Session 8 (1) - Diabetes Mellitus

Question 1

Describe the condition of Diabetes Mellitus

Answer 1

Diabetes Mellitus is a group of metabolic disorders characterised my chronic hyperglycaemia due to insulin deficiency, insulin resistance or both. There are two major types of the disease, clearly distinguished by their epidemiology and probable causation, but not always so easily separated clinically

Question 2

Describe typical presentation of someone with type 1 diabetes

Answer 2

A lean young person with a recent history of viral infection who present a triad of symptoms - Polyuria, Polydispsia and weight loss
Hyperglycaemia
Glycosuria
Keto acidocis

Question 3

What causes B cell destruction in type 1 diabetes?

Answer 3

A genetic predisposition to the type 1 diabetes interacts with an environmental trigger to produce immune activation.

Question 4

What progressively destroys B cells in type 1 diabetes?

Answer 4

killer lymphocytes and macrophages and antibodies.

Question 5

Describe Polyuria, and what causes it?

Answer 5

Excess urine production.

Not all glucose reabsorbed into blood from kidney due to hyperglycemia. Extra glucose in nephron places extra osmotic load on it, so less water reabsorbed in order to maintain osmotic pressure. More wee.

Question 6

What is polydipsia, and what causes it?

Answer 6

thirst and drinking a lot, due to polyuria. Caused by osmotic effects of glucose on thirst centres.

Question 7

What causes weight loss in type 1 diabetes?

Answer 7

Fat and protein are metabolised because insulin is absent.

Question 8

Name three metabolic effects of a lack of insulin

Answer 8

Decreased uptake of glucose into adipose tissue and skeletal muscle
Decreased storage of glucose as glycogen in muscle and liver
Increase gluconeogenesis

Question 9

How can type 1 diabetes be diagnosed?

Answer 9

Via measurement of blood glucose levels, via urine or blood

Question 10

What will happen to an individual with type 1 diabetes if it is not dealt with immediately?

Answer 10

Life threatening keto acidocis

Question 11

In addition to triad of symptoms, what are type 2 diabetics most likely to complain of?

Answer 11

Lack of energy
Persistent infections (thrush, feet)
Slow healing of minor skin damage
Visual problems

Question 12

List the four main differences between type 1 and type 2 diabetes

Answer 12

Type 1 –> Type 2

1) Commonest in young
2) Affects a large number of older individuals

1) Characterised by progressive loss of all or most of pancreatic B cells
2) Characterized by slow progressive loss of B cells, but with disorders of insulin secretion and tissue resistance

1) Rapidly fatal if not treated
2) May be present for a long time before diagnosis

1) Must be treated with insulin
2) May not initially need treatment with insulin, but all do eventually

Question 13

Describe typical pattern of presentation of type 1 diabetes

Answer 13

People may have relevant HLA markers and autoantibodies, but no G or I abnormalities

May then developed impaired glucose tolerance, then diabetes, before becoming totally insulin dependant

Question 14

Describe typical pattern of presentation of type 2 diabetes

Answer 14

Insulin resistance (obesity), then as insulin production fails develop impaired glucose tolerance.

Finally develop diabetes, but can be controlled by diet, then tablets, then insulin.

May eventually lose all insulin production.

Question 15

Give three blood tests with which diabetes can be diagnosed if triad of symptoms present

Answer 15

A random venous plasma glucose concentration > 11.1 mmol/l

A fasting plasma glucose concentration > 7.0 mmol/l (whole blood > 6.1 mmol/l

Plasma glucose concentration > 11.1 mmol/l 2 hours after 75g anhydrous glucose in a oral glucose tolerance test

Question 16

What happens if no symptoms present, but glucose plasma concentration high?

Why is it important to not misdiagnose?

Answer 16

At least one additional glucose test result on another day.

A diagnosis of diabetes has important legal and medical implications for the patient

Question 17

Explain sequence of events leading to diabetic ketoacidocis

Answer 17

High rate of B-oxidation of fats + Low insulin/anti-insulin leads to production of ketone bodies

Ketones acidic, so build up causes ketoacidocis

Question 18

How can high levels of ketones be diagnosed? (2)

Answer 18

Ketones in urine

Acetone on patients breath

Question 19

Give 6 symptoms of ketoacidocis

Answer 19

Prostration, hyperventilation, nausea, vomiting, dehydration`` and abdominal pain

Question 20

How can a diabetic become hypoglycaemic?

Answer 20

From insulin or suphnoylurea treatment, overdose or by missing a meal

Question 21

What are the symptoms of hypoglycaemia?

Answer 21

Sweating, tremor, confusion, drowsiness, coma, death

Question 22

What is hyperglycaemia?

Answer 22

Blood glucose >10mmol/l

Question 23

What do the symptoms of hyerglycaemia include?

Answer 23

polyuria, polydipsia, weight loss, fatigue, poor wound healing.
Glycosylation of plasma proteins, affecting function.

Question 24

How are type 1 diabetes and some cases of type 2 managed?

Answer 24

Insulin injections

Question 25

Why can’t insulin be ingested?

Answer 25

Peptide hormone that would be digested

Question 26

Give four ways other than insulin that type 1 diabetes has to be managed

Answer 26

Patients educated to treat themselves at appropriate times and with appropriate doses

Dietary management

Regular exercise

Frequent blood glucose measurement

Question 27

When must treatment of type 1 diabetes change?

Answer 27

When patients has infection or suffered trauma, insulin must be increased or risk ketoacidocis.

DUE TO EFFECTS OF ADRENALINE/CORTISOL WHICH SUPPRESS INSULIN

Question 28

Give two ways that type 2 diabetes can be managed

Answer 28

Diet or oral hypoglycaemic drugs

Question 29

Name two types of hypoglycaemic drugs and their effects

Answer 29

Sulphylonureas increase cell sensitivity to insulin and increase insulin release from remaining B cells.

Metforming reduces gluconeogenesis

Question 30

Why is persistent hyperglycaemia a problem for peripheral nerves, the eye and the kidney?

Answer 30

Because uptake of glucose to these tissues is determined by extracellular glucose concentration. Glucose causes damage via variety of mechanisms.

Question 31

What effect does high glucose have on glucose dependent tissues, and what is the reaction involved? What enzyme catalyses, and what reaction is it similar to?

Answer 31

Glucose + NADPH + H+ –> Sorbitol + NADP+
Catalysed by aldose reductase
Depletes NADPH, leading to increased disulphide bond formation in cellular proteins, altering structure.
Similar to conversion of galactose to galacticol in galactosaemia.
Accumulation of sorbitol also causes osmotic damage.

Question 32

What is glycosylation, and how can it be used in diagnosis?

Answer 32

Glucose reacts with free amino groups in proteins to form stable covalent linkages. Plasma proteins, such as haemoglobin, are glycosylated. This is used in HbA1c test.

Question 33

How does the HbA1c test work?

Answer 33

Glucose in blood reacts with terminal valine of the haemoglobin molecule to produce HbA1c.
% HbA1c good indicator of how effect effective glucose control. Give average blood glucose over past 2-3 months by measuring % haemoglobin glycosylated.

Question 34

What are the three macrovascular complications of chronic hyperglycaemia?

Answer 34

Increased risk of stroke
Increased risk of myocardial infarction
Poor circulation to the periphery - particularly the feet

Question 35

List four microvascular complications of chronic hyperglcaemia

Answer 35

Diabetic eye disease
Diabetic kidney disease
Diabetic neuropathy
Diabetic feet

Question 36

Briefly describe diabetic eye disease cause

Answer 36

damage to blood vessels in the retina, which can lead to blindness

Question 37

Briefly describe diabetic kidney disease

Answer 37

poor blood supply because of change in kidney blood vessels, or damage from infections of the urinary tract

Question 38

Briefly describe diabetic neuropathy

Answer 38

Damage to the peripheral nerves which directly absorb glucose causing changes of or loss of sensation, and changes due to alteration in the function of the autonomic nervous system

Question 39

Briefly describe diabetic feet

Answer 39

Poor blood supply, damage to nerves and increase risk of infection all sum up to make the feet of a diabetic vulnerable