Diabetes Mellitus Flashcards
actions of insulin
Glucose
- decrease HGO (hepatic gluc output)
- increase muscle uptake
Protein
- decrease proteolysis (liberates gluconeogenic aa from myocytes so they can enter liver)
- increases protein synthesis (also increased by IGF-1 and GH)
Fat
- decrease lipolysis
- decrease ketogenesis
- Inhibits O2 conversion to CO2
In both fasted and fed state
Glut -4 receptor
- Common in myocytes (muscle) and adipocytes (fat)
- Highly insulin-responsive
- Lies in vesicles
- Recruited and enhanced by insulin
- 7x increase in glucose uptake
- Inner hydrophillic chain and outer hyrophobic chain
Glut 1,2,3,4
Effects of insulin, GH, IGF-1, and cortisol on aas
cortisol .. proteolysis
cortisol stimulates proteolysis
gluconeogenesis
glucagon -> protein broken down into aas -> taken up by liver -> gluconeogenesis aided by cortisol -> glucose -> hepatic glucose output (HGO)
triglycerides
- Lipoprotein lipase (LPL) breaks down triglycerides (which would otherwise be unable to leave the circulation) into NEFAS and glycerol - taken up by adipocytes
- LPL relies on insulin to function
- Insulin promotes NEFAs –> triglycerides for later use
- Insulin inhibits breakdown of triglycerides when you don’t need alternative energy source
- In fasting state - encouragement of triglyce to be broken down encourgaged by growth hormone and cortisol
- Gluco can be taken up by the adipocytes thru the glut-4 - allows them to be converted into Triglycerides
insulin released via
hepatic portal
cerebral energy requirements
- glucose preferred
- Ketone bodies
- Cannot use non esterified fatty acids
ketone bodies
- produced in fasting state
- insulin is low and gluc is low
- glucagon encourages production of ketone bodies in liver
- Kb released from liver
- high levels of ketone - prob with insulin secretion
Hepatic glycogenolysis
- In fasting state - reliant on alternate energy source
- glucagon will break down glycogen into gluc - gluc released from liver
energy in muscle cells
- Glucagon and GH are counter-regulatory hormones
- Muscle cannot release glucose (unlike liver)
- NEFAs can be used as store of energy for muscles
- Gluc can be converted into glycogen again but muscle cell is not able to release the gluc into the circulation so it stays in muscle cells
in the fasting state
- low insulin : glucagon
- [glucose] 3.0-5.5mmol/l
- inc [NEFA]
- dec [amino acid] when prolonged
- inc Proteolysis
- inc Lipolysis
- inc HGO from glycogen and gluconeogensis
- Muscle to use lipid
- Brain to use glucose, later ketones but not fatty acids
- inc Ketogenesis when prolonged
in the fed state
- Stored insulin released (first phase insulin) then slower insulin release in 2nd phase
- High [insulin] : [glucagon]
- Stop HGO
- inc Glycogen
- dec gluconeogenesis
- inc protein synthesis
- dec proteolysis
- inc Lipogenesis
Diagnosis of diabetes mellitus
- Fasting glucose > 7.0mmol/L
- Random glucose >11.1mmol/L
- Oral Glucose Tolerance Test
Fasting glucose
75g glucose load
2-hour glucose
- HbA1c >48mmol/mol
- Diagnosis requires 2 positive tests or 1 positive + osmotic symptoms
pahtophysiology of type 1 diabetes
- autoimmune
- absolute insulin deficiency
diabetic ketoacidosis
- ph <7.3 , ketones +3, HCO3 < 15 , gluc >11
- Serious acute complications
- High gluc in blood and in urine
- Get water being abosrbed into urine
- Lots of urine
- Water goes into ducts by osmosis
- Will convert into ketone bodies
presentation of type 1 diabetes mellitus
- Weight loss
- Hyperglycaemia
- Glycosuria with osmotic symptoms
- Polyuria - peeing many times
- Nocturia - peeing at night
- Polydipsia - thirst
- Ketones in blood and urine
Useful diagnostic tests:
- Antibodies: GAD, IA2
- C-peptide - low in Type 1, high in Type 2
- Presence of ketones in blood /urine ONLY IN TYPE 1; Insulin produced in T2DM suppresses ketone production.
- ‘The melting of flesh to produce urine’
- Confirm hyperglycaemia (random glucose >11.1 mmol/L) (NB don’t wait for a fasting sample)
- HbA1c > 48mmol/mol (NB ‘quick onset’ means HbA1c may not always be very high – limited diagnostic use in acute presentation of T1DM)
- A diagnosis requires 2 positive tests or 1 positive test + osmotic symptoms
insulin induced hypoglycaemia
- wont occur in non diabetic people but if you take exogenous insulin - gluc in circ will continue to fall - because it is taken up into cells
counter regulatory response to hypoglycaemia
- inc glucagon
- inc catecholamines
- inc cortisol
- inc growth hormone
- inc hepatic gluc output with glycogenolysis and gluconeogenesis
- Inc lipolysis
symptoms of hypoglycaemia
Autonomic
- Sweating
- Pallor
- Palpitations
- Shaking
Neuroglycopenic
- Slurred speech
- Poor vision
- Confusion
- Seizures
- Loss of consciousness
Severe hypoglycaemia; episode where someone needs third party assistance to treat.
pahtophysiology of type 2 diabetes
- insulin resistance
- When insulin binds to insulin receptor this activates the PI3K - Akt pathway - results in metabolic actions - gluc metab and fat metab
- Although insulin does not work too well in that pathway there is an ability of body to compensate by producing more insulin
- So more insulin produced to compensate
- Can have insulin resistance for quite a long time before diabetes
- Insulin binding to receptor also activates another pathway - MAPK pathway - growth and proliferation action of insulin
- There is no insulin resistance in this pathway
- So whilst other pahway doesn’t work - more insulin produced in MAPK pathway - so amplified growth and proliferation such as growth of arteriols leading to high blood pressure
- Enough insulin to suppress ketogenesis and proteolysis
insulin resistance
- high Tg (triglyc) and low HDL (cholesterol)
- adipocytokines
- inflammatory state
- Energy expenditure
- hypertension Bp > 135/180 mmHg
- Waist circumference : men >102 cm, women >88 cm
- Fasting glucose >6.0mmol/L
presentation of t2dm
Presentation of T2DM
- Hyperglycaemia
- Overweight
- Dyslipidaemia (High total cholesterol, triglycerides and LDL; low HDL)
- Less osmotic symptoms
- With complications: Monitoring and prevention of long term diabetes-related complications
- Retinopathy
- Neuropathy
- Nephropathy
- Cardiovascular
- Insulin resistance
- Later insulin deficiency
Risk factors:
- Age
- PCOS
- inc BMI
- Family Hx
- Ethnicity
- Inactivity
Dietary recommendation for type 2
- Healthy eating or diet
- Total calories control
- Reduce calories as fat
- Reduce calories as refined carbs
- Reduce sodium
- Increase complex carbs
- Increase soluble fibre
Management of type 1
Self-monitoring of glucose
Structured education
Technology
Exogenous insulin (basal-bolus regime)
Basal bolus regime : multiple daily injections -
Longer acting insulin 1/2 per day and quick acting insulin injection just before you eat - normally 3 /day - trying to mimic normal physiology of insulin in someone without diabetes
Finger prick testing as part of self monitoring at least 4 times a day
Insulin pumps, continuous glucose monitoring technologies
management of type 2
- Diet
- Oral medication
- Structured education
- May need insulin later
