Diabetes Flashcards
1
Q
Characteristics of DM
A
Hyperglycemia Impaired metabolism Impaired insulin secretion* Insulin resistance* *or both
2
Q
% cases that are DM 1
A
5-10%
3
Q
% cases that are DM2
A
90+
4
Q
Age of onset DM 1
A
< 30 years
5
Q
Age of onset DM 2
A
> 30 years
6
Q
Genetic link DM 1
A
Weak
7
Q
Genetic link DM 2
A
Strong
8
Q
Pathogenesis DM 1
A
Absolute deficiency of insulin production
9
Q
Pathogenesis DM 2
A
Insulin resistance, defective insulin release
10
Q
Dx of DM
A
Hgb A1C >6.5%
Fasting BG > 126 mg/dL
Classic ssx + random BG > 200 mg/dL
BG > 200 mg/dL 2 hours post OGTT
11
Q
DM 1
A
Absolute deficiency of insulin production
Autoimmune
12
Q
Four main features of DM 1
A
1) long pre-clinical period
2) hyperglycemia when 80-90% of beta cells are destroyed
3) Transient remission
4) Established disease
13
Q
DM 1 Tx
A
Individualized
Goal is to mimic normal physiologic levels
Basal
Bolus
Basal-bolus (long acting for basal coverage; short acting bolus at meal times)
14
Q
Human Insulin
A
Regular Short acting 100 units/mL = standard 500 units/mL (U-500) ERROR PRONE
15
Q
Insulin Analogs
A
Rapid -> ultra short acting
or long acting
16
Q
NPH insulin
A
Intermediate acting
17
Q
Insulin mixtures
A
70/30; 50/50
18
Q
Insulin administsration
A
Oral -> destroys protein
Must be given parenterally
Usually SubQ injection (slow absorption)
19
Q
How do you give regular insulin
A
IV
20
Q
Rapid (ultra short) Acting Analogs
A
Rapid absorption due to reduced self-association
Advantage: can dose closer to meal time
21
Q
Long Acting Insulin Analogs
A
Reduced solubility
Slow absorption
Advantage: continuous coverage w/o more injections
22
Q
Glargine duration
A
Long acting (LA) 22-36 hours
23
Q
Glargine subtypes w/ units
A
Lantus: 100 units/mL
Toujeo: 300 units/mL
24
Q
Detemir duration
A
LA
12-20 hours
Dose 1-2xs/day
25
Degludec duration
LA
| >42 hours
26
Degludec subtype and units
100 units/mL
| or 200 units/mL
27
NPH insulin
```
Intermediate acting (IA)
Suspension of crystalline zinc insuline and positively charged polypeptide, protamine
Absorbed slower after SubQ injection
```
28
NPH duration
Longer than regular insulin but shorter than glargine, detemir, or degludec
29
Early insulin names
```
Humalin = made by Eli Lilly
Novolin = made by Novo Dordisk
```
30
DM 1 inslin total daily dose (TDD)
Total daily dose required about 0.4-1 units/kg/day of actual body weight
31
DM 1 basal insulin dose requirements
Should be approximately half total daily dose (TDD)
| May use intermediate or long acting (NPH is preferred because it can be mixed)
32
DM 1 bolus insulin dose requirements
Other 50% of TDD
Divided between meals based on type of meal and pt characteristics
Rapid acting or regular
33
2 injection non-intensive insulin therapy
Split-mixed dosing
2 daily injections (2/3 TDD AM; 1/3 TDD PM)
Basal insulin should be 2/3 as morning dose and 1/3 as evening dose (NPH)
34
3 injection non-intensive insulin therapy
3 daily injections -> same dosing as split mixed but moves NPH to bedtime
Decreases nocturnal hypoglycemia
Increased effect at dawn
35
Intensive insulin therapy
multiple BG checks/day
36
Types of control for sliding scale insulin
Tight or regular control
37
What 2 types of glycemic monitoring are there
Blood glucose
| HgbA1C
38
Blood glucose measure
Evaluates impact of insulin on meals
Fasting = FBG
Post-Parandial = PPG
39
HgbA1c
Assess glycemic control over 2-3 months
| 4-6% in non-diabetes
40
HgbA1c goals
AACE guidelines < 6.5%
| ADA guidelines < 7%
41
Interpreting A1C
Irreversible process
Lasts life of RBCs (120 days)
Reflects average glucose over 3 months
42
DM 2 is a disorder of:
Insulin secretion
Insulin resistance
Excess glucose production
(can be all of the above)
43
RF for DM 2
Most are modifiable
44
Tx DM 2
Individualize -> based on age and comorbidities
45
DM 2 lifestyle changes
```
Start at diagnosis w/ pharmacotherapy
Weight reduction (diet and exercise)
Tobacco cessation
Minimize alcohol
Nutritional counseling
```
46
Initial tx DM 2
At diagnosis: lifestyle changes and metformin
| *Multiple drugs being used earlier*
47
When do you start dual DM 2 tx
If not at target A1C after 3 months of monotherapy or baseline A1C > 9%
48
When do you start triple DM 2 tx
If not at target A1C after 3 months of dual therapy
49
When do you start combo injection therapy for DM 2?
Not at target A1C after 3 months of triple therapy
BG > 300-350 mg/dL
A1C > 10-12%
50
Highly effective hypoglycemia agents
Insulin
Biguanides (metformin)
Sulfonylureas (SUs)
Rapid-acting secretagogues (glinides)
51
Insulin for DM2
Used earlier now to reduce micro and macrovascular complications
52
When to start insulin in DM 2 pts
Not at A1C goal after >2 non-insulin hypoglycemics
If pt has severe fasting BG levels
A1C > 10%
*Don't use as a threat for not reaching A1C goals*
53
What kind of insulin do you start w/ in DM 2
Basal/long acting
Less hypoglycemia
NPH and LA equally effective
NPH available OTC and cheaper
54
First step in starting insulin for DM 2 pt
Start basal (LA) once daily
55
Second step for DM 2 insulin pts
Adjust once or twice weekly
56
3rd step DM 2 insulin pts
If not at goal begin prandial rapid insulin
57
Step 4 DM 2
Begin basal bolus insulin regimen
58
Biguanides DM 2
Metformin
Oral
Considered 1st line drug of choice
59
Biguanides and metformin MOA
Reduces hepatic glucose production
Reduces intestinal glucose absorption
Increase insulin sensitivity
Improved peripheral glucose uptake and utilization
60
Metformin-glucophage
Promotes modest weight loss or weight neutral
Lowers fasting BG 20% and A1C 1-2%
Syndergistic effect w/ sulfonylureas
Generally minimal side-effect profile
61
Metformin-glucophage SE
Primarily GI: NV; diarrhea; flatulence
| Can lead to lactic acidosis
62
Contraindications to metformin
Male: serum creatinine > 1.5 mg/dL
Female: serum creatinine clearance > 1.4 mg/dL
Do not use if CrCl < 30 mL/min (CKD 4/5)
Closely monitor if CrCl is between 30-59 mL/min (CKD 3)
63
First biguanide
Phenformin
64
What to monitor for when pt is on metformin
Renal issues
Dehydration
Infection/sepsis
overdose
65
Sulfonylureas (SUs)
```
Dose once daily*
*greater risk for hypoglycemia*
Second line therapy
All equally effective
Overall a moderately effective class
```
66
Are 1st generation SUs used?
Rarely
67
2nd generation SU agents
Preferred -> less hypoglycemia
1) Glimepiride
2) Glipizide
3) Glyburide
68
Glimepiride dosing interval
q 24 hours
| More hypoglycemia than glipizide
69
Glipizide dosing interval
q12-24 hours
70
Glyburide dosing interval
q12-24 hours
| Not preferred -> most hypoglycemia
71
SUs MOA
Stimulates release of insulin
| Requires presence of insulin (functioning pancreas) -> not good for DM1
72
Rapid acting secretagogues (RAS)
```
glinides
Oral antidiabetic agents
More frequent dosing than SUs
Nateglinide -> dose ac tid
Repaglinide -> dose ac 2-4xs/day (more effective in A1C reduction)
```
73
RAS MOA
Stimulate insulin release from pancreas
Similar to SUs but shorter half life
Faster onset than SUs (fast acting)
74
RAS SE
hypoglycemia (less than SUs)
| Weight gain
75
SSx of adrenergic manifestation of hypoglycemia
```
Shakiness
Nervousness
Anxiety
Palpitations Tachycardia
Sweating (absent or diminished if on beta blockers)
```
76
SSx of glucagon manifestations of hypoglycemia
Hunger
Nausea
Vomiting
Headache
77
SSx of neuroglycopenic manifestations of hypoglycemia
```
Impaired judgement/mentation
Fatigue
Lethargy
Ataxia (can seem like they are intoxicated)
Stupor
Coma
Seizures
```
78
Mild (< 50 mg/dL) hypoglycemia tx
3 glucose tabs
1/3 c fruit juice
5-6 pieces hard candy (not artificial)
Glucose gel
79
Severe (< 40 mg/dL) hypoglycemia tx
Glucagon injection
| D50 IV push
80
Moderately effective hypoglycemic agents
TZDs
DDP4Is
SGLTsIs
81
Thiazolidinediones TZDs
Rosiglitazone -> dose 1-2xs/day
Pioglitazone -> dose 1x/day
Synergistic effect when combined
82
TZD MOA
Increase insulin sensitivity by:
Increasing glucose utilization and decreasing hepatic glucose production
"Insulin sensitizer" -> needs insulin present
83
TZD SE
weight gain
edema
Increased total cholesterol, LDL, HDL
Hepatic metabolism (avoid if LFTs > 2.5 ULN)
84
What are pts at an increased risk of when on rosiglitazone
MI
85
TZD pioglitazone agent, dosing, and cost
Actos
Dosed once daily
About $10 a month
86
TZD rosiglitazone agent, dosing, cost
Avandia
1-2xs/day
$90/month
87
DPP4Is (gliptins) MOA
Inhibits enzyme that degrades incretin homrones which prolongs incretin levels
88
Incretin hormones
GLP-1
GIP
*Increase insulin secretion in response to meals
89
What are DPP4Is also known as
Incretin enhancers
90
Benefits of prolonged incretin levels
Stimulate insulin synthesis and release
| Decrease glucagon secretion from pancreatic alpha cells
91
Net result of DPP4Is
Prolonged basal insulin secretion
92
Advantages of DPP4Is
Oral dosing
Once daily
Minimal hypogylcemia
Weight neutral
93
Disadvantages of DPP4Is
Placebo
Costly -> $380/month
Concerns of increased risk of heart failure (no increased risk of hospitalization for HF)
94
Does DPP4I agent Linagliptin require renal adjustment?
NO
95
Sodium glucose cotransporter 2 Inhibitors
| SGLT2Is
Oral anti-diabetics
| Moderately effective
96
SGLT2I MOA
Inhibits SGLT2 recovery of glucose from the urine (increased urine glucose loss)
97
SGLT2I advantages
Lowers BP
| Decreases weight
98
SGLT2I adverse effects
Genital fungal infections
Dehydration
Risk of ketosis, UTIs, and pyelonephritis
99
Minimally effective hypoglycemic agents
alpha glucosiade inhibitors (agi)
Pramlintide
Glucagon-like peptide 1 receptor agonists (GLP-1 RAgs)
100
AGIs
Oral dosing
TID
Relatively low cost ($30-$60)
101
AGI MOA
Inhbits pancreatic alpha amylase and GI brush border alpha-glucosidases
This delays hydrolysis of carbs and reduces post prandial insulin and glucose peaks
102
AGI advantages
Effective for DM1 and DM2
NO hypoglycemia
Efficacy equal between all agents
103
AGI disadvantages
Usually need to combine w/ metformin, a sulfonylureas, or insulin
High rate of flatulence and mild rate of diarrhea
104
Pramlintide
Synthetic analog of human amylin
Decreases post-prandial glucose leves
No action on beta cells so can be used for DM1 and DM2
105
Advantages of pramlitnide
Neutral risk of hypoglycemia
| Weight loss
106
Pramlintide dosing
SubQ injection before each meal
107
Disadvantages of pramlintide
Very $$$ ($1500/month)
| Nausea in about half of pts
108
Liraglutide dosing (GLP-1 RAg)
once daily
109
How are GLP-1 RAg's dosed
SC injection
110
```
Exenatide dosing
(GLP-1 RAg)
```
IR = BID; ER = once weekly
111
```
Dulaglutide dosing
(GLP-1 RAg)
```
Once weekly
112
```
Albiglutide dosing
(GLP-1 RAg)
```
Once weekly
113
GLP-1 RAg MOA
Incretin mimetic
Enhances glucose dependent insulin secretion from beta cells which inhibits the release of glucagon which slows rate of gastric emptying which increases satiety
114
GLP-1 RAg advantage
weight loss
115
GLP-1 RAg former disadvangtage
Heart failure (was recently discounted)
116
Starting DM2 meds guidelines
No single method
| Keep other factors into account (pt preference, route, cost, risk of hypoglycemia)
117
Starting DM2 meds steps
1) Metformin (mild)
2) add a second drug (mod)
3) add a third drug (severe)
4) Insulin + meds (super severe)
* *Most pts will require multiple meds
118
When do you mainly see DKA?
Type 1 diabetics
119
What usually precipitates DKA
Not adhering to meds
Infection
Alcohol abuse
120
DKA presentation
```
Polyuria
Polydypsia
Polyphagia
Weakness
Fruity breath
NV
Sx of dehydration
```
121
Outpatient tx of DKA
```
This is mild DKA
Hydrate
Insulin
Potassium
Bicarbonate
Sodium
```
122
Inpatient DKA tx
```
Mod-severe DKA
Fluids
Insulin
Potassium
Bicarbonate
Sodium
```
123
Do you increase or decrease insulin for DM1 pts during the honeymoon period (transient remission)?
Decrease
