Endocrine List 1 - Diabetes Flashcards
1
Q
Give examples of diseases of the pituitary
A
Benign pituitary adenoma (most common in adults, pituitary produces less and presses on surrounding structures e.g. optic chiasm)
Craniopharyngioma
Trauma
Sheehans - pituitary infarction after labour
Sarcoid/TB
2
Q
What 3 things can result from a pituitary tumour?
A
Pressure on local structures
Pressure on normal pituitary - hypopituitarism
Functioning tumour - hyperpituitarism
3
Q
Give examples of pituitary tumour causing symptoms by putting pressure on local structures
A
Optic Chiasm pressed results in bitemporal hemianopia
Can cause hydrocephalus
Can get CSF leak
4
Q
Give examples of pituitary tumour causing symptoms by putting pressure on normal pituitary (hypopituitarism)
A
Can be fatal in case of cortisol deficiency
Males:
Pale, no body hair (takes 9 months to occur), central obesity, effeminate (female like) skin
Females:
Loose body hair
Sallow complexion
5
Q
Give examples of functional tumours of the pituitary gland (hyperpituitarism)
A
Prolactinoma (increased prolactin)
Acromegaly (increased GH)
Cushing’s (increased CTH)
6
Q
Describe features of Prolactinoma
A
Increased prolactin Results in increased milk production in breast (some seeps out - galactorrhea) Reduced fertility Menstruation stops (Amenorrhoea) Common in young women
7
Q
Give example of treatment and drug for Prolactinoma
A
Treated using dopamine agonist which in turn will inhibit prolactin release
e.g. CABERGOLINE
8
Q
Describe features of Acromegaly
A
Increased GH
Thick, greasy, sweaty skin
Enlarged organs e.g. heart thus increase risk of heart disease and death
9
Q
Describe features of Cushing’s
A
Increased CTH
Too much Cortisol
Central obesity
Bruising, thin skin, osteoporosis, ulcers, purply stretch marks
10
Q
Define Diabetes Mellitus
A
Syndrome of chronic hyperglycaemia due to relative insulin deficiency, resistance or both.
Hyperglycaemia results in serious microvascular or macrovascular problems.
DM is a vascular disease.
11
Q
Give examples of microvascular and macrovascular changes that can occur as a result of Diabetes Mellitus
A
Microvascular - Retinopathy, Nephropathy, Neuropathy
Macrovascular - Strokes, Renovascular disease, limb ischaemia
12
Q
What is normal blood glucose level?
A
3.5-8.0mmol/L under all conditions
13
Q
What is the principle organ of glucose homeostasis and why?
A
Liver
• Stores & absorbs glucose as glycogen - in post-absorptive state
• Performs gluconeogenesis from fat, protein and glycogen
• If blood glucose is HIGH then the liver will make glycogen (convert glucose to glycogen) in a process called glycogenesis - in the long term the liver will make triglycerides (lipogenesis)
• If blood glucose is LOW then the liver will split glycogen (convert glycogen to glucose) in process called glycogenolysis - in the longer term the liver will make glucose (gluconeogenesis) from amino acids/ lactate
14
Q
How much glucose is produced and utilised each day
A
200g
15
Q
What is most glucose derived from in body (not including glucose eaten/direct from gut)
A
More than 90% is derived from Liver GLYCOGEN and Hepatic GLUCONEOGENESIS
(remainder is Renal gluconeogenesis)
16
Q
What organ in the body is the major consumer of glucose
A
Brain
its function depends on an uninterrupted supply of this substrate
(glucose is oxidised to CO2 and water)
17
Q
Why is the brain’s function dependent on just glucose?
A
Free fatty acids CANNOT CROSS the BLOOD BRAIN BARRIER
Therefore brain cannot use free fatty acids to be converted to ketones (which can then be converted to Acteyl-CoA and used in the Kreb’s cycle for energy production)
18
Q
True or False:
Insulin can affect glucose uptake by the brain
A
False
Glucose uptake by the brain is OBLIGATORY and is not dependent on insulin
19
Q
What is name of receptors found in muscle and fat tissue that responds to insulin?
A
Insulin-responsive glucose transporters
absorb glucose in response to postprandial peaks in glucose and insulin
20
Q
What is meant by postprandial peaks in glucose and insulin?
A
Post-meal peaks
21
Q
What are 2 things that can happen to glucose in muscle
A
Stored as glycogen
Metabolised to lactate or CO2 and water
22
Q
What does fat tissue use glucose for?
A
Substrate for triglyceride synthesis
23
Q
What is released/produced from Lipolysis of triglycerides
A
Fatty acids and glycerol
Glycerol is then used as a substrate for hepatic gluconeogenesis
24
Q
What are to 2 keys hormonal regulators of carbohydrate metabolism?
A
Insulin
Glucagon
25
What are the functions of insulin?
Suppresses hepatic glucose output - decreases glycogenolysis and gluconeogenesis
Increases glucose uptake into insulin sensitive tissues:
-Muscle = glycogenesis and protein synthesis
-Fat = Fatty acid synthesis
-Suppresses Lipolysis and Breakdown of muscles (decreased ketogenesis)
26
What is meant by the biphasic insulin release?
- B-cells can sense the rising glucose levels and aim to metabolise it by releasing insulin - glucose levels are the major controlling factor in insulin release
- First phase response is the RAPID RELEASE of stored insulin
- If glucose levels remain high then the second phase is initiated, this takes longer than the first phase due to the fact that more insulin must be synthesised
27
Where is insulin produced and what chromosome codes for its production?
Beta cells of Islets of Langerhans of Pancreas
| Chromosome 11
28
Describe the production of insulin
• Proinsulin is the precursor of insulin
• It contains the Alpha & Beta chains of insulin which are joined together
by a C PEPTIDE
• When insulin is being produced, the proinsulin is cleaved from its C peptide and is then used to make insulin which is then packaged into insulin secretory granules
• Thus when there is insulin release there will also be a high level of C peptide in the blood from the cleavage of the proinsulin from it
• Synthetic insulin DOES NOT have C peptide - thus the presence of C peptide in the blood determines whether release is natural (then C peptide will be present) or synthetic (then C peptide will not be present)
29
What is the main action of insulin in a fasting state?
Regulate glucose release by the liver
30
What is the main action of insulin in the post-prandial state?
Promote glucose by fat and muscle
31
What % of secreted insulin is extracted and degraded in the liver
50%
32
What is function of GLUT-1 transporters
Enables basal NON-INSULIN-STIMULATED glucose uptake into many cells
33
Where are GLUT-2 transporters found?
Beta cells of pancreas
| Also found in the Renal Tubules and Hepatocytes
34
What is the purpose of GLUT-2 transporters having a low affinity?
only allows glucose in when there is a high concentration of glucose and thus want insulin release
35
What is purpose of GLUT-2 transporters?
Transports glucose into beta cells, thus enabling these cells to sense glucose levels. Low affinity transporter so only detects high glucose levels (to release insulin)
36
What is function of GLUT-3 transporters?
Enables NON-INSULIN-MEDIATED glucose uptake into BRAIN NEURONES and PLACENTA
37
What GLUT receptors are found on Renal Tubules?
GLUT-2
| also on beta cells of pancreas and hepatocytes
38
What GLUT receptors are found on placenta?
GLUT-3
| Also on brain neurones
39
What is function of GLUT-4 receptors?
Mediates much of the PERIPHERAL ACTION of INSULIN.
It is the channel through which glucose is taken up into MUSCLE and ADIPOSE TISSUE cells, following stimulation of the insulin receptor by INSULIN binding to it
40
What GLUT receptors are found on adipose tissue?
GLUT-4
| also muscle
41
Insulin receptor:
a) What type of molecule is it?
b) Which chromosome codes for it?
a) Glycoprotein
| b) short Arm of chromosome 19
42
Insulin receptor:
| Describe what happens when insulin binds
When insulin binds to the receptor it results in the activation of tyrosine kinase and initiation of a cascade response - one consequence of which is the migration of the GLUT-4 transporter to the cell surface and increased transport of glucose into the cell
43
What are different actions of insulin?
* Accelerate diffusion of glucose INTO cells
* Speed up the conversion of glucose into glycogen
* Increase the uptake of amino acids and increase protein synthesis • Speed up the synthesis of fatty acids
* Slow glycogenolysis (breakdown of glycogen to glucose)
* Slow gluconeogenesis (formation of new glucose)
44
True or False:
| Hypoglycaemia stimulates the release of glucagon
True
45
What are functions of glucagon on the liver?
Convert glycogen into glucose
Form glucose from lactic acid and amino acids
(Glycogenolysis and gluconeogenesis)
46
Give examples of diseases that can result in secondary diabetes
• Pancreatic pathology e.g. total pancreatectomy, chronic pancreatitis, haemochromatosis
• Endocrine disease e.g. acromegaly and Cushing’s disease
• Drug induced commonly by thiazide diuretics and corticosteroids
• Maturity onset diabetes of youth (MODY):
- Autosomal dominant form of type 2 diabetes - single gene defect altering beta cell function
- Tends to present <25 yrs with a positive family history
47
What type of diabetes is described here:
Has insulin deficiency with no resistance and immunogenic markers
Most prevalent in Northern European countries, particularly Finland and the incidence is increasing in most populations - particularly in young children
Type 1 primary diabetes
48
Which type of primary diabetes is described here:
Common in all populations enjoying an affluent lifestyle and is also increasing in frequency - particularly in adolescents
Type 2
49
What is LADA
Latent autoimmune diabetes in adults
50
Describe LADA (Latent autoimmune diabetes in adults)
* A ‘slow burning’ variant of type 1 diabetes mellitus with slower progression to insulin deficiency occurs in later life
* May be difficult to differentiate from type 2 diabetes (which also presents in later life) - clinical clues include; leaner build, rapid progression to insulin therapy following an initial response to other therapies and the presence of circulating islet autoantibodies)
51
What is diabetes mellitus type 1
Disease of insulin deficiency caused by autoimmune destruction of beta cells of the pancreas
52
Epidemiology of diabetes mellitus type 1
Typically manifests in childhood, reaching a peak incidence around the time of puberty - but can present at any age
Usually younger - < 30yrs
Patient is usually lean
Increased in those of Northern European ancestry, especially in Finland Incidence is increasing in most populations - particularly children
(Also latent autoimmune diabetes in adults)
53
Aetiology of diabetes mellitus type 1
AUTOIMMUNE - Auto-antibodies forming against insulin and islet beta cells - INSULITIS
Idiopathic (spontaneously arises/unknown cause)
Genetic susceptibility - HLA-DR3-DQ2 or HLA-DR4-DQ8
54
Risk factors of diabetes mellitus type 1
Northern European - especially Finnish
Family history - HLA-DR3-DQ2 or HLA-DR4-DQ8 in > 90%
Associated with other autoimmune disease
Environmental factors
55
What other autoimmune diseases associate with Diabetes Mellitus type 1
* Autoimmune thyroid
* Coeliac disease
* Addison’s disease (low cortisol)
* Pernicious anaemia
56
What environmental factors associate with diabetes mellitus type 1
* Dietary constituents
* Enteroviruses such as Coxsackie B4
* Vitamin D deficiency
* Cleaner environment may increase type 1 susceptibility
57
Give example of enterovirus
```
Coxsackie B4
(DM type 1)
```
58
Pathophysiology of diabetes mellitus type 1
Results from autoimmune destruction by autoantibodies of the pancreatic insulin-secreting Beta cells in the Islets of Langerhans
Causing insulin deficiency and thus the continued breakdown of liver glycogen (producing glucose and ketones) leading to glycosuria and ketonuria as more glucose is in the blood
In skeletal muscle and fats there is impaired glucose clearance
Blood glucose is increased - when it reaches 10mmol/L body can no longer absorb glucose - you become thirsty and get polyuria (as body attempts to remove excess glucose)
Must have insulin since patient prone to diabetic ketoacidosis
Eventual complete Beta cell destruction results in absence of serum C-peptide
Present VERY LATE (often only 10% beta cells remaining)
59
At what glucose concentration can body no longer absorb glucose as too high and what is result of this
10mmol/L
| Get thirsty and get polyuria (as body tries to remove glucose)
60
Describe diabetic ketoacidosis
* Results from a reduced supply of glucose (since there will be a significant decline in circulating insulin) and an increase in fatty acid oxidation (due to an increase in circulating glucagon)
* The increased production of Acetyl-CoA leads to ketone body production that exceeds the ability of peripheral tissues to oxidise them. Ketone bodies are relatively strong acids (pH 3.5), and their increase lowers the pH of blood
* This acidification of the blood can have many consequences but most critical is the fact that it IMPAIRS THE ABILITY OF HAEMOGLOBIN TO BIND TO OXYGEN - note if a patient is in diabetic ketoacidosis, the excess ketones in the blood will result in their BREATH SMELLING OF PEAR DROPS (KETONES)
* As a result of excess fat breakdown and can result in patient becoming acidotic, anorexic (weight loss) dehydrated leading to AKI and hyperglycaemia and eventual death
61
What is Diabetes Mellitus type 2
Results from a combination of insulin resistance and less severe insulin deficiency
62
Describe epidemiology of diabetes mellitus type 2
- Common is all populations enjoying an affluent lifestyle - has increased in incidence due to the ageing population and increasing obesity in the Western world
- Older - usually >30 yrs of age - but teenagers are starting to get it
- Often overweight around the abdomen
- More prevalent in South Asian, African and Caribbean ancestry
- Middle eastern and Hispanic Americans also more at risk
63
Aetiology of diabetes mellitus type 2
- Decreased insulin secretion +/- increased insulin resistance
- Associated with obesity, lack of exercise, calorie and alcohol excess
- No immune disturbance
- No HLA disturbance but there is a stronger genetic link
- Polygenic disorder
- More common in MALES than females
64
Risk Factors of diabetes mellitus type 2
- Family history - genetics
- Increasing age
- Obesity and poor exercise - can trigger DMT2 in genetically susceptible individuals
- Ethnicity - Middle Eastern, South-east Asian and Western pacific
- Low birth weight (due to poor nutrition impairing beta-cell development and function)
65
Give environmental risk factors of diabetes mellitus type 2
- Association between low weight (as a result of poor nutrition) at birth and/or at 12 months of age, with glucose intolerance later in life
- Thought to be caused because poor-nutrition early in life impairs beta- cell development and function - predisposing to diabetes later in life
- Low birth weight also shown to predispose the heat disease and hypertension
66
Pathophysiology of diabetes mellitus type 2
Type 2 diabetes is associated with central obesity, hypertension, hypertriglyceridaemia, a decreases high-density lipoprotein (HDL) cholesterol, disturbed homeostatic variables and modest increases in a number of pro-inflammatory markers
67
Which of these does not associate with DM type 2:
Central obesity
Hypotension
Hypertriglyceridaemia
Decreases high-density lipoprotein (HDL) cholesterol
Disturbed homeostatic variables
Modest increases in a number of pro-inflammatory markers
Do they associate with insulin resistance
Hypotension
(Hypertension associated with DM2)
A lot of these are strongly associated with insulin resistance as well as an increased CVS risk
68
True or False:
| Diabetes mellitus type 2 - insulin binds normally to receptor and so insulin resistance develops post-receptor
True
| DM2 is not caused by a problem with insulin binding to receptor
69
What other symptoms or things associate with insulin resistance?
Central obesity
Accumulation of intracellular triglycerides in muscle and liver
Non-alcoholic fatty liver disease in many
70
Why are circulating insulin levels higher in DM2 compared to normal
(Hypersecretion of insulin by a depleted beta cell mass, but still inadequate to restore glucose homeostasis.)
Due to increased glucose production from liver as there is inadequate suppression of gluconeogenesis and reduced glucose uptake by peripheral tissues - insulin resistance
71
Describe the Starling curve of pancreas
Circulating insulin levels are typically higher than in non-diabetics following diagnosis and tend to rise further, only to decline again after months or years due to eventual secretory failure
72
DM2 typically progresses from a preliminary phase of IGT or IFG - what do these stand for and what is their importance?
Impaired glucose tolerance
Impaired fasting glucose
A unique window for lifestyle intervention to prevent full DMT2 progression
73
What abnormalities of glucose regulation do IGT and IFG denote?
IGT & IFG denote different abnormalities of glucose regulation (post- prandial and fasting) - there may be a lower risk of progression to DMT2 in IFG than IGT
IGT:
- Fasting plasma glucose < 7mmol/L
- Oral glucose tolerance of 2hrs glucose > 7.8mmol/L but < 11mmol/L
IFG:
- Fasting plasma glucose > 6.1mmol/L but < 7mmol/L
74
Summarise pathophysiology of type 2 diabetes mellitus
Insulin resistance and impaired insulin secretion due to a combination of genetic predisposition and environmental factors (obesity and lack of physical activity)
75
Why doesn't diabetic keto-acidosis occur in type 2 diabetes?
| Give example of when could occur
Rare because the low insulin levels are sufficient to suppress catabolism and prevent ketogenesis.
It can occur if hormones such as adrenaline rise to high levels (eg during an MI).
76
Why does obesity cause type 2 diabetes mellitus?
Obesity (particularly central) impairs insulin action. In those, already insulin resistant due to genetic factors and who have progressive impairment in insulin secretion this brings out diabetes at an early stage.
77
Why does insulin secretion become impaired in Type 2 diabetes mellitus
Not entirely clear, but related to:
- genetic predisposition (ie abnormalities of insulin secretion in first degree relatives)
- deposition of peptides within the beta cell (‘amilyn’)
- ‘glucotoxicity’ hyperglycaemia inhibits insulin secretion
- **Probably main factor is lipid deposition in the pancreatic islets which prevent normal function
78
What can result from impaired insulin action?
Reduced muscle and fat uptake after eating
Failure to suppress lipolysis and high circulating FFAs
Abnormally high glucose output after a meal
79
What other conditions associate with DM2
Central obesity
Hypertension
Hypertriglyceridaemia
Decreased High Density Lipoprotein cholesterol
Disturbed homeostatic variables
Modest increases in a number of pro-inflammatory markers
80
True or False:
| Hyperglycaemia and lipid excess are toxic to beta cells in pancreas
True
Cause glucotoxicity
Result in further deterioration of beta cells and glucose homeostasis
81
Risk factors for diabetic ketoacidosis
- Stopping insulin therapy - Infection e.g. UTI
- Surgery
- MI
- Pancreatitis
- Undiagnosed diabetes
82
Clinical presentation of DMT1
Tend to be leaner and present more marked polydipsia, polyuria, weight loss and ketosis
83
Clinical presentation of DMT2
Tends to be overweight in the abdominal area and also presents with polydipsia, polyuria and weight loss and ketosis (only when very advanced with absolute insulin deficiency) but less marked
84
What triad of symptoms would you see in an acute presentation (2-6 week history) of DMT1 (and sometimes 2) in a young person
Polyuria and Nocturia
Polydipsia
Weight loss
85
Acute presentation of DM (T1)
| Why do you get polyuria/nocturia
Since glucose draws water into the urine by osmosis - not enough glucose can be reabsorbed as kidneys have reached the renal maximum reabsorptive capacity
This results in high levels of glucose in tubule urine and thus lots of water resulting in polyuria and nocturia
86
Acute presentation of DM (T1)
| Why do you get polydipsia
Due to the loss of fluid and electrolytes from excess glucose and thus water being in the urine
87
Acute presentation of DM (T1)
| Why do you get Weight loss
Due to fluid depletion and the accelerated breakdown of fat and muscle secondary to insulin deficiency
88
Describe subacute presentation (months to years) of DM and which people more likely to show this
- Onset may be over several months or years, particularly in older patients
- Polyuria, polydipsia and weight loss are typically present but tend to be less marked
- Patients may complain of such symptoms as lack of energy, visual blurring (due to glucose-induce changes in refraction) or pruritus vulvae (itchy vulva) or balanitis (skin irritation) that is due to Candida infection
89
What complications can be presenting features of DM
* Staphylococcal skin infection
* Retinopathy found during visit to optician
* Polyneuropathy causing tingling and numbness in the feet
* Erectile dysfunction
* Arterial disease resulting in MI or peripheral gangrene
90
True or False:
| Glycosuria is diagnostic for diabetes
False
| Glycosuria (alone) is not diagnostic for diabetes but indicates the need for further investigation
91
Describe physical signs of DM
Evidence of weight loss and dehydration
Breath may smell of ketones (esp DMT1)
Older patients may present with established complications, e.g. retinopathy
Patients with severe insulin resistance (i.e. DMT2) may have acanthosis nigricans - characterised by blackish pigmentation at the nape of the neck and in the axillae
92
True or False:
| Retinopathy characteristic of DM, is diagnostic in diabetes
True
93
Describe diagnosis of DM
Random plasma glucose > 11.1mmol/L = DIABETES DIAGNOSIS
Fasting plasma glucose > 7mmol/L = DIABETES DIAGNOSIS
- For both tests one abnormal value is DIAGNOSTIC in symptomatic individuals (Hyperglycaemia symptoms e.g. polyuria, polydipsia, unexplained weight loss, visual blurring, genital thrush, lethargy)
- Two abnormal values are required in asymptomatic individuals
```
Haemoglobin A1c (measures amount of glycated haemoglobin)
HbA1c > 6.5% normal (48mmol/mol) = DIABETES DIAGNOSIS
```
94
For borderline cases of DM, what test can be done to decide on DM diagnosis and describe the test
Oral glucose tolerance tests (OGTT):
• Fasting > 7mmol/L = DIABETES DIAGNOSIS
• 2 hrs after glucose > 11.1 mmol/L = DIABETES DIAGNOSIS
95
What conditions can diabetes be secondary to?
- Pancreatitis
- Trauma/pancreatectomy
- Neoplasia of pancreas
- Acromegaly
- Cushing syndrome
- Addisons
96
What drugs can diabetes be secondary to?
* Thiazide diuretics
* Beta-blockers
* Immunosuppressives e.g. ciclosporin and tacrolimus
* Thyroid hormone
97
What % of patients present with hypertension in DMT2
50%
| a higher proportion of African and Caribbean patients
98
In diabetic treatment, describe diet with good glycemic control
- Low in sugar
- High in starchy carbohydrates with low glycaemic index e.g. pasta
- High in fibre
- Low in fat
99
Diabetic treatment - what would give for treatment of hypertension (give example)
ACE-inhibitor
| e.g. Ramipril
100
Diabetic treatment - what would give for treatment of hyperlipidaemia (give example)
Statin
| e.g. Simvastatin
101
How would you administer synthetic (recombinant) human insulin?
```
Subcutaneous injection
(in abdomen, thighs or upper arm)
```
102
Why do you need to change injection site of insulin?
Prevent lipohypertrophy
103
What are 3 types of insulin
Shorting-acting (soluble) insulins
Short-acting insulin analogues
(intermediate or) Longer-acting insulins
104
How long do Shorting-acting (soluble) insulins take to work and when would they be used
Start working within 30-60 minutes and last for 4-6 hours
Given 15-30 minutes before meals in patients on multiple dose regimens and by continuous IV infusion in labour, during medical emergencies, at the time of surgery and in patients using insulin pumps
105
When would you use Short-acting insulin analogues
Used with the evening meal in patients who are prone to nocturnal hypoglycaemia
Reduced carry-ver effect compared to soluble insulin, but overall does NOT improve diabetic control
106
What are different types of Longer-acting insulins?
Intermediate (12-24 hrs) or long-acting (more than 24hrs)
Insulin premixed with retarding agents (either protamine or zinc) precipitate crystals
Protamine insulins are also known as isophane or NPH
insulins
The zinc insulins are also known as LENTE insulins
107
Complications of insulin treatment
* Hypoglycaemia - most common (also caused by SULFONYLUREA)
* Injection site - lipohypertrophy
* Insulin resistance - mild and associated with obesity
* Weight gain - insulin makes people feel hungry
108
Describe first line treatment of DMT2
* Lifestyle and dietary changes essential - exercise, weight loss
* Dietary factors e.g. low sugar, high in starch carbohydrates with low glycaemic index e.g. pasta, high in fibre, low in fat (esp. sat. fat)
* Nutrient load should be spread throughout the day (three main meals with snacks in between and at bedtime) - which reduces swings in blood glucose
* Blood pressure control e.g. RAMIPRIL
* Hyperlipidaemia control e.g. STATINS
* Can give ORLISTAT in obesity which is an intestinal lipase inhibitor and reduces the absorption of fat from the diet - it promotes weight loss
109
Describe second line treatment of DMT2
-Used in association with diet & lifestyle changes when this alone has failed to control hyperglycaemia
-Initially give a biguanide e.g. ORAL METFORMIN
-If HbA1c > 53mmol/L 16 weeks later then add a sulfonylurea e.g. ORAL GLICLAZIDE (safest drug in the very elderly is ORAL TOLBUTAMIDE since it has a very short duration of action)
-If at 6 months the HbA1c > 57mmol/L consider adding:
-Insulin may be needed
e.g. ISOPHANE INSULIN or a long-acting analogue
or a glitazone e.g. ORAL PIOGLITAZONE which replaces
metformin or sulfonylurea (to increase insulin sensitivity)
Or GLP e.g. incretins
110
```
A 50yo Asian man is referred to the diabetes clinic after presenting with polyuria and polydipsia. His BMI = 30, BP = 137/88, Fasting plasma glucose = 7.7mmol/L (high). The most appropriate first-line treatment is:
Dietary advice and exercise
Sulphonylurea
Exenatide
Thiazolidinediones
Metformin
```
Dietary advice and exercise
Metformin is a 1st line drug but comes after lifestyle change
111
A 6yo girl presents to accident and emergency with severe abdominal pain, nausea and vomiting. Patient has a sweet (fruity) odour from her breath and is breathing fast (tachypnoeic). The most likely diagnosis is:
Diabetic ketoacidosis
Hyperglycaemia hyperosmolar state
Gastroenteritis (Infection of intestine)
Pancreatitis
Addisonian crisis
DKA
Diabetic ketoacidosis – Presence of sweet breath & other presentations & patient’s age suggest T1DM
Hyperglycaemia hyperosmolar state – For T2DM patient
Gastroenteritis – No sweet breath
Pancreatitis – No sweet breath
Addisonian crisis – No sweet breath
112
```
A 57yo woman presents with dull grey-brown patches in her mouth and the palms of her hand which she has noticed in the last week. She has also noticed she gets very dizzy when rising from a seated position and is continually afraid of fainting. The most likely diagnosis is:
SIADH
Hyperthyroidism
Hypothyroidsim
Addison’s disease
Diabetes insipidus
```
Addisons disease
none of other diseases cause pigmentation
113
Briefly outline treatment of DMT2
1. Lifestyle modification: Diet, Weight control, Exercise
2. Monotherapy: Metformin (1st line biguanide drug)
3. If HbA1C rises to 58mmol/mol, consider dual therapy:
Metformin + DPP4 inhibitor (eg: sitagliptin)
Metformin + pioglitazone
Metformin + sulphonylurea (SU)
Metformin + SGLT-2i (glifazon)
4. If still no HbA1C change, consider triple therapy:
Metformin + DPP4 inhibitor + SU
Metformin + pioglitazone + SU
Metformin + pioglitazone/SU + SGLT-2i
Insulin-based therapy
5. If still not working, either give insulin or 'Metformin + SU + GLP 1 mimetic'
114
Treatment of DMT1
Insulin supplementation
115
*Define pre-diabetic (also diagnosis)
Fasting plasma glucose 5.5-7
116
What is metformin
Biguanide
Metformin works by reducing the amount of sugar your liver releases into your blood. It also makes your body respond better to insulin. Insulin is the hormone that controls the level of sugar in your blood.
For DMT2
117
Best test for long term diabetes diagnosis
HbA1c - measures amount of glycated haemoglobin
| not in children, <2 months symptoms, very ill, pregnant, some DMT1
118
DPP4 inhibitors/gliptins
Sitagliptin
| Block action of DPP4 - an enzyme that destroys the hormone incretin
119
What do glitazones do
Increases insulin sensitivity
120
Sulphonylurea
Increase insulin secretion
121
SGLT1
Selective sodium-glucose co-transporter 2 inhibitor
| Blocks reabsorption of glucose in the kidneys and promotes excretion of excess glucose in urine
