diabetes in a nutshell Flashcards
What are the thresholds fro diagnosis diabetes
Fasting glucose >7mmol/L +
Random or 2hr OGGT =/> 11.1mmol/L +
HbA1c = 48mmol/mol +
What are the thresholds for diabetes based upon
Risk of developing diabetic retinopathy
(Apart from gestational - this one based on risk to foetus)
What is C-peptide
Is it co-secreted with insulin
Can be used to measure endogenous insulin secretion ie if c-peptide is present in the blood it must be coming from beta cells
What is HbA1c
Haemoglobin exposed to glucose
This gives a measure of glucose exposed in the last 90ish days (RBcs have a life of around 90 days)
Type 1A DM
Account for vast majority of T1DM
Involves an environmental trigger in a genetically susceptible individual - autoimmune process within the pancreatic Beta cell
This one is immune mediated
Type 1B DM
Idiopathic
Permanent insulinopenia , these people are also prone to DKA
Have no evidence of beta cell dysfunction or autoantibodies
Peak age to get T1DM
10-14 years
Genetic susceptibility of T1DM
HLA genes - DR3-DQ2 and DR4-DQ8
If both parents have HLA alleles - what is the risk of their offspring developing diabetes ?
30%
Virus associated with T1DM
Coxsackie B4
Describe the pathophysio of T1DM
T-cell mediated autoimmune response with production of autoantibodies that target and destroy Beta cells
Other than random/fasting glucose adn HbA1c what else can help diagnosing T1DM
GAD/IA2 antibodies and C-peptide
When would a patient be eligible for pancreas transplant
- episodes of severe hypoglycaemia
- severe and progressive long-term complications despite maximal therapy
- uncontrolled diabetes despite maximal treatment
Where would pancreatic islets be injected into (as part of a transplant)
Into the portal vein where they seed themselves into the liver
(Theses islets are harvested from cadavers)
Some reading on development of insulin resistance
What is Dononhue syndrome
Rare autosomal genetic trait involving mutations in the insulin receptor
Development abnormalities as well eg growth reetardation, absence of SC fat = caused by defects in insulin binding or insulin receptors signalling
What is MODY
Early onset of non-insulin dependent diabetes (usually before 25)
What are the 3 types of genetic mutation in MODY
Transcription factors (75%)
Glucokinase (14%)
MODY X (11%)
Differentiate between glucokinase mutation and transcription factor mutation
Glucokinase does well to bring down glucose after an OGGT
Transcription factor does not do well
Management of Glucokinase MODY mutation
Can be managed with diet alone
Mxm of transcription factor mutation
Diet , insulin or sulphonylureas
- these types of MODY respond well to sulphonylureas
Autoimmune destruction of beta cells is associated with what type of diabetes
T1DM
What are the abnormalities of insulin action in T2DM
Insulin resistance occurs when fat can no longer be stored in subcutaneous adipose tissue causing spill over FFA to viscera (not everyone who has T2DM is obese - some people have lower fat holding threshold)
Increased tyrosine kinase activity —> decreased expression of GLUT —> decreased cellular glucose uptake
Central obesity —> impaired insulin dependent glucose uptake
What disease is associated with T2DM
Acanthosis nigricans
Mxm of T2DM lifestyle wise
Lifestyle = weight loss (10-15% loss can result in remission)
1st line T2DM
Metformin + lifestyle change
1st line for T2DM for patients with atherosclerotic CVD
Metformin + GLP-1 receptor (eg exenatide)
1st line T2DM for patients with heart failure or CKD
Metformin + SGLT-2 (gliclazide)
What is the monogenic mutation in neonatal diabetes
Mutations in the glucose sensing mechanism - in the ATP sensitive K+ channel
Management of neonatal diabetes
(<6 months)
Sulphonylureas OR diazoxide
What other diseases are you at risk of developing if you have T1DM
Addisons
Graves
Coeliac
What is T1DM
Autoimmune disorder where insulin - producing beta cells of the islets of Langerhans in pancreas are destroyed
This results in an absolute deficiency of insulin > raised glucose levels
What is T2DM
Most common case of diabetes in developed world
Cause by relative deficiency of insulin due to an excess of adipose tissue
‘There isn’t enough insulin to go around all the excess fatty tissue, leading to glucose creeping up’
What does HbA1c measure
Glycosylated haemoglobin
Represents the average blood glucose over the past 90 days
Why is insulin administered subcutaneously
Due to ease of administration - also because insulin absorption and action in the subcutaneous space are much more consistent than when it is delivered as an IM injection
It is preferred over IM as if it injected deep into your muscles - the body will absorb it too quickly and so will not last as long
Why does a cranial DI respond to desmopressin ?
Cranial DI results from insufficient ADH secretion —> preventing kidneys from concentrating urine
Lack of ADH result in inability to concentrate urine even if a patient is hypovolaemic therefore urine osmolality is low in water deprivation
But kidneys are unaffected by cranial DI and so will respond to desmopressin (synthetic ADH) to produce a concentrated urine
(Nephrogenic DI = low urine osmolality for both)
Action of empagiflozin
SGLT-2 inhibitors reversible inhibit sodium-glucose co-transporter 2 in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion
Target blood pressure for those with hypertension under the age of 80
<140/90mmHg
What is gastroparesis
Complication of diabetes related to poor glycemic control
Is caused by nerve damage to the autonomic nervous system (vagus responsible for gastric motility)
- there is delayed gastric emptying, offensive burps, early satiety and morning nausea
1st line for diabetic neuropathy
Pregablin , gabapentin
