Unit 5 - Treatment of DM Flashcards
what are the glycemic targets for non-pregnant adults?
- HcA1c < 7.0% for II, < 130 mg/dL
- postprandial glucose < 180 mg/dL
- individualization is key
- tighter targets if young and healthy
- looser targets if older, extensive comorbidities, hypoglycemia-prone, longer duration of DM
what is the one thing you want to avoid in DM treatment?
hypoglycemia
what is the legacy effect?
even if control is worse later, an initially aggressive treatment will have overall better result in the future
explain islet cell dysfunction in DM II
- alpha cell dysfunction - secrete inappropriately high levels of glucagon after a meal
- fewer B-cells - secrete insufficient levels of insulin, and mass declines over time
incretin hormones
made in L cells, primarily ileum and colon
- produced in response to incoming nutrients
- stimulate insulin secretion
- discovered when insulin response to oral glucose exceeds response to IV glucose
- most important one in humans is glucagon-like peptide 1
what are glucagon-like peptide/hormone 1 actions?
- enhance glucose-dependent insulin secretion
- slow gastric emptying
- suppress glucagon secretion
- promotes satiety
- receptors in islet cells, CNS, elsewhere
- metabolizes rapidly (t 1/2 2-3 min) by DPP-4 (dipepetidyl peptidase-4)
what are the main pathophysiological defects in DM II?
- decreased incretin (GLP-1) effect
- decreased pancreatic insulin secretion
- increased pancreatic glucagon secretion
- decreased peripheral glucose uptake
- hepatic glucose production
what are the recommendations for therapy of DM II?
- at time of diagnosis, initiate metformin therapy + lifestyle interventions unless metformin contraindicated
- -if newly diagnosed with markedly symptomatic and/or elevated blood glucose levels or A1c, add insulin therapy at onset
- if noninsulin monotherapy at max tolerated dose doesn’t work, add a second oral agent, GLP-1 receptor agonist, or insulin
in what drugs is hypoglycemia most common? in which DM? other risk factors?
- sulfonylurea and insulin
- type I > II
- > 60 yo, impaired renal function, poor nutrition, liver disease, increased PA, longer duration of DM
symptoms of hypoglycemia?
- confusion, slurred speech, dizzy, weakness
- shaking, nervousness, sweating, palpitations
- extreme hunger, headache
- mood/behavior change
- tingling of hands, tongue, lips
- vision change, poor coordination
- unresponsive, unconscious, seizures
what is the preferred treatment of hypoglycemia?
- if conscious: glucose (15-20 g)
- if unconscious: glucgon (emergency kit), given by caregiver
- -prescribed to all at significant risk of severe hypoglycemia
- if in hospital - IV dextrose (no N/V associations)
what is in the glucagon emergency kit? who gets it?
very large dose of insulin given only if unconscious or unable to swallow
- turn on side (so don’t aspirate vomit)
- type I always has prescription
- type II should have if previous severe low blood sugar
what is oral therapy inadequacy?
(“inadequacy” used instead of “failure”) failure to reach targeted treatment goals
- primary: dietary noncompliance and physical inactivity
- secondary: stress, insulin resistance, simultaneous use of diabetogenic drugs, progressive B-cell dysfunction
how is efficacy over time?
decreases
- A1c can rise when on stable therapy or with age
- B-cell function decreases at same rate
what is amylin? amounts in DM? what does it do?
37 AA peptide released with insulin from B-cells in response to eating
- absent in DM I, variable in DM II
- slows gastric emptying
- suppresses postprandial glucagon secretion
- reduces appetite
what is pramlintide?
amylin analog used in DM I
- inject before each meal
- reduces post-prandial glucose levels (inhibits glucagon production, slows gastric emptying)
- use with short/rapidly acting insulin
- modified to prevent amyloid fibrils in B-cell
- significant risk of hypoglycemia
- may decrease appetite and promote weight loss
- GI side effects (esp. N)
when is insulin therapy appropriate for DM II?
- glucose toxicity
- insufficient endogenous insulin production
- contraindication to oral therapy
what are indications for insulin therapy in DM II
- significant hyperglycemia at presentation, and on max doses of oral agents
- decompensation
- -acute injury, stress, infection, MI
- -severe hyperglycemia w/ ketonemia and/or ketonuria
- -uncontrolled weight loss
- -use of diabetogenic medications (corticosteroids)
- surgery
- pregnancy
- serious renal or hepatic disease
what are rapid-acting insulins?
injectable, complexed to Zn to prevent breakdown
- lispro, aspart, and glulisine
- AA are changed around in a way to make easier to absorb
what are intermediate-acting types of insulin?
NPs (Neutral pH, Protamine Zn)
-Detemir, and premixed NP lispro and NP aspart
explain Detemir
intermediate-acting insulin analog
- duration of action is dose-dependent
- at lower doses, is intermediate-acting; if higher, can be up to 24 hours
- administered once/twice daily
- delayed release from subcutaneous injection site due to self-association and binding to albumin
- shouldn’t be diluted or mixed with any other insulin preparations by patient (leave it to the pros!)
what are long-acting insulin analogs?
glargine insulin (others in the works)
what is glargine insulin?
basal insulin that cannot be mixed in same syringe with any other type of insulin (pH of 4)
what is the difference between U-100 and U-500?
U-100 has 100 units of insulin/mL; most common in syringes or pens
U-500 has 500 units/mL; used for severe insulin resistance
what are pros and cons of premixed insulin?
pro: convenient, longer shelf-life, fewer dosing errors, and simple (pens)
cons: loss of flexibility (must match to carb intake, PA), harder to treat short-term high/low glucose levels, lack of clinical data, hypoglycemia risk
- rarely used in type I DM
storage of insulin?
refrigeration
- can be stable at room temp up to one month
- never freeze or expose to direct sunlight (breaks down)
administration of regular insulin?
short-acting complexed to Zn
-can be injectable, but only one given IV
what are insulin pens?
- faster and easier than syringes
- improves patient attitude and adherence
- have accurate dosing mech, but inadequate resuspension of NPH may be problematic
what is the time course and action of insulin preps?
- individual variation
- variations depend on dose
- regional differences in insulin absorption (variations in blood flow)
- -abs > arm > butt > thigh (PA)
- -rotate sites w/in region
- -use specific regions for specific times of day
