10 - Diabetes Flashcards
briefly, what is insulin ?
what stimulates and inhibits it ?
Protein secreted by β-cells in response to ↑glucose incretins (GLP-1, GIP) glucagon parasympathetic activity
Inhibited by
↓glucose
cortisol
sympathetic activity (α2)
• Role
↓hepatic glucose output via inhibition of gluconeogenesis
Inhibits glycogenolysis
Promotes uptake of fats
diabities - how is it diagnosed
what are the key symptoms present to help diagnosis
what are the risk factors for type II DM
Hyperglycaemia – random plasma glucose ≥ 11 mmol/L polyuria polydipsia weight loss - type I fatigue/lethargy
• Single raised plasma glucose without symptoms not sufficient
• Type 2 risk factors Obesity – 80-85% of risk Family history Ethnicity Diet Drugs – thiazides/thiazide-like, glucocorticoids and β-blocker
what are the two test we do of blood sugar ?
Glucose – immediate measure of glucose levels in blood mmol/L
HbA1c – haemoglobin A1c – glycated haemoglobin - percentage of redblood cells with “sugar coating” – reflects average blood sugar over last 10-12 weeks –
bonus; read
• Human insulin - recombinant DNA (bacteria/yeast)
• Usually formulated in 100 U/mL
obesity and insulin resistance
300 and 500 U/mL available to reduce volume
what is the half life, and so when so it be taken ?
more bonus
3 diff types of insulin….
Routine delivery by s.c. injection
upper arms, thighs, buttocks, abdomen
• i.v.i. for emergency treatment
• t1/2 - ~ 5 minutes in plasma – renal and hepatic metabolism and elimination
• [plasma] greatest after 2-3 hr – dose 15-30 min prior to meals
• Site of administration rotate - lipodystrophy
insulin aspart, humulin s rapid/short acting
insulin glargine - 24hr long acting
DDI and Contras
X hypoglycaemia, lipohypertrophy, lipoatrophy
renal impairment → hypoglycaemia risk
Δ ↑dose with steroids, caution – other hypoglycaemic agents
explain basal bolus dosing
may take a rapid acting bolus before meals - ie insulin aspart
and once daily long acting such as insulin glargine to keep levels up
what is a DKA, what are the symptoms ? and what may cause it ?
what do you do if it is ?
Diabetic ketoacidosis
Hyperglycaemia, acidosis, ketonaemia • Suspect DKA blood glucose ≥11mmol/L AND….. infection stress/trauma poor insulin adherence ADRs ketosis
• Fluids priority and then insulin
glucose, K+, (stat dose of insulin)
• DKA can present with low blood ketones
Hyperglycaemia may not always be present
outline type 2 Dm
dont need all of this
Slow progression of disease
•Less Insulin sensitivity into cells reduced due to cellular resistance associated with obesity
• Insulin resistance initially overcome by increased pancreatic insulin secretion
down reg of ↓insulin receptors – ↓GLP-1 secretion in response to oral glucose and response reduced at β-cells
• Glucotoxicty from fatty acids and ROS lead to β-cell dysfunction
so lowered response to insulin - less insulin uptake - lost in urine and hyperglycemia and all the associated issues
- Lifestyle!!!, surgery, education
- Initially non-insulin therapies
what is the 1st line type 2 DM treatment ?
follow nice guidelines
give metformin
mechanism of metformin
DDI
Contras
biganudes - metformin
↓↓hepatic glucose output (gluconeogenesis, glycogenolysis)
↑glucose utilisation in skeletal muscle
these reduce plasma conc
• Supress appetite so limit weight gain
• X GI upset – nausea, vomiting, diarrhoea
excreted unchanged by kidneys – stop if eGFR < 30 mL/min
• Δ ACEi, diuretics, NSAIDs – any drugs that may impair renal function
thiazide like diuretics ↑glucose so can reduce metformin action
key drug - sulfonureas
gliclazide
sulfonureas
Mechanism
DDI’s
Contras
Stimulate β-cell pancreatic insulin secretion
blocking ATP-dependant K+ channels
• Need residual pancreatic function
- Weight gain through anabolic effects of insulin
- Typically in combination with other agents or a first line option if metformin contraindicated
• X mild GI upset – nausea, vomiting, diarrhoea
hypoglycaemia (esp. with other agents- dont wanna cause), some rare hypersensitivity reactions
• Δ other hypoglycaemic agents, hepatic impairment, renal impairment
thiazide like diuretics ↑glucose so can reduce SU action
Thiazolidinediones (glitazones) - 2 key drugs
pioglitazone
rosiglitazone
Thiazolidinediones (glitazones)
mechanism
DDI
Contras
Insulin sensitisation in muscle and adipose, ↓hepatic glucose output
activation of PPAR-γ → modifys gene transcription in adipose cell to absorb more insulin
- Weight gain – fat cell differentiation
- Used much less frequently``
- X GI upset, fluid retention, fracture risk, CVD concerns, bladder cancer
- Δ other hypoglycaemic agents
