Diabetes – overview and Type 1

Question 1

Patients who cannot survive without exogenous insulin due to ? (type 1 diabetes)

Answer 1

Autoimmune destruction of the

beta-cells of the islets of Langerhans

Question 2

What is Type 2 diabetes ?

Answer 2

Failure of the body to respond properly to insulin - impaired insulin secretion and insensitivity of target cells to insulin

Question 3

What is type 2 diabetes associated with ?

Answer 3

Associated with obesity and diet, but there is a strong

genetic predisposition

Question 4

Are there symptoms for type 2 diabetes ?

Answer 4

Often asymptomatic for some time, but may have classical 
hyperglycaemic symptoms (thirst, polyuria, weight loss)

Question 5

What is Gestational diabetes?

Answer 5

This the main other type of diabetes: occurs during pregnancy when the woman’s body is unable to produce enough insulin, usually in the second half and should go away after the baby is born

Question 6

How does Gestational diabetes work ?

Answer 6

High blood sugar levels in the mother’s body are passed through the placenta to the developing baby, which can cause problems including congenital malformations, elevated birthweight and
perinatal mortality

Question 7

In gestational diabetes, effects of insulin antagonised by ?

Answer 7

Elevated levels of steroid hormones and also insulin

degradation by the placenta.

Question 8

Factors before birth and early life exposure combine with genetic risk, resulting in autoimmunity. Explain the different stages ?

Answer 8

Once autoimmunity is clearly established (stage 1) this represents disease onset with inevitable progression to β cell loss, ultimately affecting the ability to control glucose (stage 2), and final levels of glycemia diagnostic of T1D and the need for insulin (stage 3)

Question 9

Metabolic consequences of Type 1 diabetes ?

Answer 9

• Blood insulin levels are low despite the high blood glucose, whereas glucagon levels are raised
• The insulin:glucagon ratio cannot increase even when dietary glucose is entering from the gut
• Low I:G ratio leads to induction of catabolic enzymes and repression of anabolic enzymes
• Metabolism stuck in the starved phase

Question 10

The Type 1 diabetic state - Liver ?

Answer 10

• High blood glucose but very low I:G ratio so liver remains gluconeogenic
• Main substrates are lactate and amino acids from protein
  breakdown: hence muscle wasting
• Glycogen synthesis and glycolysis also inhibited: liver cannot buffer blood glucose
• Fatty acids from lipolysis provide energy to support gluconeogenesis but the excess are converted to TAGs and VLDL
• Excess acetyl CoA from fatty acid oxidation is converted to ketone bodies and if these are not used sufficiently rapidly can lead to ketoacidosis

Question 11

The Type 1 diabetic state - Muscle ?

Answer 11

• Little glucose entry into muscle and peripheral tissues because of insulin lack. This contributes to the hyperglycaemia
• Proteolysis occurs to provide carbon skeletons for gluconeogenesis leading to muscle wasting
• Fatty acid and ketone body oxidation used as the major source of fuel

Question 12

The Type 1 diabetic state – Adipose tissue ?

Answer 12

• Low glucose uptake despite high blood levels, due to lack of insulin
• Low I:G ratio enhances lipolysis, giving continuous breakdown of triacylglycerol and release of fatty acids and glycerol into the bloodstream to support energy production in peripheral tissues and gluconeogenesis in the liver.

Question 13

The Type 1 diabetic state – Plasma and Urine ?

Answer 13

• High blood glucose eventually reaches the renal threshold, glucose is excreted in the urine
  (glycosuria) with loss of water and development of thirst
• High blood glucose eventually reaches the renal threshold, glucose is excreted in the urine
  (glycosuria) with loss of water and development of thirst
• Glycation of haemoglobin by high glucose comprises O2 delivery, especially to extremities (hands, feet, etc.)
• Increases the risk of cardiovascular disease, renal failure, and damage to small blood vessels and nerves

Question 14

One method of diagnosing diabetes ?

Answer 14

Fasting blood glucose levels (WHO criteria)

1. After an overnight fast a blood glucose value of ≥7mM on at least two occasions indicates diabetes (normal range is 4.5-6.1mM)
2. Those between 6.1-7mM will need further testing

Question 15

What is another method to diagnose diabetes ?

Answer 15

Glucose tolerance test

1. Performed in morning after an overnight fast. Fasting blood sample is removed and subject drinks ‘glucola’ drink containing 75g of glucose. Blood glucose is then sampled at 0.5, 1, and 2 hours
2. Factors which may interfere with the glucose tolerance test include:
   - acute stress (surgery or an infection)
   - vigorous exercise
   - drugs, e.g. thiazide diuretics, beta-blockers, oral contraceptives, corticosteroids

Question 16

Monitoring blood sugar ?

Answer 16

• Benedict’s test uses the reduction of Cu2+ to Cu+ to detect the presence of reducing sugars
• Glucose oxidase test measures the levels of glucose only : used in monitoring devices

Question 17

Explain Insulin Treatment ?

Answer 17

• Delivery of exogenous insulin is the only way of treating T1D at present
• More sophisticated “smart” technologies are being developed to improve blood glucose regulation
• Future research is also looking into stem cell therapy and transplantation, or preventing T1D developing in the first place