosuria
Ketonuria
If a person doesn’t have pancreatic autoantibodies, does that rule out type 1 diabetes?
No, the test has a good positive predictive value but a poor negative predictive value
Some people may not have the antibodies or they may have some that haven’t been discovered
What are the three main ketone bodies produced during beta oxidation of fatty acids?
Acetone
3-hydroxybutyrate
Acetoacetate
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 acute complications of hyperglycaemia?
Diabetic ketoacidosis
What are the chronic microvascular complications of type 1 diabetes?
Retinopathy
Neuropathy
Nephropathy
What are the chronic macrovascular complications of type 1 diabetes?
Ischaemic heart disease
Cerebrovascular disease
Peripheral vascular disease
How is type 1 diabetes managed?
Self-managed:
Insulin treatment
Dietary support/structured education
Technology
Transplantation
How does short-acting insulin compare to long acting?
Short acting:
- Taken with meals
- Exact molecular replicate of human insulin (actrapid)
- Can also take analogue form (e.g. Aspart)
Long acting:
- Once a day (background)
- Bound to zinc or protamine
- Can also be an analogue (e.g. Glargine)
Why are insulin analogues used?
Differ by one or two amino acids
Improves absorption
How does insulin pump therapy work?
- Continuous delivery of short-acting insulin analogue via pump into subcutaneous space
- Device can be programmed to deliver fixed units per hour through the day (basal)
- Manually bolus for meals
Give an example of a structured education programme for type 1 diabetes
DAFNE
5-day course on skills and training in self-management
How does the closed loop pump therapy work?
Real-time continuous glucose sensor measures change in glucose and algorithm is used to calculate insulin requirement - insulin is then delivered
Still have to manually calculate for meals
Describe islet cell transplants
Islet cells from deceased human donor isolated and transplanted into hepatic portal vein
Requires life-long immunosuppression
Describe pancreas transplants
Simultaneous with kidney transplants as this results in better survival of pancreas graft
Reserved for people with end-stage kidney failure
Require life-long immunosuppression
How do we monitor glucose levels?
Capillary blood glucose
Continuous glucose monitoring (allows for greater detail)
What factors can affect HbA1c reliability?
What factors are used to guide insulin doses?
Self-monitoring of blood glucose results at home
HbA1c results every 3-4 months
When does DKA occur in those with established type 1 diabetes?
In acute illness
Missed insulin doses
Inadequate insulin doses
What are the metabolic features of DKA?
pH <7.3
Increased ketones
HCO3- <15 mmol/L
Glucose >11 mmol/L
What is one numerical definition for hypoglycaemia?
Blood glucose <3.5 mmol/L
What is severe hypoglycaemia?
Any event requiring 3rd party assistance
What are the adrenergic and neuroglycopaenic symptoms of hypoglycaemia?
Adrenergic:
- Tremors
- Palpitations
- Sweating
- Hunger
Neuroglycopaenic:
- Somnolence
- Confusion
- Incoordination
- Seizures, coma
When does hypoglycaemia become a problem?
Excessive frequency
Impaired awareness
Nocturnal hypoglycaemia
Recurrent severe hypoglycaemia
What are the risks of hypoglycaemia?
Seizure, coma or death
Impacts on emotional well-being, driving, day-to-day function and cognition
Outline acute management of hypoglycaemia
