Diabetes and Obesity

What are the two metabolic states?

Absorptive: after a meal, absorping nutrients from a diet, excess nutrenients stored in body

Postabsorptive: Between meals, stored nutrients are mobilised for energy use

Constant concentration of nutrients remains stable

How can the body/brain get ATP?

most tissues can generate ATP from fatty acids, then amino acids if starving

The brain can only get ATP from glucose, so concentration needs to remain stable

Where is glucose stored?

In the liver as glycogen

Glycogen can be broken down into glucose

What is glycogenesis?

Building glycogen from glucose

What is glycogenolysis?

Break down glycogen to release glucose

What is gluconeogenesis?

Making new glucose molecules from amino acids

What is an exocrine function in the pancreas?

A gland that secretes substances through ducts to the external environment or onto a surface

What hormones are produced by the pancreas?

Insulin (beta cells) and glucagon (alpha cells) in the islets of Langerhans

These hormones control blood glucose

What does insulin do?

Decrease blood levels of glucose, fatty acids and amino acids.

Favours the uptake and storage of glucose

How does insulin take up glucose?

Insulin binds to a receptor on the surface of the target cell

Makes GLUT4 in cell mebrane

GLUT4 transports glucose into the cells

What is important about glucose independent cells?

They are most at risk during diabetes

Function of glucagon?

Increase blood levels of glucose, fatty acids and amino acids

Stimulating glycogenolysis, inhibits glycogenesis all in the liver to release glucose into the blood

When are the hormones of the pancreas released?

Insulin: released during the absorptive state when blood glucose is increased

Glucagon: released during postabsorptive state when blood glucose is decreased

Glucose homeostasis

What is diabetes mellitus?

Impaired ability to utilise blood glucose

Characterised by hyperglycaemia (issue with glucose uptake)

How is type 1 diabetes classified?

10-15% of cases

Juvenile onset

Cause: genetic predisposition paired with environmental trigger (infection)

Autoimmune destruction of beta cells (inability to produce insulin)

Type 2 diabetes classification

85-90% of cases

Age of onset usually over 35

Cause: genetic predisposition, ethnic background, environmental factors (obesit, poor diet, lack of exercise)

Often associated with hypertension and hyperlipidaemia

Type 2 diabetes pathophysiology

1. Insulin resistance: insulin is produced but receptors are unresponsive or insufficient. Pancreas compensates by increasing insulin

2. Decreased production of insulin: beta cells become fatigued resulting in hyperglycaemia

3. Inappropriate glucose production: liver releases glucose when not needed

Type 1 v Type 2

How is diabetes diagnosed?

1. Fasting plasma glucose greater than or equal to 7 mmol/L

2. Two hour oral glucse tolerant test: plasma glucose greater than or equal to 11.1 mmol/L

3. Random plasma glucose: greather than or equal to 11.1 mmol/L (if you have diabetes symptoms)

What is the oral glucose tolerant test?

Measuring fasting plasma glucose, then measuring plasma glucose after 75g ingested

oral glucose tolerance test plasma levels

What are the types of prediabetes?

Impaired fasting glucose

OR impaired glucose tolerance

What consequences occur because of hyperglycaemia?

Glycosuria (glucose in the urine)

Polyuria (excessive urination)

Polydipsia (excessive thirst)

What other acute consequences of diabetes?

Polyphagia (excessive hunger)

Weight loss

Fatigue

Diabetic acidosis (can cause coma and death)

What chronic complications of hyperglycaemia?

Damage to blood vessels: endothelial cells ( can lead to microvascular and macrovascular disease)

What is microvascular disease - retinopathy?

Damage to blood vessels from hyperglycaemia causing damage to retina and impacting vision

What is microvascular disease nephropathy?

Damage to small blood vessels in the kidney - can cause increased blood pressure and fluid retention

What are macrovascular diseases?

Most common cause of death in type 2 diabetes, can cause:

• coronary artey disease

• stroke

• peripheral vascular disease

What are the neuropathies from diabetes?

Sensory neuropathy - change or loss in sensation

Autonomic neuropathy - faecal incontinence, urine retention, delayed gastic emptying, erectile dysfunction

What is diabetic foot?

Vascular disease causing poor blood flow and slow wound healing.

Sensory neuropathy means you cant feel it, and susceptibility to infection. Can lead to amputation!

What are adipokines?

Hormone produced by adipose cells.

1. Leptin: supresses appetitie

2. Adiponectin: increases sensistivity to insulin

3. Resistin: increases resistance to insulin

What does ghrelin do in short-term energy control?

Stimulates appetite before a meal by inhibiting PPY pathway. CCK & stomach distension after a meal stimulate satiety

Ghrelin controls appetite in the short-term, whereas leptin controls appetite in the long term.

True - ghrelin question

What are the limitations of BMI?

BMI does not distinguish between lean mass and fat mass

Overestimates body fat if body builder or broad frame

Underestimates body fat if elderly or muscle wasting