Type 1 diabetes Flashcards
What is type 1 diabetes?
autoimmune condition in which insulin-producing beta-cells in the pancreas are attacked and destroyed by the immune system
What is the result of type 1 diabetes?
a partial or complete deficiency of insulin production, which results in hyperglycaemia (life long insulin treatment)
What are the different types of diabetes?
- Type 1 Diabetes
- Type 2 Diabetes
- Hybrid forms
- Other
- Unclassified
- During pregnancy
What is latent autoimmune diabetes in adults (LADA)?
Autoimmune diabetes leading to insulin deficiency can present later in life
How can monogenic diabetes present?
phenotypically as Type 1 or Type 2 diabetes (eg. MODY, mitochondrial diabetes)
When can diabetes show?
- T2DM may present in childhood
- Diabetes may present following pancreatic damage or other endocrine disease
Can T1 be diagnosed later in life?
Yes
What are stages of development of T1 diabetes?
- Genetic predisposition
- Potential precipitating event - Overt immunological abnormalities; normal insulin release
- Progressive loss of insulin release; glucose normal
- Overt Diabets; C peptide present
- No C peptide present
- B cells reducing this whole time
Why is the immune basis of T1 important?
- Increased prevalence of other autoimmune disease
- Risk of autoimmunity in relatives
- More complete destruction of B-cells
- Auto antibodies can be useful clinically
- novel treatments
What is the first step in immune response?
presentation of auto-antigen to autoreactive CD4+ T lymphocytes
What cells do CD4+ cells activate?
CD8+ T lymphocytes
Where do CD8+ T lymphocytes travel to?
islets and lyse beta-cells expressing auto-antigen
Why is the attack of CD8+ T cells even worse?
- Exacerbated by release of pro-inflammatory cytokines
2. Underpinned also, by defects in regulatory T-cells that fail to supress autoimmunity
Are all beta cells in T1 destroyed?
No, some can produce small amounts of insulin but still need insulin therapy
What environmental factors are suggested in T1?
- Enteroviral infections
- Cow’s milk protein exposure
- Seasonal variation
- Changes in microbiota
When are pancreatic auto antibodies detectable?
in the sera of people with Type 1 diabetes at diagnosis
What are some pancreatic auto-antibodies?
- Insulin antibodies (IAA)
- Glutamic acid decarboxylase (GADA) – widespread neurotransmitter
- Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc-transporter 8 (ZnT8)
Are pancreatic auto antibodies need for diagnosis?
Not generally
What are the symptoms for type 1 diabetes?
- Excessive urination (polyuria)
- Nocturia
- Excessive thirst (polydipsia)
- Blurring of vision
- Recurrent infections eg thrush
- Weight loss
- Fatigue
What the signs of type 1 diabetes?
- dehydration
- cachexia
- hyperventilation
- smell of ketones
- glycosuria
- ketonuria
What are the aims for T1 treatment?
- Maintain glucose levels without excessive hypoglycaemia
- Restore a close to physiological insulin profile
- Prevent acute metabolic decompensation
- Prevent microvascular and macrovascular complications
What are acute complications of hyperglycaemia?
Diabetic ketoacidosis
What are chronic microvascular complications of hyperglycaemia?
- Retinopathy
- Neuropathy
- Nephropathy
What are the chronic macrovascular complications of hyperglycaemia?
- Ischaemic heart disease
- Cerebrovascular disease
- Peripheral vascular disease
What is the management of type 1 diabetes?
- Insulin Treatment
- Dietary support / structured educations
- Technology
- Transplantation
What are the types of insulin With meals (short / quick-acting insulin)?
- Human insulin – exact molecular replicate of human insulin (actrapid)
- Insulin analogue (Lispro, Aspart, Glulisine)
What are the types of insulin with Background (long-acting / basal)?
- Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH)
- Insulin analogue (Glargine, Determir, Degludec)
What is insulin pump therapy?
- 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
- Can change basal rate, and more flexible
What is the principal dietary advice given to people with T1D?
•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 inde
What can be offered according to NICE if you have T1D?
- 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
What is the process of closed loop/artifical pancreas?
- Real time continuous glucose sensor
- Algorithm to use glucose value to calculate insulin requirement
- Insulin pump delivers calculated insulin
- Changes in glucose
What is the process of islet cell transplantation?
- Isolate human islets from pancreas of deceased donor
- Transplant into hepatic portal vein
- Requires life-long immunosuppression
What are the benefits of simultaneous pancreas and kidney transplant?
- Better survival of pancreas graft when transplanted with kidneys
- Requires life-long immunosuppression
What are the aims of transplant for T1?
- try to restore physiological insulin production to the extent that insulin can be stopped
- Even if incomplete, often results in better control
What are the limitations for T1 transplants?
- availability of donors
2. complications of life-long immunosupression
How do you monitor glucose levels?
- Capillary (finger prick) blood glucose monitoring
2. Continuous glucose monitoring (restricted availability, NICE guidelines)
Why would you measure Glycated haemoglobin (HbA1c)?
- Reflect last 3 months (red blood cell lifespan) of glycaemia
- Biased to the 30 days preceding measurement
- Glycated 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 for type 1 diabetes?
- 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
When can you get diabetic ketoacidosis?
- Acute illness
- Missed insulin doses
- Inadequate insulin doses
- Life-threatening complication
- Can occur in any type of diabetes
What is the diabetic keoacidosis diagnosis?
•pH <7.3, ketones increased (urine of capillary blood), HCO3- <15 mmol/L and glucose >11 mmol/L
What is the definitions of hypoglycaemia?
- May become debilitating with increased frequency
- Numerical definition (variable) <3.6 mmol/L
What is severe hypoglycaemia?
any event requiring 3rd party assistance
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 may not be helpful in identifying hypoglycaemia?
HbA1c
What are the risk factors for hypoglycaemia?
- All people with type 1 diabetes
1. Exercise
2. Missed meals
3. Inappropriate insulin regime
4. Alcohol intake
5. Lower HbA1c
6. 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
- Behavioural psychology support
- Transplantation
What is C peptide?
Cleaved from proinsulin after release
What are the stages in Type 1 diabetes?
- Genetic risk
- Immune activation: beta cells activated
- Immune response: development of single antibody
- Stage 1: normal blood sugar
- Stage 2: abnormal blood sugar
- Stage 3: clinical diagnosis (when blood sugars risen to level that cause symptoms)
- Stage 4: Long standing T1D
What happens in early type 1 diabetes?
Immune cells crowded around islet and inflammatory response
What happens in long duration type 1 diabetes?
Immune cells disappeared and perislet fibrosis
What genes are involve in T1?
HLA, and lots of other genes
What is the diagnosis of T1 based on?
Clinical features and presence of ketones
What does insulin defiencecy lead to?
- Not take up glucose into muscle so breakdown muscle so proteinolysis so lots of AAs
- No inhibition of hepatic glucose production so high glucose
- Uninhibited lipolysis so lots of glycerol and NEFAs
Why are NEFAs important?
- NEFAs in liver undergo Beta oxidation
- Forms acetyl CoA, acetoacetate and acetone + 3OH-B
- These are ketone bodies
What is a complication of treating diabetes with insulin?
Hypoglycaemia
What is the most common regime for diabetes?
- Basal bolus regime
- TDS short acting
- Injected 15 mins before eating
- Once daily long acting
What is normal insulin process?
- Pradnial peak has two phases
- Insulin never completely suppressed
- Basal inulin has a flat profile
- Regimes try to mimic this
What is another regime?
- TDS actrapid
- Twice daily intermediate acting insulin
What blood tests helps us to monitor diabetes control overall?
Glycated haemoglobin
What can affect HbA1c?
- Alcoholism (I)
- Aspirin (D)
- Look at table
What are the adrenergic symptoms of hypoglycaemia?
- Tremors
- Palpitations
- Sweating
- Hunger
What are the neuroglycopaenic symptoms of hypoglycaemia?
- Somnolence
- Confusion
- Incoordination
- Seizures, coma
