type I diabetes mellitus

what is type I diabetes mellitus?

inability to produce or secrete insulin

which age group does TIDM usually present in?

children and adolescents

where is insulin produced and secreted from?

beta cells in the islets of langerhans

what happens to the beta cells in T1DM?

destroyed

when does hyperglycaemia usually occur in terms of beta cell destruction?

when up to 90% of the beta cell mass has been destroyed

what is thought to be the main reason for beta cell destruction?

autoimmunity

what is the main auto-antibody identified in pts with TIDM?

anti-glutamic acid decarboxylase (anti-GAD)

what type of hypersensitivity reaction is T1DM?

IV

what are the genetic associations with TIDM?

certain human leucocyte antigens (HLA)

- DR3

- DR4

(remember 4-3=type 1 diabetes)

what other autoimmune conditions are associated with TIDM?

- autoimmune thyroid disorders

- coeliac

- addison's

- pernicious anaemia

what is thought to trigger onset of the autoimmune attack of the beta cells?

external triggers:

- viral infections

- vit D deficiency

how is insulin activated?

from proinsulin cleaved into insulin and C-peptide

what stimulates insulin release from pancreas?

- increased blood glucose

- glucagon-like peptide (GLP) from L cells in small intestine

what are the functions of insulin?

- increases glycogenesis and glycolysis

- inhibits gluconeogenesis and glycogenolysis

- increases glucose uptake in peripheral tissues

- decreases lipolysis

- increases fatty acid and triglycerol synthesis

- increases protein synthesis

- decreases protein degradation

which hormones counter-regulate insulin action?

- glucagon

- adrenaline

- growth hormone

- cortisol

what do counter-regulatory hormones do?

- promote glucose production in liver

- inhibit peripheral uptake of glucose

what does a decrease in insulin from TIDM lead to?

- increase rate of glucose production in liver

- reduced peripheral glucose uptake

= hyperglycaemia

what happens as this blood gets to the kidneys?

osmotic diuresis

what does osmotic diuresis cause?

- polyuria

- polydipsia

- dehydration

- electrolyte derangement

what is polydipsia?

extreme thirst

what else can the decreased peripheral glucose uptake cause?

increase muscle and fat breakdown = weight loss

as the body cannot use glucose as an energy source what does it resort to?

fatty acids

what happens to the fatty acids?

taken up by hepatocytes and converted into ketone bodies

what happens to the ketone bodies?

released back into circulation

what is the process of metabolising fatty acids called?

ketosis

what can excess ketosis lead to?

metabolic acidosis (diabetic ketoacidosis)

what can high circulating ketones lead to?

vomiting - which further exacerbates dehydration and electrolyte derangement

what happens as the acidosis becomes more severe?

pH-dependent enzyme systems fail

what happens in diabetic ketoacidosis if left untreated?

potentially fatal:

- acute kidney injury

- cerebral oedema

- acute respiratory distress syndrome

what is it called when T1DM develops in adulthood?

latent-onset autoimmune diabetes in adults (LADA)

what are the symptoms of T1DM? (5)

- polyuria

- polydipsia

- weight loss

- vomiting

- lethargy

what are the signs of T1DM? (2)

- mild-moderate dehydration

- BMI<25 (adults)

what is the diagnostic investigation for T1DM?

either:

associated signs and symptoms and 1 abnormal random blood glucose reading

OR

2 abnormal random blood glucose reading

what random blood glucose level would indicate diabetes?

>11.1mmol/L

what investigations are done for T1DM?

autoantibody testing

which autoantibodies can be tested for? (4)

- islet cell antibodies (ICA)

- glutamic acid decarboxylase (GAD)

- insulin antibodies (IAA)

- IA-2 antibodies

what further testing can be done?

c-peptide

what are the levels of c-peptide in T1DM?

low

what should you test for in pts >60 presenting with new-onset diabetes?

pancreatic cancer - CT/MRI

what is the main management of T1DM?

life-long exogenous insulin

what are the other features of T1DM management? (4)

- blood glucose monitoring

- treatment targets

- monitoring for complications

- education

how is exogenous insulin usually administered?

subcutaneously

what are some types of exogenous insulin? (5)

- rapid-acting

- short-acting

- intermediate-acting

- long-acting

- mixed (short and intermediate)

what is an example of rapid-acting insulin?

novorapid

what is an example of short-acting insulin?

humulin R

what is an example of intermediate-acting insulin?

humulin N

what is an example of long-acting insulin?

lantus

what is an example of mixed insulin?

humulin 70/30

what are the three main insulin regimes for T1DM?

- basal-blous

- one, two or three injections per day

- continuous insulin infusion via a pump

what is the basal-bolus regime?

- rapid- or short-acting insulin before meals

- long-acting preparation for basal requirements

what is the one, two or three injections per day regime?

using both short-acting and intermediate-acting insulin multiple times a day

what is the continuous insulin infusion via a pump regime?

- rapid- or short-acting insulin throughout the day

when would the continuous insulin infusion via a pump regime need to be used?

when pts are experiencing hypoglycaemic episodes with the other regimes

what can ongoing insulin injections given in the same place cause?

lipodystrophy

what is lipodystrophy?

atrophy of subcutaneous tissue (lumps)

what are the other side effects of insulin therapy?

- weight gain

- hypokalaemia

- hypernatraemia

how does insulin cause hypokalaemia and hypernatraemia?

stimulates the Na+/K+ ATPase pump

(think about treatment for hyperkalaemia)

what is used to monitor blood glucose?

CGM - continuous blood glucose monitoring

what are the two types of CGM?

- real-time continuous CGM

- intermittently scanned CGM

what is real-time continuous CGM?

latest blood sugars automatically recorded and shown on a mobile device

what is intermittently scanned CGM?

a recording is made only when you scan a device over a sensor

what is the option for pts who do not want to use a CGM?

traditional capillary finger prick glucose - 4 times a day

what is the blood glucose target for waking up?

5-7mmol/L

what is the blood glucose target for before meals?

4-7mmol/L

what is the blood glucose target for after meals?

after 90 minutes - 5-9mmol/L

how is long-term blood glucose measured?

HbA1c

what is HbA1c measuring?

glycated haemogobin - average of over the past 3 months

what is the target HbA1c?

<48mmol/mol (6.5%)

what programme aims to educated pts with T1DM about calculating their insulin levels correctly?

The Dose Adjustment For Normal Eating (DAFNE) programme

how often do pt with T1DM need a review?

annually

what is recommended for pts with T1DM and BMI ≥ 25?

metformin