Disease Profiles: Diabetes Flashcards
What is indicated by the arrow?
Microaneurysms
Define alcoholic ketoacidosis
Metabolic acidosis caused by increased production of ketone bodies with normal or low glucose levels resulting from the combined effects of alcohol and starvation on glucose metabolism
Describe the management of a MODY patient with a glucokinase mutation
Managed with diet alone as glucokinase mutations are not associated with increased risk of microvascular disease
Why should good sugar control pre-conception be ensured in a patient with T1/T2DM planning a pregnancy?
To limit risk of congenital malformation
Which investigation would you perform 6 weeks after birth in a patient who had gestational diabetes?
Fasting glucose or GTT to ensure resolution of DM
What is indicated by the circles?
Cotton wool spots
Name the three types of mutation found in MODY patients
Glucokinase (14%), transcription factors (75%), MODY X (11%)
Why is the diagnostic criteria for gestational diabetes lower than for other forms of diabetes?
FBG>5.5 comes with significant risk of increased weight of offspring at birth
Name two CNS complications for a neonate associated with mother having gestational diabetes
Anencephaly, spina bifida
What is the most common modifiable risk factor associated with insulin resistance?
Obesity
What is DIDMOAD (Wolfram syndrome)?
Genetic condition characterized by diabetes insipidus (DI), childhood-onset diabetes mellitus (DM), a gradual loss of vision caused by optic atrophy (OA), and deafness (D)
Describe the clinical presentation of diabetic ketoacidosis
Thirst and polyuria, dehydration
Flushed, vomiting, abdominal pain and tenderness, increased RR, smell ketones on breath
Why is it beneficial for a mother to develop some insulin resistance during pregnancy?
Means more nutrients are diverted to the foetus
Education in what areas should be provided to patients with T1DM?
How to match prandial insulin dose to carbohydrate intake, pre-meal glucose and anticipated activity, as well as sick day rules
Which patient group is most likely to develop idiopathic (1B) T1DM?
Most patients are of African or Asian ancestry
Strongly inherited (not HLA associated)
What causes the microvascular complications in diabetes?
Alternative glucose metabolism pathways used to metabolise the excess glucose which result in the generation of reactive oxygen species - harmful
Describe the management of Charcot foot
Aim is to prevent/minimise bony destruction by keeping pressure off the foot - non-weight bearing, total contact cast or aircast boot
Consolidation and stabilisation will take 6-12 months
What would be visible on a β-cell biopsy of a patient with T1DM?
Insulitis with lymphocytic infiltrate
Name two consequences of diabetic nephropathy
Hypertension, relentless decline in renal function
How does increased flux of glucose through the sorbitol-polyol pathway cause vascular damage?
Sorbitol accumulates which cause changes in vascular permeability, cell proliferation and capillary structure via stimulation of protein kinase C and TGF-β
What is C-peptide?
Substance co-secreted with insulin that is not part of injected insulin; can be used to measure ‘endogenous’ insulin secretion
When should aspirin be started in a pregnant patient with T1/T2DM?
12 weeks
Describe the clinical presentation of Leprechaunism (Donohue syndrome)
Severe insulin resistance and developmental abnormalities e.g. growth retardation, abscence of SC fat, caused by defects in insulin binding or insulin receptor signalling
Describe the structure of the KATP channel of the β-cell
Inward rectifier (pore) subunit and a sulphonylurea receptor
How can a glucokinase mutation cause MODY?
Glucokinase activity impaired, resulting in a glucose sensing defect - blood glucose threshold for insulin secretion is increased
Which investigation will show maculopathy?
Optical coherence tomography (refer if indicated from retinal screen)
What causes insulin resistance in adipose tissue?
Obesity-induced inflammation via pro-inflammatory cytokines e.g. TNF-⍺ which reduces glucose uptake
Which investigation can be used to confirm the type of MODY mutation?
Genetic screening
How are advanced glycation end products (AGE) formed?
When a wide variety of proteins are exposed to increase glucose concentrations, glucose binds irreversibly to the protein to form AGE
Describe the pathophysiology of hyperglycaemic hyperosmolar syndrome
Similar to DKA but enough insulin is produced to suppress lipolysis and therefore ketogenesis
However, insulin level is not high enough to lower blood glucose to a safe level
Name two causes of diabetic ketoacidosis
Insulin deficiency e.g. poor self management
Increased insulin demand e.g. infection
How does gestational diabetes cause macrosomia?
Maternal hypoglycaemia is transferred across the placenta, resulting in foetal hyperglycaemia
This causes foetal hyperinsulinaemia - insulin is a MAJOR growth factor
Name a genital/GI abnormality for a neonate associated with mother having gestational diabetes
Ureteric duplications
What is congenital hyperinsulinism?
Inappropriate and unregulated insulin secretion, which results in severe, persistent hypoglycemia in newborn babies, infants, and children
When should folic acid be started in a patient with T1/T2DM planning a pregnancy?
At least 3 months prior to conception
Describe the management of a patient with DKA
Replace fluid losses - NaCl 0.9%
Replace electrolyte losses - NaCl 0.9%, IV potassium
Insulin replacement
What causes Maturity Onset Diabetes of the Young (MODY)?
Single gene mutation (monogenetic) which is dominantly affected and predominantly affects β-cell function
How would you confirm DKA?
Diagnosis is confirmed by demonstrating hyperglycaemia (BG) with ketonaemia (ketone monitor) or heavy ketonuria (urine dipstick), and acidosis (ABG)
Name a skeletal abnormality for a neonate associated with mother having gestational diabetes
Caudal regression syndrome
What is the most common form of monogenetic diabetes?
MODY
Name the hormone produced by trophoblast cells that are surrounding a growing embryo, which eventually forms the placenta after implantation
HCG
Which T1DM patient group is associated with GAD 65 antibodies?
Females <10 years
Describe the clinical presentation of a MODY patient with a transcription factor mutation
Hyperglycaemia starts at adolescence/YA and is progressive
How would you diagnose hyperglycaemic hyperosmolar syndrome?
Profound hyperglycaemia (BG >33.3mmol/L), hyperosmolarity (serum osmolarity) and no ketoacidosis (ABG)
What are the cardinal features of Bardet-Biedl syndrome?
Truncal obesity, intellectual impairment, renal anomalies, polydactyly, retinal degeneration and hypogenitalism
How would you diagnose T1DM?
Fasting or random blood glucose above diagnostic threshold, repeat test if asymptomatic
If doubt - GAD/IA2 antibodies and C peptide may help
HbA1c is not used
What is the first line treatment for T2DM?
Metformin + lifestyle management
Describe the management of retinopathy
Pan retinal photocoagulation
What is diabetic ketoacidosis?
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; serious complication of type 1 diabetes and, much less commonly, of type 2 diabetes
What percentage of patients with Bardet-Biedl syndrome are affected by diabetes?
Up to 45% of patients
Describe the management of hyperglycaemic hyperosmolar syndrome
Fluid replacement - NaCl 0.9%
Consider 0.45% saline if sodium dropping too quickly
Start low dose
IV insulin only if significant ketones (>1) or BG falling at a slow rate
Describe the clinical presentation of a patient with hypoglycaemia
Pallor, sweating, tremor, palpitations, nausea, hunger, confusion
Which patient group normally presents with hyperglycaemic hyperosmolar syndrome?
People present in middle or later life, often with previously undiagnosed diabetes
Which T1DM patient group is associated with IA-2 antibodies?
Males, decreases with age
Which patient group is most likely to develop T2DM?
Usually occurs later in life (> 45 years), individuals of South Asian, African and Afro-Carribean descent are at greater risk
Name a topical options for the management of painful peripheral neuropathy where oral drug treatment isn’t suitable
Topical capsaicin cream
Name 3 non-modifiable risk factors for the development of T2DM
Age, genetics, ethnicity
What is IRMA in retinopathy?
Abnormalities of blood vesssels/precursor to neovascularisation but blood vessels are patent (not leaking)
What are the two peaks for diagnosis of T1DM?
85% of DM in under 20s, peak 10-14 years
25% diagnosed as adults - small peak in late 30s
Describe the insulin regimen of most patients with T1DM
Basal (long-acting once daily) bolus (short-acting with meals) regimen which aims to mimic normal endogenous insulin production
What is the BP target for a diabetic patient?
<140/80 mmHg
Describe the drug treatment of a pregnant T2DM patient
Metformin, will probably need insulin later
Name the gold-standard investigation for measurement of insulin sensitivity
Hyperinsulinemic-euglycemic clamp
What causes T2DM?
Contribution of genetics and environmental influences, usually the development of insulin resistance and obesity
Describe the genetic susceptibility with regards to development of T2DM
Some patients can safely store lots of fat, in others FFAs from obesity will spill into the viscera causing insulin resistance
Some patients have β-cells which are less able to cope with the lipotoxicity and glucotoxicity
What percentage of people with susceptible HLA genes will develop T1DM?
5%
Describe the clinical presentation of Rabson Medenhall syndrome
Severe insulin resistance, hyperglycaemia and compensatory hyperinsulinaemia
Other clinical features include developmental abnormalities and acanthosis nigricans
Hyperinsulinaemia causes fasting hypoglycaemia
Patients very prone to DKA
Name the fasting blood glucose value for diagnosis of diabetes
>/= 7mmol/L
Name the most common side effect of insulin therapy
Hypoglycaemia
Define hyperglycaemic hyperosmolar syndrome
Severe hyperglycaemia withouth significant ketosis; the characteristic metabolic emergency of T2DM
Describe the results of an oral glucose test in a MODY patient with a glucokinase mutation
High fasting blood glucose (~7 mmol) but bring their glucose down very well when given oral challenge
Monogenetic diabetes resulting in defective insulin action involves mutations in genes involved in which processes?
Insulin signalling pathway or fat storage
Define retinopathy
Damage to the retina
Name 3 autoimmune conditions associated with T1DM
Thyroid disease, coeliac disease, Addison’s disease
How can a transcription factor mutation cause MODY?
Play key roles in pancreas foetal development and neogenesis, also regulate β-cell differentiation and function
Define proteinuria (overt nephropathy)
ACR >30 or PCR >50
Will show up on urine dipstick
Describe the clinical presentation of diabetes (high blood glucose)
Polyuria
Thirst and polydipsia
Blurred vision
Genital thrush
Fatigue
Weight loss
Which investigation will show retinopathy?
Retinal screening
Describe the pathophysiology of T2DM
- Obesity
- Insulin resistance
- Hypersecretion of insulin with loss of biphasic pattern
- Hyperglycaemia persists as increased insulin is still insufficient
- β-cells are damaged by lipotoxicity and glucotoxicity
- Insulin production decreases
What percentage of patients with T1DM diagnosed under 30 have one or both high risk HLA genotypes DR3-DQ2/DR4-DQ8?
~95%
Name two eye pathologies associated with diabetes other than retinopathy and maculopathy
Cataract, glaucoma
Name the 2hr blood glucose in OGTT value for diagnosis of diabetes
>/= 11.1
What type of CF mutations are associated with the development of CFRD?
‘Severe’ mutations i.e. 𝝙508
What causes hard exudates seen on retinal screening of a patient with retinopathy?
Lipid breakdown products left behind by blood leaking from microaneurysms/haemorrhages
How can autonomic neuropathy affect the digestive system?
Gastric slowing/frequency → constipation/diarrhoea (sometimes both)
Gastroparesis
Oesophagus nerve damage - may make swallowing difficult
How does pan retinal photocoagulation treat retinopathy?
Reduces oxygen requirement of the retina so reduces the ischaemia that is driving the retinopathy
Which investigation should you perform in a thin patient with gestational diabetes?
GAD antibodies
Describe the management of microalbuminuria (nephropathy)
ACEi/ARB, SGLT2i, management of other vascular complications including BP
What is the goal of islet transplantation?
Prevent severe hypoglycaemia but about 50-70% of people receiving islet cell transplants also achieve insulin independence after 5 years
Define macular oedema (maculopathy)
Macular oedema involves clinically significant retinal thickening and oedema involving the macula, hard exudates and macula ischaemia
May occur in all stages of NPDR and PDR
Describe a consequence of painless trauma due to peripheral neuropathy
Patient may continue to walk on a wounded foot - worsens injury and may lead to infection
Define insulin resistance
The reduced ability of organs to respond to ‘physiological’ insulin levels, thought to primarily occur through reduced insulin sensing and/or signalling
What is the HbA1 target in T2DM?
7.0% (53 mmol/mol)
What are the indications for islet transplantation in T1DM?
Episodes of severe hypoglycaemia
Severe and progressive long-term complications despite maximal therapy
Uncontrolled diabetes despite maximal treatment
What is Bardet-Biedl syndrome?
Genetic condition that impacts multiple body systems e.g. eyes, brain, kidneys and is associated with consanguineous parents
Describe the auto-immune response in T1DM
T-cell mediated autoimmune response with production of autoantibodies that target and destroy β-cells
Describe the pathophysiology of alcoholic ketoacidosis
Accumulation of ketone bodies due to depleted glycogen stores from malnutrition, increased lipolysis and FFA release and volume depletion from e.g. vomiting
Name the two hormones released in pregnancy which produce insulin resistance in the mother
Placental progesterones and hPL
Name the investigation used to differentiate between Charcot foot and infection
MRI
What causes claw foot in a diabetic patient with peripheral neuropathy?
Interosseous wasting results in unbalanced traction by the long flexor muscles → high arch and clawing of toes
What causes insulin resistance in skeletal muscle?
Impairment of insulin signalling
Describe the clinical presentation of T2DM
Gradual onset, majority of patients are asymptomatic
Symptoms of complications may be the first clinical sign of disease
When symptomatic, the characteristic features of hyperglycaemia e.g. thirst, polyuria, blurred vision, may not be severe
How can a baby of a mother with gestational diabetes become hypoglycaemic shortly after birth?
After birth, the baby takes a while to downregulate the hyperinsulinaemia
How can autonomic neuropathy affect heart rate?
Heart rate may stay high, instead of rising and falling in response to normal bodily functions and physical activity
Why do MODY patients with a transcription factor mutation respond well to sulphonylureas?
Usually have β-cell function available so are ~4 x more sensitive than patients with T2DM
How many non-HLA genes have been associated with T1DM?
47
Which values would a patient with T1DM monitor?
Patients should have a method of self-monitoring their blood glucose and also have access to a ketone monitor
HLA genes represent what percentage of familial risk of T1DM?
~50%
How can autonomic neuropathy affect the blood vessels?
BP may drop sharply after sitting or standing, causing a person to feel light-headed/faint (postural hypertension)
________ _________ in severe non-proliferative diabetic retinopathy may help prevent long-term visual loss
Laser therapy
Name the gene which codes for the inward rectifier subunit of the β-cell KATP channel
Kir6
Describe the clinical presentation of a MODY patient with a glucokinase mutation
Hyperglycaemia starts at birth and is stable
Describe the management of severe hypoglycaemia (confusion, coma)
IM glucagon or IV glucose
Describe the management of hypoglycaemia (non-severe)
15-20g oral glucose
What is acanthosis nigricans?
Insulin-driven epithelial overgrowth seen in hyperinsulinaemic states (severe insulin resistance)
What causes the dehydration of patients in hyperglycaemic hyperosmolar syndrome?
Hyperglycaemia and osmotic diuresis (hyperosmolar urine)
Discuss co-morbidities related to hyperglycaemic hyperosmolar syndrome
Comorbidities more likely:
Screen for vascular event e.g. silent MI
LMWH for all patients (unless contraindicated)
High risk of feet complications
Describe the management of a patient with gestational diabetes
Lifestyle, metformin, may need insulin
What is Rabson Medenhall syndrome?
Monogenetic severe insulin resistance which presents with severe insulin resistance, hyperglycaemia and compensatory hyperinsulinaemia
How can a Kir6.2 mutation lead to neonatal diabetes?
Constitutively activated KATP channels or increase in KATP numbers
What causes T1DM?
Environmental trigger in a genetically susceptible individual mediated by an auto-immune process within the pancreatic β-cell
What are the indications for a whole pancreas transplant in T1DM?
Severe hypoglycaemia/metabolic complications, incapacitating clinical or emotional problems
Why should patients with T1DM rotate the insulin injection site?
Avoid lipohypertrophy
Name 3 modifiable risk factors for the development of T2DM
Obesity, poor diet, physical inactivity
Name two macrovascular complications of diabetes
Ischaemic heart disease, stroke
Define microalbuminuria
ACR <30 or PCR <50
At least 2/3 positive
What is LADA?
Latent autoimmune disease in adults - a ‘slow-burning’ variant of type 1A diabetes with slower progression to insulin deficiency that occurs in later life
What is Maturity Onset Diabetes of the Young (MODY)?
Early onset (usually before age 25) of non-insulin dependent diabetes
What is the normal physiological function of ketones?
Important molecules of energy metabolism for heart muscle and renal cortex - converted back into acetyl-CoA, which enters TCA cycle
Which T1DM patient group is associated with ZnT8 antibodies?
Older patients of both sexes
Name a respiratory complication for a neonate associated with mother having gestational diabetes
Respiratory distress due to immature lungs
Why should most patients with T1DM use insulin analogues?
Reduces hypoglycaemia risk
Name the HbA1c value for diagnosis of diabetes
48 mmol/mol (6.5%)
Describe the management of alcoholic ketoacidosis
IV pabrinex, IV fluid (5% dextrose in 0.9% NaCl), IV anti-emetics, insulin may be required
Further management - address alcohol dependency
Why is proliferative retinopathy dangerous to eyesight?
Vitreous haemorrhage can occur of the new blood vessels leading to sudden loss of vision
What is the diagnostic threshold for diabetes based on (except in gestational diabetes)?
Risk of developing diabetic retinopathy
Name the gene which codes for the sulphonylurea receptor of the β-cell KATP channel
SUR1
Describe idiopathic (1B) T1DM
Involves patients with permanent insulinopenia and who are prone to DKA but have no evidence of β-cell dysfunction or autoantibodies
Accounts for a minority of patients with T1DM (~5%)
What is focal neuropathy?
Sudden weakness in one nerve or a group of nerves causing muscle weakness or pain e.g. carpal tunnel syndrome, cranial nerve palsy
List the microvascular complications of diabetes
Neuropathy, nephropathy, retinopathy
What is indicated by the circles?
Hard exudates
What is Leprechaunism (Donohue syndrome)?
Monogenetic severe insulin resistance caused by mutations in the insulin receptor
What causes hypoglycaemia?
Occurs when more insulin is injected than is needed
How would you prevent a patient who has had gestational diabetes from developing T2DM in later life?
Keep weight as low as possible - healthy diet, exercise
Monitor with annual fasting glucose
How does the presence of FFAs in skeletal muscle result in insulin resistance?
Decreases the activity of tyrosine kinase (insulin receptor) and its downstream proteins
Means GLUT4 does not get translocated to the skeletal muscle cell membrane, so it is unable to take up glucose into the cell
Describe the clinical presentation of hyperglycaemic hyperosmolar syndrome
Polyuria, polydipsia, dehydration
N+V, stupor/coma
Define diabetes
An elevation of blood glucose above a diagnostic threshold
Why is insulin resistance in the liver described as pathway-selective?
Glucose uptake is reduced but hepatic lipogenesis remains elevated in insulin-resistant subjects
What causes gestational diabetes?
Placental progesterones and hPL produce insulin resistance in the mother
If mother is insulin resistant before pregnancy, developing further insulin resistance will raise blood glucose too high and result in gestational diabetes
When is a patient who injects insulin most at risk of hypoglycaemia?
Before meals, during the night and during or after excercise
Describe the administration of insulin for most patients
MDI (3-4x injections per day) or CSII
What is Charcot foot?
Complication of severe neuropathy that occurs in a well-perfused foot
What is T1DM?
Autoimmune destruction of the pancreatic beta-cells resulting in beta-cell deficiency and therefore absolute insulin deficiency
What causes increased lipogenesis in obese, insulin-resistant patients?
Increase of FFAs seen in obesity which allows VLDL secretion to increase
Which investigations would you perform in suspected alcoholic ketoacidosis?
↑ ketones (blood or urea), acidotic ABG
BG usually normal, may be low
What are the blood glucose targets for a pregnant patient with T1/T2DM or GDM?
Pre meal <4-5.5 mmol
2 hr post meal <6-6.5 mmol/l
Describe the clinical presentation of alcoholic ketoacidosis
N+V, abdominal pain, increased RR, dehydration
Name three environmental factors associated with the development of T1DM
Maternal factors, viral infections, vitamin D deficiency
What is metabolic syndrome?
At least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum HDL
Associated with increased risk of CHD, MI, stroke and CV death
What is autonomic neuropathy?
Neuropathy which affects the nerves regulating heart rate and blood pressure as well as control of internal organs such as those involved in GI motility, respiratory function, urination, sexual function and vision
Describe the clinical presentation of neonatal diabetes
Polydipsia, polyuria, dehydration, DKA which presents < 6 months (chance of T1DM at this age is >1%)
Describe the management of neonatal diabetes
Sulphonylureas - inhibit KATP
Name three complications of the foetus of a mother with gestational diabetes
Macrosomia, polyhydramnios, interuterine death
What is indicated by the circles?
Dot and blot haemorrhages
Which patient group is most likely to develop proximal neuropathy?
Elderly T2DM
Describe the management of a vitreal haemorrhage
Vitrectomy
What is CFRD?
Cystic fibrosis related diabetes
At what week of gestation does foetal organogenesis begin?
Week 5
What is peripheral neuropathy?
Pain/loss of feeling in feet/hands
What ECG results would indicate a diabetic patient has lost autonomic control of cardiac function due to autonomic neuropathy?
Loss of R-R variability with respiration
Describe the clinical presentation of Charcot foot
Acute onset of a hot, swollen foot +/- pain
If treatment is delayed, the foot can become deformed as bone is destroyed
What is HbA1C?
Level of glycated haemoglobin which is proportional to glucose; can give a measure of blood glucose over the last 90 days
What is the first line treatment for T2DM patients with heart failure or chronic kidney disease?
Metformin + an SGLT2i
Name two mutations which can cause congenital hyperinsulinism
Kir6.2 or SUR1
What is diabetic neuropathy?
Damage to the peripheral nervous tissue
Describe the management of autonomic neuropathy affecting the sweat glands
Topical glycopyrolate, clonidine, botulium toxin
When is a whole-pancreas transplantation most often performed?
Most often undertaken in people with T1DM and end-stage kidney disease at the same time as a kidney transplant
What causes cotton wool spots seen on retinal screening of a patient with retinopathy?
Micro-infarcts (ischaemia) due to occluded vessels
What is the first line treatment for T2DM patients with atherosclerotic CVD (e.g. previous MI)?
Metformin + GLP-1 receptor antagonist
What is proximal neuropathy?
Pain in the thighs, hips or buttocks leading to proximal muscle weakness and painful wasting
Often associated with weight loss
How can ketoacidosis occur in starvation?
Oxaloacetate is consumed for gluconeogenesis and when glucose is not avaliable fatty acids are oxidised to provide energy; the excess acetyl-CoA will be converted into ketones
What is the calculation for serum osmolarity?
(2 x Na+) + glucose + urea
What is Kussmaul’s respiration?
Deep, rapid breathing pattern associated with severe metabolic acidosis e.g. in DKA
Describe the results of an oral glucose test in a MODY patient with a transcription factor mutation
Normal fasting blood glucose but don’t respond well to glucose challenge
Which T1DM patient group is associated with IAA antibodies?
Children of both sexes
Name 3 investigations performed at a patient’s yearly diabetic review which screen for diabetic complications
Digital retinal screening, foot risk assessment, urine albumin-to-creatinine ratio and serum creatinine
What investigations should be performed at an annual review assessment of a patient with T1DM?
Weight
Blood pressure
Bloods: HbA1c, renal function and lipids
Retinal screening
Foot risk assessment
Why can a missed insulin dose lead to accumulation of ketones and therefore DKA?
Body switches to fatty acid oxidation so acetyl-CoA levels will increase
The excess acetyl-CoA is diverted to ketones as glycolysis is reduced due to lack of glucose
What is neonatal diabetes?
Rare form of monogenic diabetes much of which is caused by mutations in the glucose sensing mechanism e.g. in the ATP sensitive K channel
Describe the management of congenital hyperinsulinism
Diazoxide - stimulates KATP
Describe the clinical presentation of peripheral neuropathy
Numbness/insensitivity
Tingling/burning
Sharp pains or cramps
Sensitivity to touch
Loss of balace and coordination
Describe the management of maculopathy
Intravitreal anti-VEGF
Define monogenetic diabetes
Diabetes caused by a mutation in a single gene (Mendelian disease)
What are the main transcription factor mutations in MODY?
HNF-1⍺, HNF-1β, HNF-4⍺
What is diabetic nephropathy?
Progressive kidney disease caused by damage to the capillaries in the glomeruli
What is indicated by the circle?
Intra-retinal vascular abnormality (IRMA)
How do advanced glycation end products (AGE) cause tissue injury and inflammation?
Via stimulation of pro-inflammatory factors, such as complement and cytokines
A mother with gestational diabetes increases the risk of the neonate experiencing hypoglycaemia/hypocalcaemia at birth, both of which can cause _____
Fits
If both patients have HLA alleles what is the percentage risk of the offspring developing T1DM?
30%
What is proliferative retinopathy?
Blockage of blood vessels leads to ischaemia
Ischaemia causes the release of vascular growth factors which cause new blood vessels to grow in the retina
Name some pharmacological options for the management of painful peripheral neuropathy
Amitriptyline, duloxetine, gabapentin or pregabalin
How does the high glucose excretion of a patient in DKA exacerbate the acidosis caused by the ketone accumulation?
High glucose excretion creates an osmotic diuresis, resulting in electrolyte loss and dehydration; this decreases renal function
What causes increased gluconeogenesis in T2DM?
Glucagon secretion is increased in T2DM due to decreased intra-islet insulin
What is indicated by the circle?
Neovascularisation
What is the second line treatment for T2DM patients with heart failure or chronic kidney disease?
Metformin + GLP-1 receptor antagonist
Which patient group is most likely to develop alcoholic ketoacidosis?
Malnourished individuals with AUD; associated with recent episodes of binge drinking complicated by poor food intake, dehydration, and vomiting
Describe the management of a MODY patient with a transcription factor mutation
Diet + treatment with insulin or sulphonylureas
What is non-proliferative (background) retinopathy?
Early stages of retinopathy, rated from mild-severe
Name the random blood glucose value for diagnosis of diabetes
>/= 11.1
Name three complications of the foetus of a mother with T1/T2DM
Congenital malformation, prematurity, intra-uterine growth retardation (IUGR)
Name a complication of the brain which can occur due to DKA, most commonly in children/YAs
Cerebral oedema
How can autonomic neuropathy affect the sweat glands?
Prevents the sweat glands from working properly so the body cannot regulate its temperature as it should
Nerve damage can also cause profuse sweating at night or while eating - gustatory sweating
Describe the drug treatment of a pregnant T1DM patient
May require increased insulin dose
Name two complications of hypokalaemia which can follow DKA
Cardiac arrest and paralytic ileus
How can a patient with DKA develop hypokalaemia?
Although K+ is often raised in DKA, as soon has insulin is given K+ will drop as insulin promotes co-transport of potassium along with glucose into cells
What is indicated by the white arrow?
Flame haemorrhage
