diabetes Mgx (see DM) Flashcards
what is diabetes mellitus
a metabolic disorder characterised by chronic hyperglycaemia due to defects in insulin secretion/action
4 actions of insulin in the body
- increases glycogenesis
- increased peripheral glucose uptake
- inhibition of hepatic glucose production
- inhibition of lipogenesis/lipolysis
4 drug classes that can induce diabetes
- steroids
- thiazides (e.g. diuretics for HF)
- anti-psychotics
- BBs
impaired fasting glucose test values
> 6.1mmol/L but <7.0mmol/L
impaired glucose tolerance test values
fasting <7.0mmol/L;
OGTT >7.8 but <11.0mmol/L
what type of hormone is insulin
a peptide hormone
what is the precursor molecule to insulin
preproinsulin
proinsulin -> insulin pathway (check this)
proinsulin -> cleaved by proprotein convertase (removes the middle C-peptide) -> carboxypeptidase -> insulin
what is the half life of insulin?
6 minutes
what are the 4 types of manufactured insulin doses and how long dose each last
short acting: 4-6 hrs
intermediate: 12-10hrs
long: 24hrs
mixed: comprises of short + intermedite acting
what are the blood glucose targets for T1 diabetes (3)
On waking: fasting blood glucose 5–7 mmol/L;
Before meals: blood glucose 4–7 mmol/L;
Post meals: test after 90 minutes, blood glucose 5–9 mmol/L;
what is HbA1c
glycated haemoglobin - average blood glucose (sugar) levels for the last two to three months; Glycated haemoglobin occurs due to non-enzymatic irreversible modification of the beta globin chain in haemoglobin
what is the “honeymoon period” (T1 diabetes)
The honeymoon period can occur in newly diagnosed patients in whom there is residual beta cell function -> This may negate the need for exogenous insulin for a period
what are diabetes sick day rules (5)
a number of recommendations in T1DM with an intercurrent illness. Advice includes:
1. Continue insulin therapy, alterations may be required, advice from a specialist may be sought;
2. Increase frequency of blood glucose monitoring;
3. Consider ketone monitoring;
4. Maintain good hydration and when possible a normal meal pattern, meals may be replaced by carbohydrate based drinks;
5. Seek urgent medical attention if unable to tolerate oral intake, drowsy or sustained vomiting
why do diabetics often get foot complications
Due to loss of sensation and poor blood supply, patients are at risk of a number of complications including diabetic ulcers, secondary infection (e.g. cellulitis, osteomyelitis), skin necrosis and eventually amputation
what is charcot’s joint
complex neuropathic arthropathy that results from loss of sensation and subsequent repeated micro-trauma to the foot
what is the main macrovascular complication of diabetes
atherosclerosis
4 prophylactic measures to reduce CVD risk
- Smoking cessation
- Nutritional support & exercise
- Consideration of anti-lipid therapy (e.g. atorvastatin)
- Blood pressure control
what is the MOA of Sulphonylureas
block K+ Ch opening => cell membrane depol occurs leading to Ca2+ influx and thus insulin release
what amino acid increases the chance of beta-cell depol and why
Arganine, it is positively charged
metformin MOA (3)
- Metformin decreases blood glucose levels by decreasing hepatic glucose production (gluconeogenesis);
- decreases the intestinal absorption of glucose
- increases insulin sensitivity by increasing peripheral glucose uptake and utilization
2 side effects of sulphonylureas
- hypoglycaemia
- weigh gain (1-4kg in 6 months)
meglitinides MOA
insulin secretagogues -> stimulates the release of insulin from beta cells e.g. repalinide potentiates the effect of extracellular glucose on ATP-sensitive potassium channel (relies on there being some beta-cell function)
2 examples of meglitinides
- natiglinide
- repaglinide
2 side effects of meglitinides
weight gain; hypoglycemia
what is prandial glucose
prandial = while eating food => prandial glucose is glucose acquried from eating
α-glucosidase inhibitors MOA
prevents the cleaving of carbohydrates into monosaccharides thus lowering prandial glucose
thiazonlidinediones MOA (pioglitazone)
agonist of peroxisome proliferator activated receptor gamma - a receptor in adipose tissue, muscle, liver, vascular endothelium and beta cells -> reduced hepatic gluconeogenesis, promotes adipogenesis, insulin sensitivity, tissue glucose uptake and reduces inflammation
by how much does pioglitazone reduce HbA1c reduction?
0.5-1.4%
how fast does pioglitazone produce results
gradual onset - reaches maximal effect in 2-3 months
side effects of thiazolidinediones (3)
- increased risk of fracture
- oedema
- weight gain (2-3kg per 1% HbA1c reduction)
what conditions are thiazolidinediones contraindicated in (3)
- heart failure;
- uninvestigates macroscopic haematuria;
- bladder cancer
what do DPP4 inhibitors increase the risk of?
pancreatitis
SGLT-2 inhibitor MOA
inhibits the action of SGLT2 (proximal convoluted tubule) ->allows for glucose to be excreted in the urine rather than be reabsorbed into the blood
side effects of SGLT-2 inibitors (6)
- mild diuresis (risk of hypovolemia and dizziness)
- calorie loss
- reduced blood pressure
- weight loss
- risk of genital/urinary tract infections
- euglycemic/hyperglycemia DKA
what does euglycemic mean
when blood glucose is within the normal range
GLP1 receptor agonist MOA
activates GLP1 receptors which increase the level of incretin hormone -> increases insulin secretion and reduces glucagon secretion
what drug is a true analogue of GLP1
liraglutide
side effects of GLP1 receptor agonists (4)
- enhanced satiety;
- delayed gastric emptying;
- weight loss (avg 3.2Kg);
- reduced BP
what is the HbA1c reduciton with using GLP1 receptor agonists
0.5-1.5%
what can be given for hyperglycaemic rescue therapy
insulin or sulfonylurea
target HbA1c levels in T2 diabetes
48mmol/L-53mm/L
who should intensive glycaemic control treatment be given to
uncomplicated, young pts, who will benefit the most out of glycaemic control and avoiding future complications
what is a red flag for nephropathy
microalbuminuria
OGTT prediabetic values
7.8-11.0 mmol/L
What drugs should be stopped according to sick day rules
DAMN drugs - diuretics, ACEi/ARBs, metformin, NSAIDs
When do sick day rules apply
When dehydrated (check this)
