Biochemistry Diabetes and Hypoglycaemia Flashcards Preview

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Flashcards in Biochemistry Diabetes and Hypoglycaemia Deck (60)
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1
Q

Definition

A

A group of disorders characterised by a relative or absolute deficiency of insulin secretion and/or action leading to hyperglycaemia, disturbed metabolism of carbohydrate, fat and protein and the development of chronic complications.

2
Q

Natural History of Type 2 Diabetes

A

Altered Glucose Metabolism
IGT
Diagnosis of T2D
Progression of T2D

3
Q

Pattern of Disease

A
Rising Insulin resistance
B-cell function decrease
Insulin Resistance increasing
Post-meal glucose increasing
Fasting glucose increasing
4
Q

Before diagnosis unnoticed

A

Micro and macro vascular disease

50% beta cell dysfunction

5
Q

Beta cell dysfunction

A

A range of functional abnormalities is present:
➢ Abnormal oscillatory insulin release
➢ Increased pro-insulin levels
➢ Abnormal 2nd-phase insulin response
➢ Progressive loss of beta-cell functional mass

6
Q

Insulin Physiology

A

Peptide hormone, MW 6000

7
Q

Insulin secreted by

A

Beta-cells

Produced as pro-insulin

8
Q

Insulin structure

A

Two chains (alpha and beta) joined by two disulphide bridges

9
Q

Insulin production process

A

Proteolysis of C-peptide → equimolar amounts

10
Q

Insulin action

A

Acts by binding to specific receptors in the plasma membranes of target cells thus enhancing glucose entry into cells.

11
Q

Insulin actions on muscle

A

Increased uptake and utilisation of glucose and amino acids

Increased cell uptake of potassium, phosphate, amino acids

12
Q

Insulin actions on liver

A
  • Increased glycogen synthesis
  • Decreased liver glycogen breakdown
  • Decreased gluconeogenesis from fats and AAs
  • Increased protein synthesis
13
Q

Insulin action on adipocytes (fat cells)

A
  • Inhibits fat breakdown (reduced lipolysis)

* Increased fat synthesis

14
Q

Glucagon action

A

Increases hepatic glycogenolysis

15
Q

Adrenalin action

A

Increased glycogenolysis, increased lipolysis

16
Q

Growth hormone action

A

Increased protein synthesis
Increased lipolysis
Decreased utilisation of glucose

17
Q

Cortisol action

A

Increased gluconeogenesis + protein breakdown

Decreased glucose uptake

18
Q

Catabolic Hormones:

A

Glucagon action
Adrenalin action
Growth hormone action
Cortisol action

19
Q

Diabetes can be diagnosed in one of 4 ways:

A
  1. Random plasma glucose >11.1 mmol/L
  2. Fasting plasma glucose >7.0 mmol/L
  3. 2h plasma glucose >11.1 mmol/L during oGTT
  4. HbA1c
20
Q

Diagnostic criteria

A
  • Confirmation on a second day by any of the above methods is required unless hyperglycaemic: symptoms are present (thirst, polyuria, weight loss, infections etc.)
  • Diagnosis should not be based on samples taken during stress
21
Q

Blood glucose process

A

Whole blood 10-15% lower than plasma
Preservations not 100% effective
• Heparin/serum – loss of 0.33 mmol/L per hour
• Fluoride oxalate – loss of about 10% overnight

22
Q

OGGTT (glucose tolerance tests)

A

Used to be the ‘gold standard’ for diagnosing diabetes in UK
Dynamic function test
Baseline sample for glucose after overnight fast
75g of glucose given (Polycal)
Second sample at 120 minutes

23
Q

Haemoglobin A1c (HbA1c): Looking for

A

Insulin/glycated Hb/fructosamine

Non-enzymatic glycation of N-terminal valine of haemoglobin beta chains

24
Q

Haemoglobin A1c (HbA1c): Process

A

Non-diabetic HbA1c values vary markedly between subjects, while values in the same individual change little over time:
There may be high or low ‘glycators’
Kidney threshold for glucose

25
Q

Haemoglobin A1c (HbA1c): Expressed as

A

The percent of total haemoglobin (normal 4-6%) (20 mmol/mol – 42 mmol/mol)

26
Q

Advantages of using HbA1 c

A
  • Gives an idea of chronic glucose exposure
  • Does not reflect recent food intake or exercise
  • Reflects both fasting and post-prandial hyperglycaemia
  • Knowledge of HbA1c seems to alter behaviours
Patient Preference:
•	No need to fast
•	No need to consume glucose which can b unpalatable
•	No need to wait around for 2 hrs
Test more experience
•	Probably offset by cost of oGTT
27
Q

Circumstances in which HbA1c to diagnose diabetes

A
Young adults children (false negative) – reflects mean blood glucose over the past 2-3 months
Recent onset of symptoms of diabetes
Pregnancy
Abnormal Hb variants
Abnormal red cell survival – haemolysis
Anaemia
Polycythaemia (falsely high)
Renal impairment
Iron deficiency
28
Q

HbA1c is proportional to

A

Mean plasma glucose

29
Q

Other glycosylated proteins

A

Fructosamine

Glycosylated albumin

30
Q

Fructosamine

A
  • Mirrors glycosylation if plasma proteins
  • Indicates previous 3 weeks glycaemic exposure
  • Used pregnancy/children, patients with haemolytic anaemia
31
Q

Glycosylated Albumin

A
  • Indicates previous several days glycaemic exposure

* Not commonly used

32
Q

Self Monitoring –Pitfalls

A
Sample collection
•	Hand washing
•	Sample size
Meter use
•	Calibration
•	Cleaning
•	Follow protocol
33
Q

Monitoring for Ketosis

A

➢ Urine test strips used by patients to self monitor for ketones
➢ Recommended for Type 1 DM patients when blood glucose is >14 mmol/L
➢ Especially during “sick” days

34
Q

Looking for complications

A
Need to monitor for long-term consequences:
Renal
➢	Plasma creatinine, eGFR
➢	Urinary microalbumin
Lips
➢	Fasting lipid profile
Thyroid function test
➢	Autoimmune association IDDM
➢	May be justified especially in elderly females
35
Q

Microalbuminuria – Risk for factor

A

Nephropathy
Cardiovascular disease
Total mortality

36
Q

Microalbuminuria – Reversibility

A

Microalbuminaemia is reversible

37
Q

Adult Hypoglycaemia → Pathophysiology

A

Imbalance between factors raising and lowering blood glucose levels

38
Q

Adult Hypoglycaemia → Increase glucose via

A

Food

Counter-regulatory hormones

39
Q

Adult Hypoglycaemia →Decrease blood glucose

A

Insulin/Oral Meds

Physical Activity

40
Q

Adult Hypoglycaemia → Definition

A

Threshold for symptoms varies between individuals

Venous plasma glucose <2.5 mmol/L without symptoms during fasting

41
Q

Spectrum of hypoglycaemia

A

Paediatrics – inborn errors of metabolism
Diabetes mellitus – treatment with insulin and sulphony;ureas
Adult hypoglycaemia – in absence of diabetes

42
Q

Symptoms of hypoglycaemia

A

Are frequently non-specific, depend on the degree of hypoglycaemia, the age of the patient and how rapidly the blood glucose falls
Onset may be sudden without warning
Early recognition and intervention can prevent an emergency
1. Adrenergic
2. Neuroglycopenic

43
Q

Adrenergic symptoms

A
Sympathetic NS activation
➢	Tremor
➢	Palpitations
➢	Sweating
➢	Hunger
➢	Anxiety
➢	Nausea
44
Q

Neuroglycopenic symptoms

A
Confusion
Behavioural change
Seizures/Neurological
Tiredness, Headache
Coma
45
Q

Neuroglycopenic symptoms due to

A

Result from more gradual decline in blood glucose

Unusual to appear in patients with fasting hypoglycaemia, unless blood glucose falls below 2.2 mmol/L

46
Q

Somogyi effect and nocturnal hypo’s

A

Hypoglycaemia at night is often slept through

47
Q

Symptoms include

A

Morning headaches
Hangover feeling on wakening
Nocturnal sweating
High levels of blood glucose noted before breakfast

48
Q

Hypoglycaemia treatment

A

Glucose, monitor closely after event

Ensure sufficient CHO to restore liver glycogen stores

49
Q

Severe hypo

A

Glucagon

  • Unconscious/Unresponsive
  • Seizure
  • Uncooperative
50
Q

Classification of adult hypoglycaemia

A

Fasting

Postprandial

51
Q

Fasting

A

Under-production of glucose

Increased insulin action

52
Q

Post-prandial

A

Following gastric surgery

‘idiopathic reactive’

53
Q

Other Causes of Hypoglycaemia:

A

Underproduction of glucose
Increased insulin action
Drug induced hypoglycaemia

54
Q

Underproduction of glucose

A

Endocrine (adrenal, pituitary insufficiency
Severe liver disease
Renal Failure

55
Q

Drug induced hypoglycaemia

A
ETOH
Salicylates
Quinine
Quinidine
Pentamidine
Haloperidol
Trimethoprim and Sulfamethoxade
NSAIDS
Colchicine
Fibrates
Chloramphenicol
Ketaconazole
PAS
MAO-Is
Thalidomide
Selegeline
56
Q

Increased Insulin Action

A

Insulinoma
Non-islet cell tumours
Factitious insulin administration
Factitious sulphonylurea

57
Q

Biochemical diagnosis of Insulinomas

A

➢ Measure glucose (insulin and C-peptide) at time of symptoms. Reagent strop glucose may be unreliable
➢ Measure glucose (insulin and C=peptide) after overnight fast or more prolonged fast (48 or 72h if index of suspicion high)
➢ Sulphoulurea screen if insulin and C-peptide are elevated

58
Q

Non-Islet cell Tumours

A

➢ Rare mesenchymal tumours such as sarcoma or hepatoma
➢ Paraneoplastic release of insulin-like substances such as IGF-1 or 2
➢ Extremely poor prognosis at time of presentation
➢ Maintaining euglycaemia may be difficult outside the hospital

59
Q

Factitious insulin administration

A

➢ Hypoglycaemic symptoms
➢ Low blood glucose
➢ Elevated insulin
➢ Suppressed C-peptide (due to Exogenous insulin)
➢ Psychiatric history
➢ Often health professionals (access to insulin)

60
Q

Post-prandial hypoglycaemia

A

➢ Post-gastrectomy, there is rapid transit of glucose into the small intestine and release of hormones that stimulate (excessive) insulin secretion leading to hypoglycaemia

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