Endocrinology Part One

• Glucose is vital for energy, particularly for red blood cells and nerve cells.

Glucose Regulation

• Insulin reduces blood glucose levels and is considered hypoglycaemic.
• Glucagon, cortisol, catecholamines, and growth hormone elevate blood glucose levels, making them hyperglycaemic.
• After meals, glucose is stored as glycogen in the liver and fat tissues.
• During fasting, glucose is retrieved through glycogenolysis in the liver, and gluconeogenesis from amino acids.
• Insulin, a polypeptide hormone from beta cells in the Islets of Langerhans, facilitates glucose absorption into cells, promoting fat and protein synthesis.
• Glucose control is designed to maintain stable blood sugar levels, store energy, and provide energy when needed.
• The brain can absorb glucose from the blood independently of insulin control, but it is vulnerable to conditions affecting blood sugar levels.
• Glucagon, produced by alpha cells in the Islets of Langerhans, increases blood glucose levels in response to hypoglycemia, opposing insulin's effects.
• Catecholamines, released by the adrenal medulla during stress, raise blood glucose to fuel the fight-or-flight response.
• Cortisol and growth hormone promote gluconeogenesis, which elevates glucose levels.
• Hyperglycemia typically develops from an imbalance in glucose regulation, either from lack of insulin or from excess glucagon, cortisol, or catecholamines.

Diabetes Mellitus

• Diabetes mellitus is characterized by chronic hyperglycemia due to insulin deficiency, tissue resistance, or both.
• Insulin's main role is to convert glucose to glycogen for storage when blood glucose levels are too high.
• Diabetes mellitus is classified as primary, often insulin-dependent (Type 1), indicating hormone failure.
• Diabetes mellitus can occasionally be secondary to conditions like pancreatitis, Cushing's syndrome, acromegaly, or due to drugs like steroids and thiazide diuretics.
• Type 2 diabetes mellitus is insulin-independent, often diagnosed in older patients where the tissues are resistant to the effects of insulin.

Type 1 vs Type 2 Diabetes

• Type 1 Diabetes:
  • Typically occurs in younger patients (10-20 years old).
  • Has an acute onset.
  • Patients are usually lean.
  • More common in people of European descent.
  • Uncommon family history.
  • Linked to the HLA system (DR3/DR4).
  • 30-35% risk to identical twins.
  • Autoimmune or viral etiology.
  • Always requires insulin.
• Type 2 Diabetes:
  • Typically occurs in older patients (over 40 years old).
  • Has a chronic onset.
  • Patients are often obese.
  • Found in all racial groups.
  • Frequent family history.
  • No HLA links.
  • Over 90% risk to identical twins.
  • Associated with obesity.
  • Managed with diet and oral hypoglycemics, sometimes requiring insulin.
• Type 1 diabetes results from a viral infection in genetically predisposed individuals, leading to autoimmune destruction of insulin-producing pancreatic beta cells.
• Type 2 diabetes involves a 50% reduction in beta cell mass, resulting in inadequate insulin secretion and peripheral tissue insulin resistance.

Complications of Diabetes Mellitus

• Long-term complications include neurological conditions, diabetic ketoacidosis, autonomic symptoms (palpitations, sweats), oral candidiasis, and increased risk of cardiovascular and kidney diseases, vision loss, and infections.
• Symptoms of hyperglycemia include frequent urination caused by excess glucose exceeding the kidney's re-absorption limit.

Diabetes & Diet

• Dietary adjustments include reducing fat intake to 30-35% (mainly unsaturated), protein to 10-15%, and increasing complex carbohydrates to 50% of total energy intake.

Diabetes & Medication

• Oral hypoglycemics are used if diet control alone is insufficient:
  • Sulphonylureas: Increase beta cell insulin secretion and reduce peripheral resistance to insulin action.
  • Glibenclamide: Long-acting with renal excretion, so it should be avoided in elderly patients and those with renal failure.
  • Tolbutamide: Short-acting with liver metabolism, which makes it suitable for older patients and those with renal failure.
  • Biguanides (Metformin): Decreases gut glucose absorption and increases peripheral tissue insulin sensitivity without increasing appetite.

Diabetes & Life Expectancy

• Poor control and earlier onset reduce life expectancy, mainly due to diabetic nephropathy.

Macrovascular Complications

• Accelerated atheroma risk factors are hypertension, hyperlipidaemia and smoking.
• Macro-vascular complications include stroke, ischemic heart disease, MI, and ischemic limbs/gangrene.

Microvascular Complications

• Microvascular diseases include diabetic retinopathy (blindness), diabetic nephropathy (renal failure), and diabetic neuropathy (loss of sensation in fingers and feet, autonomic systemic failures).

Avoiding Complications

• Meticulous glycemic control and urine testing for albuminuria can help delay and avoid complications.

Diabetes & Infections

• Diabetes can affect wound healing in the oral cavity and extraction sockets and can cause oral candidiasis.
• Poorly controlled diabetes reduces polymorph function, which increases the risk of UTI and skin infections.
• Skin infections include lipodermatosclerosis (fatty lumps at injection sites), necrobiosis lipoidica diabeticorum (red/waxy brown deposits on shins), and granuloma annulare (fleshy nodules over extensor surfaces of fingers).