Diabetes Flashcards
Define Diabetes ?
A metabolic disorder characterised by persistent hyperglycaemia resulting from defects in insulin secretion, insulin action or both.
What are the types of diabetes ?
Type 1
Type 2
Gestational
What are the differences between the types of diabetes ?
Type 1 - absolute insulin deficiency causes hyperglycaemia
Type 2 - insulin resistance and a relative deficiency resulting in hyperglycaemia
Gestational - develops during pregnancy and resolves after delivery. Increased risk of getting Type 2 in the future.
What are the causes of type 1 DM ?
Genetic factors - autoimmune destruction of the insulin producing beta cells in the pancreas.
Environmental factors - exposure to vitamin D or obesity triggers DM
What are some complications of T1DM ?
Nephropathy
Retinopathy
Neuropathy
Atherosclerosis
MI, stroke and peripheral arterial disease
DKA
Other autoimmune disorders
Skin and urinary infections
What is used to make a diagnosis of T1DM in adults ?
Diagnosis made on clinical grounds in adults presenting with hyperglycaemia ( random plasma glucose more than 11mmol/L ) with one of the following :
. Ketosis
. Rapid weight loss
. Age of onset younger than 50
. BMI lower than 25
. Family history of autoimmune disorders
How is a diagnosis of T1DM made in a child ?
A child or young person resenting with hyperglycaemia ( random plasma glucose over 11 mmol/L ) and some of the following :
. Polyuria
. Polydipsia
. Weight loss
. Excessive tiredness
When is a DKA suspected ?
A person with known DM or significant hyperglycaemia with the following features :
. Increased thirst and urinary frequency
. Weight loss
. Inability to tolerate fluids
. Persistent vomiting or diarrhoea
. Abdominal pain
. Visual disturbances
. Lethargy
. Fruity smell on breath
. Dehydration
. Shock
If a DKA is suspected what should be tested for ?
.Assess for precipitating factors such as infection, stress, poor medication adherence or other medical conditions
. Test for ketones
What is the target level for HbA1c for someone with T1DM ?
48 mmol/L or less than 6.5%
Other factors should be taken into consideration such as co-morbidities
Measure the HbA1c every 3-6 months
How often should a person with T1DM be self monitoring glucose levels ?
4 times a day ( before meals and before bed )
What is the optimal targets for glucose self monitoring in T1DM ?
Fasting 5 - 7 mmol/L
Plasma 4 - 7 mmol/L
What are lifestyle management is needed for someone with T1DM ?
Diet advice - carb counting
Maintain healthy BMI
Avoid drinking alcohol on an empty stomach
Encourage exercise but monitor glucose carefully while exercising
Avoid smoking
How is a DKA managed ?
Admit the person immediately for confirmation of diagnosis and emergency treatment with fluids and IV insulin
What categories of insulin therapy are there ?
Rapid and short acting - fast onset and are used to replicate the insulin produced by the body in response to glucose absorption from a meal
Intermediate or long acting - slow onset and mimic the effect of endogenous basal insulin.
What are some regimes for insulin therapy ?
Multiple daily injection basal bolus
Mixed biphasic regime
Continuous insulin infusion
What is the main adverse effect if insulin therapy ?
Hypoglycaemia ( blood glucose less than 3.5 mmol/L )
What are some symptoms of hypoglycaemia from insulin therapy ?
Hunger
Anxiety
Irritability
Palpitations
Sweating or tingling lips
Convulsions
Loss of consciousness or coma
What should be given for severe hypoglycaemia where someone has reduced consciousness ?
IM glucagon
What clinical features are common to all forms of DM ?
Polydipsia
Polyuria
Glycosuria
What are the characteristics of T2DM ?
Onset often after 40 years old
No HLA associations
No islet cell antibodies
Insulin resistance
Obesity
Not prone to ketoacidosis
What are some causes of T2DM ?
Lack of exercise
Obesity
HTN
Western diet
Genetic factors
What are some clinical features of T2DM ?
Polydipsia
Polyuria
Glycosuria
Nocturia
What is hyperglycaemic hyperosmolar state ?
A syndrome characterised by extreme elevations in serum glucose concentrations hyperosmolality and dehydration without significant ketosis.
What are the features that differentiate HHS from DKA ?
Hypovolaemia
Marked hyperglycaemia without significant hyperketonaemia
Osmolality
What are some precipitating factors for HHS ?
Intercurrent diseases such as :
. Acute MI
. Cushing’s syndrome
ACTH producing tumour
Infection
. Pneumonia
. UTI
. Cellulitis
. Sepsis
Medications
. CCB
. Loop diuretics
Substance abuse - alcohol and cocaine
What are the clinical features of HHS ?
Hyperglycaemia
Dehydration
Marked drowsiness
Usually old
Convulsions
Coma
What are some diagnostic criteria for HHS ?
Plasma glucose concentration
Arterial pH more than 7.3
Serum bicarbonate more than 15
Small ketonuria
Effective serum osmolality more than 320
What are some symptoms of HHS ?
Weakness
Visual disturbance
Leg cramps
Nausea and vomiting
Lethargy
Confusion
Dehydration
Low grade fever
What are some investigations when suspecting HHS ?
Blood glucose
Serum osmolality
ABG
Urinalysis
Renal function tests and electrolytes
Creatinine levels
What is the management of HHS ?
Seek expert advice
Insulin infusion
What is there a high risk of in HHS and what should be given ?
Thromboembolism
Give subcut heparin
What are some forms of diabetic nephropathy ?
Pyelonephritis
Glomerulonephritis
Atherosclerosis and HTN changes
What are some features of diabetic nephropathy ?
Microscopic albuminuria is a sensitive early predictor of subsequent overt renal disease
Proteinuria
HTN
Nodular sclerosis
What are some investigations of diabetic nephropathy ?
Measure urinary albumin : creatinine ratio
Measure serum creatinine annually
What are some preventative measures of diabetic nephropathy ?
Well controlled blood glucose
Reduce over co-existing cardiac risk factors
What are some causes of diabetic eye disease ?
Diabetic retinopathy
Diabetic cataract
What is diabetic retinopathy ?
A chronic progressive potentially sight-threatening disease of the retinal micro vasculature associated with the prolonged hyperglycaemia and other conditions linked to DM such as HTN.
What are the treatment principles of diabetic retinopathy ?
Maintain good blood glucose control
Maintain good blood pressure control
Check visual acuity
Laser photocoagulation, intravitreal steroids and surgical vitrectomy for sight threatening condition
What are some complications of diabetic foot ?
Foot ulcers
Painful necrosis
Extensive spreading skin necrosis
Chronic ulceration
What are some treatment options for painful diabetic neuropathy ?
Maintain good glycaemic control
Gabapentin
Phenytoin and carbamazepine
Pregabalin
What are some management options for diabetic foot ?
Neuropathy - check sensation
X rays
Prevention with good glycaemic control and foot health
Check for infection
Necrotic tissue removal
What is the polyol pathway ?
A 2 step metabolic pathway that converts glucose into fructose. The pathway plays a prominent role in the pathogenesis of complications in patients with end stage diabetes.
Why does the sorbitol / polyol pathway become upregulated ?
When glucose levels become very high such as in diabetics the pathway is increased to cope with the high levels
What is the polyol or sorbitol pathway ?
First step - glucose is converted to sorbitol via aldose reductase. This step utilises a H+ which is donated by NADPH. This is a rate limiting reaction
The second step - conversion of sorbitol into fructose via the enzyme sorbitol dehydrogenase. This step donates H+ to NAD + creating NADH. This step is reversible.
What is an issue about the sorbitol pathway ?
Not all tissues have the enzyme sorbitol dehydrogenase such as retina, kidneys and Schwann cells.
This causes sorbitol to accumulate to toxic levels and cause the complications of diabetes.
What diet would you advice for someone with T2DM ?
Encourage high fibre,
low glycaemic index sources of carbohydrates
Low fat dairy products
Low amounts of trans-fatty acids, high sugary drinks and high salt foods
What advice would you give on physical activity in T2DM ?
Minimise time spent sedentary
Advise regular exercise
What advice would you give for drinking alcohol with T2DM ?
Advise to stick to recommended amounts
Eat a snack before and after drinking alcohol
What is the second line treatment for diabetes if Metformin is not tolerated due to symptoms ?
Modified release metformin
What is the mechanism of action of Metformin ?
Reduces hepatic gluconeogenesis and increases insulin sensitivity and therefore glucose uptake intracellularly.
What are some adverse effects of metformin ?
GI upset - nausea, vomiting, diarrhoea and abdominal pain
Lactic acidosis - rare
What is a contraindication of Metformin ?
Low kidney function - GFR lower than 30
What is an example of sulfonylurea ?
Gliclazide
What is a positive of sulfonylureas ?
Bring down HbA1c quickly
What is a negative of sulfonylureas ?
Very high risk of hypoglycaemia
What shouldn’t be given if someone is on a sulfonylurea ?
Beta blocker as it masks the symptoms of hypoglycaemia
What is a contraindication of sulfonylurea ?
Ketoacidosis
Severe renal impairment
What are some adverse effects of sulfonylureas ?
GI upset - abdo pain, nausea, vomiting, diarrhoea
Hepatic impairment
Skin - rash, pruritus and urticaria
What are some examples of DPP4 inhibitors ?
Linogliptin
Sitagliptin
How do DPP4 inhibitors work ?
Block the DPP4 enzyme which normally decreases incretin. This means incretin increases which causes increased release on insulin and decreases glucagon secretion.
What are some positives of DPP4 inhibitors ?
Weight loss or weight neutral
Linogliptin can be used even with a GFR lower than 15
Little risk of hypoglycaemia
what are negatives of DPP4 inhibitors ?
Risk of pancreatitis
What are some positives of GLP1 agonists ?
Causes weight loss
Decreases appetite
No risk of hypoglycaemia
What are negatives of GLP 1 agonists ?
Risk of pancreatitis
What are some examples of GLP1 agonist ?
Exenatide
What is an example of a glitazone ?
Pioglitazone
What are some negatives of glitazones ?
Increased risk of HF and bladder cancer
What is the mechanism of action of an SGLT-2 inhibitor ?
Increases renal secretion of glucose causing glycosuria
What are some positives of SGLT 2 inhibitors ?
No risk of hypoglycaemia
Causes weight loss
Reduces risk of HF
What are the negatives of SGLT 2 inhibitors ?
Risk of thrush
Risk of UTI
