Diabetes Flashcards
What is diabetes mellitus?
Diabetes mellitus is a condition associated with an elevated blood glucose.
This is a consequence of deficiency of INSULIN, or of its reduced action, or of a combination of both.
What are the actions of insulin?
Promotes uptake of glucose into cells for energy
Prevents breakdown of fat and protein
What do islets of langerhans look like histiologically?
What are the different cells contained within the islets of langerhans?
Rich blood supply so hormones can be released
What is the function of somatostatin hormone?
In your pancreas, somatostatin inhibits the release of pancreatic hormones, including insulin, glucagon and gastrin, and pancreatic enzymes that aid in digestion
How is glucose secretion from beta cells controlled?
Glucose enters beta cells directly via GLUT2 transporters. It is a permissive process that is directly related to the amount of glucose in the blood
Glucose is then metabolised (glycoloysis) then pyruvate enters TCA cycle
The ATP produced directly inhibits a K+ channel opening, so intracellular K+ levels rise which causes a membrane depolarisation which opens a voltage gated Ca+ channel, allowing Ca+ to come into beta cell. That promotes exocytosis of insulin molecules
What is the difference between endogenous and exogenous insulin produced?
In the body, endogenous pro-insulin is converted to insulin and C peptide
C-peptide can be used as a measure of endogenous insulin secretion in people with diabetes
This is because exogenous insulin manufactered by companies does not have C peptides
What tissues does insulin act on and what are the principle actions?
Increased Glucose uptake in FAT and MUSCLE and Glycogen storage in LIVER and MUSCLE
Increased Amino Acid uptake in MUSCLE and Protein Synthesis
Increased Lipogenesis in ADIPOSE TISSUE
Decreased Gluconeogenesis from 3-Carbon precursors and Ketogenesis (in LIVER)
Increased Cell proliferation
Decreased Apoptosis
What is the basic action of insulin?
Binds to a cell membrane receptor
Many pathways after this that lead to transformation of GLUT4 transporters from the cytoplasm to the surface of the cell in fat and muscle
This allows insulin-dependent glucose uptake into cells
What substances can gluconeogenesis occur from?
Glycerol
Lactate
Pyruvate
Alanine (protein)
What hormones increase the levels of blood glucose?
Adrenalin, noradrenalin, glucocorticoids, growth hormone and glucagon
Why is Blood Glucose Maintained within a Narrow Range by Homeostatic Mechanisms?
- Optimal functioning of brain
- Maintenance of energy source for most tissues
- Integrity and health of blood vessels
What can cause a deficiency in insulin?
Toxic insults to pancreas- chemical, surgery, autoimmune= absolute deficiency in insulin
What are conditions that can cause a severe resistance to insulin and what can occur in these conditions?
- Leprechaunism
- type A insulin resistance
- Rabson-Menderhall syndrome
Due to single gene mutations in receptors or proximal downstream messengers. Cause profound resistance and are rare
Can develop catnthosis nigricans, dry, dark patches of skin that usually appear in the armpits, neck and groin
What type of obesity is associated with increased insulin resistance?
Central adiposity
Visceral fat produces hormones- these can affect insulin. Likely to be part of the cause
What endocrine conditions can cause insulin resistance?
GH, cortisol and adrenalin can stop insulin actions in fight or flight. Pathogenic states of these will cause insulin resistance e.g. acromegaly, phaeochromocytoma or cushings disease
What are the cut off levels of blood fasting glucose in diabetes?
Lines are drawn where complications (microvascular) of diabetes occur- these shown are fasting blood glucose. > 7 mmol/L
Between 6-7= pre-diabetic state
What are the definitions of diabetes in biochemical results?
Oral glucose tolerance test- give a measured dose of glucose then measure after 2 hours
What is glycated haemoglobin?
Rate of formation of glycated haemoglobin is directly proportional to ambient blood glucose concentration
Reflects integrated blood glucose (BG) concentrations during lifespan of erythrocyte (120 days)
Blood sample can be taken at any time of day, irrespective of food consumption
When should HbA1c not be used as a diagnostic test for diabetes?
- Rapid onset
- Pregnancy
- Conditions where RBC survival may be impacted
- Renal dialysis
- Iron and vit B12 deficiency
What is the oral glucose tolerance test?
Used to assess state of glucose tolerance
75g oral glucose load
No restriction or modification of carbohydrate intake for preceding three days
Fast overnight
Test is performed in morning – seated; no smoking
Blood samples for plasma glucose taken at 0hrs and 2 hrs
What are pre-diabetic states?
Intermediate state between normal glucose metabolism and diabetes
Increased risk of vascular complications
Increased mortality from cardiovascular disease (doubled)
Weight loss can help
What are risk factors for type 2 diabetes?
Genetics
Ethnicity
Increasing age
Central obesity
Low birth weight
What is the genetic component of type 2 diabetes?
Genome-wide association studies have identified >400 gene variants associated with an increased risk of Type 2 diabetes
Most relate to beta cell function or mass, rather than obesity/insulin resistance
40% of the overall risk of Type 2 diabetes is determined by genetic factors-