Exam 3 Flashcards
1
Q
National Organ Transplant Act
A
Passed by congress in 1984 to address the nations critical donor shortage and improve the organ matching process.
Established OPTN
2
Q
Indications for renal transplant (RTx)
A
End stage renal disease (ESRD) regardless of the cause.
Diabetes is the primary cause
3
Q
Absolute contraindications to RTx
A
Severe cardiovascular or pulmonary disease
Chronic illness with short life expectancy
Active or recently treated cancer
Active sepsis or life threatening infectious disease
Active substance abuse
Poorly controlled mental illness
4
Q
Relative contraindications to RTx
A
Current tobacco use BMI Age Dementia Lacking social support Non-Adherence Limited or no health insurance Pharmacologic
5
Q
RTx- Donor evaluation
A
Must be at least 18 years old in good physical and mental health
Must be willing to donate (do not feel like you must)
Be well informed and have a good grasp on the risks and benefits.
Have a good support system
6
Q
DBD: Donation after brain death
A
Death declared by physician (Not OPO)
Once, declared, OPO involved
Pt remains on ventilator throughout organ recovery which takes 3-4 hours
7
Q
DCD: Donation after cardiac death
A
Family/NOK decide to withdrawal care Once decided, OPO involved Ventilator support withdrawn and death declared by physician 5 minutes after ceased circulation. Organ recovery in 1-2 hours Lack of blood flow may damage organs
8
Q
Donor/ recipient Compatibility
A
- ) Blood type matching
- ) Tissue type matching
- ) Crossmatching
9
Q
Blood type A matching
A
antibodies- anti-a
antigens-A
Compatible blood types- A and O
10
Q
Blood Type B matching
A
Antibodies- anti B
Antigens- B
Compatible blood types- B or O
11
Q
Blood Type AB matching
A
Antibodies- none
Antigens- A and B
Compatible blood types- A, B, AB, O
12
Q
Blood Type O matching
A
Antibodies- anti-a, anti-b
antigens-none
compatible blood type- O
13
Q
Tissue type matching
A
Determines the number of antigens the donor and recipient share
The more antigens matched, the more successful the transplant
14
Q
Cross matching
A
Used to identify the presence of preformed antibodies against a donor (events: pregnancy, blood transfusion, prior transplant)
Panel Reactive Antibody (RBA)- recipient serum is tested against donor lymphocytes contained from a panel of about 100 donors.
%PRA=0= donor not sensitized, donor and recipient cells do not react together.
15
Q
Desensitization
A
Process (plasmapheresis +/- medication therapy) to reduce harmful donor specific antibodies
16
Q
Acute transplant rejection
A
Can occur at any time post-transplant and may lead to allograft loss.
Diagnosis: biopsy, decline in function, organ-specific factors
Kidney- rise in SCr
Liver- Elevated LFTs
Heart- no specific symptoms
17
Q
Risk factors for rejection (kidney)
A
Number of HLA mismatches Younger recipient age Older donor age AA ethnicity Panel reactive antibody (>40%) Cold ischemia time >24 hours
18
Q
General concepts of immunosuppressants
A
Lifelong immunosuppression is required after transplant
Risk of rejection is higher in the beginning
Induction immunosuppression- potent drugs given at time of transplant to quickly resolve immune response. Not always necessary
Maintenance immunosuppression- Started within the 1st week and continued long term. Higher doses in first 6-12 months
Infections are common
PTLD, tumors, and skin cancer common
19
Q
BBW for most immunosuppressants
A
Increased risk of infection that may lead to hospitalization or death
May be associated with the development of malignancies that can lead to hospitalization or death
20
Q
How to take immunosuppressants
A
No missed doses
Take on a fixed schedule
Take the same way each day (with or w/o food)
Must be up to date in vaccines prior to transplant, avoid live vaccines after transplant
21
Q
The three signal model of T cell activation
A
Signal 1: Activation of T cell receptor (TCR)
- Located on T lymphocyte surface
- Recognizes foreign antigen presented by antigen-presenting cells
Signal 2: Co-Stimulation: Interaction between cell surface markers between the APC and T cell
Signal 3: Activation of IL-2 receptor on the T cell surface. Stimulates T cell proliferation
22
Q
Classes of immunosuppressant drugs
A
Calcineurin inhibitors Costimulation inhibitors Antimetabolites m-TOR inhibitors Corticosteroids Monoclonal and polyclonal antibodies
23
Q
Calcineurin inhibitors
A
Cyclosporine
Tacrolimus
Inhibit T cell activation by preventing the phosphatase enzyme calcineurin from acting on the nuclear factor of activated T cells (NFAT), the function of which is to upregulate the expression of IL-2
24
Q
Cyclosporine varieties, absorption, and metabolism
A
Available in different dosage forms that are no bioequivalent.
Cyclosporine USP- oral and injectable
Cyclosporine USP modified- a microemulsion, oral only
Absorption-
Cyclosporine USP- poor and erratic, bile dependent
Cyclosporine modified- Improved not bile-dependent
Metabolism- Gut and hepatic CYP3A4, p-glycoprotein
25
Cyclosporine (CSA) major adverse events
Nephrotoxicity
- Acute- reversible and dose-dependent vasoconstriction of afferent arteriole
- chronic- irreversible damage to the nephrons
Neurotoxicity- tremor, HA, insomnia, confusion, PRES
Cosmetic effects- acne, hirsutism, gingival hyperplasia
Hyperkalemia
Hyperlipidemia
Hypertension
26
Cyclosporine dosing
Initial doses are weight-based and dosed Q12H
Titrated to achieve target trough levels of 100-400ng/mL
IV- 33-50% of oral dose as continuous infusions or in 2 divided doses
- Must be non-PCV bags.
- Associated with anaphylaxis and additional nephrotoxicity
27
Tacrolimus dosage forms, absorption, and metabolism
Calcineurin inhibitor
Available in different dosage forms-not bioequivalent
IR and ER formualtions
Absorption- variable, not bile-dependent, decreased by food (take consistently with regard to food)
Metabolism- CYP3A4 and p-glycoprotein
28
Tacrolimus AE
Same as cyclosporine, but more tolerable
More common- hyperglycemia, neurologic effects
Less common- HTN, hyperlipidemia, cosmetic effects
Additional AE- diarrhea, alopecia
29
Tacrolimus dosing
Initial doses are weight based and dosed Q12H
Titrated to achieve target trough values of 5-20ng/mL
IV- 25-33% PO dose as continuous infusion, must uses non-PCV bags, risk of anaphylaxis
Sublingual- open capsule contents under tongue and allow to dissolve. 50% PO dose.
30
Cyclosporine VS Tacrolimus
Study done in 1998
| Three year graft and treatment failure significantly in the tacrolimus group
31
DDI with CNIs
Enzyme inducers lower CSA/TAC levels
- This increases the risk of rejection
- Phenytoin, carbamazepine, phenobarbitol, Rifampin, St. Johns wort
Enzymes inhibitors raise CSA/TAC levels
- Increases risk of toxicities
- Erythromycin, clarithromycin, azole antifungals, diltiazem, verapamil, nifedipine, metoclopramide, grape fruit juice
32
Trough levels
Whole blood concentrations drawn immediately before next dose
33
Belatacept
Costimulation inhibitor (Signal 2)
Binds CD80 ad CD86 receptors on APCs
-Blocks the binding to CD28 on T cells
Approved for kidney transplant only
IV infusion given monthly
Major benefit over CNIs- Decreased nephrotoxicity
34
Belatacept vs Cyclosporine
Belatacept is superior in kidney transplant
35
Antimetabolites
Azathioprine
Mycophenolate
Inhibit purine nucleotide synthesis which is necessary for T cell proliferation
Signal 3
36
Azathioprine
Prodrug, converted to 6-MP which competes with other purines to inhibit purine nucleotide synthesis
- prevents proliferation
- Acts within de novo and salvage pathways
6-MP is metabolized by several pathways, one of which is xanthine oxidase
37
Azathioprine AE
Hematologic- leukopenia, anemia, thrombocytopenia
N/V (take with food)
Alopecia, hepatotoxicity, pancreatitis
38
Azathioprine dosing
Oral- initial doses are weight based and dosed QD
Doses decrease with time away from transplant
IV=PO
Titrated to WBC count 3500-6000 (low-normal)
39
Mycophenolate
```
Mycophenolate mofetil (MMF)
Enteric-coated mycophenolate sodium (EC-MPS)
```
Both are prodrugs for mycophenolic acid (MPA)
MMF is rapidly converted into MPA by 1st pass metabolism (desterification)
EC-MPS is released in small intestine
40
Mycophenolate MOA
MPA inhibits inosine monophosphate dehydrogenase (IMPDH)
-This inhibits lymphocyte proliferation
More specific than AZA for lymphocytes
41
Mycophenolate metabolism and elimination
After oral intake there is a rapid hydrolysis to MPA, seen as first peak concentration
MPA is converted back into MPAG in liver and some of it goes into enterohepatic recirculation appearing as a "second peak"
Complex metabolism=no trough levels
Excreted by the kidneys as either MPA or MPAG
Both metabolites may accumulate with renal insufficiency
42
Mycophenolate AR
GI: N/V/D, abdominal pain, peptic ulcers
-Take on an empty stomach (decreases Cmax with food) but food does not affect the overall AUC so you can take with or w/o food
Leukopenia, anemia
43
Mycophenolate dosing
Given BID, can split up more frequently prn for GI AE
MPA AUC equations are available
44
mTOR inhibitors
Sirolimus and Everolimus
Structurally related to macrolide abx and tacrolimus
-Diff MOA as TAC so can be used together
MOA: Inhibit mammalian target of rapamycin and inhibit vascular endothelial growth factor
45
Sirolimus
Poor absorption
Variably affected by food- take consistently with regard to food
Metabolism- CYP 3A4 and p-glycoprotein substrate
Mean 1/2 life of 60hrs
Time to steady state- 2 wks
Trough concentrations 1-2 weeks after dose changes
46
Sirolimus AE
```
Leukopenia, anemia, thrombocytopenia (dose related)
Hyperlipidemia (particularly TGs)
Delayed wound healing
Mouth ulcers
Interstitial pneumonitis
Hepatic artery thrombosis after OLTXP
Proteinuria
```
47
Sirolimus dose
Loading doses may be given if needed to get to therapeutic levels quickly
Dosed QD
Titrated to trough levels 5-25ng/mL
No IV formulations
48
Everolimus
2 types: kidney and liver transplant (tab), oncology (tabs and tabs for suspension)
49
Everolimus metabolism, ARE, dosing
Metabolism- Substrate of CYP3A4 and P-glycoprotein
1/2 life- 30 hours
Similar AE to sirolimus, but slightly better
Dosed BID
Titrated to trough levels 3-8ng/mL
50
Corticosteroids
Methylprednisolone and prednisone
Broad spectrum immunosuppressants
Decrease adhesion molecule synthesis
Inhibit transcription factors
51
Corticosteroids metabolism
Hepatic, active metabolite- prednisolone
| Long biologic 1/2 life- give QD
52
Corticosteroids AE
Hyperglycemia, osteoporosis, cataracts, acne, CNS stimulation, HPA axis suppression, acid reflux, GI ulceration
53
Corticosteroids dose
Initially given in very high doses
Gradually tapered
Usual maintenance doses <10mg/day
Combination with other IS agents for lower doses
54
Monoclonal and Polyclonal antibodies
Target various immune cell surface markers, particularly on B and T lymphocytes
Indications vary- induction agents and acute rejection
55
Alemtuzumab
Mech- Anti-CD 52 monoclonal antibody
-causes antibody-dependent cellular-mediated lysis
Uses- B-cell chronic lymphocytic leukemia
Txp- induction therapy and acute rejection
56
Alemtuzumab dosing and AE
One dose IV injection on day of transplant
| AE: neutropenia, anemia, thrombocytopenia, infusion reactions
57
Basiliximab
```
Chimeric- mouse-human monoclonal antibody
Mechanism- IL-2receptor antagonist
Use for induction therapy only
Given IV x 2 doses
AE- infusion reactions rare
```
58
Additional MABs used in kidney transplant
Rituximab-anti CD20 antibody, eliminates B lymphocytes
Use to treat rejection
Eculizumab- binds to compliment protein
Prevents compliment-mediated damage that can occur with rejection
59
Rabbit antithymocyte Globulin (rATG)
Polyclonal
Manufactured by introducing human lymphoid tissue into rabbits
Causes T cell depletion
Used in induction therapy and for tx of acute T cell-mediated rejection
60
Antithymocyte Globulin
Given in slow IV infusion for 3-14 days
| AE: neutropenia, anemia, thrombocytopenia, infusion rxns, thrombophlebitis, serum sickness
61
ATG (equine) and IV immune globulin polyclonal antibodies
ATG- similar to rATG but less effective
| IVIG0 multiple mechanisms to reduce circulating HLA antibody levels
62
Proteosome inhibitors
Bortezomib and Carfilzomib
Reversibly (B) or irreversibly (C) bind to intracellular proteasomes
Causes cell death in a variety of cell types that are dependent on proteasome function (plasma cells)
Elimination of plasma cells reduces antibody function
63
Hyperacute rejection
occurs minutes to hours after organ reperfusion
Requires preformed circulating antibodies
Crossmatch and blood matching techniques make this very rare
64
Acute rxn
3 subtypes: T cell-mediated (cellular), antibody mediated, or mixed
Can occur any time 1 week or longer
Diagnosed via biopsy
May or may not be reversible
65
Creating IS regimens
Combine drugs that act in different areas of the 3-signal model
+/- induction therapy- varies by organ
Maintenance therapy- CNA (CSA/TAC) or belatacept + antiproliferative (AZA, MMF, mTOR) + prednisone
Most common: TAC+ MMF+ Pred
66
Gluconeogenesis
Production of glucose from noncarbohydrate precursors
67
Glycogenesis
Conversion of glucose to glycogen for storage
68
Glycogenolysis
Breakdown of stored glycogen to glucose
69
Glycolysis
Breakdown of stored glycogen to glucose
70
Pancreatic islet cells
The pancreatic islet cells and their endocrine precursors:
alpha- glucagon
beta- insulin, amylin
delta- somastatin
The exocrine pancreas is involved in digestion
71
How does glucagon raise blood glucose
It stimulates glycogenolysis and gluconeogenesis
| It also stimulates fat breakdown
72
How does insulin lower blood glucose?
Insulin is anabolic (a builder)
It stimulates glucose uptake
It suppresses glucose produced by the liver
It suppresses free fatty acids (FFA) release from fat cells. FFAs inhibit uptake of glucose and stimulate gluconeogenesis. Chronic FFa release will cause insulin resistance
Insulin suppresses glucagon release
73
Fasting state
Glucose-disposal
Non-insulin dependent tissues (75%)
Liver and muscle (25%)
Glucose production primarily in liver
74
Non-insulin dependent tissues
```
Beta cells
Red blood cells
Intestines
Central nervous system
Kidney
```
75
Fed state
Glucose disposal
Muscle- 80-85%
Adipocyte- 4-5%
Do mild physical activity after eating to stimulate glucose disposal
76
Pathogenesis of Type 1 Diabetes
Autoimmune disease with progressive beta cell destruction, resulting in physiologic dependence on exogenous insulin
77
Stage 1 Type 1 Diabetes
Characteristics- autoimmunity, normoglycemia, presymptomatic
| Diagnostic criteria- Multiple antibodies, no IGT or IFG
78
Stage 2 Type 1 diabetes
Characteristics- autoimmunity, dysglycemia, presymptomatic
Diagnostic criteria- Multiple antibodies, Dysglycemia: IFG and/or IGT
FBG: 100-125mg/dL
A1C: 5.7-6.4% or greater than 10% increase
79
Stage 3 Type 1 Diabetes
Characteristics- New-onset hyperglycemia, symptomatic
| Diagnostic criteria- Clinical symptoms, diabetes from normal criteria
80
Coexistent autoimmunity in type 1 diabetes
Celiac disease- have gluten free diet
| Thyroid disease, generally hypothyroidism
81
Pathogenesis of Type 2 diabetes
Caused by multiple defects:
- Impaired insulin secretion
- Insulin resistance involving muscle, liver, and adipocytes
- Excess glucagon secretion
- Deficiency and resistance to insulin hormones
- Sodium0glucose cotransporter upregulation in the kidney
82
Insulin secretion
Glucose gets into the cells and closes the ATP-K channel, this opens the Ca channel and insulin is released
Insulin is not involved in glucose getting into beta cells
83
What phase of insulin response is impaired in T2DM?
Phase 1- insulin is not being stored completely
84
Impaired insulin secretion T2DM
Beta cell mass and function is reduced
This failure is progressive, there is a 5-7% loss of beta cells per year
-Caused by glucose toxicity, age, lipotoxicity, insulin resistance, genetics, incretin deficiency
85
Glucose toxicity
As glucose increases insulin increases. Glucose is toxic to beta cells and they can't keep up with chronically high levels of glucose, causing loss of cells and function
86
Insulin Resistance T2DM
Liver- Hepatic glucose production increased in mild to moderate fasting hyperglycemia.
-Failure to suppress glucagon in response to a meal (two sources of glucose production in fed state)
Peripheral (skeletal muscle)- major site of postprandial glucose disposal. Onset of insulin action is delayed for about 40 minutes. Glucose uptake reduced by 50%
Peripheral (adipocyte)- Fasting plasma FFA levels increased and fail to suppress after glucose ingestion. FFAs stored as TGs in adipocytes and insulin is a potent inhibitor of lipolysis
87
Obesity and insulin resistance
Weight gain leads to insulin resistance
Visceral adipose tissue (VAT)
-fat cells located w/in abdominal cavity
-correlates with insulin resistance
-waste circumference is good marker
-Higher rate of lipolysis means increased FFA production
-Produces adipocytokines, increased FFA production
-Produces adipocytokines, causing insulin resistance, HTN, and hypercoagulability
88
Glucagon secretion T2DM
Failure to suppress glucagon after a meal
| Paradoxical rise in glucagon levels because of insulin resistance and GLP-1 resistance
89
The incretin effect
Glucagon-like peptide-1 (GLP-1) is secreted by L cells
- Levels decreased in T2DM
- Stimulated insulin secretion and suppresses glucagon secretion.
- Slows gastric emptying
- Reduces food intake by increasing satiety
Glucose-dependent insulinotropic peptide (GIP)- secreted by K cells
- Insulin secretion during near-normal glucose levels
- insulin sensitizer in adipocytes
90
```
Characteristics of diagnosis for Type 1 Diabetes
Age
C-peptide
ICA, GAD65, IA-2, IAA
Circulating Insulin
Time to requiring insulin
```
```
Age- <35
C-peptide- Very low
ICA, GAD65, IA-2, IAA- Often positive
Circulating Insulin- Rapidly deficient
Time to requiring insulin- At onset
```
91
```
Characteristics of diagnosis for Type 2 Diabetes
Age
C-peptide
ICA, GAD65, IA-2, IAA
Circulating Insulin
Time to requiring insulin
```
Age- >35
C-peptide- Normal to high
ICA, GAD65, IA-2, IAA- Negative
Circulating Insulin- Excessive and resistant
Time to requiring insulin- Can be many years
92
```
Characteristics of diagnosis for LADA
Age
C-peptide
ICA, GAD65, IA-2, IAA
Circulating Insulin
Time to requiring insulin
```
```
Age- >/= 30
C-peptide- Low
ICA, GAD65, IA-2, IAA- Can be positive
Circulating Insulin- Gradually resistant
Time to requiring insulin- Within 6 months (variable)
```
93
Gestational Diabetes Mellitus (GDM)
Any degree of glucose intolerance with on set or first recognition during pregnancy
- Test for GDM at 24-48 weeks of gestation in pregnant women not previously known to have diabetes (A)
- Test for undiagnosed type 2 diabetes at the first prenatal visit in those with risk factors (B)
If first trimester, it is T2DM not GDM
Second trimester, GDM unless clearly otherwise
94
Screening for GDM
75g glucose load, check fasting levels 1 hr and 2 hr after.
Diagnosis if fasting- 95mg/dL
1hr- 180mg/dL
2 hr- 155mg/dL
3hr- 140mg/dL
95
Long term risk of GDM
Strongest known predictor of T2DM- 50% diagnosed 10 years postpartum
Test women with GDM for prediabetes or diabetes at 4-12 weeks postpartum
2/3rds chance of GDM in future pregnancies
Increased lifetime risk of HTN and stroke
96
Medications related to hyperglycemia
```
Fluoroquinolones (cipro)
Atypical antipsychotics (Risperidone, quetiapine, olanzapine)
Beta-blockers
Glucocorticoids
Calcineurin inhibitors
Protease inhibitors
Thiazides and thiazide like diuretics
```
97
Criteria for diabetic testing in asymptomatic adults
```
Testing should be considered in overweight or obese adults who have one or more of the following risk factors:
-1st degree relative with diabetes
-History of CVD
-HTN
-Hyperhcolesterolemia
-Women with PCOS
- Physical inactivity
-High risk ethnicity
Begin testing at 45 for all patients
Test q 3 years for women that have had GDM
Prediabetics should be tested yearly
All other patients should be tested q 3 years
```
98
Clinical presentation of diabetes
```
Polyuria
Polydipsia
Polyphagia
Lethargy/fatigue
Weight loss
Blurred vision
```
99
Diagnostic criteria for diabetes
A1C- >/= 6.5%
FPG- >/= 126mg/dL
2-hr PG- >/= 200mg/dL during an OGTT
Classic symptoms of hyperglycemia and random PG >/= 200mg/dL
100
Diagnostic criteria for prediabetes
A1C- 5.7-6.4%
FBG- 100-125mg/dL
2-h PG- 140-199mg/dL
101
Hemoglobin A1C
Glucose enters erythrocytes and glycates amino terminals of hemoglobin
- Represents glycemic exposure over 2-3 months
- Does not require fasting
- Levels may vary with race/ethnicity
- Hemoglobinopathies/RBC turnover
102
Estimated average blood glucose (eAG) eqn
eAG= 28.7 x A1C -46.7
103
Strengths of A1C
Reflects chronic hyperglycemia
Less biologic variability than 1-2h glucose
Eliminates need for fasting
Unaffected by acute illness or recent activity
Used as a guide to adjust treatment
Better predictor of complications that fasting BG
104
Limitations of A1C
Certain conditions interfere with the interpretation of results (hemolytic anemia, recent transfusion, pregnancy, loss of blood)
Lack of standardization in other countries
Cost
105
Symptoms of hypoglycemia
Tremor, nervous/anxious, diaphoresis, tachycardia, hunger, lightheaded/HA, irritable, confusion, drowsiness
106
Hyperglycemic crisis
Type 1- diabetic ketoacidosis
| Type 2- Hyperglycemic hyperosmolar state
107
Microvascular complications of diabetes
Retinopathy
Nephropathy
Peripheral neuropathy
Autonomic neuropathies (gastroparesis, erectile dysnfunction)
108
Macrovascular complications of diabetes
CAD, cerebrovascular disease, peripheral artery disease
109
DCCT trial
Intensive treatment of decreasing A1Cs decreases the risk of microvascular complications but not macrovascular
110
ADA glycemic targets
A1C- <7%
Preprandial- 80-130mg/dL
Peak postprandial PG- <180mg/dL
111
Monitoring for diabetes
Perform the A1C test at least 2 times a year in patients who are meeting treatment goals and who still have glycemic control
-Perform A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic control
112
Self-monitoring of blood glucose
Intensive insulin regimen- prior to meals/snacks, bedtime, occasionally postprandially, prior to exercise, when hypoglycemia expected, after treating hypoglycemia, prior to critical tasks (driving)
113
Continuous glucose monitoring
Measures interstitial glucose
Real-time CGM- continuously report glucose levels. Alarms for hypo and hyperglycemia
Intermittently scanning CGM (isCGM)- adult use only, no alarms, lower cost, does not communicate continuously
Limitations- Invasive, some require daily calibrations, requires very motivated pts
114
CGM- based targets
Goal target range 70-180 and be in this range >/= 70% of the time
115
Risks of uncontrolled diabetes in pregnancy
```
Spontaneous abortion
Fetal anomalies
Preeclampsia
Fetal demise
Macrosomia
Neonatal hypoglycemia
Neonatal hyperbilirubinemia
```
116
Pregnancy diabetes recommendations
A1C- <6.5%
Preconception counseling
Medication evaluation
117
Preeclampsia and aspirin
Women with type 1 and type 2 diabetes should be prescribed low dose aspirin from the end of the first trimester until the baby is born in order to lower risk of preeclampsia
118
Childrens and adolescents with diabetes
Mainly Type 1
Insulin doses may need to change based on sexual maturity and physical growth
Assess the ability to provide self-care
Supervision in childcare/school
Neurological vulnerability to hypoglycemia/hyperglycemia
Less stringent A1C goals than other pts due to risk of hypoglycemia
119
Older adults diabetes
Less stringent A1C goals
120
Cystic fibrosis related diabetes (CFRD)
Associated with worse nutritional status, more severe inflammatory lung disease, greater mortality.
Primary defect is insulin insufficiency related to partial fibrotic destruction of the islet mass
Annual screenings should begin at age 10 with OGTT
Do not use A1C
Patients should be treated with insulin!
121
Posttransplantation Diabetes Mellitus (PTDM)
Describes presence of diabetes in posttransplant setting irrespective of timing to diabetes onset
OGTT= gold standard test
122
Angioplasty
Damage of blood vessels
123
Microvascular disease
Damage to small blood vessels
124
Macrovascular disease
Damage to the arteries
125
Macrovascular complications of diabetes
Cerebrovascular disease, CAD, peripheral vascular disease
126
Microvascular complications of diabetes
Retinopathy, Nephropathy, autonomic neuropathy, peripheral neuropathy
127
What is the mechanism behind complications in diabetes?
Chronic exposure to hyperglycemia
-Interaction of glucose with proteins causes advanced glycosylation end products and leads to tissue damage and injury
-Accumulation of metabolic products of aldose reductase system affects cellular energy metabolism and contributes to cell injury and death
128
ASCVD
```
Acute coronary syndromes
H/O MI
Stable or unstable angina
Coronary or other arterial revascularization
Stroke
Transient ischemic attack
Peripheral arterial disease
```
129
ASCVD and HTN
HTN is a major risk factor for ASCVD and microvascular complications
Type 1 diabetes- often underlying nephropathy
Type 2 diabetes- coexists with other cardiometabolic risk factors
130
BP goals for diabetes patients
ACC/AHA- <130/ <80
ADA
Diabetes + HTN+ 10-year risk >15%- <130/<80
Diabetes + HTN + 10 year risk <15%- <140/<90
131
Diabetes + BP <160/100 treatment
Lifestyle management
Start with one agent
Albuminuria? Yes- ACE/ARB
No- ACE/ARB/CCB/Thiazide
132
Diabetes + BP >160/100 treatment
Lifestyle management
Start with 2 agents
Albuminuria? Start ACE or ARB + thiazide or CCB
no- Any 1st line agents
133
ASCVD lipid management
Increased prevalence of lipid abnormalities in T2DM
Low HDL associated with high TG
Use statin
134
Statin benefit groups
1. ) Clinical ASCVD
2. ) Primary elevation of LDL >190mg/dl
3. ) 40-75 yo w/ diabetes w/ LDL 70-189mg/dL
4. ) W/O clinical ASCVD or diabetes aged 40-75 w/ LDL 70-189mg/dL and 10 year risk >7.5%
135
What intensity statin should be recommended for statin benefit groups?
Moderate to high intensity
136
ADA statin recommendations primary prevention
40-75= moderate intensity statin
20-39 w/ ASCVD risk factors= may be reasonable Multiple ASCVD risk factors or 50-79= High-intensity statin
ASCVD risk >20% and LDL reduction <50%= add ezetimibe
137
ADA statin recommendations secondary prevention
High-intensity statin
| Very high risk and LDL>70= add ezetimibe or PCSK9 inhibitor
138
ASCVD risk factors
```
LDL >100mg/dL
HTN
Smoking
CKD
Albuminuria
Family h/o premature ASCVD
```
139
Vascepa
Icosapent ethyl (Vascepa)
FDA approval in 2019 for pts with controlled LDL on a statin but elevated TG (135-499)
REDUCE-IT trial
140
Fibrates and Niacin
Combination therapy with statin has not been shown to improve ASCVD outcomes or provide additional CV benefit and is generally not recommended
141
ASCVD antiplatelet agents
Everyone should be on an aspirin for secondary prevention
| Primary prevention based on risk factors
142
Diabetic nretinopathy
Prevalence strongly related to duration of diabetes and glycemic control
Chronic hyperglycemia, nephropathy, HTN, dyslipidemia all increase risk
143
Nonproliferative diabetic retinopathy (NPDR)
Hyperglycemia contributes to changes in the integrity of blood vessels within the retina
Alterations in blood-retinal barrier and vascular permeability
Release of angiogenic factors related to hypoxia and ischemia
Occlusion of retinal capillaries
144
Proliferative diabetic retinopathy (PDR)
Neovascularization and accumulation of fluid within the retina (macular edema) contribute to vision impairment
145
Stages of diabetic retinopathy
Mild nonproliferative- microaneuryisms
Moderate nonproliferative- some blood vessels in retina become blocked
Severe nonproliferative- many blood vessels blocked. New blood vessels begin to form.
Proliferative- New BV have thin and weak walls and leak. This causes severe vision loss and potential blindness.
146
Screening for diabetic retinopathy
Type 1- at least w/in 5 years of onset
Type 2- at onset
After onset screen yearly
147
Diabetic nephropathy
Leading cause of ESRD
| Caused by hemodynamic alterations in renal microcirculations and structural changes in glomerulus
148
Screening for diabetic nephropathy
Assess UACR and eGFR annually
| Twice annually if UACR >30 and/or eGFR <60
149
Treatment for diabetic kidney disease
Glycemic and BP control
ACE/ARB not recommended for primary prevention
ACE/ARB recommended for UACR >30
Non-dialysis pts protein intake should be 0.8g/kg/day
150
Diabetic neuropathy
Distal symmetric polyneuropathy (DSPN)
| other autonomic neuropathies
151
DSPN
Symptoms vary
small fibers- pain, burning, tingling
large fibers- numbness and loss of protective sensation
Screen annually
152
DSPN treatment
Pregabalin, duloxetine, gabapentin all 1st line
153
Diabetic foot care
Annual food exam
therapeutic footwear
screen for PAD
Do Ankle-brachial index testing
154
Ankle-brachial index testing (ABI)
```
Normal: 0.9-1.30
Mild obstruction- 0.7-0.9
Moderate obstruction- 0.40-0.69
Severe obstruction- <0.40
Poorly compressible >1.3
```
155
Peripheral artery disease
Needs to be on antiplatelet therapy (clopidogrel or aspirin)
| Preventative foot care
156
Autonomic neuropathies
Cardiovascular autonomic neuropathy- resting tachycardia (>100bpm)
Orthostatic hypotension
GI- constipation, gastroparesis
GU- erectile and bladder dysfunction
157
Gastroparesis
Food stays in a diabetic pts stomach longer
Tx- small meals, low-fat, low-fiber, 4-5 times per day
Prokinetic agents- metoclopramide and erythromycin
158
Immunizations for diabetes pts
Influenza
Pneumoccocal
Hep B
