How can you diagnose diabetes?
Symptoms and blood glucose >11.1mmol/l or no symptoms and HbAC1>48mmol/l or 6.5% on two occasions and fasting plasma glucose >7mmol/l and 2 hours after glucose 11.1mmol/l on 2 occasions
What proportions of the islets secrete each hormone?
60-80% are insulin secreting beta cells. 20-40% are glucagon secreting alpha cells and somatostatin secreting delta cells
What does insulin and SST do to the other pancreatic hormones?
What does glucagon do to the other pancreatic hormones?
How is insulin secreted?
Glucose enters the cell via GLUT-2 converted to pyruvate- TCA and ox phos creating ATP which binds to Katp closing the channel causing a build up of K in the cell, depolarising the membrane activating voltage dependent Ca channels allowing it to enter the cell facilitating exocytosis of the secretory granules from the cell
Other factors which affect insulin secretion
Incretins released from GI tract in response to food potentiate secretion and NA inhibits secretion as does Adr whereas Acetylcholine stimulates secretion
What is the role of glucagon?
Codes for GLP-1 in gut L cells. Stimulated by low blood glucose and acts on receptors linked to adenylate cyclase to break down glycogen to glucose especially in the liver
What is normal metabolism in the fed state?
Glucose to liver to be stored as glycogen excess stored as VLDLs in adipose tissue, muscles and adipose take up glucose using GLUT-4. AAs taken up by tissues for protein synthesis
What is metabolism in the fasting state?
Glycogen from the liver is degraded to glucose, brain and RBCs still use glucose but muscle uses FA instead of glucose. After time muscle protein is degraded to ketone bodies whihc can be used by the brai and muscles. AA breakdown causes increased urea
What is metabolism in type 1 diabetes?
Glucose from gluconeogenesis even if blood glucose is high. Muscle breakdown is uncontrolled, TAG broken down, ketone and glucose in the urine and blood
What are the cellular effects of insulin?
Increased glycogen synthesis, glucose uptale in lier and muscle, FA synthesis in the liver, DNA replication and protein synthesis
What is the mechanism for a insulin receptor?
Insulin binds to the tyrosine kinase receptor causing phosphorylation of the tyrosine of protein and can then phosphorylate other proteins causing either the PI3-K pathway (immediate metabolism, increases glut-4 on muscle and adipose) or MAP kinase pathways (cell growth and differentiation through ras and raf)
Does phosphorylating glycogen synthase kinase activate or inactivate it?
Inactivate- cant phosphorylate the glycogen synthase so it remains active allowing the translocation of GLUT 4 to the membrane
Doe the removal of cAMP by phodiesterase cause HSL to be active or inactive?
Inactive- TAG not broken down to glycerol and FAs
How is the insulin signal terminated?
Dephosphorylation of the proteins using protein phospatases. Phosphorylate serine/ theonine sites of IRS rather than tyrosine
What is cyclosporine?
An immunosuppresor which stops the activation of Th and Tc so the islets cannot be killed- risk of malignancy
If young at diagnosis what T cells would you expect to see?
If older at diagnosis what T cells would you expect to see?
Mixed regulatory and destructive
Why is there metabolic alkalosis in diabetes?
Pulmonary compensation- ketones produced are acidic so hydrogen ions increase and shift equilibrium left so increased CO2- Kaussmaul breathing
Renal compensation- inability for kidney to buffer H- Na and K lost in the urine
Why is potassium lost in diabetes?
Normally insulin causes glucose to be taken up and K follows but this doesnt happen and K is excreted as too much in the blood
What are the diagnostic criterea in gestational diabetes?
2 hour plasma glucose >7.8mmmol/l
Why do we use fluoride oxalate in plasma glucose bottles?
To stop the glucose conc falling due to glycolysis in RBCs
How much is a normal amount of glucose in urine?
What is serum fructosamine?
Testing for glycated albumin over previous 2 weeks, usefull in pregnancy
Ketone testing disadvantage on strips
Doesnt detect beta-hydrocubutyric acid
Blood ketone testing range
<0.6 normally, >1.5 DKA
Normal urine protein
<100mg over 24 hours
What is microalbuminuria defined as?
30-300mg over 24 hours- 20x risk of diabetic renal disease and progression of CVD
How do you diagnose DKA?
<11mmol or know diabetes, ketones >3mmol or >2+ ketonuria, bicarbonate <15 or venous pH <7.3
What is DKA?
Hyperglycaemia, hyperketonaemia and metabolic acidosis