Diabetes Type 1 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 are the 6 types of diabetes mellitus
Type 1 Diabetes Type 2 Diabetes Hybrid forms Other Unclassified During pregnancy
What causes type 1 diabetes
Environment and genetics
what does type 1 diabetes do and how is this different to type 2
1) autoimmune destruction of inlet
2) absolute insulin deficiency
3) hyperglycaemia
type 2
1) insulin resistance due to lifestyle
2) relative insulin defiance
3) hyperglycaemia
When does diabetes present in life for type 1 and for type 2
Autoimmune diabetes leading to insulin deficiency can present later in life = latent autoimmune diabetes in adults (LADA)
T1 normally present during childhood but now discovering that it can present at every stage of life
T2DM may present in childhood
Diabetic ketoacidosis can be a feature of T2DM
Monogenic diabetes can present phenotypically as Type 1 or Type 2 diabetes (eg. MODY, mitochondrial diabetes)
Diabetes may present following pancreatic damage or other endocrine disease
what is Monogenic diabetes
other type of DM but can present aw T1 or T2 diabetes ie ( MODY )
What are the stages of development of type 1 diabetes
1) genetic predisposition
2) Potential precipitating event –>
3) over immunological abnormalities( beta cells attacked and autoantibodies developed) , normal insulin release
4) progressive loss of insulin release, glucose normal
5) clinical diagnosis of overt diabetes, C peptide present
6) no c peptide
present
see google doc
What is C peptide
Side protein made by splitting of proinsulin –> c peptide + insulin
why is it important to find out if pateint has other immune diseases in T1 diabetes
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
Describe the mechanism of how immune cells attack beta cells
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
Note not all beta cells are destroyed Some people with type 1 diabetes continue to produce small amounts of insulin
Not enough to negate the need for insulin therapy
Why do some ppl with T1 diabetes still prod insulin
not all beta cells are destroyed Some people with type 1 diabetes continue to produce small amounts of insulin
Not enough to negate the need for insulin therapy
which genes give you susceptibility to T1 diabetes
HLA-DR3 and HLA-DR4 deletions pose a significant risk to chance of getting T1DM (DR - human leukocyte ag)
see graph on docs
what environmental factors are established to cause T1
Multiple factors implicated, but causality has not been established
Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota
What autoantibodies are tested for in ppl eiwth diabetes
In pancreas
Detectable in the sera of people with Type 1 diabetes at diagnosis.
Not generally needed for diagnosis in most cases
Insulin antibodies (IAA)
attackes:
Glutamic acid decarboxylase (GADA) – widespread neurotransmitter
Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc-transporter 8 (ZnT8)
What are the symptoms of T1
Excessive urination (polyuria) Nocturia Excessive thirst (polydipsia) Blurring of vision Recurrent infections eg thrush Weight loss Fatigue
what are the signs ( medical) of T1 diabetes
dehydration cachexia hyperventilation smell of ketones glycosuria ketonuria
How to diagnose diabetes T1
DIAGNOSIS IS BASED ON CLINICAL FEATURES and presence of ketones (in some cases pancreatic autoantibodies / C-peptide may be measured)
What are the effects of insulin deficiency
Proteolysis ( break down of muscle into AA)
stops hepatic glucose output ( HGO)
lipolysis ( fast –> gly + NEFA)
Why are ketone bodies formed in T1 diabetes
No insulin means no suppression of glucagon
1) glucagon acts on liver to turn fatty acyl coA –> acetyl co A –> acetoacetate –> acetone + 3OH-B –> ketone bodies
what should we aim for in the treatment of ppl with T1
People with type 1 diabetes, require insulin FOR LIFE
Aims:
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
1) Acute
Diabetic ketoacidosis
2) Chronic Microvascular Retinopathy Neuropathy Nephropathy
3) Macrovascular
Ischaemic heart disease
Cerebrovascular disease
Peripheral vascular disease
4) Of treatment itself
Hypoglycaemia
How can you manage T1
Insulin Treatment
Dietary support / structured educations
Technology
Transplantation
Type 1 diabetes is a condition that is ‘self-managed’
when do you inject insulin
before a meal –> insulin has 2 phases
what are teh 2 types of insulin and what are they used for
1) With meals (short / quick-acting insulin) Human insulin – exact molecular replicate of human insulin (actrapid) Insulin analogue (Lispro, Aspart, Glulisine)
2) Background (long-acting / basal) Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH) Insulin analogue (Glargine, Determir, Degludec)
When do you take short active vs long acting insulin
short acting 3x a day before meals
long acting in teh morning ( once a day or 2 daily intermediate to try to act like normal insulin)
what is insulin pump therapy and what does it do
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
extra
exra
what dietary advice should be given to ppl with T1
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
what happens with a closed loop / artificial pancreas
1) Algorithm to use glucose value to calculate insulin requirement
2) Insulin pump delivers calculated insulin
3) changes in glucose
4) real time continuous glucose sensor
Many advances in this field – some closed loop systems developed. Hybrid closed loop systems available on the NHS
what are the 2 types of transplants for T1
and what are the limitations of this method of treatment
1) Islet cell transplants
Isolate human islets from pancreas of deceased donor
Transplant into hepatic portal vein
Requires life-long immunosuppression
2)Simultaneous pancreas and kidney transplants
Better survival of pancreas graft when transplanted with kidneys
Requires life-long immunosuppression
Aim: try to restore physiological insulin production to the extent that insulin can be stopped
Even if incomplete, often results in better control
Limitations: availability of donors, complications of life-long immunosuppression
How do we monitor glucose levels
1) capillary finger prink blood glucose monitoring
2) continuous glucose monitoring using closed loop system ( restricted availability , Nice guidelines
3) HbA1C
what is HbA1C and what do we use it for
Test for hyperglycaemia
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
N terminal valine residue B chain + glulose –> schiff base ( fast hrs) ( reversible reaction)
Schiff base –> amadori product ( slow days)
Why is HbA1C not perfect
1) erythropoiesis
2) altered haemoglobin
3) glycation
4) erythrocyte destruction
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 T1
Diabetic ketoacidosis
Uncontrolled hyperglycaemia
Hypoglycaemia
what is diabetes 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
Diabetic ketoacidosis diagnosis
pH <7.3, ketones increased (urine or capillary blood), HCO3- <15 mmol/L and glucose >11 mmol/L
what is hypoglycaemia and why does it happen in T1
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
when does hypoglycaemia become a problem for T1
Excessive frequency
Impaired awareness (unable to detect low blood glucose)
Nocturnal hypoglycaemia
Recurrent severe hypoglycaemia
HbA1c itself may not be helpful in identifying hypoglycaemia
What are the risks of 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 and what are some risk factors
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 management strategies can be used to combat hypoglycaemia
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 manage an acute hypoglycaemic episode
1) If alert and orientated :
oral carbohydrates that are rapid acting ie juice/ sweets or longer acting ie sandwich
2) drowsy / confused but can still swallow :
buccal glucose eg hypostop / glycogel
complex carbohydrates
3) unconscious / unable to swallow
Iv access –> give 20% glucose IV
Deteriorating /refractory /insulin induced /difficult IV access: consider IM /SC 1mg Glucagon
What does a normal physiological insulin profile look like
Insulin is never 0 → prevents DKA and breakdown of muscle
Flat production of insulin between meals
When you eat you get a sharp rise in insulin production and then you get another peak afterwards
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