Diabetes Mellitus Flashcards
1
Q
What is the main hormone in the fasting state?
A
Glucagon
2
Q
What releases glucagon
A
Alpha cells (islet of langerhan of endocrine pancreas
3
Q
What is the hepatic action of glucagon
A
Increase hepatic glucose output by increasing
Gluconeogensis
Glycogenolysis
4
Q
What effect does glucagon have on peripheral tissue
A
Decreases glucose uptake
Stimulates the release of gluconeogenic precursors (glycerol/ AA)
5
Q
What are gluconeogenic precursors and how are they formed
A
Glycerol and AA
through lipolysis and muscle glycogenolysis
6
Q
Give examples of counter-regulatory hormones of insulin
A
Glucagon, adrenaline, cortisol, GH
7
Q
What releases insulin?
A
Beta cells (islet of langerhan- endocrine pancreas)
8
Q
What effect does insulin have on glucagon?
A
Inhibitory paracrine effect
9
Q
Summarise how glucose causes insulin to be secreted by B cells (normal action)
A
- Glucose enters B cell through GLUT2 glucose transporter
- Glucose is metabolised by glucokinase
- This causes K+ channels to close -> cell depolarisation
- Causes Ca2+ channels open -> Ca2+ influx
- Causes insulin secretory granules to release insulin out of cell
10
Q
Summarise how insulin acts on fat and muscle cells (normal mechanism action)
A
- Insulin binds to insulin sensitive receptors
- Causes signalling cascade
- Causes mobilization of intracellular GLUT4 vesicles to CSM
- Integration of vesicles to CSM
- This allows entry of glucose into cell
11
Q
What are the normal actions of insulin?
A
Liver: decr hepatic glucose output-> suppresses gluconeogenesis and glycogenolysis
Increases glucose uptake in insulin sensitive tissue
Suppresses lipolysis and breakdown of muscle
12
Q
What occurs when fasting - energy source for different tissues?
A
- Glucose is from liver (hepatic gluconeogenesis and glycogenolysis)
- Glucose is supplied to insulin independent tissue (brain and rbc)
- Low insulin level and high glucagon levels
- Lipolysis (12hrs<)
- Muscle use FFA for fuel
13
Q
What process does insulin inhibit?
A
Lipolysis
14
Q
What is the distribution to ingested glucose
A
40% liver
60% peripheries (mostly muscle)
15
Q
Define T2DM
A
Chronic hyperglycaemia due to insulin resistance and disorder of carb metabolism
16
Q
Describe the epidemiology for T2DM
A
- South Asians, Africans, Caribbean
- 40 yrs<
- Men
17
Q
What are the risk factors for T2DM?
A
- Lifestyle (obese, sedentary, high alcohol intake, poor diet)
- Ethnicity
- Sex
- Hypertension
- Hypercholesterolaemia
- Increasing age
- Large waist size
- Family history - much stronger than t1dm
18
Q
Describe the clincal presentation for T2DM
A
Symptoms:
- Polydipsia, polyuria, glucouria, blurred vision, unintentional weight loss,
- fatigue, central obestity, recurrent infections, genital thrush
- may be asymptomatic
Signs:
- Acanthosis nigricans (skin condition causing dark pigmentation of skin folds eg neck) - severe insulin resistance
19
Q
What are the 4 main investigations and results for T2DM
A
- HbA1c >48mmol/L (6.5%)
- Fasting plasma glucose >7.0mmol/L with symptoms
- Random plasma glucose >11.1mmol/L with symptoms
- OGTT
fasting >7mmol/L
2hr >11.1mmol/L
20
Q
What are the causes for T2DM
A
- genes and environement
- pregnancy (gestational diabetes)
- medication (thiazides, steroids)
- other endocrine diseases (hyperthyroidism, cushings, acromegaly)
21
Q
What is the first line treatment for T2DM
A
Diet and exercise changes to target weight loss and reduce carb intake
22
Q
Describe the pathophysiology of T2DM
A
- Periperhal insulin resistance = decr. glucose uptake
insulin can bind but malfunction in insulin intracellular pathway activation
so decr. in GLUT4 expression so decr. in glucose uptake - Decr. in insulin secretion due to B cell destruction (glucotoxicity) b amyloid deposits in pancreas
- Hepatic insulin resistance = excessive glucose production
- This causes hyperglycaemia
- Causing glycosuria
23
Q
What is the first oral mono-therapy used for T2DM?
A
Metformin (biguanide)
24
Q
What is the action of metformin?
A
Increases insulin sensitivity inskeletal muscle
Helps with weight loss
Reduces hepatic gluconeogeneis
25
What 3 factors define diabetic ketoacidosis?
Hyperglycaemia (plasma glucose >11mmol/L)
Raised plasma ketones (plasma ketone >3mmol/L)
Acidosis (Blood pH <7.3, bicarb <15mmol/L)
26
What is diabetic ketoacidosis?
Uncontrolled catabolism with associated insulin deficiency
27
What are the clinical features of DKA?
Vomiting
Abdo pain
Dehydration
Polydipsia and polyuria
Fruity breath
Hyperventilation- deep breathing (kussmaul HV)
Coma
Tachy/ hypotension
Low BP
28
What is the management for DKA?
- IV: fluid replacement
- IV insulin
- Electrolytes (K+)
29
What are the complications of DKA
Cerebral oedema
aspiration pneumonia
Hypokalaemia/magneasemia/phosphateaemia
Thromboembolism
Death
30
What are the tests and results for DKA?
Urine stick: glycosuria, ketonuria
Blood test:
Raised urea, creatinine (bc pre-renal failure)
Bicarb (<15mmol/L)
Hyperglycaemia (plasma glucose >48mmol/L)
Blood ketone (>3)
Blood pH <7.3
Raised K+ on presentation
31
What can trigger ketoacidosis?
Infection
Surgery
Error in insulin treatment
Undiagnosed diabetes
32
Does DKA often occur in T2DM?
Rare due to low insulin production/ not complete resistance which inhibits lipolysis
May occur in very late stages w absolute insulin def.
More common in T1DM
33
Describe the pathophysiology of ketoacidosis
- insulin deficiency -> lipolysis -> incr. FFA
- FFA in liver (for gluconeogenesis) -> ketones (oxidised by ketogenesis)
- causes metabolic acidosis
- causes vomiting -> dehydration
- glucose and ketones -> urine, also causes osmotic diuresis
- dehydration, loss of electrolytes and loss in circulating BV -> coma
34
What occurs in metabolic acidosis?
vomiting -> h2o and electrolyte loss
hyperventilation -> resp. compensation
dehydration = worse renal excretion of H+ and ketones= exacerbation
stress hormone accelerates this (cortisol/ adrenaline/ glucagon)
35
What line of treatment should never be stopped with T1DM
Insulin
36
What forms of diabetes is included in T2DM?
Gestational and medication induced
37
How is asymptomatic T2DM diagnosed compared to symptomatic?
Asymptomatic needs 2 glucose tests w positve hyperglycaemic results on 2 separate occasions
Symptomatic can have 1 result
38
What is T2DM a risk factor for?
Hypertension
Silent myocardial infarct
Nephrotic syndrome
CVD
39
What glucose results class as pre-diabetic?
Impaired glucose intolerance-
fasting 6-7mmol/L
OGTT 2hrs after 7.8-11mmol/L
40
What does the HbA1c test investigate?
Glycated haemoglobin levels
Amount of glucose attached to rbc
Indicates average prior 3 months glucose levels
41
What is the management for pre-diabetes?
No medication
Diet and exercise modifications
Annual review and check up
42
What is impaired fasting intolerance?
Abnormal fasting glucose results - not high enough for diabetes
Pre-diabetic
6-7mmol/L
43
What is impaired glucose intolerance?
Abnormally high 2hr-post prandial result- not high enough for diabetes
Pre-diabetic
7.8-11mmol/L
44
What are the normal results for random, fasting and 2hr post-prandial glucose test?
Random <11.1mmol/L
Fasting <6.1 mmol/L
2hr <7.8 mmol/L
45
What are incretins and give an example of 1
Class of hormones secreted from the SM in response ot the ingestion of food
GLP-1 (glucagon like peptide)
46
What physiological effects do incretins have?
Influence and control glucose homeostasis...
Reduce appiteite and promote satiety
Acts on B cells to incr. insulin secretion (in response to glucose)
Acts on A cells to decr. glucagon secretion
Decr. hepatic glycogenolysis
47
What are the side effects and CI's of metformin?
SE = GI distrubances- abdo pain, nausea, diarrhoea
CI- Kidney problems
48
Does metformin typically cause hypoglycaemia?
No
49
What is the second line double therpy for T2DM
Metformin w 1 of the following
- SGLT2 inhibitors
- DPP4 inhibitors (Sitagliptin)
- Sulfonylurea (Gliclazide)
- Thiazolidinediones (Glitazone)
50
What causes decr. insulin secretion in T2DM?
- B amyloid deposits in pancreatic islet
- B cell destruction due to hyperglycaemia
51
What are the micro-vascular complications of T2DM?
- diabetic nephropathy
- diabetic retinopathy
- diabetic neuropathy (diabetic foot)
- DKA (rare- absolute insulin resistance)
52
Briefly describe hallmarks and treatment of diabetic nephropathy
Changes to the glomerular filration barrier results in
1. Proteinuria (mostly albumin) (hallmark)
2. Progress to renal failure
Seen w eGFR, incr. serum creatinine and urea - late onset
Microalbuminuria may be present at diagnosis
Use ACE inhibitor- BP control
53
What is the pathopyisology of diabetic retinopathy
54
What are the macro-vasuar complications of T2DM?
- Stroke
- MI
55
What is the treatment for diabetic reintopathy?
Laser eye treatment - SE deteriorates night vision
56
Define T1DM
Insulin deficiency due to autoimmune destruction of beta pancreatic cells resulting in persistent hyperglycaemia
57
Describe the epidemiology of T1DM
Lean
North european eg finnish
Early onset usually 5-15 - but can be any age ``
58
Describe the pathophysiology of T1DM
- Autoimmune destruction of pancreatic b cell result in insulin deficiency
- Due to autoantibodies binding to HLA receptors of B cells
- failure of insulin secretion = hepatic glycogenolysis and suppression of peripherial glucose uptake
- causing hyperglycaemia
- renal threshold exceeded (10mmol/L)
- leaves in urine -> glycosuria and causes osmotic diruesis -> polyuria
- unrestrained lipolysis and skeletal muscle breakdown for energy production and metabolism -> ketones
59
What are the risk fators for t1dm?
family history (HLA)
Autoimmune conditions
Northern european
60
What is the clinical presentation of t1dm?
polyuria, glucosuria, ketouria
weight loss
fatigue
ketosis
adults usually present w ketosis, rapid weight loss, bmi <25 and history of autoimmune disease
61
What are the investigations and results for t1dm?
fasting plasma glucose >7mmol/L
random plasma glucose >11.1mmol/L
62
If on insulin therapy, must inform...?
DVLA
63
What are the treatments for t1dm
Insulin therapy- continuous
- basal bolus
64
Recommended diet for diabetics
low sugar, low fat, high starch
65
Why shoul those w t1dm be advised not to binge drink?
Risk of delayed hypoglycemia
66
What are the complications of t1dm and which is the main?
DKA
diabetic retinopathy, neuopathy, nephropathy
67
How long should bolus insulin be taen before a meal?
15 min
68
What is the routine of insulin for t2dm?
basal in morning
then bolus prandial insulin w biggest meal of the day
then with other meals if necessary
69
What is the most common insulin treatment used with t1dm?
basal bolus
70
What is the plasma glucose level for hypoglycaemia?
<3mmol/L plasma glucose
71
What are the symptoms for hypoglycaemia?
Autonomic: anxiety, trembling, palpitations
Neuroglycopenic: confusion, weakness, drowsiness, dizziness
72
In hypoglycaemia do autonomic or neuroglycopenic symptoms appear first?
Autonomic
73
What are the 3 classifications of hypoglycaemia?
level 1: alert value - plasma glucose <3.9mmol/L -low blood glucose
level 2 : serious biochemical - plasma glucose <3mmol/L
level 3 : severe hypoglycaemia - <3mmol/L, requires 3rd party assistance due to coginitive dysfunction
(non-severe- patient is symptomatic but can self-treat)
74
What are the potential physiological effects of hypoglycaemia?
Cognitive dysfunction, blackouts, seizures
Falls, inflammation
Incr. risk Mi/ arrhythmias
75
What is a hyperosmolar hyperglycaemic state? And its common cause
Hyperglycaemia, hyperosmolality with no ketosis
Most common cause is infection esp pneumonia
76
What are the clinical features of hyperosmolar hyperglycaemic state?
dehydration due to osmotic diureses
Decr. levels of conciousness - due to raised plasma osmolality
polyuria
77
What is the mamagement for hyperosmolar hyperglycaemic state?
IV fluids
insulin if severe
78
What are the risks for hyperosmolar hyperglycaemic state?
incr. in blood viscosity = more likely to clot = MI, stroke, DVT
79
What is MODY diabetes?
Maturity onset diabetes of the young
Monogenic
Autosomal dominant conditon of beta cell function gene defect
Non-insulin dependent
<25yrs diagnosis
80
Is MODY diabetes often mistaken for t1/t2dm?
T1
as young onset
81
Name 3 endocrine pancreatic causes of diabetes
Acromegaly- incr. insulin resistance
Cushings - incr. insulin resistance, incr. gluconeogenesis
Drug induced
