Diabetes Flashcards
Define diabetes mellitus?
- An elevation of blood glucose above a diagnostic threshold
What is the threshold for diabetes diagnosis based upon?
- The risk of developing retinopathy
For the diagnostic criteria of diabetes mellitus what is the critical value for fasting plasma glucose that defines diabetes?
- Fasting plasma glucose >7mmol/L
For the diagnostic criteria of diabetes mellitus what is the critical value for 2hr plasma glucose that defines diabetes?
- 2 hour plasma glucose >11.1 mmol/L
For the diagnostic criteria of diabetes mellitus what is the critical value for HbA1c that defines diabetes?
- HbA1c > 48mmol/L
What is gestational diabetes referring to?
- Diabetes during pregnancy
- Risk to fetus
The diagnostic criteria for gestational diabetes is __lower/higher___ than that for diabetes mellitus?
- Lower
Insulin is secreted from___
- beta cells in the pancreatic islet in response to blood glucose levels
Insulins main function is to___
- lower blood glucose levels
Glucagon is secreted from____
- alpha cells in the pancreatic islet in response to blood glucose levels
Glucagon ____ blood glucose levels?
- Increases blood glucose level
Explain c-peptide
- Useful way to measure endogenous insulin
- c-peptide + insulin = pro-insulin, which is then cleaved to produce insulin
- c-peptide is not found in injectable insulin therefore is a marker of insulin production
What are the 2 scales of diabetes?
- Failure of production of insulin
- Insulin resistance
Name some disorders of insulin secretion?
- type 1 diabetes
- MODY
- Pancreatitis caused by alcohol, CF, haemochromatosis
Name some disorders of insulin action
- Donohue-syndrome
- obesity
- type 2 diabetes
- NAFLD
Type 2 diabetes is __homogenous/heterogenous___
- highly heterogenous
Type 1 diabetes is characterised by what?
- pancreatic autoantibodies
- autoimmune condition of beta-cells
- anti GAD
- 1A2
What are some symptoms of diabetes?
- polyuria
- thirst
- blurred vision
- fatigue
- weight loss
What microvascular complications are associated with diabetes?
- neuropathy
- retinopathy
- nephropathy
What macrovascular complications are associated with diabetes?
- MI
- stroke
- PVD
A HbA1c level of ___ in a diabetic indicates good control?
- 48mmol/mol
What is the HbA1c blood test assessing?
- control of diabetes over 3 months (90 days)
- glycated haemoglobin which is proportional to sugar levels
What will the affect of haemolytic anaemia have on the HbA1c test?
- reduced life-span of RBC
- not a true level of control
What percentage weight loss can put diabetes type 2 into remission?
- 10-15%
Explain what is meant by a relative insulin deficiency in T2DM?
- Insulin resistance and beta cell dysfunction
What are some environmental risk factors for T2DM?
- Obesity
- age
- pregnancy
- calorie dense diet
- sedentary lifestyle
How will the islet of langerhans appear in the microscope?
- highly vascularised
- dense collection of cells
What do delta cells of the pancreas secrete?
- somatostatin
What is the role of somatostatin from the pancreas?
- inhibits both insulin and glucagon release
How does obesity affect insulin production?
- fat reduces insulin action
- beta cells produce more insulin as compensation
- long term compensation may lead to T2DM
What stabilises insulin vesicles within the beta cell before they are exocytosed?
- zinc
What would a long term diabetes pancreas appear like down the microscope?
- marked reduction in the quantity of beta cells
- known as degranulation
1st phase of the biphasic release of insulin releases what type of insulin?
- readily releasable
Explain the cascade of low glucose in an alpha cell?
- low glucose
- K/ATP channels open
- Na+ gates open
- Ca2+ channels open
- glucagon exocytosis
What happens in the alpha cell when glucose is increased?
- Closure of K/ATP channel
- SGLT2
- Ca2+ gates closed
- no glucagon released
What is the role of glucagon?
- Acts on the liver to promote hepatic glucose production
- raises blood glucose levels
Paracrine signalling requires___?
- the 2 cells to be close together
Explain the incretin effect?
- insulin secretion is greater from oral glucose relative to an isoglycaemic IV infusion
Name 2 incretin hormones?
- GLP-1
- GIP
GLP-1 is released from what cells?
- L cells of the gut
Name a GLP-1 receptor agonist drug?
- liragluitde
How does GLP-1 RA drugs work?
- bind to GLP-1 GPCR
- Increases insulin secretion
- promotes beta cell proliferation
What other positive effects of GLP-1 RA are there other than insulin increase?
- reduced appetite
- delayed gastric emptying
- inhibition of glucagon secretion
What breaks down GLP-1?
- DPP 4
Name a DPP4 inhibitor drug?
- sitagliptin
Natural form of GLP-1 has a __long/short__ half life?
- short
- for drugs analogues are given
Insulin resistance can be linked to what other conditions?
- diabetes
- neurodegenerative diseases
- chronic kidney disease
- gout
- heart failure
What is the gold standard for measurement of insulin sensitivity?
- Hyperinsulinemic-euglycemic clamp
Explain how the hyperinsulinemic-euglycemic clamp works?
- keeps glucose levels static
- fixed increased insulin dose
- measure how much glucose is required to maintain levels
More glucose required to maintain levels on the hyperinsulinemic-euglycemic clamp suggests what?
- good insulin sensitivity