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Endocrinology > Diabetes > Flashcards

Diabetes Flashcards

2
Q

In fasting state where does all glucose come from?

A

Liver
Bit from kidney
Breakdown of glycogen
Gluconeogenesis

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2
Q

What happens when we have high insulin and glucose levels in the body?

A

High insulin and glucose levels suppress lipolysis and levels of non-esterified fatty acids (NEFA or FFA) fall

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3
Q

What are the 3 carbon precursors to synthesise glucose?

A

lactate, alanine and glycerol

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4
Q

In fasting state where is glucose delivered to?

A

insulin independent tissues, brain and red blood cells

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5
Q

How many hours of glucose store do we have?

A

6

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6
Q

After eating what happens?

A

Rising glucose (5-10 min after eating) stimulates insulin secretion and suppresses glucagon

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7
Q

Where does the ingested glucose go once we eat?

A

40% of ingested glucose goes to liver and 60% to peripheral tissue, mostly muscle
Ingested glucose helps to replenish glycogen stores both in liver and muscle

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8
Q

Where is the site of insulin and glucagon secretion in endocrine pancreas?

A

Islets of langerhans

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9
Q

What secretes insulin?

A

Beta cell

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10
Q

What secretes glucagon?

A

Alpha cell

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11
Q

What happens when we have high amounts of insulin?

A

– beta cells keep alpha cells in a state of chronic inhibition – paracrine effects
paracrine ‘crosstalk’ between alpha and beta cells is physiological, ie local insulin release inhibits glucagon an effect lost in diabetes

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12
Q

What is diabetes mellitus?

A

A disorder of carbohydrate metabolism characterised by hyperglycaemia
Main issue= High sugar levels
High sugars for long period of time – causes complications
Glucose – draws water across cell membranes – lot of glucose being stored not in the right place
Start to pee a lot of water
Make glucose from ketones – lose more water ketones acidic
Vomit = lose more water
Diabetic ketoacidosis

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13
Q

How does diabetes mellitus affect cause morbidity and mortality?

A

Acute hyperglycaemia: if untreated leads to acute metabolic emergencies diabetic ketoacidosis (DKA) and hyperosmolar coma (Hyperosmolar Hyperglycaemic State )

Chronic hyperglycaemia: leading to tissue complications (macrovascular and microvascular)

Side effects of treatment- hypoglycaemia

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14
Q

What are some serious complications associated with diabetes?

A

Diabetic retinopathy: Affects over one-third of people with diabetes; leading cause of vision loss in working-age adults1

Diabetic Nephropathy: Leading cause of end stage renal disease

Stroke: Increases risk from 2 to 6 fold

CVD: Most common cause of death in diabetics

Diabetic neuropathy: Up to 28% of foot ulcers may result in some
form of lower extremity amputation

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15
Q

What are the type of diabetes?

A

Type 1
Type 2
Maturity onset diabetes of youth (MODY), also called monogenic diabetes – rare form which is distinct from type 1 or type 2
Pancreatic diabetes - Type 3C
“Endocrine Diabetes” (Acromegaly/Cushings)
Malnutrition related diabetes
Gestational diabetes

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16
Q

Definition (blood levels) of diabetes:

A

Symptoms and random plasma glucose > 11 mmol/l

Fasting plasma glucose > 7 mmol/l

No symptoms - Glucose Tolerance Test (75g glucose) fasting > 7 or 2h value > 11 mmol/l (repeated on 2 occasions) – oral glucose tolerance test
HbA1c of > 48mmol/mol (6.5%)

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17
Q

What are some symptoms of diabetes?

A

Polyuria
Weightloss
Tiredness/ fatigue
Polydipsia - thirstiness

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18
Q

What is HbA1C?

A

RBC have lifespan of 3 months – glucose latches onto RBC – measure amount of glucose latched onto Hb – that is the HbA1c

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19
Q

What is the pathogenesis of Type 1 diabetes?

A

An insulin deficiency disease characterised by loss of beta cells due to autoimmune destruction
Beta cells express antigens of HLA histocompatability
Activates a chronic cell mediated immune process leading to chronic ‘insulitis’

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20
Q

What does failure of insulin secretion do in type 1?

A

Continued breakdown of liver glycogen
Unrestrained lipolysis and skeletal muscle breakdown providing gluconeogenic precursors
Inappropriate increase in hepatic glucose output and suppression of peripheral glucose uptake

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21
Q

What does the rising glucose concentration result in?

A

increased urinary glucose losses as renal threshold (10mM) is exceeded

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22
Q

What happens if we fail to treat type 1 diabetics with insulin?

A

Increase in circulating glucagon (loss of local increases in insulin within the islets leads to removal of inhibition of glucagon release), further increasing glucose

perceived ‘stress’ leads to increased cortisol and adrenaline

progressive catabolic state and increasing levels of ketones

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23
Q

If there is no insulin what do you end up breaking down?

A

break down fat – lose loads of weight

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24
Q

How can hyperglycaemia occur?

A

Glucagon increases glucose levels as well – lack of insulin and unrestricted glucagon levels also causes hyperglycaemia
Enter catabolic state

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25
Q

Whats the aetiology of type 2 diabetes?

A

Progressive hyperglycaemia
and high free fatty acids >

Impaired insulin secretion + Insulin resistance
> Impaired glucose tolerance
> Type 2 diabetes

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26
Q

Whats the difference in type 2 diabetes and normal glucose and insulin profiles?

A

Normal circumstances someone has breakfast and insulin spikes and glucose level rises and goes back down – always for all meals

Type 2 diabetes – breakfast glucose is high and insulin is not doing a good job – glucose comes down a bit – takes so much longer – starting off at a higher baseline point

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27
Q

What is the natural history of Type 2 diabetes?

A

Starts with Impaired glucose tolerance (IGT)
Undiagnosed diabetes
Known diabetes
Insulin resistance increases across these stages
Insulin secretion increases from first 2 stages then dips in known diabetes
Fasting glucose increases
Starlings curve of the pancreas

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28
Q

What is type 2 diabetes a consequence of?

A

insulin resistance and progressive failure of insulin secretion (but insulin levels are always detectable)

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29
Q

Impaired insulin action leads to what in type 2 diabetes?

A

Reduced muscle and fat uptake after eating
Failure to suppress lipolysis and high circulating FFAs
Abnormally high glucose output after a meal

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30
Q

Low levels of insulin can prevent what?

A

prevent muscle catabolism and ketogenesis so profound muscle breakdown and gluconeogenesis are restrained and ketone production is rarely excessive

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31
Q

What happens in type 1 ketoacidosis?

A

Type 1 diabetes no insulin – breakdown free fatty acids and make ketones which are acidic – make you nauseous and blood becomes acidic – get diabetic ketoacidosis – give them insulin and ketones go down and acidosis goes down as well

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32
Q

What happens in type 2 ketoacidosis?

A

Early on pancreas makes insulin – not gonna break down free fatty acids early on so not necessarily get diabetic ketoacidosis – will get hyperglycaemia –
15 years of type 2 diabetes – will get diabetic ketoacidosis – cant suppress ketones anymore late stage diabetes

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33
Q

Pathophysiology of type 1 diabetes :

A

Absent insulin secretion : No hepatic insulin effect and no muscle/fat insulin effect

Unrestrained glucose + ketone production > more glucose enters the blood > Hypergylcaemia and raised plasma ketones (leads to glycosuria/ ketonuria) > less glucose enters peripheral tissues > Impaired glucose clearance + muscle fat breakdown

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34
Q

Pathophysiology of type 2 diabetes :

A

Impaired insulin secretion : hepatic insulin resistance and muscle/fat resistance

Excessive glucose production > more glucose enters the blood > Hypergylcaemia (glycosuria) > less glucose enters peripheral tissues > Impaired glucose clearance

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35
Q

Summary of pathophysiology of type 1 diabetes:

A

Severe insulin deficiency due to autoimmune destruction of the beta cell (initiated by genetic susceptibility and environmental triggers)

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36
Q

Summary of type 2 diabetes pathophysiology:

A

Insulin resistance and impaired insulin secretion due to a combination of genetic predisposition and environmental factors (obesity and lack of physical activity)
lipid deposition in liver and pancreas lead to both insulin resistance and impaired insulin secretion
Fats sit on liver and pancreas for type 2 diabetes
High sugar levels toxic to beta cell – pancreas fails cuz its working super hard – rising levels of sugar start to become toxic to beta cells – double whammy

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37
Q

Treatment of type 2 diabetes:

A

Ideally consists of weight loss and exercise which if substantial will reverse hyperglycaemia

Lifestyle changes are important if they can be achieved
but most with Type 2 diabetes have been making the ‘wrong’ lifestyle choices all their lives and rarely respond to these approaches

At present, management usually consists of medication to control BP, blood glucose and lipids

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38
Q

What are Sulphonylureas (gliclazide, glibenclamide)?

A

stimulate insulin release by binding to B-cell receptors

Improve glycaemic control (1-2% in HbA1c) at the expense of significant weight gain

Do not prevent the gradual failure of insulin secretion

Can cause hypoglycaemia (occasionally prolonged and fatal, particularly in the elderly and when renal function is impaired)

Use gliclazide in most people

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39
Q

What are Thiazolidinediones (pioglitazone - ACTOS)?

A

Bind to the nuclear receptor PPAR (peroxisome proliferator-activated receptor)

Activate genes concerned with glucose uptake and utilisation and lipid metabolism

Improve insulin sensitivity

Need insulin for a therapeutic effect

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40
Q

What are glitazones?

A

relatively rarely used but may be useful in some sub-groups
Increase weight
Increase the risk of heart failure
Increase the risk of fractures

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41
Q

What is GLP-1?

A

Secreted from L cells of intestine
Stimulates insulin secretion
Suppresses glucagon secretion
Improves insulin sensitivity
Enhances glucose disposal
Slows gastric emptying
Reduces food intake

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42
Q

What happens to native GLP-1?

A

rapidly degraded by DPP-IV

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43
Q

What drugs Lower glucose Reduce weight and CVD independent of glucose lowering ?

A

Exenatide(BYETTTA) twice daily
Once weekly exenatide (BYDUREON)
Liraglutide (VICTOZA) once daily
Lixisenatide (LYXUMIA) once daily
Dulaglutide (TRULICITY) once weekly
Semaglatide (OZEMPIC) once weekly
Oral semaglutide (RYBELSUS) daily

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44
Q

DPP-IV inhibitors (oral)

A

Vildagliptin (GALVUS)
Sitagliptin (JANUVIA)

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45
Q

What do SGL2 inhibitors do?

A

SGLT2 inhibitors block the reabsorption of glucose in the kidney, increase glucose excretion, and lower blood glucose levels

Agents include: empagliflozin, canagliflozin, dapagliflozin

May have specific benefit in reducing CV mortality

Reduce risk of heart failure readmissions

Reduce risk of heart attacks and kidney disease

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46
Q

Side effects of SGL2 inhibitors

A

genital thrush, increased risk of euglycaemic ketoacidosis* including in type 2 diabetes, now licensed in type 1 diabetes

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47
Q

DRUGS TO USE

A

Metformin first line

Sulphonylureas are no longer the second line agents of choice
DPP-IV inhibitors, GLP1 analogues, SGLT-2 inhibitors are replacing sulphonylureas

Use of glitazones rarely used

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48
Q

Why doesn’t DKA occur in Type 2 diabetes?

A

It is 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)

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49
Q

Why does obesity cause type 2 diabetes?

A

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.

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50
Q

What is a basal insulin?

A

Long acting insulin

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51
Q

Examples of basal insulin?

A

NPH insulin
(INSULATARD and HUMULIN I)

Insulin glargine (100 and 300 U/ml)
(LANTUS and TOUJEO)

Insulin detemir
(LEVEMIR)

Insulin degludec
(TRESIBA)

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52
Q

What are some meal time insulins?

A

Insulin lispro
Insulin glulisine
EDTA/citrate human insulin
Faster-acting insulin aspart

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53
Q

T1DM features:

A

Autoimmune condition (β-cell damage) with genetic component
Profound insulin deficiency

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54
Q

T2DM Features:

A

Insulin resistance
Impaired insulin secretion and progressive β-cell damage but initially continued insulin secretion
Excessive hepatic glucose output
Increased counter-regulatory hormones including glucagon

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55
Q

Whats the modern insulin therapy T1D?

A

Separation of basal from bolus insulin to mimic physiology

Pre-meal rapid acting boluses adjusted according to pre-meal glucose and carbohydrate content of food to cover meals

Basal insulin should control blood glucose in between meals and particularly during the night

Basal insulin given as either twice daily insulin levemir (basal analogue or once daily degludec) adjusted to maintain fasting blood glucose between 4–7 mmol/L
Quick acting insulin 15 minutes b4 meal so insulin can catch up

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56
Q

Why are insulin analogues important?

A

have longer action of duration

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57
Q

When do people with T2DM require insulin?

A

particularly later in the disease course or in individuals with poor glycaemic control on other medications

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58
Q

Long-acting basal insulin are assosicated with what?

A

lower risk of symptomatic, overall and nocturnal hypoglycaemia
In general, basal insulin is initiated followed by addition of a prandial insulin where necessary

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59
Q

Whats once-daily basal insulin used in?

A

Just type 2 diabetes

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60
Q

Whats twice daily mix insulin used in?

A

Type 1 and type 2

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61
Q

What is basal-bolus therapy used in?

A

Mostly used in type 1 diabetes
Sometimes used in type 2 diabetes

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62
Q

What are the advantages of basal insulin in type 2 diabetes?

A

Simple for the patient, adjusts insulin themselves, based on fasting glucose measurements
Carries on with oral therapy, combination therapy is common
Less risk of hypoglycaemia at night

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63
Q

What are the disadvantages of basal insulin in type 2 diabetes?

A

Doesn’t cover meals
Best used with long-acting insulin analogues which are considered expensive.

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64
Q

What are the advantages of pre-mixed insulin in diabetes?

A

Both basal and prandial components in a single insulin preparation
Can cover insulin requirements through most of the day

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65
Q

What are the disadvantages of pre-mixed insulin in diabetes?

A

Not physiological
Requires consistent meal and exercise pattern
Increased risk for nocturnal hypoglycaemia
Increased risk for fasting hyperglycaemia if basal component does not last long enough
Often requires accepting higher HbA1c goal of <7.5% or ≤8% (<58 or ≤64 mmol/mol)

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66
Q

What is considered the best treatment for T1DM?

A

Intensive basal-bolus insulin therapy is considered the best treatment for T1DM

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67
Q

What is the best treatment approach for T2DM?

A

a treatment approach in which basal insulin is added to oral therapy can improve glycaemic control and reduce hypoglycaemia but bolus insulin for one or two meals is often required

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68
Q

What is level 1 hypoglycaemia?

A

Alert value
Plasma glucose <3.9 mmol/l (70 mg/dl) and no symptoms

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69
Q

What is level 2 hypoglycaemia?

A

Serious biochemical
Plasma glucose <3.0 mmol/l
(55 mg/

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70
Q

What is non-severe hypoglycaemia?

A

Patient has symptoms but can self-treat and cognitive function is mildly impaired

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71
Q

What is level 3 hypoglycaemia?

A

Patient has impaired cognitive function sufficient to require external help to recover - need 3rd party help such as doctors

72
Q

Who are more likely to have level 3 hypoglycaemia?

A

Type 1 diabetes as they are on insulin sooner

73
Q

On average how many hypoglycaemic episodes will have type 2 diabetes patients have?

A

1

74
Q

Hypoglycaemia effect on brain:

A

Cognitive dysfunction
Blackouts, seizures, comas
Psychological effects

75
Q

Hypoglycaemia effect on musculoskeletal:

A

Falls, accidents,
driving accidents
Fractures
Dislocations

76
Q

Hypoglycaemia effect on heart:

A

Increased risk of myocardial ischaemia
Cardiac arrhythmias

77
Q

Hypoglycaemia effect on circulation:

A

Inflammation
Blood coagulation abnormalities
Haemodynamic changes
Endothelial dysfunction

78
Q

What are some autonomic (sympathetic and parasympathetic) hypoglycaemic symptoms?

A

Trembling
Palpitations
Sweating
Anxiety
Hunger

79
Q

What are some Neuroglycopenic hypoglycaemic symptoms?

A

Difficulty concentrating
Confusion
Weakness
Drowsiness, dizziness
Vision changes
Difficulty speaking

80
Q

Non specific hypoglycaemic symptoms

A

Nausea
Headache

81
Q

What are normal physiological responses in preventing hypoglycaemia? (protective mechanisms)

A

4.6 mmol/L: inhibition of endogenous insulin secretion
3.8 mmol/L: Glucagon released
3.5 mmol/L: Adrenaline
3.2-3.0 nmol/L: Autonomic - Neuroglycopenic symptoms

82
Q

What are normal physiological responses in preventing hypoglycaemia? (consequences of hypoglycaemia)

A

3 mmol/L: Widespread ECG changes
2.8 mmol/L: Neurophysiologicaldysfunction
Evoked responses
3-2.4 mmol/L: Cognitive dysfunction
Inability to perform complex tasks
>1.5 mmol/L: Severe neuroglycopenia
Reduced conscious level
Convulsions
Coma

83
Q

Causes of hypoglycaemia:

A

Long duration of diabetes
Tight glycaemic control with repeated episodes of non severe hypoglycaemia
Increasing age
Use of drugs
Sleeping
Increased physical activity

84
Q

How to screen for risk of severe hypoglycaemia?

A

Low HbA1c; high pre-treatment HbA1c in T2DM
Long duration of diabetes
A history of previous hypoglycaemia
Impaired awareness of hypoglycaemia (IAH)
Recent episodes of severe hypoglycaemia
Daily insulin dosage >0.85 U/kg/day
Physically active (e.g. athlete)
Impaired renal and/or liver function

85
Q

Strategies to prevent hypoglycaemia?

A

Discuss hypoglycaemia risk factors and treatment with patients on insulin or sulphonylureas
Educate patients and caregivers on how to recognize and treat hypoglycaemia
Instruct patients to report hypo episodes to their doctor/educator
Consider enrolling patients with frequent hypoglycaemia in a blood glucose awareness training programme

86
Q

Treatment for hypoglycaemia

A
  1. Recognize symptoms so they can be treated as soon as they occur
  2. Confirm the need for treatment if possible (blood glucose <3.9 mmol/l is the alert value)
  3. Treat with 15 g fast-acting carbohydrate to relieve symptoms
  4. Retest in 15 minutes to ensure blood glucose >4.0 mmol/l and re-treat (see above) if needed
  5. Eat a long-acting carbohydrate to prevent recurrence of symptoms
87
Q

Diseases assosciated with PPG?

A

1.Lack of vasopressin = AVP deficiency (cranial diabetes insipidus)
Uncommon but life threatening
2. Resistance to action of vasopressin = AVP resistance (nephrogenic diabetes insipidus)
Not common but life threatening
3. Too much vasopressin release when it should not be released = syndrome of anti- diuretic hormone secretion – SIAD – (also from ectopic source – e.g. carcinoma of lung)
Really common, and can be life threatening
NB – other causes of hyponatraemia MUST be identified – different management

88
Q

Symptoms of AVP resistance and deficiency (Diabetes insipidus - DI)

A

polyuria
polydypsia - overdrinking
no glycosuria

89
Q

Diagnosis for DI?

A

measure urine volume - DI unlikely if urine volume
<3L/day
check renal function and serum calcium

90
Q

Biochemistry for DI

A

inappropriately dilute urine for plasma osmolality
serum osmo >300 AND urine osmo<200 consistent with Diabetes Inspidis
normonatraemia or hypernatraemia
water deprivation test
hypertonic saline infusion and measurement of AVP
If you have a concentrated level in blood – urine should be really concentrated – can get inappropriately dilute urine
Primary polydipsia – drinking too much – wash out concentrating urine in kidney – vasopressin not very effective – end up peeing too much – hard to differentiate between Diabetes insipidis and primary poydypsia

91
Q

What are the acquired causes for Cranial DI - AVP deficiency?

A

Idiopathic

Tumours - craniopharyngioma, germinoma, metastases,
‘never’ anterior pituitary tumour

Trauma

Infections – TB, encephalitis, meningitis,

Vascular – aneurysm, infarction, Sheenan’s,
sickle cell

Inflammatory - neurosarcoidosis, Langerhans’s histiocytosis, Guillain Barre, Granuloma

92
Q

What are the primary causes of AVP deficiency - Cranial DI?

A

genetic:
DIMOAD (wolfram syndrome)
Autosomal dominant
Rarely autosomal recessive

developmental:
septo-optic dysplasia

93
Q

What are the familial causes of nephrogenic DI?

A

Familial – rare
X-linked – V2 receptor defect
Autosomal - aquaporin 2 defect
Less common DI

94
Q

What are the acquired causes of nephrogenic DI?

A

Either reduction in medullary concentrating gradient or antagonism of effects of AVP

Osmotic diuresis (eg diabetes mellitus)
Drugs – e.g. Lithium, demeclocycline, tetracycline
Chronic renal impairment
Post obstructive nephropathy
Metabolic – hypercalcaemia/hypokalaemia
Renal infiltration – e.g amyloid

95
Q

What is the management for AVP defiency (Cranial DI)?

A

treat any underlying condition

desmopressin – high activity at V2 receptor

tablets 100-600 micrograms/day
Nasal spray 10-20 micrograms/day
Injection 1-2 micrograms/day

96
Q

Management of Nephrogenic DI?

A

try and avoid precipitating drugs

congenital DI - very difficult
free access to water
very high dose desmopressin

97
Q

Why is diabetes a public health issue?

A

Mortality – common underlying cause of death, under-reported on death certificates

Disability – blindness, renal failure, amputation (neuropathy and peripheral vascular disease)

Co-morbidity – other physical and mental health conditions (eg obesity, depression)

Reduced quality of life – chronic condition; long term self management and monitoring

98
Q

Why is type 2 diabetes a public health issue?

A

1) Increasing in prevalence and affecting younger age groups

2) Lack of effective global, national or local policy that has influenced trends in population obesity and sedentary lifestyles that are driving the global “epidemic” of type 2 diabetes

3) Major inequalities in prevalence and outcomes with higher prevalence in BAME communities and poorer outcomes in deprived communities

99
Q

Number of people in the UK with diabetes?

A

3.8m

100
Q

Type 2 diabetes cost and prevalence

A

£8.8bn anually for the NHS
90% of people are Type 2 diabetics

101
Q

What does diabetes prevalence depend on?

A

Primary prevention: Incidence of condition decreases
Secondary prevention: % of incident cases diagnosed increases
Tertiary prevention: Survival from diagnosis increases

102
Q

Relative risk of Diabates and BMI

A

Very positive correlation

103
Q

How can we reduce the risk of type 2 diabetes?

A

identifying people at risk of diabetes
preventing diabetes (“Primary” prevention)
diagnosing diabetes earlier (“Secondary” prevention)
effective management and supporting self-management (“Tertiary” prevention)

104
Q

How can we identify who is at risk?

A

Lifestyle and environmental factors that increase risk of diabetes:

Sedentary job, sedentary leisure activities

Diet high in calorie dense foods/low in fruit and vegetables, pulses and wholegrain

“Obesogenic” environment

105
Q

What is an obesogenic environment?

A

Physical environment: eg TV remote controls, lifts, “car culture”

Economic environment: eg cheap TV watching, expensive fruit and veg

Sociocultural environment: eg safety fears, family eating patterns

106
Q

What are the mechanisms that maintain your obesity?

A

Physical/physiological - more weight = more difficult to exercise (arthritis, stress incontinence) and dieting -> metabolic response

Psychological - low self-esteem and guilt, comfort eating

Socioeconomic - reduced opportunities employment, relationships, social mobility

107
Q

What are known risk factors that may already be in a clinical record?

A

Age, sex, ethnicity, family history
Weight, BMI, waist circumference
History of gestational diabetes
Hypertension or vascular disease
Impaired Glucose Tolerance (IGT) or Impaired Fasting Glucose (IFG)

108
Q

What are some currently available screening tests?

A

HbA1c
Random capillary blood glucose
Random venous blood glucose
Fasting venous blood glucose
Oral glucose tolerance test (venous blood glucose 2 hours after oral glucose load

109
Q

What is the diagnostic range for IGT?

A

7.8 – 11.0 mmol/l

110
Q

What is the diagnostic range for IFG?

A

6.1 – 6.9 mmol/l

111
Q

What is the Diagnostic threshold for diabetes (WHO criteria)?

A

FBG ≥ 7.0 or 2 hr Glu ≥ 11.1 mmol/l

112
Q

What do effective interventions require?

A

Sustained increase in physical activity
Sustained change in diet
Sustained weight loss

113
Q

NICE changing guidelines 2012

A

PRIORITISE interventions for those with HbA1c = 44–47 mmol/mol OR fasting plasma glucose 6.5–6.9 mmol/l

use metformin if BMI >35 + HbA1c increasing OR lifestyle intervention not possible + HbA1c increasing

114
Q

What are some ways we can prevent type 2 diabetes?

A

Focus on ethnic minority and socio-economically deprived communities at increased risk

Focus on culturally appropriate interventions (for both diet and activity)

115
Q

3 ways of diagnosing diabetes earlier

A

Raising awareness of diabetes and possible symptoms in the community

Raising awareness of diabetes and possible symptoms in health professionals

Using clinical records to identify those at risk and/or using blood tests to screen before symptoms develop

116
Q

How can we screen for type 2 diabetes?

A

Current practice is to screen as part of CHD prevention (NHS Health Check – every 5 yrs from 40 to 74yrs)

Screening at review of hypertension management

Other risk groups MAY be screened
30% of adult at risk population may have blood glucose measurement even without systematic screening

117
Q

Why is NHS England investing in type 2 diabetes prevention?

A

Trials show that changes in diet, weight loss and increased physical activity reduces risk of progression from impaired glucose tolerance

Pilot programme suggests it is feasible to identify high risk individuals who would benefit from lifestyle change by screening so they can be offered interventions

118
Q

How is the NHS investing in type 2 diabetes prevention?

A

“Healthier You: The NHS Diabetes Prevention Programme”

Programme of lifestyle education, weight loss support, and group physical exercise

From 2016, 20,000 places available in 27 areas (including Sheffield)

National roll out by 2020, with 100,000 referrals available annually

119
Q

How do we support self care for diabetes?

A

Self monitoring – helpful for some, particularly if on insulin, but not all

Diet - Support for changing eating patterns
Exercise - Support for increasing physical activity

Drugs - Support for taking medication
Education – professionals/expert patients

Peer support – Health Champions/ Health Trainers

120
Q

What are the presenting features of diabetes?

A

Thirst -osmotic activation of hypothalamus, ongoing all the time and several times a night

Polyuria -osmotic diuresis

Weight loss and fatigue -lipid and muscle loss due to unrestrained gluconeogenesis

Hunger- Lack of useable energy source

Pruritis vulvae and balanitis -Vaginal candidiasis

Chest / skin infections

Blurred vision - Altered acuity due to uptake of glucose/water into lens - more water in the lens – more glucose in lens drags more water in lens gets thicker – during the day itll get worse

121
Q

What are the suggestive features of type 1 diabetes?

A

Onset in childhood / adolescence
Lean body habitus – more likely in lean people
Acute onset of osmotic symptoms
Prone to ketoacidosis
High levels of islet autoantibodies
Autoimmune disease
IN type 1 diabetes – symptoms are quite acute
Get older risk goes down but not 0
More aggressive in younger people

122
Q

Why can type 1 diabetes occur at any age?

A

Can occur at any age, the spectrum of presentation depends on the rate of b-cell destruction

123
Q

What are the clinical features of newly diagnosed type 1 diabetes?

A

Severe weight loss
Short history (weeks) of severe symptoms
Moderate or large urinary ketones

124
Q

What are the suggestive features of type 2 diabetes?

A

Usually presents in over-30s
Onset is gradual
FH is often positive
Almost 100% concordance in identical twins
Diet, exercise and oral medication can often control hyperglycaemia; insulin may be required later in the disease
Genetic propensity larger in type 2 then type 1
Parents usually have type 2

125
Q

What is the commonest age of diagnosis of type 1 diabetes?

A

Commonest age at diagnosis, 5-15y, but can occur at any age

Relatively rare (prevalence of 3/1000 among children and adolescents)

~370,000 in the UK

126
Q

Is there a genetic component in type 1 diabetes?

A

Offspring of affected fathers are more unwell than those of affected mothers, with longer duration of symptoms, more than twice as likely to present in ketoacidosis.

127
Q

What are the 4 different antibodies we test for for type 1 diabetes?

A

Anti GAD
Pancreatic islet cell Ab
Islet antigen-2 Ab
ZnT8

128
Q

What happens in fat metabolism?

A

Reduced insulin leads to fat breakdown and formation of glycerol (a gluconeogenic precursor) and free fatty acids - fat breaks down into glucose

129
Q

What happens to the free fatty acids?

A

Impair glucose uptake
Are transported to the liver, providing ‘energy’ for gluconeogensis
Are oxidised to form ketone bodies (beta hydroxy butyrate, acetoacetate and acetone)
Ketone bodies - acidotic - makes you unwell

130
Q

What happens in ketoacidosis?

A

Absence of insulin and rising counterregulatory hormones leads to increasing hyperglycaemia and rising ketones

Glucose and ketones escape in the urine but lead to an osmotic diuresis and falling circulating blood volume

Ketones (weak organic acids) cause anorexia and vomiting

Vicious circle of increasing dehydration, hyperglycaemia and increasing acidosis eventually lead to circulatory collapse and death

131
Q

What is the definition of diabetic ketoacidosis?

A

Hyperglycaemia (plasma glucose usually <50 mmol/l)
Raised plasma ketones (urine ketones > 2+)
Metabolic acidosis – plasma bicarbonate < 15 mmol/l

Need all 3 of these
More common in type 2

132
Q

What are the causes of DKA?

A

Intercurrent illness
-infection
-myocardial infarct

Treatment errors – stop/reduce insulin dose

Previously undiagnosed diabetes

Unknown

133
Q

What happens in diabetic ketoacidosis as there is not enough insulin?

A

Glycogen gets broken down in the liver
Muscle breakdown is not so bad it releases some AA and is converted to glucose
Glucose and ketones circulate in bloodstream

134
Q

Symptoms of DKA

A

develop over days
polyuria and polydipsia
nausea and vomiting
weight loss
weakness
abdominal pain (confused with surgical abdomen)
Drowsiness / confusion

135
Q

What are the signs of DKA

A

hyperventilation (Kussmaul breathing)
dehydration (average fluid loss 5-6 litres)
hypotension
Tachycardia
coma

136
Q

What is the biochemical diagnosis?

A

hyperglycaemia (<50 mmol/l)
HCO3- <15 mmol/l
urea and creatinine - raised due to pre-renal failure
urinary ketones dipstix >2+ ketones
blood ketones >3.0

137
Q

Why is potassium homeostasis important for DKA?

A

K+ – high on presentation despite total body K+ deficit (due to acute shift of K out of cell with acidosis), subsequently fall with insulin
and rehydration, anticipate fall in K+

High potassium or low potassium can kill you due to arrhythmias either way

138
Q

What is the management of DKA?

A

rehydration (3L first 3 hrs)

insulin (inhibits lipolysis, ketogenesis, acidosis, reduces hepatic glucose production, increase tissue glucose uptake)

replacement of electrolytes (K+)

treat underlying cause

Treatment must be started without delay

Follow DKA protocol in hospital

139
Q

What are the possible complications of DKA?

A

cerebral oedema (deterioration in conscious level) - As we get older brains shrink a bit – too much fluid too quickly causes CO as brains still big not much space between brain and skull – could cause death
- children more at risk

adult respiratory distress syndrome

thromboembolism – venous and arterial - check signs for DVT or PE

aspiration pneumonia (in drowsy/comatose patients)

death

140
Q

Whats the percentage of people in the UK that will develop diabetic nephropathy?

A

CV mortality with no nephropathy x2, but with nephropathy x30
Those with nephropathy tend to develop proliferative retinopathy and severe neuropathy with major effect on quality of life

141
Q

What is the treatment of Type 1 diabetes?

A

To restore the physiology of the beta cell:
Insulin treatment -
Twice daily mixture of short/medium acting insulin
Basal bolus, (once or twice daily medium acting insulin plus pre meal quick acting insulin)

Ability to judge CHO intake
Awareness of blood glucose lowering effect of exercise

142
Q

Why is the treatment of type 1 diabetes not perfect?

A

Injecting isulin in subcutaneous tissue – doesn’t go straight into bloodstream
Trying to mimic normal physiology but its not perfect

143
Q

Symptoms for lack of insulin?

A

Shaking
Fast heartbeat
Dizziness
Impaired vision
Hunger
Irritable

144
Q

How do Inappropriately high insulin levels confer a high risk of hypoglycaemia?

A

Acute deprivation of glucose within the brain leads to cerebral dysfunction (loss of concentration, confusion, coma)

145
Q

What are the physiological defenses to hypoglycaemia?

A

Release of glucagon, adrenaline
Symptoms of
Sweating, tremor, palpitations (autonomic activation)
Loss of concentration, ‘hunger’
may be overwhelmed by the glucose lowering effect of insulin

146
Q

Hypoglycaemia physiology

A

Glucose level:
4.6mM - inhibition of insulin secretion
3.8mM - counter-regulatory hormone release (glucagon and adrenaline)
3.8-2.8mM - autonomic symptoms sweating, tremor, palpitations
<2.8mM - neuroglycopenic symptoms confusion, drowsiness, altered behaviour, speech difficulty, incoordination
<1.5mM - severe neuroglycopenic convulsions, coma, focal neurological deficit ie hemiparesis

147
Q

What is the level you want your HbA1c to be for good diabetes control?

A

8.1 - 9.6 mmol/l

148
Q

What is the dilemma for those with type 1 diabetes?

A

Setting higher glucose targets will reduce the risk of hypoglycaemia but increase the risk of diabetic complications

Setting lower glucose targets will reduce the risk of complications but increase the risk of hypoglycaemia

149
Q

What are the Factors making it difficult for people with diabetes to sustain effective self management ?

A

Risk of hypoglycaemia
Too arduous a treatment
Risk of weight gain
Interference with lifestyle
Lack of sufficient training from diabetes teams

150
Q

What is the commonest type of monogenic diabetes?

A

Maturity-onset diabetes of the young- MODY

151
Q

What are the features of MODY?

A

Commonest type of monogenic diabetes (~1% diabetes)
Diagnosed <25y
Autosomal dominant
Non-insulin dependent
Single gene defect altering beta cell function
Tend to be non-obese
Strong family history
Diagnosed at young age
Tend to look like type 1 but don’t need insulin
Hepatic nuclear factors that alter insulin production
Can use sulphonylurea

152
Q

What is GCK?

A

Glucokinase gene

153
Q

What happens in a GCK mutation?

A

MODY
GCK is the glucose-sensor of beta cells, rate determining step in glucose metabolism, controlling the release of insulin

Higher set point, but still tight glycaemic control

Mild diabetes, no treatment required

Need glucokinase to get insulin release
Part of chain making glucose into glucose 6 phosphate
Different threshold – run slightly higher glucose levels than normal

154
Q

What is MODY typically misdiagnosed as?

A

Type 1
Young onset Type 2
MODY has parent affected W

155
Q

Which patients might be MODY?

A

Parent affected with diabetes
Absence of islet autoantibodies
Sensitive to sulphonylurea
Don’t tend to produce ketones
End up with ketones with absolute deficiency of insulin
Some circulating ketone there will be some glucose getting to muscles so don’t lead to fat breakdown which lead to ketosis

156
Q

Is there evidence that MODY patients might have evidence of non- insulin dependence?

A

Good control on low dose insulin
No ketosis
Measurable C-peptide

157
Q

Which transcription factor can cause MODY?

A

Hepatic nuclear factor (HNF) mutations alter insulin secretion, reduce beta cell proliferation

158
Q

What happens in HNF1A mutation (MODY 3)?

A

Very sensitive to sulphonylurea treatment (tablet), so often do not need insulin (~80%)

159
Q

What happens in HNF4A mutation (MODY 1)?

A

FH, young age of onset, non-obese, Sus, AND
Macrosomia (>4.4kg at birth)
Neonatal hypoglycaemia

160
Q

What is C-peptide?

A

Not present in synthetic insulin

C-peptide longer half-life, 30 vs 3 mins

In Type 1 diabetes C-peptide is negative within 5 years (due to complete autoimmune beta cell destruction)

Type 2 and MODY C-peptide persists

161
Q

Why do we routinely measure c peptide levels?

A

Routinely measure c peptide levels
Pro insulin – insulin + c peptide – measure this
Find sig levels of this know theyre making their own insulin
Type 2 producing some of there own but not type 1

162
Q

Whats permanent neonatal diabetes?

A

Diagnosed <6 months
Mutations encode Kir6.2 and SUR1 subunits of the beta cell ATP sensitive potassium channel

Rising ATP closes the channel as a result of hyperglycaemia, depolarising the membrane and insulin is secreted

Mutations prevent closure of the channel, and thus beta cells unable to secrete insulin

Sulphonylureas close the KATP channel

163
Q

Permanent neonatal diabetes physiology

A

Need glucose entering beta cell – converted by gluco kinase into gluco 6 phosphate which leads to increased levels of ATP – closes ATP DEPENDENT channel and depolarises membrane – leads to calcium entering the beta cell which leads to the secretion of insulin
Cant close channel don’t release insulin as easily and end up with diabetes
Give them drug that does close the channel

164
Q

What is Maternally inherited diabetes and deafness (MIDD)?

A

Mutation in mitochondrial DNA
Loss of beta cell mass
Similar presentation to Type 2
Wide phenotype

165
Q

What is Lipodystrophy?

A

Selective loss of adipose tissue
Associated with insulin resistance, dyslipidaemia, hepatatic steatosis, hyperandrogenism, PCOS

need vast amounts of insulin – look normal – look hench – need huge amounts of insulin for glucose to be normal – fat not in muscles everywhere else

166
Q

What is an acute inflammatory disease of the exocrine pancreas?

A

usually transient hyperglycaemia, due to increased glucagon secretion

167
Q

Chronic pancreatitis - inflammatory

A

Alcohol – leading cause in uk
Alters secretions, formation of proteinaceous plugs that block ducts and act as a foci
for calculi formation
Stop alcohol, treat with insulin

168
Q

Things that affect the pancreas might…

A

Effect exocrine function of pancreas could effect endocrine system and beta cells
Destroy part of exocrine function lead to thick secretions which blocks ducts and cant get insulin release like normal – tell these people to stop drinking

169
Q

What is hereditary Haemochromatosis?

A

Autosomal recessive – triad of cirrhosis, diabetes and bronzed hyperpigmentation
Excess iron deposited in liver, pancreas, pituitary, heart and parathyroids
Most need insulin

170
Q

What happens in deposition?

A

Amyloidosis / cystinosis
Amyloidosis – anything that gets deposited and gets built up in the organs leads to malfunction – this and cystinosis very rare

Iron can be deposited anywhere leading to heart arrhythmias and pituitary dysfunction – if deposited with pancreas leads to stopping of normal insulin secretion

171
Q

What is pancreatic neoplasia?

A

Common cause of cancer death
4-5 resections per week at STH
Require sc insulin
Prone to hypoglycaemia due to loss of glucagon function
Frequent small meals, enzyme replacement
Insulin pumps
Common cause of diabetes in amongst 5 percent

172
Q

Pancreas

A

Pancreas sits inside the c shape of the duodenum – has head and tail – better to have cancer in the tail than head as head is near major blood vessels
If you take pancreas out no beta cells
Cant eat normally as they don’t produce digestive enzymes – have to have enzyme replacement on all their food

173
Q

Cystic fibrosis

A

Cystic fibrosis transmembrane conductance regulator (CFTR) gene located on chromosome 7q22
Regulates chloride secretion
Viscous secretions lead to duct obstruction, and fibrosis
Incidence is 25 to 50% in adults
Ketoacidosis rare
Insulin treatment required
CF survival better, so microvascular complications increasing

174
Q

Acromegaly and diabetes

A

Excessive secretion of growth hormone
Similar to Type 2
Insulin resistance rises, impairing insulin action in liver and peripheral tissues
Acromgealy to much growth hormone – increases your insulin resistance
Insulin resistance increases then need to produce more insulin to get glucose back down to normal
Sometimes if that resistance is too much then end up with glucose too high and body cant produce enough insulin

175
Q

Cushings syndrome and diabetes

A

Increased insulin resistance, reduced glucose uptake into peripheral tissues
Hepatic glucose production increased through stimulation of gluconeogenesis via increased substrates (proteolysis and lipolysis)
Far too much glucocorticoids
If you can cut out tumour then you can remove glucocorticoid excess – sometimes caused by tumour

176
Q

What are some drugs that induce diabetes?

A

Glucocorticoids increase insulin resistance
Thiazides / protease inhibitors (HIV) / antipsychotics – mechanisms not clearly understood
Steroids most important group that increase insulin resistance
Don’t help uptake glucose into muscles
Less insulin induced vasodilatation in muscle leading to reduced glucose delivery to muscle beds, reducing opportunity of muscle to clear glucose from the blood

177
Q

Metformin

A

Increases body sensitivity to insulin

Endocrinology (17 decks)

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