Type 2 Diabetes Mellitus

Question 1

What is Type 2 Diabetes Mellitus (T2DM)?

Answer 1

Condition in which the combination of insulin resistance & beta-cell failure result in hyperglycaemia

Question 2

What are the 3 stages of development of T2DM?

Answer 2

• Normal
• Intermediate state
• T2DM

Question 3

What fasting glucose is considered normal?

Answer 3

≤ 6 mmol/L

Question 4

What 2-hr glucose (OGTT) is considered normal?

Answer 4

< 7.7 mmol/L

Question 5

What HbA1c is considered normal?

Answer 5

< 42 mmol/mol

Question 6

What fasting glucose is considered indicative of T2DM?

Answer 6

≥7 mmol/L

Question 7

What 2-hr glucose (OGTT) is considered indicative of T2DM?

Answer 7

≥11 mmol/L

Question 8

What HbA1c is considered indicative of T2DM?

Answer 8

≥ 48 mmol/mol

Question 9

How is beta-cell function different in T2DM than in T1DM?

Answer 9

• T2DM slower fall of beta-cell function compared to T1DM
  
  • Not enough to overcome insulin resistance
    
    • There is a relative deficiency of insulin
• In long-duration T2DM, beta-cell failure may progress to complete insulin deficiency

Eventually they will need insulin but at presenting time it would be ineffective

Question 10

What factors affect insulin secretion & action (7)?

Answer 10

• Body weight
• Physical activity
• Smoking
• Heavy alcohol consumption
• Genetic predisposition
• Gene-environment interaction
• Epigenetics

Question 11

Outline the pathophysiology of T2DM (3).

Answer 11

1. Factors affect the insulin secretion & action
2. Leads to insulin resistance & beta-cell dysfunction
   -> Visceral fat cause the release of pro-inflammatory factors
3. Increased hepatic glucose production AND Decreased glucose uptake in adipose tissue and skeletal muscle

Question 12

What are the consequences of insulin resistance?

Answer 12

• Liver: Excessive glucose production
• Muscle: Glucose not uptaken by muscle tissue efficiently
• Adipocytes: Production of non-esterified & breakdown of fat with excessive triglycerides

Question 13

Why does T2DM lead to ketoacidosis?

Not usual to other forms of hyperglycaemia.

Answer 13

Question 14

What is the diagnosis for diabetic ketoacidosis (4)?

Answer 14

• pH < 7.3
• Increased ketones (urine of capillary blood)
• HCO₃^- < 15mmol/L
• Glucose > 11mmol/L

Question 15

What is the fate of non-esterified fatty acids in a hyperglycaemic state?

Answer 15

• Non-esterified fatty acids undergo beta-oxidation resulting in the production of fatty Acyl-CoA
  
  • Carnitine shuttle facilitates the transport of fatty acids through the mitochondrial membrane
  • Insulin exerts an inhibitory effect on the shuttle → Downregulates ketone body formation
  • Glucagon potentiates the rate at which fatty-acyl-CoA undergoes ketogenesis to synthesise ketone bodies

Question 16

What is the role of obesity to T2DM?

Answer 16

• Major risk factor for T2DM
  
  • Central vs visceral obesity
• Weight reduction useful treatment

80% T2DM are obese

Question 17

Other than obesity what other associations have been identified with T2DM (2)?

Answer 17

• Perturbations in gut microbiota
• Intra-uterine growth retardation

Question 18

How does T2DM present (7)?

Answer 18

• Hyperglycaemia
• Overweight
• Dyslipidaemia
• Fewer osmotic symptoms
• With complications
• Insulin resistance
• Later insulin deficiency

Question 19

What are the risk factors of T2DM (6)?

Answer 19

• Age
• PCOS
• Increased BMI
• Family Hx
• Ethnicity
• Inactivity

Question 20

How is T2DM diagnosed?

Answer 20

• 1x HbA1c >=48mmol/L with symptoms
  OR
• 2x HbA1c >=48 mmol/mol if aysymptomatic

Question 21

What is glycated haemoglobin (HbA1c)?

Answer 21

• HbA1c represents 3 months of glycaemia (red blood lifespan)
  
  • Biased to the 30 days preceding measurement

Question 22

Which amino acid terminal is glucose associated with in HbA1C?

Answer 22

• Associated with the N-terminal valine residue of the B-chain
  
  • Linear relationship
  • Irreversible reaction

Question 23

What are the 4 limitations to using HbA1c as a marker?

Answer 23

• Erythropoiesis
  
  • Increased HbA1c:
    
    • Iron
    • Vitamin B12 deficiency
    • Decreased erythropoiesis
  • Decreased HbA1c:
    
    • Administration of erythropoietin / iron / vitamin B12
    • Reticulocytosis
    • Chronic liver disease
• Altered Haemoglobin
  
  • Variable HbA1c:
    
    • Genetic or chemical alterations in haemoglobin:
      
      • Haemoglobinopathies
      • HbF
      • Methaemoglobin
• Glycation
  
  • Increased HbA1c:
    
    • Alcoholism
    • Chronic renal failure
    • Decreased intra-electrolyte pH
  • Decreased HbA1c:
    
    • Aspirin
    • Vitamin C and E
    • Certain haemoglobinopathies
    • Increased intra-erythrocyte pH
  • Variable HbA1c:
    
    • Genetic determinants
• Erythrocyte destruction
  
  • Increased HbA1c - Increased erythrocyte lifespan:
    
    • Splenectomy
  • Decreased HbA1c - Decreased erythrocyte lifespan:
    
    • Haemoglobinopathies
    • Splenomegaly
    • Rheumatoid arthritis
    • Drugs such as antiretrovirals, ribavirin and dapsone

Question 24

What is the management of T2DM (4)?

Answer 24

• Diet
• Oral medication
• Structured education
• May need insulin later

Question 25

What are the dietary recommendations and education of T2DM (6)?

Answer 25

* Total calories control * Reduce calories as fat * Reduce calories as refined carbohydrate * Increase calories as complex carbohydrate * Increase soluble fibre * Decrease sodium

Question 26

What drugs are used in the treatment of T2DM (7)?

Answer 26

* Metformin * Thiozolidinediones * Sulphonylureas * DPP4-inhibitors * GLP-1 Agonists * Alpha glucosidase inhibitor * SGLT-2 inhibitor