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Diabetes
How Insulin Works
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin_phys.html
The 10% to Retain
Definition
A disorder of metabolism characterized by high plasma levels of glucose
Classification
Type-1
Autoimmune disease against ß cells
in the pancreas. Possibly viral
Type-2
Insulin (high, normal or low) present
but cannot be utilized (insulin resistance).
Gestational
Diabetes during pregnancy.
Pre-Diabetic Conditions
State between normal and diabetes
Impaired Fasting Glucose (IFG)
Plasma glucose high when fasting
IFG high = 6-7 mmol/dL
(Fasting glucose preferred test)
Impaired Glucose Tolerance
Oral glucose test (OGT) performed.
OGT - 75grams of Glucose given orally
- 2 hrs post 7-11mmol/dL
Risk Factors
Family Hx
Obesity
Age
Hypertension
CAD, PVD
Dyslipidaemia
Previous Gestational DM
Diagnosis
Plasma random glucose > 11.1 mmol/L along with symptoms of diabetes mellitus
Plasma glucose > 7.0mmol/L after 8hrs fasting
OGT test value > 11.1mmol/L 2 hrs after 75g glucose PO.
Tests most reliable in morning and normally repeated on a different day for confirmation.
Symptoms Type 1
The symptoms of Type I diabetes often come on suddenly and very severely.
They include:
being exceptionally thirsty
dry mouth
the need to urinate often
weight loss (even though you may be hungry and eating well)
feeling weak and tired
blurry vision
Symtoms Type 2
Sometimes, people with Type II diabetes don't notice any symptoms or the symptoms are experienced gradually.
They include:
blurry vision
cuts or sores that are slow to heal
itchy skin, yeast infections
increased thirst
dry mouth
need to urinate often
leg pain
Short Term/Acute Complications
Acute hyperglycemic complications
HONK
DKA
Acute hypoglycemic complications
Hypoglycemia
Somogyi effect (Low & High)
HONK
Metabolic derangement characterized by:
Principally in Type 2 diabetics
Hyperglycemia
Hyperosmolarity
Absence of Ketones
Preceding probable:
Infection most common cause (Pneumonia, UTI)
Decrease hydration (Dementia, immobility, vomiting)
MI
Some drugs (Diuretics, H2 blockers)
Hyperosmolar hyperglycemic nonketotic coma (HHNC) is a metabolic derangement that occurs principally in patients with adult-onset diabetes. The condition is characterized by hyperglycemia, hyperosmolarity
osmotic diuresis due to a high concentration of osmotically active substances in the renal tubules (e.g., urea ,sodium sulfate ), which limit the reabsorption of water and an absence of significant ketosis.
Pathophysiology:
HHNC most commonly develops in diabetic patients who have some concomitant illness that leads to a reduced fluid intake.
Infection is the most common cause, but many other conditions can cause altered mentation and/or dehydration.
Frequently, this concomitant illness is not identifiable.
Hyperglycemia and hyperosmolarity lead to osmotic diuresis and an osmotic shift of fluid to the intravascular space, resulting in further intracellular dehydration.
DKA
Clinically, uncontrolled diabetes that requires emergency treatment with insulin and intravenous fluids.
Biochemically, an increase in the serum concentration of ketones greater than 5 mEq/L, a blood glucose level of greater than 200 mg/dL, and a blood pH of less than 7.2. (200/18 = 11.1)
DKA
DKA present at diagnosis of type 1 diabetes due to acute insulin deficiency (occurs in 25% of patients)
Poor compliance with insulin through the omission of insulin injections either due to lack of patient or guardian education or as a result of psychological stress, particularly in adolescents Intercurrent illness (eg, UTI, vomiting)
Medical, surgical, or emotional stress
Brittle diabetes Idiopathic (no identifiable cause) Insulin infusion catheter blockage
Mechanical failure of insulin infusion pump
Causes of DKA
DKA present at diagnosis
Poor compliance
Intercurrent illness (e.g., UTI, vomiting)
Medical, surgical, or emotional stress
Brittle diabetes
Idiopathic (no identifiable cause)
Insulin infusion catheter blockage
Mechanical failure of insulin infusion pump
Hypoglycaemia
A reduction in plasma glucose concentration to a level that may induce symptoms of low blood sugar.
To diagnose hypoglycemia, the Whipple triad characteristically is present.
This triad includes the documentation of low blood sugar, presence of symptoms, and reversal of these symptoms when the blood sugar level is restored to normal.
Somogyi Effect
Swing to high plasma glucose from overnight low plasma glucose
? Swing due to stress hormone release
AM readings may cause nighttime adjustment of insulin and compound problem.
Treatment involves adjusting supper snacks.
Somogyi speculated (1930s) that hypoglycemia induced by insulin could cause a counter-regulatory hormone response that produces Hyperglycemia.
Unappreciated nocturnal hypoglycemia could lead to morning hyperglycemia, and the physician or patient may increase the evening insulin, exacerbating the problem.
This phenomenon actually is less common than morning hyperglycemia due to hypoinsulinemia resulting from the dawn phenomenon.
Debate continues in the scientific community as to the actual presence of this reaction to hypoglycemia.
Long Term Complications
Micro vascular
Retinopathy
Nephropathy
Macro vascular
Lower Extremity Arterial Disease
Coronary Artery Disease
Cerebrovascular disease
Neurological
Neuropathy
Retinopathy
Normal Retina
Diabetic Retinopathy
The eyes can be affected in several ways by diabetes mellitus.
Diabetic retinopathy is one of the leading causes for irreversible blindness in the United States.
This retinopathy can occur with either type I or type II diabetes mellitus, usually a decade or so after the onset of diabetes.
Most persons with type I diabetes and many of those with type II diabetes develop some background (non-proliferative ) retinopathy.
Proliferative retinopathy is more ominous and is more likely to occur when diabetes mellitus is poorly controlled.
In severe retinopathy, neovascularization may lead to adhesions (synechiae) between iris and cornea or iris and lens.
Neovascularization of the iris leads to secondary glaucoma with blindness.
Cataracts are more common in diabetics.
This predilection for development of cataracts is felt to result from hyperglycemia leading to accumulation of sorbitol that results in osmotic damage to the crystalline lens.
Nephropathy
Thickening of the glomerular blood supply and then glomerular tissue.
A condition known as microalbuminuria provides the earliest clinical evidence of nephropathy. Microalbuminuria is characterized by low but abnormal levels of albumin (≥30 mg/day or 20 µg/min) in the urine (ADA, 2002c).
If left untreated, it may progress to overt nephropathy or clinical albuminuria (≥300 mg/day or ≥200 µg/min).
In patients with type 1 diabetes, hypertension is usually detected around the time that microalbuminuria develops and is usually caused by diabetic nephropathy (ADA, 2002c).
Hypertension is defined as a blood pressure at or above 140/90 mm Hg, and it is associated with faster progression of diabetic nephropathy.
Patients with hypertension should be advised to make lifestyle modifications, including losing weight, decreasing salt and alcohol intake, and exercising.
Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are antihypertensive medications that may slow the progression of nephropathy (ADA, 2002c).
NB - study up effects of renal failure on other body systems I.e. gut, bones etc.
Macro-vascular
Peripheral Vascular Disease
Coronary Artery Disease
Cerebro-Vascular Disease
Macrovascular disease
refers to changes in the medium to large-size blood vessels.
The blood vessel walls thicken and become hard and non-elastic (arteriosclerosis).
Blood vessels also become clogged with mounds of plaque (atherosclerosis).
Eventually, the flow of blood may be blocked. Three types of this disease are:
Peripheral vascular disease
refers to diseased blood vessels that supply the legs and feet.
If blood flow is only partially interrupted, cramps, weakness, "charley horse," or pain in the legs when walking (claudication) may result.
A completely blocked artery will cause severe pain and the leg will become cold and pale.
Treatments include replacing the diseased artery surgically or opening the blood vessel by compressing plaque against the artery wall (angioplasty).
Coronary artery disease
refers to diseased heart arteries. Cramping and angina may occur when blood flow is decreased.
Complete blockage of an artery results in myocardial infarction (heart attack).
Symptoms of angina and heart attack include chest pressure, cramping, heavy feeling in the chest, shortness of breath, and extreme fatigue.
Treatments include coronary bypass surgery and angioplasty.
Cerebral vascular disease
refers to diseased arteries in the brain.
Partial blockage may result in temporary reductions of blood supply to a part of the brain (transient ischemic attacks).
A complete loss of blood supply to an area of the brain due to clogging or breaking of a blood vessel results in a cerebral vascular accident (stroke).
Symptoms include lightheadedness, dizziness, loss of ability to speak, slurred speech, confusion, and inappropriate behavior.
If you experience symptoms of any form of macrovascular disease, go to a hospital emergency room at once.
Neuropathy
Peripheral
This is the commonest form of nerve damage. As the name indicates it occurs in the extremities most often in the feet (especially the toes) and less often in the hands.
Early symptoms can be pins & needles and cramp which if blood sugar control is poor may lead to numbness, loss of sensation or pain in the feet and toes.
Symptoms
are often worse at night. Infection after accidental damage can lead to foot ulcers and gangrene.
The current advice where some sensation has been lost in the feet is - Do not self treat corns or injuries to feet.
Make regular visits to a foot care specialist. Wear well fitting supporting footwear (lace ups are recommended). Check feet every day.
Check for sharp objects inside shoes. Don't go bare foot. Cushion-soled trainers are recommended if foot ulcers or foot infections are present.
Unlike Peripheral Neuropathy however it seems to cause no long term damage and individual attacks gradually improves with time.
Neuropathy
Focal Can affect:
Vision
Hearing
Face
Pain
Focal Neuropathy affects specific nerves and appears suddenly.
It can affect vision (causing difficulty in focusing or double vision), hearing, cause facial paralysis on one side of the face (Bell's Palsy) (Cranial nerve VII) or pain (in the inner thigh, pelvis, lower back, chest, stomach, flank, shin or the inside of the foot).
Autonomic
Affected part of body & symptoms
Stomach: Heartburn, bloating, nausea, and vomiting
Bowel: Alternating bouts of diarrhea and constipation
Bladder: Difficulty in emptying & controlling bladder
Sexual Organs: Erectile dysfunction in men, vaginal dryness in women
Blood Vessels: Dizziness or lightheadedness upon rising
Heart: Rapid or irregular heart beat
Skin: Abnormal sweating
Autonomic neuropathy can affect - The Heart, Lungs, Digestion, Sexual
Organs (causing impotence in men), Sweat glands & Bladder.
Autonomic problems may be indicated if there is a fast heart rate or a fall in blood pressure on standing (indicated by fainting, feeling light headed or dizzy).
Autonomic Digestive problems are likely to cause blood sugar control to get worse with stomach bloating, constipation or diarrhea.
Autonomic neuropathy produces chronic venous swelling.
Motor peripheral neuropathy or Charcot osteoarthropathy can produce bony deformity, which, combined with the loss of protective sensation, can produce skin ulceration from pressure or from shear forces.
Associated factors are history of foot infection or ulceration and previous partial or whole-foot amputation.
The Diabetic Foot
Neuropathy
Sensory neuropathy
Autonomic neuropathy
Motor Neuropathy
Ischaemic Peripheral vascular disease
Immune deficiency
Glycosated immune proteins (decrease efficiency)
More prone to infection
End result diabetic foot that is difficult to resolve.
Sensory neuropathy
deprives the patient of early warning signs of pain or pressure from footwear, from inadequate soft tissue padding, or from infection.
This neuropathy appears in a stocking-glove distribution, with many of these individuals complaining of burning or searing pain.
Autonomic neuropathy
produces chronic venous swelling. Motor peripheral neuropathy or Charcot osteoarthropathy can produce bony deformity, which, combined with the loss of protective sensation, can produce skin ulceration from pressure or from shear forces.
Associated factors are history of foot infection or ulceration and previous partial or whole-foot amputation.
Motor neuropathy
leads to muscle weakness and intrinsic muscle atrophy in the hands and feet. These patients can develop bunion, claw toe, and hammertoe deformities due to muscle imbalance.
They lose normal vascular tone and thermal regulation, often developing severe venous swelling that can be managed only with compression hose.
Severe tissue swelling
can lead to ulceration and infection.
They develop dry cracked skin due to autonomic dysfunction.
This skin is prone to developing cracks, allowing the entry of bacteria.
Nail deformity or pathologic proliferation may make the areas adjacent to the nails foci for skin breaks or for infection.
Ischemic peripheral vascular disease
is the second risk factor for developing diabetic foot ulcer and infection.
This used to be considered a small vessel disease, but current research links the vascular pathology to the basement membrane of the arterial wall.
The disease
is similar to that in those with vascular disease who are not diabetic, except that the distribution is somewhat more scattered and geographic in persons who are not diabetic, as opposed to progressive in a distal direction in persons who are diabetic.
The third major risk factor
is related to the immune deficiency seen in this patient population.
Glycosylated immune proteins lose efficiency, and granulocytes do not perform adequately, leaving these patients prone to infection from organisms that would not affect a healthy host.
Each of these potential abnormalities
make the diabetic foot susceptible to abnormal mechanical stresses that can lead to a break in the normal soft tissue envelope, which can initiate a foot infection that cannot be resolved easily.
Diabetic Foot Ulcer
Charcots Joint/Foot
After selecting the initial dose, adjust the amounts, types, and timing depending on plasma glucose levels. Adjust the dose to maintain preprandial plasma glucose at 80-150 mg/dL (ie, 4.44-8.33 mmol/L).
The insulin dose often is adjusted in increments of 10% at a time, and the effects are assessed over about 3 days before making any further changes. More frequent adjustments of regular insulin can be made if risk of hypoglycemia is present
Insulins
Rapid acting (Humalog)
Peak 1-2 hrs
Duration 4-5 hrs.
Short acting (actrapid, humulin S)
Peak 2-3 hrs
Duration approx 8hrs
Intermediate acting (Humulin I)
Peak 6-8 hrs
Duration 12-18 hrs
Type 1 Treatment
Type 1 Diabetes
Exogenous Insulin required
Daily dose calculated using weight
Dose usually divided
1/2 pre breakfast
1/4 pre dinner
1/4 pre bedtime
Dose adjusted to keep BG ~ 4.5 - 8.5
Adjustment slow (3 days) to avoid hypos.
Type 1 Treatment (con’t)
Diet
50-60% CHO (no more than 10% CHO from sucrose or refined CHO)
<30 % fat
10-20% Protein
Within cultural limitations
Activity
Encourage regular exercise
Maintain hydration
Reduction of insulin or snack to reduce chance of hypoglycemia.
Initiation of insulin therapy in adults
: The initial daily dose is calculated depending upon the weight of the patient. This dose usually is divided so that one half is administered before breakfast, one fourth before dinner, and one fourth at bedtime.
After selecting the initial dose, adjust the amounts, types, and timing depending on plasma glucose levels.
Adjust the dose to maintain preprandial plasma glucose at 80-150 mg/dL (ie, 4.44-8.33 mmol/L).
The insulin dose often is adjusted in increments of 10% at a time, and the effects are assessed over about 3 days before making any further changes.
More frequent adjustments of regular insulin can be made if risk of hypoglycemia is present
Type 2 Treatment
Diet
Often requires caloric restriction
Within cultural milieu
Activity
Aerobic exercise improves insulin resistance
Graduated
Older adult evaluate CV risk.
Type 2 Medications
Sulfonylurea Agents (glyburide,glipizide)
Increase insulin secreation
Biguanides (metformin)
Increase sensitivity of insulin by decreasing hepatic gluconeogenesis
Increase peripheral insulin sensitivity.
Can cause some weight loss
Alpha-glucosidase inhibitors (acarbose)
Inhibits AG enzyme responsible for digesting CHO
Aims of Treatment
Stabilize BG
Stabilize weight
Stabilize HbA1c <7%
Macro vascular risk reduction
Lipid control
BP control
Smoking cessation
Self monitoring
Reg eye exams
BG
Autonomic complications
Foot care (orthotics, podiatry, self examination.)
Footwear choice
Dietary and exercise modification
Three P’s
“The normality of blood sugar relieves the depressing thirst and consequently there is a diminished intake and output of fluid. Since the tissue cells are properly nourished by the increased diet, there is no longer the constant calling for food, hence hunger pain of the severe diabetic is replaced by normal appetite. “
Dr Frederick G. Banting (Co-inventor of insulin)