type 1 diabetes Flashcards
presenting features of diabetes
- Thirst
osmotic activation of hypothalamus - Polyuria
osmotic diuresis - Weight loss and fatigue
lipid and muscle loss due to
unrestrained gluconeogenesis - Hunger
Lack of useable energy source - Pruritis vulvae and balanitis
Vaginal candidiasis
Chest / skin infections - Blurred vision
Altered acuity due to uptake of glucose/water into lens
suggestive features of type 1 diabetes
- Onset in childhood / adolescence
- Lean body habitus
- Acute onset of osmotic symptoms
- Prone to ketoacidosis
- High levels of islet autoantibodies
can type 1 diabetes occur at any age
yes
what does the spectrum of type 1 diabetes depend on
on the rate of β-cell destruction
3 clinical features of newly diagnosed type 1 diabetes
- weight loss
- Short history (weeks) of severe symptoms
- Moderate or large urinary ketones
Any 2 of these three features indicate Type 1 diabetes and are an indication for immediate insulin treatment at ANY age
when does type 1 diabetes onset
childhood/adolescne
when does type 2 diabetes onset
usually over 30s
is type 2 diabetes genetic
yes almost 100% concordance in identical twins
suggestive features of type 2 diabetes
- Usually presents in over-30s
- Onset is gradual
- FH is often positive
- Almost 100% concordance in identical twins
- Diet, exercise and oral medication can often control hyperglycaemia; insulin may be required later in the disease
distinguishing factors between type 1 and 2 diabetes
Type 2 is diagnosed in younger patients, including childhood
Type 1 patients can be obese
Uncontrolled Type 2 can present with weight loss and ketouria
what to do if in doubt
treat with insulin
commonest age of type 1 diabetes diagnosis
5 - 15 years
but can occur at any age
prevalence of type 1 diabetes
Relatively rare (prevalence of 3/1000 among children and adolescents)
~370,000 in the UK
risk of developing type 1 diabetes if the mother has it
2%
risk of developing type 1 diabetes if the father has it
8%
risk of developing type 1 diabetes if both parents has it
up to 30%
risk of developing type 1 diabetes if a brother or sister has it
10%
risk of developing type 1 diabetes if a non identical twin has it
15%
risk of developing type 1 diabetes if an identical twin has it
40%
what happens to index if a family member of a child has t1 diabetes
If a family member has diabetes then the index case is less unwell compared to sporadic cases
Less autoimmunity in familial vs sporadic cases
Parents diagnosed 13% of the time after the birth of the index child
are offspring of affected fathers more unwell or affected mothers?
Offspring of affected fathers are more unwell than those of affected mothers, with longer duration of symptoms, more than twice as likely to present in ketoacidosis.
what is autoimmunity associated with
antibodies and other autoimmune diseases
what antibodies is autoimmunity associated with
Anti GAD
Pancreatic islet cell Ab
Islet antigen-2 Ab
ZnT8
what other autoimmune diseases is autoimmunity associated with
Hypothyroidism
Addisons
Coeliac disease
what happens if the diagnosis for type 1 diabetes is missed
fat metabolism
formation of ketone bodies
why does missed diagnosis cause fat metabolism
Reduced insulin leads to fat breakdown and formation of glycerol (a gluconeogenic precursor) and free fatty acids
why does missed diagnosis cause formation of ketone bodies
Free fatty acids (FFA) impair glucose uptake
Are transported to the liver, providing ‘energy’ for gluconeogenesis
Are oxidised to form ketone bodies (beta hydroxy butyrate, acetoacetate and acetone)
why does absence of insulin cause ketoacidosis
Absence of insulin and rising counterregulatory hormones leads to increasing hyperglycaemia and rising ketones
Glucose and ketones escape in the urine but lead to an osmotic diuresis and falling circulating blood volume
what do ketones cause
anorexia and vomiting
how does ketoacidosis lead to death
Vicious circle of increasing dehydration, hyperglycaemia and increasing acidosis eventually lead to circulatory collapse and death
characteristrics of diabetic ketoacidosis
Hyperglycaemia (plasma glucose usually <50 mmol/l)
Raised plasma ketones (urine ketones > 2+)
Metabolic acidosis – plasma bicarbonate < 15 mmol/l
causes of diabetic ketoacidosis
Intercurrent illness
- infection
- myocardial infarct
Treatment errors – stop/reduce insulin dose
Previously undiagnosed diabetes
Unknown
diabetic ketoacidosis triad
Hyperglycaemia
Ketones
Acidosis
symotopms of dieabteic ketoacidosis
develop over days
polyuria and polydipsia
nausea and vomiting
weight loss
weakness
abdominal pain (confused with surgical abdomen)
Drowsiness / confusion
signs of diabetic ketoacidosis
hyperventilation (Kussmaul breathing)
dehydration (average fluid loss 5-6 litres)
hypotension
Tachycardia
coma
biochemical diagnosis of diabetic ketoacidosis - hyperglycaemia
hyperglycaemia (<50 mmol/l)
biochemical diagnosis of diabetic ketoacidosis - K+
K+ – high on presentation despite total body K+ deficit (due to acute shift of K out of cell with acidosis), subsequently fall with insulin and rehydration, anticipate fall in K+
biochemical diagnosis of diabetic ketoacidosis - HCO3-
HCO3- <15 mmol/l
biochemical diagnosis of diabetic ketoacidosis - urea and creatinine
urea and creatinine - raised due to pre-renal failure
biochemical diagnosis of diabetic ketoacidosis - urinary ketones dipstick
urinary ketones dipstix >2+ ketones
blood ketones >3.0
management of diabetic ketoacidosis
rehydration (3L first 3 hrs)
insulin (inhibits lipolysis, ketogenesis, acidosis, reduces hepatic glucose production, increase tissue glucose uptake)
replacement of electrolytes (K+)
treat underlying cause
Treatment must be started without delay
Follow DKA protocol in hospital
complications of diabetic keto acidosis
cerebral oedema (deterioration in conscious level)
children more at risk
adult respiratory distress syndrome
thromboembolism – venous and arterial
aspiration pneumonia (in drowsy/comatose patients)
death
aims of tretment with type 1 diabetes
Relieve symptoms and prevent ketoacidosis
Prevent microvascular and macrovascular complications
how much life do people with type 1 diabetes lose
On average, people with Type 1 diabetes lose 8 years of life (mostly from cardiovascular disease)
how many t1 diabetes patients develop diabetic nephropathy
Around 30% in the UK will develop diabetic nephropathy
impact of diabetic nephropathy
Those with nephropathy tend to develop proliferative retinopathy and severe neuropathy with major effect on quality of life
key goal of type 1 diabetes treatment
To restore the physiology of the beta cell
what needs to be done to restore physiology of beta cell to treat t1 diabetes
Insulin treatment
- Twice daily mixture of short/medium acting insulin
- Basal bolus, (once or twice daily medium acting insulin plus pre meal quick acting insulin)
Ability to judge CHO intake
Awareness of blood glucose lowering effect of exercise
All combined to keep blood glucose close to normal (and so prevent diabetic complications)
what do innapropiatley high insulin levels confer
high risk of hypoglycaemia
Acute deprivation of glucose within the brain leads to cerebral dysfunction (loss of concentration, confusion, coma)
physiological defences to hypoglycaemia
Release of glucagon, adrenaline
symptoms of hypoglycaemia
Symptoms of
Sweating, tremor, palpitations (autonomic activation)
Loss of concentration, ‘hunger’
what happens to hypoglycaemia when glucose level is 4.6 mM
inhibition of insulin secretion
what happens to hypoglycaemia when glucose level is 3.8 mM
counter-regulatory hormone release (glucagon and adrenaline)
what happens to hypoglycaemia when glucose level is 3.8 - 2.8 mM
autonomic symptoms
- sweating, tremor, palpitations
what happens to hypoglycaemia when glucose level is <2.8 mM
neuroglycopenic symptoms
- confusion, drowsiness, altered behaviour, speech difficulty, incoordination
what happens to hypoglycaemia when glucose level is <1.5 mM
severe neuroglycopenic
- convulsions, coma, focal neurological deficit ie hemiparesis
what is the dilemma for people with type 1 diabetes
Setting higher glucose targets will reduce the risk of hypoglycaemia but increase the risk of diabetic complications
Setting lower glucose targets will reduce the risk of complications but increase the risk of hypoglycaemia
what factors make it difficult for people with diabetes to sustain effective self management
- Risk of hypoglycaemia
- Too arduous a treatment
- Risk of weight gain
- Interference with lifestyle
- Lack of sufficient training from diabetes teams
what should diabetes treatment reduce the risk of
- cardiovascular morbidity and mortality
- chronic kidney disease
- microvascular complications
what are incretins
hormones secreted by intestinal endocrine cells in response to nutrient intake
Incretins influence glucose hom
how do incretins influence glucose homeostasis
via multiple actions including glucose-dependent insulin secretion, postprandial glucagon suppression, and slowing of gastric emptying
