DM is the _ leading cause of death
6th
Types of Diabetes:
Major types of DM:
1) Type 1 diabetes mellitus:
-Formerly called: Juvenile onset or insulin-dependent diabetes mellitus [IDDM]
2) Type 2 diabetes mellitus:
-Formerly called: Adult onset or Non-insulin dependent diabetes mellitus [NIDDM]
3) Gestational DM:
Long-term complications of DM:
-Heart disease
-Hypertension
-Stroke
-Blindness: Diabetic retinopathy
-Renal dysfunction/failure
-Neuropathy & other nervous system disorders
-Amputations and sores on legs due to decreased circulation
-Peridontal disease- more gingivitis, peridontal
Short-term complications of DM:
-Hypoglycemia: Serum glucose level too low
-Hyperglycemia: Serum glucose too high
Physiology of DM: The pancreas
1) Exocrine gland: Produces hormones and enzymes.
-Lipase, amylase, proteolytic & other enzymes for digestive processes.
2) Endocrine gland (Islets of Langerhans):
-Beta cells: Proinsulin ? Insulin & C peptide, Amylin
-Alpha cells: Glucogan
C-Peptide (released from Beta cells)
-Formed during conversion of pro-insulin to insulin
-One molecule of C peptide & one molecule of insulin
-Primary role - synthesis of insulin
-More reliable indicator of insulin secretion. If you want to check insulin levels, you can check C-peptide b
Insulin and Glucagon r/t metabolism
*Blood glucose levels increase:
-Beta cells increase output of C Peptide & Insulin
-Alpha cells decrease output of glucagon.
*Both are secreted:
-As basal rate ( low steady amount )
-Bolus amount (a large amount) at meal times
-Consumption of carbohydrate
Insulin normal range and role:
*Normal range:
70-110 mg/dl
*Role:
Insulin is the only hormone that lowers blood glucose levels:
-Facilitates entry of glucose into cells
-Stimulates liver to store glucose as glycogen
Plus:
-Stimulates amino acid uptake
-Promotes synthesis of fats in the
The other substance that is secreted with insulin is, and its function:
Amylin
Role:
-Compliments effects of insulin in postprandial glucose control:
Suppresses postprandial glucagon secretion, slows gastric emptying, and signals satiety
Whenever someone has DM, amylin cannot be used.
Other hormones r/t DM: GI Hormones
*Incretin hormones:
-Gastric inhibitory polypeptide (GIP)
-Glucagon-like peptide-1 (GLP-1)
Released when nutrients enter GI tract.
*Affects the:
-Brain - in controlling ingestion
-Stomach - rate of emptying
-Periphery - metabolism in the periphery
Glucogan:
Brings blood sugar back up. Main counter-regulatory hormone
*Main effect:
-Increase/maintain glucose levels between meals & during exercise
-Secreted in response to low glucose levels
-Inhibited by high serum glucose
-Stimulates glycogenolysis :
Liver gly
Other hormones that act as counter-regulatory hormones to increase serum glucose:
-Growth hormone:
Reduces rate of cellular glucose utilization by the cells = increased glucose levels. Produced in the morning.
-Corticotropin:
Stimulates glucocorticoid (cortisol) = increased gluconeogenesis & decreased glucose utilization by the cells.
What happens when we take in a meal:
Within minutes of beginning a meal:
Blood glucose rises
-1st phase insulin secretion - available and stored insulin reduces plasma glucose; then begins to rise again.
-2nd phase insulin secretion - about 10 minutes later.
Newly secreted insulin secreted i
Type 1 Diabetes Mellitus - 5-10%:
Destruction of beta cells = absolute insulin deficiency
Type 1A:
-Idiopathic; no evidence of autoimmunity dysfunction
Type 1B:
-Autoimmune disorder "triggered" by something.
Time frame for overt disease- months to years.
Type 1 DM: Epidemiology
-More common in the young.
-Presents: < age 30; mean age 9-12
-Both genders - equally.
-Usually thin, well within ideal body weight.
-Increased incidence -Finland, Scandinavia, Scotland
-Lower incidence - Southern Europe , middle east
Very low - Asia.
Type 1 DM: S/S and treatment
Onset:
-Usually sudden
-Latent autoimmune disorders more insidious
Classic symptoms:
-Polyuria (frequent urination), polydipsia (thirsty), polyphagia (hungry)
-Fatigue; weight loss
-Ketosis (ketoacidosis) that can be fatal. Occurs at onset and during peri
Type 2 Diabetes mellitus - 80-85%: Epidemiology
-Onset - insidious; relatively stable disorder
-Usually >35 - 40 y/o; rapid increase in children & adolescents
-Markedly overweight/obese
-Ethnic populations at risk:
African Americans
Hispanic/Latino Americans
American Indians
Pacific Islanders
So
Type 2 DM: Clinical Manifestations
-May be asymptomatic
-May have recurrent infections
-Ketosis (ketoacidosis) rare; but possible during stress events or infections
-Macro- & microvascular changes may be present for several years.
-Chronic complications over time.
Type 2 DM: Treatment
-Life-style changes,
-Oral diabetic medications
-Insulin may be added
DM Type 2: Risk Factors
-Being overweight ? lbs overweight or a BMI ? 25
-Family history of diabetes
At risk populations
- >35 yrs of age; sedentary lifestyle.
-Increases risk for MI & stroke
-Many have metabolic syndrome: (Central obesity, apple shape)
Central obesity
Tr
DM Type 2: Pathogenesis
-Beta cell failure & impaired insulin secretion
-Insulin resistance -higher concentrations of insulin needed to maintain normal blood glucose
-Serum glucose levels remain high
-Pancreas continues to produce insulin until beta cell failure increases
-I
Pre-diabetes (increased risk of diabetes):
Presence of:
-Impaired glucose tolerance (IGT)
-Impaired fasting glucose (IFG)
-Elevated A1c
All three tests higher than normal but not at designated diagnostic levels.
Statistically likely to develop overt DM within 10 yrs.
May have acanthosis nigricans
Diagnostic criteria diabetes mellitus: Normal Values
Normal values
-Fasting plasma glucose range- 70- 110 mg/dl
-FPG (fasting plasma glucose) - < 100 mg/dl
OGTT (oral glucose tolerance test) -2 hr post prandial plasma glucose - ? 140 mg/dl
-A1c - 4.5-6.0%
Diagnostic criteria diabetes mellitus: pre-diabetes
-FPG (fasting plasma glucose) - 100-125 mg/dl
-OGTT (oral glucose tolerance test) - fasting & consumes glucose-risk drink: 2 hrs later - 140-199 mg/dl.
-A1c - 5.7%-6.4%
Diagnostic criteria diabetes mellitus: diabetes
-FPG (fasting plasma glucose) ?126 mg/dl
-OGTT (oral glucose tolerance test)- 2 hr postprandial glucose ?200 mg/dl
-A1c ? 6.5%
All three must be confirmed on a subsequent day to make diagnosis of DM
In persons with classic symptoms of hyperglycemic crises
What is the A1c?
-Glycolysated hemoglobin (A1c )
-Measured as % age of total hemoglobin q 3 months
(average life of RBC - 120 days)
-RBC couples with HBA ("sugared")
-%age of HBA proportional to length of time RBC exposed to elevated glucose levels
-Normal range 4.5-6.0 %
Urine test for ketones (Ketonuria):
-Reserved for type 1 diabetics who are ill usually
-Normally ketones not present in urine
-Test is dip strips or by the lab
-Presence of ketones in urine indicate fats are being used for energy source.
Testing is done:
-During acute illness or severe stre
Acute complications of DM:
-Hypoglycemia:
-Hyperglycemia
-Diabetic ketoacidosis
-Hyperosmolar hyperglycemic state (HHS)
infections
Other phenomenon:
-Somogyi effect
-Dawn phenomenon
Long-term complications of DM:
1) Macrovascular changes:
-Cardiovascular diseases
2) Microvascular changes:
-Neuropathy
-Retinopathy
-Nephropathy
3) Skin disorders
-Increased incidence of fungal infections/skin abscesses, etc.
4) Feet problems
5) Dental problems (gum disease)
Management of DM:
1) Life-style changes (nutrition, weight loss, exercise)
2) Pharmacotherapy
-Insulin
-Oral medications
-Glucose monitoring
*GOALS OF PHARMACOLOGIC TREATMENT:
-STIMULATE BETA INSULIN PRODUCTION (OR REPLACE WITH EXOGENOUS INSULIN)
-Improve insulin sensitivi
Insulin treatment:
**Only medication available to treat type 1 DM
-May be used with oral diabetic medication in type 2 DM
-Goal - keep blood glucose at normal or near-normal levels.
Types of insulin:
-Rapid acting
-Short acting
-Intermediate acting
-Long acting
Insulin type
Insulin secretion pattern in persons without diabetes:
-Small amounts of insulin secreted at basal levels between meals.
-Greater amounts of insulin secreted at meal times.
-Lowest levels of insulin secretion between 3-4 AM
-Insulin levels begin to rise between 5-8 AM (dawn phenomenon)
For Diabetics:
-Basal d
Insulin therapy: Risks
-Hypoglycemia - reduced with glucose monitoring & compliance with therapy
Insulin therapy: Benefits
-Good glycemic control; feeling of well-being
-Long term use slows/prevents diabetic complications
Insulin - absorption rate & bioavailability depends on:
1) Site of injection, depth of injection, insulin dose
2) Exercise, heat application
3) Varies with speed of onset, peak & duration
-Most quickly absorbed - abdomen
-Next quickly absorbed - arm
-Slowest absorption - thigh
*Not for oral use
Points regarding insulin & food:
1) U100 & U500 strengths available in US
2) Unopened vials stored in refrigerator
3) Opened vials do not need refrigeration:
-Maintain potency for 30 days unless temperature >86F or < 37F
4) Avoid prolonged exposure to sunlight
5) Pre-filled syr
Points regarding insulin administration & action:
1) Exercising muscle group before injection increases absorption; as does heat or massage of site.
2) IM injection more rapid than subcutaneously.
3) PZI never mixed with other insulin
4) Regular insulin - clear, other newer insulin formulations also clea
Insulin delivery systems:
1) Needle & syringe (most commonly used in US)
2) Insulin pens
-Size of large pen with disposable Cartridge & needle.
-Cartridges comes in 1.5 ml & 3.0 ml (with 1.5 being phased out)
3) Pre-filled pens using pre-mixed insulin marketed for use
Using the pen:
-Load the cartridge, screw on pen needle
-Some may need to be primed to remove air
-If using insulin suspension, gently shake first
-Dial in desired dose, inject needle, press button to deliver insulin
-Hold pen in place for several seconds after insulin
Insulin pump: Overview
-Continuous subcutaneous insulin infusion
-Worn externally; attached to body with a thin, flexible plastic tubing with needle placed beneath the skin
-Pump programmed to give small dose of insulin continuously
-Meal time - programmed for bolus dose
Insulin Pump: Advantages and Disadvantages
Advantage:
-Flexibility in meals & other activities
-Do not require daily injections; changed q48-72 hrs
Disadvantage:
-Cost greater
-Careful monitoring essential; infection at site possible
Procedure for mixed combination:
-Wash hands
-Rotate NPH bottle
-Wipe tops with alcohol sponge
-Draw amount of air equal to both doses
-Inject air into NPH and regular vials
-Withdraw regular insulin first
-Withdraw NPH insulin last
-Cleansing the skin with alcohol is not necessary
Insulin dose adjusted according to:
-BS (blood sugar) levels
-Food intake
-Exercise
-Departure from normal (illness or severe stress)
In-hospital glucose target should be about-
90-159 mg/dl - checked before meals.
May order insulin based on a sliding scale:
Example
-Different amounts depend on BG levels:
Give ____ R insulin (& ___NPH) if BS _____
Give ____R insulin if BS _______
Insulin regimens for type 1 DM:
-At least two injections of mixtures of short/rapid-acting & long/intermediate-acting insulin.
-Better control achieved with intensive regimen & 3-4 injections per day or with insulin pump - most closely mimics endogenous insulin secretion
Other Medications: Pramlintide acetate (Symlin) - amylin analog
-Used for type 1 & type 2 DMs (it increases the action of insulin)
-Does not cause hypoglycemia by itself BUT increases the risk of insulin-induced hypoglycemia particularly in type 1 DMs, usually within 3 hrs of injection
-Cannot be mixed with insulin
-A
Oral diabetic medications - type 2 DM only
Sites of action:
-Liver, pancreas, peripheral tissues
Goals:
-Decrease insulin resistance; increase insulin utilization
-Augment insulin secretion & action
-Delay/reduce digestion & absorption of dietary carbs.
Sulfonlyureas (Insulin secretagogues):
-Stimulates beta cells to secrete insulin
-May cause hypoglycemia
-Contraindicated with sulfa allergy
-Causes weight gain
-Monotherapy or in combination with another oral diabetic medication class &/or insulin.
Biguanides (insulin sensitizer):
-Metformin (Glucophage; Glucophage XR)
-Initial drug of choice for most type 2 DMs
Action:
-Decreases hepatic glucose output
-Enhances glucose uptake by decreasing insulin resistance in liver & muscle
-Promotes mild weight loss
-Positive effect on lip
Thiazolidinediones ("glitazones")(insulin sensitizers):
-Pioglitazone (Actos)
-Specifically targets insulin resistance by increasing insulin sensitivity.
-DOES NOT stimulate insulin production
-These drugs also suppress hepatic glucose production keeping blood glucose levels more even.
-Does not cause hypoglyc
Meglitinides (insulin secretagogues):
Action:
-Increases insulin production
-Short-acting - 1 hr
-Acts similarly to sulfonylureas but pharmacologically distinct -May be used in those with allergy to sulfonylureas
-Some risk for hypoglycemia
-Some weight gain
Medication:
-Rapaglinide (Prandin)
Alpha glucosidase inhibitors (starch blockers):
Action:
-Decreases/delays glucose absorption in the gut
-Primary effect is on postprandial glucose
-Inhibits metabolism of sucrose to glucose & fructose
-Duration - 2 hrs
-Types: acarbose (Precose); miglitol (Glyset)
-tid with meals (take with first &
GLP-1 Based therapies - Incretin mimetics:
-Exenatide (Byetta)
-Synthetic form of glucagon-like peptide (GLP-1)
-Adjunctive therapy for type 2 diabetics; given subcut.
Action:
-Slows gastric emptying; increases satiety
-Suppresses postprandial glucagon
-Enhances glucose -dependent insulin secretio
Diabetic teaching:
1) Medications -oral medications:
-Dosage , types, side effects
-Insulin: type, dosage & time intervals, storage, preparation, administration
2) Relationship between meal times & the action of insulin or oral medication
3) Blood glucose testing -
Blood glucose monitoring: Advantages
-Empowers patient to be active in self-case
-Immediate information about blood glucose level
-Produces accurate record of blood glucose pattern
Blood Glucose Testing: Frequency
Depends on:
-Glycemic goals
-Type of diabetes and need for medication
Usually:
-Type 1 - before meals and bedtime
-Type 2 - variable
-Usually before meals; before and after exercising.
-Whenever one feels ill
Recommendations for daily intake: Nutrition
-Carbohydrate & mono-unsaturated fat together - 60-70&%
-Protein - 15-20%
-Fats - < than 10%
-Those with LDLs >100 may benefit from <7% saturated fats
-Dietary cholesterol <300 mg/day
-Fiber - 15-30 grams/daily
Alcohol:
-Limit - <1
Nutrition guidelines:
-Consistent timing of meals, snacks
-Portion control
-Eat variety of foods q/day including fruits & vegetables
-Achieve & maintain desirable weight
-Reduce total calories if overweight or obese to lose weight
-Read nutrition labels
-Eat foods high in fibe
Physical activity (exercise):
Individualize :
-Adjust diet needs & insulin/oral medications
-Time of day, type & duration of exercise
-Persons 35 + - recommend cardiac stress test first.
Benefits:
-Lowers blood glucose
-More glucose enter cells without insulin receptor carrier
-Decrea
Desirable blood glucose levels:
-Preprandial: Goal :
<120mg/dl; Not desirable <60 mg/dl
(60-120)
-Postprandial: Goal
<140 mg/dl; Not desirable >200 mg/dl
(140-200)
-Bedtime: Goal
100-140 mg/dl; Not desirable <100 or >160 mg/dl.
(100-140)
Hypoglycemia:
-Blood glucose <70 mg/dl
More common in type 1 diabetics, but can happen in type 2.
Some causes:
-Too much insulin or oral diabetic medication; too little food or not eating.
-Exercise without additional food
-Disruption in normal triggering of counter-re
Hypoglycemia: Clinical Manifestations
Clinical manifestations:
-Adrenergic (Catecholamine) effects:
Shakiness, Nervousness, irritability, tremor, tachycardia, palpitations, hunger, diaphoresis, pallor, paresthesias
-Neuroglycopenic effects (on brain):
Headache, confusion, difficulty concentra
Hypoglycemic unawareness :
-Persons with autonomic neuropathy or tightly controlled blood glucose levels may not be aware of impending hypoglycemia & may be at risk.
-Persons with hypoglycemia unawareness ( no adrenergic symptoms but present with neuroglycemic symptoms) should be e
Hypoglycemia: Treatment
P.O treatment for hypoglycemia:
-115 gms carbohydrates
-4 oz orange juice; 3 glucose tablets
-� cup regular soda; 1 tube glucose gel
-6-8 life savers; 2 tsp sugar
-Test glucose levels; follow with protein
i.e. meat sandwich & � glass milk
Other treatm
Somogyi effect (phenomenon):
-Hypoglycemia followed by rebound hyperglycemia
-Involves counter-regulatory hormones
Causes:
-Excessive evening insulin dosing
-OR - rebounding effect from ingesting too much food following a hypoglycemic event
Treatment:
-Administer smaller dose of insu
Dawn phenomenon:
-Early morning rise in blood glucose (3-8 AM) without preceding nocturnal hypoglycemia
Cause:
-Rise in cortisol & growth hormones
-Growth hormone, increased insulin clearance
-Diuranal variation in counter-regulatory hormones
Occurrence:
-Type 1 &
Hyperglycemia: Precipitating factors
-Infection - most common
-New onset type 1 DM
-Poor compliance with insulin regimen
-Acute major illnesses
-Psychological problems associated with eating disorders & insulin omission + rebellion, stress, drugs, alcohol & other factors
-"britt
Untreated hyperglycemia leads to:
-Diabetic ketoacidosis (DKA) (usually in younger persons)
-Hyperosmolar hyperglycemic state (HHS), aka - nonketotic hyperglycemia (usually in older persons)
Diabetic ketoacidosis (DKA):
-Usually evolves rapidly over 24 hr period
-The blood glucose usually > 250 mg/dl; < than 800 mg/dl
Common S&S:
Early:
-Nausea & vomiting
-Abdominal pain
-Hyperventilation
With progression:
-Neurologic symptoms: lethargy, focal deficits, fruity breath, hy
Diabetic ketoacidosis involves:
-Ketosis
-Dehydration
-Electrolyte imbalance
-Metabolic acidosis - leading to coma & death if not treated & reversed
-Is life-threatening
Diabetic ketoacidosis treatment:
-Restore hydration & electrolyte balance
-Provide IV insulin until blood glucose levels near normal; then subcutaneous route
-Monitor vital signs
Diabetic feet:
Combination of vascular and neurologic disease
Prevalence:
- 32% overall
->50% in persons > age 60
-Neuropathy present in >80% of those with foot ulcers.
Foot care instructions:
-Keep BS, BP & weight under control
-Wash & inspect feet & between the toes every day
-Keep skin soft & smooth with lotion - do not apply between the toes.
-Wear shoes & socks at all times
-Protect feet from hot & cold
-Don't
Diabetic dermopathy:
-Shin spots, pigmented pretibial patches
-Most common cutaneous finding >30% of DM pts -
-Frequently located over bony prominences - may be response to trauma
Diabetic retinopathy:
-Appears late in 1st decade or early second decade of DM
-Retinal vascular microaneurysms, hemorrhages & cotton wool spots
-Neovascularization (newly formed vessels) because of retinal hypoxia
New arterioles:
-Rupture more easily leading to vitreous hemor