Diabetes Flashcards
What is the central problem in all types of diabetes?
The central problem in all types of diabetes is that blood glucose (BG) remains high (hyperglycemia) due to decreased insulin secretion from the pancreas, decrease insulin sensitivity, or both. Chronic hyperglycemia can lead to damage throughout the body, including organ and nerve damage
What is insulin and what is it responsible for??
Insulin is a hormone produced by beta-cells (also called islet cells) in the pancreas. It is responsible for moving glucose out of the blood and into body cells to be used as energy. The glucose is either moved to muscle cells (primarily) for immediate use, or stored for later us by liver cells (as glycogen) or adipose (fat) cells
What is glucagon and what is it responsible for?
Glucagon is produced by alpha-cells in the pancreas and works when BG is low. Glucagon pulls glucose back into the circulation by releasing glucose from glycogen. If glycogen is depleted, glucagon will signal fat cells to make ketones as an alternative energy source
What is type 1 diabetes?
Type 1 diabetes is caused by an autoimmune destruction of beta-cells in the pancreas. Once the beta-cells are destroyed, insulin cannot be produced.
What is a possible complication of type I diabetes?
Without insulin, glucose cannot enter muscle cells. The body goes into starvation mode, and starts to metabolize fat into ketones to use as an alternative energy source. Ketones are very acidic. Very high ketone levels can cause diabetic ketoacidosis (DKA) which is a medical emergency
When is TID typically diagnosed?
Most TID is diagnosed in children, but it can develop at any age. Family history is the biggest risk factor
What is the C-peptide test and how can it be used to diagnose TID?
The C-peptide test is used to determine if the patient is still producing insulin. C-peptide is released by the pancreas only when insulin is released. TID is diagnosed when there is a very low or absent (undetectable) C-peptide level
How should patients with TID be treated?
Patients with TID must be treated with insulin and should be screened for other autoimmune disorders
What is type 2 diabetes?
Type 2 diabetes is due to both insulin resistance and insulin deficiency. the pancreatic beta-cells produce less insulin over time as they become damaged
What is T2D typically associated with?
Obesity, physical inactivity, family history and the presence of other comorbid conditions
How is T2D typically treated?
T2D is usually diagnosed in older patients and can be managed with lifestyle modification alone (in a small number of patients) or in combination with oral and/or injectable medications
What is prediabetes?
Prediabetes means there is an increased risk of developing diabetes. In prediabetes the BG is higher than normal, but not high enough for diabetes diagnosis.
What can reduce the risk of progression from prediabetes to diabetes?
Following dietary and exercise recommendation
How can Metformin be helpful in prediabetes?
Metformin can be used to help improve BG levels, especially in patients with a BMI > 35, age < 60 years and women with a history of gestation diabetes.
What are the two types of diabetes in pregnancy?
Diabetes that was present prior to becoming pregnant or diabetes that developed during pregnancy
What happens to babies born to mothers with hyperglycemia during pregnancy?
Babies are larger than normal (macrosomia) and are at high risk for developing obesity and diabetes later in life
When are most pregnant women tested for GDM and what test do they use?
Most pregnant women are tested for GDM at 24-28 weeks gestation using the oral glucose tolerance test (OGTT)
How should diabetes in pregnancy be treated?
Hyperglycemia, if present, should be treated first with lifestyle modifications (diet and exercise). If medication is needed, insulin is preferred. Metformin and glyburide are sometimes used
What are some major risk factors of diabetes?
Physical inactivity, overweight (BMI > 25 or 23 in Asian-Americans), high risk race or ethnicity (African-American, Asian-American, Latino/Hispanic Americans, Native American or Pacific Islander), History of gestational diabetes, A1C > 5.7, first-degree relative with diabetes. HDL < 35 mg/dL or TG > 250 mg/dL, hypertension, CVD history or smoking history, conditions that cause insulin resistance (acanthosis nigricants, PCOS)
What are the classic symptoms of hyperglycemia?
Polyuria (excessive urination), polyphagia (excessive hunger or increased appetite), polydipsia (excessive thirst)
What are other symptoms of diabetes?
Other symptoms include fatigue, blurry vision, erectile dysfunction and vaginal fungal infections
When should people be screened for diabetes?
Everyone, even those with no other risk factors, should be tested beginning at 45 years old. All asymptomatic children, adolescents and adults who are overweight, with at least one other risk factor should be tested. If the result is normal, repeat testing every 3 years
What are the three types of test used to identify if prediabetes or diabetes is present?
1) Hemoglobin A1C indicates the average BG over approximately the past 3 months
2) Fasting plasma glucose (FPG) gives the BG at that moment, and is taken after fasting for > 8 hours
3) The OGTT determines how well glucose is tolerated by measuring the BG level 2 hours after drinking a liquid that is high in sugar (glucose)
What A1c indicates prediabetes?
5.7-6.4
What A1c indicates diabetes?
> 6.5
What FPG is considered prediabetes?
100-125
What FPG is considered diabetes?
> 126
What OGTT result is prediabetes?
140-199
What OGTT results shows diabetes?
> 200
What is the A1c goal of someone who has diabetes and is not pregnant?
< 7
*An A1c goal of < 6.5% may be acceptable if it can be reached without significant hypoglycemia. A less-stringent goal of < 8% may be appropriate (e,g, if severe hypoglycemia, or with a limited life-expectancy)
How often should A1c be measured?
Quarterly (every 3 months) if not yet at goal or biannually (every 6 months or twice per year) if at goal
What is the estimated average glucose (eAG)?
The estimated average glucose (eAG) is an interpretation of the A1C value that makes it appear similar to a glucose meter value. An A1c of 6% is equivalent to an eAG of 126 mg/dL. Each additional 1% increases the eAG by ~28 mg/dL
What are some lifestyle modifications recommended for patients with diabetes?
Weight loss, individualized medical nutrition therapy, physical activity, smoking cessation
What is the goal waist circumference?
Goal waist circumference is < 25 inches for females and < 40 inches for males
How much weight should overweight or obese patients be encouraged to lose?
> 5%
What are some recommendations with individualized medical nutrition therapy?
- Consume natural forms of carbohydrates and sugars
- Avoid alcohol or drink in moderation
- Patients with TID should use carbohydrate-counting where the prandial (mealtime) insulin dose is adjusted to the carbohydrate intake
What is considered a carbohydrate serving?
A carbohydrate serving is measured as 15 grams, which is approximately one small piece of fruit, 1 slice of bread or 1/3 cup of cooked rice/pasta
How much physical activity should patients with diabetes perform?
- Perform at least 150 minutes of moderate-intensity aerobic activity per week spread over at least 3 days
- Reduce sedentary (long hours of sitting) habits by standing every 30 minutes, at a minimum
What is recommended in terms of smoking cessation with diabetes patients?
Encourage all patients who smoke to quit
What is the goal of treating diabetes?
Treatment is aimed at preventing the long-term complications of diabetes
What are the categories of complications of diabetes?
Microvascular or macrovascular
What is considered microvascular disease?
Retinopathy, diabetic kidney disease, peripheral neuropathy, increased risk of foot infections and amputations, autonomic neuropathy
What is considered macrovascular disease?
Coronary artery disease, cerebrovascular disease, peripheral artery disease
*Macrovascular disease is the same as atherosclerotic cardiovascular disease
What does the American Diabetes Association generally recommend for monitoring, preventing and treating complications of uncontrolled diabetes?
Antiplatelet therapy, cholesterol control, diabetic retinopathy monitoring, vaccinations, neuropathy monitoring, blood pressure control, foot care counseling, diabetic kidney disease
What is the antiplatelet therapy recommendation for diabetes patients?
- Aspirin 75-162 mg/day (usually given as 81 mg/day) is recommended for ASCVD secondary prevention (if allergy, use clopidogrel 75 mg/day)
- Not recommended for primary prevention (in most); the risk of bleeding is about equal to the benefit. Can consider if high risk
- CAD/PAD: aspirin + low-dose rivaroxaban can be added
- Used in pregnancy to decrease risk of preeclampsia
What is the recommendation for monitoring for diabetic retinopathy?
Eye exam with dilation at diagnosis. If retinopathy, repeat annually. If not, repeat every 1-2 years
What is the recommendation for cholesterol control in patients with diabetes?
- High intensity statin: diabetes + ASCVD or Age 50-75 years with multiple ASCVD risk factors
- Moderate intensity statin: diabetes + age 40-75 years with no ASCVD or diabetes + age < 40 years + ASCVD risk factors
- Add-on treatment: Ezetimibe if ASCVD 10-yr risk > 20% or Vascepa if LDL is controlled by TGs are 135-499 mg/dL
- Monitoring: lipid panel annually and 4-12 weeks after starting a statin or increasing the dose
What are the recommended vaccinations for patients with diabetes?
Required in addition to all childhood vaccines: Hepatitis B virus series, influenza annually, pneumovax 23 (1 dose between ages 2-64, and another dose at age > 65)
What is the blood pressure goal of patients with diabetes?
< 130/80 if ASCVD or 10 year risk > 15% or <140/90 acceptable if ASCVD risk < 15%
What is the treatment recommendation for blood pressure control of patients with diabetes?
- No albuminuria: thiazide, CCB, ACE inhibitor or ARB
- Albuminuria: ACE inhibitor or ARB
- CAD: ACE inhibitor or ARB
What is the recommendation for neuropathy monitoring for patients with diabetes?
- Annually: a 10-g monofilament test and 1 other test to assess sensation (feeling)
- Comprehensive foot exam at least annually. If high-risk, refer to podiatrist
What are possible treatment options for neuropathy for patients with diabetes?
Pregabalin, duloxetine or gabapentin
What is the recommended foot care counseling for patients with diabetes?
- Every day: wash, dry and examine feet. Moisturize the top and bottom of the feet, but not between the toes
- Each office visit: take off shoes to have feet checked
- Annual foot exam by a podiatrist
- Trim toenails with nail file; do not leave sharp edges from the clipper
- Wear socks and shoes. Elevate feet when sitting
How often should diabetic kidney disease be monitored?
Check urine albumin and eGFR annually if normal kidney function or twice yearly if reduced kidney function (eGFR 30-60 mL/min/1.73 m2 or urine albumin > 300)
What are some natural products that can decrease BG with low or minimal efficacy?
Products used to decrease BG include cassia cinnamon, alpha lipoic acid, chromium, magnesium and Panax/American ginsengq
What are the goals of treatment for type 2 diabetes?
The goals of treatment are to maintain BG levels in the target range (while avoiding hypoglycemia) and to reduce long-term complications of hyperglycemia
What is considered first line treatment for type 2 diabetes?
Metformin is the first-line treatment and should be used indefinitely unless contraindications are present or it is not tolerated
When is it recommended to start two medications to treat type 2 diabetes?
- Start two drugs at baseline if the A1C is 8.5-10%
- Start two drugs at baseline regardless of A1C if the patient has ASCVD, heart failure or CKD. A drug with proven benefit for these conditions should be used
When should you add on a drug after Metformin?
Add on a second drug if the A1C remains above goal on Metformin. In this case, treatment is driven by patient-specific factors (e.g. cost, risk of hypoglycemia and weight). Continue adding medications in this way until the A1C goal is met
When should insulin be used initially for the treatment of T2D?
Insulin can be used initially if hyperglycemia is severe (A1C > 10% or BG > 300 mg/dL)
What is the recommended second drug added if a patient has ASCVD or high risk?
GLP-1a or SGLT2i with benefit
What is the recommended second drug added if a patient has HF?
SGLT2i with benefit
What is the recommended second drug added if a patient has CKD?
SGLT2i or GLP1a with benefit
What is the recommended second drug added if a patient has no ASCVD, HF or CKD?
Any class. Consider hypoglycemia risk, weight loss/gain potential, cost
- Best for hypoglycemia risk: DPP-4i, GLP1a, SGLT2i, TZD
- Best for weight loss: GLP-1a or SGLT2i
- Best for cost: SU or TZD
What are the SGLT2i with benefit?
Empagliflozin, canagliflozin or dapagliflozin
What are the GLP-1a with benefit?
Dulaglutide, liraglutide, SC semaglutide
What should be added as a third drug if a patient with ASCVD or HF or CKD still has an A1c above goal?
GLP-1a or SGLT-2i (if not started), TZD, basal insulin, SU, DPP-4
What should be added as a third drug if a patient with no ASCVD, HF or CKD has an A1c above goal?
Any drug class not yet started
What are combination medications that should be avoided?
- DPP-4i + GLP1a
- SU + insulin
What is the MOA of Metformin?
Metformin primarily works by decreasing hepatic glucose production, decrease intestinal absorption of glucose and increasing insulin sensitivity
What is a boxed warning of Metformin?
Lactic acidosis: risk increases with renal impairment, radiological studies with contrast, excessive alcohol or certain drugs
What is a contraindication of Metformin?
eGFR < 30, acute or chronic metabolic acidosis (includes DKA)
What are some warnings associated with Metformin?
- Not recommended to start if eGFR 30-45; reassess if already taking and eGFR falls < 45
- Vitamin B12 deficiency
What are some side effects of Metformin?
GI effects: nausea, diarrhea, flatulence, cramping; usually transient (resolve over time)
What are some notes about Metformin?
- Decreases A1C by 1-2%, weight neutral, no hypoglycemia
- ER: swallow whole; can leave a ghost tablet (empty shell) in the stool
What are some significant Metformin drug interactions?
- Intravascular iodinate contrast media can increase the risk of lactic acidosis. Discontinue metformin before the imaging procedure. Metformin can be restarted 48 hours after the procedure if eGFR is stable
- Alcohol can increase the risk for lactic acidosis; excessive intake, acute or chronic, should be avoided
- The combination of Metformin and Topiramate can increase the risk of metabolic acidosis
What is the sodium glucose co-transporter protein responsible for?
The sodium glucose co-transporter 2 (SGLT2) protein, expressed in the proximal renal tubules, is responsible for the reabsorption of filtered glucose
What is the benefit of SGLT2 inhibitors?
By inhibiting SGLT2, these drugs reduce reabsorption of glucose and increase urinary glucose excretion, which decrease BG concentrations
How are SGLT2 inhibitors dosed?
SGLT2 inhibitors are dosed based on eGFR
What are some examples of SGLT2 inhibitors?
Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance), Ertugliflozin (Steglatro)
What is a contraindication of SGLT2 inhibitors?
Dialysis
What are some warnings about SGLT2 inhibitors?
- Ketoacidosis (d/c prior to surgery due to risk)
- Genital mycotic infections, urosepsis and pyelonephritis, necrotizing fasciitis of the perineum
- Hypotension, AKI and renal impairment (due to intravascular volume depletion)
What is a warning specifically associated with Canagliflozin?
Increased risk of leg and foot amputations, higher risk with history of amputation, PAD, peripheral neuropathy and/or diabetic foot ulcers, hyperkalemia risk when used with other drugs that increase potassium; risk of fractures
What are some side effects of SGLT2 inhibitors?
Weight loss, increased urination, increased thirst, hypoglycemia, increased Mg/PO4
What are some notes about SGLT2 inhibitors?
- Decreases A1C by 0.7-1%, low hypoglycemia risk (unless used with insulin)
- Canagliflozin, dapagliflozin and empagliflozin have shown reductions in HF and CKD progression. Most renal data is with canagliflozin and dapagliflozin. Most heart failure is with empagliflozin and dapagliflozin
What are some significant SGLT2 inhibitor drug interactions?
- Increased risk of intravascular volume depletion (causing hypotension and AKI) if used in combination with diuretics, RAAS inhibitors or NSAIDs
- Uridine diphosphate glucuronosyltransferase (UGT) inducers can decrease levels of canagliflozin; consider using 300 mg dose if used in combination and eGFR > 60 mL/min/1.73 m2
What is the MOA of glucagon-like peptide 1 (GLP-1) agonists?
GLP-1 agonists are analogs of the incretin hormone GLP-1, which increases glucose-dependent insulin secretion, decreased glucagon secretion, slows gastric emptying, improves satiety and can result in weight loss
Wha are key similarities between all GLP-1 agonists?
They are all SC injections available in either single-dose or multidose pens, except semaglutide also comes as an oral tablet. Some are available in combination with long-acting insulin
What are some examples of GLP-1 agonists?
Liraglutide (Victoza), Dulaglutide (Trulicity), Exenatide (Byetta), Exenatide ER (Bydureon), Lixisenatide (Adlyxin), Semaglutide (Ozempic-SC, Rybelsus-PO)
What is a boxed warning for al GLP-1 agonists except Byetta and Adlyxin?
Risk of thyroid C-cell carcinomas; do not use if personal or family history of medullary thyroid carcinoma (MTC) or with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
What are some warnings about GLP-1 agonists?
- Pancreatitis (can be fatal, risk factors: gallstones, alcoholism or increased TGs)
- Not recommended in patients with severe GI disease, including gastroparesis
What is a warning specific to Bydureon?
Serious infection-site reactions (e.g. abscess, cellulitis, necrosis) with or without SC nodules
What is a warning specific to Ozempic?
Increased complications with diabetic retinopathy
What are some side effects of GLP-1 agonists?
Weight loss, nausea, vomiting, diarrhea, hypoglycemia, injection site reactions
What are some notes about GLP-1 agonists?
- Decreases A1C by 0.501.5%: decreased postprandial BG, low hypoglycemia risk
- Do not use with DPP-4 inhibitors (overlapping mechanism)
- Liraglutide, dulaglutide and semaglutide have demonstrated ASCVD benefit
- Betta and Adlyxin: give dose within 60 minutes of meals (others anytime)
- Pen needles are not provided with Byetta, Victoza or Adlyxin; provided with all others (which are the weekly injections)
What are some GLP-1 agonist drug interactions?
- Therese drug slow gastric emptying and can reduce the absorption of orally administered drugs. Use caution with narrow therapeutic index drugs or drugs that require threshold concentrations for efficacy. Take oral contraceptives at least one hour before exenatide and at least 11 hours after Adlyxin
- Can increase the INR in patients on warfarin
What are the two insulin secretagogues?
Sulfonylureas and meglinitides
How do insulin secretagogues work?
They work by stimulating insulin secretion from the pancreatic beta-cells to decrease postprandial BG
What is the difference between meglitinides and sulfonylureas?
Meglitinides have a faster onset (15-60 minutes) and a shorter duration of action compared to SUs
What are some examples of sulfonylureas?
Glipizide, Glimepiride, Glyburide
What are some contraindications of sulfonylureas?
Sulfa allergy (not likely to cross-react)
What are some warnings about sulfonylureas?
Hypoglycemia
What are some side effects of sulfonylureas?
Weight gain, nausea
What are some notes about sulfonylureas?
- Decreases A1c by 1-2%: decreased efficacy after long-term use (as pancreatic beta-cell function declines)
- Patients with G6PD deficiency can be at increased risk of hemolytic anemia with sulfonylureas
What is a counseling point of Glipizide IR?
Take 30 minutes before a meal; all other products are taken with breakfast or the first meal of the day; may need to hold doses if NPO
What is a counseling point of Glucotrol XL?
Glucotrol XL is an OROS formulation and can leave a ghost tablet (empty shell) in the stool
What is a counseling point of Glimepiride and Glyburide?
Glimepiride, glyburide not preferred in elderly (on the Beers criteria) due to hypoglycemia risk
What are some examples of Meglitinides?
Repaglinide and Nateglinide
What are contraindications of Meglitinides?
Type 1 diabetes, DKA
What are some warnings of Meglitinides?
Hypoglycemia, caution with severe liver/renal impairment