Intro To Diabetes Mellitus Flashcards
(31 cards)
GLUT-4
Glucose transport Common in myocytes and adipocytes Highly insulin-responsive Lies in vesicles Recruited and enhanced by insulin 7-fold increase glucose uptake
Hormonal effects on protein synthesis and breakdown
Protein breakdown is inhibited by insulin but is increased by cortisol
Protein synthesis for storage is increased by insulin, GH, insulin growth factor (IGF-1)
Gluconeogenic amino acids can leave the muscle cells so they can enter the liver
Gluconeogenesis
AAs released from muscle cells then taken up by liver. Enhanced by presence of glucagon (like during fasting). Insulin will encourage AAs to be converted into proteins but inhibit gluconeogenesis (conversion of AAs into glucose) and thereby reduce hepatic glucose output. Glucagon encourages protein breakdown into AAs and gluconeogenesis. Cortisol also encourages gluconeogenesis.
Compare carbs, protein and fat as fuel stores
Carbohydrates - 16kJ/kg
Protein - 17kJ/kg
Fat - 37kJ/kg
What happens to triglycerides
Lipoprotein lipase (LPL) breaks down triglycerides that would otherwise be unable to leave the blood. This is encouraged by insulin. Glycerol and non-esterified fatty acids (NEFA) can then be taken up by adipocytes where glucose is also taken up through GLUT-4 encouraged by insulin. The glycerol and NEFA within the adipocytes can also be converted using help of insulin for later use. Insulin acts as an inhibitor for the breakdown of triglycerides within adipocytes as another source of energy is no longer required. However GH and cortisol still encourage the breakdown of the triglycerides and to leave the adipocytes.
Hepatic glucose conversion and output
Glycerol transported into the liver as glycerol-3-phosphate. If glucose not needed then it can be stored as triglycerides in the liver. Otherwise Gly-3P then undergoes gluconeogenesis. This increases hepatic glucose output.
Cerebral energy requirement
Brain has an inability to utilise fatty acids as fuel making it unique among body tissues. It prefers glucose and ketone bodies.
How are ketone bodies produced?
NEFAs released from adipocytes can then be taken up by the liver. Fatty acyl-CoA is converted into Acetoacetate by presence of glucagon. However when not fasting insulin inhibits the breakdown of non-esterified fatty acids which have been converted into fatty Acyl-CoA into ketone bodies.
What happens to circulating glucose in the blood?
Glucose is transported into the liver by transporters. This is converted into glucose-6-P which under the influence of insulin is then stored as glycogen in the liver. Otherwise glucagon encourages the conversion of glycogen into glucose-6-P which is then converted into glucose and released from the liver (hepatic glycogenolysis)
Muscle Cells
When Glucose levels are high it is taken up by muscles cells with the help of insulin but inhibited by glucagon and GH. Glycogen stores can also be broken down into glucose (and vice versa) and used with NEFAs as energy sources for aerobic respiration of muscle cells.
Fasted State
Low insulin to glucagon ratio
3-5.5mmol/l
Increased NEFA levels
Decreased AA levels when prolonged
Increased proteolyisis, lipolysis, HGO from glycogen and gluconeogenesis
Muscle to use lipids while brain uses glucose (ketones over time)
Increased ketogenesis when prolonged
Fed State
Stored insulin released then 2nd phase
High insulin to glucagon ration
Stop HGO
Increased glycogen, protein synthesis and lipogenesis
Decreased gluconeogenesis and proteolysis
Diagnosis of Diabetes Mellitus
Fasting glucose > 7.0 mmol/L Random glucose > 11.1mmol/L Oral glucose tolerance test: - fasting glucose - 75g glucose load - 2hr glucose HbA1c (>48mmol/mol) - gives average of your glucose over last 3 months A diagnosis requires 2 positive tests or 1 positive test + symptoms
Pathophysiology in type 1 diabetes
Autoimmune condition
Leads to T cell mediated destruction of insulin producing beta cells in the pancreas
Eventually leads to Absolute insulin deficiency
Pancreas does not release any insulin so causes proteinolysis (increased AAs), hepatic glucose output (increased glucose) and lipolysis (increased glycerol and NEFAs - later ketone levels increase too)
What is osmotic diuresis
Increased glucose levels in blood and in urine, so increased osmosis into the urine increasing urine production. Causing a lot of water loss.
Diabetic Ketoacidosis
pH < 7.3 Ketones +3 HCO3- < 15 Glucose > 11 Serious scute complications
Presentations of type 1 diabetes Mellitus
Weight loss
Hyperglycaemia
Glycosuria with osmotic symptoms (polyuria/ nocturia/ polydipsia)
Ketones in blood and urine
Useful diagnostic tests:
Antibodies GAD, IA2
C-peptide
Presence of ketones
Insulin Induced Hypoglycaemia
Too much exogenous insulin can induce hypoglycaemia
Too much insulin administered which bypasses the pancreas and eventually stop hepatic glucose optic so glucose levels with fall even further.
Insulin will remain in the circulation and will be taken up by the muscle and glucose in your blood will continue to fall
Counterregulatory response to hypoglycaemia
Increased glucagon, catecholamines,cortisol and growth hormone causes increased hepatic glucose output with glycogenolysis and gluconeogenesis and increased lipolysis
Impaired awareness of hypoglycaemia
Reduced ability to recognise symptoms of hypoglycaemia
Due to loss of counter regulatory response
Recurrent hypoglycaemia
Symptoms and signs of hypoglycaemia (autonomic)
Sweating
Palpitations
Shaking
Pallor
Symptoms and signs of hypoglycaemia (neuroglycopenic)
Slurred speech Poor vision Confusion Seizures Loss of consciousness
Severe hypoglycaemia
Defined as an episode where a person needs third party assistance to treat
Pathophysiology in type 2 diabetes - insulin resistance
Insulin resistance resides in liver, muscle and adipose tissue
All metabolic sites and all arms of intermediary metabolism glucose and fatty acids
Enough suppression of insulin causes ketogenesis and proteolysis
