Diabetes Flashcards
1
Q
What is diabetic ketoacidosis?
A
An acute metabolic complication of diabetes characterised by hyperglycaemia, hyperketonemia and metabolic acidosis 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
2
Q
Specific Symptoms of DKA
A
Polydipsia
Polyuria
Kussmaul breathing
Other Symptoms: Nausea Vomitting Abdominal pain Poor appetite Tiredness Weakness Coma Cerebral Oedema Thrombotic Events Death
3
Q
Three characteristics of DKA?
A
Hyperglycaemia
Hyperketonemia
Metabolic acidosis
4
Q
Counter regulatory hormones that increase glucose production?
A
Glucagon
Cortisol
Catecholamines
5
Q
Most common causes of DKA?
A
Not taking medication
Infection
Alcohol abuse
6
Q
What does adrenaline do?
A
Stimulates glucagon release and lipolysis, increasing fatty acids but not ketones
7
Q
Cortisol and gluoneogenesis?
A
Cortisol stimulates gluconeogenesis in the liver from amino acids, lactate, glycerol and propionate
8
Q
Which hormone stimulates gluconeogenesis from amino acids, lactate, glycerol and propionate?
A
Cortisol
9
Q
Growth hormone, glucose and lipolysis?
A
GH reduces hepatic uptake of glucose
GH stimulates lipolysis
10
Q
pH and bicarbonate levels in DKA?
A
pH <15mmol/l
11
Q
Why would you check blood gases in DKA?
A
To look at H+ and bicarbonate levels
12
Q
Why would you check urea and electrolytes in DKA?
A
Indication of dehydration (urea, creatinine)
Individual ion and anion levels
Indication of hyperkalaemia
13
Q
What would urine show in diabetic ketoacidosis?
A
Low pH (<7.30)
Glucose
Ketones
14
Q
What is a common trigger for illness in a person with diabetes?
A
Urinary infection
15
Q
Three main ketone bodies?
A
Acetone
Acetoacetate
Beta hydroxybutyrate
(all of these, especially beta hydroxybutyrate will make the patient feel v. sick. This is important to realise as if the patient is sick then this will make their fluid and electrolyte loss even worse)
16
Q
Why is alcohol of significance in DKA?
A
It gives the person the fruity breath smell
17
Q
What will blood gases show in patient with Kussmaul breathing?
A
Low partial pressure of CO2
Low bicarbonate
High oxygen saturation (99-100% unless patient has pathologies that prevents this, e.g. COPD)
18
Q
What would hyponatremia suggest in a patient with DKA?
A
That they have been vomitting
lose sodium when they vomit, also lose through urine due to osmotic diuresis caused by hyperglycemia
19
Q
What causes dehydration in DKA?
A
Dehydration is caused by volume depletion from 2 main causes:
1) Renal loss due to the osmotic diuresis caused by hyperglycemia
2) Fluid loss from vomitting caused by the ketosis
20
Q
Specific DKA symptoms
A
Polyuria
Polydipsia
Kussmaul breathing
21
Q
General symptoms of DKA
A
Vomitting Nausea Abdominal Pain Weakness Tiredness Coma Cerebral oedema Thrombotic events
22
Q
Immediate effects of low insulin
A
Hyperglycemia
Increased hepatic gluconeogenesis
Increased levels of chatecholamines
23
Q
Best way to treat CVD risk in type 2 diabetes?
A
Statins/anti-hypertensives
(insulin resistance -> macrovascular complications -> CVD risk etc -> statins/ anti-hypertensives )
(beta cell dysfunction -> hyperglycemia -> MICROvascular complications -> treat with intensive glucose control)
24
Q
What is diabetes mellitus?
A
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
25
Drugs which can cause diabetes
High dose corticosteroids (glucocoritcoids), beta-blockers and diuretics
Medications such as anti-pyscotics can also increase risk
26
Infection that could cause diabetes
Cytomegaolvirus
27
How is T1DM characterised?
By the presence of anti-GAD/anti-islet antibodies
| T2DM is a diagnosis of exclusion
28
Useful discriminatory tests used to diagnose between T1DM and T2DM?
- Anti-GAD and anti-islet antibodies
- Ketones
- C peptide (plasma)
29
Syptoms of Cushings
Obesity - with fat around the main body area (trunk) rather than the arms and legs. The arms and legs can become quite thin compared with the obese body.
Facial puffiness, and the face often looks redder than usual.
Diabetes.
Facial hair in women.
High blood pressure.
Muscle weakness. In particular a proximal muscle weakness. The proximal muscles are the ones in your arms and legs nearest to the body. So, the muscles around the thigh, pelvis, shoulders and upper arms are the proximal muscles.
Thin skin which bruises easily.
Purple/pink stretch marks (striae) may appear - similar to those seen on some pregnant women.
Tiredness.
Aches and pains - particularly backache.
Mood swings - such as being more irritable, depressed, or anxious than usual.
Lack of sex drive (libido).
Periods may become irregular, or stop, in women.
Osteoporosis ('brittle bones'). You may fracture a bone more easily than usual.
Oedema ('water retention') around the ankles.
Excess thirst.
Increased susceptibility to infections.
Affected children tend to be obese, but grow slowly so are short for their age.
30
Name an alpha glucosidase inhibitor
Acarbose
| -slows absorption of starchy foods from the intestine
31
SIGN guidance for cholesterol medication for diabetes?
Simvastatin 40mg
| Atorvastatin 10mg
32
Blood pressure target for diabetics
130/80
33
HbA1c target for diabetics
<7.5%
34
Is low dose aspirin recommended for diabetes?
No
35
Commencing insulin therapy
Once daily bedtime NPH insulin should be used when adding insulin to metformin and/or sulphonylurea therapy. Basal insulin analogues should be considered if there are concerns regarding hypoglycaemia risk. (Grade A)
When commencing insulin therapy, bedtime basal insulin should be initiated and the dose titrated against morning (fasting) glucose. If the HbA1c level does not reach target then addition of prandial insulin should be considered. (Grade A)
Soluble human insulin or rapid-acting insulin analogues can be used when intensifying insulin regimens to improve or maintain glycaemic control. (Grade A)
36
Metabolic acidosis
Arterial blood pH <22mol/L
37
Rapid acting insulins
e.g. Humalog* (insulin lispro), NovoRapid, Apidra
38
Short acting insulin (soluble/regular)
e.g., Humulin S (Human insulin), Actrapid, Insuman Rapid
39
Intermediate acting (isophane)
e.g. Insulatard, Humulin I (Isophane human), Insuman Basal
40
Long-acting analogue
e.g. Lantus or Levemir
41
Rapid acting analogue-intermediate analogue
e.g. Humalog Mix25 / Mix50 or NovoMix30
42
Short acting-intermediate mixture
e.g. Humulin M3,
| Insuman Comb 15, 25, 50
43
Another name for aspart?
NovoRapid
44
Another name for lispro?
Humalog
45
Another name for Glulisine?
Aphidra
46
What type of insulin is in an insulin pump?
Short acting
47
Pancreatic insulin secretion vs Insulin Pump
```
Pancreatic insulin secretion:
-directly into blood stream
-rapidly prevents post-meal hyperglycaemic spike
-rapidly cleared
Insulin injection or pump:
- into subcutaneous tissue
-peak too slow to prevent post-meal hyperglycaemic spike
-slow clearance
```
48
Issues with inhaled insulin?
- Non-linear dosing
- Cost
- Risk of lung cancer
49
Issues with oral insulin
Cost
Variable absorption
Effects of concurrent diet and illness
Only pre-prandial
50
Smart Insulin
Smart Insulin works via competitive binding:
insulin, attached to a sugar group, binds with a sugar-binding molecule in solution.
When glucose in the body is high, it competes with insulin to bind to the sugar-binding molecules, displacing insulin and releasing it into the bloodstream as needed
51
Anti-CD3 monoclonal antibody
Treatment with the monoclonal antibody against C3 improves insulin production
52
What is a kidney-pancreas transplantation?
A kidney-pancreas transplant is an operation to place both a kidney and a pancreas — at the same time — into someone who has kidney failure related to type 1 diabete
53
Rapid acting vs Short Acting Insulin
```
Rapid Acting Insulin:
-onset of action 10-15 mins
-Peak action 60-90 mins
-Duration of action 4-5 hours
Short Acting Insulin
-onset of action 30-60 mins
-Peak of action 2-4 hours
-duration of action 5-8 hours
```
54
The 2 components of advanced carbohydrate counting?
1) insulin to carbohydrate ratio
| 2) Insulin sensitivity factor/correction factor
55
Islet amyloid is a pathogenic feature of which condition?
Type 2 diabetes
Islet amyloid deposition is a pathogenic feature of type 2 diabetes, and these deposits contain the unique amyloidogenic peptide islet amyloid polypeptide.
56
HLA association and T1DM?
HLA genes represent ~50% risk of T1DM
57
Highest risk genotype for T1DM
DR3-DQ2 / DR4-DQ8
| 95% of patients diagnosed under 30 have one or both of those genotypes
58
Islet auto-antibodies
IA-2 (tyrosine phosphatase islet antigen)
IAA (islet auto-antibodies)
GAD65 (glutamic acid decarboxylase)
ZnT8 (zinc transporter 8)
59
Islet cell antibodies to really look out for because the lecturer highlighted them
GAD65
| IA-2
60
Features of clinical T1DM that were highlighted in red in the lecture?
Raised glucose
| Ketones
61
Enuresis
Bed wetting
62
Classic T1DM presenting triad?
Polyuria (enuresis in children)
Polydipsia
Weight loss
63
When might hospital management be needed for initial treatment of T1DM?
- DKA
- Significant ketonemia
- Severe vomitting
- Under 2 years old
- emotional/social needs
- live a long way from the hospital
64
HbA1c target level for T1DM children?
<7.5%
65
Annual review assessment for T1DM esp. children
```
Weight
Blood pressure
Bloods: HbA1c, lipids, renal function
Retinal Screening
Foot risk assessment
```
66
Conditions that can lead to secondary diabetes
```
Cystic fibrosis
Hemochromatosis
Chronic pancreatitis
Polycystic ovary syndrome (PCOS)
Cushing's syndrome
Pancreatic cancer
Glucagonoma
Pancreatectomy
```
67
Drug induced Diabetes
```
Corticosteroids
Thiazide diuretics
Beta-blockers
Antipsychotics (e.g. Phenytoin)
Statins
```
68
If children are diagnosed with diabetes <6 months, are they more likely to have monogenic or T1DM?
Monogenic :P
69
Antibodies found in LADA?
GAD
| ICA (islet cell antibodies)
70
Which CF gene mutations are more severe and therefore give a greater chance of developing diabetes?
∆508
Diabetes common
>25% at 20 years
Usually found in ‘severe’ mutations, i.e. ∆508
Prone to complications
Insulin therapy preferred
Screening with OGTT from age 10 years recommended
71
What type of therapy is preferred for CF diabetic patients?
Insulin
72
What type of screening should you give CF children to check for diabetes?
OGTT from age ten years recommended
73
Are patients with CF and diabetes prone to complications?
Yes
74
DIDMOAD/Wolfram
```
Diabetes Insipidus
Diabetes Mellitus
Optic Atrophy
Deafness
Renal Problems
Neurological Problems
Chronic Fatigue
Other features of Wolfram Syndrome include fertility problems and gastrointestinal problems causing constipation or diarrhoea
```
75
Chronic Fatigue and Wolfram/DIDMOAD
Patients with wolfram have progressively declining physical stamina
They will need increasing amounts of sleep
76
Renal problems in Wolfram/DIDMOAD?
Bed wetting
Increased frequency of urination
Loss of bladder control
You may be able to treat the symptoms of diabetes in Wolfram/DIDMOAD but these renal problems will still occur because the problem itself is to do with the renal tract
77
Neurological problems in DIDMOAD/Wolfram
```
Loss of balance
Sudden muscle jerks
Depression (25% will have mental health problems at some point)
LOSS OF TASTE AND SMELL
BREATHING PROBLEMS
DEPRESSION
```
78
Deafness in Wolfram/DIDMOAD
May have trouble hearing high pitched sounds
May have trouble hearing in a crowd
25% will need a hearing aid
79
Antibodies in MODY?
Negative
80
Autoimmune conditions associated with diabetes
```
Common:
-Thyroid disease
-Coeliac
-Addisons
-Pernicious Anaemia
-IgA deficiency
Rare and Very Rare:
-Auto-immune polyglandular syndromes [Type 1 and Type 2]
-AIRE mutations
-IPEX syndrome
```
81
Albumin and calcium levels in coeliac?
Low
82
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
83
Diabetic ketoacidosis diagnosis
Ketonemia > 3mmol/L (or significant ketonuria >2+ on standard urine stick)
Blood glucose >11mmol/L or known diabetes (nb. euglycaemic DKA)
Bicarbonate <7.3
84
WBC and DKA?
WBC median count around 25
Does not always infer infection
Stress effect of acidosis on bone marrow
85
Amylase in DKA
Amylase very frequently raised, does not necessarily indicate pancreatitis
Can be salivary in origin
86
Normal ketone levels
<0.6mmol/L
87
What does blood ketone testing measure?
Beta hydroxybutyrate
88
What does urine ketone testing measure?
Aceto acetate
- Indicates levels of ketones from 2-4 hours earlier
- Ketonuria persists after clinical improvement due to mobilisation of ketones from fat tissue
89
Why does ketonuria persist after clinical improvement?
Ketonuria persists after clinical improvement due to mobilisation of ketones from fat tissues
90
When should you consider hospital admission for DKA?
```
Unable to tolerate oral fluids
Persistent vomiting
Persistent hyperglycaemia
Persistent positive/increasing levels of ketones
Abdominal pain / breathlessness
```
91
Where does lactate come from?
Red blood cells
Skeletal muscle
Brain
Renal medulla
92
Lactic acidosis: classification
```
Type A:
Associated with tissue hypoxaemia:
-Infarcted tissue, eg ischaemic bowel
-Cardiogenic shock
-Hypovolaemic shock (Sepsis [endotoxic shock] , Haemorrhage)
```
Type B:
May occur in Liver disease
-Associated with drug therapy, eg Metformin
-Associated with Diabetes
-10% of cases of DKA associated with lactate >5 mmol/L.
-With Metformin usually in severe illness states or renal failure
-Also consider rare inherited metabolic conditions if well and non-diabetic
93
Type A lactic acidosis
Associated with tissue hypoxaemia:
- Infacted tissue
- Cardiogenic shock
- Hypovolaemic shock: sepsis, haemorrhage
94
Type B lactic acidosis
- May occur in liver disease
- May be caused by drug therapy e.g. Metformin
- Associated with diabetes
- 10% of cases of DKA are associated with lactate >5mmol/L
- With metformin, usually in severe illness states or renal failure
- Also, consider RARE, INHERITED CONDITIONS if well and non-diabetic
95
Lactic acidosis in Diabetes
High ion gap yet low ketone level
Exclude other causes of high ion gap
End product of anaerobic metabolism of glucose
Lactate comes from red cells, skeletal muscle, brain and renal medulla
Clearance requires hepatic uptake and aerobic conversion to pyruvate then glucose.
96
Clinical signs of lactic acidosis
Hyperventilation
Confusion
Stupor/Coma if severe
97
Lab findings of lactic acidosis
Reduced bicarbonate
Raised anion gap [(Na+ + K+) – (HCO3 + Cl-)]
Other causes: uraemia, alcohol, ethylene glycol, methanol, renal tubular acidosis, salicylate or paraldehyde poisoning.
Glucose variable – often raised
Absence of ketonaemia
Raised phosphate
98
Causes of a high anion gap
Lactic acidosis, uraemia, alcohol, ethylene glycol, methanol, renal tubular acidosis, salicylate or paraldehyde poisoning
99
Phosphate levels in lactic acidosis
Raised
100
How to calculate anion gap?
(Na+ & K+) - (HCO3 & Cl-)
101
Is there ketonemia present in lactic acidosis?
No it is absent
102
Bicarbonate in lactic acidosis
Lowered
103
Treatment of lactic acidosis
```
Underlying condition:
-Fluids
-Antibiotics
Withdraw offending medication:
-Usually medication
```
104
Renal function in HHS?
Significant renal impairment
105
How to calculate osmolality
2x[Na + K) + Urea + Glucose
106
Normal Osmolality
285-295
107
Medication that can cause HHS?
Diuretics and steroids
108
Kind of usual age and type of person who would suffer HHS?
'Older' type 2
109
LMWH and HHS?
LMWH for all unless contraindicated
110
Which type of acidosis is associated with Diabetes?
Type B
Diabetes associated with type B lactic acidosis
-10% of DKA cases associated with lactate >5mmol/L
-with metformin usually in severe illness or renal failure
111
Where does lactate come from lol
Red blood cells
Skeletal muscle
Brain
Renal medulla
112
Lab findings of lactic acidosis
Reduced bicarbonate
Raised anion gap [(Na+ + K+) – (HCO3 + Cl-)]
(Other causes: uraemia, alcohol, ethylene glycol, methanol, renal tubular acidosis, salicylate or paraldehyde poisoning.)
Glucose variable – often raised
Absence of ketonaemia
Raised phosphate
113
Biochemistry of HHS
Higher glucose than in DKA
Median around 60
Significant renal impairment
Sodium often raised on admission
Significant elevation of osmolality – around 400
Osmolality=2x[Na+K] + Urea + Glucose
2 [145+5] + 30 + 65 = 395 [Normal 285 to 295]
Less ketonaemic/acidotic as compared to DKA
114
Cause of HHS?
STEROIDS/DIURETICS
Fizzy drinks
Under diagnosed DM
Carbohydrate
115
Drugs which can cause HHS?
Diuretics, steroids
116
Anti-coagulant you should give when treating HHS and why?
LMWH
| Complications more likely, screen for vascular event, e.g. silent MI, sepsis
117
Patients with HHS may develop lactic acidosis, why?
They may be on metformin with marked RENAL FAILURE/may be septic
118
Hypothyroidism and effects of glucose?
Prolongs effects of insulin
119
Renal impairment and effects of insulin
Prolongs effects of insulin
120
Liver failure and effects of insulin
Prolongs effects of insulin
121
Alcohol and gluconeogensis
Alcohol suppression of gluconeogenesis
122
Growth hormone and glucose
Raises blood glucose level
- GH reduces hepatic uptake of glucose from blood
- GH stimulated lipolysis
123
What is the limiting factor of good glycemic control?
Hypoglycemia
124
Amyotrophy and possible sypmtom
Progressive muscle weakness
| -muscle pain is also a symptom
125
Types of neuropathy?
Peripheral
Autonomic
Focal
Proximal
126
Autonomic neuropathy?
i.e. change in bowel habit, bladder function, sexual response, blood pressure, heart rate, hypoglycaemic unawareness, sweating
127
changes in bowel, bladder function, sexual response, sweating, heart rate, blood pressure, hypoglycaemic unawareness are what type of neuropathy?
Autonomic
128
Give an example of proximal neuropathy?
e.g.pain in the thighs, hips or buttocks leading to weakness in the legs (Amyotrophy)
129
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
130
Neuropathy more likely in type 1 or type 2 diabetes?
Type 1
131
Complications of peripheral neuropathy?
Infections/ Ulcers
Deformities (hammertoes/ collapse of mid-foot)
Amputations- 50%of ampuations may be preventable
132
What are oxycodone and tramadol?
Opiods
133
Painful neuropathy treatment algorithm?
-simple analgesia (paracetemol)
-TCAs (amitryptiline -> small dose at night)
-Gabapentin
-Duloxitine 60mg / Pre Gabalin (50mg bd - 200mg)
-Stronger opiods (oxycodon+tramadol)
Topical Capsaicin Cream
Allodynia - may be helped by use of a plastic film
