10. Diabetes

Question 1

what is diabetes mellitus

Answer 1

chronic hyperglycaemia (>6mmol/L) due to insulin deficiency, insulin resistance of both

Question 2

what causes type 1 DM

Answer 2

autoimmune condition: antibody production against and progressive loss of pancreatic beta cells

likely involves genetic predisposition (e.g. HLA-DR3, HLA-DR4) interaction with environmental trigger (e.g. viral infection)

Question 3

describe the typical presentation of T1DM

Answer 3

usually presents in teenage years

classical triad of symptoms:
1- polyuria (excessive urination)
2- polydypsia (excessive thirst)
3- weight loss

Question 4

why does polyuria occur in T1DM

Answer 4

hyperglycaemia causes exceeding of renal threshold… not all glucose is reabsorbed in proximal tubule… extra osmotic load on nephron so less water is reabsorbed to maintain isosmotic character of this section of nephron… extra water excreted as copious urine

Question 5

why does polydypsia occur in T1DM

Answer 5

1. osmotic effect of glucose on thirst centres

2. excess water loss

Question 6

why does weight loss occur in T1DM

Answer 6

insulin deficiency… fat and protein metabolism

Question 7

how is diabetes diagnosed

Answer 7

glucosuria

Question 8

what is ketoacidosis

Answer 8

production of huge amounts of ketone bodies (acetoacetate, acetate, beta-hydroxybutyrate) in T1DM… H+ associated with ketone bodies produces metabolic acidosis

Question 9

why does ketogenesis occur in T1DM

Answer 9

increased rate of fatty acid beta-oxidation coupled with low insulin:glucagon ratio

Question 10

describe the signs/symptoms of ketoacidosis

Answer 10

symptoms
1- prostration
2- hyperventilation
3- dehydration
4- abdominal pain, nausea and vomiting

signs
1- acetone smell of breath

Question 11

describe the typical presentation of T2DM

Answer 11

• typically develops in older, overweight patients
• may present with classical triad but more likely to have variety of symptoms, e.g. lack of energy, persistent infections (esp. thrush), foor infections, slow healing minor skin damage, visual problems

Question 12

how is diabetes diagnosed

Answer 12

presence of symptoms plus:

• random venous plasma glucose conc. >11.1 mmol/L OR
• fasting plasma glucose conc. >7 mmol/L OR
• plasma glucose conc. >11.1 mmol/L 2hrs after oral glucose tolerance test

Question 13

describe the management of T1DM

Answer 13

1. insulin injections
2. dietary management and exercise
3. monitoring blood glucose (BM stick and reader)

Question 14

why must insulin be injected and not taken orally

Answer 14

is glycopeptide hormone so would be broken down to constituent amino acids in GI tract

Question 15

describe the management of T2DM

Answer 15

early T2DM
1. diet or “oral hypoglycaemic” drugs, e.g. SULPHONYLUREAS, esp. METFORMIN

late T2DM
1. insulin injections

2. dietary management and exercise
3. monitoring blood glucose (BM stick and reader)

Question 16

what is the MOA of sulphonylureas amd metformin

Answer 16

sulphonylureas:

• increase insulin release from remaining beta cells
• reduce insulin resistance

metformin:
- reduces gluconeogenesis

Question 17

how can endogenous insulin production be measured in patients taking injected insulin

Answer 17

measuring C-peptide, which is released with insulin in equimolar amounts (but is not included in synthetic insulin preparations)

Question 18

what is measured in blood to indicate blood glucose control effectiveness

Answer 18

glycated haemoglobin: HbA1c

indicates average blood glucose conc. over preceding 2-3 months

Question 19

in which tissues does intracellular glucose conc. increase in hyperglycaemia and why

Answer 19

peripheral nerves, eye and kidney - transport via GLUT regulated by extracellular glucose conc. rather than insulin

Question 20

why does hyperglycaemia damage cells

Answer 20

1) increased intracellular glucose metabolised by aldose reductase to sorbitol + NADP+… depletes cellular NADPH
2) increased disulphide bond formation in cellular proteins… alters structure and function
3) sorbitol accumulation… osmotic damage to cell

Question 21

why does hyperglycaemia damage plasma proteins

Answer 21

glycation: glucose spontaneously forms stable covalent linkages with free amino groups in proteins… changes net charge and structure of protein

Question 22

name 3 long term macrovascular complications of diabetes

Answer 22

1. stroke
2. MI
3. poor circulation to periphery, esp. feet - gangrene

Question 23

name 4 organs/body parts affected by microvascular complications in diabetes

Answer 23

1. eyes
2. kidneys
3. peripheral nerves
4. feet

Question 24

how does hyperglycaemia affect the eyes

Answer 24

1. glaucoma: osomotic effects of glucose… changes in lens… visual probs.
2. retinopathy: damage to BVs in retina… leak and form protein exudate in retina or rupture and bleed… blindness

Question 25

how does hyperglycaemia affect the kidneys (nephropathy)

Answer 25

1. damage to glomeruli 2. changes in kidney BVs... poor blood supply 3. damage from urinary tract infections causes microalbuminuria (increased amount of protein in urine)

Question 26

what is metabolic syndrome

Answer 26

Cluster of most dangerous risk factors associated with CVD: (1) abdominal obesity, (2) high BP, (3) insulin resistance, (4) raised fasting glucose, (5) dyslipidaemia (↑ LDL & VLDLs, ↓ HDLs). Clustering of these abnormalities in same individual confers substantial risk, above sum of individual risks.

Question 27

what are the 2 main factors causing metabolic syndrome

Answer 27

1. central obesity | 2. insulin resistance

Question 28

how should metabolic syndrome be managed

Answer 28

Primary interventions: promote healthy lifestyle, moderate calorie restriction, moderate increase in physical activity, healthy diet. Secondary interventions: statins to reduce LDL-cholesterol, anti-hypertensive drugs to lower BP (e.g. ACE inhibitors), possibly anti-diabetic drugs to treat hyperglycaemia.