Diabetes Type 2 Characteristics

Diabetes Mellitus

• Diabetes type 2: usually later onset, insulin resistance, milder than type 1, associated with diet and lifestyle (e.g. obesity), increasing incidence (including in children)
• Hyperglycemia but usually no ketoacidosis, often responds to diet and oral hypoglycaemic agents

Metabolic Pattern in Uncontrolled Diabetes Mellitus

• Resembles starvation, but effects are more exaggerated
• In starvation, insulin is low, glucagon acts unopposed
• KB produced in starvation stimulate insulin release, limiting muscle protein breakdown, FA release from adipocytes, and uncontrolled KB production
• This mechanism does not operate in diabetes

Metabolism in Diabetes

• High glucagon, low insulin
• Glucose and KB production

Chronic Complications of Diabetes Mellitus

• Microangiopathy: changes in small blood vessel walls, thickening of basement membrane
• Retinopathy: blindness 25 times more common in diabetic patients
• Nephropathy: renal failure 17 times more common
• Neuropathy: postural hypotension, impotence, foot ulcers

Treatment

• Type 1: exogenous insulin by injection

Fuel Reserves in the Average Man

• Total fuel reserves: 167,850 Kcal (697.8 MJ)
• Glycogen: 300g (muscle), 80g (liver), energy value: 1460 Kcal (6.1 MJ), 330 Kcal (1.4 MJ)
• Glucose: 15g (body fluids), energy value: 60 Kcal (0.3 MJ)
• TAG: 15kg (adipose tissue), energy value: 140,000 Kcal (580 MJ)
• Protein: 6kg (muscle), energy value: 26,000 Kcal (110 MJ)

The Fasting (Post-Absorptive) State

• Blood glucose concentrations peak an hour after eating, return to normal by 2 hours
• Blood glucose is removed for oxidation or storage
• Concentration of insulin drops, glucagon rises

Metabolism in the Fasting State

• Early events: liver and adipose tissue
• Liver maintains blood glucose concentrations at about 4mM
• Adipose tissue provides greatest source of energy as TAGs
• Hormone-sensitive lipase activated by glucagon and adrenaline
• FA transported to liver bound to albumin

Glucose Production by the Liver

• Liver glycogen is the first supplier of blood glucose
• Gluconeogenesis follows from lactate, glycerol, and amino acids
• After 24 hours of fasting, all blood glucose comes from gluconeogenesis

Sources of Blood Glucose After Ingestion of 100g Glucose

• Not shown in the original text, but mentioned as a topic

Fatty Acids are NOT Gluconeogenic Precursors

• Reaction catalysed by Pyruvate dehydrogenase is IRREVERSIBLE
• PDH is activated by insulin and inhibited by glucagon
• Ensures that in fasting, gluconeogenic substrates are channelled into glucose production, not acetyl CoA formation

Fed State, Liver:

• Glycolytic enzymes are activated, pyruvate dehydrogenase is activated, and excess acetyl CoA is channelled into FA synthesis

Fasting State, Liver:

• FA can be used as fuel by liver, adipose tissue, and muscle; draining of gluconeogenic substrates into acetyl CoA is inhibited, and conversion to glucose is favoured

Ketone Body Formation

• FA oxidation in hepatocyte leads to high concentrations of Acetyl CoA
• It exceeds the capacity of the TCA cycle
• It is channelled into ketone body formation
• Acetoacetate and β-hydroxybutyrate are released into the bloodstream
• Most tissues oxidize a mixture of FA and KB
• Erythrocyte uses glucose
• Brain uses glucose and small amount of KB

Prolonged Fasting (Starvation)

• If the early pattern continued, body protein would be severely depleted
• Only about a third of body protein can be lost without severe or fatal consequences

Fuel Concentration in the Blood in Prolonged Fasting

• Not shown in the original text, but mentioned as a topic

Metabolism in Starvation

• As starvation continues, more KB are recovered from the kidney
• Muscle uses FA rather than KB
• FA concentrations plateau, KB rise
• Brain can use more KB and less glucose
• Need for gluconeogenesis is reduced, muscle protein breakdown decreases
• Urea production decreases

Ketone Bodies

• Act on pancreas to stimulate insulin release
• Limit muscle proteolysis and adipose tissue lipolysis
• Muscle tissue is conserved

Eventually

• Amount of adipose tissue is an important determinant of survival
• Death comes from fuel exhaustion, loss of function from loss of protein, and impairment of the immune system
• Death from starvation is often due to infection
• About 40 days (young and fit, may be longer)

Glucose Tolerance Curves of Normal and Diabetic Subjects

• Not shown in the original text, but mentioned as a topic

Diabetes Mellitus

• Affects 6% of population in UK
• 90% of all endocrine disorders
• Major cause of blindness, amputations, premature deaths
• 10% of total health care budget

Learn about the characteristics of diabetes type 2, including its onset, symptoms, and treatment options. This quiz covers insulin resistance, association with diet and lifestyle, and the metabolic pattern in uncontrolled diabetes.