Type 1 Diabetes Flashcards
What causes type 1 diabetes?
What does type 1 diabetes result in?
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 are the different types of diabetes?
Type 1 Diabetes Type 2 Diabetes Hybrid forms (starts in adulthood but presents like type 1) Other Unclassified During pregnancy
What is LADA?
Latent autoimmune diabetes in adults
Autoimmune diabetes leading to insulin deficiency in, presenting in adults
Can T2DM present in childhood?
Can diabetic ketoacidosis be a feature of T2DM?
Yes
Yes - although more typical in type 1
What event might diabetes present after?
Following pancreatic damage or other endocrine disease
What challenges might clinicians face when trying to diagnose type 1 and type 2 diabetes?
Clinicians are faced with a challenge, trying to differentiate adult-onset type 1 diabetes from the much large numbers of cases of type 2 diabetes
What are the stages of development of type 1 diabetes?
Genetic predisposition
Potential precipitating event (a triggering event)
Overt immunological abnormalities; normal insulin release
Progressive loss of insulin release; glucose normal
Overt diabetes; C-peptide present
No C-peptide present
What do we measure when looking at beta cell function?
C-peptide cleaved from pro-insulin (C-peptide more stable in the blood)
Pro-Insulin is cleaved to make insulin and c peptide in a 1:1 ration
Why is the immune basis of T1DM 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)
Summarise immunology of T1DM?
Primary step is the presentation (by APC) of auto-antigen to autoreactive CD4+ T lymphocytes
CD4+ cells activate CD8+ T lymphocytes (cytotoxic)
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
Are all the beta cells destroyed in T1DM?
Not always, some beta cells escape the immune response
Some people with type 1 diabetes continue to produce small amounts of insulin and have C-peptide
Not enough to negate the need for insulin therapy
What is HLA?
What HLA is associated with diabetes?
Human Leukocyte antigen
HLA-DR = If you have these polymorphisms you are 6x more likely to develop T1DM
What are the environmental factors involved with T1DM?
Multiple factors implicated, but causality has not been established
Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota
When are auto-antibodies detectable?
Are auto-antibodies needed for diagnosis?
Detectable in the sera (serums) of people with Type 1 diabetes at diagnosis
Not generally needed for diagnosis in most cases
When are pancreatic auto-antibodies made?
Made when the beta cells content is exposed
What are the different types of pancreatic auto-antibodies ?
Insulin autoantibodies (IAA) Glutamic acid decarboxylase (GADA) – widespread neurotransmitter (prevents GABA production in pancreatic cell) Insulinoma-associated-2 autoantibodies (IA-2A) Zinc-transporter 8 (ZnT8) autoantibody
What are symptoms of T1DM?
Excessive urination (polyuria) Nocturia Excessive thirst (polydipsia) Blurring of vision Recurrent infections eg thrush Weight loss Fatigue
Why does T1DM lead to blurry vision?
Glucose goes into eyeball
Causes osmotic change in lens
What are the signs of T1DM?
Dehydration Cachexia (wasting) Hyperventilation (resp. compensation) Smell of ketones Glycosuria Ketonuria
What are the 4 Ts of T1DM?
Toilet
Thirsty
Tired
Thinner
What is the mechanism of ketone body production in T1DM?
- Insulin deficiency- less suppression of fatty acyl-coa metabolism (Also stimulated by glucagon)
- NEFAs enter liver
- Fatty acyl-coa converts NEFA to Acetyl COA -> acetoacetate -> acetone + 3OH-B
- These are ketone bodies and are acidic so bad lead to diabetic ketoacidosis
What happens with insulin deficiency?
Proteolysis (inc. AAs)
Hepatic glucose output (inc. glucose)
Lipolysis (inc. Glycine and NEFA
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 is the only thing can prevent patients from taking insulin for life?
Transplant
What are the acute complications of hyperglycaemia?
What are the microvascular chronic complications of hyperglycaemia?
What are the macrovascular chronic complications of hyperglycaemia?
Acute:
Diabetic ketoacidosis
Microvascular:
Retinopathy
Neuropathy
Nephropathy
Macrovascular:
Ischaemic heart disease
Cerebrovascular disease
Peripheral vascular disease
How is T1DM managed?
Is self-managed with:
Insulin Treatment
Dietary support / structured educations
Technology
Transplantation
What are the main features of physiological profile of insulin?
Basal insulin has a flat profile
Prandial (after eating) peak has two phases (the second phase is to break down remaining glucose- it’s a much smaller peak)
Insulin is never completely suppressed
What are the different types of insulin with meals?
short / quick-acting insulin
Human insulin – exact molecular replicate of human insulin (actrapid) Insulin analogue (Lispro, Aspart, Glulisine)- genetically altered in lab to be more rapid acting
What are the different types of long-acting insulin?
Background insulin
Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH)- delay absorption of insulin Insulin analogue (Glargine, Determir, Degludec)
What is the typical regime for taking insulin?
Typical basal bolus regime
Background once a day
Short acting 3x a day (but can be more with snacks)
OR
Short acting (actrapid) 3x day
Intermediate acting 2x day
What are the main features of 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
What is CSII?
Alternative name for pump therapy
Continuous subcutaneous insulin infusion
What are the principles of dietary advice for T1DM?
What are the NICE guidelines for diet and T1DM?
Dose adjustment for carbohydrate content of food.
All people with type 1 diabetes should receive training for carbohydrate counting
Where possible substitute refined carb containing food with complex carbs (low glycaemic index)
NICE:
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 substitutes should be made in diet?
Where possible, substitute refined carbohydrate containing foods (sugary / high glycaemic index) with complex carbohydrates (starchy / low glycaemic index
What is the closed-loop/artificial pancreas?
Real-time continuous glucose sensor- detects change in glucose
Algorithm which uses glucose value to calculate insulin requirement
Insulin pump delivers calculated insulin (basal insulin)
Still need to log your carb intake so the pump can deliver short acting insulin
Takes about 15 mins to detect glucose levels s pump acts 15 mins before time
`Hybrid closed loop systems are available on the NHS
What are Hybrid closed loop systems?
Not quite closed loop
The pump still needs to be told before a meal
Available on NHS
What are the two types of transplant?
What are the main features of these?
Islet cell transplants - isolate human islets from pancreas of deceased donor
Transplant into hepatic portal vein
Requires life-long immunosuppression
Simultaneous pancreas and kidney transplants - better survival of pancreas graft when transplanted with kidneys
Requires life-long immunosuppression
Why are transplants not more frequently used?
Limited organ availability
Pancreas is not generally viable
Risks of long-term immunosuppressants
What are the aims of transplantation?
Try to restore physiological insulin production to the extent that insulin can be stopped
Even if incomplete, often results in better control
How do you measure glucose levels?
Capillary (finger prick) blood glucose monitoring
Continuous glucose monitoring (HCL- restricted availability, NICE guidelines)
What are the main features of HbA1c?
What are the limitations of 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
Not perfect
Things affect it
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 main features of diabetic ketoacidosis?
Can be a presenting feature of new-onset type 1 diabetes
Occurs in those with established type 1 diabetes. Causes:
-Acute illness
-Missed insulin doses
-Inadequate insulin doses
Life-threatening complication
Can occur in any type of diabetes
How is diabetic ketoacidosis diagnosed?
pH <7.3, ketones increased (urine or capillary blood), HCO3- <15 mmol/L and glucose >11 mmol/L
What are the main features of hypoglycaemia?
To some extent an inevitable feature of the self-management of type 1 diabetes
‘Lost normal physiology and homeostasis’
May become debilitating with increased frequency
Numerical definition (variable) <3.6 mmol/L
Severe hypoglycaemia: any event requiring 3rd party assistance
What are the symptoms of a hypo?
Adrenergic
- Tremors
- Palpitations
- Sweating
- Hunger
Neuroglycopaenic
- Somnolence (drowsiness)
- 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 the risk factors for a 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
How do you acutely manage a hypoglycaemia when they are alert and orientated?
Oral carbohydrates
Rapid acting juice/sweets
Sandwich (longer acting)
How do you acutely manage a hypo when they are Drowsy / confused but swallow intact?
Buccal glucose
e.g. Hypostop / glucogel
Complex carbohydrate
How do you acutely manage a hypo when they are unconscious or concerned about swallow?
IV access
20% glucose IV
What is monogenic diabetes?
A rare type of diabetes caused by mutation to a single gene
Differs from type 1 and type 2
e.g. MODY, mitochondrial diabetes
What are the stages in development of T1DM?
Genetic risk: 15x increased risk of T1DM in those with relatives w/ disease
Immune activation: Beta cells attacked
Immune response: Development of single autoantibody
Stage 1: Normal blood sugar: >/= 2 autoantibodies
stage 2: abnormal blood sugar: >/= 2 autoantibodies
Stage 3: clinical diagnosis: >/= 2 autoantibodies
stage 4: Log-standing T1DM
Whats the problem with the basal bolus regime?
Short acting insulin doesnt replicate the 2 phases of the prandial peak
Background insulin does not have the same flat basal profile
What factors can affect HbA1c?
Erythropoiesis:
Inc. HbA1c- low iron, vit b deficiency
Dec. - administration of erythropoietin, iron, vit b12
Altered Hb: haemoglobinopathies, HbF
Glycation:
Inc. - alcoholism, chronic renal failure
dec. aspirin, vit C and E
Erythrocyte destruction:
Inc. HbA1c - increased erythrocyte life span (splenectomy)
Dec. - splenomegaly, RA, drugs such as antiretrovirals
What should you do if a hypoglycemic person is deteriorating or its difficult to get IV access?
IM/SC insulin injection
