Diabetes Flashcards
Characteristics of DM
Hyperglycemia Impaired metabolism Impaired insulin secretion* Insulin resistance* *or both
% cases that are DM 1
5-10%
% cases that are DM2
90+
Age of onset DM 1
< 30 years
Age of onset DM 2
> 30 years
Genetic link DM 1
Weak
Genetic link DM 2
Strong
Pathogenesis DM 1
Absolute deficiency of insulin production
Pathogenesis DM 2
Insulin resistance, defective insulin release
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
DM 1
Absolute deficiency of insulin production
Autoimmune
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
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)
Human Insulin
Regular Short acting 100 units/mL = standard 500 units/mL (U-500) ERROR PRONE
Insulin Analogs
Rapid -> ultra short acting
or long acting
NPH insulin
Intermediate acting
Insulin mixtures
70/30; 50/50
Insulin administsration
Oral -> destroys protein
Must be given parenterally
Usually SubQ injection (slow absorption)
How do you give regular insulin
IV
Rapid (ultra short) Acting Analogs
Rapid absorption due to reduced self-association
Advantage: can dose closer to meal time
Long Acting Insulin Analogs
Reduced solubility
Slow absorption
Advantage: continuous coverage w/o more injections
Glargine duration
Long acting (LA) 22-36 hours
Glargine subtypes w/ units
Lantus: 100 units/mL
Toujeo: 300 units/mL
Detemir duration
LA
12-20 hours
Dose 1-2xs/day
Degludec duration
LA
>42 hours
Degludec subtype and units
100 units/mL
or 200 units/mL
NPH insulin
Intermediate acting (IA) Suspension of crystalline zinc insuline and positively charged polypeptide, protamine Absorbed slower after SubQ injection
NPH duration
Longer than regular insulin but shorter than glargine, detemir, or degludec
Early insulin names
Humalin = made by Eli Lilly Novolin = made by Novo Dordisk
DM 1 inslin total daily dose (TDD)
Total daily dose required about 0.4-1 units/kg/day of actual body weight
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)
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
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)
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
Intensive insulin therapy
multiple BG checks/day
Types of control for sliding scale insulin
Tight or regular control
What 2 types of glycemic monitoring are there
Blood glucose
HgbA1C
Blood glucose measure
Evaluates impact of insulin on meals
Fasting = FBG
Post-Parandial = PPG
HgbA1c
Assess glycemic control over 2-3 months
4-6% in non-diabetes
HgbA1c goals
AACE guidelines < 6.5%
ADA guidelines < 7%
Interpreting A1C
Irreversible process
Lasts life of RBCs (120 days)
Reflects average glucose over 3 months
DM 2 is a disorder of:
Insulin secretion
Insulin resistance
Excess glucose production
(can be all of the above)
RF for DM 2
Most are modifiable
Tx DM 2
Individualize -> based on age and comorbidities
DM 2 lifestyle changes
Start at diagnosis w/ pharmacotherapy Weight reduction (diet and exercise) Tobacco cessation Minimize alcohol Nutritional counseling
Initial tx DM 2
At diagnosis: lifestyle changes and metformin
Multiple drugs being used earlier
When do you start dual DM 2 tx
If not at target A1C after 3 months of monotherapy or baseline A1C > 9%
When do you start triple DM 2 tx
If not at target A1C after 3 months of dual therapy
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%
Highly effective hypoglycemia agents
Insulin
Biguanides (metformin)
Sulfonylureas (SUs)
Rapid-acting secretagogues (glinides)
Insulin for DM2
Used earlier now to reduce micro and macrovascular complications
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
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
First step in starting insulin for DM 2 pt
Start basal (LA) once daily
Second step for DM 2 insulin pts
Adjust once or twice weekly
3rd step DM 2 insulin pts
If not at goal begin prandial rapid insulin
Step 4 DM 2
Begin basal bolus insulin regimen
Biguanides DM 2
Metformin
Oral
Considered 1st line drug of choice
Biguanides and metformin MOA
Reduces hepatic glucose production
Reduces intestinal glucose absorption
Increase insulin sensitivity
Improved peripheral glucose uptake and utilization
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
Metformin-glucophage SE
Primarily GI: NV; diarrhea; flatulence
Can lead to lactic acidosis
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)
First biguanide
Phenformin
What to monitor for when pt is on metformin
Renal issues
Dehydration
Infection/sepsis
overdose
Sulfonylureas (SUs)
Dose once daily* *greater risk for hypoglycemia* Second line therapy All equally effective Overall a moderately effective class
Are 1st generation SUs used?
Rarely
2nd generation SU agents
Preferred -> less hypoglycemia
1) Glimepiride
2) Glipizide
3) Glyburide
Glimepiride dosing interval
q 24 hours
More hypoglycemia than glipizide
Glipizide dosing interval
q12-24 hours
Glyburide dosing interval
q12-24 hours
Not preferred -> most hypoglycemia
SUs MOA
Stimulates release of insulin
Requires presence of insulin (functioning pancreas) -> not good for DM1
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)
RAS MOA
Stimulate insulin release from pancreas
Similar to SUs but shorter half life
Faster onset than SUs (fast acting)
RAS SE
hypoglycemia (less than SUs)
Weight gain
SSx of adrenergic manifestation of hypoglycemia
Shakiness Nervousness Anxiety Palpitations Tachycardia Sweating (absent or diminished if on beta blockers)
SSx of glucagon manifestations of hypoglycemia
Hunger
Nausea
Vomiting
Headache
SSx of neuroglycopenic manifestations of hypoglycemia
Impaired judgement/mentation Fatigue Lethargy Ataxia (can seem like they are intoxicated) Stupor Coma Seizures
Mild (< 50 mg/dL) hypoglycemia tx
3 glucose tabs
1/3 c fruit juice
5-6 pieces hard candy (not artificial)
Glucose gel
Severe (< 40 mg/dL) hypoglycemia tx
Glucagon injection
D50 IV push
Moderately effective hypoglycemic agents
TZDs
DDP4Is
SGLTsIs
Thiazolidinediones TZDs
Rosiglitazone -> dose 1-2xs/day
Pioglitazone -> dose 1x/day
Synergistic effect when combined
TZD MOA
Increase insulin sensitivity by:
Increasing glucose utilization and decreasing hepatic glucose production
“Insulin sensitizer” -> needs insulin present
TZD SE
weight gain
edema
Increased total cholesterol, LDL, HDL
Hepatic metabolism (avoid if LFTs > 2.5 ULN)
What are pts at an increased risk of when on rosiglitazone
MI
TZD pioglitazone agent, dosing, and cost
Actos
Dosed once daily
About $10 a month
TZD rosiglitazone agent, dosing, cost
Avandia
1-2xs/day
$90/month
DPP4Is (gliptins) MOA
Inhibits enzyme that degrades incretin homrones which prolongs incretin levels
Incretin hormones
GLP-1
GIP
*Increase insulin secretion in response to meals
What are DPP4Is also known as
Incretin enhancers
Benefits of prolonged incretin levels
Stimulate insulin synthesis and release
Decrease glucagon secretion from pancreatic alpha cells
Net result of DPP4Is
Prolonged basal insulin secretion
Advantages of DPP4Is
Oral dosing
Once daily
Minimal hypogylcemia
Weight neutral
Disadvantages of DPP4Is
Placebo
Costly -> $380/month
Concerns of increased risk of heart failure (no increased risk of hospitalization for HF)
Does DPP4I agent Linagliptin require renal adjustment?
NO
Sodium glucose cotransporter 2 Inhibitors
SGLT2Is
Oral anti-diabetics
Moderately effective
SGLT2I MOA
Inhibits SGLT2 recovery of glucose from the urine (increased urine glucose loss)
SGLT2I advantages
Lowers BP
Decreases weight
SGLT2I adverse effects
Genital fungal infections
Dehydration
Risk of ketosis, UTIs, and pyelonephritis
Minimally effective hypoglycemic agents
alpha glucosiade inhibitors (agi)
Pramlintide
Glucagon-like peptide 1 receptor agonists (GLP-1 RAgs)
AGIs
Oral dosing
TID
Relatively low cost ($30-$60)
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
AGI advantages
Effective for DM1 and DM2
NO hypoglycemia
Efficacy equal between all agents
AGI disadvantages
Usually need to combine w/ metformin, a sulfonylureas, or insulin
High rate of flatulence and mild rate of diarrhea
Pramlintide
Synthetic analog of human amylin
Decreases post-prandial glucose leves
No action on beta cells so can be used for DM1 and DM2
Advantages of pramlitnide
Neutral risk of hypoglycemia
Weight loss
Pramlintide dosing
SubQ injection before each meal
Disadvantages of pramlintide
Very $$$ ($1500/month)
Nausea in about half of pts
Liraglutide dosing (GLP-1 RAg)
once daily
How are GLP-1 RAg’s dosed
SC injection
Exenatide dosing (GLP-1 RAg)
IR = BID; ER = once weekly
Dulaglutide dosing (GLP-1 RAg)
Once weekly
Albiglutide dosing (GLP-1 RAg)
Once weekly
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
GLP-1 RAg advantage
weight loss
GLP-1 RAg former disadvangtage
Heart failure (was recently discounted)
Starting DM2 meds guidelines
No single method
Keep other factors into account (pt preference, route, cost, risk of hypoglycemia)
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
When do you mainly see DKA?
Type 1 diabetics
What usually precipitates DKA
Not adhering to meds
Infection
Alcohol abuse
DKA presentation
Polyuria Polydypsia Polyphagia Weakness Fruity breath NV Sx of dehydration
Outpatient tx of DKA
This is mild DKA Hydrate Insulin Potassium Bicarbonate Sodium
Inpatient DKA tx
Mod-severe DKA Fluids Insulin Potassium Bicarbonate Sodium
Do you increase or decrease insulin for DM1 pts during the honeymoon period (transient remission)?
Decrease
