Development of Diabetes Mellitus

Question 1

Where is the normal blood glucose maintained between?

Answer 1

4-6mM

Question 2

What does diabetes mellitus result from?

Answer 2

Insulin deficiency and/or insulin resistance. Disruption of glucose metabolism can lead to hyperglycaemia (blood glucose above 11mM)

Question 3

What are the three types of diabetes mellitus?

Answer 3

• Type 1,
• Type 2 (insulin independent),
• Gestational diabetes

Question 4

Describe features of type 1 diabetes mellitus

Answer 4

To develop T1DM must have a genetic predisposition and exposure to an environmental trigger such as viral infections.
It causes pancreatic beta-cell destruction leading to insulin deficiency.

Question 5

What are the symptoms of diabetes 1?

Answer 5

Presents when over 80% of beta cells have been destroyed. Symptoms are; polyuria, polydipsia, weight loss and fatigue with hyperglycaemia.

Question 6

How does diabetic ketoacidosis develop?

Answer 6

In uncontrolled diabetes the low insulin causes increase in lipolysis and a decrease in re-esterification in the liver. This causes triglycerides to be converted into excess acetyl-CoA. This causes increase in plasma free fatty acids which can be used in TCA cycle or cellular respiration however not all Acetyl-CoA can be used this was and so the excess is converted into ketone bodies which lowers blood pH leading to metabolic acidosis.

Question 7

what occurs with a lack on insulin on a cellular level?

Answer 7

Lack of activation of insulin receptors so no recruitment of GLUT4 receptors and so there is excess of glucose in the blood = hyperglycaemia.

Question 8

Describe features of type 2 diabetes mellitus?

Answer 8

• Development is influenced by Genetic predisposition and progressive loss of insulin sensitivity (due to overstimulisation) and defective insulin receptor signalling.
• Associated with metabolic syndrome which starts with energy imbalance (high food consumption with low energy expenditure). This causes fat deposits in visceral organs which leads to altered insulin signalling, insulin resistance and beta cell damage.

Question 9

Describe the progression from prediabetes to diabetes

Answer 9

• In prediabetes there is lower insulin sensitivity which results in compensatory hyperinsulinemia.
• Beta cells now working much harder which can lead to progressive beta cell failure.

Question 10

What is the criteria for prediabetes/diabetes?

Answer 10

When you have a fasting glucose level between 6.1-6.9 = prediabetes. If fasting glucose levels are above 7mM then this is diabetes.
So oral glucose tolerance test is used to measure diabetes and prediabetes.

Question 11

What are the varieties of prediabetes conditions?

Answer 11

• Impaired fasting glucose,
• Impaired glucose tolerance,
• Or can have a combination of both.
  Underlying pathophysiology is different

Question 12

Describe what occurs to the glucose levels in a normal pregnancy

Answer 12

• At the beginning of the second trimester, hormones such as foetal, placental, cortisol, placental lactogen and placental growth hormone promote a state of insulin resistance. This raises the blood glucose ensuring glucose is able to be transported across the placental to fuel growth of foetus (glucose goes to foetus first)
• Normal compensation if hypertrophy and hyperplasia of pancreatic beta cells of mother and increased glucose stimulated insulin secretion.
• Normally maternal insulin sensitivity will return to pre-pregnancy levels within a few days of delivery

Question 13

Describe what occurs with gestational diabetes mellitus

Answer 13

In GDM the normal pregnancy adaptations do not take place on the background of chronic insulin resistant.

Question 14

What are the risks of gestational diabetes mellitus?

Answer 14

To mother - Increased risk of miscarriage, maternal CVD, preeclampsia and type two diabetes.
To foetus - Increased risk of macrosomia, perinatal mortality and birth complications

Question 15

What are risk factors for GDM?

Answer 15

• Ethnicity (Chinese, black African or black-Caribbean),
• Prior pregnancy where baby weighted more than 4.5kg,
• BMI over 30

Question 16

What is the HbA1c measurement?

Answer 16

Measures the amount of glycated haemoglobin (HbA1c) as glucose naturally binds to haemoglobin. HbA1c > 6.0-6.4% = prediabetes. HbA1c >6.5% = diabetes

Question 17

What are the WHO guidelines for the diagnosis of diabetes?

Answer 17

• Symptoms plus; random venous plasma glucose conc > 11.1, or FPG conc of > 7.0, or 2 hour PG conc > 11.1 after OGTT.
• HbA1c >6.5%

Question 18

What are the acute effects of uncontrolled diabetes type 1?

Answer 18

• Reduction of glucose uptake by cells leads to intracellular glucose deficiency and polyphagia.
• The increase in hepatic glucose uptake and the reduced glucose uptake by cells leads to hyperglycaemia which causes glucosuria and osmotic diuresis which causes polydipsia and polyuria which leads do dehydration and cell shrinkage.
• Reduction in triglyceride synthesis and increased lipolysis leads to increase in free fatty acids in the blood which leads to ketosis then metabolic acidosis and consequently increased ventilation.
• Reduced uptake of amino acids into cells and protein degradation causes increased AA in blood and increased gluconeogenesis. Protein degradation causes muscle wasting and weight loss.

Question 19

What occurs as a result of dehydration and cell shrinking in type 1 diabetes?

Answer 19

Reduction in blood volume which causes peripheral circulatory failure which causes renal failure which can lead to death. The reduction in BV can also lead to low cerebral blood flow which can lead to nervous system malfunction which can lead to death.

Question 20

What occurs as a result of the increased ventilation?

Answer 20

Diabetic come due to the low pH of the blood which results in death

Question 21

What are the long term pathologies of diabetes mellitus

Answer 21

The increase in fat mobilization leads to increased plasma levels of FFA, TG and cholesterol which leads deposition of fats in arterial walls. Hyperglycaemia also leads to increased glycation and glycoxidation of proteins which also leads to deposition of fats in arterial walls. This leads to damage to vascular endothelium resulting in loss of arterial compliance which leads to diabetic atherosclerosis and hypertension ventilation. This causes CVD resulting in angina, cardiac arrhythmias and renal disease