Diabetes Mellitus T2 Flashcards
def of T2DM
increased peripheral resistance to insulin, impaired insulin secretion & increased hepatic glucose output
aetiology of T2DM
combination of genetics & environment
1 genetic (risk for a 1st-degree relative of a patient with T2DM is 5-10 times higher)
2 obesity
-high plasma free FA levels & adipokines (leptin, TNF-a) secreted from adipocytes contribute to peripheral insulin resistance
-chronic hyperglycaemia can damage beta cells
-high free FA levels can damage beta-cell function
3 secondary diabetes
-pancreatic diseases (chronic pancreatitis, pancreatic cancer, resection)
-endocrinopathies (Cushing’s, acromegaly)
-drugs (corticosteroids)
epi of T2DM
5-10% prevalence in UK
people of asian, african & hispanic descent are at greater risk
incidence has increased as obesity has increased
history of T2DM
polyuria & polydipsia
patients may present with hyperosmolar hyperglycaemic state (hyperosmolar non-ketotic state)
infections (foot ulcers, candidiasis)
examination findings in T2DM
determine BMI, waist circumference, blood pressure
observe for diabetic foot (ischaemic such as dry skin, reduced foot pulses, ulcers & neuropathic)
investigations for suspected T2DM
diagnosed if one or more of the following are present:
-symptoms of diabetes & random plasma glucose >11.1mmol/l
-fasting glucose >7mmool/l
-two hour plasma glucose >11.1mmol/l after a 75g oral glucose tolerance test
additionally monitor hba1c, UEs, lipid profile
overview of management of T2DM
1 glycaemic control
2 screening for & management of complications
3 screening & treatment of CVS risk factors
4 advice & patient education
5 hyperosmolar hyperglycaemic state
(glycaemic control) management of T2DM
monitor control of symptoms
monitor capillary blood glucose
monitor hba1c every 3 months
Step 1 (diagnosis)
-lifestyle & metformin
-if hba1c >7% after 3 months progress to step 2
Step 2
-lifestyle & metformin & sulphonylurea
-if hba1c >7% after 3 months progress to step 3
Step 3
-lifestyle & metformin & basal insulin
-if hba1c >7% after 3 months & fasting blood glucose <7mmol/l progress to step 4
Step 4
-add premeal rapid-acting insulin
metformin inhibits hepatic gluconeogenesis
sulphonylureas (gliclazide) block ATP-sensitive K channels in beta cells stimulating insulin release
thiazolidinedione (pioglitazone) activates PPAR-gamma and reduces insulin resistance
if weight loss is desired use SC exenatide (GLP-1 agonist - glucose-like-peptide-1 agonist)
GLP-1 is produced by the L-cells in the gut & increase glucose-stimulated insulin secretion, decrease glucagon release, gastric emptying & appetite
(screening for & management of complications) management of T2DM
retinopathy (regular digital retinal photography)
nephropathy (monitor UEs, K, & estimated GFR, BP control, ACE inhibitors/ARBs)
neuropathy (examination for foot ulcers)
vascular disease (examination of foot pulses)
diabetic foot (examine feet regularly)
(screening & treatment of CVS risk factors) management of T2DM
lose weight
stop smoking
BP control
all diabetic patients should be started on a statin (CARDS trial)
aspirin given in patients with diabetes & an additional CVS risk factor
(advice & patient education) management of T2DM
INFORM PT
Information (diabetic nurses, websites, etc. explaining diabetic control, complications)
Nutrition (complex carbs as opposed to simple sugars, reduce fat intake)
Foot care (regular inspection)
Organisations (support groups)
Recognition & treatment of hypoglycaemia
Monitoring of capillary glucose
Pregnancy (strict glycaemic control & planning conception)
Treatment (action, duration, administration technique for insulin, change injection site to avoid lipohypertrophy, explain need of exercise)
(hyperosmolar hyperglycaemic state) management of T2DM
similar to treatment of DKA
but use 0.45% saline if serum Na >170mmol/l & a lower rate of insulin infusion
DVT prophylaxis with SC heparin
complications of T2DM
1 hyperosmolar hyperglycaemic state
-due to insulin deficiency like DKA
-patient is usually older than DKA patients
-longer history
-dehydration, high Na, high glucose (>35mmol/l), high osmolality (>340mmol/kg)
-no acidosis
2 neuropathy
-distal symmetrical sensory neuropathy
-mononeuritis (IIIrd nerve palsy)
-autonomic neuropathy (postural hypotension)
-impotence
-urinary retenion
3 nephropathy
-microalbuminuria, proteinuria & eventually renal failure
4 retinopathy
-background (dot and blot haemorrhages, hard exudates)
-pre-proliferative (cotton wool spots & venous bleeding)
-proliferative (new vessels on disc)
-maculopathy (macular oedema, exudates &/ haemorrhage within 1 disc of fovea associated with decreased visual acuity)
-also prone to glaucoma & cataracts
5 macrovascular complications
-IHD
-stroke
-peripheral vascular disease
prognosis of T2DM
intensive glycaemic control decreases the risk & progression of microvascular complications
early intensive glycaemic control decreases risk of MI and overall mortality
pre-diabetes
- diagnosed based on fasting blood glucose or an oral glucose tolerance test
- impaired fasting glucose (IFG) defined as fasting plasma glucose of 5.6-6.9mmol/l
- impaired glucose tolerance (IGT) defined as plasma glucose of 7.8-11mmol/l measured 2h after 75g oral glucose
patients with IFG & IGT are at considerable risk of developing T2DM over next 5yrs (40%)
what are GLP-1 receptor agonists
glucagon-like receptor agonists
for treatment of T2DM
lower risk of causing hypoglycaemia
also inhibits appetite & aids with weight loss
liraglutide
long acting GLP-1 receptor agonist
what are dipeptidyl peptidase 4 inhibitors
also known as gliptins oral hypoglycaemic blocks DDP-4 treats T2DM e.g. sitagliptin
as glucagon increases blood glucose levels, DPP-4 inhibitors reduce glucose & therefore blood glucose levels
DDP-4 inhibitors increase incretin levels (GLP-1 & GIP) by preventing breakdown, which inhibits glucagon release, which in turn increase insulin secretion and result in decreased blood glucose levels
what is the normal non-diabetic hba1c
<36mmol/mol
what is the hba1c level for diabetics
> 48mmol/mol
metformin
first line treatment for T2DM
often true for overweight patients
also used as treatment for PCOS
part of the biguanide class
MOA
-decreases hepatic glucose production
-increases insulin sensitivity across the body
used because it is cheap, functional, & weight neutral (patients will not gain weight while using this)
gliclazide
for T2DM
a sulfonylurea
increases insulin levels
however can cause weight gain & hypos
thiazolidinedione
also know as glitazones
for treatment of T2DM
activates PPAR-gamma receptor (are PPAR-gamma agonists)
causes an increase in FA storage in adipocytes
therefore decreases FAs in circulation
as a result increase in cellular glucose oxidation, causing decreased blood glucose levels
decreased insulin resistance
pioglitazone
side effects include water retention leading to HF
what are the contraindications of metformin use
renal failure
EGFR<30
SGLT2 inhibitors
sodium-glucose like transporters
giflozins
inhibits renal glucose reabsorption in the kidneys
causes an increase in glycosuria
causes weight loss due to loss of glucose
lowers BP
decreases risk of cardiac events
however increases risk of UTI in due to increase glucose in urine
used for T2DM as glucagon:insulin ratio is affected
how does regular exercise help diabetes
during & after exercise muscles increase expression of GLUT4 receptors
glucose is taken up by GLUT4 receptors into the muscles
blood glucose levels decrease
hyperosmolar hyperglycaemia
in T2DM
common in elderly, those with recent infection
causes an increase in glucose
what happens if sodium levels are corrected too quickly
osmotic demyelination occurs
central pontine myelinolysis
what is diabetes mellitus
a chronic condition characterised by abnormally raised blood glucose levels
what is T1DM
autoimmune disorder where insulin producing beta cells of islets of langerhans in the pancrease are destroyed by immune system
this results in an absolute deficiency of insulin which causes raised glucose levels
what are the signs + symptoms of T1DM
weight loss
polydipsia
polyuria
what are the signs + symptoms of diabetic ketoacidosis in T1DM
abdominal pain
vomiting
reduced consciousness
what are the signs + symptoms of T2DM
polydipsia
polyuria
why does polydipsia and polyuria occur
water is removed from the body due to the osmotic effects of glucose being excreted in the urine
what are the 4 main investigations for blood glucose
1 finger-prick bedside glucose
2 one off blood glucose (fasting or non-fasting)
3 HbA1c
4 glucose tolerance test
what are the diagnostic criteria for diabetes mellitus set out by the WHO
patient symptomatic: -fasting glucose >7.0mmol/l -random glucose >11.1mmol/l patient asymptomatic: -above criteria must occur on two separate occasions
what is the level by which the HbA1c is diagnostic of DM
HBA1c >6.5% (48mmol/mol)
what are the diagnostic criteria for prediabetes
HbA1c 42-47mmol/mol or 6-6.4%
fasting glucose 6.1-6.9mmol/l
what must all T1DM patients be treated with
insulin
as they have an absolute insulin deficiency
what is the ROA for insulin
subcutaneous
what are the SEs of insulin
hypoglycaemia
weight gain
lipodystrophy
what is the MOA of metformin
increases insulin sensitivty
decreases hepatic gluconeogenesis
what is the ROA for metformin
oral
what are the SEs of metformin
GI upset
lactic acidosis
when can metformin not be given
an eGRF <30ml/min
what is the MOA for sulfonylureas
stimulates pancreatic beta cells to secrete insulin
what is the ROA of sulfonylureas
oral
what are the SEs of sulfonylureas
hypoglycaemia
weight gain
hyponatraemia
give 2 examples of sulfonylureas
gliclazide
glimepiride
what is the MOA of thazolidinediones
activates PPAR-gamma receptor in adipocytes to promote adipogenesis and FA uptake
what is the ROA of thazolidinediones
oral
what are the SEs of thazolidinediones
weight gain
fluid retention
what is the MOA for DPP4 inhibitors (gliptins)
increases incretin levels which inhibit glucagon secretion
what is the ROA for DPP4 inhibitors (gliptins)
oral
what is the risk of DPP4 inhibitors (gliptins)
increased risk of pancreatitis
what is the MOA for SGLT-2 inhibitors (gliflozins)
inhibits reabsorption of glucose in the kidney
what is the ROA of SGLT-2 inhibitors (gliflozins)
oral
what is the risk of SGLT-2 inhibitors (gliflozins)
UTI
what type of drug is gliclzide
sulfonylureas
what is the MOA of GLP-1 agonists (-tides)
incretin mimetic which inhibits glucagon secretion
what is the ROA of GLP-1 agonists (-tides)
subcutaneous
what are the SEs of GLP-1 agonists (-tides)
N+V
pancreatitis
what do SGLT-2 inhibitors (gliflozins) + GLP-1 agonists (-tides) result in
weight loss
