- caused by either insufficient production/transport/release of ADH, or inadequate response of the renal tubules to ADH

- thirst

- polyuria

- syndrome of inappropriate antidiuretic hormone secretion

- high levels of ADH

- common cause is ectopic production of ADH by tumours in other organs (duodenum, stomach, bladder, etc.)

- common cause in elderly is medications

- diabetes insipidus

- SIADH

- inadequate supply of hypothalamic-releasing hormones or inability of the pituitary gland to produce hormones

- common cause is problem w/in the pituitary gland: infarction, tumour, aneurysm

- brought on through head trauma, infections, etc.

- result in deficiency in some or all pituitary hormones depending upon w/c area of the pituitary is affected

- dificiency in some or all pituitary hormones

- caused by a tumour (adenoma)

- may get oversecretion of hormone by tumour, accompanied by undersecretion of hormones fr. tissues surrounding tumour

- tumuor may cause disturbance in vision (optic chiasm is adjacent)

- hypopituitarism

- hyperpituitarism

- glucose accumulates in the blood

- appears in the urine

- polyuria and thirst

- wide fluctuations in blood glucose occur

- protein and fat breakdown occur, resulting in weight loss

- high levels of circulating ketones (diabetic ketoacidosis DKA)

- non-insulin dependent diabetes mellitus

- genetic-environmental interaction appears to be responsible

- age

- obesity

- hypertension

- physical inactivity

- family history

- a collection of disorders that confer a high risk of developing type 2 diabetes

- central obesity

- dyslipidemia

- prehypertension

- elevated fasting blood glucose level

- compensatory hyperinsulinemia occurs due to insulin resistance (beta cells produce more and more insulin)

- this prevents the clinical appearance of diabetes for many yrs

- however, beta-cell dysfxn develops eventually and leads to: decrease in the # of beta-cells & reduction of normal beta-cell fxn

- the remaining fxning beta cells undergo "exhaustion" fr. increased demand for insulin biosynthesis

- like type 1 diabetes, there's an increase in glucagon secretion, w/c leads to further hyperglycemia

Primary - problem w/the target gland responsible for producing the hormone

Secondary - problem w/the pituitary gland releasing/inhibiting hormone release

Tertiary - problem w/the hypothalamus production of the controlling hormone for the pituitary

Thyroid (thyroxin)

Adrenal cortex (cortisol)

- characterized by hyperglycemia resulting fr. defects in insulin secretion, action or both

- thyrotoxicosis results fr. increased levels of thyroid hormones (T3 and T4)

- primary: graves disease

- secondary: TSH secreting pituitary adenoma

- exophthalmic goiter

- weight loss

- heat sensitivity

- increased metabolic rate

- fr. Type 2 hypersensitivity rxn

- AB have been produced agnst the TSH receptors on thyroid gland cells, resulting in stimulation of thyroid hormone production

- most common disorder of thyroid fxn

- primary:

- autoimmune rxn (hashimoto disease: autoAB + autorctve T lymphcytes, induced apoptosis, etc. w/c destroys thyroid gland)

- drugs

- radiation therapy

- secondary:

- pituitary tumour compressing surrounding pituitary cells (or treatment of pituitary tumour) = decreased TSH

- low metabolic rate

- cold intolerance

- lethargy

- myxedema (dry skin, swellings around the lips and nose, mental deterioration, and a subnormal basal metabolic rate)

hyperthyroidism

hypothyroidism

1. Type 1: beta-cell destruction, leading to absolute insulin deficiency

2. Type 2: ranging fr. insulin resistance w/ relative insulin deficiency to an insulin secretory defect w/ insulin resistance

3. other specific types eg. genetic defects in beta cell fxn

4. gestational diabetes

- most common pediatric chronic disease

- slowly progressive autoimmune T cell-mediated disease that destroys beta cells of the pancreas

- destruction is related to genetics and the environment

- Type 1 diabetes cause AG (autoAG) to develop on the surface of pancreatic beta cells and then circulate in the bloodstream/lymphatics

- immune system responds and destroys beta cells

- hyperglycemia develops (80-90% destroyed betacells)

How does glucagon secretion play a role in Type 1 diabetes?

- insulin suppresses the secretion of glucagon - hormone that stimulates glycogenesis and gluconeogenesis 

- a decrease in the production/secretion of insulin allows glucagon secretion to increase leading to glycogenesis and glucogenesis = increased hyperglycemia

- more children and adolescents but generally affects those under 30yrs

- individual often: overweight, dyslipidemic, hyperinsulinemic, hypertensive

- polyuria

- polydipsia

- often have nonspecific symptoms such as fatigue, pruritus, recurrent infections, visual changes

- below optimal response of insulin-sensitive tissues (liver, muscle and adipose tissue) to insulin

- associated w/ obesity, w/c contributes to the development of insulin resistance

- genetic defects in beta-cell fxn

- diseases of the exocrine pancreas

- drug or chemical induced beta-cell dysfxn

- any degree of glucose intolerance w/ onset or first recognition during pregnancy

- many women were type 1/2, this was jst recognized during pregnancy eg. disease continued to worse after delivery

- women who have this have a 35-60% chance of developing diabetes mellitus in the next 10-20 yrs

1. hypoglycemia

2. diabetic ketoacidosis

3. somogyi effect

4. dawn phenomenon

5. HHNKS - hyperosmolar hyperglycemic nonketotic syndrome

- insulin shock/rxn

- symptoms: pallor, tremor, tachycardia, palpitations, dizziness, confusion, seizures, coma

- more in type 1 than type 2

- individuals w/ type 2 still have mechanisms to increase blood glucose levels but can occur w/ those on insulin replacement therapy

- requires immediate replacement of glucose

- diabetic ketoacidosis

- w/ insulin deficiency, more w/ type 1, lipolysis is enhanced = more fatty acids delivered to the liver

- gluconeogenesis also is occurring, leading to the production of more ketones

- build up of ketones results in metabolic acidosis

- symptoms: hyperventilation, dizziness, nausea, CNS depression

- hypoglycemia-hyperglycemia alternating episodes

- insulin induced hypoglycemia occurs, w/c causes the release of epinephrine, growth hormone, corticosteroids (cortisol)

- these hormones stimulate gluconeogenesis, leading to hyperglycemia (treat it w/ insulin)

- "rebound hyperglycemia"

- blood glucose levels rise in early morning w/no hypoglycemia during the night

- related to increased release of growth hormone during the night (decreases metabolism of glucose by muscle and fat)

- hyperosmolar hyperglycemic nonketotic syndrome

- complication of type 2, can be fatal 

- high glucose levels + high plasma osmolarity + dehydration, but no ketoacidosis (enough insulin to inhibit lipolysis but not enough to decrease glucose levels in blood)

- if blood glucose is high, the kidneys excrete more fluid; if not replaced dehydration occurs eg. result of illness

- excessive dehydration pulls water out of the cells, including brain cells

- symptoms: weakness, dehydration, polyuria, neurological signs/symptoms (eg. aphasia)

- common in elderly people; onset can be very gradual and may be mistaken for a stroke

1. Metabolic

- tissues that don't require insulin to import glucose such as kidneys, rbcs, blood v., eye lens, nerves can't down-regulate the uptake

- so excess glucose is converted to sorbitol, and build up causes nerve problems (schwann cell, and conduction damage, last swollen eyes due to osmotic pressure damage)

- long term problem cause glucose permanently binding to proteins inside/outside cells and interfering w/ cell metabolism

2. Macrovascular: lesions in large and medium sized arteries

- due to attachment of glycosylated compounds (cmpnds containing glucose) to proteins in the vessel wall

- increased risk for:

- accelerated atherosclerotic disease

- coronary artery disease (most common cause of morbididy and mortality in people w/ DM)

- stroke

- peripheral vascular disease - gangrene, ulcers

- often involves arteries below the kneww

- occlusions of the small arteries cause most of the gangrenous changes of lower extremities

3. Microvascular: diseases of the capillaries

- thickening of capillary basement membrane, endothelial hyperplasia, thrombosis

1. Diabetic retinopathy

- leading cause of blindness

- results fr. increased capillary permeability, ischemia, etc.

2. Diabetic nephropathy

- common cause of end stage kidney disease

- hyperglycemia contributes to kidney disease

- glomeruli are injured by protein denaturation and high renal blood flow fr. hyperglycemia

3. Diabetic neuropathy

- due to metabolic factors (build up of sorbitol) and vascular factors (ischemia)

- sensory deficits more common than motor and often involve the extremities

4. Infection

- those w/ DM are at increased risk of infection due to impaired senses (more likely to have an accident), impairment of the immune system, increase in pathogen growth due to higher level of glucose in body fluids