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LS1 Metabolism > Diabetes > Flashcards

Diabetes Flashcards

1
Q

How is it thought that the pancreatic beta cells are progressively lost in type 1 diabetes?

A

A genetic disposition interacts with an environmental trigger to cause auto-immune destruction (killer lymphocytes, macrophages and antibodies) of the beta cells.

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2
Q

What genetic markers is the genetic predisposition in type 1 diabetes associated with?

A

HLA DR3 and HLA DR4

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3
Q

Why is there a suspected viral link to type 1 diabetes?

A

There is strong seasonal variation in onset.

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4
Q

In type 1 diabetes the classic presentation is a young person with a recent viral infection and which triad of symptoms?

A
  1. Polyuria
  2. Polydypsia
  3. Weight loss
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5
Q

Why is Polyuria a symptom of diabetes?

A

In diabetic individuals their kidneys are filtering higher than normal levels of glucose. This is normally fully reabsorbed in the isoosmotic proximal tubules of nephrons. At these high glucose levels, however, not all glucose is reabsorbed. This puts an osmotic pressure on the nephrons. The tubules reabsorb less water in order to maintain the isoosmotic character of the tubules, causing more water and the glucose to be lost in the urine.

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6
Q

Why do untreated type 1 diabetics feel thirsty?

A
  1. They are losing a lot of water in their urine.

2. The osmotic effects of gluose on the first centres.

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7
Q

Why do untreated type 1 diabetics experience weight loss?

A

The lack of insulin means their bodies cannot utilise as much glucose from the blood and therefore metabolise fat and protein stores.

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8
Q

What is the affect of the lack of insulin on skeletal muscle, adipose tissue and the liver?

A
  1. Skeletal muscle - decreased uptake of glucose by the muscle and decreased storage of glucose as glycogen
  2. Adipose tissue - decreased uptake of glucose
  3. Liver - decreased storage of glucose as glycogen and increased gluconeogenesis
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9
Q

If untreated what life-threatening crisis can type 1 diabetics experience?

A

Diabetic ketoacidosis

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10
Q

How do type 2 diabetics present?

A

Typically older and overweight.
Tend to retain approx. 50% of beta-cells at diagnosis.
Insidious onset, can have triad of symptoms but often variable symptoms: tiredness, persistent infections (typically thrush of genitalia), slow healing minor skin damage or visual problems.

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11
Q

Why might a type 1 diabetic suddenly have to increase their insulin injections?

A

Due to the effects of infection or trauma.

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12
Q

What does a type 1 diabetic treatment regime compose of?

A

Insulin injections (varying time courses of action)
Dietary management
Regular exercise

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13
Q

How can type 2 diabetes be managed?

A
  1. Lifestyle factors: diet and exercise
  2. Oral hypoglycaemic drugs:
    Metformin - reduces gluconogenesis
    Sulfonylureases - increase insulin secretion from beta cell and decrease insulin resistance
  3. Insulin injections
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14
Q

What are macrovascular complication of diabetes?

A

Increased risk of stroke
Increased risk of MI
Poor circulation to the periphery - especially the feet

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15
Q

What are microvascular complications of diabetes?

A

Diabetic eye disease
Diabetic kidney disease
Diabetic feet
Diabetic neuropathy

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16
Q

Explain what diabetic eye disease is

A

Problems to vision caused by diabetes. The most important problem is retinopathy - damage to the small blood vessels in the eye. Damaged blood vessels can leak protein exudates onto the retina and can rupture causing bleeding in the eye. Proliferation reti opathy can also occur, when new blood vessel are formed which are very weak and prone to bleeding. Glaucoma can also happen as high levels of glucose change the osmotic potential of the lens and more water flow in. Cataracts can also develop.

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17
Q

Explain what diabetic kidney disease (Nephropathy) is

A

The kidney is affected by:

  1. Damage to the glomeruli
  2. Poor blood supply due to changes in kidney blood vessels
  3. Damage caused by infections of the urinary tract - which are more common in diabetes
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18
Q

What is an early sign of nephropathy?

A

An increase in the amount of protein in the urine (microalbuminuria).

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19
Q

What is diabetic neuropathy?

A

In diabetes damage to the peritheral nerves occurs by a number of ways. This has a variety of effects: loss of sensation, changes to sensation and changed due to the alteration of the function of the autonomic nervous system.

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20
Q

What is meant by the term ‘diabetic feet’?

A

Damage to the nerve supply, blood supply and increased risk of infection make the feet of diabetics particularly vulnerable. In the past loss of feet due to gangrene was not uncommon. Diabetics need to take care and keep their feet in good condition.

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21
Q

Clinical features of type 1 diabetes

A 
Childhood
Sudden onset
Severe symptoms
Recent weight loss
Usually lean
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22
Q

Biochemical features of type 1 diabetes

A

Spontaneous ketosis
No C-peptide
Markers for auto-immunity

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23
Q

Clinical features of type 2 diabetes

A 
Middle age
Gradual onset
May be few acute symptoms, but long-term chronic effects can be severe
Often no weight loss
Usually obese
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24
Q

Biochemical features of type 2 diabetes

A

Non-ketotic
C-peptide detectable
No markers for auto-immunity

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25
Q

Explain the clinical consequences of severe protein deficiency in children.

A

Protein deficiency results in an inadequate intake of essential amino acids. This leads to a reduced rate of protein synthesis and a reduced rate of synthesis of other nitrogen containing compounds. The signs and symptoms could include:

  1. Growth failure- height and weight below normal
  2. Impaired physical development (tiredness, weakness and poor exercise tolerance due to reduced muscle mass)
  3. Impaired mental developmental (low IQ)
  4. Negative nitrogen balance - Nin
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26
Q

What are the group of metabolic disorders. diabetes mellitis, characterised by?

A

Chronic hyperglycaemia due to insulin deficiency, insulin resistance or both

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27
Q

What are the characteristics of Type 1 diabetes?

A

Commonest onset in young
Characterised by the progressive loss of beta-cells of all or most of the beta-cells
Rapidly fatal if not treated
MUST be treated with insulin

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28
Q

What are the characteristics of Type 2 diabetes?

A

Affects a large number of usually older individuals
Characterised by SLOW progressive loss of beta-cells along with disorders of insulin secretion and tissue resistance to insulin.
May be present a long time before diagnosis
May not initially need treatment with insulin but sufferers usually progress to a state where they eventually do

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29
Q

Can people who will develop diabetes Type 1 be identified before they develop glucose or insulin abnormalities and finally become insulin dependent?

A

Yes - people can be found with the relevant human leucocyte antigen (HLA) markers and autoantibodies who MAY go on to develop Type 1 diabetes

30
Q

Can people who will go on to develop type 2 diabetes be identified at early stages?

A

Yes - people can be found with insulin resistance, then as insulin production fails they develop impaired glucose tolerance. Finally they will develop diabetes which can be initially managed with diet, then tablets and then insulin (if the process occurs long enough for them to lose all insulin production)

31
Q

What percentage of diabetics have type 2?

A

90%

32
Q

Approximately how many people in the UK have diabetes?

A

3.9 million

33
Q

How many people in the UK are believed to have undiagnosed diabetes?

A

0.59 million

34
Q

Which is the most common age group for diagnosis of Type 1 diabetes?

A

Teenage years. Age-related rate is otherwise similar up to old age

35
Q

What is glycosuria?

A

The presence of glucose in the urine

36
Q

Why are large amounts of ketones produced in untreated type 1 diabetes?

A
  1. High rates of beta-oxidation of fats in the liver

2. Low insulin/ anti-insulin ratio (affects the conversion of HMG-CoA to acetoacetate (ketone bodies))

37
Q

Name three ketone bodies produced in high rates in untreated Type 1 diabetes

A

Acetoacetate
Acetone
Beta-hydroxybutyrate

38
Q

What molecule can be smelt as a pear drop smell on a patient’s breath due to ketosis?

A

Acetone - volatile ketone body

39
Q

Why does the high rates of ketone bodies produced in untreated Type 1 diabetes cause keto-acidosis?

A

Acetoacetate and beta-hydroxybutyrate are relatively strong acids and therefore high concentration of them cause metabolic acidosis.

40
Q

List some diseases which can cause metabolic acidosis?

A

Type 1 diabetes - keto-acidosis
Inborn errors of the metabolism
Chronic kidney failure

41
Q

The causes of metabolic acidosis can be divided into two main categories. What are they?

A

Increased production of acidic substrates

Kidneys not removing enough acid from the body

42
Q

What are the clinical features of keto-acidosis?

A 
Prostration
Hyperventilation
Nausea
Vomiting
Dehydration
Abdominal pain
43
Q

Why is important to test for ketones when assessing diabetic control?

A

Keto-acidosis is a very dangerous condition, if a diabetics control is poor enough that the concentration of ketones in the blood has exceeded the renal threshold and ketonuria occured - there needs to be some rapid changes to treatment

44
Q

Why does ketoacidosis cause hyperventilation?

A

Carbonic acid equilibrium in blood means that the higher the H+ concentration the more the equilibrium favours the production of CO2 (in attempt to buffer blood acidity). Hyperventilation occurs to lower this blood CO2 concentration by removing more CO2 from the alveoli to the ambient air and consequently removing CO2 from blood as the ppCO2 in alveoli are roughly in equilibrium with the CO2 concentration in blood.

45
Q

What are the potential causes of type 2 diabetes?

A

Evidence for genetic disposition and involvement of the immune system

46
Q

Diabetes is diagnosed IN THE PRESENCE OF SYMPTOMS plus one of three diagnostic tests:

A
  1. Random venous plasma glucose concentration >=11.1mmol/L
  2. Fasting plasma glucose concentration >=7.0mmol/L (whole blood >=6.1mmol/L)
  3. Plasma glucose concentration >=11.1/L 2 hours after 75g anhydrous glucose in oral glucose tolerance test (OGTT)
47
Q

If an individual has no symptoms of diabetes, how can they be diagnosed?

A

Diagnosis should not be made on a single glucose determination. At least one additional test result on another day, within a value in the diabetic range, is essential (fasting, random sample or OGTT).
If the fasting or random values are not diagnostic the OGTT should be used.

48
Q

What should a diagnosis of diabetes NEVER be made on and why?

A

Glycosuria and stick reading of a finger prick blood glucose (though these are good for screening purposes). Diagnosis should be made through glucose measurement at an appropriate laboratory, as a diagnosis has important legal and medical implications for the patient’s life

49
Q

Why are insulin injections taken at specific times, doses and formulations (long acting vs short acting)?

A

To mimic as closely as possible the behaviour of pancreatic islets in controlling glucose.

50
Q

What does BM meter stand for?

A

Boehringer Mannherim, the german pharmaceutical company (now called Roche) who first made these finger prick blood testing kits

51
Q

What do the oral hypoglycaemic drugs sulphonylureas do?

A

A class of drugs which Increase insulin release from remaining beta-cells and reduce insulin resistance

52
Q

Who does the oral hypoglycaemic drug metformin do?

A

Reduces gluconeogenesis in the liver

53
Q

What can significantly reduce the chance of an individual getting type 2 diabetes?

A

Control of diet and exercise

54
Q

Why are some tissues affected more than other by persistent hyperglycaemia?

A

Uptake of glucose in some tissues (peripheral nerves, eye, kidney) does not require insulin and is determined by extracellular glucose concentration.
Therefore during hyperglycaemia the intracellular concentration of glucose in these tissues increases and glucose is metabolised by the enzyme aldose reductase.

55
Q

What is the result of high concentrations of glucose in peripheral nerves, eye and kidney on these tissues’ metabolism?

A

Aldose reductases catalyses the reaction:
Glucose + NADPH + H+ -> Sorbitol + NADP+
This reaction depletes cellular NADPH, leading to increased disulphide bond formation of cellular proteins.

56
Q

Why does an increase in disulphide bonds and sorbitol concentration damage the cells of the eye, kidney and peripheral nerves?

A

Disulphide bonds alter the structure and function of cellular proteins.
An increase in sorbitol concentration causes osmotic damage to the cells

57
Q

What occurrence is associated with persistent hyperglycaemia and plasma proteins?

A

Non-enzymatic glycosylation

58
Q

How does non-enzymatic glycosylation occur?

A

Glucose reacts with free amino groups in proteins to form stable covalent linkages

59
Q

What does the extent of glycosylation of a plasma protein depend upon?

A

Glucose concentration

Half-life of the plasma protein

60
Q

How does glycosylation of plasma proteins affect their function?

A

It changes their net charge and 3-D structure

61
Q

How is HbA1c produced?

A

Glucose reacts with the terminal valine of the haemoglobin molecule to produce glycated haemoglobin

62
Q

Why is HbA1c a good indicator of long-term blood glucose control?

A

Red blood cells normally spend about 120 days circulating in the blood. The % HbA1c is related to the average blood glucose concentration over the preceeding 2-3 months

63
Q

What is HbA1c?

A

A glycosylated haemoglobin molecule

64
Q

What is the normal levels of HbA1c seen in healthy individuals versus poorly controlled diabetics?

A

healthy - 4-6%

poorly-controlled - can increase above 10%

65
Q

What is the most important problem in diabetic eye disease?

A

Diabetic retinopathy - damage to blood vessel in the retina which can lead to blindness

66
Q

What are the benefits of exercise for diabetics?

A
  1. Body composition changes (decreased adipose, increased muscle)
  2. Glucose tolerance improves (muscle glycogenesis increases)
  3. Insulin sensitivity of tissues increases
  4. Blood TAGs decrease (decreased VLDL&LDL and increased HDL)
  5. Blood pressure falls
67
Q

What is the function of the glucose transport protein GLUT-4 and why is this important?

A

GLUT-4 is found in skeletal muscle and adipose tissue. It is sensitive to insulin. High levels of insulin increase the uptake of glucose into these tissues by increasing the number of glucose transport proteins in the plasma membrane

68
Q

Why is the concentration of glucose in the blood kept relatively constant?

A

Some tissues have an absolute requirement for glucose and the rate of glucose uptake into these tissues is dependent on the concentration in the blood

69
Q

What is the primary abnormality in patients presenting with diabetic ketoacidosis?

A

Absolute insulin deficiency leading to ketone production

70
Q

What range of values for a fasting blood glucose test would indicate a diagnosis of Type II diabetes?

A

> 6.0mM

71
Q

What are microvacular complications associated with type 2 diabetes?

A

Retinopathy (diabetic eye disease)
Neuropathy
Diabetic feet disease
Diabetic kidney disease (nephropathy)

72
Q

An elevated concentration of which substances can cause an individual with type I diabetes to have a blood pH of 7.1?

A

Ketone bodies:
acetoacetate
beta-hydroxybutyrate
acetone

LS1 Metabolism (18 decks)

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