Diabetes Mellitus

Question 1

Define diabetes mellitus.

Answer 1

Diabetes mellitus is a metabolic disorder characterised by chronic hyperglycaemia due to defects in insulin secretion and/or insulin action.

Question 2

How is diagnosis of diabetes confirmed in any person?

Answer 2

Hyperglycaemic symptoms (polyuria, polydipisa) with random or postprandial blood glucose more than or equal to 11.1mmol/L or fasting plasma glucose more than or equal to 7mmol/L

Question 3

How is the oral glucose tolerance test (OGTT) used to diagnose diabetes?

Answer 3

Overnight fast (more than or equal to 8 hours) Fasting plasma glucose 75g anhydrous glucose to drink 2nd blood sample 2 hours later.

Question 4

What are the WHO criteria (2006) for diagnosing patients in PRESENCE of symptoms? What about asymptomatic patients?

Answer 4

Random plasma glucose ≥ 11.1 mmol/L OR Fasting plasma glucose ≥ 7 mmol/L OR 2 hour plasma glucose ≥ 11.1 mmol/L 2 hours post 75g OGTT Asymptomatic - at least one of above confirmed on 2 seperate occassions.

Question 5

What are the WHO criteria (2011) for diagnosing patients using HbA1c?

Answer 5

HbA1c ≥ 48mmol/mol (6.5%) with symptoms and plasma glucose ≥ 11.1 mmol/L Or HbA1c ≥ 48mmol/mol (6.5%) in asymptomatic.

Question 6

In which patients should the HbA1c test not be used?

Answer 6

• Children/young people - T1DM - Pregnancy - Medications eg steroids that cause sudden increase in glucose - symptoms onset within 2 months - Genetic, haemaologic and illness factors that affect haemoglobin.

Question 7

What does glycosylated haemoglobin reflect exactly?

Answer 7

Formed by glycation fo Hb as exposed to plasma. It reflects average plasma glucose over previous 8-12 weeks.

Question 8

What is the difference between impaired fasting glycaemia /IFG and impaired glucose tolerance/IGT? What do you need to do in these groups of patients?

Answer 8

Impaired glucose tolerance/IGT = fasting plasma glucose <7 mol/L And 2 hour plasma glucose ≥ 7.8 but <11.1mmol/L on an OGTT Impaired fasting glycaemia /IFG = fasting plasma glucose 6.1-6.9 mmol/L Patients with either or both of above are at risk of diabetes - educate on lifestyle changes and monitor glucose with blood tests every 1-2 years.

Question 9

which groups of patients should be offered screening for diabetes ?

Answer 9

• Overweight/obese - atherosclerotic disease - first-degree relative with Type II diabetes melitus - African Caribbean/Middle Eastern/South Asian origin - IFG and IGT - Woman who had gestational diabetes but tested normal following delivery - Obese women with polycystic ovary syndrome

Question 10

What are the two ways of monitoring long-term control of diabetes?

Answer 10

1. Hb1Ac 2. Fructosamine (if haemoglobulinopathies)

Question 11

What are the two ways of monitoring short-term patterns in patients with diabetes?

Answer 11

1. Blood capillary glucose using blood monitors > diary > reviewed by diabetic team 2. Continuous glucose monitoring.

Question 12

What is continuous glucose monitoring?

Answer 12

A device the displaced subcutaneously and worn from 24 hours to several days to note patterns in blood glucose variation.

Question 13

Why is continuous glucose monitoring useful?

Answer 13

In patients who have problematic control it helps to alter insulin doses or settings of these on insulin pump therapy.

Question 14

Aside from type one and type two diabetes give other causes for development of diabetes.

Answer 14

• Endocrine disorders such as acromegaly, Cushing’s syndrome, glucagonoma (excess GH, cortisol and glucagon antagonise insulin) - Drugs eg steroids increase gluconeogenesis and increase insulin resistance - Gestational diabetes - genetic defects in beta-cell function, e.g. maturity onset diabetes of the young, neonatal diabetes - genetic defects in insulin action e.g. type A insulin resistance - Pancreatic diseases eg chronic pancreatitis, infection, trauma, cystic fibrosis - damage the pancreas. - other syndromes eg Turner’s, Down’s Kleinfelter’s

Question 15

What is the main difference between type I and type II diabetes?

Answer 15

Type I - 5-10% of diabetes. Cellular mediated process causing destruction of beta cells of pancreas causing an absolute insulin deficiency. Type II - 95-90% diabetes. Associated with obesity, caused by both insulin resistance and defect in insulin secretion. In both cases genetic predisposition plays a part (more so in Type II diabetes, but it is also polygenic and more difficult to understand). In type I diabetes environmental factors also play a part.

Question 16

Name at least three potential environmental triggers for T1DM.

Answer 16

• Chemicals viruses e.g. rubella - bacteria - intrauterine factors e.g. pre-eclampsia, birth weight - Diet (vit D deficiency) - Stress

Question 17

Name at least three auto antibodies in a T1DM.

Answer 17

• Islet antigen 2 (IA-2) - Insulin (IAA) - Glutamic acid decarboxylase (GAD)

Question 18

In three steps summarise the pathophysiology of T1DM.

Answer 18

1. Beta-cell destruction mediated by CD8 T lymphocyte 2. Chronic inflammatory changes and infiltration of lymphocytes and macrophages causes insulinitis 3. Destruction of beta-cell causes loss of beta cell mass 4. Insulinopenia 5. Absence of insulin action in adipose and muscle tissue 6. Glucose not transported into cells by GLUT4 transporter 7. Clinical manifestation.

Question 19

Over what period of time the symptoms of T1DM develop?

Answer 19

1-4 weeks

Question 20

What is the peak onset age of T1DM?

Answer 20

12 years. (type II - over 40)

Question 21

What are the common osmotic symptoms of T1DM?

Answer 21

Thirst Polydipsia Weight loss Hyperglycemia - increased osmotic effect - dehydration - hypovolaemia - blurred vision (osmotic changes in lens) - recurrent gnital Candida infections

Question 22

What are the catabolic symptoms of T1DM?

Answer 22

Absolute insulin deficiency - protein breakdown - muscle wasting - fatigue - weight loss

Question 23

What is the acute presentation of T1DM?

Answer 23

Diabetic ketoacidosis

Question 24

what lifestyle advice do you need to give to patients with T1DM?

Answer 24

• Advise on hypoglycaemic effects of foods - effects of foods on glycaemia - snacks between meals and bedtime - healthy eating to decrease arterial risk - alcoholic drinks - physical activity - self monitoring - insulin dose adjustment insulin around exercise - smoking cessation

Question 25

What are the three types of insulin available?

Answer 25

1. Soluble insulin - subcutaneous - intravenous (emergency) 2. Isophane insulin - basal insulin with prolonged insulin action 3. Insulin analogues - Rapid acting analogues (insulin lispro, aspart) - more readily absorbed than soluble insulin. - Long acting analogues (insulin detemir, glargine) - stable basal insulin conc.

Question 26

What are the two common insulin regimens used in patients with T1DM?

Answer 26

1. Twice daily insulin regimen 2. Multiple daily injections (MDI) / basal bolus regimen.

Question 27

Describe the twice daily insulin regimen.

Answer 27

2 x day injection of premixed insulin (combo of short and intermediate acting insulin) Given BEFORE breakfast and evening meal Diasdvantages - little flexibility in timing and size of meals, increased risk of hypoglycaemia

Question 28

Describe multiple daily injections MDI/basal bolus regimen.

Answer 28

1 x day basal insulin (isophane or analogue eg detemir, glargine) in combo with short acting soluble/ analogue insulin Given AT mealtimes/snacks Adv - more flexibility and timing and quantity of meals, decreased risk of hypo and better glycemic control.

Question 29

What sort of insulin education is given to patients with T1DM?

Answer 29

• resuspension of insulin - use of insulin pens - injection technoques - insulin dose adjustment

Question 30

Why do you need to monitor injection sites regularly in patients with T1DM?

Answer 30

To ensure no lipohypertrophy - Build up of subcutaneous fat at injection sites which causes variable insulin absorption Encourage rotation of sites within an area.

Question 31

Normally patients use handheld capillary blood glucose monitors and MDI regimen to achieve control. What is continuous subcutaneous insulin infusion/CSII ?

Answer 31

For patients in the UK who failed to achieve adequate glycaemic control on an MDI without major hypoglycaemia Or those who have Hb1Ac ≥ 69mmol/L despite being on MDI with lots of education needed Insulin pump devices are made of an insulin reservoir containing short acting insulin that is continuously infused into subcutaneous tissue. Basal rates set for different times of day while bonuses can be given a mealtimes. CSII can improve glycemic control and reduce hypoglycemia.

Question 32

Describe the process of pancreatic transplantation

Answer 32

Islet cells retrieved from pancreas of brain-dead donors under local anaesthesia cells are inserted percutaneouslu into the portal vein and infused into the liver.

Question 33

List two potential diabetes treatments for T1DM

Answer 33

1. The artifcial pancreas 2. Immunotherapy

Question 34

What is the peak age of onset of Type II diabetes?

Answer 34

Over 40 years old

Question 35

List different ethnic populations which are at higher risk of diabetes.

Answer 35

South Asian African Caribbean Middle Eastern

Question 36

Which environmental factors are important in development of insulin resistance and Type II diabetes?

Answer 36

Obesity especially central adiposity/increased waste circumference Sedentary lifestyle/ lack of physical exercise Intrauterine env. - low and high birth weight associated with insulin resistance.

Question 37

What is Type II diabetes characterised by

Answer 37

Defect in both insulin sensitivity and insulin secretion

Question 38

Where in the body does insulin resistance occur and what is the consequence of this?

Answer 38

Insulin resistance occurs at the level of peripheral tissues e.g. skeletal muscle, adipose tissue and liver > reduced glucose uptake in skeletal muscle and impaired inhibition of the hepatic glucose output

Question 39

What happens to adipose tissue when it is insulin resistant?

Answer 39

Insulin resistance causes increased non-esterified fatty acid production which stimulates gluconeogenesis and triglyceride synthesis.

Question 40

How does the patient pass from IGT to type II diabetes?

Answer 40

1. Rising insulin resistance 2. Initial compensatory hyperinsulinaemia 3. Eventual B cell exhaustion causing rise in glucose

Question 41

How does Type II diabetes present clinically?

Answer 41

1. 1/3 - incidental finding 2. Half of patients - classic polydipsia, polyuria and tiredness secondary to hyperglyceamia 3. 25% - emergency in hyperglycemic hyperosmolar state