Session 8

Question 0

List the main differences between type 1 and type 2 Diabetes

Answer 0

Type 1 - early onset, insulin deficiency, autoimmune or non-autoimmune
Type 2 - insulin deficiency and insulin resistance (genetic defects of B cells or insulin action, drug induced - steroids/diuretics, haemochromatosis - bronze diabetes, iron deposited)

Question 1

Describe the condition Diabetes Mellitus

Answer 1

Hyperglycaemia (>7 mmol/L) leading to small and large vessel damage in which there is premature death from cardiovascular diseases
Inability to produce insulin due to B cell failure and/or insulin production is adequate but insulin resistance prevents insulin working effectively

Question 2

Describe and explain the typical pattern of presentation of type 1 and type 2 Diabetes

Answer 2

Polydipsia, polyuria, blurring of vision, urogenital infections (thrush)
Tiredness, weakness, lethargy, weight loss (insulin is anabolic, breaks down fat)

Question 3

Explain the sequence of events leading to ketoacidosis in the uncontrolled diabetic

Answer 3

Absolute lack of insulin –> glucose remains in blood and is not absorbed –> body thinks there is no glucose –> uses ketones –> ketonuria (ketostik) –> ketoacidosis
Ketoacidosis - nausea, vomiting, coma, death, dehydration, tachypnoea (metabolis acidosis)

Question 4

Explain the causes and consequences of hypoglycaemia and hyperglycaemia

Answer 4

Hypoglycaemia - BGL slurred speech, dizziness

Hyperglycaemia - BGL >7 mmol/L - too much glucose –> inadequate energy utilisation

Question 5

Describe, in broad outline, the principles of management of diabetes

Answer 5

Type 1:
Injection of exogenous insulin subcutaneously several times a day
Type 2:
Lifestyle
Non-insulin therapies (biguanides, sulphonylureas, thiazolinedione, GLP1 analogues - increase insulin release. DPP4 inhibitors, a-glucosidase inhibitors, SGLT2s - block reabsorption of glucose in kidneys)
Insulin

Question 6

Explain the principle and practise of measuring glycosylation of haemoglobin as an index of blood glucose control in the diabetic

Answer 6

Increased glucose in blood --> attaches to Hb --> glycated Hb
Elevated HbA1c (>6.5%)

Question 7

List the common long term side effects of diabetes, including: cardiovascular problems, diabetic eye disease, diabetic kidney disease, diabetic neuropathy and diabetic foot

Answer 7

Microvascular - neuropathy, retinopathy (haemorrhage), nephropathy (peripheral neuropathy e.g. foot as sensation to feet is impaired)
Macrovascular - CHD, stroke, heart attack

Question 8

Describe the actions of insulin and glucagon

Answer 8

Insulin:
Released by B-cells
Lowers BGLs
Targets liver, adipose, skeletal muscle
Affects metabolism of carbohydrates, lipids, proteins 
Anabolic 
Glucagon: 
Released by a-cells
Raises BGLs
Targets liver, adipose
Affects metabolism of carbohydrates, lipids
Catabolic

Question 9

Describe how the ultrastructure of the B-cell relates to the synthesis and storage of insulin

Answer 9

Synthesis - big peptide, consists of two unbranched peptide chains connected by 2 disulphide bridges (stable, rigid), preproinsulin –> proinsulin (removal of signal peptide during insertion to ER) –> insulin (endopeptidases excise C protein)
Storage - insulin and C peptide stored in secretory granules in cytoplasm
Secretion - increased BGLs –> glucose transported by facilitated diffusion into cell through GLT2 –> membrane depolarization, influx of calcium –> exocytosis of insulin

Question 10

Explain the roles of insulin and glucagon in the control of metabolism

Answer 10

Insulin - increases glucose uptake into target cells and glycogen synthesis (insertion of GLT4 channels), increases uptake of aa (protein synthesis), inhibits breakdown of aa, increases storage of TAGs, inhibits breakdown of fatty acids
Glucagon - increases glycogenolysis and gluconeogenesis, stimulates lipolysis (increase plasma fatty acid)