Diabetes + Endocrine Disorders

Question 1

Define diabetes mellitus

Answer 1

A chronic metabolic disease in which the body’s ability to produce or respond to the hormone insulin is impaired, resulting in abnormal metabolism of carbohydrates and hyperglycaemia

There are two main types of diabetes mellitus

Type 1 - Where the pancreas cannot produce insulin, this type is usually is diagnosed in childhood. Caused by either autoimmune or idiopathic B cell destruction

Type 2 - Develops due to prolonged hyperglycaemia in adults or adolescents, over time the bodies cells stop responding to insulin

Question 2

Define diabetes insipidus

Answer 2

An endocrine disorder involving under secretion of ADH by hypothalamus, causing extreme thirst (polydipsia) and increased urination (polyuria)

Question 3

What is the function of the pancreas?

Answer 3

Endocrine Function - Islets of langerhans cells secrete hormones (insulin and glucagon) into blood vessels to control blood glucose levels

Exocrine Function - Acinar cells secrete digestive enzymes into the pancreatic duct to help digest food (particularly protein)

Question 4

Name some clinical features of type 1 diabetes mellitus

Answer 4

Sudden onset with severe symptoms of thirst and ketoacidosis.

Recent marked weight loss - Subject is usually lean.

Spontaneous ketosis

Requires insulin to sustain life

Absent c-peptide

Markers of auto-immunity present (e.g. islet cell antibodies)

Question 5

Name some clinical features of type 2 diabetes mellitus

Answer 5

Usually insidious onset with associated fatigue, thirst, polyuria and nocturia.

Symptoms may be minimal and/or ignored by patient

No ketoacidosis

Usually overweight or obese with no associated weight loss.

Frequent infections e.g. urine, soft tissue, chest.

C-peptide detectable.

Other features of metabolic syndrome i.e. hypertension

Question 6

What factors contribute to the development of type 2 diabetes?

Answer 6

Obesity

Hypertension

Hyperlipdemia

Smoking

Sedentary lifestyle

Question 7

What is HbA1c a measure of?

Answer 7

The level of glucose adherence to haemoglobin over the last 3 months

Question 8

What does a HbA1c result of 48 mmol/mol (6.5%) or greater mean?

Answer 8

A level of 48 mmol/mol or higher supports a diagnosis of diabetes

Question 9

What is considered a normal HbA1c level for non-diabetic individual?

Answer 9

Below 42 mmol/mol (<6.0%)

Question 10

What are the two main short term complications of type 1 diabetes?

Answer 10

Ketoacidosis and coma (Diabetic ketoacidosis or DKA)

Hypoglycaemia

Question 11

What is DKA and why does it happen?

Answer 11

A state of severe uncontrolled diabetes caused by insulin deficiency, characterised by hyperglycaemia, hyperketonaemia (accumulation and elevation of circulating ketones) and metabolic acidosis (an increase in the hydrogen ion concentration that results in low serum bicarbonate levels)

The glucose in the blood stream of a type 1 diabetic goes largely unused since the absence of insulin means glucose cannot be transported into the cells for energy.

This condition means the body uses stored fat as an alternative means of energy.

This process produces acidic ketones, which then build up as ketones require insulin to break them down.

The presence of acidic ketones in the bloodstream causes the blood to more acidic than the body tissues, which creates a toxic condition.

Question 12

What are some common DKA symptoms?

Answer 12

High blood sugar levels

Frequent urination (polyuria) and thirst

Fatigue and lethargy

Blurred vision

Vomiting & Nausea

Abdominal pain

Fruity odour to breath

Rapid, deep breathing

Muscle stiffness, aching or cramps

Coma (10% of cases)

Question 13

What factors can precipitate DKA?

Answer 13

Infection

Insulin administration error or omission

Cardiovascular or cerebrovascular event (e.g MI or CVA)

Pancreatitis

Pulmonary embolism

Excessive alcohol consumption

Steroid use

Question 14

What are the main 3 macro-vascular complications of diabetes mellitus?

Answer 14

Cardiovascular disease - MI, heart failure e.t.c

Cerebrovascular Disease - Stroke, cognitive impairment e.t.c

Peripheral Vascular Disease - Acute and chronic limb ischaemia, gangrene, amputation

Question 15

What are the main 3 micro-vascular complications of diabetes mellitus?

Answer 15

Diabetic Retinopathy

Diabetic Nephropathy

Diabetic Neuropathy

Question 16

What is the main pathological factor in the development of macro-vascular complications in diabetes?

Answer 16

Atherosclerosis - the formation of fatty plaques (atheroma) on the inner wall of an artery (tunica intima), the plaques harden over time and cause narrowing of the vessel (sclerosis)

Question 17

What are the main pathological mechanisms involved in the development of micro-vascular diabetes complications?

Answer 17

The kidneys, retina and vascular endothelium are insulin independent tissues, meaning glucose moves freely across the cell membrane of these tissues regardless of the action of insulin - in diabetes this causes intracellular hyperglycaemia

Which causes…

Increased production of vascular endothelial growth hormone (VEGF)

Oxidative stress

Excessive sorbitol production (over-activation of the polyol pathway)

The non-enzymatic formation of advanced glycated end products (AGEs)

These mechanisms are thought to induce microvascular endothelial dysfunction - causing diabetic nephropathy, neuropathy and retinopathy

Question 18

What pathological mechanisms contribute to the development of atherosclerosis in diabetes?

Answer 18

Hyperglycaemia

Hypertension

Dyslipidemia - Imbalance of lipids (low density lipoprotein cholesterol, triglycerides and high density lipoproteins)

Advanced Glycoslated Endproduct (AGE) production

Increased oxidative stress

Inflammation

Question 19

Why is the risk of cardiovascular and cerebrovascular disease higher in patients with type 2 diabetes?

Answer 19

Type 2 diabetes usually occurs in the setting of metabolic syndrome: Abdominal obesity, hypertension, hyperlipidemia, increased coagulability and insulin resistance

These factors are all associated with the development of atherosclerosis, a major contributing factor to conditions such as coronary artery disease, myocardial infarction, TIA, CVA e.t.c

Question 20

How are the macro-vascular complications of diabetes managed?

Answer 20

Lifestyle Modification - Recommend diet adjustment, exercise and smoking cessation if applicable

Management of Hyperglycaemia - Type 1 = Insulin, Type 2 = Metformin

Management of Hypertension - ACE inhibitors (Ramipril, Lisinopril), ARBs (Candesartan, Irbesartan), Calcium channel blockers (Amlodipine, nifedipine)

Management of Dislipidemia - Statins/ HMG-CoA reductase inhibitors (Atorvastatin, Fluvastatin)

Question 21

What is the polyol pathway?

Answer 21

A metabolic pathway that converts glucose into glucose alcohol (sorbitol). This is also known as the sorbitol-aldose reductase pathway (aldose reductase is the inital enzyme in the intracellular polyol pathway)

This pathway is only triggered when there is high levels of glucose in the body: as in a hyperglycaemic state the affinity of aldose reductase for glucose rises, which causes the accumulation of sorbitol

Question 22

How is the polyol pathway involved in diabetic micro-vascular complications?

Answer 22

Chronic hyperglycaemia leads to excessive activation of the polyol pathway - increasing intra and extra cellular sorbitol and fructose

Which causes changes in vascular permeability, cell proliferation and capillary structure via stimulation of the protein kinase C and transforming growth factor-beta

This process also results in…
Intracellular oedema and osmotic stress - which results in electrolyte imbalances and membrane damage

Oxidative stress - due to decreased levels of NADPH

Formation of AGEs - due to increased phosphorylation of fructose

Question 23

How does oxidative stress contribute to the development of micro-vascular diabetes complications?

Answer 23

High glucose levels can stimulate the production of free radicals and formation reactive oxygen species (ROS), which causes oxidative stress, leading to vascular dysfunction

Question 24

How does the formation of AGEs and vascular endothelial growth factor contribute to the development of micro-vascular complications in diabetes

Answer 24

Hyperglycaemia promotes the non-enzymatic formation of advanced glycated end products (AGEs) - which is associated with pericyte (cells present in the walls of capillaries, small arterioles and venules - they regulate blood flow) loss, tissue injury and inflammation

Production of endothelial growth factor (VEGF), growth hormone and transforming growth factor beta is increased in diabetic retinopathy and is thought to be a response to retinal hypoxia

Question 25

What is the most common micro-vascular complication of diabetes?

Answer 25

Diabetic retinopathy

Question 26

What are the 3 stages of diabetic retinopathy?

Answer 26

Stage 1 - Background Retinopathy: Micro-aneurysms and ‘dot’ haemorrhages appear within inner layer of the retina, sight not yet affected Stage 2 - Pre-Proliferative Retinopathy: More severe changes including retinal haemorrhage and oedema, high risk of developing vision loss Stage 3 - Proliferative Retinopathy: Neovascularisations (new blood vessels) form on retina, significant bleeding occurs. Potential for retinal detachment and very high risk of vision loss

Question 27

What is diabetic nephropathy and how does it progress?

Answer 27

Progressive deterioration of renal function caused by the micro-vascular damage associated with diabetes mellitus. Prolonged hyperglycaemia causes renal hypertrophy (kidneys increase in size - approximately 25%) and an increased glomerular filtration rate Renal function begins to decline, causing persistant microalbminuria and proteinuria (elevation of albumin and presence of protein in urine) and decreased glomerular filtration rate This progresses to overt diabetic nephropathy with massive microalbuminuria, will progress to ENRF within 8 years if not treated Finally, GFR declines to <10ml/min - end stage renal failure, dialysis or transplantation necessary

Question 28

What is the most common form of neuropathy in diabetes?

Answer 28

Chronic sensorimotor distal symmetrical polyneuropathy - otherwise known as ‘stocking and glove’ neuropathy

Question 29

How does diabetes cause neuropathy?

Answer 29

Prolonged hyperglycaemia leads to microvascular damage of the vessels supplying nerves, this causes necrosis of the nerve fibres leading to potential sensory, motor and autonomic peripheral neuropathy.

Question 30

What is the function of the thyroid gland?

Answer 30

To regulate the body’s overall metabolism by secreting thyroid hormones: Thyroxine (T4) and Triiodothyronine (T3)

Question 31

What are the two common types of hyperthyroidism?

Answer 31

Grave’s Disease & Toxic Multinodular Goitre

Question 32

What are the common signs and symptoms of hyperparathyroidsm?

Answer 32

Heat intolerance - sweating and irritability Weight loss Tremor Palpitations Exophthalmos - protruding eyes Muscle wastage Tachycardia Diarrhoea Restlessness Osteoporosis - accelerated bone remodelling, can also cause hypercalciuria and hypercalcaemia

Question 33

What is Grave’s disease?

Answer 33

An autoimmune disorder that involves over activity of the thyroid gland, associated with typical symptoms of hyperthyroidism (exophthalmos, heat intolerance, weight loss e.t.c), an enlarged thyroid, pre-tibial myxedema (infiltrative dermopathy characterised by oedema and a waxy orange peel appearance of affected area) and pernicious anemia (lack of red blood cell production due to vitamin b12 deficiency)

Question 34

How is hyperthyroidism treated?

Answer 34

Medication to reduce thyroid hormone production - Carbimazole and Propylthiouracil Radioactive Iodine Therapy to destroy cells in the thyroid gland Surgical excision of all or part of the thyroid gland

Question 35

What are some signs and symptoms of hypothyroidism?

Answer 35

Weight gain Intolerance to cold Fatigue and lethargy Muscle cramping Slow reflexes Dry pale skin and brittle hair Hoarse voice Constipation Dementia or psychosis Bradycardia Hypertension Heart enlargement (late stages)

Question 36

How is hypothyroidism treated?

Answer 36

Synthetic Thyroid Hormone - Levothyroxine

Question 37

What is the function of the parathyroid gland?

Answer 37

To control and regulate the levels of calcium within the body - does this by secreting parathyroid hormone

Question 38

What are some signs and symptoms of hyperparathryoidism?

Answer 38

Fatigue Muscle weakness Nausea & loss of appetite Confusion & depression Hypercalaemia (High levels of calcium in the blood) Renal calculi/ kidney stones Peptic ulcers Pancreatitis Hypertension Bone or joint pain Irregular heartbeat

Question 39

What are some signs and symptoms of hypoparathyroidism?

Answer 39

Tingling (Paraesthesia) of the fingers, toes and lips Facial twitch/ fasiculations Muscle cramping , especially in legs, feet and abdomen Anhidrotic skin Coarse hair Hypocalcaemia Hyperphosphatemia - high levels of phosphate in the blood

Question 40

What is the function of the adrenal glands?

Answer 40

Maintain and regulate sodium levels, blood pressure, renal function and overall fluid levels in the body - does this by secreting adrenaline, aldosterone and cortisol

Question 41

What is Cushing’s disease?

Answer 41

A condition characterised by the over-production of cortisol. This can cause… Hyperglycaemia Osteoporosis Abdominal obesity with slim arms and legs Thin skin GI distress ‘Moon face’ - puffy rounded appearance of face Redness of the cheeks Deposition of fat on the back of the neck and shoulders

Question 42

What is Addison’s disease?

Answer 42

Also known as primary adrenal insufficiency or hypoadrenalism, is a disorder in which the adrenal glands do not produce enough cortisol or aldosterone. This can cause: Hypoglycaemia Postural hypotension Weight loss Bronze pigmentation of the skin Muscle weakness Adrenal crisis - Profound fatigue, dehydration, vascular compromise, reduce BP, reduced serum NA and increased serum K

Question 43

What is the function of the pituitary gland?

Answer 43

To control the activity of many other endocrine glands. It releases: TSH - Thyroid stimulating hormone ACTH - Adrenocortictropic hormone to regulate adrenal glands FSH - Follicle stimulating hormone to regulate ovaries and testes Prolactin - To stimulate breast milk production in women Growth Hormone - to stimulate growth metabolism ADH - Anti-diuretic hormone (produces by hypothalamus but stored in the pituitary) Oxytocin - To contract the uterus in childbirth

Question 44

What is acromegaly?

Answer 44

A rare condition characterised by the over-production of growth hormone by the pituitary gland, often caused by a pituitary adenoma. This can cause: Abnormally large hands and feet Hypertrophy of the sweat and sebaceous gland - oily skin and hyperhydrosis Large, prominent facial features (I.E a prominent suborbital ridge) Coarse, thickened skin Headaches Sexual dysfunction Hypertension Blurred vision Joint pain Cardiomyopathy