Week 11: Diabetes
Advantages of ultra-long-acting insulin
-stable glucose lowering effect -Flexibility for pt -lower risk for nocturnal hypoglycemia -good at room temp for 8wks -200 U/mL formulation for pts who need large volumes of insulin
Dosing of alpha glucosidase inhibitors
3x daily with meals
Dosing of meglitinides
3x daily with meals; skip dose if skip meal
Explain the 2 Step Strategy for Diagnosing pregnant women with GDM
1. 50g GLT test; if 1hr glucose is 140 or more, proceed to step 2 2. 100g OGTT when pt is fasting; check fasting, 1hr, 2hr, and 3hr glucose levels and if two or more of these levels are high diagnose GDM
What are the 8 main classes of non-insulin diabetes medications?
1. Biguanide (metformin) 2. Thiazolidinones (pioglitazone, rosiglitazone) 3. Sulfonylureas (glipizide, glyburide) 4. Meglitinides (repaglinide, nateglinide) 5. DPP-4 Inhibitors (sitagliptin) 6. Alpha-gluconidase inhibitors (acarbose, miglitol) 7. Na glucose co-transporter 2 inhibitors (-flozin) 8. Dopamine agonists (bromocriptine) 9. Bile acid sequestrants (colesevelam or welchol) 10. GLP 1 receptor agonist (exenetide, victoza/liraglutide)
What are the two classes of insulin sensitizers (increase sensitivity to insulin)?
1. Biguanides (metformin) 2. Thiazolidinones (pioglitzone, rosiglitazone)
Diabetes is a dysfunction characterized by hyperglycemia which is caused by what three factors?
1. Deficiency of insulin 2. Insulin resistance 3. Excessive glucagon secretion
What are the short acting insulins?
1. Humulin 2. Novolin
What are the main rapid acting insulins?
1. Insulin aspart: Novalog 2. Insulin glulisine: Apidra
What are two common issues with continuous insulin injections
1. Lipohypertrophy 2. Lipoatrophy
What are the 4 different therapy options for diabetes?
1. Monotherapy: Metformin 2. Dual Therapy: Metformin + one other med 3. Triple Therapy: Metformin + two other meds 4. Combination injectable therapy
What are the effects of insulin on organs?
1. Simulates skeletal muscle fibers 2. Simulates liver cells 3. Acts on fat cells 4. Inhibits production of certain enzymes *Triggers all of these by binding to receptors
What are the actions of insulin?
1. amino acid uptake > protein synthesis 2. glucose uptake > glycogen fat synthesis 3. enzyme production > glycogen breaking
What test would you perform if using the 1 step strategy for GDM?
75g OGTT; measure fasting, 1hr and 2hr glucose levels
What is the Ominous Octet?
8 Core Defects in Type 2 Diabetes: 1. Decreased insulin secretion from beta cells 2. Increased hepatic glucose production 3. Decreased cellular uptake of glucose 4. Increased lipolysis 5. Decreased incretin effect 6. Increased glucagon release from alpha cells 7. Increased glucose reabsorption (in kidneys) 8. Neurotransmitter dysfunction (appetite control)
How often are long acting insulins usually injected?
1x daily
Dosing of DPP 4 Inhibitors
1x daily with or without food at the same time each day
The drugs recommended by the American Academy of Pediatrics for use in children with diabetes (depending upon type of diabetes) are Select one: a. Metformin and insulin b. Sulfonylureas and insulin glargine c. Split-mixed dose insulin and GPL-1 agonists d. Biguanides and insulin lispro
A
The family nurse practitioner would expect which symptom to be a side effect of metformin (Glucophage)? A. GI upset B. Photophobia C. Hypoglycemia D. Skin eruptions
A
Which medication class produces GI discomfort, including gas production, to the point that many patients discontinue them secondary to these side effects Select one: a. Alpha-glucosidase inhibitors b. TZDs c. Amylin analogs d. GLP-1 agonists
A
When do you test pregnant women for gestational diabetes?
24-28wks gestation
What is the 50/50 rule?
50% basal for low continuous dose 50% bolus for meal time coverage
Dosing of metformin
500-2500mg 1x or 2x daily
When is the best time to give short acting insulin for best effect?
30-60min before meals
When should a provider use monotherapy for a diabetic pt?
ALWAYS unless: A1C 9% or more
A patient with type II diabetes is taking glipizide (Glucotrol) 10 mg PO b.i.d. In evaluating the medications effectiveness, the nurse practitioner knows that glipizide reduces blood glucose by: A. Delaying the cellular uptake of potassium and insulin B. Simulating insulin release from the pancreas C. Decreasing the bodies need for and utilization of insulin at the cellular level D. Interfering with the absorption and metabolism of fat and carbs
B
An adult male patient with type II diabetes has a creatinine level of 1.8 mg/dL which of the following drugs is contraindicated? A. Pioglitazone B. Metformin C. Rapaglinide D. Acarbose
B
Metformin is a primary choice of drug to treat hyperglycemia in type 2 diabetes because it Select one: a. Substitutes for insulin usually secreted by the pancreas b. Decreases gluconeogenesis by the liver c. Increases the release of insulin from beta cells d. Decreases peripheral glucose utilization
B
Mr. Smith has recently been discharged from the hospital with a diagnosis of acute pancreatitis and returns to your office for follow up. Which of the following medications is contraindicated for control of his Type 2 Diabetes, given this new diagnosis? Select one: a. Insulin b. GLP-1 agonists c. Metformin d. Amylin
B
One reason diabetic patients have difficulty losing weight is due to the effects of exogenous insulin. Which of the following effects most specifically relates to this inability to lose weight? Select one: a. Insulin acts on glucose cell membrane transporters and prevents the transport of glucose. b. Insulin increases the conversion of insulin to fat. c. Insulin acts on adipose tissue, increasing circulating free fatty acids. d. Insulin acts on muscle cell growth, promoting protein synthesis
B
Sulfonylureas may be added to a treatment regimen for type 2 diabetics when lifestyle modifications and metformin are insufficient to achieve target glucose levels. Sulfonylureas have been moved to Step 2 therapy because they Select one: a. Increase endogenous insulin secretion b. Have a significant risk for hypoglycemia c. Address the insulin resistance found in type 2 diabetics d. Improve insulin binding to receptors
B
What underlying physiological issue occurs in type 1 diabetes?
Absolute deficiency of insulin secretion usually due to autoimmune destruction
What are the to Alpha Glucosidase Inhibitors?
Acarbose, Miglitol
What is a major advantage of long acting insulins?
Allows more flexibility for pts and families
What are the main Long Acting Insulins?
Are basal insulins: 1. Glargine (Lantus) 2. Detemir (Levemir)
How long do you have to wait between dosing for ultra long acting insulin?
At least 8hrs between dosing
A patient who was just recently started on repaglinide (Prandin) has called in to ask for your advice. She will not be able to take time to eat lunch today and because she is on the medication three times daily, she needs to know what to do about her usual lunchtime dose. How should you advise her? Select one: a. Continue to take the medication as prescribed. b. Skip the lunch dose and double the dose for dinner. c. Skip the lunch dose and continue with the normal dose for dinner. d. Skip both the lunch and dinner doses
C
According to the ADA guidelines, SGLT-2 inhibitors are indicated to treat which type of patient Select one: a. Newly diagnosed patient with T1DM with moderate renal impairment (GFR< 45 ml/min) b. Newly diagnosed patient with T1DM who has not started insulin therapy c. Established T2DM patient whose HA1C remains elevated with metformin d. Established T2DM with moderate renal impairment (GFR < 45ml/min)
C
An example of a sulfonylurea is A. Glyburide B. Glipizide C. Both a and b D. Metformin
C
Both angiotensin-converting enzyme inhibitors and some angiotensin II receptor blockers have been approved in treating Select one: a. Hypertension in diabetic patients b. Diabetic nephropathy c. Both A and B d. Neither A nor B
C
Insulin is used to treat both types of diabetes. It acts by Select one: a. Increasing beta cell response to low blood-glucose levels b. Stimulating hepatic glucose production c. Increasing peripheral glucose uptake by skeletal muscle and fat d. Improving the circulation of free fatty acids
C
Patients started on metformin (Glucophage) need to be monitored closely for what potential side effects A. Significant increase in weight B. Elevation of LDL C. Lactic acidosis D. Increase in insulin requirements
C
The primary physiological problem in T2DM includes: Select one: a. Destruction of pancreatic beta cells b. Secondary disease such as pancreatitis c. Insulin resistance in tissues d. Decreased insulin production
C
Which of the following statements best describes the MOA of the GLP-1 agonists Select one: a. This oral medication stimulates to beta cell to increase insulin secretion regardless of food intake. b. This oral medication blocks the breakdown of the GLP-1 peptide. c. This injectable medication improves the glucose mediated insulin release from the beta cell. d. This injectable medication is a long acting insulin.
C
Are DPP 4 inhibitors used as monotherapy or in combination?
BOTH
MOA of Metformin
Decreases liver gluconeogenesis Decreases intestinal glucose absorption Increases insulin tissue sensitivity
Are large insulin dose injections absorbed faster or slower?
Delayed in action and duration
What are the consequences of type 2 diabetes?
Diabetic nephropathy Diabetic neuropathy Diabetic reinopathy Stroke, Heart disease, Vascular disease
Lifestyle changes for Diabetes
Dietary: decrease carbs, cholesterol and sweets Physical activity: 150 min/wk Smoking cessation
Are amylin analogs used in type 1 or 2 diabetes?
Can be used in either
What is the standout adverse effect of GLP1 agonists?
Can cause thyroid hyperplasia so contra in anyone with family history of thyroid cancer
How would you monitor the basal insulin effectiveness?
Check fasting blood glucose
How would you monitor the bolus insulin effectiveness?
Check postprandial blood glucose
When is minidose glucagon given?
Child/adolescent with type 1 diabetes can't consume/absorb oral carbs bc of N/V associated with gastroenteritis *Given to prevent impending hypoglycemia
Contraindications of Thiazolidinediones
Children DKA Black box warning for hepatic dysfunction and HF
Which medications can increase hyperglycemia?
Corticosteroids Estrogens Lithium Morphine sulfate Niacin Thiazide Diuretics HIV/AIDS treatment Organ transplant
Which factors should you consider when selecting diabetes treatment
Cost Age Obesity level Duration of diabetes Lifestyle Current meds Comorbidities Hypoglycemia history Lipid levels
Nonselective beta blockers and alcohol create serious drug interactions with insulin because they Select one: a. Increase blood glucose levels b. Produce unexplained diaphoresis c. Interfere with the ability of the body to metabolize glucose d. Mask the signs and symptoms of altered glucose levels
D
The action of DPP-4 medications is different from other antidiabetic agents because they Select one: a. Have a low risk for hypoglycemia b. Are not associated with weight gain c. Close ATP-dependent potassium channels in the beta cell d. Act on the incretin system to indirectly increase insulin secretion
D
Which of the following medications are not recommended for use in older adults with type 2 diabetes due to the risk of hypoglycemia? Select one: a. DPP-4 inhibitors b. Metformin c. Pioglitazone d. Second generation sulfonylureas
D
True/False: GLP 1 agonists are safe to use in type 1 diabetes
FALSE
True/False: GLP 1 receptor agonists can be used in type 1 diabetes
FALSE
True/False: Mixed insulins are used for intensive therapy
FALSE
True/False: mothers with gestational diabetes have to be diabetic previous to pregnancy
FALSE
True/False: Long acting insulin can be combined with other insulins
FALSE; cannot be combined with other insulins
For ONE step Strategy: At which glucose levels would you diagnose GDM for: -Fasting: -1hr glucose: -2hr glucose:
Fasting: >92 1hr: >180 2hr: >153
For TWO step Strategy: At which glucose levels would you diagnose GDM for: -Fasting: -1hr: -2hr: -3hr:
Fasting: >95 1hr: >180 2hr: >155 3hr: >140
What are the best sites for insulin injection?
Fatty areas; abdomen, thighs, back of arms, buttocks, flank areas
What is required in order to use mixed insulin injections?
Fixed meal times and stable carb intake
How should diabetes management be different for older adults?
For Functional, cognitively intact older adults the diabetes care/goals should be the same that are used for younger adults
Adverse effects of GLP 1 Receptor Agonists
GI effects: N/V/D Less common: pancreatitis, renal failure
Adverse effects of colesevelam use
GI effects: nausea, bloating, constipation Increased TG
Contraindications to alpha glucosidase inhibitors
GI issues: Short bowel syndrome, IBD, increased liver transaminases Renal impairment bc metabolites excreted in kidney
Adverse effects of Alpha Glucosidase Inhibitors
GI issues: gas, bloating, abd. pain
What are the two main non-insulin injectables?
GLP 1 agonists: 1. Exenatide 2. Victoza
Which diabetic medication is a non-insulin injectable formulation?
GLP 1 receptor agonist
What is the main incretin and what are its functions?
GLP-1 released from intestine in response to food intake >enhances glucose dependent insulin secretion >decrease glucagon secretion by alpha cells >promote satiety by activity in brain >slow gastric emptying to decrease appetite
Contraindications of GLP 1 Receptor Agonist use
Gastroparesis Thyroid hyperplasia
Which insulin can be used with exanetide?
Glargine or lantus
Which sulfonylurea has the least potential for prolonged hypoglycemia and is therefore considered the safest?
Glipizide
What is given for severe hypoglycemia? What does it do?
Glucagon IV or IM; promotes hepatic glycogenolysis and glucogenesis
Are DPP 4 inhibitors dependent or independent on glucose?
Glucose dependent release of insulin
What are the contraindications of TZDs
Heart failure Hepatic dysfunction **BLACK BOX
Which conditions increase lactic acid and therefore metformin therapy should NOT be used?
Heart failure Severe lung disease Severe liver disease or alcohol abuse Shock/sepsis
What instances increase absorption rate of injected insulin?
Heat Injection in Abdomen
Contraindications of Sulfonylureas
Hepatic dysfunction
When should a provider change the diabetes regimen from monotherapy to dual therapy?
If A1C target not achieved after 3 months If A1C target not achieved after 3 months of dual therapy move on to triple therapy
Which factors might necessitate insulin dose adjustments?
Illness Medication Physical activity Change in routine Change in diet
Both biguanides and thiazolidinediones improve the action of insulin without ____________________
Improve the action of insulin without directly increasing insulin secretion
MOA of DPP-4 Inhibitors
Increase insulin and decrease glucagon secretion by inhibiting the degradation of incretins
MOA of GLP 1 Receptor Agonists
Increase insulin secretion Decrease glucagon secretion Slow gastric emptying Promote satiety
MOA of Meglitinides
Increase insulin secretion DEPENDENT on food intake by binding to ATP potassium receptors on pancreas beta cells
MOA of Sulfonylureas
Increase insulin secretion INDEPENDENT of food intake by binding to ATP potassium receptors on pancreas beta cells
MOA of Sodium-glucose co-transporter 2 Inhibitors (SGL2)
Increase renal glucose excretion by decreasing renal glucose reabsorption and decreasing renal threshold for glucose
Long acting insulins
Lantus or glargine Levemir or detemir
Do you take colesevelam with or without meals?
Take with meals
How would you dose minidose glucagon?
Two units for 2year old; 1 more unit for each year older until 15; if >15, receive only 15 units
Indication for SGLT 2 Inhibitors
Type 2 who are failing with metformin therapy and weight is a large problem
Adverse effects of SGL 2 Inhibitors
UTI Increased urination Hypotension Hypoglycemia Increased LDL Electrolyte abnormalities: increased potassium
MOA of Bromocriptine
Unclear how dopamine agonists aid in diabetes
Which organ systems are affected by diabetes?
Urinary; polyuria, glycosuria Gastric: N/V, abd. pain Eyes Breath Neuro: polydipsia, polyphagia, lethargy Systemic: weight loss Respiratory: kussmaul breathing
Your first treatment of diabetes is always what?
Lifestyle modifications
When should open ryzodeg pens be discarded?
Within 56 days
Is the 50/50 rule a good starting point for both type 1 and type 2 patients?
YES
Do you take metformin with food?
Yes
Should unopened insulin be refrigerated?
Yes
Is the injection technique of an insulin pen the same as a traditional syringe and vial?
Yes, except the needle needs to be held in place for 5-10 seconds
What is an advantage to rapid acting insulin use?
Low risk of hypoglycemia; quick onset and short duration
What is the benefit of using ryzodeg?
Lower risk of hypoglycemia
Which med is considered the drug of choice for all type 2 diabetes?
METFORMIN (biguanide)
Which diabetic medications have modest effects on lowering A1C? 1% or less
Meglitinides .5-1% DPP 4 Inhibitors .5-1% Alpha Glucosidase Inhibitors .5-1% Sodium glucose co-transporter 2 Inhibitor .5-1% Colesevelam .5% Bromocriptine .5%
What is the onset of action and duration of action of long acting insulins
Onset: 1-2hrs Duration: 24hrs
What is the onset of action and duration of action of ultra long acting insulin?
Onset: 3-4 days Duration: more than 42hrs
What is the onset of action and duration of action of Short Acting Insulins?
Onset: 30-60 min Duration: 6 hours
Contraindications to colesevelam use
Pancreatitis Constipation issues
Contraindications of DPP 4 Inhibitors
Pancreatitis HF: may worsen it
What are the signs/symptoms of lactic acidosis?
N/V Abd. pain Tachycardia Increased RR
Adverse effects of bromocriptine
N/V Fatigue Hypotension, HA, syncope, dizziness
Side effects of glucagon
N/V HTN Tachycardia
Do patients with type 2 diabetes require insulin?
NO
Can you prescribe both a meglitinide and sulfonylurea together?
NOT recommended
What is the main intermediate acting insulin and what is its duration of action?
NPH 12 hour duration
Symptoms of diabetes
Polyuria Polyphagia Polydipsia Blurry vision Glycosuria N/V/abd. pain Acetone breath Kussmaul breathing Weight loss Lethargy
Indication for Alpha Glucosidase Inhibitors
Postprandial hyperglycemia Poor dietary adherence or high carb diet
Name the different types of insulin?
Rapid Acting Short Acting Intermediate Acting Long Acting Ultra-long Acting Pre Mixed
Which insulin is clear and which insulin is cloudy in appearance?
Rapid acting are clear Intermediate acting are cloudy
What is the major pre mixed insulin?
Ryzodeg Mix of long acting (Degludec) with rapid acting (aspart)
How is the mechanism of action different between meglitinides and sulfonylureas?
Same MOA but sulfonylureas work independently of glucose intake and meglitinides are dependent on glucose intake to have an effect
What sites should be avoided for insulin injection?
Scarring/hypertrophy Lipohypertrophy; delays absorption
Which insulin is usually used to treat diabetic ketoacidosis as IV insulin?
Short acting insulins (humulin, novolin)
Dosing of Sulfonylureas
Start at lowest possible dose Begin: 1x/daily dose at bfast Increase dose q2wks until desired response
What can be done to minimize side effects of metformin?
Start treatment at bedtime Prescribe extended release
When adding insulin to an oral diabetic regimen for a type 2 diabetes patient, what insulin dose do you start with and when?
Start with lantus (long acting) at 10 units and give at night; increase it from there
What should the starting dose be for Ultra-Long-Acting Insulin for Type 1 diabetes
Starting dose: 1/3 to 1/2 total prescribed daily insulin dose
What should the starting dose be for ultra-long acting insulin in a type 2 diabetic pt?
Starting dose: 10 units/day
For Normal Insulin Regimens: Starting insulin dose is based on ______ Average requirement range from ___ to _____ Basal requirement is ___ of total daily dose Bolus requirement is ___ of total daily dose
Starting insulin dose is based on weight Average requirement ranges from .4-1 unit/kg/day Basal requirement is 50% of total daily dose Bolus requirement is 50% of total daily dose
Storage of insulin in the home
Stored at room temp for 28days Never freeze Roll, don't shake Can store in fridge if unopened Shouldn't be any particles
What is LADA diabetes?
Subset of type 1 diabetes called latent autoimmune diabetes in adults which develops slowly over many years
Decrease ___________ dose to prevent hypoglycemia if used in conjunction with GLP 1 agonists
Sulfonylurea
What are the most common add ons to metformin administration?
Sulfonylurea (high effect, low cost) DPP 4 inhibitors (high tolerability) TZD GLP 1 receptor agonist Insulin
Which diabetes medications could cause hypoglycemia?
Sulfonylureas >contraindicated in elderly bc of this Meglitinides SLG 2 Inhibitors
Why would you recommend a sulfonylurea over a meglitinide?
Sulfonylureas are less expensive and have higher improvements on A1C than meglitinides
How can insulin be administered subcutaneously?
Syringe Insulin Pen Continuous insulin infusion pump
TRUE/FALSE: The action of alpha glucosidase inhibitors is limited to the intestine and they primarily decrease postprandial glucose levels
TRUE
TRUE/FALSE: insulin is the main management of type 1 diabetes and the treatment for type 2 diabetes
TRUE
True/False: Alpha glucosidase inhibitors are not associated with hypoglycemia, weight gain and are not used as monotherapy
TRUE
True/False: Amalyn analogues can be used in type 1 diabetes
TRUE
True/False: Caution use of SGL 2 inhibitors in patients taking digoxin
TRUE
True/False: D/C metformin 24-48hrs prior to diagnostic and surgical procedures
TRUE
True/False: DPP 4 inhibitors are weight neutral and reduce both pre and post prandial glucose levels
TRUE
True/False: GLP 1 has an indirect benefit on beta cell workload since decreased glucagon secretion will produce decreased postprandial hepatic glucose output.
TRUE
True/False: Glucose levels return to normal after delivery in gestational diabetes
TRUE
True/False: Glycemic goals for some older adults might be relaxed, but hyperglycemia leading to risk of acute hyperglycemic complications should still be avoided
TRUE
True/False: Insulin injection sites should be rotated
TRUE
True/False: Insulin should be given at room temperature
TRUE
True/False: Manual mixed insulins are declining in use and pre mixed insulins are increasing due to medical errors
TRUE
True/False: Metformin reduces fasting and postprandial hyperglycemia
TRUE
True/False: Mixed insulin are at fixed ratio formulations
TRUE
True/False: Older adults >65 have a higher risk for diabetes, polypharmacy, premature death, and depression
TRUE
True/False: Correction of the fasting blood glucose level by PM insulin may improve OA action
TRUE: Basal insulin at bedtime Dosing 6-1- units at bedtime and increase by 2 units every 2-3 days until FPG reaches goal
True/False: Mixed insulin is declining in use
TRUE: Basal/Bolus is more flexible
True/False: Rapid acting insulins have activity profiles similar to endogenous insulins
TRUE; developed to address problems with human insulins and provide better glucose control
True/False: Alpha glucosidase inhibitors do not act directly on defects of diabetes type 2
TRUE; just slow down carb breakdown
What is the additional benefit of colesevelam use?
additionally lowers LDL by 20%
What is the underlying physiological problem in type 2 diabetes
combo of resistance to insulin and inadequate insulin secretion
If you are maxed out on 2 medications but A1C is >9 and not yet at goal level you should ______________
consider adding a basal insulin
Which neurotransmitters control appetite?
dopamine, serotonin
Caution sulfonylurea use in which patients?
elderly; more risk for hypoglycemia
What is the standout se of TZDs?
increased risk of bone fractures
What do you have to evaluate when dosing DPP4 Inhibitors?
renal function
Why is it important to rotate insulin injection sites?
to stop lipohypertrophy from happening
Which diabetes medications do you take with food?
**Sulfonylureas: SKIP dose if SKIP meal **Meglitinide: SKIP dose if SKIP meal Metformin Bromocriptine Colesevelam Alpha glucosidase inhibitors
What is the formula for TDD insulin calculations?
.4-1unit/kg/day
What is considered a conservative insulin dose?
.5 unts/kg/day
How long until the full effects of Thiazolidinediones will be seen?
1-2 months
4 Common Issues that cause hyperglycemia
1. Abnormal islet cell function 2. Increased glucagon production by pancreatic cells further increases hepatic glucose production 3. Insulin resistance in target tissues 4. Abnormalities in the incretin system
What are your three options if: FPG >130 OR 2 hour postprandial >180 OR A1C > 7%
1. Add third OA 2. Add exenatide 3. Add insulin
What are the 3 Situations in which PreDiabetes Should be diagnosed?
1. FPG 100-125 2. 2hr glucose 140-199 3. A1C 5.7%-6.4%
What are the 4 Situations in which Diabetes Should be diagnosed?
1. FPG 126 or greater 2. 2hr glucose 200 or greater 3. A1C 6.5% or greater 4. Symptoms and random glucose 200 or greater
What are the treatment goals of diabetes?
1. FPG of 100 or less 2. 2hr glucose 70-130 3. A1C <7%
What are the 4 oral therapy and insulin combinations?
1. Sulfonylurea + insulin 2. Metformin + insulin 3. Acarbose + insulin 4. Pioglitazone + insulin
What are the two classes of insulin secretagogues (increase endogenous insulin)
1. Sulfonylureas (glyburide, glipizide) 2. Meglitinides (repaglinide, nateglinide)
How long until the full effects of GLP 1 Receptor agonists will be seen?
1.5-2 months
When would you inject ryzodeg?
1/2 injections/day with main meal
How long are premixed insulin and intermediate acting insulin pens good for?
10-14 days
When should you administer a rapid acting insulin for best results?
15 min. before meals
Calculate the insulin dosage for a pt who weighs 150lbs if you want to start with .5unit/kg/day
150/2.2 = 68kg 68kg x .5 units = 34unts/day Basal: 50% or .5 X 34 = 17 units/day Bolus: 50% or .5X 34 = 17 units/3 meals per day = 6 units with every meal
Are 1st or 2nd generation sulfonylureas more commonly used?
2nd more commonly used bc more potent
How long until the full effects of alpha glucosidase inhibitors will be seen?
2 weeks
How long until the full effects of Sulfonylureas will be seen?
2 weeks (like metformin)
How long until the full effects of metformin will be seen?
2 weeks; titrate q2wks
Dosing of sulfonylureas
2x daily with biggest meals; skip dose if skip meal
How often are mixed insulins usually injected?
2x/day
How long are prefilled pens with aspart, glulisine, lispro, detemir, glargine and regular good for?
28 days
About how long do rapid acting insulins last?
4 hours
What is the FG goal for diabetics?
<130
What is the postprandial glucose goal for diabetics?
<180
What are the A1C goals for diabetics?
<7% for most people less stringent = <7.5-8% more stringent = <6-6.5
What is the standard A1C treatment goal for non-pregnant adults?
<7% or ideally <6.5% <8% for pts with H/O severe hypoglycemia
Uncontrolled diabetes is marked by an A1C level of what?
>8%
How would you add insulin to an oral medication therapy if glucose levels are not controlled?
Add basal insulin ie. glargine or detemir at bedtime Dose 6-10units or .1unit/kg/day at bedtime and increase by 2 units every 2-3 days until reach goal
When do you want to dose other medications in adjunction with colesevelam?
Administer separately because colesevelam can bind to and inactivate other medications
Which substances can cause hypoglycemia?
Alcohol Beta blockers Sulfonamides Tetracyclines
Which sulfonylurea is considered the best for use and which is considered the worst?
Best: glipizide bc no active metabolites (safest on kidneys and lowest risk of hypoglycemia) Worst: glyburide bc metabolites are active (highest risk for hypoglycemia and renal injury)
Which diabetic medications are weight neutral or cause weight loss?
Biguanides: neutral or weight loss DPP 4 Inhibitors: weight loss GLP 1 receptor agonists: weight loss SGL 2 Inhibitors: weight loss
Which diabetes medications rarely cause hypoglycemia?
Biguinaides Thiazolidinediones Bromocriptine GLP 1 receptor agonists DPP 4 Inhibitors Alpha glucosidase inhibitors Colesevelam
Monitoring for Minidose Glucagon
Blood glucose q30min 1st hour; then hourly until blood glucose is 100 If glucose unchanged in 30min, can repeat and double dose
Cystic Fibrosis related diabetes
Caused by defect in a single gene Occurs in maturity
Adverse effects of Thiazolidinediones
Common: fluid retention, edema, weight gain Uncommon: liver injury, fractures Possible: MI risk with rosiglitazone Possible: bladder cancer risk with plioglitazone
Adverse effects of Sulfonylureas
Common: hypoglycemia, weight gain Uncommon: photosensitivity, rash, N/V
Which diabetic medication has the ability to cause pancreatitis?
DPP 4 Inhibitors
Which class of diabetic medication are incretin enhancers?
DPP-4 Inhibitors
MOA of Thiazolidinediones
Decrease liver gluconeogenesis Increase insulin tissue sensitivity
MOA of Bile acid sequestrants (Colesevelam)
Decrease liver glucose production by enhancing liver insulin sensitivity Also decrease intestinal glucose absorption
Contraindications of bromocriptine
Don't use in conjunction with antihypertensives bc can increase risk of hypotension
How would you dose ultra-long acting insulin for established type 1 or type 2 insulin users?
Dose equivalent to usual total dose of long or intermediate acting insulin
Which two medications should be used for patients with type 2 diabetes and cardiovascular disease? Why?
Empagliflozin OR Liraglutide Because reduce cardiovascular mortality
What are the benefits to Thiazolidinediones?
Highly durable with long lasting effects Rarely causes hypoglycemia
Pharmacodynamic factors of Thiazolidinediones
Highly protein bound Metabolism by CYP450
What is insulin?
Hormone produced by beta cells in islets of Langerhans in PANCREAS
Are Rapid-acting insulins from animals or humans?
Human analogs
Short acting insulins
Humulin Novolin Regular
Which condition may increase the need for insulin?
Hyperthyroidism
When are meglitinides contraindicated?
Hypoglycemia unawareness ie. elderly Poor renal function
When are sulfonylureas contraindicated?
Hypoglycemia unawareness ie. elderly Poor renal function
Adverse effects of meglitinides
Hypoglycemia, weight gain Increased uric acid
Which condition may decrease the need for insulin?
Hypothyroidism
In which situations does metformin use need to be temporarily discontinued?
IV contrast studies: hold day of, restart in 48hrs Before surgery
What are the benefits to Sulfonylureas?
Inexpensive (like metformin) Decreased microvascular risk with long term use
Which diabetic medications have the greatest effect on lowering A1C? between 1-2%
Insulin >1.5% Biguanides 1-2% Sulfonylurease 1-2% TZDs 1-1.5% GLP 1 receptor agonists 1-1.5%
Which diabetic medications are ok during pregnancy?
Insulin; preferred Glyburide Metformin
What do the pre mixed insulins consist of?
Intermediate insulin and short acting insulin SO.... NPH + humulin NPH + novolin NPH + novolog
What is the main ultra-long-acting insulin?
Is a basal Insulin: 1. Degludec (Tresiba)
Adverse effects of DPP 4 Inhibitors
Liver dysfunction although rare
When is metformin contraindicated
Liver impairment Alcoholism Renal impairment (creatinine >1.5)
What are the adverse effects of metformin?
Mostly GI; N/V, abd. pain Rarely lactic acidosis or B12 deficiency
What does insulin do?
Moves glucose from the plasma into cells to be stored or used for energy
What are the two ways to administer basal bolus dose insulin?
Multiple day injections OR Continuous subcutaneous insulin (CSII)
Rapid acting insulins
Novolog or aspart Humalog or lispro
What is the major cause of the increase in insulin resistance? (ie. type 2)
Obesity
Which conditions are associated with insulin resistance?
Obesity Acanthosis nigricans PCOS
Which factors put patients at increased risk for diabetes?
Obesity GDM Physical inactivity Family with diabetes HDL <35 or TG >250 HTN or CVD A1C > 5.7%
Name a specific amylin analog and the MOA
Pramlintide Delays gastric emptying which decreases postprandial glucose release, decrease glucagon release by alpha cells, increases satiety
When is metformin contraindicated?
Renal Impairment (bc fully eliminated by kidneys) GFR <30mL/min or creatinine >1.5: contraindicated GFR 30-45mL/min: precaution or dose reduction
Contraindications to SGL 2 Inhibitor use
Renal impairment, bladder cancer Stroke
How do insulin dose requirements differ in insulin resistance (type 2)
Require larger doses: >200units/day Standard formulation: 100unit/mL New formulations: 200 units/ mL or more
MOA of Alpha-glucosidase Inhibitors
Slow carb breakdown to glucose by inhibiting alpha enzymes in small intestine
What are the benefits to Metformin use?
Significantly reduces A1C: 1-2% No associated weight gain Inexpensive Rarely causes hypoglycemia Lowers MI and all cause mortality
What are the S/S of hypoglycemia?
Sweating Hunger Fatigue Shakiness, tremors Confusion N/V Dizziness
Describe the honeymoon period after initiation of insulin in type 1 patients
There is some recovery of B cell function > lower insulin requirement needed Max benefit to preserve beta cell function > highest dose that doesn't cause hypoglycemia
Which diabetic medications can cause weight gain?
Thiazolidinediones (TZDs) Sulfonylureas Meglitinides
What should the total dose of ultra-long-acting insulin be for type 1 diabetes pts that are insulin naive?
Total dose for insulin naive pt: .2-.4 unit/kg body weight Combine with short acting insulin with meals for full coverage
Do type 1 patients usually require less or more insulin?
Usually less insulin bc not insulin resistant
If you are maxed out on 2 medications but A1C <9 but not yet at goal level, you should add _____________
a third diabetic medication
What are the max doses of rosiglitazone and pioglitazone?
rosiglitazone: 8mg daily pioglitazone: 45mg daily
Which type of diabetes are completely dependent on exogenous insulin
type 1
Which type of diabetes is particularly at risk for ketoacidosis
type 1
Is diabetes type 1 or 2 more common?
type 2; 95% of all cases