Endocrine System Review Flashcards
Hypoglycemia
- Definition
- Level 1 & 2
- S/s
Blood glucose <50 mg/dL
- More common in people with DM1 (only 5-10% is type 1; average of 2 episodes/week)
- If severe hypoglycemia is uncorrected → coma and/or death
- Nondiabetic hypoglycemia is rare and is either reactive (diet related) or fasting (diseae related)
Level 1 hypoglycemia: glucose alert as fasting BG (FBS) of ≤70 mg/dL
Level 2: BG ≤54 mg/dL
- This low BG indicates serious, clinically important hypoglycemia
Signs & Symptoms
- weakness
- hand tremors
- anxiety
- feels like passing out
- difficulty concentrating
- irritability
Overview: Type 1 DM
1. Definition/ Etiology
2. S/s
3. Labs
4. Complications
- School-age child w/ recent onset of persistent thirst (polydipsia), frequent urination (polyuria), and weight loss
- Diagnosis peaks at ages 4-6 and again from ages 10-14 years
- School-age child w/ recent onset of persistent thirst (polydipsia), frequent urination (polyuria), and weight loss
- feeling of hunger even though eating an ↑ amount of food; weight loss
- polydipsia
- polyuria
- blurred vision (osmotic effect on lens)
- “fruity” odor breath
- may report recent viral-like illness before onset of symptoms
- feeling of hunger even though eating an ↑ amount of food; weight loss
- large # of ketones in urine
- Diabetic Ketoacidosis (DKA) + neurologic symptoms (drowsiness, lethargy, can progress to coma)
Overview: Thyroid Cancer
1. Definition/ Etiology
2. S/s
- A single thyroid nodules, usually located on upper half of one lobe
- may be accompanied by enlarged cervical lymph node lump, swelling, or pain
- higher incidence in Asian race
- Radiation therapy during childhood for certain cancers (Wilm’s tumor, lymphoma, neuroblastoma) and/or a low-iodine diet ↑ risks
- higher prevalence in women (3:1)
- highest incidence from 20-55 years
- Positive family hx of thyroid cancer
- metastasis is by lymph route - c/o hoarseness, problems w/ swallowing (dysphagia, dyspnea, or cough)
Overview: Pheochromocytoma
1. Definition/ Etiology
2. S/s
- rare hormone-releasing adrenal tumor
- generally occurs in persons age 20-50 but can appear at any age
- episode resolve spontaneously
- in b/w attacks, VSS normal
- Triggers: physical exertion, anxiety, stress, surgery, anesthesia, changes in body position, labor & delivery, or foods high in tyramine (some cheeses, beers, wines, chocolates, dried or smoked meats) + MAOIs and stimulant drugs are other triggers - random episodes of headache (mild - severe)
- diaphoresis
- tachycardia
- hypertension
- random episodes of headache (mild - severe)
Overview: Hyperprolactinemia
1. Definition/ Etiology
2. S/s
3. Labs
4. Complications
- can be a sign of pituitary adenoma
- slow onset
- women may present w/ amenorrhea
- galactorrhea in both males and females
- can be a sign of pituitary adenoma
- when tumor is large enough to cause a mass effect → headaches and vision changes
- serum prolactin ↑
Endocrine System: Normal Findings
- Endocrine system works as a “negative feedback” system
- If lower level of “active’ hormones → stimulates production.
- inversely, if level of hormones is high → stops production
- Hypothalamus stimulates the anterior pituitary gland into producing the stimulation hormones (follicle-stimulating [FSH], luteinizing hormone [LH], thyroid-stimulating hormone [thyrotropin; TSH])
- These stimulating hormones tell target orangs (e.g., ovaries, thyroid) to produce “active” hormones (e.g., estrogen, thyroid hormone)
- High level of these “active’ hormones work in reverse → the hypothalamus directs the anterior pituitary into stopping production of the stimulating hormones (e.g., TSH, LH, FSH)
Endocrine Glands: These glands interact to form the HPA axis
HPA axis: hypothalamic-pituitary-adrenal axis
Hypothalamus: TRH, GnRH, CRH, GHRH, Somatostatin
“On or Off” Switches → (for target organs)
Anterior Pituitary: TSH, FSH, TH, GH, ACTH, NSH, Prolactin
Posterior Pituitary: Antidiuretic hormone and oxytocin
Target Organs
- Thyroid (TSH): T3 and T4
- Ovaries/Testes (FSH/LH): estrogen, propgesterone, androgens, testosterone
- Adrenal cortex (ACTH): glucocorticoids, mineralocorticoids
- Body (GH): somatic growth
- Uterus (oxytocin): uterine contractions, bonding
- Kidneys (vasopressin): blood volume
- Pineal (melatonin): circadian rhythm
- Breast (prolactin): milk production
Hypothalamus function
Coordinates the nervous and endocrine system by sending signals via pituitary gland; gland interacts to form the HPA axis; produces neurohormones that stimulate or stop production of pituitary hormones
Pituitary Gland function
Located at sella turcica (base of the brain)
- stimulated by hypothalamus into producing the stimulating hormones such as FSH, LG, TSH, adrenocorticotropic hormone (ACTH), and growth hormone (GH)
Anterior Pituitary Gland function
Adenohypophysis
- Has two lobes (anterior and posterior)
- The anterior pituitary gland produces hormones that directly regular the target organs (e.g., ovaries, testes, thyroid, adrenals)
Posterior Pituitary Gland function
Secretes antidiuretic hormone (vasopressin) and oxytocin, which are made by the hypothalamus but stored an secreted by the posterior pituitary
FSH
Follicle-stimulating hormone
- stimulations the ovaries to enable growth of follicles (or eggs)
- production of estrogen
LH
Luteinizing hormone
- Stimulates the ovaries to ovulate
- Production of progesterone (by corpus luteum)
- In males, LH stimulates the testicles (Leydig cells) to produce testosterone
TSH
Thyroid-stimulation hormone
- stimulates thyroid gland
- production of triiodothyronine (T3) and thyroxine (T4)
GH
Growth hormone
- stimulates somatic growth of the body
ACTH
Adrenocorticotropic hormone
- Stimulates the adrenal glands (two portions of the gland: medulla and cortex)
- Production of glucocorticoids (cortisol) and mineralocorticoids (aldosterone)
Prolactin
- affects lactation and milk production
Melanocyte-stimulating hormone
- Production of melatonin in response to UV light; highest levels at night b/t 11pm and 3am
Thyroid Gland function
A butterfly-shaped orang (two lobes) located below the prominence of the thyroid cartilage (Adam’s apple)
- 2 inches long, and loves are connected by the isthmus
- uses iodine to produce T3 and T4
Parathyroid Glands function
- Locate behind the thyroid glands (two glands behind each lobe)
- produces parathyroid hormone (PTH), responsible for calcium balance of the body by regulating the calcium loss or gain from the bones, kidneys, and GI tract (calcium absorption)
Pineal Gland function
Pea-sized gland located inside brain that produces melatonin, which regulates sleep-wake cycle
- darkness stimulates melatonin production and light suppresses it
Primary Hyperthyroidism
1. Definition/Etiology
2. Clinical Presentation
3. Objective Finding
AKA Thyrotoxicosis
1. - Classic finding is very low (or undetectable) TSH with ↑ in both serum free T4 and T3 levels
- most common cause for hyperthyroidism (60-80%) in US
- chronic autoimmune disorder → Graves’ disease
- middle-aged woman loses a large amount of weight rapidly
- anxiety
- insomnia
- cardiac symptoms (d/t overstimulation); palpitations
- hypertension
- atrial fibrillation
- premature atrial contractions
- warm and moist skin with ↑ perspiration
- may present w/ ophthalmopathy and lid lag (Graves’ ophthalmopathy)
- More frequent BMs (looser stools)
- Amenorrhea
- Heat intolerance
- Enlarged thyroid (goiter) and/or thyroid nodules present
- May be accompanied by pretibial myxedema (thickening of skin usually located in shins and gives an orange-peel appearance)
- middle-aged woman loses a large amount of weight rapidly
- Thyroid: Diffusely enlarged gland (goiter), toxic adenoma, or multinodular goiter; may be tender to palpation or asymptomatic
- Extremities: Fine tremors in both hands, sweaty palms, pretibial myxedema
- Eyes: Lid lag; exophthalmos in one or both eyes
- Cardiac: Tachycardia, atrial fibrillation, CHF, cardiomyopathy
- Integumentary: Fine hair, warm skin
- Neurologic: Brisk deep tendon reflexes
- Thyroid: Diffusely enlarged gland (goiter), toxic adenoma, or multinodular goiter; may be tender to palpation or asymptomatic
Graves’ Disease
Accounts for 60-80% of all types of hyperthyroidism
- An autoimmune disorder causing hyperfunction and production of excess thyroid hormones (T3 and T4).
- Higher incidence in women (7:1); these women are also at higher risk for other autoimmune diseases such as RA and pernicious anemia and for osteopenia/osteoporosis d/t ↑ metabolism
Primary Hyperthyroidism
4. Labs
- Very low TSH (<0.05 mU/L) w/ ↑ T4 and T3
- If Graves’ disease → positive thyrotropin receptor antibodies (TRAb), aka thyroid-stimulation immunoglobulins (TSIs)
- Thyroid peroxidase antibody (TPO) is positive with Graves’ disease as well as Hashimoto’s disease
- Very low TSH (<0.05 mU/L) w/ ↑ T4 and T3
WORK UP:
- Check TSH → If low, order thyroid panel
* Look for very low TSH (<0.05 mU/L) w/ ↑ T3 and T4
- In some pts w/ very low TSH, only either the T4 or T3 will be elevated
- Next step → order antibody tests to confirm whether Graves’ disease is present (TRAb and TPO or TSI)
- If thyroid has a single palpable mass/nodule → order thyroid ultrasound → Refer to endocrinologist for management
Imaging:
- Thyroid ultrasound, 24-hr radioactive iodine uptake (RAIU) shows diffuse uptake (goiter)
- If solitary toxic nodule, shows warm or “hot” nodule or “cold” nodule
- Absolute contraindications for this test: Pregnancy and Breastfeeding
Primary Hyperthyroidism
5. Treatment (Meds + Adjunctive)
Medications:
- Methimazole (Tapazole) → shrinks thyroid gland/↓ hormone production
- Propylthiouracil (PTU) → shrinks thyroid gland/↓ hormone production; PTU is preferred treatment for mod-severe hyperthyroidism (can cause liver failure)
Side effects:
- Skin rash
- granulocytopenia/aplastic anemia
- thrombocytopenia (check CBC w/ platelets)
- hepatic necrosis (monitor CBC, LFTs)
Pregnancy → For hyperthyroidism, PTU is preferred treatment if needed. For high-risk pregnancy → Refer to obstetrician
Adjunctive Treatment: Given to alleviate symptoms of hyperstimulation (e.g., anxiety, tachycardia, palpitations)
- Beta-blockers are effective (e.g., propranolol, metoprolol, atenolol)
Radioactive Iodine: Permanent destruction of thyroid gland resulting in hypothyroidism for life (needs thyroid supplementation for life)
- CONTRAINDICATION: Pregnancy or lactation
- Alternative/natural medication (controversial): Armour thyroid is produced from desiccated (dried) pig thyroid glands (contains both T3 and T4)
** Some practitioner chooses to prescribe this - Drug-induced thyroid disease: Lithium, amiodarone, high dose of iodine, interferon alfa, dopamine. → Monitor TSH
** ALL hyperthyroid patients should be referred to an endocrinologist ASAP!
Primary Hyperthyroidism
6. Complications
- Thyroid Storm (thyrotoxicosis) → During thyroid storm, an individual’s heart rate, BP, and body temp can soar to dangerously high levels
- Acute worsening of symptoms d/t stress or infection
- Look for ↓ LOC, fever, abdominal pain
- Life-threatening! → Immediate hospitalization!
** People w/ subclinical and overt hyperthyroidism are at ↑ risk of bone (osteopenia/osteoporosis) and cardiac (afib) complications
** If new onset of Afib, check TSH; Keep TSH between 1.0-4.0 mU/L as goal for thyroid hormone supplementation
Thyroid Gland Tests
- Thyroid gland ultrasound: Used to detect goiter (generalized enlargement of gland), multinodular goiter, single nodule, and solid versus cystic masses
- Fine-needle biopsy: Diagnostic test for thyroid cancer
- Thyroid Scan (24-hr thyroid scan w/ RAIU): shows metabolic activity of thyroid gland
- Cold spot: Not metabolically active (more worrisome; r/o thyroid cancer); fine-needle aspiration biopsy
- Hot spot: Metabolically active nodule with homogenous uptake; usually benign; helpful in diagnosing recurrent disease
Laboratory Findings of Thyroid Disease
TSH
- Normal range: 0.5 - 5.0 mU/L (third-generation test)
- TSH is used for both screening and monitoring response to treatment
- Recheck TSH Q6-8 weeks
- Dose of levothyroxine (Synthroid) is based on the TSH level
- Goal is TSH <5.0 mU/L
- When TSH is stable, recheck Q6-12 months
Primary Hypothyroidism
1. Definition/Etiology
2. Clinical Presentation
3. Labs
4. Treatment
- high TSh w/ low free T4 levels (do not confuse w/ total T4)
- Diagnosis is based on the lab findings
Common causes:
- Hashimoto’s thyroiditis (most common cause)
- postpartum thyroiditis
- thyroid ablation w/ radioactive iodine
- middle-aged-to-older woman, overweight c/o:
- fatigue
- weight gain
- cold intolerance
- constipation
- menstrual abnormalities
- may have alopecia on outer 1/3 of both eyebrows
- serum cholesterol ↑
- may have hx of another autoimmune disorder (e.g., RA, PA)
- Alopecia of outer 1/3 eyebrow and myxedema os symptoms of hypothyroidism
- middle-aged-to-older woman, overweight c/o:
- TSH (TSH >5.0 mU/L) → if ↑, order TSH w/ free T4N (free thyroxine)
- If TSH ↑ and serum-free T4 is ↓ = hypothyroidism
- Next step: order TPOs to confirm Hashimoto’s thyroiditis
- If TPOs ↑ = confirms Hashimoto’s thyroiditis (GOLD STANDARD for diagnosing Hashimoto’s)
- TSH (TSH >5.0 mU/L) → if ↑, order TSH w/ free T4N (free thyroxine)
- Starting dose of levothyroxine (Synthroid) ranges from 25-50 mcg/day
- Start w/ lowest dose for older adults/pt with hx of heart disease (watch for angina, acute MI, atrial fibrillation)
** Advise pt to crush Synthroid tablets w/ teeth before swallowing w/ water for better absorption; these tablets are synthetic T4 (levothyroxine)
- Starting dose of levothyroxine (Synthroid) ranges from 25-50 mcg/day
- ↑ Synthroid dose every few weeks until TSH is normalized (TSH <5.0 mU/L)
- Recheck TSH Q6-8 weeks until TSH normal. When under control, check TSH Q12 months - If TSH is 0.05 - 5.0 mU/L → WNL, pt is at right dose of Synthroid
- Do not check earlier than 6 weeks
- Advise pt to report if palpitations, nervousness, or tremors → means that Synthroid dose is too high (↓ dose until symptoms are gone and TSH is normal)
** Chronic amenorrhea and hypermetabolism → osteoporosis. Supplement w/ calcium and w/ Vit D 1,000 mg; engage in weight-bearing exercises
Hashimoto’s Thyroiditis
A chronic autoimmune disorder of the thyroid gland
- generally no pain w/ this thyroid swelling
- body produces destructive antibodies (TPOs) against they thyroid gland that gradually destroys them
- almost all pt (90%) w/ Hashimoto’s → elevated TPOs
- most develops goiter
- more common in women, 8:1
Subclinical Hypothyroidism (Nonpregnant Adults)
If TSH is >5.0 mU/L (elevated), but serum T4 is WNL → subclinical hypothyroidism (asymptomatic to mild symptoms of hypothyroidism).
Decision to tx with Synthroid should be individualized. Some choose not to treat but recheck same labs again in 6-12 months
** Many pts with subclinical hypothyroidism will eventually develop overt hypothyroidism
Myxedema
Severe hypothyroidism (myxedema); rare
- ENDOCRINE EMERGENCY!
- Presents with neuro symptoms:
- slow thinking
- poor short-term memory
- depression (or dementia)
- hypotension
- hypothermia
Lab results in Thyroid Disease:
- TSH, Free T4, and T3 in the following:
1. Hypothyroidism
2. Subclinical hypothyroidism
3. Hyperthyroidism
4. Subclinical hyperthyroidism
- TSH > 5.0 mU/L; Free T4 ↓; T3 ↓
- TSH > 5.0 mU/L; Free T4 normal, T3 normal
- TSH < 5.0 mU/L; Free T4 ↑; T3 ↑
- TSH < 5.0 mU/L; Free T4 normal; T3 normal
Diabetes Mellitus (DM)
1. Definition
2. Examples of microvascular damage
3. Examples of macrovascular damage
4. Target organs
- Chronic metabolic disorder affect body’s metabolism of carbohydrates and fat → microvascular and macrovascular damage, neuropathy, and immune system effects
- Retinopathy, nephropathy, and neuropathy
- Atherosclerosis, heart disease (CAD), MI
- Eyes, kidneys, heart/vascular system, peripheral nerves, esp in feet
** DM is most common reason for chronic renal failure requiring dialysis and LE amputation in US
DM Type 1: Definition
Massive destruction of B-cells in the islets of Langerhans → abrupt cessation of insulin production
If uncorrected, body fat will be used for fuel → Ketones, the metabolic product of fat breakdown, build up in the body until → diabetic ketonic acidosis (ketoacidosis) and coma
Most pts are juveniles, occasionally in adults (maturity onset diabetes of the young [MODY]_
- CDC reports 5-10% of US cases
DM Type 2: Definition
Progressive ↓ secretion of insulin (with peripheral insulin resistance) → chronic state of hyperglycemia and hyperinsulinemia
- Strong genetic component
- 90-95% of US cases
- Obesity epidemic ↑ rates in younger pts
** Morbidly obese pt, bariatic surgery can result in remission of DM2
Risk Factors for DM2
* Screen these patients
- Overweight or obese (BMI ≥25)
- abdominal obesity; sedentary lifestyle
- Metabolic syndrome
- Hispanic, African American, Asian, Pacific Islander, or American Indian ancestry or positive family hx
- Hx of gestational diabetes or infant weight >9 lb at birth
- Impaired fasting blood sugar/glucose (IFG) or impaired glucose intolerance (IGT) is considered at higher risk for DM2 (prediabetes)
Metabolic Syndrome: Criteria
Other names: Insulin-resistance syndrome and Syndrome X
- Affected people have ↑ risk of DM2 and cardiovascular disease
- Presence of any 3 of the following 4 traits:
- Obesity, abdominal obesity - Waist size:
- Male >40 inches (102 cm)
- Females >35 inches (88 cm)
- Hypertension: BP >130/85 mm Hg
- Dyslipidemia: Triglycerides > 150 mg/dL; high-density lipoprotein (HDL) <40 in males or <50 in females
- Hyperglycemia: Fasting plasma glucose (FPG): >100 mg/dL or DM2
Increased Risk of DM (Prediabetes)
- Glycosylated hemoglobin (A1C) b/w 5.7-6.4%
OR - Fasting glucose of 100-125 mg/dL (impaired FPG)
OR - Two-hour oral glucose tolerance test (OGTT; 75 mg load) of 140-199 mg/dL
Diagnostic Criteria for DM
- A1C ≥ 6.5%
- A1C is average blood glucose level in previous 3 months (12 weks)
OR - FPG ≥ 126 mg/dL (fasting is no caloric intake for at least 8 hours)
- Symptoms of hyperglycemia (polyuria, polydipsia, polyphagia) + random blood glucose ≥ 200 mg/dL
OR - Two-hour plasma glucose ≥ 200 mg/dL during an OGTT with a 75g glucose load
Diabetes Mellitus
5. Labs/Diagnostics
6. PCP Evaluations
- Newly diagnosed diabetes: Check A1C Q3months until BG controlled or when changing therapy, then check twice a year (Q6months)
- Lipid profile at least once a year w/ 9-12 hour fasting
- Random or “on-spot” urine for microalbuminuria at least once a year
– Urine albumin-to-creatinine ratio between than microalbumin test (spot urine sample) for evaluating microalbumin (the earliest sign of diabetic renal disease)
– If positive → order 24-hour urine for protein and creatinine
- ACEi, ARBs, or ARNI w/ tighter control of BG/A1C ↓ progression and ↓ mortality from kidney disease
- Check electrolytes (K, Mg, Na) LFT, and TSH
- Newly diagnosed diabetes: Check A1C Q3months until BG controlled or when changing therapy, then check twice a year (Q6months)
- Every visit: Check BP, feet, weight & BMI, BG
- Check feet:
– Vibration sense (128-Hz tuning fork): place on body prominence of the big toe (metatarsophalangeal [MTP] joint); if unable to sense vibration or asymmetry, pt has peripheral neuropathy
– Lighter & deep touch; numbness: place at right angle on plantar surface, push into skin until it buckles slightly (monofilament tool)
– Check pedal pulses, ankle reflexes, and skin for acanthosis nigricans, insulin injection or insertion sites, llipodystrophy
- Every visit: Check BP, feet, weight & BMI, BG
Recommendations (Labs) for Nonpregnant Adult Diabetics
1. Blood pressure
2. LDL cholesterol
3. A1C
4. Preprandial capillary plasma glucose (fasting)
5. Peak postprandial capillary plasma glucose (2 hours after meal)
- <140/80 mmHg
- <100 mg/dL
- <7% (exceptions exist)
- 70-130 mg/dL
- <180 mg/dL
Diabetes Mellitus
Preventive Care Recommendations
- The CDC recommends adults >50 years to be given Shingrix in 2 doses; 2-6 mons apart
- Influenza immunization every year
- Pneumococcal polysaccharide vaccine: if vaccinated before 65 years, give one-time revaccination in 5 years; if age 65, give one dose of vaccine only
- Aspirin 81mg if high risk for MI, stroke (if <30 years, not recommended)
- Ophthalmologist: yearly dilated eye exam needed. If DM2, eye exam at diagnosis; if DM1, first eye exam needed 5 years after diagnosis
** Diabetics are at ↑ risk for cataracts and glaucoma - Podiatrist: Refer to once or tice a year, esp w/ older diabetics
- BP goal: 130/80
- Dental/tooth care: Important (poor oral health associated w/ heart disease)
Diabetes Mellitus
Dietary and Nutrition REcommendations (or Macronutrients)
- Alcohol: Advise females not to exceed one drink/day and males 2 drinks/day
- Monitor carb intake (i.e., carb counting)
- Saturated fat (animal fats, beef fate) intake should be <7% of total calories
- ↓ intake of transfat (will ↓ LDL and ↑ HDL), such as most friend foods and “junk” foods
- Refer pt to dietitian at least once or more often if problems w/ diet
- Routine vitamin supplementation of antioxidants is not yet advised
Hypoglycemia
- Levels & clinical presentation
- Treatment
High risk
- Level 1 hypoglycemia (glucose alert): FBS ≤ 70 mg/dL
- Level 2 hypoglycemia: Blood glucose ≤ 54 mg/dL
Look for:
- Sweaty palms
- tiredness
- dizziness
- rapid pulse
- strange behavior
- confusion
- weakness
If pt on beta-blockers, the hypoglycemic response can be blunted or blocked
Treatment Plan
- Glucose (15 g) is preferred treatment for conscious pt; other options are 4 oz of orange juice, regular soft drunk, hard candy.
- Think of the “15-15 Rule:” 15g of carb to ↑ blood sugar; recheck in 15 minutes. When blood glucose is normal → eat a meal or snack afterward (complex carbs, protein)
- Glucagon: Prescribe for pt at significant risk for severe hypoglycemia. Severe hypoglycemia is defined as BG <54 mg/dL
Diabetes Mellitus: Illness and Surgery
- Do not stop taking antidiabetic med; keep taking insulin or oral meds as scheduled unless FBG is ↓ than norm
- requires frequent self-monitoring of BG
- Eat small amounts of food Q3-4 hrs to keep FBG as normal as possible
- Contact health provider if: dehydrated, vomiting, or diarrhea for several house; BG is >300; changes in LOC feel sleepier than norm/cannot think clearly; urine with 1+ or higher ketones)
Diabetes Mellitus: Exercise
- ↑ glucose utilization by muscles. Pt may need to reduce usual dose of med (or eat snacks before activity and afterward to compensate)
- If pt does not compensate (↓ dose of insulin, ↑ caloric intake, snacking before and after), there is an ↑ risk of hypoglycemia within a few hours
- Ex: If pt exercises in afternoon, high risk of hypoglycemia at night/bedtime if they do not compensate by eating snacks, eating more food at dinner, or lowering insulin dose
Diabetes Mellitus: Snacks for Exercise
- Eat simple cabs (candy, juices) before or during exercise
- Eat complex carbs (granola bars) after exercise (avoids postexercise hypoglycemia)
DM: Dawn Phenomenon
Normal physiologic event; a hormonal surge in all people causing an elevation in FBG occurs daily, early in the morning between 4-8am
Without normal insulin response, diabetics experience rising FBG levels (healthy people can produce insulin to combat this phenomenon)
Somogyi Effect (Rebound Hyperglycemia)
+ Diagnosis and treatment
Severe nocturnal hypoglycemia stimulates counterregulatory hormones (glucagon) to be released from the liver. The high levels of glucagon in systemic circulation → high FBG at 7am. Condition is d/t overtreatment w/ evening and/or bedtime insulin (dose is too hight)
- More common in people with DM1
Diagnosis: Check blood glucose very early in the AM (3am) for 1-2 weeks
Treatment: Eat a snack before bedtime or eliminate dinnertime intermediate-acting insulin (NPH) dose or ↓ the bedtime dose for both NPH and regular insulin
Diabetic Retinopathy
Definition
When to screen for DM1 and DM2?
- Neovascularization (new growth of fragile arterioles in retina), microaneurysms (dot and blot hemorrhages d/t neovascularization), cotton-wool spots or soft exudates (nerve fiber layer infarcts), and hard exudates
- cotton-wool sports (soft exudates), neovascularization, microaneurysms w/ dot, and blot hemorrhages
**HTN retinopathy are silver wire/copper wire arterioles, arteriovenous nicking
DM1: Screen after age 10 years
DM2: Refer to ophthalmology after diagnosis; then eye exam needed Q6-12 months
Diabetic Foot Care
Definition & Cares
Pt w/ peripheral neuropathy should avoid excessive running or walking to minimize the risk of foot injury
- DM2: Refer to podiatrist at least once a year
- Wear shoes that fit properly; NEVER go barefoot
- Check feet daily esp soles of feet (use mirror)
- Trim nails squarely (not rounded to prevent ingrown toenails)
- Report redness, skin breakdown, or trauma to healthcare provider immediately (main cause of LE amputations in US)
Charcot’s Foot and Ankle (Neuropathic Arthropathy)
Deformity of the foot that is caused by joint and bone dislocation and fractures d/t neuropahty and loos of sensation to foot and ankle. May affect only one foot or both feet
- If severe, foot deformity includes collapse of midfoot arch (rocker-bottom foot)
Diabetic Medications: Biguanides
First-line (DM2): Metformin (Glucophage)
- ↓ gluconeogenesis and ↓ peripheral insulin resistance. Very rarely may cause hypoglycemia. Prescribe in addition to diet and exercise (lifestyle)
- Preferred for obese pts; reported that metformin is neutral for weight change and has a potential for a modest weight loss; Metformin may cause GI SE, such as diarrhea and nausea
- For ↓ vit B12 levels (7%), consider vitamin supplementation
Contraindications:
- Do not use if renal disease, hepatic disease acidosis, alcoholics, hypoxia
- Labs: Monitor renal function (serum creatinine, GFR, UA, and LFTs)
- ↑ risk for lactic acidosis (pH <7.25): occurs during hypoxia, hypoperfusion, renal insufficiency
- IV contrast dye testing: Hold metformin on day of procedure and 48 hr after. Check baseline creatinine and recheck after procedure. If serum creatinine remains elevated after procedure, do NOT restart metformin. Serum creatinine must be normalized before drug can be resumed
Diabetic Medications: Sulfonylureas
- Stimulate beta cells of the pancreas to secrete more insulin
First-generation: Administer chlorpropamide (Daibinese) daily or BID; long half-life (12 hours); not commonly used because of high risk of severe hypoglycemia
Second-generation: Administer…
- glipizide (Glucotrol, Glucotrol XL) max dose of 40 mg/day
- glyburide (DiaBeta) max dose of 20 mg/day
- glimepiride (Amaryl) max dose 8 mg/day
Adverse Effects
- FDA has special warning on ↑ risk of cardiovascular mortality, based on studies of an older sulfonylurea (tolbutamine)
- Hypoglycemia (diaphoresis, pallor, sweating, tremor); ↑ risk of photosensitivity (use sunscreen)
- Blood dyscrasias (monitor CBC)
- Avoid if impaired hepatic or renal function (monitor LFTs, creatinine, UA)
- Causes weight gain (monitor weight & BMI)
Diabetic Medications: Thiazolidinediones
- Pioglitazone (Actos): enhances insulin sensitivity in muscle tissue (↓ peripheral tissue resistance) and ↓ hepatic glucagon production (gluconeogenesis); take daily w/ meal at breakfast
** Actors can cause water retention, which can precipitate CHF; contraindicated if hx of HR or NYHA class III/IV (mod-severe HF) - Can be combined w/ metformin, sulfonylureas, glucagonlike peptide 1 (GLP-1), sodium-glucose co-transporter-2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, insulins
Contraindications:
- FDA BBW: DO NOT use w/ New York Heart Association (NYHA) class III and class IV heart disease, symptomatic heart failure (congestive heart failure [CHF])
- causes water retention and edema (aggravates or will precipitate CHF)
- Avoid if bladder CA or hx of bladder CA (UA, urine cytology), active liver disease, DM1, pregnancy
- Causes weight gain (monitor weight and BMI)
Labs: monitor LFTs
Diabetic Medications: Bile-Acid Sequestrants
- Cholestyramine (Questran), colesevelam (Welchol), colestipol (Colestid)
- ↓ hepatic glucose production and may ↓ intestinal absorption of glucose
- Take w/ meals; ↓ LDL
SE:
- GI related (nausea, bloating, constipation, ↑ triglycerides)
- SE common reason for noncompliance; start pt on low dose and titrate up slowly
- Kidney and liver effects (check serum creatinine, GFR, LFTs)
Diabetic Medications: Meglitinide (Glinides)
- Repaglinide (Prandin), nateglinide (Starlix)
- Stimulates pancreatic secretion of insulin
- indicated for DM2 w/ postprandial hyperglycemia
- Weight neutral; may cause hypoglycemia
- Rapid-acting w/ very short half-life (<1 hr)
- Take before meals or up to 30 min after meal
- hold dose if skipping a meal
- SE: bloating, abdominal cramps, diarrhea, flatulence
Diabetic Medications: Insulin
Rapid-acting analogs
1. Onset
2. Peak
3. Duration (Mean)
Inuslin lispro/aspart/glulisine
Rapid-acting insulin: Humalog (insulin lispro)
- Used mostly by DM1 before each meal
- 15 min
- 30 min to 2.5 hrs
- ~4.5 hrs
** All insulins cause hypoglycemia and weight gain
Diabetic Medications: Insulin
Short-acting
1. Onset
2. Peak
3. Duration (Mean)
Regular human insulin; Humulin R (Regular)
- 30 min
- 1-5 hrs
3 6-8 hrs
** All insulins cause hypoglycemia and weight gain
Diabetic Medications: Insulin
Intermediate
1. Onset
2. Peak
3. Duration (Mean)
Intermediate NPH; Human NPH
- can be used once or twice a day
- 1 hr
- 6-14 hrs
- 18-24 hrs
** All insulins cause hypoglycemia and weight gain
Diabetic Medications: Insulin
Basal insulin
1. Onset
2. Peak
3. Duration (Mean)
Basal insulin analogs:
- Insulin glargine (Lantus)
- Insulin detemir (Levemir)
- 1 hr
- None
- 24 hr; insulin detemir usually BID
- Peaks in 1 hour and thens teady level for most of the day
- Humulin N
- Lantus (insulin glargine) Levemir (insulin determir)
- Give once a day at the same time
** All insulins cause hypoglycemia and weight gain
Diabetic Medications: Insulin
Premixed
1. Onset
2. Peak
3. Duration (Mean)
Humulin 70/30 (70% NPH/30% regular)
Humulin 50/50
Other types available
* If mixing NPH and regular insulin, use the mixture immediately
- Rapid-acting insulin can be mixed with NPH, but it should be used 15 min before a meal
- 30 min
- 4.4 hrs
- 24 hrs
** All insulins cause hypoglycemia and weight gain
Diabetic Medications: Insulin Pumps
Requires intensive training; they are expensive
- Can be used for both type 1 & 2
- Pt should remove pump when swimming or showering or during certain sports (e.g., wrestling) requiring insulin pump to be disconnected during activity
** All insulins cause hypoglycemia and weight gain
Diabetic Medications: Alpha-Glucosidase Inhibitor
- Slows intestinal carb digestion and absorption; a nonsystemic oral drug
- Doe snot cause hypoglycemia; modest effect on A1C level
- GI side effects are flatulence, diarrhea
Diabetic Medications: Glucagon-Like Peptide-1 REceptor Agonists (GLP-1 RAs)
- Exenatide (Byetta) BIS or liraglutide (Victoza) once/daily injections
- Stimulate GLP-1, causing ↑ insulin production and inhibiting postprandial glucagon release (will ↓ postprandial hyperglycemia: ↑ satiety
- ↓ cardiovascular ds events/deaths; slow progression and death from kidney disease
- cause weight loss, suppress appetite, does not cause hypoglycemia
- may cause pancreatitis (monitor amylase, lipase), medullary thyroid tumors in animals and C-cell hyperplasia
- WARNING: Contraindicated if personal or fam hx of medullary thyroid carcinoma, multiple endocrine neoplasia syndrome type 2 (MEN-2)
Diabetic Medications: Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2 inhibitors)
- Canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance)
- Block glucose reabsorption by kidney (proximal nephron) and ↑ glucosuria
- Effective in all stages of DM2; no hypoglycemia
- ↓ CVD events/death; help to slow progression of CKD disease
- cause weight loss, hypotension (volume depletion)
FDA warning: May lead to DKA; symptoms including difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness - Renal s/s: Polyuria, ↑ creatinine; ↑ UTIs and pyelonephritis (urosepsis)
- Warning: ↑ risk of leg and foot amputations
Diabetic Medications: Dipeptidyl Peptidase-4 Inhibitors (DPP-4 Inhibitors)
- Sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin )(Tradjenta), others
- Inhibit dipeptidyl peptidase-4 (DPP-4) activity; ↑ active incretin concentrations
- ↑ insulin secretions and ↓ glucagon; no hypoglycemia
- FDA warning: may cause joint pain, can be severe and disabling (may occur on day 1 or years later; may cause angioedema/urticaria, acute pancreatitis
- Have renoprotective effect by delaying kidney disease progression and ↓ albuminuria
** Do not combine incretin mimetics (Byetta, Victoza) with any incretin enhancers (Januvia, Onglyza); both act on incretin
Diabetic Medications: Dipeptidyl Peptidase-4 Inhibitors (DPP-4 Inhibitors)
- Sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin )(Tradjenta), others
- Inhibit dipeptidyl peptidase-4 (DPP-4) activity; ↑ active incretin concentrations
- ↑ insulin secretions and ↓ glucagon; no hypoglycemia
- FDA warning: may cause joint pain, can be severe and disabling (may occur on day 1 or years later; may cause angioedema/urticaria, acute pancreatitis
- Have renoprotective effect by delaying kidney disease progression and ↓ albuminuria
** Do not combine incretin mimetics (Byetta, Victoza) with any incretin enhancers (Januvia, Onglyza); both act on incretin** All insulins cause hypoglycemia and weight gain
Diabetic Medications: Amylin Mimetic/Analog (Symlin)
- ↓ glucagon secretion; slows gastric emptying; leads to feeling satiety early; causes weight loss
- Route: Injectable, frequent dosing, requires pt training
- Causes hypoglycemia if used w/ insulin (↓ insulin dose)
Summary of Prescribing Medications for DM2
- Try lifestyle changes (weight loss) for 3-6 months if mild A1C elevation
- In addition to lifestyle, metformin is first-line treatment for most DM2. Start on metformin 500 mg daily (max dose 2,000 mg/dL or 2g)
– If metformin is at max and BG or A1C is still high → add sulfonylurea (e.g., Glucotrol XL 20 mg/day)
OR - if pt is on a sulfonylurea at max dose (ex: Glucotrol XL 40 mg/day) and BG/A1C is still elevated → add metformin
- Choice of 2nd or 3rd agent is any other drug class to treat DM2
- If max metformin dose (2g), other choices to add are DPP-4 inhibitors (Januvia, Onglyza), incretin mimetic (Byetta), and/or thiazolidinediones (TZDs; Actos), etc
- Do NOT combine insulins w/ meglitinides (severe hypoglycemia)
- Presence of CVD and/or chronic kidney disease, or HFrEF, started on SGLT-2 inhibitor and/or GLP-1 RA
- If BG/AC is still elevated and pt is on both metformin and sulfonylurea, consider starting pt on basal insulin (Lantus SC once a day)
- If pt refuses insulin, other options are tioglitazones (Actos), Byetta, others
** Keep in mind contraindications for each drug class!
Meds: Effect on Weight
Causes weight loss: Metformin, incretin mimetic, GLT-2 inhibitors
Causes weight gain: Insulins, sulfonylureas, TZDs (Actos)
Weight neutral: Meglitinides (Starlix, Prandin), bile-acid sequestrants (Welchol), alpha-glucosidase inhibitors
Diabetes Mellitus: Management
- Refer to dietician to learn about carb counting; ADA recommends fat and protein counting as well. lifestyle changes are first-line treatment!
- SGLT-2 inhibitors and GLP-1 RAs protect the heart and kidneys and promotes weight loss
- Eating more fiber and whole grains (brown rice, whole wheat) may help
- Exercise ↑ cellular glucose uptake in the body
- DM2 not well controlled on multiple oral agents and diet and lifestyle changes are good candidates for basal insulin therapy
- If A1C is ≥9, start on basal insulin; or if on 2 oral drugs and A1C is ≥9, start on basal insulin
Diabetic Medications: Possible Complications
- Eyes: Cataract,s diabetic retinopathy, blindness
- Cardiovascular: hyperlipidemia, coronary artery disease, MI, hypertension
- Kidneys: Renal disease, renal failure
- Feet: Foot ulcers, skin infections, peripheral neuropathy, amputation
- Gynecologic/genitourinary: Balanitis (candidal infection of the glans penis), candidal vaginitis
Diabetic Medications: Primary Prevention
For individuals at high risk for DM2:
- encourage weight loss (7% of body weight) and regular physical activity (150 min/week)
- ↑ dietary fiber and foods w/ whole grains
Solving Insulin-related Questions
- Just remember these for peak and duration of each type of insulin:
- Rapid-acting insulin covers “one meal at a time”
- Regular insulin lasts “from meal to meal”
- NPH insulin lasts “from breakfast to dinner”
- Lantus is “once a day”
Solving Insulin-related Questions
- Just remember these for peak and duration of each type of insulin:
- Rapid-acting insulin covers “one meal at a time”
- Regular insulin lasts “from meal to meal”
- NPH insulin lasts “from breakfast to dinner”
- Lantus is “once a day”
