Lecture 16 (Endocrine)- Exam 6 Flashcards
1
Q
Anatomy for endocrine system
What are the main endocrine glands?(6)
A
The main endocrine glands are the pituitary, thyroid, parathyroids, pancreas, adrenals and gonads: testes and ovaries
2
Q
Anatomy for endocrine system
- What do the endocrine glands do?
- Although some endocrine glands, e.g. parathyroid glands and pancreas, respond directly to what?
A
- These glands synthesize hormones which are released into the circulation and act at distant sites.
- Although some endocrine glands, e.g. parathyroid glands and pancreas, respond directly to metabolic signals, most are controlled by hormones released from the pituitary gland
3
Q
* Anatomy for endocrine system
What is a wide variety of molecules act as hormones?(7)
A
- peptides, e.g. insulin
- glycoproteins, e.g. thyroid-stimulating hormone (TSH)
- amines, e.g. noradrenaline (norepinephrine)
- steroid hormones, e.g. cortisol
- estrogen
- triiodothyronine
- vitamin D
4
Q
Common Clinical Symptom/Sign with DDx in endocrine disease
* Weight Gain:
* Weight Loss:
* Short stature:
* Delaneyed puberty:
A
- Weight gain: Hypothyroidism, polycystic ovary syndrome (PCOS), Cushing’s syndrome
- Weight loss: Hyperthyroidism, diabetes mellitus, adrenal insufficiency (Addison’s disease)
- Short stature: Constitutional, non-endocrine systemic disease, e.g. celiac disease, growth hormone deficiency
- Delayed puberty: Constitutional, non-endocrine systemic disease, hypothyroidism, hypopituitarism, primary gonadal failure
5
Q
Common Clinical Symptom/Sign with DDx in endocrine disease
* Menstrual disturbance:
* Diffuse neck swelling:
* Excessive thirst:
* Hirsutism:
A
- Menstrual disturbance: PCOS, hyperprolactinemia, thyroid dysfunction
- Diffuse neck swelling: Simple goiter, Graves’ disease, Hashimoto’s thyroiditis
- Excessive thirst: Diabetes mellitus or insipidus, hyperparathyroidism, Conn’s syndrome
- Hirsutism: Idiopathic, PCOS, Cushing’s syndrome, congenital adrenal hyperplasia
6
Q
Common Clinical Symptom/Sign with DDx in endocrine disease
* Sweating:
* Flushing:
* Resistant hypertension:
* Erectile dysfunction:
A
- Sweating: Hyperthyroidism, hypogonadism, acromegaly, pheochromocytoma
- Flushing: Hypogonadism (especially menopause), carcinoid syndrome
- Resistant hypertension: Conn’s syndrome, Cushing’s syndrome, pheochromocytoma, acromegaly, renal artery stenosis
- Erectile dysfunction: Primary or secondary hypogonadism, diabetes mellitus, non-endocrine systemic disease
7
Q
Common Clinical Symptom/Sign with DDx in endocrine disease
* Muscle weakness:
* Bone fragility and fractures:
* Altered facial appearance:
A
- Muscle weakness: Cushing’s syndrome, hyperthyroidism, hyperparathyroidism, osteomalacia
- Bone fragility and fractures: Cushing’s syndrome, hypogonadism, hyperthyroidism
- Altered facial appearance: Hypothyroidism, Cushing’s syndrome, acromegaly, PCOS
8
Q
Diabetes Mellitus
* The term diabetes mellitus describes what?
* It is associated with what?
A
- The term diabetes mellitus describes diseases of abnormal carbohydrate metabolism that are characterized by hyperglycemia.
- It is associated with a relative or absolute impairment in insulin secretion, along with varying degrees of peripheral resistance to the action of insulin.
9
Q
⭐️
- What is type one and two DM?
A
- Type 1- Early onset, autoimmune disease of the destruction of the pancreatic beta cells leading to absence of insulin, DKA may be initial presentation in 25% with new Dx, and association with HLA DR3-DQ2 and DR4 genes.
- Type 2-Most common (>90%), usually later onset, associated with obesity, + FH. Hyperglycemia usually due to progressive loss of insulin secretion from the beta cell superimposed on a background of insulin resistance, resulting in relative insulin deficiency.
10
Q
Pance Prep:
Type one DM:
* What is the cause?
* These patients require what?
* When is the onset?
* Not associated with what?
A
- Insulin deficiency due to pancreatic beta cell destruction
- These patients require exgenous insulin
- Onset usually under 30 yo (3/4 in childhood)
- Not associated with obesitiy
11
Q
Pance Prep
Type one DM:
* What are the clinical manifestations?
A
- Hyperglycemia without acidosis: most common inital presentation-polyuria, polydipsia, pilyphagia
- Weight loss. Lethargy
- Diabetic ketoacidosis second most common initial presentation (more common in type 1). HHS more in type 2
- Silent (asymptomatic incidental discovery)
12
Q
Pance prep
Type two diabetes:
* What is the cause?
* Likely due to what?
* Common in what age?
* What are causes of insulin resistance?
A
- Combo of insulin insensitiy (resistance) and relative impariment of insultin secretion (increased insulin levels early in the disease but may diminish with disease progression)
- genetic and enverimental factors especially, obestity being the greatest risk factor and decreased phyical activity
- Over 40 yo
- Insulin resistance: CHAOS-> Chronic HTN, Atherosclerosis, obestity (central), stroke
13
Q
Type 2 DM
* What are the clinical manifestations?
A
- Most are asymptomatic
- Classic symptoms: polyuria, polydipsia, polyphagia
- Poor wound healing, increased infections.
- HHS
14
Q
Diabetes Mellitus
* What are the classic symptoms? (5)
A
Classic symptoms of hyperglycemia include polyuria, polydipsia, nocturia, blurred vision, and weight loss.
15
Q
Epidemiology: DM
* How much of the US population?
* How many people?
* Type 1 most prevalent in who?
* Less common where?
A
- Nearly 10% of the US population
- > 30 million people, 1.5 mil with type 1
- Type 1 most prevalent in Scandinavia – incidence rates higher in US among populations of Scandinavian descent
- Genetic component to type 1
- Less common nearer the equator
16
Q
Epidemiology: DM
* Type 2- genetic and environmental factors cause what?
* What is the most important environmental factor (primary factor for insulin resistance)? ⭐️
A
- Type 2- genetic and environmental factors cause insulin resistance and beta cell loss
- Obesity is the most important environmental factor (primary factor for insulin resistance)
17
Q
Actions of Insulin
* What stimulates insulin release?
* Transports what? where?
* Promotes what? (3)
* Lowers what?
* Stimultates what?
A
- Glucose and amino acids stimulate Insulin release
- Transports glucose into muscle and fat cells
- Promotes lipogenesis and storage of fat in fat cells
- Promotes protein synthesis
- Lowers hepatic output of glucose
- Stimulates glycogen synthesis
18
Q
Hormonal Regulation of Blood Glucose: Glucagon
* Levels increase by two-or threefold in response to what?
* What stimulates glucagon release?
* Enhances release of what?
A
- Levels increase by two-or threefold in response to hypoglycemia & decrease in presence of hyperglycemia
- Protein stimulates glucagon release
- Enhances release of glucose from glycogen
19
Q
Hormonal Regulation of Blood Glucose: Glucagon
* Enhances synthesis of what?
* Effect is to raise what?
* Encourages what?
* Inhibits what?
A
- Enhances synthesis of glucose from amino acids
- Effect is to raise blood glucose
- Encourages ketone production from FFA(free fatty acids)
- Inhibits hepatic lipogenesis
20
Q
Hormonal Regulation of Blood Glucose: Epinephrine
* Released from what?
* Enhances release of what? (2)
* Effects what?
A
- Released from adrenal medulla
- Enhances release of glucose from glycogen
- Enhances release of fatty acids from adipose tissue
- Effect is to raise blood glucose
21
Q
Hormonal Regulation of Blood Glucose: Cortisol
* Released from what?
* Enhances what?
* Serves as what?
* What does it effect?
A
- Released from adrenal cortex
- Enhances synthesis of glucose from amino acids or fatty acids
- Serves as insulin antagonist
- Effect is to raise blood glucose
22
Q
Type 1 Diabetes
* What is it caused by?
* Insulin acts as what?
* Absolute deficiency of insulin =
A
- Due to destruction of pancreatic beta cells from autoantigens (type 1A) or idiopathic (rare and is type 1B)
- Insulin acts as a chemical messenger to cell to accept glucose into cell for metabolism, and is always required in the treatment
- Absolute deficiency of insulin = accumulation of circulating glucose and fatty acids
23
Q
Type 1 Diabetes
* Increased levels of what?
* What are common clinical features?
* What are less common sxs?
A
- Increased osmolality & Increased ketones
- Common clinical features – increased urination, thirst, blurry vision
- Less common – weight loss, reduced muscle mass, postural hypotension, hypokalemia, weakness, paresthesia, anorexia, nausea, vomiting
All dependent on severity of onset – acute vs. subacute
24
Q
Type 2 Diabetes
* What is it?
* Insidious onset hyperglycemia leading to what?
* What may be present?
* Many are what initally?
A
- Insulin resistance + impairment of insulin secretion
- Insidious onset hyperglycemia leading to uptake of glucose to liver, adipose tissue and skeletal muscle
- Thirst and increased urination may be present
- Many are asymptomatic initially
25
Type 2 Diabetes
* What is common?
* If remains occult for a long time, what can present? (women and men)
Skin infections common, delayed healing
If remains occult for a long time – CV or neuropathic complaints may be presenting feature
* In women: Chronic candida infections – vulva/vaginal, large birthweight babies, unexplained fetal loss
* In men: Inflammation of glans penis and foreskin
26
# ⭐️
Metabolic Syndrome
* What is it?
* What does it include? (think labs) (3)
* What is a risk factor for HTN?
* A syndrome of insulin resistance – can be as severe as people with type 2
* Includes dyslipidemia, hypertension, hyperinsulinemia
* Hyperglycemia is a risk factor for hypertension
27
# ⭐️
Metabolic Syndrome
* Results in increased what?
Results in increased morbidity and mortality from cerebrovascular and cardiac issues
28
# ⭐️
What is the Metabolic Syndrome Criteria?(5)
3 or more of the following:
* **Waist circumference >40 inches in men or >35 inches in women.**
* Triglycerides >150 or on medicine.
* HDL-cholesterol <40 mg/dl in men or <50 mg/dl in women or on medicine.
* BP >130/85 or on medicine.
* Fasting plasma glucose 100mg/dl or more.
29
Risk Factors for DM
* What are the risk factors?(7)
* Physical Inactivity and Obesity
* Family Hx (1st degree relative)
* Race: Blacks, Native Americans, Pacific Islanders, Asian Americans, Latinos
* Women who birthed a >9lbs newborn or those with gestational DM
* HTN, hyperlipidemia
* PCOS
* Genetic: Leprechaunism, Stiff Man Syndrome and many more genetic causes of beta cell function
30
# ⭐️
Diabetes Clinical Presentation
* What are the 3 P's?
* What are some other sxs?
* 3 P’s:Polyuria, Polydypsia, Polyphagia
* Fatigue, weakness
* Vision changes
* Paresthesia
* Dry skin and slow wound healing
* Weight loss, N/V
31
DM Diagnosis
* What are all the labs you need to order?
Labs with or without symptoms
* Urine glucose
* Urine and blood ketones
* Only acetoacetic acid is detected on UA
* Acetone or beta-hydroxybutyric acid in serum
* **Urine Microalbumin (Urine creatinine to albumin ratio)**
* Plasma or serum glucose
* Oral glucose tolerance test
* Hgb A1c
32
# ⭐️
## Footnote
Fasting glucose is gold standard
33
What are the microvascular and macrovascular complications of DM? (think of the picture given)
34
# ⭐️
Ocular Complications of DM
* What is present?
Diabetic retinopathy – intraretinal hemorrhages, microaneurysms, cotton wool spots, hard exudates
* #1 cause of blindness in US
35
Diabetic retinopathy
* What are two types?
* Nonproliferative (Background)
* Proliferative retinopathy
36
What is nonproliferative (background) and proliferative retinopathy?
Nonproliferative (Background) Retinopathy
* Initial Background/nonproliferative retinopathy does not cause vision impairment
Proliferative retinopathy – growth of new capillaries & fibrous tissue within the retina and into the vitreous chamber – caused by retinal hypoxia due to small vessel occlusion
* More Common in Type I
* Retinal detachment is common
* Occurs later, often within 5 years of death from vascular issues
37
When to Refer to Ophthalmologist
* When do you refer? (2)
* Statistically, any new diagnosis of DM =
* Severe nonproliferative retinopathy
* Macular edema in nonproliferative retinopathy (most common cause of visual impairment in Type 2 DM)
* ANY proliferative retinopathy
* Statistically, any new diagnosis of DM = patient is 5 years behind of f/u with eye specialist
38
39
Diabetic Nephropathy
* How many cases?
* How many of ESRD? What do they need?
* What is the percentage between type one and two?
* ~4000 cases of ESRD among DM patients per year
* 1/3 of ESRD patients and is most common cause of need for dialysis
* Type 1 – 30-40% chance of having nephropathy after 20 years
* Type 2 – 15-20%
40
# ⭐️
Diabetic Nephropathy
* What is the first sign? How do you test it?
* First sign – albuminuria, then increased BUN and creatinine
* Microalbumin is the earliest sign of diabetic complication requiring intensive management
41
Diabetic Nephropathy
* What can cause transient albuminuria?
* Eventual ESRD can be predicted based on what?
* Be aware – exercise, UTI, hyperglycemia, heart failure, acute febrile illness can all cause transient albuminuria
* Eventual ESRD can be predicted based on persistent urinary albumin exceeding 30 mcg/mg creatinine, azotemia or nephrosis
42
# ⭐️
Diabetic Nephropathy
* How much microalbuminuria and macroalbuminuria?
Microalbuminuria
* 30-300 mg microalbumin/24 hrs
Macroalbuminuria
* > 300 mg microalbumin/24 hrs
* Once macroalbuminemia begins (>300 mg/d), GFR declines about 1 ml/min per month
43
# ⭐️
Screening for microalbuminuria
44
What is the flow chat for testing of microalbuminuria?
45
Reducing risk of Nephropathy
* What are ways to reduce nephropathy risk?(3)
* Glycemic control
* Protein diet of ~0.8 g/kg/day
* **ACEI (even in normotensive patient)**
46
# ⭐️
Diabetic Neuropathy
* What is the most common form?
* Dulled what?
* Pain?
* Peripheral – most common form – sensory deficits typically occur first
* Glove and stocking syndrome
* Dulled perception of vibration, pain and temperature
* Pain can be mild to severe
47
# ⭐️
Diabetic Neuropathy
* What are clinical signs?
* What is a late sign?
* May also have what?
* Clinical signs include Pes Cavus, clawing of the toes, altered biomechanics of the foot resulting in increased risk of foot injury (Charcot’s foot)
* Glove & Stocking distribution of neuropathy (late)
* May also have an “isolated peripheral neuropathy” along distribution of one or several nerves
48
What is this?
49
What can significantly relieved the pain of diabetic neuropathy?
Vitamin D supplements significantly relieved the pain of diabetic neuropathy in patients whose vitamin D levels were low
50
Autonomic Neuropathy
* Typically occurs in who?
* BP?
* What is going on with GI? manged how?
* _ dysfunction
* Typically occurs mainly in patients with long-standing DM
* HTN
* GI – nausea, vomiting, reflux, dysphagia, constipation or diarrhea, fecal incontinence. **Gastroparesis** in Type 1
* Gastroparesis managed with reglan and erythromycin
* Erectile dysfunction
51
Cardiovascular Complications
* What type of cardiomyopathy do they have?
* What is more common?
* What do they have an increase risk of?
* Heart disease without coronary artery disease = congestive cardiomyopathies
* More common – heart disease due to coronary atherosclerosis
* Myocardial Infarction is 3 to 5 x more common in patients with diabetes
52
Cardiovascular Complications
* BP?
* markedly accelerated what?
* What happens to the feet?
* HTN
* Peripheral vascular disease (ischemic) – markedly accelerated atherosclerosis in the larger arteries.
* Gangrene of feet – 30 x risk with DM vs non-DM population
53
Skin and Mucous Membrane
* Chronic what?
* What is common?
* What can happen due to high triglyceride levels?
* Diabetic _
* Chronic skin infections
* Candidiasis infections common
* Eruptive xanthelasmas due to high triglyceride levels
* Diabetic Dermopathy
54
Bone and Joint Complications
* What happens to skin of joints?
* Shoulder?
* What type of syndrome?
* _ contracture
* What is common in T2D
* What happens with shoulders and hips?
* Stiffness and contracture of skin of joints
* Frozen shoulder (adhesive capsulitis)
* Carpal tunnel syndrome
* Dupuytren contracture
* Acute and tophaceous gout common in Type 2 diabetes
* Bursitis of shoulders and hips
55
Diabetes – Pharm & Non-Pharm Therapies
* Morbidity from diabetes involves both what?
* Interventions can limit what?
* Morbidity from diabetes involves both macrovascular (atherosclerosis) and microvascular (retinopathy, nephropathy, and neuropathy) disease.
* Interventions can limit end-organ damage, and therefore, patients with diabetes require initial and ongoing evaluation for diabetes-related complications.
56
Diabetes – Pharm & Non-Pharm Therapies
* Perform what two to four times a year? Why?
* Glycemic control can minimize risks for what?
* Perform a history and physical examination two to four times yearly to obtain information on nutrition, physical activity, reduction of cardiovascular risk factors, current management, and diabetes-related complications.
* Glycemic control can minimize risks for retinopathy, nephropathy, and neuropathy in both type 1 and type 2 diabetes and has been shown to decrease the risk for cardiovascular disease (CVD) for type 1 diabetes.
57
Management
* What do you need to control? How?
Many diabetics are hypertensive. Control of BP lowers the risk of vascular complications. Get BP down to 130/80.
* ACE-inhibitors or Angiotensin II Receptor blockers are usually choice agents. Can add thiazides or vasodilatory beta-blockers like carvedilol (Coreg CR).
58
BP in DM
* What has an inverse relationship to BP?
* What can it also help?
* An inverse relationship has been reported between UV light contact or plasma 1,25-OH-hydroxyvitamin D3 and blood pressure
* Using vitamin D and giving 1,25-OH-hydroxyvitamin D3 lowered the blood pressure of the patients with hypertension
* Vitamin D can also improve glycemic control
59
# ⭐️
Management
* Glycated hemoglobin (A1C) goals in patients with diabetes should be tailored to what?
* A reasonable goal of therapy might be an A1C value of what?
* Glycated hemoglobin (A1C) goals in patients with diabetes should be tailored to the individual, balancing the improvement in microvascular complications with the risk of hypoglycemia.
* A reasonable goal of therapy might be an A1C value of ≤7.0 percent for most patients (using an assay in which the upper limit of normal is 6.0-6.9 percent).
60
# ⭐️
Management
* Glycemic targets in older adults?
* Glycemic targets for pregnancy?
* Glycemic targets are generally set somewhat higher (eg, <8 percent) for older adult patients and those with comorbidities or a limited life expectancy and little likelihood of benefit from intensive therapy.
* More stringent control (A1C <6 percent) may be indicated for individual patients with type 1 diabetes and during pregnancy.
61
Management
* Prevention of cardiovascular morbidity is a major priority for patients with what?
* Cardiovascular morbidity can also be significantly reduced with aggressive management of what?
* Prevention of cardiovascular morbidity is a major priority for patients with diabetes, especially type 2. Smoking cessation is essential for patients who smoke.
* Cardiovascular morbidity can also be significantly reduced with aggressive management of hypertension, cholesterol, use of **aspirin** (81 to 162 mg/day), and use of certain glucose-lowering medications in patients with or at high risk for cardiovascular disease (CVD).
62
Management
* What may be important in delivering improved care?
Many patients with diabetes are not receiving recommended levels of health care, and development of systems of care involving disease management principles may be important in delivering improved care
63
Caring for the hospitalized patient with DM
* What will be adjusted?
* What typically results in hyperglycemia?
* Always check what?
* Avoid what?
* Outpatient regimens will have to be adjusted
* Surgery typically results in hyperglycemia
* Always check renal function prior to restarting outpatient Metformin
* Avoid NSAIDs (other than ASA) in diabetics
64
Caring for the Pregnant Diabetic Patient
* Tight control?
* Poor control in early pregnancy=
* Poor control in late pregnancy =
* Tight glycemic control to normal HbA1c
* Poor control in early pregnancy = increased risk of spontaneous abortion and congenital malformations
* Poor control in late pregnancy= increased risk of pre-term labor, preeclampsia, stillbirth
65
# ⭐️
Caring for the Pregnant Diabetic Patient
* Typically controlled with what?
* What do some studies say?
* Typically controlled with regular insulin
* Some studies are discussing metformin and glyburide, although ADA shows minimal teratogenicity potential
66
Prognosis of DM
* What is key?
* What contributes to outcomes?
* Obese patients typically develop what?
* Glycemic control is key
* Patient IQ, motivation and understanding of potential complications contribute to outcomes
* Obese patients typically develop complications regardless of glycemic control
67
Pharm Therapy
* What is recommended for the majority of patients with type 1 diabetes?
* For most patients with type 2 diabetes, care can be delivered by who?
* Patients in need of what?
* Intensive insulin therapy is recommended for the majority of patients with type 1 diabetes, and therefore, patients with type 1 diabetes should be referred to an endocrinologist for management of diabetes.
* For most patients with type 2 diabetes, care can be delivered by primary care providers and their health care teams in coordination with other specialists where appropriate. Patients in need of multiple daily injections of insulin therapy should be managed by or in consultation with an endocrinologist, if at all possible.
68
Pharm Therapy
* The decision to refer to an endocrinologist with expertise in diabetes management usually hinges on what?
The decision to refer to an endocrinologist with expertise in diabetes management usually hinges on the complexity of the patient, the ability of the primary care team to achieve established goals of care in an individual, the need to manage diverse complications, and other factors such as the capacity of the primary care practitioner to teach self-management skills such as monitoring and insulin injections.
69
Summary of DM 1 Drugs
* Generally, DM therapy requires what?
Generally, DM therapy requires 0.5-1.0 U/kg per day of insulin divided into multiple doses, while combination of insulin preparations with different times of onset & duration of action should be used
70
# ⭐️
What are the different types of insulin?
* Fast-Acting Insulin (Rapid (Lispro) vs Regular Human Insulin/Humulin)
* Intermediate-Acting Insulin (NPH vs Pre-mixed)
* Long-Acting Insulin (Glargine/Detemir)
71
# ⭐️
Fast-Acting Insulin (Rapid (Lispro) vs Regular Human Insulin/Humulin)
* What is the onset and duration?
Intermediate-Acting Insulin (NPH vs Pre-mixed)
* Onset and duration?
* Great for what?
* What is premixed?
Fast-Acting Insulin (Rapid (Lispro) vs Regular Human Insulin/Humulin)
* Takes 5-30 minutes to onset, last 4-8 hours
Intermediate-Acting Insulin (NPH vs Pre-mixed)
* Takes 1-2hrs to onset, lasts up to 12-18hrs
* Great for overnight or between meals
* Premixed: Combo of NPH and fast-acting (70/30 or 75/25)
72
# ⭐️
Long-Acting Insulin (Glargine/Detemir)
* What is the onset and duration?
* What does it cause?
* Onset of 2hrs, can last 24hrs
* Low peak causing stabilizing plateau
73
# ⭐️
74
# ⭐️
75
# ⭐️
Summary of DM 2 Drugs
* MOA of Alpha-glucosidase inhibitors ?
* MOA of Biguanides (metformin)?
* Alpha-glucosidase inhibitors (acarbose/miglitol), slow the breakdown of starches into glucose after a meal and slows down the increase in blood sugar levels (GI side effects)
* Biguanides (metformin), reduce the production of glucose in the liver and make muscle tissue more sensitive to insulin to improve the absorption of glucose. Will never cause hypoglycemia
76
# ⭐️
Summary of DM 2 Drugs
* MOA of bile acid sequestrants? safe for who?
* GLP-1 agonists help with what? Examples?
* MOA of DPP-4 inhibitors?
* Bile acid sequestrants (BASs), reduce cholesterol and blood sugar and are safe for people who also have liver problems, as they do not enter the bloodstream
* GLP-1 agonists (liraglutide/exenatide) help with weight loss and some decrease cardiovascular events (by injection only->Ozempic/Wegowy)
* DPP-4 inhibitors, (linagliptin/saxagliptin), help improve the binding of glucose to the blood without causing low blood sugar (HF). Prevent degradation of GLP-1, but may increase thyroid/pancreatic cancer risks
77
# ⭐️
Summary of DM 2 Drugs
* MOA of Meglitinides?
* MOA of SGLT2 inhibitors?
* Meglitinides, (nateglinide/repaglinide), stimulate the release of insulin but might cause low blood sugar, but is short-acting
* SGLT2 inhibitors. (canagliflozin/dapagliflozin), help block the reabsorption of glucose in the kidneys, resulting in sugars leaving the body in the urine (UTI/AKI/euglycemic DKA)
78
# ⭐️
Summary of DM 2 Drugs
* MOA of Sulfonylureas?
* MOA of Thiazolidinediones/TZDs
* Sulfonylureas (glimepiride/glipizide/glyburide) stimulate the release of insulin in the pancreas (Very long-acting and can cause weight gain). Should be avoided in kidney disease (GFR<50)
* Thiazolidinediones/TZDs (rosiglitazone/pioglitazone) improve the function of insulin in the fat and muscle and slow glucose production in the liver (Fluid retention/HF/bladder cancer); i.e. fight insulin resistance May worsen HF
79
# ⭐️
* What can you not use in HF?
* What can you not use in GFR less than 50
* Can can you not in family history of thyroid/pancreatic cancer
* HF: Thiazolidinediones/TZDs (rosiglitazone/pioglitazone)
* Kidney: Sulfonylureas (glimepiride/glipizide/glyburide)
* Cancer: GLP-1 agonists (liraglutide/exenatide)
80
81
Fill in the covered part?
82
Insulin pearls:
* Calculate what?
* What is the weight based insulin?
* What happens in NPO?
* Never completely discont?
83
Insulin pearls
* Assess for what?
* Consider discont what?
* Adjust what?
84
85
fill in covered part
86
87
What is the first line for t2d?
Metformin and lifestyle
88
# Dr. V
Txt for T2D
* What do you give for ASCVD?
* What do you give for HF?
89
# Dr. V
Txt of T2D
* What do you give for renal disease?
90
# dr.v
Txt of T2D
* When do you do combination therapy?
91
Monitoring and Education
* What do you need to get at every visit?
* Annual what?
* What do you get if indicated?
* Patient should receive education of what?
* Pre-meal glucose level goal is what?
92
The Incretin Story
* Incretins are a group of what?
* Incretins are released after what?
* Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels.
* Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood glucose-dependent mechanism
93
The Incretin Story
* Ultimately, more insulin is released after what?
* No studies on what?
* Ultimately, more insulin is released after oral instead of IV glucose; therefore, sugar is better controlled when insulin promoters are ingested (GLP-1, exenatide, DPP-4 inhibitors)
* No studies so far regarding inhaled insulin
94
# ⭐️
Phenomena
* What is Somogyi?
Somogyi – posthypoglycemic hyperglycemia
* Getting insulin and sugar gets worse so they give more insulin; it continues to worsen. At night – sugar goes too low so body is overcompensating via gluconeogenesis and gets too high once insulin is used up.
* Noctural hypoglycemia followed by rebound hyperglycemia (dt surge in GH)
* LOWER the insulin to treat really high sugars
* From ROSH: "A paradoxical rise in the early morning glucose levels caused by insulin-induced late evening hypoglycemia"
95
# ⭐️
Phenomena
* What is dawn?
Dawn – due to the decreased levels of endogenous insulin secreted at night, leading to hyperglycemia (b/c of high insulin in the morning)
* Normal glucose until rise in serum glcose levels between 2am-8am
* Does NOT include hypoglycemic episodes
## Footnote
Pance: treat with bedtime injection of NPH, avoiding carbohydreate snack late at night
96
# ⭐️
Phenomena
* Both are indication of what?
* Test by what?
* Both are indication of overtreatment of DM
* Test by reducing insulin at night and look for effect
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What are two of the most serious acute complications of diabetes?
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS, aka hyperosmotic hyperglycemic nonketotic state or hyperosmolar nonketotic state [HHNK/HONK])
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What is DKA? HHS?
DKA is characterized by ketoacidosis and hyperglycemia, while HHS usually has more severe hyperglycemia with volume depletion but no ketoacidosis
* DKA – primarily affects DM1
* HHS – primarily affects DM2
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* For both DKA and HHS-The most common events are what?
* What can promote the development of severe dehydration and HHS?
* For both DKA and HHS-The most common events are infection (often pneumonia or urinary tract infection) and discontinuation of or inadequate insulin therapy.
* Compromised water intake due to underlying medical conditions, particularly in older patients, can promote the development of severe dehydration and HHS.
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Pathophysiology
* What initates HHS?
Elevated levels of counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone) initiate HHS by stimulating hepatic glucose production through glycogenolysis and gluconeogenesis.
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Clinical Presentation
* What is the onset of DKA ?
* What are common symptoms?(5)
* Diabetic ketoacidosis (DKA) usually evolves rapidly, over a 24-hour period.
* Hyperventilation and abdominal pain with nausea/vomiting are common symptoms.
* Acetone odor and dry mucous membranes are common
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Clinical Presentation DKA and HHS
* Hyperosmolar hyperglycemic state (HHS) develop more insidiously with what? What is common and unusual in HHS?
* Hyperosmolar hyperglycemic state (HHS) develop more insidiously with polyuria, polydipsia, and weight loss, often persisting for several days before hospital admission.
* Neurologic symptoms are most common in HHS, Abdominal pain is unusual in HHS
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Clinical Presentation DKA and HHS
* As the degree or duration of hyperglycemia progresses how?
* Signs of volume depletion are common in both DKA and HHS and include what?
* As the degree or duration of hyperglycemia progresses, neurologic symptoms, including lethargy, focal signs, and obtundation, can develop. This can progress to coma in later stages.
* Signs of volume depletion are common in both DKA and HHS and include decreased skin turgor, dry axillae and oral mucosa, low jugular venous pressure, tachycardia, and, if severe, hypotension.
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Diagnosis
* The initial evaluation of patients with hyperglycemic crises should include assessment of what?
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The initial laboratory evaluation of a patient with suspected DKA or HHS should include determination of what?
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Treatment
* What is the txt of HHS?(3)
* IV Fluids (Check volume status and consider CHF as a factor)
* **Isotonic saline** vs LR vs ½ NS depending on state
* Potassium (Insulin drives K+ into the cell) monitoring
* Insulin (Typically Regular) – goal of 250-300 mg/dL
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What is the DKA txt?(4)
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Treatment of DKA continued
* When glucose down to 250, add what?
* Watch what? Put what in IV fluids?
* Generally switch to SQ insulin when?
* Interesting phenomenon:
* When glucose down to 250, add dextrose to general IV fluids. But patient still needs insulin to avoid DKA return.
* Watch serum electrolytes and EKG. Put some potassium in IV fluids when urine output present if potassium not high.
* Generally switch to SQ insulin when eating or get to 250.
* I**nteresting phenomenon: Euglycemic DKA – seen with SGLT2 inhibitors**
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Hypoglycemia
* What is the serum glucose?
* Most common with who?
* Rare with who?
Serum Glucose <70 mg/dL
Most common with diabetics
* Sulfonylureas
* Using insulin without eating
* Insulinoma
Rare without DM
* Church Induced
* Non/DM drug induced
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What are the clinical manifestations of hypoglycemia?
* Autonomic: Sweating, tremors, palpitations, nervousness, tachycardia, pallor, cool clammy skin
* CNS: HA, lightness, confusion, slurred speech, dizziness, irriability, difficulty concentrating, blurred vision, nausea, syncope
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Insulinomas
* What are they?
* How many are malignant?
* Yearly incidence estimated to be what?
* Rare tumors->90% benign, & treatable cause of potentially fatal hypoglycemia.
* About 5 to 10% are malignant, as evidenced by presence of metastases.
* Yearly incidence estimated to be 1 in 250,000 and ~ 60% of cases occur in women
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Insulinomas
* Median age presentation is what?
* Arise within what?
* Size?
* Localized how?
* Treat how?
* Median age presentation is 50 years in sporadic cases, & in third decade when associated with multiple endocrine neoplasia (MEN) type
* Arise within the substance of pancreas in > 99% of cases
* Usually small (1 to 2 cm).
* Localize with CT/MRI
* Treat via surgical reseaction
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Treatment Overview-hypoglycemia
* What do you need to check?
* What do you give for conscious and able to swallow, In AMS?
* When do you recheck?
Must replace glucose
* Obtain Accucheck
* If conscious and able to swallow – replace orally (glucose tabs/juice)
* In AMS – D5/D50 bolus or Glucagon (not in severe alcoholics)
* Recheck Glucose every 10-15 minutes in AMS, every hour in A&O patients
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