Type 2 Diabetes Mellitus

Question 1

Define Diabetes Mellitus

Answer 1

A state of chronic hyperglycaemia sufficient to cause long-term damage to specific tissues, notably the retina, kidney, nerves, and arteries

Question 2

Describe the features of T2DM that may distinguish from T1DM

Answer 2

T2DM is not ketosis prone
T2DM is not mild
T2DM often involves weight, lipids and blood pressure

Question 3

Describe the epidemiology of T2DM

Answer 3

10% at 60yr
Increases with age
Varies enormously 
Increasing prevalence 
Being diagnosed younger 
Greatest in ethnic groups that move from rural to urban lifestyle

Question 4

Describe the pathophysiology of T2DM

Answer 4

Maturity Onset Diabetes of the Young is relatively uncommon
Genes + intrauterine environment + adult environment
Insulin resistance and insulin secretion defects
Fatty acids important in pathogenesis and complications

Question 5

Describe MODY

Answer 5

Maturity onset diabetes of the young
Several hereditary forms (1-8)
Autosomal dominant
Ineffective pancreatic B cell insulin production
Mutations of transcription factor genes, glucokinase gene
Positive FH, no obesity
Specific treatment for type

Question 6

Describe metabolism and the presentation of T2DM

Answer 6

Heterogeneous
Obesity
Insulin resistance and insulin secretion deficit
Hyperglycaemia and dyslipidaemia
Acute and chronic complications

Question 7

Describe the metabolism of glucose in diabetes

Answer 7

Converted to glycogen in muscle

1. Taken to an adipocyte
2. Lipolysis to form triglycerides
3. Glycerol and NEFA produced
4. Glycerol taken to liver
5. Glycerol + glycogen -> glucose
6. NEFA chopped -> VLDL-TG (Very low density lipoprotein triglyceride - Atherogenic)

Question 8

What are the effects of T1DM on fatty acids

Answer 8

Elevated 
Increase:
Whole body muscle and liver 
Liver TG secretion 
Organ fat, oxidative stress

Decreased B cell function

Question 9

What substances are involved in T1DM mechanisms

Answer 9

Fatty acids 
Glucocorticoids 
Endocannabinoids
Adiponectin 
Visfatin 
Apelin 
Resistin 
Leptin 
TNF-alpha IL-6

Question 10

Describe the association of obesity with T2DM

Answer 10

Fatty acids and adipocytokines important
Central or omental obesity
80% T2DM are obese
Weight reduction useful treatment

Question 11

How are perturbations in gut microbiota involved in T2DM

Answer 11

Obesity, insulin resistance T2DM

1. Lipopolysaccharides fermented by gut bacteria
2. Short chain FA
3. Enter circulation and modulate bile acids
4. Modulate host metabolism (i.e. cause obesity) and are involved in adipocytokine pathways (modulating insulin resistance)

Question 12

Describe the presentation of T2DM

Answer 12

Osmotic symptoms
Infections

Acute; hyperosmolar coma,
Chronic; ischaemic heart disease, retinopathy

Question 13

What are the microvascular complications of T2DM

Answer 13

retinopathy
nephropathy
neuropathy

Question 14

What are the microvascular complications of T2DM

Answer 14

Ishcaemic heart disease
Cerebrovascular
Renal artery stenosis
PVD

Question 15

What are the metabolic and treatment complications of T2DM

Answer 15

Lactic acidosis
Hyperosmolar

Hypoglycaemia

Question 16

What are the basic management focuses for T2DM

Answer 16

Education
Diet
Pharmacological treatment
Complication screening

Question 17

Describe the diet recommended to T2DM patients

Answer 17

Control total calories/increase exercise (weight)
reduce refined carbohydrate (less sugar)
increase complex carbohydrate (more rice etc)
reduce fat as proportion of calories (less IR)
increase unsaturated fat as proportion of fat (IHD)
increase soluble fibre (longer to absorb CHO)
Address salt (BP risk)

Question 18

What should be monitored in T2DM

Answer 18

Weight
Glycaemia
Blood pressure
Dyslidiaemia

Question 19

Describe Metformin

Answer 19

Insulin sensitiser (biguanide) 
Given when diet has not succeeded 
Reduces insulin resistance 
Reduces hepatic glucose output and increases peripheral glucose disposal 
No weight gain
GI side effects

Question 20

What are the contraindications for Metformin

Answer 20

Severe liver failure
Severe cardiac failure
Mild renal failure

Question 21

Describe glibenclamide (sulphonylurea)

Answer 21

Makes pancreas secrete more insulin by blocking ATP sensitive potassium channel -> influx of calcium -> insulin secretion

Causes weight gain and hypoglycaemia

Question 22

Describe acarbose

Answer 22

Alpha glucosidase inhibitor
Prolongs absorption of oligosaccharides (carbs)
Allows insulin secretion to cope with first phase insulin loss

Side effects flatus

Question 23

Describe thiazolidinediones

Answer 23

PPAR-γ agonists 
Pioglitazone
Insulin sensitizer, mainly peripheral
Peripheral weight gain
Improvement in glycaemia and lipids
Side effects of older types hepatitis, heart failure

Question 24

Describe glucagon like peptide-1

Answer 24

Secreted in response to nutrients in gut by L cells
Stimulates insulin, suppresses glucagon
Increases satiety
Restores B cell glucose sensitivity
Short half life, rapid degredation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor)

Question 25

Describe GLP-1 agonists

Answer 25

Exenatide, liraglutide
Injectable
Long acting GLP-1 agonist
Decrease [glucagon]
Decrease [glucose]
Weight loss

Question 26

Describe DPPG-4 inhibitors / Gliptins

Answer 26

Increase half life of GLP-1

Not as effective as GLP-1 agonist

Question 27

Describe empaglifozin

Answer 27

Inhibits Na-Glu transporter, increases glycosuria 0 glucose resorption reduced
HbA1c lower

Question 28

Describe the changes in insulin resistance and insulin secretion with age

Answer 28

(childhood unknown)
Decrease in secretion and increase in resistance throughout childhood
Slight increase in secretion then decrease rapidly (non-linear)
Resistance increases linearly after childhood

Question 29

What are the effects of insulin resistance

Answer 29

1. Unable to stop the breakdown of triglycerides -> glycerol release from adipocytes -> NEFA formation
2. Dyslipidaemia - stimulates the mitogenic pathway, increasing smooth muscle hypertrophy -> increase in BP
3. Damages beta cells -> gradual beta cell failure so insulin cannot be produced to cover the decreased insulin sensitivity -> hyperglycaemia
4. Loss of 1st phase insulin
   2nd phase insulin can still be produced, but takes longer and is immature -> hyperglycaemia
5. Absolute insulin deficiency