DM lecture 2 Flashcards
What is Diabetes Mellitus (DM)?
a disorder characterized by hyperglycemia, due to altered metabolism of carbohydrates, fats and proteins.
What is Type-1 diabetes?
insulin-dependent
What is Type-2 diabetes?
non-insulin-dependent
Classical symptoms of DM?
Hyperglycemia
Polydipsia (dry mouth and itchy skin)
Polyphagia
Glucosuria
Polyuria
What are other symptoms of DM?
Blurred vision (if progressed retinopathy)
Peripheral neuropathy, leading to amputation
Fatigue
Weight loss
Poor wound healing (cuts, scrapes, etc)
Recurrent infections such as vaginal yeast infections, groin rash, or external ear infections (swimmers’ ear)
impotence (male)
Diagnosis of DM?
Fast blood glucose test
Oral glucose tolerance test
Random glucose level measurement
hemoglobin A1C test
Type 1 DM
-most common age 10-16
-resulting from destruction of pancreatic beta cells
-catabolic disorder (no insulin, high glucagon, no beta cell response to insulin releasing stimuli)
-most severe from of diabetes (untreated leads to ketosis/ketoacidosis)
-exogenous insulin needed!!!!!!!
What are the 4 different types of insulin preps?
- rapid-acting (very fast onset within 5-10 min, short duration)
- short-acting (with fast onset action within 30 min)
- intermediate acting
- long acting (slow onset and very long duration of action)
Ayo what is insulin?
-it is derived from pro-insulin, a long single-chain protein, which is cleaved to insulin (51AA) and C-peptide (31AA)
-pro insulin has a mild hypoglycemic action
Sources of Insulin?
-human insulin (less expensive, less immunogenic meaning causing allergy and insulin resistance), is produced by recombinant DNA tech
- Human pro-insulin gene is inseted into E. coli (Humulin) and yeasts (Novolin)
What is ultra-short acting?
-insulin lispro
-rapidly acts in 5-15 min and peaks in 1 hr
-duration of action is 4-5 hr
-does not caused delayed hypoglycemia bc has lowest variability of abs 5%
-preferred for continuous sc infusion devices
Other rapid acting insulins?
-insulin aspart (aspartic acid instead of proline at B28)
- insulin glulisine (glutamic acid instead of lysine at B29 and asparagine instead of lysine at B3)
characteristics of short-acting insulin prep?
-soluble crystalline zinc insulin
-onset of action is within 30 min
-peaks between 2-3 hr and last for 5-8 hr (risk of postprandial hyperglycemia and delayed hypoglycemia exists)
-only form of insulin to be administered to IV (VERY useful in treatment of ketoacidosis or other conditions that insulin requirements change rapidly)
-less costly than lispro
Characteristics of intermediate-acting?
-NPH
-onset is delayed by combining app amts of protamine and insulin (1:10)
-onset of action 2-5 hr and duration of 4-12 hr
-mixed with rapid acting or short acting insulin and given 2–4 times daily for insulin replacement
-action is unpredictable due to its erratic abs leading to significant decline in use
Characteristics of long acting?
-insulin glargine (long acting, soluble peakless insulin analog)
-produced by adding two arginine molecules at the C-Terminus and substitution of a glycine for asparagine at the A21.
-slow onset of action (60-90 min) and max within 4-6 hrs and maintained for 11-24 hr or longer
What is Insulin Detemir?
-another long acting insulin analog
-the terminal threonine B30 is removed and a myristic acid is attached to lysine at B29
_____ of insulins provides a better glycemic control
mixture
which one of these insulin prep will have most variability in abs? (Dr L question)
NPH (highest variability at 50%)
NPH peaks within several hours and thus addition of a rapid- or short-acting insulin provides a better postprandial glycemic control compared to NPH alone
why use mix of insulin? (Dr L question )
peak, onset, duration is different so when combine, provide better glycemic control
Mixtures of insulin preps
some long acting must be given seperate bc they are not miscible
Concentration
U-100 common in pharmacy
Insulin delivery systems
-main one is SC injection (standard mode)
-portable pen injectors
-infusion
-inhaled
- Afrezza (inhaled) introduced in 2014
Treatment with insulin
-used in type 1 pts with DM
insulin therapy
The goal of conventional SC therapy is to replicate normal physiological insulin secretion
Intensive therapy attempts to restore near normal glucose patterns throughout the day while minimizing the risk of _________?
hypoglycemia
monitor especially elders and kids <7 yr old
frequent monitor needed
Hypoglycemia could be due to
-delay in eating a meal
-physical exertion
-large doses of insulin
-tight control without frequent monitoring\
Signs of hypoglycemia
-hyperactivity of both sympathetic (tachycardia, palpitation, sweating, tremulousness) and parasympathetic (nausea, hunger) systems is observed that may progress to convulsions and coma
How do you treat Mild Hypoglycemia (pt conscious and able to swallow)
-orange juice or any sugar containing bev
Hypoglycemia (unconscious) treatment?
-2–50 mL of 50% glucose solution IV
-if IV glucose not available, 1 mg of glucagon (sc or IM)
-if glucagon not available, small amount of honey or syrup in buccal pouch (oral feeding contraindicated in unconsciousness)
What are complications of therapy?
antibodies are produced (IgA, IgD, IgE, igG, IgM) which could lead to
-insulin allergy
-insulin resistance
Insulin allergy?
-is an intermediate hypersensitivity and is a rare case in which local or systemic urticaria will develop (due to histamine release from the mast cells in response to an anti-insulin IgE Ab)
-the use of human insulin or insulin analogs obtained by the recombinant tehcnology from the onset of therapy should eliminate the risk of allergy
Insulin resistance?
low titer of circulating IgG anti-insulin Abs develop in pts with some degress of tissue insensitivity to insulin, leading to extremely high insulin requirement
complicaitons of therapy
-lipodystrophy at injection sites
