Diabetes Flashcards
What percentage of UK adults have diabetes?
4.9 percent
What percentage of DM cases are type 2?
85 to 95 percent
Is type 1 DM acute onset?
yes
What can be said about the onset of type 2 DM?
Subacute and insidious
What is the name given to the type of symptoms of T2DM?
Osmotic
Which infections are more common amongst DM patients?
Staph aureus
Oral and genital candidiasis
What macrovascular complications can occur in DM?
Stroke
Myocardial infarction
What eye change is commonly seen on retinoscopy with DM?
Diabetic retinopathy
What is the gold standard test for DM?
OGTT
What is the normal value for HbA1c?
Less than 42mmol/l
What is the target HbA1c for DM patients?
Less than 53mmol/l
How can a diagnosis of DM be definitively made?
- Two abnormal blood tests
- One abnormal blood results with symptoms
- One abnormal OGTT
What is the aetiology of T1DM?
Autoimmune destruction of beta cells in the pancreas leading to dysfunction
Which antibodies are positive in T1DM?
ICA and GAD
What is idiopathic T1DM?
no antibodies present
What are the features of latent autoimmune diabetes in adults?
- Diagnosed in adulthood
- Usually non-acute (can be often misdiagnosed as T2DM)
- Give insulin soon after diagnosis
- GAD and ICA antibody positive
What is the peak age of onset for T1DM?
5 to 7 years
Which pathogens are linked to the causation of T1DM?
Cocksackie
Parvovirus
Which environmental factors influence T1DM?
Puberty
European
Season
? Cows milk protein
Which genes increase the susceptibility of T1DM?
HLA genes on 6q-HLA DR3/DR4 (high risk)
Genes on chromosomes 2q, 15q, 11q
Which lymphocytes attack beta cells in T1DM?
T lymphocytes
What percentage of beta cells are destroyed before symptoms develop?
90 percent
What is the pathogenic sequence of T1DM?
genetic susceptibility > environmental insult > insulitis > immune attack of beta cells
How often should a diabetic review take place?
Every 2 years
What should be checked in the diabetic review?
Symptoms HbA1c BP, cholesterol, urine dip, ACR Eyes, feet, kidney function Discuss targets
What is the first step in management for DM?
Lifestyle advice
Stop smoking
BP control
What is the target BP in DM?
140/80
130/80 in cardiovascular or renal disease
What should be given to reduce blood pressure in DM patients?
ACE-I
CCBs
What is the cholesterol target in DM?
Total
How should eyes be checked for diabetic changes?
Annual digital retinal photography
How often should feet be checked in DM?
Yearly
How often should ACR/GFR be checked in DM?
Yearly
What is the pre prandial glucose target in DM?
4-7 mmol/l
What is the post prandial 2 hour target in DM?
5-9 mmol/l
When are fructosamine levels useful?
To look at long term glycemic control in haemoglobinopathy or pregnancy
What dietary/lifestyle advice is useful in DM?
Low salt/fat/sugar
Low GI carbs
30 mins exercise 3 times a week
Weight loss
What is the target weight reduction in DM?
3-5 percent
On average, how long does lifestyle work for?
One year
What is the second line treatment in T2DM?
Oral hypoglycaemic drugs
What are insulin secretagogues?
Stimulate insulin secretion from beta cells
How do sulfonyureas work?
They stimulate insulin secretion
Give an example of a sulfonylurea?
Gliclazide
What are the side effects of sulfonylureas?
Risk of hypo
Weight gain
Give an example of a biguanide?
metformin
how do biguanides work?
increase glucose uptake in liver and muscle cells by improving sensitivity to insulin
decrease gluconeogenesis
What are the side effects of biguanides?
Nausea and vomiting
Lactic acidosis if eGFR
What type of drug is acarbose?
Alpha glucosidase inhibitor
How do alpha glucosidase inhibitors work?
Reduce intestinal glucose absorption by inhibiting alpha glucosidase
What are the side effects of alpha glucosidase inhibitors?
Diarrhoea and flatulence
Give examples of glitazones
Poiglitazone
Thiazolidinediones
How do glitazones work?
PPAR GAMMA agonists that stop FFA binding
Improve insulin sensitivity in the muscle and adipose tissue to increase glucose uptake and put less stress on the beta cells in the pancreas
What are the side effects of glitazones?
Weight gain Oedema Heart failure Post menopausal bone fractures Bladder cancer
How does a prandial glucose regulator work?
Increase insulin secretion from beta cells
Give an example of a prandial glucose regulator?
(linides) - repaglinide
How do gliptins work?
Stop GLP-1 breakdown by inhibiting DPP-IV
Which enzyme does a gliptin inhibit?
DPP-IV
Give an example of a gliptin?
Sitagliptin
When should a gliptin be used?
3rd line
Are gliptins well tolerated?
Yes
Which cells normally make GLP-1?
L cells mainly in the ileum
What is the precursor to GLP-1?
Proglucagon
What naturally causes the release of GLP-1?
Meal ingestion
Which family of hormones does GLP-1 belong to?
Incretins
What is the function of GLP-1?
Delays gastric emptying so promotes satiety
Increases insulin secretion
Reduced glucagon secretion
Preserves beta cell mass
How does GLP-1 effect beta cells?
Promotes insulin secretion
Preserves mass
Give examples of GLP-1 analogues?
Liraglutide
Exanantide
Lixsenatide
How many amino acids in GLP-1?
31
How do gliptins work?
By inhibiting DPP-IV enzyme that normally breaks down GLP-1
What are the side effects of gliptins?
Nasopharyngitis
Pancreatitis
What are the side effects of GLP-1 analogues/agonists?
Nausea and diarrhoea
Pancreatitis
Pancreatic cancer
Why must GLP-1 analogues be given as an injection?
Peptide so will be digested in the gut
What does a GLP-1 analogue do in relation to DM?
Increase insulin secretion
Suppresses appetite
When should a GLP-1 analogue be given?
BMI>35 and poor glycemic control
How do gliflozins work?
Stop reabsorption of glucose in the kidney by inhibiting SGLT2
When should insulin be given in T2DM?
When oral glycemic drugs fail
Where is glucose normally absorbed?
Small intestine
What hormone stimulates insulin release from the pancreas?
Incretins
In which tissues does insulin stimulate glucose uptake?
Liver
Muscle
Adipose
When should you give insulin in T1DM?
Always
When is insulin given in T2DM?
Poor glycemic control Pregnancy Symptomatic hyperglycaemia Infection Foot ulcers Intolerance to drugs
If blood glucose is high in the morning, what adjustment should be made to insulin therapy?
Reduce night time long acting insulin
How is endogenous insulin usually secreted?
Basal bolus (baseline insulin with increased secretion at meal times)
What are the types of insulin?
Human
Analogue
What types of human insulin are available?
Short acting
Immediate acting
Biphasic (Short and immediate acting)
What types of analogue insulin are available?
Rapid acting
Long acting - basal
Biphasic (Long and rapid acting)
Where should insulin be injected?
Into subcutaneous fat
Thigh
Abdomen
Buttocks
Which site of insulin injection has the fastest absorption?
Abdomen
What type of insulin is given with once or twice daily therapy?
Long acting
What should once to twice daily therapy be used with?
Oral hypoglycaemics
When is the insulin normally taken in once/twice daily therapy?
Before bed or in the morning
When should pre mixed (biphasic) insulin be taken?
Once before breakfast and again before dinner
Which insulin regimen mimics regular physiology?
Basal bolus therapy
When is the long acting insulin taken in basal bolus therapy?
In the morning or before bed
When should rapid acting insulin be used?
Before main meals
Should the units of insulin be included in prescriptions?
No
For which conditions does DM increase mortality by 2.5x?
Cardiovascular disease
Coronary heart disease
Cerebrovascular disease
What is the most common complication at the time of diagnosis of DM?
Retinopathy
Where some other complications of DM?
Erectile dysfunction
Abnormal ECG
How does DM cause vascular disease?
Long term exposure to hyperglycaemia causes full/partial vessel closure and increased vessel permeability
What are the risk factors for DM complications?
Smoking
Hypertension
Dyslipidaemia
Hyperglycaemia
What is the biggest risk factor for DM complications?
Smoking
What is the least potent risk factor for DM complications?
Hyperglycaemia
Is diabetic retinopathy common?
Yes
What is the most common reason for blindness in the UK?
Diabetic retinopathy
What percentage of people who have had diabetes for 10 years get diabetic retinopathy?
50 percent
Does proliferative retinopathy involve the macula?
No
How does severe diabetic retinopathy appear?
Cotton wool spots (soft exudates indicating retinal ischaemia)
What does fundoscopy show in mild to moderate diabetic retinopathy?
Microaneurysms
Dot haemorrhages
Hard exudates (lipid deposits)
What is proliferative retinopathy?
Retinal ischaemia leading to the production of growth factors and new vessel formation
In proliferative retinopathy, where do the new vessels appear?
On the disk (NVD)
Elsewhere (NVE)
What is diabetic maculopathy?
Retinopathy within 1 disc diameter around the macula
What types of diabetic maculopathy are there?
Focal or exudative
What can exudative diabetic maculopathy lead to?
Oedema
How is diabetic retinopathy monitored?
Yearly digital retinal screen
How is diabetic retinopathy treated?
HbA1c less than 53
Good BP and cholesterol control
Laser photocoagulation
What are the types of diabetic neuropathy?
Peripheral sensory
Autonomic
Proximal motor (amyotrophy)
Mononeuropathy (cranial nerve palsy)
What distribution is often seen in peripheral neuropathy?
Glove and stocking
What are common complications of peripheral neuropathy?
Ulceration and amputation
What symptoms are seen in peripheral neuropathy?
Numbness
Pins and needles
Burning
Shooting
What is the most common cause of neuropathic ulceration?
Diabetic neuropathic ulceration
Which 3 systems can autonomic neuropathy affect?
Genitourinary
GI
Cardiovascular
How does autonomic neuropathy affect the genitourinary system?
Erectile dysfunction
Atonic bladder leading to urinary incontinence and difficulty voiding
Which GI symptoms are seen in autonomic neuropathy?
Gustatory sweating
Gastroparesis
Constipation or diarrhoea
Which cardiac symptoms are seen is autonomic neuropathy?
Postural hypotension
What is the most common cause of end stage renal failure in the UK?
Diabetic nephropathy
Which ethnicities are at greater risk of diabetic nephropathy?
South Asians and Afro Carribeans
Which histological lesion is seen in on biopsy of diabetic nephropathy?
Kimmelstein - Wilson Lesion
Which 3 criteria are needed to diagnose diabetic nephropathy?
Declining renal function
Hypertension
Albuminuria
Which factors need to be controlled in diabetic nephropathy?
BP
How should blood pressure be controlled in diabetic nephropathy?
ACE-I
When should metformin be stopped in diabetic nephropathy?
eGFR less than 30ml/min
When should you refer to nephrology with diabetic nephropathy?
eGFR
When may a simultaneous kidney and pancreas transplant be needed?
T1DM
When is HbA1c acceptable at 58mmol/l?
Diabetes longer than 10 years
How should an MI be treated in diabetic vascular disease?
Aspirin, primary angioplasty, IV glucose and insulin
What is the 2 year mortality in those that present with peripheral neuropathy?
20 percent
In a stroke, when can can thrombolysis be used?
Within 4h
What should be given acutely with ischaemic stroke in diabetic vascular disease?
ACE-I, statins, aspirin, glucose and insulin infusion
What are the complications of peripheral vascular disease?
Intermittent claudication
Rest pain
Buttock pain
How is peripheral vascular disease managed?
Aspirin and vasodilators
Which surgical interventions are available in peripheral vascular disease?
Angioplasty/reconstructive surgery
Amputation
What are the musculoskeletal manifestations of diabetes?
Charcots neuroarthropathy Diffuse idiopathic skeletal hyperostosis Flexor tendniopathy Diabetic osteoarthropathy Diabetic cheiroarthropathy (due to limited joint mobility)
Which liver condition is more common in DM?
NAFLD
How can NAFLD progress?
NASH
Cirrhosis and fibrosis
What do LFTs show with NAFLD?
Raised ALT and AST
When should a raised ALT and AST prompt further investigation?
When more than 2x normal limit
What liver disease needs to be excluded with raised ALT and AST?
Haemochromatosis
Which investigations should be carried out in NAFLD?
LFTs
Liver biochemistry
USS
Ferritin
How is poiglitazone useful in NAFLD?
Stops progression to cirrhosis
How can the progression to cirrhosis be halted in NAFLD?
Poiglitazone
Rigorous glycemic and diabetic risk factor control
When do patients start to experience symptoms of hypoglycaemia?
Blood glucose less than 3.6mmol/l
What is false hypoglycaemia?
if patients are constantly hyperglycaemic they begin to exhibit hypoglycaemia symptoms when in normoglycemia
Which function tumour can cause hypoglycaemia?
Insulinoma
Which renal condition is associated with hypoglycaemia?
CKD
Which endocrine conditions cause hypoglycaemia?
Hypothyroid
Hypoadrenalism
Hypopituarism
Insulinoma
Which diabetic treatments are most likely to cause hypoglycaemia?
Sulphonylureas
Insulin
What autonomic symptoms are seen in hypoglycaemia?
Nausea Hunger Anxiety and palpitations Sweating Tremor
When do neuroglycaemic symptoms begin to occur in hypoglycaemia?
Glucose less than 2.7mmol/l
What percentage of T1DM may not recognise a hypo?
25 percent
What are the risk factors for a hypo in T1DM?
Autonomic neuropathy
Very tight glycemic control
Duration of diabetes
Are there any restrictions on insulin users and driving?
Not if they are compliant with treatment and have not had a hypo whilst driving
What is the first line management of a hypo?
Give carbs
Relax glycemic control
What is the second line treatment of a hypo?
Switch to analogue insulin
Continuous subcutaneous insulin infusion therapy
When may a driving licence be revoked in relation to a hypo?
Severe hypo that needed 3rd party assistance
How may nocturnal hypoglycaemia present?
Rebound hyperglycaemia
Headaches
How can nocturnal hypoglycaemia be diagnosed?
3am blood glucose
Subcutaneous glucose monitor for 5 days
What is the management of nocturnal hypoglycaemia?
Pre bed snack
Reduce night time insulin
Insulin pump
Switch to analogue insulin
What is DKA?
Relative or absolute insulin deficiency resulting in hyperglycaemia and accumulation of ketoacids in the blood
What type of acidosis is seen in DKA?
Metabolic
What capillary glucose is often seen in DKA?
Over 14 mmol/l
How is ketosis diagnosed?
Elevated blood or urine ketones
What bicarbonate level is often seen in DKA?
Less than 15mmol/l
How does insulin deficiency lead to DKA?
Insulin normally inhibits gluconeogenesis
How does catecholamine excess promote the pathogenesis of DKA?
Promotes triglyceride breakdown to FFA and glycerol which stimulates gluconeogenesis
Where do the ketones come from in DKA?
FFA metabolism
Which ketones are usually present in DKA?
3-OH-butyric acid
Acetoacetic acid
Which type of respiration is seen in DKA?
Kaussmauls
What signs and symptoms are seen in DKA?
Kaussmauls respiration Reduced GCS Ketones on breath Abdominal pain and vomiting Dehydration and tachycardia
What can precipitate DKA?
MI, infection, pregnancy, insulin admission
How is DKA initially diagnosed?
VBG showing acidosis
Capillary blood glucose greater than 14
+/- raised urea/creatinine
+/- raised urea/plasma ketones
Which level of care should DKA patients be admitted to?
HDU
How is DKA managed?
Fluids (plus potassium), glucose and insulin
How is normal saline given in DKA?
1l stat and 1l over 1hour
Then 1l over 2 hours and 1l over 4 hours both with 20mmol potassium
When should glucose (5 percent) be given in DKA?
When the blood glucose drops below 12
At what rate should the glucose be given in DKA?
125ml/hour
When should 10 percent glucose be given in DKA?
When insulin infusion has started
How should insulin be given in DKA?
If know diabetic continue long acting insulin on admission
Commence stat IV insulin infusion with 50u actrapid (in 50ml NaCl)
Insulin 0.1kg/hour after
When should the insulin infusion be given at an increased rate in DKA?
When the glucose falls below 6mmol/l
What is the desired bicarb in DKA?
3mmol/hour
How can the insulin infusion be changed to raise bicarbonate at a faster rate in DKA?
Raise the rate of infusion by 1u/hour
What complication of DKA especially arises in children?
Cerebral oedema
How is cerebral oedema in DKA treated?
Dexamethasone or mannitol
When can a patient be returned to their normal insulin regime following DKA?
When eating and drinking reliably
In which type of diabetes does HHS occur?
T2DM
What capillary blood glucose is often seen in HHS?
over 40 mmol/l
What is the osmolality of blood in HHS?
Over 340
In HHS, are patients often hypernatremic?
yes
When are ketones seen in HHS?
If the patient is not eating
What type of acidosis is present in HHS?
Lactic acidosis (metabolic)
How is HHS treated?
No insulin for first 12 hours then give 1u/hr (DO NOT GIVE INSULIN BOLUS)
What is the maximum rate the glucose should be corrected at in HHS?
2mmol/l/hour
What complication arises when glucose levels are fixed too rapidly in HHS?
Cerebral pontine myelinolysis - due to sodium shifts
How is fluid administered in HHS?
1l stat and 1l over 1hr
Then 1l over 2 hours and 1l over 4 hours both with potassium
Why should normal saline, and not 0.45 percent saline be used in correcting HHS?
Sodium declines rapidly with insulin
What consideration must be made when giving IV fluids?
If the patient is elderly or in congestive heart failure
Should we accept normal biochemistry for a couple of days after correcting HHS?
Yes
What are the sick day rules for patients with DM?
Glucose checked more regularly Give insulin to those on oral therapy Go to hospital if vomiting More fluid and sugary food/fluid Increased insulin if on insulin therapy