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Endocrine MBCHB > Diabetes > Flashcards

Diabetes Flashcards

1
Q

What is gestational diabetes?

A
  • Placental progesterone and hPL produce insulin resistance in the mother, meaning more nutrients diverted to foetus
  • If mother is insulin resistant before pregnancy, developing further insulin resistance will raise blood glucose too high and result in gestational diabetes
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2
Q

What are complications associated with T1/T2DM and pregnancy?

A
  • Congenital malformation
  • Prematurity
  • Intra-uterine growth retardation (IUGR)
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3
Q

What are the complications associated with gestational diabetes and pregnancy?

A
  • Macrosomia (>90th centile for size, birth weight >4kg)
    • Maternal hypoglycaemia is transferred across the placenta, resulting in foetal hyperglycaemia
    • This causes foetal hyperinsulinemia - insulin is a MAJOR growth factor
    • After birth, the baby takes a while to downregulate the hyperinsulinemia which puts the baby at risk of neonatal hypoglycaemia
    • Problems with delivery
  • Polyhydramnios
  • Intrauterine death
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4
Q

What are the complications in neonate with diabetes?

A
  • Respiratory distress due to immature lungs
  • Hypoglycaemia/hypocalcaemia → fits
  • CNS defects - anencephaly, spina bifida
  • Skeletal abnormalities - caudal regression syndrome
  • Genital and GI abnormalities - ureteric duplications
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5
Q

What is the management of T1 and T2DM in pregnancy?

A
  • Pre-pregnancy counseling
    • Good sugar control pre conception to limit risk of congenital malformation
  • Folic acid 5mg (not 400ug as in non-DM pregnancy) at least 3 months prior to conception
  • Consider change from tablets to insulin as some T2DM oral medications are contraindicated in pregnancy
  • Regular eye checks (10, 20, 30 weeks gestation) to check for any accelerated retinopathy
  • Avoid ACEi and probably avoid statins
    • For BP use labetalol, nifedipine, methyldopa
  • Start aspirin 150mg at 12 weeks (as in all high risk pregnancies)
    • Reduces the risk of pregnancy-induced hypertension
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6
Q

What is the general management of T1, T2DM and GDM in pregnancy?

A
  • Diabetic diet
  • Aim for good blood sugar control
    • Pre meal <4-5.5 mmol
    • 2 hr post meal <6-6.5 mmol/l
  • Use continuous glucose monitoring
  • Monitor HbA1c
  • Monitor BP
  • Maintian glood blood glucose during labour - IV insulin and IV dextrose
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7
Q

What is the pharmacological management of T1DM in pregnancy?

A
  • Insulin
  • May require increased dose
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8
Q

What is the pharmacological management of T2DM in pregnancy?

A
  • Metformin
  • Will probably need insulin later
  • If patients are on many drugs for T2DM it is better to convert to insulin prior to pregnancy rather than trying to convert during pregnancy
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9
Q

What is the pharmacological management of GDM in pregnancy?

A
  • Lifestyle
  • Metformin
  • May need insulin
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10
Q

What is the management and monitoring available afterbirth for mothers who had GDM ?

A
  • 6 week post natal fasting glucose or GTT to ensure resolution of DM
  • If the diabetes persists, patient has T2DM
  • <5% of patients with GDM will go on to develop T1DM
    • In thin patients with GDM check GAD antibodies
  • 50% of patients with GDM will develop T2DM 10-15 years after pregnancy
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11
Q

What are the prevention measures of diabetes after GDM?

A
  • Keep weight as low as possible
  • Healthy diet e.g. low refined sugar, low saturated fat
  • Aerobic exercise
  • May consider starting on drug treatment at this stage but as evidence for lifestyle changes is stronger this is rarely done
  • Annual fasting glucose
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12
Q

What is T1DM?

A

Autoimmune destruction of the pancreatic beta cells resulting in beta cell deficiency and therefore absolute insulin deficiency.

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13
Q

What is the aetiology of T1DM?

A
  • Type 1 diabetes is subdivided into 1A (immune mediated) and 1B (non-immune mediated)
  • Type 1A accounts for the vast majority of T1DM patients and involves an environmental trigger in a genetically susceptible individual mediated by an auto-immune process within the pancreatic β-cell
    • A ‘slow-burning’ variant of type 1A with slower progression to insulin deficiency occurs in later life and is termed latent autoimmune disease in adults (LADA)
  • Type 1B (idiopathic) 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%)
    • Most patients are of African or Asian ancestry
    • Strongly inherited and not HLA associated
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14
Q

What are the risk factors for T1DM?

A
  • peak around 10-14 years and a small peak in late 30s (LADA)
  • HLA genes represent ~50% of familial risk of T1DM (DR3-DQ2 and DR4-DQ8)
  • If both patients have HLA alleles risk of offspring developing diabetes is 30%
  • Strong environmental contribution - only 5% of those with susceptible HLA genes develop DM
  • Maternal factors - gestational infection and older age
  • viral infections - enteroviruses such as Coxsackie B4
  • Environmental toxins e.g., alloxan
  • childhood obesity
  • psychological stress
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15
Q

What is the pathophysiology of T1DM?

A
  1. Genetic susceptibility
  2. Environmental trigger (often associated with previous viral infection)
  3. T-cell mediated autoimmune response with production of autoantibodies that target and destroy beta cells. Insulitis visible on beta cell biopsy with lymphocytic infiltrate
  4. Absolute insulin deficiency → elevated blood glucose levels.
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16
Q

What is the clinical presentation of T1DM?

A
  • usually, acute onset
  • polydipsia
  • polyuria
  • thrush
  • weakness, fatigue
  • blurred vision
  • infections
  • severe weight loss
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17
Q

What are the investigations for T1DM?

A
  • Fasting glucose ≳7.0 mmol/l with symptoms, if asymptomatic repeat test OR
  • Random glucose ≳11.1 mmol/l with symptoms, if asymptomatic repeat test
  • Often T1DM is diagnosed on positive findings as above, history and presentation (e.g. DKA) but if in doubt GAD/IA2 antibodies and C peptide may help
  • HbA1c not used in diagnosis of T1DM but is used to monitor disease after diagnosis
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18
Q

What is the pharmacological management of T1DM?

A

Insulin:

  • usually basal (long acting once daily) bolus (short-acting with meals) regimen which aims to mimic normal endogenous insulin production.
  • Most people should be treated with MDI (3-4x injections per day or CSII
  • Most people with T1DM should use insulin analogues to reduce hypoglycaemia risk
  • Rotate injection site to avoid lipohypertrophy
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19
Q

What are the non-pharmacological managements of T1DM?

A

Education and Self-monitoring:

  • patients should have a method of self-monitoring their blood glucose and also have access to a ketone monitor
  • most people should be educated how to match prandial insulin dose to carbohydrate intake, pre-meal glucose and anticipated activity as weel as sick day rules
  • regular DSN and dietician contact
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20
Q

What are the surgical management for T1DM?

A

Islet Transplantation:

  • pancreatic islets harvested from cadavers and then are injected into the portal vein where they seed themselves in the liver
  • typically reserved for those with episodes of severe hypoglycaemia, severe and progressive long-term complications and uncontrolled diabetes despite maximal treatment.
  • the goal of treatment is to prevent severe hypoglycaemia but about 50-70% of people receiving islet cell transplants also achieve insulin independence after 5 years.

Whole-pancreas transplantation:

  • most often undertaken in people with T1DM and end-stage kidney disease at the same time as a kidney transplant.
  • pancreas transplant may be performed after a kidney transplant or alone.
  • Indications - severe hypoglycaemia/metabolic complications, incapacitating clinical or emotional problems.
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21
Q

What is the review/monitoring available for T1DM?

A

Annual Review Assessment:

  • weight
  • blood pressure
  • bloods - HbA1c, renal function and lipids
  • retinal screening
  • foot risk assessment
  • record severe hypoglycaemic episodes or admission with DKA.
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22
Q

What is insulin resistance?

A

The reduced ability of organs to respond to ‘physiological’ insulin levels, thought to primarily occur through reduced insulin sensing and/or signalling

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23
Q

What is the aetiology of insulin resistance?

A
  • Insulin resistance is most commonly associated with obesity, however near complete absence of adipose also results in insulin resistance
  • Normal adipose functionality should be considered a key mediator of insulin sensitivity (rather than fat being considered an antagonist of insulin action)
  • There are also some genetic forms of insulin resistance
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24
Q

What is the pathophysiology of insulin resistance?

A
  • Different tissues will have different mechanisms of insulin resistance
  • In skeletal muscle, insulin resistance is caused by impairment of insulin signalling
    • FFAs decreases insulin receptor tyrosine kinase which decreases the activation of downstream proteins
    • End result is that GLUT4 does not get translocated to the skeletal muscle cell membrane, so it is unable to take up glucose into the cell
  • In adipose tissue, insulin resistance is caused by obesity-induced inflammation as adipose tissue secretes pro-inflammatory cytokines e.g. TNF-⍺
    • Cytokines can move into other tissues e.g. liver, skeletal muscle to cause systemic resistance
  • Liver: pathway-selective hepatic insulin resistance
    • Hepatic lipogenesis remains elevated in insulin-resistant subjects - insulin signalling to glucose metabolism is impaired so glucose uptake is reduced, but insulin signalling to lipid metabolism is intact
    • The increased lipogenesis is caused by the increase of FFAs seen in obesity which allows VLDL secretion to increase
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25
Q

What is Leprechaunism (Donohue Syndrome)?

A
  • Rare autosomal genetic trait involving mutations in the insulin receptor
  • Severe insulin resistance and developmental abnormalities e.g. growth retardation, abscence of SC fat, caused by defects in insulin binding or insulin receptor signalling
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26
Q

What is Rabson Medenhall Syndrome?

A
  • Rare autosomal recessive trait which presents with severe insulin resistance, hyperglycaemia and compensatory hyperinsulinaemia
  • Other clinical features include developmental abnormalities and acanthosis nigricans
  • Patients have fasting hypoglycaemia (due to hyperinsulinaemia)
  • Patients are very prone to diabetic ketoacidosis
  • Severe cases linked to mutations in the insulin receptor that reduce sensitivity
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27
Q

What are the investigations for insulin resistance?

A
  • Risk factors can be reviewed by heath providers
  • If at risk, blood glucose levels should be checked for pre-diabetes/diabetes
  • The hyperinsulinemic-euglycemic clamp is the gold standard for the measurement of insulin sensitivity
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28
Q

What are the risk factors for insulin resistance?

A
  • Overweight
  • Physically inactive
  • FHx of diabetes
  • Genetics
  • Race (African Americans, Hispanic/Latinos)
  • PCOS
  • Gestational diabetes
  • High blood pressure
  • Low HDL
  • High blood triglyceride
  • Heart disease
  • Smoking
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29
Q

What is T2DM?

A

Results from a combination of insulin resistance and less severe insulin deficiency

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30
Q

What is the aetiology of T2DM?

A
  • Accounts for 90-95% of diabetes
  • Greatest prevalence is in lower and middle income countries
  • T2DM is thought to be polygenic - contribution of environmental influences, usually the development of insulin resistance and obesity
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31
Q

What are the non-modifiable risk factors for T2DM?

A
  • Usually occurs later in life (> 45 years)
    • β-cell function declines with age
  • Genetics - polygenetic disease with 400 genetic variants identified to date (‘common complex disease’)
  • Ethnicity - individuals of South Asian, African and Afro-Carribean descent are at greater risk
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32
Q

What are the modifiable risk factors for T2DM?

A
  • Obesity - 9 out of 10 people with T2DM are overweight/obese (BMI of 25 or above)
  • Diet - high dietary fat, particularly saturated fat, red and processed meat, fried food, increased intake of white rice and sugary drinks
  • Physical inactivity and sedentary behaviours
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33
Q

What is the pathophysiology of T2DM?

A
  • Autoimmune destruction of the beta-cell does not occur
  • Patients do not have any other known cause for their diabetes
  • Ranges from predominantly insulin resistance with relative insulin deficiency to predominantly an insulin secretory defect with insulin resistance
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34
Q

What are the abnormalities of insulin action?

A
  • Insulin action is diminished in T2DM through the development of insulin resistance
    • Central obesity→ increasedplasma levels of free fatty acids→ impaired insulin-dependentglucose uptake into hepatocytes, myocytes and adipocytes
    • Increasedtyrosine kinaseactivity in liver, fat andskeletal musclecells→ decreased activation of downstream proteins → decreasedexpression of GLUTchannels→ decreasedcellular glucose uptake
  • Insulin resistance occurs in genetically susceptible individuals due to modifiable lifestyle related factors
    • Insulin resistance occurs when fat can no longer be stored in subcutaneous adipose tissue causing spill over of FFA to the viscera, which explains why not everyone with obesity develops diabetes
    • People with ‘healthy’ obesity are able to safely store lots of fat, whereas others have a low fat storage threshold and these are the people who develop T2DM
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35
Q

What are the abnormalities of insulin secretion?

A
  • As insulin resistance develops, the body’s response is to increase insulin secretion and so early T2DM is often associated with insulin hypersecretion
  • An early sign is the loss of the first phase of the normal biphasic insulin secretion
  • The compensatory increased insulin is still insufficient to restore glucose homeostasis, so hyperglycaemia persists
  • Hyperglycaemia and the increased levels of FFAs and adipokines are toxic to the β-cells
  • The hyperglycaemia and lipid excess damage the β-cells → decrease in insulin production
    • People with increased genetic risk of T2DM have β-cells which are less able to cope with the lipotoxicity and glucotoxicity - another explanation for why not all obese people are diabetic
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36
Q

What is the clinical presentation of T2DM?

A
  • gradual onset, majority of patients are asymptomatic
  • symptoms of complications may be first clinical sign of disease
  • when symptomatic → thirst, polyuria, blurred vision, weight loss, recurrent infections and tiredness
  • acanthosis nigricans - insulin-driven epithelial growth seen in hyperinsulinemia states
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37
Q

What are the investigations and diagnosis of T2DM?

A

Symptomatic patients can be diagnosed on the basis of one positive result (but may wish to perform a second test to confirm)

In asymptomatic patients, the diagnosis of diabetes should never be based on a single abnormal HbA1c or fasting plasma glucose level. A last one additional abnormal HbA1c or plasma glucose level is essential.

Other:

  • BP
  • Ketones - if random blood glucose > 15mM
  • cholesterol
  • pancreatic autoantibodies
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38
Q

What is the pharmacological management of T2DM?

A
  • Metformin + lifestyle management first line in all patients with T2DM
  • Diabetic patients with atherosclerotic CVD (e.g. previous MI) should be given metformin + GLP-1 receptor antagonist
  • Diabetic patients with heart failure or chronic kidney disease should be given metformin + an SGLT2i as first line (GLP-1 receptor antagonist second line)
  • Others: DPP4i, SUs, TZDs,
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39
Q

What are the targets for T2DM?

A
  • A target of HbA1c target of 7.0% (53 mmol/mol) among people with type 2 diabetes is reasonable to reduce the risk of microvascular and macrovascular disease
  • Targets should be set with individuals in order to balance benefits with harms, in particular hypoglycaemia and weight gain
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40
Q

What are prevention measures for T2DM?

A

Weight loss in people BMI >30 reduces risk of developing T2DM significantly

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41
Q

What is MODY?

A

Early onset (usually before age 25) of non-insulin dependent diabetes

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42
Q

What is the aetiology of MODY?

A
  • Single gene mutation (monogenetic) which is dominantly affected and predominantly affects β-cell function
  • Most common form of monogenetic diabetes
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43
Q

What is the pathophysiology of MODY?

A
  • Common clinical features to both type 1 and type 2 diabetes
  • Genetic defective glucose sensing in the pancreas and/or loss of insulin secretion
  • At least 150 different mutations (6 genes) have been identified
  • 3 types of mutation:
    • Glucokinase (14%)
      • Glucokinase activity impaired, resulting in a glucose sensing defect - blood glucose threshold for insulin secretion is increased
      • Everything else about the β-cell is normal
    • Transcription factors (75%)
      • The main transcription factor mutations are HNF-1⍺, HNF-1β, HNF-4⍺
      • Play key roles in pancreas foetal development and neogenesis
      • Also regulate β-cell differentiation and function - glycolytic flux, expression of GLUT2 transports, insulin secretion etc.
    • MODY X (11%)
      • Unknown causative gene
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44
Q

What is the presentation of MODY?

A

Glucokinase Mutations:

  • onset at birth
  • stable hyperglycaemia

Transcription factor mutations:

  • adolescence/ Young adult onset
  • progressive hyperglycaemia
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45
Q

What are the investigations for MODY?

A

Oral Glucose Tolerance Test:

  • Patients with a glucokinase mutation will have a high fasting blood glucose (~7 mmol) but bring their glucose down very well when given oral challenge
  • Patients with a transcription factor mutation will have a normal fasting blood glucose but don’t respond well to glucose challenge

Genetic Screening:

  • Can be used to confirm type of mutation
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46
Q

What is the management of MODY?

A

Glucokinase Mutations:

Not associated with an increased risk of microvascular disease and can be managed with diet alone

Transcription Factor Mutations:

  • Diet + treatment with insulin or sulphonylureas
    • Respond very well to sulphonylureas (~4 x more sensitive than patients with T2DM) as MODY patients usually have β-cell function available
    • Patients previously misdiagnosed as T1DM who are on insulin can safely switch to low dose SUs
  • Complications frequent
47
Q

What is neonatal diabetes?

A

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

48
Q

What is the aetiology of neonatal diabetes?

A
  • Monogenic mutation
  • Many genes responsible, 35 genes can explain up to 82% of neonatal diabetes
49
Q

What is the pathophysiology of Neonatal diabetes?

A
  • The KATP channel consists of:
    • An inward rectifier (pore) subunit (KIR) - Kir6
    • A sulphonylurea receptor (regulatory subunit) - SUR1
    • Both are required to form a functional channel
  • In humans, Kir6.2 mutations can lead to neonatal diabetes
    • Due to constitutively activated KATP channels or increase in KATP numbers
50
Q

What is the presentation of neonatal diabetes?

A
  • Diabetes diagnosed < 6 months (chance of T1DM at this age is >1%)
  • Polydipsia, polyuria
  • Dehydration
  • DKA
51
Q

What are the investigations of neonatal diabetes?

A

Blood glucose

52
Q

What is the management of neonatal diabetes?

A
  • In many of these patients the β-cells are responsive to sulphonylureas which inhibit KATP - recover euglycaemia fairly quickly
  • Patients previously misdiagnosed as T1DM who are on insulin can safely switch to high dose SUs
53
Q

What are other KATP channel mutations?

A
  • Some Kir6.2 or SUR1 mutations lead to congenital hyperinsulinism
  • Congenital hyperinsulinism is characterised by inappropriate and unregulated insulin secretion, which results in severe, persistent hypoglycemia in newborn babies, infants, and children
  • Management: diazoxide stimulates KATP so can help inhibit insulin secretion if channels are still getting to the membrane
54
Q

What are the associated conditions of diabetes?

A

Cystic fibrosis
DIDMOAD or Wolfram syndrome
Barget-Biedl Syndrome
Autoimmune conditions such as:
Relatively common

  • Thyroid disease
  • Coeliac disease
  • Pernicious anaemia
  • Addison’s disease
  • IgA deficiency

Rare/very rare

  • Autoimmune polyglandular syndromes
  • AIRE mutations
  • IPEX syndrome
55
Q

What is retinopathy?

A

damage to the retina

56
Q

What is the pathophysiology of non-proliferative retinopathy?

A
  • Early stages of retinopathy, rated from mild-severe (with severe being last stage before proliferative retinopathy)
  • Damage to the wall of small vessels cause microaneurysms and then intraretinal haemorrhages (dot, blot, flame)
  • Leaked blood leaves behind hard exudates (lipid breakdown products)
  • Micro-infarcts (ischaemia) due to occluded vessels cause cotton wool spots
  • Laser therapy in severe NPDR may help prevent long-term visual loss
57
Q

What is the pathophysiology of proliferative retinopathy?

A
  • Blockage of blood vessels leads to areas of non-perfusion and ischaemia
  • Ischaemia in these areas cause the release of vascular growth factors e.g. VEGF which cause new blood vessels to grow in the retina (neovascularisation)
  • IRMA - abnormalities of blood vessels/precursor to neovascularisation but blood vessels are patent (not leaking)
  • Vitreous haemorrhage can occur of the new blood vessels leading to sudden loss of vision
  • Lifetime risk of developing proliferative retinopathy in a diabetic patient is ~35%
58
Q

What is the management of retinopathy?

A
  • Laser - panretinal photocoagulation
    • Reduces oxygen requirement of the retina so reduces the ischaemia that is driving the retinopathy
  • Vitrectomy in a vitreal haemorrhage
59
Q

What is maculopathy?

A

disease affecting the macula

60
Q

What is the pathophysiology of maculopathy?

A
  • 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
61
Q

What are the investigations of diabetic retinopathy?

A

Fundus photo
Optical Coherence Tomography

62
Q

What is the management of maculopathy?

A

Intravitreal anti-VEGF (anti-vascular endothelial growth factor)

63
Q

What are the other eye pathologies in diabetes?

A
  • Cataract - clouding of the lens, develops earlier in people with diabetes
    • Increased sugar contents in lens
    • Conversion of glucose to sortbitol
    • Altered osmotic gradients → swelling and fibre disruption
  • Glaucoma - increase in fluid pressure in the eye leading to optic nerve damage, 2x more common in diabetes
    • Rubeotic glaucoma - new vessel formation forming angle (rare and late complication)
  • Acute hyperglycaemia causes visual blurring (reversible)
64
Q

What is diabetic nephropathy?

A

Progressive kidney disease caused by damage to the capillaries in the glomeruli

65
Q

What is the pathophysiology of nephropathy?

A
  • It is characterised by proteinuria and diffuse scarring of the glomeruli
  • Also known as Kimmelsteil-Wilson Syndrome or Nodular Glomerulosclerosis
66
Q

What are the investigations of diabetic nephropathy?

A
  1. If ACR <30 or PCR <50 = microalbuminuria
    1. Repeat twice as false positive readings are common
    2. Established microalbuminuria if 2/3 positive
    3. Microalbuminuria will not show up as protein++ on urine dipstick
  2. If ACR >30 or PCR >50 = proteinuria (overt nephropathy)
    1. Repeat on EMU
    2. Proteinuria will show up on a urine dipstick
67
Q

What is the management of diabetic nephropathy?

A
  • Presence of microalbuminuria requires treatment with ACEi/ARB
    • Dilate renal arterioles so decrease filtration pressure → decrease proteinuria (also decreases GFR - allow up to 20% deterioration in GFR)
  • Diabetic patients with microalbuminuria should be started on an SGLT2i (irrespective of HBA1c)
  • Manage other vascular complications e.g. discourage smoking, assess fasting lipid profile, screen for cardiovascular disease and hypertension
    • Target BP is <140/80 mmHg for all patients with diabetes
  • Aggressive treatment of blood pressure, glycaemia and use of ACEi/AGLT2i can prevent decline in renal function
68
Q

What are the prevention measures for diabetic nephropathy?

A

Good glycaemic control (53mmol/mol) in patients with T2DM should be maintained to reduce the risk of developing diabetic neuropathy (depending on age and other risk factors

69
Q

What are the complications of diabetic nephropathy?

A
  • Development of hypertension
  • Relentless decline in renal function
    • Reduction in GFR of 1ml/min/month if untreated
  • Accelerated vascular disease
  • Microalbuminuria is a sign of damage to the glomeruli causing protein leak
    • Marker of ‘high risk’ of other vascular problems
70
Q

What is peripheral neuropathy?

A

pain/loss of feeling in feet and hands in a distal symmetrical or sensorimotor neuropathy

71
Q

What are the risk factors of diabetic neuropathy?

A
  • Increased length of diabetes
  • Poor glycaemic control
  • More common in T1DM
  • High cholesterol/lipids
  • Smoking
  • Alcohol
  • Genetics
  • Mechanical injury
72
Q

What are the symptoms of diabetic neuropathy?

A
  • Numbness/insensitivity
  • Tingling/burning
  • Sharp pains or cramps
  • Sensitivity to touch
  • Loss of balance and coordination
73
Q

What are the complications of diabetic neuropathy?

A

Painless trauma
Charcot foot
Foot ulcer
Claw foot and callus formation
Argyll Robertson pupil

74
Q

What is charcot foot and how does it occur?

A
  • Complication of severe neuropathy that occurs in a well-perfused footPathophysiology
    1. Acute onset of a hot, swollen foot +/- pain
    2. Bony destruction - if treatment is delayed, the foot can become deformed as bone is destroyed
    3. Radiological consolidation and stabilisation - after 6-12 months
75
Q

What are the investigations of charcot foot?

A

MRI can differentiate between Charcot foot and infection

76
Q

What is the management of charcot foot?

A
  • Aim is to prevent/minimise bony destruction by keeping pressure off the foot - non-weight bearing, total contact cast or aircast boot
  • Any resulting deformity can alter the pressure distribution across the foot and predisposes the foot to future ulceration
77
Q

What is argyll robertson pupil?

A
  • Small bilateral pupils that do not constrict when exposed to bright light but do constrict when focused on a nearby object
  • Highly specific sign of neurosyphilis but may also be a sign of diabetic neuropathy
78
Q

What is low risk on the foot risk assessment?

A
  • Sensation unimpaired, foot pulses present
  • Requires annual screening by health-care professional
79
Q

What is moderate risk on the foot risk assessment?

A
  • Sensation unimpaired, foot pulses present OR
  • Inability to self-care for feet
  • Requires annual assessment by podiatrist
80
Q

What is high risk on the foot risk assessment?

A
  • Sensation unimpaired, foot pulses present with skin callus or foot deformity OR
  • Sensation impaired, foot pulses absent OR
  • Previous foot ulcer/amputation
  • Requires annual assessment by podiatrist
81
Q

What is active disease on the foot risk assessment?

A
  • Current foot ulcer, gangrene, critical ischaemia, infection, or unexplained red, hot swollen foot
  • Requires urgent referral to specialist team
82
Q

What is the management of painful peripheral neuropathy?

A
  • Amitriptyline, duloxetine, gabapentin or pregabalin
  • Topical capsaicin cream can be used for localised neuropathic pain in patients who do not want or can’t tolerate oral treatments
83
Q

What is autonomic neuropathy?

A
  • 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
  • Usually in those with a long history of very poor diabetes control
  • Can be intractable - recurrent admissions with vomiting or collapse
84
Q

What is the management of gastroparesis in diabetes?

A
  • Improved glycaemic control
  • Diet - smaller more frequent meals, low fat, low in fiber, if severe may need liquid meals
  • Promotility dugs e.g. metoclopramide
  • Anti-nausea medications e.g. prochlorperazine, and serotonin antagonists e.g. ondansetron
  • Analgeisia: NSAIDs, low dose tricyclic antidepressants, gabapentin, tramadol and fentanyl for abdominal pain
  • Severe cases: consider botulinum toxin, gastric pacemaker
85
Q

What is proximal neuropathy?

A
  • Caused by damage to the nerves of the lumbosacral plexus
  • Involves pain in the buttocks, hips, thighs or legs which is then followed by variable weakness in the proximal muscles of the lower limbs and then muscle wasting
  • Rare, more commonly in elderly T2DM
  • Often associated with weight loss
86
Q

What is focal neuropathy?

A

e.g. sudden weakness in one nerve or a group of nerves causing muscle weakness or pain e.g. carpal tunnel syndrome, cranial nerve palsy

87
Q

What is the aetiology of hypoglycaemia?

A
  • Occurs when more insulin is injected than is needed
  • Irregular eating habits, unusual exertion and alcohol excess may precipitate a hypoglycaemic episode
  • Insulin errors and variation in insulin absorption e.g. as a result of lipohypertrophy are also important
  • The times of greatest risk are before meals, during the night and during or after exercise
88
Q

What is the presentation of hypoglycaemia?

A
  • Pallor
  • Sweating
  • Tremor
  • Palpitations
  • Confusion
  • Nausea
  • Hunger
  • Cognitive impairment
  • Coma
89
Q

What is the management of hypoglycaemia?

A
  • 15-20g oral glucose
  • Severe hypoglycaemia (confusion, coma) is managed with IM glucagon or IV glucose
90
Q

What is diabetic ketoacidosis?

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 e.g. glucagon, adrenaline, cortisol and growth hormone

91
Q

What is the aetiology of diabetic ketoacidosis?

A
  • Serious complication of type 1 diabetes and, much less commonly, of type 2 diabetes

Insulin deficiency

  • Initial presentation of unknown diabetes
  • Non-adherence to insulin/poor self-management

Increased insulin demand

  • Infections: pneumonia, UTIs, cellulitis
  • Inflammatory: pancreatitis, cholecystitis
  • Intoxication: alcohol, cocaine, salicylate, methanol
  • Infarction: acute MI, stroke
  • Iatrogenic: steroids, surgery
92
Q

What is the pathophysiology of the formation of ketone bodies?

A
  • Formed in liver mitochondria (mainly acetoacetate and 3 hydroxybutyrate) from acetyl-CoA (which is from beta oxidation of fats)
  • Diffuse into the bloodstream and to peripheral tissues
  • Ketones are important molecules of energy metabolism for heart muscle and renal cortex
    • Converted back into acetyl-CoA, which enters TCA cycle
  • If supply of pyruvate/oxalonacetate is limited (e.g. if glycolysis is reduced, limiting glucose) the excess acetyl-CoA is diverted to ketones
93
Q

How do ketones occur in diabetes?

A
  • Insulin normally inhibits lipolysis, reducing risk of ketone body overload
  • In T1DM, DKA is a danger if insulin supplementation is missed and hyperglycaemia ensues - amount of glucose taken up from the blood into tissues and amount of glycolysis will reduce, so body switches to fatty acid oxidation
  • DKA is more rare in T2DM where there is still some inhibition of lipolysis, but can occur as insulin resistance and deficiency increases, alongside increase in glucagon
  • Ketoacidosis can also occur in starvation - oxaloacetate is consumed for gluconeogenesis and when glucose is not available fatty acids are oxidised to provide energy; the excess acetyl-CoA will be converted into ketones
94
Q

What are the consequences of the formation of ketone bodies?

A
  • Excessive accumulation of ketone bodies can lead to acidosis
  • High glucose excretion creates an osmotic diuresis, resulting in electrolyte loss and dehydration; this decreases renal function and exacerbates acidosis
  • Can lead to coma, death
95
Q

What is the presentation of diabetic ketoacidosis?

A
  • thirst
  • polyuria
  • dehydration
  • flushed
  • vomiting
  • abdominal pain
  • increased respiratory rate - Kussmaul’s respiration → deep, rapid breathing pattern associated with severe metabolic acidosis
  • distinctive smell on breath (not present in all individuals)
  • associated with underlying sepsis and gastroenteritis
96
Q

What are the investigations for diabetic ketoacidosis?

A

Diagnosis is confirmed by demonstrating hyperglycaemia with ketonaemia or heavy ketonuria, and acidosis:

  • Ketonaemia ≳3 mmol/L, or significant ketouria (≳2 on standard urine stick)
  • Blood glucose > 11.0/L or known DM
    • Euglycaemic DKA is possible if a patient has given themselves some insulin, but not enough to switch off ketogenesis
    • Euglycaemic DKA is also a rare complication of SGLT2i
  • Bicarbonate <15 mmol/L and/or venous pH <7.3

Other biochemistry

  • Potassium often >5.5 mmol/L but drops as soon has insulin is given - can cause hypokalaemia
    • Insulin promotes co-transport of potassium along with glucose into cells
  • Creatinine often raised
  • Sodium often low or low end of normal
  • Amylase often raised (rarely pancreatitis, origin can be salivery)
  • White cell count raised (median 25) - does not always equate infection, sign of inflammatory response
97
Q

What is the immediate management of diabetic ketoacidosis?

A

Replace fluid losses

  • 1000mL NaCl 0.9% in the first hour
  • 20000mL NaCl by end of hour 2
  • 30000mL NaCl by end of hour 4
  • Once blood-glucose concentration falls below 14 mmol/litre, IV glucose 10% should be given in addition to the sodium chloride 0.9% infusion

Replace electrolyte losses

  • NaCl 0.9% as above
  • IV Potassium
  • Phosphate rarely replaced
98
Q

What is further treatment of diabetic ketoacidosis?

A

Restoration of acid-base balance

  • Bicarbonate rarely replaced as once the circulating volume is restored the metabolic acidosis is rapidly compensated

Insulin replacement

  • IV insulin 0.1 units/kg per hour to suppress ketogenesis, lower the glucose and correct the electrolyte disturbance
  • Continue ‘usual’ SC daily basal insulin
  • Continue IV insulin until ketoacidosis has been resolved; to prevent hypoglycaemia give 10% glucose IV alongside the 0.9% NaCl once blood-glucose concentration falls below 14 mmol/L
99
Q

What monitoring is needed for diabetic ketoacidosis?

A

Monitoring

  • Monitor blood-ketone and blood-glucose concentrations hourly
  • Blood gas and electrolytes every 2-4 hours

Other measures

  • Seek underlying cause e.g. infection if suspected
  • Patient may aspirate vomit so consider NG tube
  • Dehydration, increased blood viscosity and coagulability of DKA increase risk of thromboembolism - all patients should receive prophylactic LMWH
100
Q

What preventative measures should be done for diabetic ketoacidosis?

A

Prevention of recurrence

  • Education and support before discharge
  • Provide patient with ketone meter
  • Arrange DSN follow-up and inform GP
101
Q

What are the complications of diabetic ketoacidosis?

A
  • Cerebral oedema - mostly happens in children/YAs
  • Hypokalaemia can cause cardiac arrest and paralytic ileus
  • Aspiration pneumonia
  • ARDS
102
Q

What is hyperglycaemic hyperosmolar syndrome?

A

Severe hyperglycaemia without significant ketosis; the characteristic metabolic emergency of T2DM

103
Q

What is the aetiology of hyperglycaemic hyperosmolar syndrome?

A
  • People present in middle or later life, often with previously undiagnosed diabetes
  • Common precipitating factors include consumption of glucose-rich fluids, concurrent medication such as thiazide diuretics or steroids, and intercurrent illness
104
Q

What is the pathophysiology of hyperglycaemic hyperosmolar syndrome?

A
  • Pathophysiology is similar to DKA, but HHS, there are stillsmall amounts of insulinbeing secreted by the pancreas
  • This is sufficient toprevent DKA by suppressing lipolysis and, in turn, ketogenesis, but level is not high enough to lower blood glucose to a safe level
  • HHSis characterized by symptoms ofmarked dehydration(andloss of electrolytes) due to the predominating hyperglycaemiaandosmotic diuresis (hyperosmolar urine)
105
Q

What is the presentation of hyperglycaemic hyperosmolar syndrome?

A
  • Dehydration due to polyuria
  • Polydipsia
  • Nausea and vomiting
  • Stupor/coma
    • Impaired consciousness is directly related to degree of osmolarity
106
Q

What are the investigations for hyperglycaemic hyperosmolar syndrome?

A

HHS is characterised by:

  • Profound hyperglycaemia (glucose >33.3mmol/L)
  • Hyperosmolality (serum osmolarity >320mmol/kg)
    • Can be measured directly or calculated as (2 x Na+) + glucose + urea
  • Volume depletion in the absence of ketoacidosis (pH >7.3 and bicarbonate >15mmol/L)

Other features

  • Significant renal impairment
  • Sodium often high normal or raised
107
Q

What is the management of hyperglycaemic hyperosmolar syndrome?

A
  • Assess severity of dehydration and use 0.9% saline for fluid replacement WITHOUT insulin - fluids alone will reduce osmolarity
    • Be aware of increased risk of fluid overload
  • Sodium - avoid rapid fluctuations, if dropping too quickly consider 0.45% saline
  • Monitor and chart BG, osmolarity and sodium
  • Start low dose IV insulin only if significant ketones (>1) or BG falling at a slow rate
  • Comorbidities more likely
    • Screen for vascular event e.g. silent MI
    • LMWH for all patients (unless contraindicated)
    • High risk of feet complications
108
Q

What is alcoholic ketoacidosis?

A

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

109
Q

What is the aetiology of alcoholic ketoacidosis?

A
  • Most commonly occurs in malnourishedindividuals with AUD
  • Associated with recent episodes ofbinge drinkingcomplicated by poor food intake, dehydration, and vomiting
110
Q

What is the pathophysiology of alcoholic ketoacidosis?

A

Accumulation of ketone bodies as a result of:

  • Depleted glycogen stores in the liver from malnutrition/decreased carbohydrate intake
  • Increased lipolysis and FFA release
  • Volume depletion from e.g. vomiting, poor oral fluid intake which impairs renal perfusion and decreases ability to excrete ketone bodies
111
Q

What is the clinical presentation of alcoholic ketoacidosis?

A
  • Nausea, vomiting
  • Abdominal pain
  • Increased respiratory rate
  • Dehydration
112
Q

What are the investigations of alcoholic ketoacidosis?

A
  • Ketonaemia >3 mmol/L, or significant ketonuria (2+ on standard urine stick)
  • Bicarbonate usually <15 mmol/L or venous pH <7.3 in severe cases
  • Glucose usually normal, may be low
113
Q

What is the management of alcoholic ketoacidosis?

A
  • IV pabrinex - high dose vitamins including thiamine to prevent Wernicke encephalopathy
  • IV fluid - 5% dextrose in 0.9% NaCl
  • IV anti-emetics
  • Insulin may be required on occasion

Further management

  • Address alcohol dependency

Endocrine MBCHB (13 decks)

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