ENDO; Lecture 15, 16, 17 and 18 - Type 1 DM, Type 2 DM, Microvascular complications and Macrovascular complications and the Diabetic Foot Flashcards
1
Q
What are the different types of diabetes?
A
Type 1 and T2, MODY, Latent autoimmune diabetes in adults (LADA)
2
Q
What is the WHO classification of obesity?
A
3
Q
What is the pathogenesis of T1DM?
A
4
Q
How is T1DM a relapsing-remitting disease?
A
The immunological response to T1D is cyclic. An increase in the numbers of autoreactive effector T cells is controlled by an increase in the number of regulatory T cells. However, over time, a gradual disequilibrium of the cyclical behavior could occur, leading to the number of autoreactive effector T cells surpassing the number of regulatory T cells, which would no longer be capable of containing autoreactive effector T-cell responses and thereby lead to a decline in pancreatic islet function
5
Q
What happens in T1DM?
A
Beta-cells are destroyed so increased number of immune cells and inflammatory factors present
6
Q
Which HLA genes do you need to have genetic susceptibility to T1DM?
A
NB: DR3, DR4 are important
7
Q
What are the environmental factors that affect T1DM?
A
Though to have infection type of onset as it is more common in winter months
8
Q
Which blood markers should you test in T1DM patients?
A
9
Q
What is the presentation of diabetes?
A
10
Q
What happens if there is a lack of insulin?
A
If you lack insulin, then protein breakdown isn’t stopped, glucose isn’t taken up by the muscles, fats get broken down to make more glucose
11
Q
What happens if there is no insulin acting on adipocytes?
A
Can also produce a lot of ketones in the body, which are the ones that produce ketoacidosis
12
Q
How is T1DM treated?
A
Reduce early mortality, avoid acute metabolic decompensation -> need exogenous insulin to preserve life with ketones defining insulin deficiency; preventing long term complications like retinopathy, neuropathy, nephropathy, vascular disease
13
Q
What diet should T1DM patients have?
A
Reduce calories as fat and refined carbs, increase calories as complex carbs and soluble fibre; balanced distribution of food over course of day with regular meals and snacks
14
Q
How does insulin treatment work?
A
Short acting insulin given with meals, made from human insulin or insulin analogue (lispro, aspart, glulisine); Long acting for background levels given non-c bound to zinc or protamine OR insulin analogue (Glargine, Determir, Degludec)
15
Q
How long does Short/long acting insulin last?
A
SAI 4-6, LAI 12h
16
Q
How have insulin analogues been modified?
A
Genetically engineered to alter absorption, distribution, metabolism and excretion
17
Q
What is an insulin pump?
A
Continuous insulin delivery, preprogrammed basal rates and bolus for meals; doesn’t measure glucose, no completion of feedback loop -> no new needle every time
18
Q
What are islet cell transplants?
A
Much better glucose control
19
Q
How do we check glucose levels?
A
Capillary monitoring -> pricking the finger; MiniLink transmitter -> on the abdomen but not as reliable; measure HbA1c
20
Q
What is HbA1c?
A
In red cells and reacts with glucose irreversibly; lifespan of RBC is 120d so it can be measured for around 4 months -> determine the rate of glycation, faster in some individuals -> however can be unreliable in Hbopathy and renal failure; forms ideal measure of long term glycaemic control and has been shown to be related to risk of complications, also lowering HbA1c associated lower risk of complication particularly microvascular complication
21
Q
What is ketoacidosis?
A
Rapid decompensation of t1DM causing hyperglycaemia, metabolic acidosis
22
Q
Why is hyperglycaemia caused in ketoacidosis?
A
Reduced tissue glucose utilisation, increased hepatic glucose production
23
Q
Why is metabolic acidosis caused in ketoacidosis?
A
Circulating acetoacetate and hydroxybutyrate, osmotic dehydration and poor tissue perfusion
24
Q
What are the causes of ketoacidosis?
A
Now presentation, insulin omission, infection/other illness
25
What is hypoglycaemia?
Plasma glucose of \<3.6 mmol/L, severe hypo = any hypo needing help of another person to treat
26
How can hypo's affect the patient?
Most mental process impaired at \<3mmol/L, consciousness impaired at \<2mmol/L, severe hypo may contribute to arrhythmia and sudden death; may have long-term effects on the brain, recurrent hypos result in loss of warnings
27
Who do hypos affect?
Main risk factor is quality of glycaemic control, more frequent in patients with low HbA1c
28
When do hypos occur?
Anytime but often a clear pattern, pre-lunch hypos common, nocturnal hypos very common but not recognised
29
Why do hypos occur?
Unaccustomed exercise, missed meals, inadequate snacks, alcohol, inappropriate insulin regime
30
what are the symptoms and signs of hypoglycaemia?
x
31
How do you treat hypoglycaemia?
32
What is T2DM?
State of chronic hyperglycaemia sufficient to cause long-term damage to specific tissues, notably the retina, kidney, nerves, and arteries -\> Not ketoacidosis prone, not mild and often involves weight, lipids and blood pressure
33
How do you screen for diabetes?
You do a fasting glucose and glucose tolerance
34
What is the epidemiology of T2DM?
35
What is the pathophysiology of T2DM?
36
What is MODY?
37
How do microvascular/macrovascular diseases come about?
38
How does T2DM genetic input appear?
Behaves as an autosomal dominant condition; light birth weight associated as well
39
How does insulin resistance and secretion change during age in T2DM?
40
How does T2DM present?
41
What is the relationship between insulin secretion and glucose tolerance?
Secretion deteriorates with progressive impairment of glucose tolerance
42
What contributes to increased fasting glucose in T2DM?
/impaired glucose disposal and increased hepatic glucose production -\> diminished ability to store or oxidize glucose in muscle due to impaired insulin activity reduces the metabolic clearance rate of glucose (top graph), and an excessive amount of glucose is converted to lactate.1 Lactate then returns to the liver to be metabolized back to glucose (Cori cycling). The early increase in FPG in the progression to T2DM is often a result of Cori cycling from the previous night’s meal.
43
What is the glucose flow in insulin resistance?
High hepatic glucose output and dyslipidaemia
44
Which factors are affected in T2DM?
45
How does obesity affect T2DM?
More than precipitant, central/omental obesity, 80% of T2DM are obese -\> weight reduction is useful treatments as FA and adipocytokines are important
46
How do preturbations in gut microbiota affect T2DM?
Occurs in obesity and insulin resistance, host signalling, bacterial lipopolysaccharides fermentation to short chain FA, bacterial modulation bile acids -\> causes inflammation and signaling metabolic pathways are changed
47
What is a common side effect of diabetes treatments?
Weight gain, which is undesirable -\> mechanism is different with each agent but with secretagogues, increased insulin levels reverse the catabolic effects of diabetes, leading to increases in weight. Thiazolidinediones (TZDs) increase adipocyte proliferation and also cause fluid retention, both of which can result in weight gain.
48
How do different risk factors affect T2DM onset?
49
How does T2DM present?
Osmotic symptoms, infection, screening test, at complication = acute: hyperosmolar coma; chronic: IHD, retinopahy
50
What are the complications in T2DM?
51
What is the basic management of T2DM?
Education, diet, pharmacological treatment, complication screening
52
What part of T2DM do you treat?
Symptoms, reduce chance of acute metabolic complications and chance of long term complications; education
53
What should T2DM eat?
Control total calories/increase exercise (weight), reduce refined carbs (less sugar), increase complex carbs (more rice), reduce fat as proportion of calories (less IR), increase unsaturated fat as proportion of fat (IHD), increase soluble fibre (longer to absorb carbs)
54
How do you monitor T2DM treatment?
Weight, glycaemia, BP, dyslidiaemia
55
What drugs should you use to treat liver, pancreas, obesity, GI, muscles in T2DM?
56
What is metformin and what is its function?
57
Where does glibenclamide work on and what is it?
Sulphonylurea -\> insulin secretagogue; lean patients with T2DM where diet alone hasn't succeeded, s/E hypoglycaemia, weight gain
58
What is Acarbose?
59
What are thiazolidinediones?
60
What is GLP-1?
61
What is the difference between GLP-1 and gliptins (DPPG-4 inhibitor)?
LHS = GLP-1
62
What is empagliflozin?
63
What other aspects of control are needed to be thought about in T2DM?
64
What are the risk factors associated with Diabetes mellitus?
65
How do you screen for diabetes?
Can be difficult to know when to screen
66
Which intervention works the best with T2DM - Placebo, Metformin, Lifestyle?
67
How are diabetes T1 and T2 compared?
68
What does poor control of diabetes cause?
Higher risk of both micro/macrovascular complications
69
What are the sites of microvascular complications?
Retinal arteries, glomerular arterioles (kidney), vasa nervorum (tiny blood vessels that supply the nerves)
70
If glycaemic control isn't good enough then what happens to relative risk of retinopathy, nephropathy, neuropathy, microalbuminuria?
71
What are the different microvascular complications of T2DM?
Severity of hyperglycaemia, hypertension, genetic, hyperglycaemic memory, tissue damage thorugh originally reversible and later irreversible alterations in proteins
72
What are the mechanisms of glucose damage?
73
What is diabetic retinopathy?
Main cause of visual loss in people with diabetes and the main cause of blindness in people of working age
74
How does hyperglycaemia affect the body in DM?
x
75
What can appear in background diabetic retinopathy?
Hard exudates (cheese colour, lipid), microaneurysms (dots), blot haemorrhages
76
What is preproliferative diabetic retinopathy?
Cotton wool spots (soft exudates), retinal ischemia
77
What is proliferative retinopathy?
Visible new vessels on disk or elsewhere in retina
78
What is maculopathy?
Hard exudates near the macula, same disease as background but near macula and can threaten direct vision
79
How do you manage background diabetic retinopathy?
Improve control of blood glucose, warn patient that warning signs are there
80
How do you manage preproliferative diabetic retinopathy?
Suggests general ischemia and if left alone new vessels will grow but needs pan-retinal photocoagulation
81
How do you manage proliferative diabetic retinopathy?
Pan-retinal photocoagulation
82
How do you manage maculopathy?
Problem around macula so need only a grid of photocoagulation (NOT PRPC)
83
What is diabetic nephropathy?
Caused by hypertension, progressively increasing proteinuria and deteriorating kidney function, classic histological features
84
What are the glomerular changes of diabetic nephropathy?
Mesangial expansion, basement membrane thickening, glomerulosclerosis
85
What epidemiological factors affect nephropathy in T2DM?
Age at development of disease, racial factors, age at presentation, loss due to cardiovascular morbidity
86
What are the clinical features of diabetic nephropathy?
Progressive proteinuria, increased BP, deranged renal function
87
How is proteinuria measured?
Using urine dipstick with normal range \<30mg/24h; nephrotic range of \>3000mg/24h -\> urinary excretion of albumin is increased and serum albumin will be low and tend to be quite oedematous
88
What are the strategies for intervention?
Diabetic control, BP control and inhibition of activity of RAAS system, stopping smoking
89
What are the negative effects of Angiotensin 2?
90
What is diabetic neuropathy?
Most common cause of neuropathy and therefore lower limb amputation - small vessels supplying nerves are called vasa nervorum and these get blocked during neuropathy
91
What are the different types of diabetic neuropathy?
92
How does the neuropathy initiation progress occur?
x
93
What does peripheral neuropathy affect?
Longest nerves supply feet, loss of sensation, more common in tall people -\> danger is that patients will not sense injury to foot
94
Who does peripheral neuropathy affect?
Tall patients and patients with poor glucose control
95
How do you examine peripheral neuropathy?
Monofilament examination
96
What are the symptoms of peripheral neuropathy?
Loss of sensation, loss of vibration sense, loss of ankle jerks, multiple fractures on foor X-ray (Charcot's joint)
97
What are the symptoms of mononeuropathy?
Usually sudden motor loss, wrist drop, foot drop, cranial nerve palsy, double vision due to 3rd nerve palsy
98
What is pupil sparing third nerve palsy?
Eye is usually down and out as 6th nerve pulls out and 4th down; pupil does respond to light; parasympathetic fibres on outside so don't immediately lose blood supply in diabetes
99
What are the signs that there is a space occupying lesion causing third nerve palsy?
Will press on PSNS fibres first causing fixed dilated pupil
100
What is mononeuritis multiplex?
Random combination of peripheral nerve lesions
101
What is radiculopathy?
Pain over spinal nerves, usually affecting a dermatome on the abdomen/chest wall
102
What is autonomic neuropathy?
Loss of sympathietic and PSNS nerves to GI tract, bladder, CVS
103
How does autonomic neuropathy affect the GI tract?
Difficulty swallowing, delayed gastric emptying, constipation/nocturnal diarrhoea, bladder dysfunction
104
What can autonomic neuropathy cause?
Psotura hypotension (disabling, collapsing on standing), cardiac autonomic supply (case reports of sudden cardiac death)
105
What are the different types of macrovascular disease?
Early widespread atherosclerosis, IHD, Cerebrovascular disease, peripheral vascular disease, renal artery stenosis
106
What are the sequences of atherosclerosis?
x
107
How do different types of atheroma form?
108
What is the metabolic syndrome?
Insulin resistance is implicated in non-diabetic macrovacular disease
109
What is hyperglycaemia associated with?
Significantly reduced life expectancy
110
What is the relative risk of CV events in people with diabetes?
111
What does microvascular disease cause c.f. macrovascular disease?
Micro causes morbidity; macro causes morbiity and mortality
112
What are the causes of death of the general popn c.f. diabetics?
113
Where is macrovascular disease present?
Systemic disease and is commonly present in multiple arterial beds
114
What is IHD?
Major cause of morbidity and mortality in diabetes; mechanisms similar with/out diabetes
115
What is cerebrovascular disease?
Earlier than without diabetes and is more widespread
116
What is peripheral vascular disease?
Contributes to diabetic foot problems with neuropathy -\> death of foot tissues
117
What is the effect of renal artery stenosis?
May contribute to renal failure
118
What effect does hyperglycaemia treatment have on CVD risk?
Minor effect
119
How do you prevent macrovascular disease?
Requires aggressive management of multiple risk factors; insulin resistance before hyperglycaemia itself contributes
120
What are the risk factors for macrovascular disease?
121
What are the different blood-glucose lowering therapy?
122
How do you manage blood pressure?
123
How do you manage blood lipids?
124
Which diabetes complications predispose to foot disease?
Neuropathy (sensory, motor and autonomic) and peripheral vascular disease
125
What is the pathway to foot ulceration?
Sensory neuropathy -\> motor neuropathy -\> limited oint mobility -\> autonomic neuropathy -\> peripheral vascular disease -\> trauma (repeated minor/discrete episode) -\> reduced resistance to infection -\> other diabetic complications (retinopathy)
126
What are the 3 types of foot ulceration?
Neuropathic foot, Ischaemic foot and neuro-ischaemic foot
127
What are the features of the neuropathic foot?
Numb, warm, dry, palpable foot pulses, ulcers at points of high pressure loading
128
What are the features of the ischaemic foot?
Cold, pulseless, ulcers at the foot margins
129
What are the features of the neuro-ischaemic foot?
Numb, cold, dry, pulseless. ulcers at points of high pressure loading and at foot margins
130
How do you assess the foot of a diabetic patient?
Appearance (deformity?, callus?) -\> Feel (hot/cold?, dry?) -\> foot pulses (dorsalis pedis and posterior tibial pulse) -\> neuropathy (vibration sensation, temp, ankle jerk reflex, fine touch sensation
131
How do you manage the foot ulcers?
Hyperglycaemia, hypertension, dyslipidaemia, stop smoking, education
132
How do you do preventative management for foot ulcers?
133
What is the difference with osteomyelitis and active charcot?
134
What factors precipitate diabetic ketoacidosis?
New diagnosis of T1DM, not taking insulin, intercurrent stress (pneumonia, heart attack), fasting and not taking enough insulin
135
What do the blood gases look like in metabolic acidosis?
pH is low, basic lesion is low HCO3, compensation is low CO2
136
Why is HCO3 low in Diabetic Ketoacidosis?
Impaired production and increased H+ buffering
137
How does an electrolyte disturbance occur in DKA?
Water lost in urine -\> Na lost in urine -\> K lost in urine (although acidosis shows high [K], total body K is low)
138
What are the physiological symptoms of DKA?
139
What are the clinical features of DKA?
Dehydration, insulin deficiency, total body K deficiency, acidotic, risk of arrhythmia/infection/dilated stomach, polyuria polydipsia, hyperventilation (Kussmaul), abdominal pain/vomiting, coma, glycosuria, ketonuria
140
Which investigations would you carry out for DKA?
Capillary glucose, plasma glucose, creatinine, K/Na, FBC, ABG, amylase, ECG, CXR, Septic screen
141
How would you treat DKA?
Fluid (osmotic diuresis), insulin, K, Bicarbonate, other measures
142
Which fluids would you give to treat DKA?
H2O 100ml/Kg,Na 8mmol/Kg -\> 500ml in 15 min, then 2\*500ml in 20min, 2\*500ml in 60 min, 500ml in 120min
143
How would you give insulin in DKA?
Intravenous sliding scale meaning capillary glucose is measured once and hour and insulin is adjusted accordingly
144
How do you give K in DKA?
Sliding scale is used with DKA, checking K during treatment
145
What are the risks and dangers of giving bicarbonate?
146
What other measures are used in DKA to treat it?
Caridac monitor for arrhythmias, catheterise, antibiotics, NG tube (gastroparesis), consider heparin and arterial line (v. acidotic) and central line (elderly/cardiac failure)
147
What is the second phase of treatment in DKA?
When glucose \< 10mmol/L, change to 5%dextrose, continue insulin and potassium and may need more saline
148
What are the causes of death in DKA?
Overwhelming diseasse, self-neglect, social factors, delay seeking help and primary care, inappropriate treatment
149
How do you prevent DKA?
Education, never stop insulin, check glucose and modify insulin if ill, admit if vomiting
150
What factors precipitate diabetic ketoacidosis?
New diagnosis of T1DM, not taking insulin, intercurrent stress (pneumonia, heart attack), fasting and not taking enough insulin
151
What do the blood gases look like in metabolic acidosis?
pH is low, basic lesion is low HCO3, compensation is low CO2
152
Why is HCO3 low in Diabetic Ketoacidosis?
Impaired production and increased H+ buffering
153
How does an electrolyte disturbance occur in DKA?
Water lost in urine -\> Na lost in urine -\> K lost in urine (although acidosis shows high [K], total body K is low)
154
What are the physiological symptoms of DKA?
x
155
What are the clinical features of DKA?
Dehydration, insulin deficiency, total body K deficiency, acidotic, risk of arrhythmia/infection/dilated stomach, polyuria polydipsia, hyperventilation (Kussmaul), abdominal pain/vomiting, coma, glycosuria, ketonuria
156
Which investigations would you carry out for DKA?
Capillary glucose, plasma glucose, creatinine, K/Na, FBC, ABG, amylase, ECG, CXR, Septic screen
157
How would you treat DKA?
Fluid (osmotic diuresis), insulin, K, Bicarbonate, other measures
158
Which fluids would you give to treat DKA?
H2O 100ml/Kg,Na 8mmol/Kg -\> 500ml in 15 min, then 2\*500ml in 20min, 2\*500ml in 60 min, 500ml in 120min
159
How would you give insulin in DKA?
Intravenous sliding scale meaning capillary glucose is measured once and hour and insulin is adjusted accordingly
160
How do you give K in DKA?
Sliding scale is used with DKA, checking K during treatment
161
What are the risks and dangers of giving bicarbonate?
x
162
What other measures are used in DKA to treat it?
Caridac monitor for arrhythmias, catheterise, antibiotics, NG tube (gastroparesis), consider heparin and arterial line (v. acidotic) and central line (elderly/cardiac failure)
163
What is the second phase of treatment in DKA?
When glucose \< 10mmol/L, change to 5%dextrose, continue insulin and potassium and may need more saline
164
What are the causes of death in DKA?
Overwhelming diseasse, self-neglect, social factors, delay seeking help and primary care, inappropriate treatment
165
How do you prevent DKA?
Education, never stop insulin, check glucose and modify insulin if ill, admit if vomiting
166
What are the negative physiological effects of DM?
High glucose, ketone production, destruction of adipocytes and muscle
