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Flashcards in Diabetes Deck (123):
1

Characteristics of DM

Hyperglycemia
Impaired metabolism
Impaired insulin secretion*
Insulin resistance*
*or both

2

% cases that are DM 1

5-10%

3

% cases that are DM2

90+

4

Age of onset DM 1

< 30 years

5

Age of onset DM 2

> 30 years

6

Genetic link DM 1

Weak

7

Genetic link DM 2

Strong

8

Pathogenesis DM 1

Absolute deficiency of insulin production

9

Pathogenesis DM 2

Insulin resistance, defective insulin release

10

Dx of DM

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

DM 1

Absolute deficiency of insulin production
Autoimmune

12

Four main features of DM 1

1) long pre-clinical period
2) hyperglycemia when 80-90% of beta cells are destroyed
3) Transient remission
4) Established disease

13

DM 1 Tx

Individualized
Goal is to mimic normal physiologic levels
Basal
Bolus
Basal-bolus (long acting for basal coverage; short acting bolus at meal times)

14

Human Insulin

Regular
Short acting
100 units/mL = standard
500 units/mL (U-500)
ERROR PRONE

15

Insulin Analogs

Rapid -> ultra short acting
or long acting

16

NPH insulin

Intermediate acting

17

Insulin mixtures

70/30; 50/50

18

Insulin administsration

Oral -> destroys protein
Must be given parenterally
Usually SubQ injection (slow absorption)

19

How do you give regular insulin

IV

20

Rapid (ultra short) Acting Analogs

Rapid absorption due to reduced self-association
Advantage: can dose closer to meal time

21

Long Acting Insulin Analogs

Reduced solubility
Slow absorption
Advantage: continuous coverage w/o more injections

22

Glargine duration

Long acting (LA)
22-36 hours

23

Glargine subtypes w/ units

Lantus: 100 units/mL
Toujeo: 300 units/mL

24

Detemir duration

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