Type 1 Diabetes Flashcards

1
Q

What is type 1 diabetes?

A

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

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2
Q

What causes type 1 vs type 2 diabetes

A

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

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3
Q

Why do we measure c peptide instead of insulin

A

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

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4
Q

What are the stages of development of type 1 diabetes?

A

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

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5
Q

Why is the immune basis important

A

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

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6
Q

Explain a brief overview of immunology in type 1 diabetes

A

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

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7
Q

Why is it a positive that some Beta cells are not destroyed in type 1 diabetes

A

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

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8
Q

What allele does the biggest genetic susceptibility come from?

A

HLA -DR allele
(Human leukocyte antigen)
DR3 +4

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9
Q

What are environmental factors for type 1 diabetes

A

Dip during Summer
Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota

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10
Q

What are pancreatic auto-antibodies detectable in the sera of people with type 1 diabetes at diagnosis

A

Insulin antibodies (IAA)
Glutamic acid decarboxylase (GADA) – widespread neurotransmitter
Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc-transporter 8 (ZnT8)

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11
Q

What are the presenting symptoms of type 1 diabetes

A

Excessive urination (polyuria)
Nocturia
Excessive thirst (polydipsia)
Blurring of vision
Recurrent infections eg thrush
Weight loss
Fatigue

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12
Q

What are the presenting signs of type 1 diabetes

A

dehydration
cachexia
hyperventilation
smell of ketones
glycosuria
ketonuria

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13
Q

What is the diagnosis of type 1 diabetes based on

A

DIAGNOSIS IS BASED ON CLINICAL FEATURES and presence of ketones (in some cases pancreatic autoantibodies / C-peptide may be measured)

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14
Q

What happens with an insulin deficiency

A

Protienolysis into amino acids
Hepatic glucose output increases (counter-intuitive)
Lipolysis increases so more glycerol and NEFA

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15
Q

What happens when NEFA is taken up by the liver

A

More Beta oxidation and ketone bodies made

Can cause ketoacidosis

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16
Q

What are the aims of treatment in type 1 diabetes

A

Maintain glucose levels without excessive hypoglycaemia
Restore a close to physiological insulin profile
Prevent acute metabolic decompensation
Prevent microvascular and macrovascular complications

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17
Q

What are the complications of hyperglycaemia

A

Acute
Diabetic ketoacidosis

Chronic
Microvascular
Retinopathy
Neuropathy
Nephropathy
Macrovascular
Ischaemic heart disease
Cerebrovascular disease
Peripheral vascular disease

18
Q

What are the effects of treatment itself?

A

Hypoglycaemia

19
Q

How to manage type 1 diabetes

A

Insulin Treatment
Dietary support / structured educations
Technology
Transplantation

20
Q

Describe an insulin profile

A

Second phase insulin release half an hour after meal
Insulin never 0, just at basal insulin level

21
Q

What are examples of short/quick-acting insulin

A

Human insulin – exact molecular replicate of human insulin (actrapid)
Insulin analogue (Lispro, Aspart, Glulisine)

22
Q

What are background - long acting/basal - types of insulin

A

Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH)
Insulin analogue (Glargine, Determir, Degludec)

23
Q

How does insulin pump therapy work

A

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

24
Q

What is the dietary advice offered for those with type 1 diabetes

A

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

25
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
26
How does islet cell transplant work
Isolate human islets from pancreas of deceased donor Transplant into hepatic portal vein Requires life-long immunosuppression
27
Is it better to transplant both pancreas and kidney
Better survival of pancreas graft when transplanted with kidneys Requires life-long immunosuppression
28
How do we monitor glucose levels
Capillary (finger prick) blood glucose monitoring Continuous glucose monitoring (restricted availability, NICE guidelines)
29
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
30
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
31
What are acute complications from type 1
Diabetic ketoacidosis Uncontrolled hyperglycaemia Hypoglycaemia
32
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
33
How to diagnose diabetic ketoacidosis
pH <7.3, ketones increased (urine or capillary blood), HCO3- <15 mmol/L and glucose >11 mmol/L
34
What are symptoms of hypoglycaemia
Adrenergic: -Tremors -Palpitations -Sweating -Hunger Neuroglycopenic: Somnolence Confusion Incoordination Seizures, coma
35
What is severe hypoglycaemia
Any event requiring 3rd part assistance
36
When does hypoglycaemia become a problem?
Excessive frequency Impaired awareness (unable to detect low blood glucose) Nocturnal hypoglycaemia Recurrent severe hypoglycaemia
37
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
38
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
39
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
40
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