Diabetes Mellitus & the endocrine pancreas

Question 1

List the main difference between type 1 & type 2 diabetes

Answer 1

type 2: gradual onset, usually insulin deficient / resistance, central obesity MAIN factor, more complications e.g. thrush, blurred vision, infections (normally diagnose from complications), adult onset, treated by altered lifestyle, doesn’t normally develop ketoacidosis, strong genetic component

Question 2

Describe and explain the typical presentation of type 1 & type 2 diabetes

Answer 2

hyperglycaemia - lack of insulin, lack of glucose store in adipose & muscle
glucose in urine - hyperglycaemia (glycosuria)
polyuria - from glycosuria
polydipsia - from polyuria
weight loss - proteolysis & lipolysis from lack of insulin (fat & protein metabolised instead)
ketoacidosis: lipolysis produce ketones in liver (acetyl CoA –> HMG CoA –> acetacetate –> acetone)

Question 3

How does type 1 diabetes normally present in young poeple?

Answer 3

acute clinical emergency - ketoacidosis

Question 4

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

Answer 4

1. increased lipolysis - release fatty A (substrate of ketone body formation - beta oxidation)
2. activation of ketogenic enzymes in liver

Question 5

Explain the cause and consequence of hypoglycaemia

Answer 5

plasma glucose

Question 6

Describe the cause and consequence of hyperglycaemia

Answer 6

blood glucose >10mmol/l

lead to: polyruia, polydipsia, weight loss, fatigue, blurred vision, poor wound healing

Question 7

Describe in broad outline the management of type 1 diabetes

Answer 7

diet: reduce refined sugar & lipid intae
increase exercise
drugs: antidiabetic (decrease blood gluc.), antihypertension (decrease BP), statins (decrease blood lipids), exogenous subcutaneous insulin injections

Question 8

The principles of management of type 2 diabetes

Answer 8

reduce weight: diet decrease carbs & increase exercise
measure HbA1c - monitor glucose conc.
check for complications: feet, eyes, bp
introduce drug therapy: decrease blood gluc & lipids, eventually insulin injections

Question 9

Explain the principle and practise of measuring HbA1c (glycosylation of haemoglobin) as an index of blood glucose control in diabetes

Answer 9

HbA1c: index of glycaemic control
glucose reacts with VALINE of haemoglobin (HbA1c)
extent of glycation depends on blood glucose conc. & 1/2 life of haemoglobin
high blood gluc = elevated HbA1c = poor control > 10% HbA1c
good control = normal blood glucose levels about 5% HbA1c

Question 10

Explain how type 1 diabetes can lead to hyperglycaemia

Answer 10

reduced uptake of glucose by adipose tissues & skeletal muscle
reduced storage of glucose by liver & skeletal muscles (decrease glycogenesis, increase glycogenolysis)
increasing production of glucose by liver: increase gluconeogenesis, decrease glycolysis

Question 11

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

Answer 11

MACROvascular: increase risk of stroke & MI
poor circulation to peripheral especially foot & vessels
MICROvascular: eye disease: glaucoma (pressure in eye), cataracts (disulphide), retinopathy (retina damage)
nephropathy, neuropathy (loss of sensation to peripheral nerves), erectile dysfunction, diabetic feet (risk of ulceration & infection)

Question 12

How does diabetes lead to kidney damage?

Answer 12

increase glucose causing disulphide bond formation depleting NADPH

Question 13

Describe the action of insulin

Answer 13

STIMULATE: glucose transport –> adipose tissue & skeletal muscles (uptake & use)
glycogenesis: inhibits glycogenolysis in muscle & liver (store)
INHIBITS: glucogenesis in liver (making glucose), lipolysis in adipose tissue

Question 14

Insulin

Answer 14

forms glycogen
stops breakdown of glucose
stops formation of glucose in liver

Question 15

Type 2 diabetes insulin resistance sign & symptoms

Answer 15

1. weight gain
2. glycosuria, polyuria, polydipsia
3. tiredness / weakness
4. visual problems: retinopathy / cataracts
5. thrush / skin infection
6. erectile dysfunction - neuropathy (nerve damage)

Question 16

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

Answer 16

lots of mitochondria: synthesis, storage & secretion of proteins
extensive RER: synthesis export proteins
extensive golgi: form hormone storage vesicles
storage vesicles: ready for hormone secretion
microtubules & microfilaments: exocytosis

Question 17

How come insulin & C-peptide in beta cells are expressed in the same amounts?

Answer 17

proinsulin (pre-cursor of insulin): A&B chains joined by connecting peptide (C-peptide)
sotrage vesicle: proinsulin –> insulin through proteolysis
products: insulin, C-peptide, 4AA (equal amounts) - secreted together in exocytosis

Question 18

Describe the condition of diabetes mellitus

Answer 18

a group of metabolic disorders characterised by chronic hyperglycaemia due to insulin deficiency / resistance or both
there are 2 major types of this disease, clearly distinguished by their epidemiology & probable cause, but not always separated clinically