essay 8 - diabetes mellitus - etiology, pathogenesis, pathobiochemistry, complications

Define diabetes

it is a heterogeneous group of disorders of carbohydrate metabolism involving absolute or relative insulin deficiency. the common feature is hyperglycemia

The Classifications of diabetes

• Type One Diabetes mellitus + LADA (Latent autoimmune Diabetes in adults)

• type Two Diabetes mellitus

• gestational diabetes

• other specific = drug induced, endocrinopathies, Destructive diseases of pancreas + MODY (maturity Onset diabetes of the young)

Describe Type One Diabetes mellitus

• insulin dependent and usually onset is during childhood, except for LADA

• there is a autoimmune destruction of pancreatic beta cells, this condition is genetically predisposed and usually triggered by environmental factors such as viral infections

1. the destruction of pancreatic beta cells leads to absolute insulin deficiency

2. loss of insulin production means that there is an inability to lower blood glucose

3. When insulin is present, it tells α‑cells: “Stop releasing glucagon, we have enough glucose.” increase Glucagon levels stimulate glucogenesis (making of new glucose) and glucogenolysis (breakdown glycogen into gucose) leading to severe hyperglycaemia. there is also lipolysis and ketone formations, providing a risk of ketoacidosis

• consequences are = weight loss, fatigue, Polyurea, polydipsia and polyphagia

describe type Two Diabetes mellitus

• due to insulin resistance usually onset during adulthood. there is genetic and environmental predisposition such as family history, obesity, sedentary lifestyle

1. development of insulin resistance; Target tissues (skeletal muscle, liver, adipose) becomes less responsive to insulin

2. beta cell compensation and hyperinsulinemia (high insulin in blood)

3. over time the beta cells become exhausted and this leads to insulin deficiency

4. progressive hyperglycaemia; as insulin secretion falls and resistance persists, blood glucose rises

• consequences = persistent hyperglycemia (polyurea, polydipsia, fatigue) and in the long term there is microvascular and macrovascular consequences

describe gestational diabetes mellitus

• a form of glucose intolerance that is first recognised during pregnancy. it occurs because pregnancy is a state of natural insulin resistance, mediated by placental hormones

1. placental hormones induce insulin resistance in maternal tissues

2. maternal pancreas must increase insulin secretion to maintain normal glucose

3. in some women the beta cells fail to adequately compensate and relative insulin deficiency develops

4. maternal hyperglycemia → increased glucose transfer to foetus → foetal hyperinsulinemia

• consequences for the mother are = higher risk of preeclampsia and cesarean section, high risk of developing type 2 diabetes within 5-10 months postpartum

• consequences for the baby are = excessive foetal growth, increased risk of obesity and type 2 diabetes

carbohydrate metabolism in diabetes

• impaired cellular uptake of glucose

• increase glucogenesis and glycogenolysis in liver

lipid metabolism in diabetes

• increase lipolysis

• in type 1 = Uncontrolled lipolysis
  → massive breakdown of triglycerides

• ↑ Free fatty acids flood the liver

• Liver converts them into ketone bodies

• Ketones accumulate → metabolic acidosis

• In Type 2 = risk of atherosclerosis due to dyslipidemia

protein metabolism

• increase proteolysis and muscle wasting

acute complications

• diabetic ketoacidosis (mainly type 1)

• hyperoglycaemic hyperosmolar non ketonic syndrome (mainly in type 2)

chronic complications

• microvascular = peripheral neuropathies, diabetic neuropathy, retinopathy

• macrovascular = CAD, peripheral vascular disease and cerebrovascular disease

• diabetic foot ulcers