Diabetes Flashcards
Define Diabetes Mellitus
An absolute or relative deficiency of insulin causing hyperglycaemia
What is the problem of hyperglycaemia?
Proteins become glycosylated and lose their function
To diagnose DM, what does the fasting blood glucose have to be above?
7
To diagnose DM, what does the random blood glucose level have to be below?
11.1
To diagnose DM, what does the HbA1c have to be above?
6.5%
Describe DM1
Absolute insulin deficience
Childhood diagnosis
Autoimmune islet damage
Describe DM2
Genetic and environmental factors
Insulin deficiency and resistance
When is DM1 diagnosed?
Childhood
What are the 3 main symptoms of diabetes?
Thirst, polyuria, nocturia
What is Gestational diabetes?
Occurring for the first time in pregnancy
What are some causes of secondary DM?
Pancreatic disease, congenital abnormalities, drugs, endocrine disorders.
What is Insulin stimulated by?
High blood glucose AAs FAs GI hormones Sulphonylureas
What does insulin do? (4)
Stops liver releasing glucose
Decreases gluconeogenesis and glycogenolysis in liver
increases glycogenesis
increases muscle and adipose uptake of glucose
What are the two important Glucose transporters in DM?
GLUT2 (beta cells) and GLUT4 (insulin sensitive on muscle and adipose)
How does insulin cause extra glucose uptake to muscle and fat?
Stimulates GLUT4 to move to the membrane to provide more receptors to which Glucose can bind.
What does insulin promote the synthesis of?
lipoproteins, TGs, proteins
Is GH mainly anabolic or catabolic?
anabolic
What is Glucagon stimulated by?
Low blood glucose, High AAs, and exercise
What inhibits Glucagon?
Insulin, KBs
When might Glucose and Insulin work together?
To prevent hypoglycaemia when high protein foods are eaten.
Where is GH secreted from?
Anterior pituitary
What does GH do?
Protein synthesis
Lipolysis
glycogenesis
What is IGF and what does it do?
Insulin like growth factor. Growth, cell division, protein synthesis.
What are IGFs stimulated by?
Insulin and GH
When is cortisol released?
stress, low glucose
What does cortisol do?
Proteolysis
gluconeogenesis
inhibits glucose use.
What are catecholamines stimulated by?
Stress
low glucose
What do catecholamines do?
Glycogenolysis
Lipolysis
Gluconeogenesis
How does insulin resistance happen?
Constant xs of glucose in the blood causes constant stimulation of the insulin receptors, causing them to downregulate
Why is there decreased insulin secretion in DM2 as well as resistance?
When there first started being hyperglycaemia, the beta cells would overwork to produce enough insulin to combat the raised glucose. Eventually, this wears them out and they stop secreting insulin.
What happens during starvation?
Muscles break down and so does fat to allow gluconeogenesis. TGs are hydrolysed into FAs which are used to make KBs.
(Glycogenolysis happens in fasted state)
What are the risks of DM?
Ketoacidosis (DM1)
Dehydration
Hypertriglyceridemia
Hypoglycaemia
What are some of the genetic causes of DM1?
IDD1, IDD2, IDD3 mutations = poor T cell activation regulation
How would you dx DM1?
Clinical symptoms and a biochemical test for autoantibodies
Explain the Immunology of DM1
Islet cell virus =
cytokines released =
Dendritic cell activation =
DC takes up beta cell antigen =
DC presents this to CD4 via MHC2 =
CD4 then presents it to B cells which become plasma cells =
Plasma cells produce autoantibodies against the beta cells.
The DC also presents to CD8 via MHC1 =
CD8 becomes cytotoxic and releases granules containing perforin when it finds beta cells
What is diabetic ketoacidosis?
Medical emergency
Uncontrolled catabolism in DM1
What are the symptoms of DKA?
Polyuria, thirst, weight loss, vomiting, hypotension, confusion, coma, tacchcardia, tacchpnoea, sweet smelling breath
What is the metabolic cause of DKA?
Increased catabolic hormones (inc ketogenesis)
KBs are acidic. Depletes bicarb buffering stuff.
How does cortisol play a part in DKA?
Its released during dehydration and acidosis which further increases glucose by catabolism.
Is glucose high or low during DKA?
HIGH!
What happens to respiration during DKA?
Tacchypnoea - compensation for metabolic acidosis
Why is there dehydration in DKA?
KBs in urine draws water out. Loss of ion gradients - Na and K depleted.
How do you treat DKA?
Insulin, IV fluids, Potassium
Waist circumference risk levels?
M - 102cm F - 88cm
Is a lower GI index slower absorbed or faster?
Slower
What does alcohol do to gluconeogenesis?
Suppresses it - may cause hypo!!!
What is a basal bolus?
Insulin 4 times a day. Less fluctuations in base levels of insulin.
what is carb counting?
Matching the amount of insulin given to the amount of car consumed. Only with basal bolus.
Disadvantages of subcut insulin?
Too much to periphery, not enough to liver
No feedback mechanism
Carb counting is hard
What are the symptoms of hypoglycaemia?
Shaking, sweating, palpitations, headache, confusion, fits, unconscious
What might cause a hypo?
Too much insulin given
reduced clearance
Decreased insulin requirement (alcohol and exercise)
How do you treat a hypo?
Glucose, glucagon
What are some of the lifestyle advice changes for DM2?
Weight loss, exercise, diet
What are the drugs for DM2?
Sulphonylureas - TOLAZIDE
Post prandial glucose regulators - REPAGLINIDE
Bigilanide (insulin sensitisor) - METFORMIN
Thiazolidinedione (insulin sensitiser) - PIOGLITAZONE
GLP-1 with DPP4 antagonist (SAXAGLIPTIN)
SGLT2 inhibitor - DAPAGLIFLOZIN
How do sulphonylureas work?
Close Potassium channels on beta cell, altering membrane potential. This causes calcium channels to open, causing insulin exocytosis.
How do postprandial glucose regulators work?
Close Potassium channels on beta cell, altering membrane potential. This causes calcium channels to open, causing insulin exocytosis.
How does Metformin work?
Increases muscle and adipose glucose uptake
Increases gluconeogenesis
Decreases glucose absorption from gut
What are the side effects of Metformin?
decreased appetite
GI upset
lactic acidosis
What are the side effects of Sulphonylureas?
Hypoglycaemia and weight gain
How often do you take METFORMIN?
3 times a day
How do Thiazolidinediones work?
Transcription of insulin sensitive genes
Decrease live glucose output, and increase muscle uptake.
What are the side effects of Thiazolidinediones?
Weight gain, cardiac failure. hypos
Hot does GLP1 work?
Transmits signals from gut to pancreas to increase insulin and dec glucagon.
What is GLP1 broken down by?
DPP4
How do SGLT2 inhibitors work?
Blocks glucose reabsorption and increases renal glucose excretion
What is common in babies born to diabetic mums?
Macrosomia, hypoglycaemia (due to xs insulin production), RDS. May have low birthweight
Long term obesity and diabetes.
What are the complications of DM?
Glomerulosclerosis Arteriosclerosis causing hypertension Infections Diabetic foot Retinopathy Erectile dysfunction
What causes diabetic foot?
Damaged nerves causes anaesthesia and compromised blood flow means poor healing = ulcers and necrosis.
Charcot foot
What is charcot foot?
brittle bones break easily
How do you treat diabetic foot?
Antibiotics, immobilise, stents, regular foot review, amputation
What types of retinopathy is seen in DM?
microaneurysms hard exudates dilated vessels cotton wool spots macula oedema traction from fibrosis causing blindness
