Diabetes Flashcards
What are the four cell types found in the islets of langerhans in the pancreas?
Beta cells - make and secrete insulin
Alpha cells - secrete glucagon
Delta cells - secrete somatostatin
PP cells - secrete pancreatic polypeptide
Where is insulin synthesized? What is its precursor? What process converts this to insulin? What components does a molecule of insulin have? What is proinsulin? What is the role of preinsulin?
Insulin is synthesized in the rough endoplasmic reticulum of pancreatic beta cells as a larger single chain preprohormone – called preproinsulin.
It is then cleaved to form insulin.
Insulin contains two polypeptide chains linked by disulfide bonds.
Connecting (C) peptide, a byproduct of cleavage, has no known physiologic function.
Proinsulin – provides a tertiary structure which is recognised by insulin receptors.
Give the five types of insulin preparation and their relative length of time in the blood
Ultrafast/ultra short acting - lispro Short acting - regular Intermediate acting - NPH + lente Long-acting - ultralente Ultra long acting - glargine
Briefly decribe the stages of insulin, from glucose entering the cell to release of insulin
Glucose enters the beta cell through the GLUT2 glucose transporter
Glucose is phosphorylated by glucokinase, creating glucose phosphate
Glucose phosphate is metabolised, leading to the production of ATP
ATP blocks removal of K+ from the cell by inhibiting the ATP-sensitive K+ channel (called KATP)
This causes depolarization of the membrane
Voltage gated Ca2+ channels open
Influx of Ca2+
Causes fusion of secretory vesicles with the cell membrane
Insulin is released
What is the typical pattern of release of insulin?
Why is this?
Release of insulin is biphasic – 2nd phase if 1st phase hasn’t increased blood glucose levels.
There are two phases because:
- Only 5 % of insulin granules are immediately available for release i.e. the RRP – readily releasable pool
- Reserve pool must undergo preparatory reactions to become mobilised and available for release
Which two proteins make up KATP channels?
How can these be altered?
What can this cause?
Kir6
SUR1
Genetic mutations can alter these
Problems with insulin secretion
What is MODY?
The activity of what is impaired?
This is a type of monogenic diabetes with a genetic defect in beta cell function.
It is a familial form of early-onset type diabetes, with the primary defect being in insulin secretion.
Activity of glucokinase is impaired
What are the three basic steps in signalling cascades?
- Reception – signal molecule binds to the receptor
- Transduction – signal transduction pathway how the initial binding triggers a cellular response
- Response – activation of cellular responses
The insulin receptor is a member of which family?
Receptor tyrosine kinase family
What is the diagnostic criteria for diabetes?
Any of the following criteria:
- HbA1c >48 m/m
- Fasting glucose above 7 mmol/L
- 2-hr glucose in OGTT >11.1 mmol/L
- Random glucose >11.1 mmol/L
The WHO recommends normal BG as what?
What should this really be?
WHO - <6.1 mmol/L
Should be <5.6 mmol/L
Which antibodies are typically present at diagnosis of T1DM?
GAD
What are three useful discriminatory tests between T1DM and T2DM?
GAD/ Anti-Islet Cell antibodies
Ketones
C-peptide (plasma)
What is type III diabetes?
List some causes
This is when other diseases cause secondary diabetes
Pancreatic disease
- Chronic or recurrent pancreatitis Haemochromatosis
- Cystic Fibrosis
Endocrine disease - Cushing’s syndrome, Acromegaly, Phaechromocytoma, Glucagonoma
Drug induced
- Glucocorticoids
- Diuretics
- B-blockers
What five things should you look out for in monogenic diabetes?
Strong Family History Associated Features (renal cysts etc) Young Onset GAD-negative C-peptide positive
Define gestational diabetes
Any degree of glucose intolerance arising or diagnosed during pregnancy.
Basic criteria for diagnosing T1DM?
Fasting glucose ≥ 7.0mmol/l
Random ≥ 11.1mmol/l AND symptoms, OR repeat test
Why can’t you use HbA1c in T1DM?
Can’t HbA1c to test for type I diabetes due the rapid onset of the disease.
Is the risk of getting T1DM more, less or the same if your mother or father has diabetes?
8% if father
3% if mother
What % of familial risk of T1DM does HLA make up?
What are the two highest risk genotypes?
50%
DR3-DQ2
DR4-DQ8
How does seasonality affect the risk of T1DM?
Seasonality – it is less common in those born in the summer months, particularly July
What are some possible triggers for T1DM?
Viral infection
Maternal factors
Weight gain
Autoantibodies in T1DM
- Which two are commonly used?
- Which is used if all others are negative?
- Which is better in children?
- Which is better in the older?
GAD (female) and IA-2 (male) are commonly used
Zn transporter can be used if all others are negative
IAA (insulin autoantibody) is better in children
Zn transporter is better in the older
Which “risk factors” accelerate the progression of T1DM?
Infection Insulin resistance Puberty Diet/weight Stress
What are four biochemical markers of increased disease progression?
Raised glucose ketones
Decreased insulin
Decreased B-cell mass
Decreased C-peptide
What is the classic triad of presenting features in T1DM?
What other things should you look out for?
- Polyuria
- Polydipsia
- Weight loss
Other things
- Fatigue
- Blurred vision
- Thrush
- FHx of autoimmune conditions e.g. thyroid
How should you manage a newly diagnosed patient with T1DM?
- Blood glucose and ketone monitoring
- Insulin - usually basal bolus regimen
- CHO estimation
- Regular dietician contact
- Appropriate medical clinic review
- Regular check of prevailing glycaemic control - HbA1c (ideal range 48-58 mmol/L)
What five things should you do at an annual review assessment for T1DM?
Weight Blood pressure Bloods: HbA1c, Renal Function and Lipids Retinal screening Foot risk assessment
What is LADA?
What is the commonest age range for diagnosis?
Latent autoimmune diabetes – a form of type I with endogenous secretion for about first four years after diagnosis.
20-30
Definition - ‘A diagnosis of LADA is established by the presence of elevated levels of pancreatic auto-antibodies in patients with ‘recently diagnosed’ diabetes who do not initially require insulin’.
You have to have lost what % of beta cell mass before getting raised blood sugar?
What % do you need to lose to get insulin dependence?
Which type of diabetes is slower at losing beta cell mass?
50%
>90%
LADA is slower at losing B cell mass.
When should you suspect LADA?
Occurs in young adults 25 to 40 Male preponderance Usually non-obese Auto-antibody positive Associated auto-immune conditions Non-insulin requiring at diagnosis Sub-optimal control on oral agents
Name five clinical features of DIDMOAD aka Wolfram syndrome
Diabetes Insipidus Diabetes Mellitus Optic Atrophy Deafness Neurological anomalies
What are some autoimmune conditions commonly associated with T1DM?
Thyroid disease Coeliac disease - 5% in Type 1 DM; 1% in the population Pernicious Anaemia Addison’s disease IgA deficiency
What are the two important things that HbA1c correlates with?
As HbAc1 concentration increases, incidence of microvascular complication decreases
As HbAc1 concentration increases, incidence of hypos increases
Secretion of insulin at a basal rate accounts for what % of total insulin production?
50%
How many units of insulin, and at what times would you prescribe for a 60 kg male aged 16?
- e.g. start at 0.3 units/kg body weight
- Divide it around 50% prandial 50% Basal
- Total= 18 units
- Lantus (long acting) - 9 units pre-bed (2200hrs)
- Prandial – 3 /3 /3 units pre-meals
What is advanced CHO counting?
Who is it suitable for?
Synchronizing the amount of insulin taken to amount of carbohydrate consumed.
Who is it suitable for?
- For those on multiple daily injections (MDI)
- For people on continuous subcutaneous insulin infusion (SCII) pumps
What is the goal of pancreatic islet transplantation in T1DM?
To restore the symptoms of hypos again
What is the natural history of beta cell function in T2DM?
initially, the beta cells compensate for increasing insulin resistance.
The body tries to compensate for resistance by increasing insulin production, you ultimately get to a point where the pancreas burns out and insulin production starts to lower in the pancreas. At this point, blood glucose tends to rise.
What is is that we think anatomically decreases beta cell function?
Excess fat around the pancreas
What four things is central adiposity (apple shape) associated with?
High blood pressure
High Triglycerides
Low HDL
Insulin resistance
What is the most common external manifestation of insulin resistance?
Acanthosis nigricans = thickening and slight pigmentation of the skin, around folding areas e.g. around the neck
What is the natural history of T2DM?
B-cell decline precedes the development of Type 2 diabetes by up to 15 years.
Following the development of insulin resistance there is a compensatory increase in insulin secretion by the β-cells of the pancreas (hyperinsulinaemia) in order to achieve normal blood glucose levels.
Eventually, β-cell function starts to decline, leading to impaired glucose tolerance (IGT) and Type 2 diabetes.
What are the four main types of neuropathy found in T2DM?
Briefly describe each
- Peripheral – this is the classic case; glove and stocking type lesions; can either be symptomatic with lots of pain, or asymptomatic with loss of sensation e.g. pain/ loss of feeling in feet, hands
- Autonomic e.g. changes in bowel, bladder function, sexual response, sweating, heart rate, blood pressure, hypoglycaemic unawareness
- Proximal – most often seen when you lose the dermatomal distribution of a single neuron e.g. pain in the thighs, hips or buttocks leading to weakness in the legs (Amyotrophy)
- Focal Neuropathy e.g. sudden weakness in one nerve or a group of nerves causing muscle weakness or pain e.g. carpal tunnel, ulnar mono neuropathy, foot drop, bells palsy, cranial nerve palsy
What are the risk factors for neuropathy in diabetes?
Increased length of diabetes Poor glycaemic control Type 1 diabetes > Type 2 diabetes High Cholesterol/ Lipids Smoking Alcohol Inherited Traits (genes) Mechanical Injury
What are the two type of peripheral nerve damage in diabetes?
Peripheral nerve damage can be distal symmetric or sensorimotor neuropathy.
What are some features of the symptoms of peripheral nerve damage?
- Numbness/ insensitivity
- Tingling/ burning – people describe an odd sensation in their feet, like walking on hot coals, or pressure etc
- Generally worse through the night
- Sharp pains or cramps
- Sensitivity to touch
- Loss of balance and coordination
What three things can peripheral nerve damage lead to in the foot?
Charcot foot
Painless trauma
Painless ulcer
Give some symptoms of the following types of neuropathy:
- Sensory
- Autonomic
- Motor
Sensory – loss of sensation in stocking lesion; tested by 10g monofilament
Autonomic – get a very dry foot, which causes cracking and allows bacteria to get inside; warm; distended veins
Motor – neurons supplying nutrients to the small muscles of the foot, so foot loses its transverse and lateral arch, so you get clawing of the foot
What are the five steps of the treatment of painful neuropathy?
- Simple Analgesia (paracetamol)
- TCAs (Amitryptiline (small dose at night))
- Gabapentin
- Duloxetine (60mg)/ Pre-Gabalin (50mg bd-200mg)
- Stronger opiods e.g. oxycodone/ tramadol
Name some common forms of focal neuropathy in terms of the symptoms they cause
Inability to focus eye Double vision Aching behind eye Bell’s palsy Pain in thigh/ chest/ lower back/ pelvis Pain on outside of foot
What is entrapment neuropathy?
Weakness in one nerve or a group of nerves causing muscle weakness or pain e.g. carpal tunnel syndrome.
Note that this is not specific to diabetes, but very common in diabetes.
Proximal neuropathy Examples? How does it start? Who is it more common in? What is it often associated with?
For example, lumbosacral plexus neuropathy, femoral neuropathy or diabetic amyotrophy.
Starts with pain in the thighs, hips, buttocks or legs, usually on one side of the body. More common in elderly T2D.
Often associated with marked weight loss.
Give four systems/things that autonomic neuropathy can affect
Digestive system
Sweat glands
Heart and blood vessels
Eyes
What are the three main problems in digestive system neuropathy?
- Gastric slowing/ frequency - constipation/ diarrhea (sometimes both); gradually over time the size of the stomach increases
- Gastroparesis (slow stomach emptying) - persistent nausea and vomiting, bloating, and loss of appetite; can make blood glucose levels fluctuate widely, due to abnormal food digestion
- Oesophagus nerve damage- may make swallowing difficult -> can lead to weight loss
When should you consider the diagnosis of gastroparesis?
Consider the diagnosis of gastroparesis in an adult with erratic blood glucose control or unexplained gastric bloating or vomiting, taking into consideration possible alternative diagnoses.
Give some possible treatments for digestive system neuropathy
- Improved glycaemic control
- Dietary - smaller, more frequent food portions; low fat (fat further delays gastric emptying); low in fiber (Bezoars); if severe may need liquid meals
- Promotility drugs such as metoclopramide, domperidone, and erythromycin anti-nausea medications such as prochlorperazine and serotonin antagonists such as ondansetron. Abdominal pain in gastroparesis include nonsteroidal anti-inflammatory drugs (NSAIDs), low dose tricyclic antidepressants, gabapentin, tramadol and fentanyl.
- Consider a trial of metoclopramide, domperidone, or erythromycin
- Botulinum Toxin – if you have an oesophageal or pyloric sphincter which is not opening up
- Gastric Pacemaker – out electrodes into the stomach wall which stimulate motility
Autonomic neuropathy of the sweat glands
What are some typical symptoms?
What is gustatory sweating?
Treatment?
The body cannot regulate its temperature as it should. Nerve damage can also cause profuse sweating at night or while eating.
‘Gustatory Sweating’ – upper body sweats profusely, but the lower body is dry.
Treatment: Topical glycopyrrolate, clonidine, botulinum toxin
What are the two main problems in autonomic neuropathy of the heart and blood vessels?
- Blood pressure may drop sharply after sitting or standing, causing a person to feel light-headed/ faint
- Heart rate may stay high, instead of rising and falling in response to normal body functions and physical activity
I.e. postural hypotension and tachycardia
What are two useful diagnostic tools for neuropathy?
Nerve conduction studies or electromyography can determine the type and extent of nerve damage, and how well muscles respond to electrical signals transmitted by nearby nerves.
What is diabetic nephropathy?
This is a progressive kidney disease caused by damage to the capillaries in the kidneys’ glomeruli. It is characterized by nephrotic syndrome and diffuse scarring of the glomeruli.
What are three serious consequences of diabetic nephropathy?
- Development of hypertension – affecting the whole angiotensin system
- Relentless decline in renal function - reduction in GFR of 1 ml/min/month if untreated
- Accelerated vascular disease – most people who develop nephropathy end up dying from cardiovascular disease as they cannot clear a lot of the toxins etc from the body
What should you use to screen for diabetic kidney disease?
What are the normals for men and women?
What else should you look for in the urine sample?
Urinary albumin creatinine ratio (ACR) - Male <2.5 mg/mmol creatinine
- Female <3.5 mg/mmol creatinine
Look for microalbuminuria
Name five risk factors for diabetic nephropathy progression
Hypertension Cholesterol Smoking Glycaemic control Albuminuria
What are the treatment recommendations for diabetic nephropathy?
- Blood pressure should be maintained <130/80 mm Hg in all patients with diabetes; target in SIGN = 130/70
- Patients with microalbuminuria or proteinuria should be commenced on an ACE inhibitor or ARB
- Good glycaemic control (HbA1c around 53 mmol/mol) in patients with diabetes should be maintained to reduce the risk of developing diabetic nephropathy
Name four eye pathologies that people with diabetes get
- Diabetic retinopathy
- Cataract - clouding of the lens (develops earlier in people with diabetes)
- Glaucoma - increase in fluid pressure in the eye leading to optic nerve damage -> 2 x more common in diabetes
- Acute hyperglycaemia -> visual blurring (reversible)
What are the four stages of neuropathy?
- Mild non-proliferative (background)
- Moderate non-proliferative
- Severe non-proliferative
- Proliferative
Name four things you should look out for in the eye
- Haemorrages – e.g. dot, blot, flame
- Cotton wool spots - ischaemic areas
- Hard exudates - lipid break down products which have leaked out of the capillaries into the retinal area
- IRMA: Intra-retinal microvascular abnormalities (abnormalities of blood vessels/ precursor to neovascularisation but blood vessels are patents (not leaking))
MODY What does this stand for? What type of genetic defect? What does it cause? What is the typical age of onset?
This is a form of autosomal dominant inheritance, which causes non-insulin dependent diabetes -> patients don’t require treatment with insulin.
Typically under 25
MODY is a very heterogeneous condition, with lots of genes causing it, so you get lots of different types.
What are the two distinct types?
- Glucokinase – cell doesn’t detect glucose correctly - high fasting glucose, but everything else about their beta cell is fine; tend to find this on incidental blood testing; doesn’t tend to cause complications
- Transcription - starts in teenage years; treatment progresses from tablets to insulin
How to two two types of MODY differ on glucose tolerance test?
As the glucokinase kind is just a defect in sensing glucose, on glucose tolerance test they have high fasting glucose, and then over the two hour period their glucose doesn’t go up that much and comes down quite quickly. However, the transcription factor type glucose levels go up quite high and then back down again.
What are some clinical characteristics of the glucokinase type of MODY?
Onset at birth
Stably hyperglycaemia
Diet treatment
Complications rare
What are some clinical characteristics of the transcription type of MODY?
Adolescent/young adult onset
Progressive hyperglycemia
1/3 diet, 1/3 OHA, 1/3 insulin
How are patients with he glucokinase type MODY treated?
There is no need for insulin treatment in patients with glucokinase MODY. Patients with this kind of MODY are very sensitive to sulphonylurea type drugs.
What are the two main types of neonatal diabetes?
Transient neonatal diabetes - Usually diagnosed <1 week - Resolves median 12 weeks - Stop insulin Permanent neonatal diabetes - Usually diagnosed 0-6 weeks - Lifelong treatment with insulin (can transfer off of lifelone insulin to sulphonylureas)
What is the pathophysiology and treatment of neonatal diabetes?
The faulty gene is in the potassium channel – a rise in ATP should cause closure of the kATP channel, but the channel here just stays open and doesn’t close -> patents don’t produce insulin. Sulphonylureas work on this channel to close it and bring about insulin secretion.
What is diabetic ketoacidosis?
Diabetic ketoacidosis (DKA) is a disordered metabolic state that usually occurs in the context of an absolute or relative insulin deficiency accompanied by an increase in the counter-regulatory hormones i.e. glucagon, adrenaline, cortisol and growth hormone. By definition DKA can occur in both Type 1 and Type 2 -> increasingly seen in type II. Ultimately leads to high sugar, acidosis, and a degree of hyperosmolarity, leading to renal impairment.
What are some common precipitants of DKA?
Infection (20 to 25%) – may be an over-estimate
Illicit drugs and alcohol (10 to 15%)
Non-adherence with treatment (45 to 50%) – may be under-estimate
Newly diagnosed diabetes (25% and falling?)
What three groups can the symptoms and signs of DKA be divided into?
Osmotic related
Ketone body related
Associated conditions
What are the osmotic related symptoms of DKA?
Thirst and polyuria
Dehydration
What are the ketone body related symptoms of DKA?
Flushed Vomiting Abdominal pain and tenderness Breathless – Kussmaul’s respiration NB not all individuals can smell ketones on breath
Which conditions are associated with DKA?
Underlying sepsis
Gastroenteritis
What are the classic levels of the following on presentation with DKA? Glucose Potassium Creatinine Sodium Lactate Blood ketones
Glucose
- Median level around 40 mmol/L [Normal<6]
- Can be anything from 10 [‘euglycaemic ketosis’] to 100 mmol/L
Potassium
- Usually raised above 5.5 mmol/L
- Beware the low normal -> this is a far greater risk to the patient than high
Creatinine: often raised
Sodium: often reduced
Raised lactate is very common
Blood ketones usually raised to > 5
What is used to measure ketones in the blood vs in the urine?
Blood measure is βhydroxybutarate
Urine is acetoacetate
What four risks should you be aware of and check for in DKA?
- Aspiration: is he semi-conscious?
- Is potassium a concern? -> remember the importance of low level potassium
- Could he be septic?
- What is the thrombo-embolic risk?
In children with DKA, what is the most common cause of death?
Adults?
Cerebral oedema Adults - Hypokalaemia - Aspiration pneumonia - ARDS - Co-morbidities
How should you manage a patient with DKA?
Manage in HDU following hospital protocol.
Replace losses
- Fluid: initially with 0.9% sodium chloride, when glucose falls to about 15, switch to dextrose
- Insulin
- Potassium
- Phosphate [rarely] and bicarbonate [almost never] replaced
Address risks
- ? is a naso-gastric tube required? - Monitor K+
- Prescribe prophylactic LMWH
- Source sepsis: CXR, Blood Culture, MSSU +/- viral titres, etc.
What are some typical features of hyperglycaemic hyperosmolar syndrome?
Diabetes may be known, often not
If known, then often treatment is ‘diet alone’
Usually older individuals
Younger individuals in non-Caucasian groups
High refined CHO intake pre-event
What is the classic triad of HHS?
- Hypovolaemia +
- Hyperglycaemia (BG >30) without significant acidosis or renal impairment
- Hyperosmolar (>320 mosmol/kg)
How are the following affected in HHS? Glucose Renal Sodium Osmolarity Acidosis
Higher glucose than in DKA -> median around 60
Significant renal impairment
Sodium may be raised on admission
Significant elevation of osmolality – often around 400
Less ketonaemic/acidotic as compared to DKA
How is osmolarity calculated?
Was is the normal value?
Osmolality=2x[Na+K] + Urea + Glucose
Normal osmolality 285 to 295
How is lactic acidosis classified?
Give examples.
Type A - associated with tissue hypoxaemia
- Infarcted tissue, eg ischaemic bowel
- Cardiogenic shock
- Hypovolaemic shock e.g. sepsis [endotoxic shock], haemorrhage
Type B
- May occur in liver disease
- May occur in leukaemic states
- Associated with diabetes
- Also consider rare inherited metabolic conditions if well and non-diabetic
Clinical features of lactic acidosis?
Hyperventilation
Mental confusion
Stupor or coma if severe
Treatment of lactic acidosis
Treatment is of the underlying condition with fluids and antibiotics.
Remember to withdraw the offending medication.
How do we know that early management is very important in diabetes?
Research (graph shown opposite) also shows that after following the same patients up for 18 years, those who had been on the intensive treatment up to 18 years before had significantly lower complications.
What is the relationship between glycated haemoglobin and complications?
With only about 1% reduction of Hb1Ac, there is 75 % reduction in symptoms.
What is HbA1c?
How is it formed?
What can it give a measure of?
Largest component of the glycated hemoglobins (60-80%)
Formed by non-enzymatic glycation of haemoglobin on exposure to glucose
Measure of average blood glucose over a prolonged period of time (6-8 weeks)
What are the values for HbA1c for
Normal
Prediabetes
Diabetes
Normal - below 42 mmol/mol (6.0%)
Prediabetes - 42-47 mmol/mol (6.0-6.4%)
Diabetes - 48 mmol/mol or over (>6.5%)
Give two limitations of HbA1c
- Remember it’s a guideline, and as soon as the trial finished, they went back up by about 8%, <10% of population with diabetes will be at a low level, as it is very difficult to achieve
- It gives you an average exposure to glucose, so you ca have very little glucose variability and marked glucose variability, but the same HbA1c (shown opposite)
What are the NICE guidelines of HbA1c in :
Children with type 1 diabetes?
Adults with type 1 diabetes?
Type 2 diabetes?
Children with Type 1 diabetes - On waking and before meals: 4–7mmol/l - After meals: 5–9mmol/l. Adults with Type 1 diabetes - On waking: 5–7mmol/l - Before meals at other times of the day: 4–7mmol/l - 90 minutes after meals: 5–9mmol/l. Type 2 diabetes - Before meals: 4–7mmol/l - Two hours after meals: less than 8.5mmol/l.
Give some symptoms of hypoglycaemia
Shaking Sweating Anxious Dizziness Hunger Tachycardia Impaired vision Weakness, fatigue Headache Irritable
What is the definition of severe hypoglycaemia?
Hypoglycemia that leads to seizures, unconsciousness or the need for external assistance.
What is the relationship between HbA1c and incidence of hypos in T1DM?
There is an inverse relationship between HbA1c and risk of hypoglycaemic events.
What is impaired hypoglycaemic awareness?
What % of T1DM adults does this affect?
This is when you are gradually lose the symptoms of hypoglycaemia over time, increasing the risk of that individual experiencing more profound severe hypoglycaemia.
When hypoglycaemia occurs (<4.0 mmol/l) and individuals feel no or a change symptoms.
On average this affects 25-30% of type I adult diabetics.
Who gets impaired hypoglycaemia awareness?
Those who:
- Frequently have low blood glucose episodes
- Long duration type 1 or 2 diabetes
- Intensively-treated type 1 diabetes (remember the inverse relationship between low HbA1c and incidence of hypoglycaemic attacks)
How does your body respond to hypoglycaemia?
What happens to this response as the disease progresses?
You respond to hypoglycaemia by increasing stress hormones, e.g. glucagon, then adrenaline and noradrenaline
Within about 5 years of diagnosis of T1DM, a lot of people lose their ability to produce glucagon
What happens to the alpha cells in someone with long term T1DM?
Glucose levels drop and glucagon levels drop (usually glucagon levels should rise – in a healthy individual)
What is the relationship between intensive insulin therapy in treatment of T1DM and defence against hypoglycaemia?
Explain this.
Research has also shown that intensive insulin therapy treatment of type I diabetes impairs defence against hypoglycaemia. This is because more intensive treatment is associated with lower HbA1c. Lower Hb1Ac is associated with a higher incidence of hypoglycaemic attacks. It is proposed that hypoglycaemia itself impairs neuroendocrine responses to subsequent hypoglycaemia.
Why might reduced hypoglycaemia awareness be described as habituation?
Hypoglycemia is an internal stimulus that is similarly sensed by the brain and elicits a motor response namely counterregulatory hormone release. At the same time repeated hypoglycemia leads to a diminishment of this response, i.e. could this be habituation
Give five rare causes of hypoglycemia (and some examples)
- Primary failure of hormones to raise glucose, e.g. hypopituitarism, adrenal cortical failure, isloated GH deficiency
- Prolongation of insulin effects, e.g. exogenous injection, renal impairment, hypothyroidism, liver failure
- Exaggerated mismatch between insulin and nutrient absorption - malabsorption e.g. Coeliac disease
- Lifestyle contributors e.g. acute increase in glucose uptake with exercise
- Addisen’s disease
Metformin
Does it prevent microvascular complications?
Does it prevent macrovascular complications?
What effect on triglycerides and LDL?
Safe in pregnancy?
Yes
Yes
Reduces them
Safe in pregnancy
What are the major adverse effects of metformin?
What do you do to reduce these?
What is a very rare but severe side effect of metformin?
The major ones are GI related, so build up the dose slowly
lactic acidosis - most likely in existing severe renal, cardiac or liver failure
Metformin and renal toxicity
What values of eGFR and serum creatinine should you stop metformin at?
What value of eGFR should you hald the metformin dose?
When should you temporarily withhold metformin?
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 e.g. Angiography, CT scan
Liver toxicity in Metformin
Which liver conditions should you stop metformin in?
Which liver disease might it be beneficial in?
Discontinue if advanced cirrhosis/liver failure
Discontinue if risk of lactic acidosis e.g. encephalopathy, alcohol excess
May be beneficial in Non-alcoholic fatty liver disease (NAFLD)
At what point should you stop increasing the dose of SUs?
Stop increasing the dose at about 80-120 mg, as there isn’t much benefit above that.
Do SUs prevent microvascular and macrovascular complications?
Prevention of microvascular complications: Yes –
Prevention of macrovascular complications: No.
Give one disadvantage of GLP-1 receptor agonists
Nausea - usually resolves in 6-8 weeks
