UNIT2_Diabetes & Insulin Flashcards
What are the Rapid-Acting drugs? (3)
“-log” drugs:
- Humalog (Lispro)
- Novolog (Aspart)
- Glulisine (Apidra)
What class of insulin drugs has the following profile?
Onset in 5-15 min
Peak 1-1.5 hr
Lasts 3-5 hrs
Subcut injection or insulin pump
“-log” drugs: Rapid Acting
- Humalog (Lispro)
- Novolog (Aspart)
- Glulisine (Apidra)
How do you use the rapid-acting “-log” insulin drugs?
- Injected right before a meal to prevent post-prandial hyperglycemia.
- used for continuous infusion pumps
- can be mixed with NPH
What are the Short-Acting insulin drugs? (2)
“-lin R” drugs:
- Humulin-R
- Novolin-R
What class of insulin drugs has the following profile?
Onset in 30-60 min
Peak in 2 hrs
Lasts 6-8 hrs
Subcut injection, IV infusion
“-lin R” drugs:
- Humulin-R
- Novolin-R
Describe how you use and the details of Short-Acting insulin drugs.
- Recombinant human insulin (soluble crystalline zinc –> Zn improves stability/shelf-life)
- Inject 30 min before eating
- Usually used in hospital setting for DKA (IV infusion of insulin)
What are the long-acting insulin drugs?
Long-Acting:
- Glargine (Lantus)
- Detemir (Levemir)
What is a special fact about the long-acting insulin drugs?
Cannot be mixed in same syringe with any other insulins (because of acidic pH)
What class of insulin drugs has the following profile?
Onset of action 2-4 hrs
Peak 6-7 hrs
Lasts 10-20 hrs
Subcut injection only (2x/day)
Long-Acting:
- Glargine (Lantus)
- Detemir (Levemir)
Describe how you use and the details of Bisphasic/Mixed insulin drugs.
- Reduce number of injections; get basal and prandial insulin at same time
- NPH/Regular: 70/30 or 50/50 mixes injected before breakfast and before dinner
- Intermediate/Humalog or Novolog: admin before eating
What are the 2 major types of biphasic/mixed insulin drugs?
Biphasic/Mixed drugs:
- NPH/Regular
- Intermediate/Humalog -or- Novolog
How and when do you administer biphasic/mixed insulin?
- SubQ injection
- Rapid onset right before meal, with longer lasting basal insulin
What are the Insulin Therapy Targets values for the following:
- Fasting Glucose: ?
- 2 hr post prandial: ?
- A1C: ?
- Fasting Glucose: 70-130 mg/dl
- 2 hr post prandial <180 mg/dl
- A1c < 7; Many different factors (i.e. age, newly diagnosed, presence of complications, etc) influence whether you will have a stringent (<6.5 HbA1c) or lenient (<8) goal.
Normally, the Pancreas secretes about ___ units of insulin per day.
30 units.
basal insulin plus insulin release in response to exogenous stimuli i.e. blood glucose > 100
Prandial (post-eating) insulin has two phases:
1) first phase is ____1____.
2) second phase ____2____ min after ingestion.
insulin concentrations peak at ____3____ min after ingestion
- immediate
- 8-10 minutes
- 30-45 minutes
Long-acting (i.e. glargine) injected once per day + rapid-insulin right before meal (calculate carbs) describes the Tx for which type of diabetes?
Type I Diabetes Regimen;
“Basal Bolus” Tx
In the Tx of T1D, what are the advantages and disadvantages of a Continuous subcutaneous insulin infusion (insulin pump): rapid-acting insulin
- Advantages: eliminates multiple injections, can set different basal rates, can have partial unit, can give different bolus types.
- Disadvantages: upfront cost, significant training, motivation, ability to troubleshoot, interruption of infusion or “bad site” can lead to DKA within hrs.
When do you consider using insulin for a DM2 pt.?
- If have contraindications to other agents (i.e. renal or hepatic dysfunction, CHF)
- If lifestyle plus non-insulin medications have not resulted in sufficient decrease in HbA1c (usually occurs 10 years after onset of disease)
When do you ALWAYS use insulin for a DM2 pt.?
ALWAYS use insulin if have signs of severe insulin deficiency:
- fasting glucose >250 mg/dL
- random glucose > 300 mg/dL
- HbA1c > 10%
- Hospital admission (i.e. for DKA, hyperglycemic hyperosmolar state-HHS)
If the patient has early morning HYPERglycemia, this is usaually due to what? (3)
1) inadequate basal insulin.
2) waning effect of basal insulin.
3) Somogyi effect (nocturnal HYPOglycemia causes surge of counter-regulatory hormones in the morning)
In a hospital, inpatient setting, you stop all oral agents and administer insulin for hyperglycemia to reach targets of random BG= ___1___ and/or premeal BG= ___2___.
- Random Blood Glucose <180 mg/dL
2. Premeal BG <140 mg/dL
What are the barriers to insulin therapy?
- fear of injections
- hypoglycemia
- gaining weight
- stigma
- inconvenience
What is the general concept when it comes to adjusting insulin dosing?
eliminate the lows first and then eliminate the highs; adjust dose 10-20%
What is the first-line drug Tx for DM2?
Metformin
What diabetic drugs are the weight loss/weight neutral drugs?
Weight loss/weight neutral drugs:
- Metformin
- GLP-1 Agonist
- DPP-IV inhibitors
- Amylin
What diabetic drugs are the weight gain drugs?
Weight gain drugs:
- sulfonylureas
- TZDs
- insulin
Insulin is most potent (biggest reduction in what lab value?); followed by Metformin and sulfonylureas
HbA1c
Insulin is most potent (biggest reduction in HbA1c); followed by what drugs?
Metformin and sulfonylureas
What HLAs types increase risk for T1D? Which HLA are Protective?
- Risk: HLA-DR3/4
- Protective: HLA-DR2
HLA (accounts for 50% of genetic risk, esp HLA-D which codes MHC Class II)
Genetic risk is additive!
Describe the Insulin Gene:
Class I VNTR (tandem repeats) within 5’ region associated with increased risk –> less insulin expressed in thymus = decreased ability to distinguish insulin as self rather than pathogen.
What are some environmental factors ~w/ T1D?
- Viruses
- breastfeeding
- timing of food introduction to infants
- hygiene hypothesis
- accelerator hypothesis (obesity speeds up onset of disease)
!!!Vit. D may be protective!!!
What are the ~ commodities of T1D?
- Autoimmune thyroid (15-20%)
- Celiac (5-10%)
- Addison’s (1-1.5%)
The etiology of T1D is not completely known: genetics predisposition and/or environmental triggers cause autoimmunity that decrease beta cell mass over time; clinical onset when have lost ____ of beta cells.
80-90%
What are the clinical presentation features of T1D?
- Usually in childhood (peak incidence is 10-12 yrs old, though presenting more in < 5 yrs)
- Usually in normal weight individuals
- Polyuria/nocturia, polydipsia
- Weight loss
- Blurry vision
- Acute presentation=DKA (abdominal pain, Kussmaul, nausea/vomiting)
- 10-20% have positive family history
Do T1D pt. have low or high C-Peptide?
LOW C-Peptide ~ T1D
Absolute lack of insulin AND increased counter-regulatory hormones is classic in what complication of diabetes?
DKA;
Without insulin, both glucose and ketones are overproduced but underutilized.
Do diabetic pt. who are in DKA have HYPOnatremia?
Apparent (not real) hyponatremia:
• To correct: Need to add 2 mEq Na to lab value for every 100 mg/dL of excess serum glucose
- K looks high but is low or nl (intracell K+ exchanged for extracell H+ –> so K+ looks high –> may become hypokalemic if treated with fluids).
- HCT and Cr may be high from dehydration
What is C-peptide labs used for?
Measure C-peptide to determine if low blood sugar is due to exogenous or endogenous insulin
What are the major classes of MICROVASCULAR complications of diabetes? (4)
- Retinopathy
- Nepropathy
- Neuropathy
- Diabetic Foot Disease
What are the major issues of the MACROVASCULAR complications of diabetes?
- 77% of hospitalizations and 80% of mortality in DM is due to CVD
- MI, stroke, peripheral vascular disease (2-4x greater incidence) –> leading cause of death in DM patients
- Hyperglycemia causes endothelial cell dysfunction: decreases vasoactive peptides, secretes adhesive molecules, loses tight junctions, abnl vascular smooth muscle, decreased fibrinolysis –> increased risk of atherosclerosis and procoagulation.
- T2DM patients often have HTN (not in T1DM unless develop renal disease)
- Hyperinsulinemia (metabolic syndrome and insulin resistance) damages vessel wall and increases CV risk
- DM patients should be treated as though they have cardiovascular disease (statins, BP control, ACEi/ARBs)
What are the normal values?:
- Fasting glucose = ?
- 2-hr PG = ?
- HbA1c = ?
- Fasting glucose <100 mg/dl
- 2-hr PG < 140 mg/dl
- HbA1c <5.7
What is required to have DM2?
Insulin resistance AND decreased insulin secretion are required to develop diabetes.
In terms of the epidemiology of DM2 pts., DM2 accounts for __% of diabetes patients; __th leading cause of death in US
90% of all diabetes pt.
5th leading cause of death
w.r.t. DM2:
Insulin acts via which insulin pathway to confer a metabolic signal –> this signal is disrupted in insulin resistance.
PI3K kinase.
(distinct from MAPK signaling which is growth/mitogenic)
• Metabolic signal disrupted –> leads to lipolysis –> release FFA –> FFA triggers hepatic production of glucose AND damage of beta cells –> hyperglycemia
There is also Glucagon dysfunction in DM2, explain.
DM2 ~ glucagon dysfunction b/c alpha cells depend on beta-cell secretion to regulate:
decreased insulin –>
decreased inhibition of glucagon secretion –>
glucagon continues to stimulate liver to produce glucose –>
hyperglycemia
Is DM2 diabetes ~w/ HLA phenotype?
NO!
• Associated co-morbidities: Obesity, hyperlipidemia, polycystic ovary disease, fatty liver disease
What is the clinical presentation of DM2?
Usually post-puberty; usually overweight/obese
Usually not associated with ketoacidosis
Polyuria/nocturia, polydipsia
Weight loss
Blurry vision
>50% have positive family history
T/F?:
In DM2, the First Phase Insulin Response (FPIR=insulin released in 1st and 3rd minute following IV glucose) is usually lost completely; the second phase is normal or exaggerated.
TRUE!
In the Tx of DM2, when do pt. need insulin?
Usually require insulin after about 10 years of disease (or when A1c > 10%, whichever comes first).
How/what drugs are used to Tx DM2?
Diet and exercise
Statins
Antihypertensives
Oral agents (Metformin first line; use 2 meds if A1c is 8-10%)
Aggressive management early on can prevent or delay complications.
W.R.T diabetes, what are the levels of prevention?
- Primary: stopping before development of autoAb (i.e. with infant diet changes—studies ongoing)
- Secondary: prevent those with autoAb from developing clinical symptoms (i.e. with oral insulin—no clear delay in disease unless had very high Ab titers)
- Tertiary: prevent progression of disease (i.e. with anti-CD3 antibodies, Abatacept)
W.R.T diabetes, the prevention of those with autoAb from developing clinical symptoms (i.e. with oral insulin—no clear delay in disease unless had very high Ab titers.
Is was level of prevention?
Secondary
