Type 2 diabetes Flashcards
Is type 1 or type 2 diabetes more assoc. with a family history?
Type 2:
- 40% lifetime risk in offspring if parent diagnosed
- if both parents it’s a near to 100% risk
Describe the pathophysiology of T2DM
Obese/sedentery = fat releases fatty acids/adipokines = insulin resistance
- usually this insulin resistance is responded to by pancreatic B cells which release more insulin
- in T2DM B cells have genetic abnormality which prevents them from responding
-progressive disease, as the disease progresses more an more B cells deteriorate
What is ‘insulin resistance syndrome’?
90% T2DM are insulin resistant which is also assoc with:
- HTN
- Hyperlipidaemia
- hyperglycaemia
- PCOS
What is the metabolic syndrome?
Insulin resistance/T2DM + 2 others:
- microalbuminaemia
- obesity
- hypertension
- dyslipidaemia
=3X risk of stroke/MI/CHD/CVD
How does T2DM present?
Symptoms:
-blurred vision (sugary fluid in eye shrivels lens), recurrant UTI, tiredness, polyuria
Screening:
-overweight/obese/FH of T2DM
Concurrent illness:
-glucose measured in work up for CHD
What are the treatment principles of T2DM?
Treat symptoms: lower BG levels
Prevent microvascular complications: aim for HbA1c < 7%
Prevent cardiovascular complications: cholesterol, BP control, antiplatelets
Screen for complications whilst treatable: eye/neuropathy/renal
What is the first step in the management of T2DM?
Lifestyle
Weight loss aim 5-10kg a year
Healthy eating:
- reduce refined carbs
- reduce fat intake
- increasing fruit and veg
- reducing salt
- alcohol
Describe the pharmacological management of T2DM according to SIGN guidance
Glycaemic target <48mmol/mol or individualised for monotherapy
For dual therapy target <53mmol/mol
For triple therapy <58mmol/mol
1st line: metformin (or sulphonylurea if intolerant)
2nd line: ADD one of
- sulphonylurea
- Thiazolidinedione (pioglitazone only one) if hypo/bone fracture worry and no CHD
- DPP IV inhibitor if hypos/weight gain a concern
3rd line: ADD or SUBSTITUTE one with:
- Thiazolidinedione
- DPP IV inhibitor
- insulin injection before bed
- GLP 1 agonist injection if desire to lose weight and BMI>30 and usually <10yr from diagnosis
Treatment with SGLT-2 inhibitors monotherapy may be appropriate for some adults with type 2 diabetes if metformin is contraindicated or not tolerated and:
- a DPP-4 inhibitor would otherwise be prescribed and
- a sulfonylurea or pioglitazone is not appropriate.
Metformin
- what type of drug is this?
- how does it work?
- Desirable effects
- adverse effects
Biguanide drug
Mechanism: reduces hepatic glucneogenesis, increases glucose uptake and utilisation by skeletal muscle, reduces carb. absorption and increases fatty acid oxidation (insulin sensitiser)
Desirable effects: oral, no hypos, wt loss, prevents macro/micro complications, safe in preg. (gestational DM), used in PCOS/NAFLD, lowers lipids
Adverse effects: GI upset, accumalation in kidneys, liver failure, rash, interferes with vit B12 and folic acid, lactic acidosis rarely
Prescribing notes:
- Avoid or stop if eGFR <30ml/min or serum creatinine >150μmol/l
- Half dose if eGFR 30-45 ml/min
- Temporarily withhold if IV contrast being used eg. Angiography, CT scan (renal)
- Discontinue if advanced cirrhosis/liver failure
- Discontinue if risk of lactic acidosis eg encephalopathy, alcohol excess
- May be beneficial in Non-alcoholic fatty liver disease (NAFLD)
Gliclazide:
- what type of drug is this?
- how does it work?
- Desirable effects
- adverse effects
Sulphonylurea
Mechanism: insulin secretagogue (secretes insulin)
Desirable effects: reduces HbA1c more rapidly than insulin sensitisers
Adverse effects:
- hypoglycaemia
- wt gain
- GI upset
- headache
- blood dyscrasia
- liver dysfunction
avoid in renal or hepatic failure
Pioglitazone
- what type of drug is this?
- how does it work?
- adverse effects
Thiazolidinedione
Mechanism: PPar gamma agonist, reduces the amount of insulin needed to maintain blood glucose levels as it adapts insulin signalling
Adverse effects:
- wt gain
- heart failure due to fluid retention
- bone fractures
Gliptins e.g. vildagliptin
- what type of drug is this?
- how does it work?
- Desirable effects
- adverse effects
DPP-IV inhibitor (DPP-IV inactivates GLP-1 and GIP which are hormones that stimulate insulin release)
Mechanism: enhance insulin release and decrease glucagon release
Desirable effects: no hypos, weight neutral
Adverse: not that potent
Exenatide
- what type of drug is this?
- how does it work?
- Desirable effects
- adverse effects
GLP-1 agonist
Mechanism: mimic action of GLP-1 (hormone that stimulates insulin release) but are longer lasting
Desirable:
- little hypo risk
- early satiety
- reduces appetite
- decrease hepatic fat accumalation
Adverse:
- nausea
- injections
Dapaglifozin
- what type of drug is this?
- how does it work?
- Desirable effects
- adverse effects
SGLT2 inhibitor
Mechanism: blocks reabsorption of glucose at the SGLT2 transporter in the proximal tubule = glucose voided with water
Desirable: weight loss and no or little chance of hypo
Adverse effects: sugar in urine = thrush/UTI
Blood pressure in diabetes: what are the targets? what therapy is used?
Target systolic: <130mmHg
Target diastolic: 80mmHg or less
-ACE-Inhibitor
If Afro-carribean give ACEI + thiazide diuretic/calcium channel blocker
DONT GIVE B BLOCKER ANY DIABETES INCREASE INSULIN RESISTANCE
Statin use in T2DM?
simvastatin 40mg or atorvastatin 10mg if aged >40yrs regardless baseline cholesterol
what is the risk of severe hyperglycaemia in T2DM?
Hyperosmolar hyperglycaemic state
=severe hyperglycaemia with no significant ketosis
-METABOLIC EMERGENCY
Hypovolaemia. Marked hyperglycaemia (30 mmol/L or more) without significant hyperketonaemia (<3 mmol/L) or acidosis (pH>7.3, bicarbonate >15 mmol/L). Osmolality usually 320 mosmol/kg or more.
(sodium is often raised on admission, signif. renal impairment)
what are the common precipitants of hyperosmolar hyperglycaemic state?
- consumption glucose rich food
- concurrant medication e.g. steroids/thiazide diuretic
What are the typical features of hyperosmolar hyperglycaemic state?
- DM may be known or unknown
- usually older or younger non-caucasion groups
Symptoms:
Patients usually notice early symptoms of generalised weakness, leg cramps or visual impairment.
Nausea and vomiting may occur but this is much less so than for DKA.
As the condition progresses, patients may become bed-bound, confused and lethargic.
Focal neurological symptoms such as weakness on one side or hemisensory abnormalities may develop and be easily confused with stroke.
Seizures are present in up to 25% of cases. Seizures may be generalised, focal, movement-induced or myoclonic-jerk type.
Despite the condition’s name, coma is a relatively rare feature affecting only about 10% of those who present with the relevant metabolic abnormalities. Progression to coma represents severe disease.
How does the treatment of hyperosmolar hyperglycaemic state differ from DKA?
- fluids replenished more slowly as risk cerebral oedema
- insulin more slowly as more sensitive
- sodium: avoid rapid fluctuations, consider 0.45% saline
- co-morbidities more likely so screen for vascular event, sepsis, LMWH for all unless contraindicated.
How is type 2 diabetes diagnosed?
Fasting glucose >7 and symptoms = diabetes
Fasting glucose 6.1-6.9 = impaired fasting glucose, send for glucose tolerance test
- glucose tolerance greater than 11.1mmol/l = diagnostic
- glucose tolerance 7.8-11.1mmol/l = glucose tolerance
- glucose tolerance <7.8mmol/l = impaired fasting glucose
