Diabetes Flashcards
Characteristics of adults who should be screened for diabetes?
Adults:
- BMI ≥ 25 (Asian Am ≥23) + ≥1 risk factor
- Prediabetes Dx
- ≥ 45yo
Characteristics of children who should be screened for diabetes?
overweight + ≥ 2 additional risk factors
Criteria for prediabetes diagnosis
Any one of:
- FPG 100-125 mg/dL
- 2hr PG 140-199mg/dL after 75g OGTT
- HbA1c 5.7-6.4%
Criteria for diabetes diagnosis
Any one of*
- FPG ≥ 126
- 2hr PG ≥ 200 after 76g OGTT
- Random PG ≥200 + classic Sx hyperglycemia
*repeat test to confirm unless unequivocal hyperglycemia
Sx Hypoglycemia
• Confusion • Diaphoresis • Tachycardia • Nausea • Tremulousness • Weakness • Coma • Seizures
BBs and hypoglycemia
BBs can match Sx e.g., tachycardia & tremors
Significance of hypoglycemic events
1+ severe hypoglycemic events = more likely to die in next 5yrs
Studies that showed evidence for tight glycemic control
DCCT
EDIC
UKPDS
ADVANCE
DCCT
Diabetes Control & Complications Trial
• check BG, intensive insulin, diet + exercise, monthly visits → reduced diabetic retinopathy nephropathy, neuropathy
EDIC
Epidemiology of Diabetes Interventions & Complications
10 more years w/DCCT Ptsl→ reduced CVD, nonfatal MI, stroke, death from CV cause
UKPDS
UK Prospective Diabetes Study 10 yr RCT
- diet alone vs intensive Tx w/insulin & sulfonylurea +/- metformin if needed
- tight BP control w/ACEi, BB, or CCB
GC & BP control → reduced microvascular complications metformin significantly reduced risk MI & stroke
ADVANCE
Action in Diabetes & Vascular Disease: Preterax & Diamicron Modified Release Controlled Evaluation
- Perindopril + indapimide reduced mortality compared to placebo
- HbA1c <6.5% no change in mortality
- 6yr f/u study confirmed initial findings
- HbA1c target reduced progression to ESRD
Recommended Goal HbA1c (ADA)
6.0-6.5% in selected pts
<7% most adult pts
HbA1c Treatment goals Advanced Age (ADA)
- Usual goals if pt functional, cognitively intact, significant life expectancy
- May consider lower, e.g., <8% if above criteria not met
HbA1c Treatment goals Pediatric
<7.5% pediatric patients w/DMI
When should HbA1c Treatment goals be more liberal? (ADA)
More liberal goals if - episodes of severe hypoglycemia / hypoglycemia unawareness - complex comorbid conditions, limited life expectancy (3-5years before benefits of tight glyc control seen. Focus on BP or lipids instead)
General guidelines for non-pharm therapy? (ADA)
- Medical nutrition therapy
- Wt loss if overweight (≥ 7%)
- Whole grains & fibers
- reduced sat & trans fats, sugary bevs, sodium
- etoh in moderation
- 150 min/week moderate intensity aerobic
- resistance training 2x week unless C/I’d
- Separate recs for pedi, e.g., ~ 1 hr daily
Guidelines for non-pharm therapy in advanced age? (ADA)
- Symptomatic hyper/hypoglycemia should always be prevented / treated
- Lifestyle & metformin comparable in younger, but older pts shown to have no benefit from metformin but significant benefit from lifestyle modification (Caspersen et al., 2012)
2015 ADA guidelines emphasize…
individualized Tx plan: patient preference, comorbidities
Guidelines for DMI pharm therapy in adults (ADA)
Insulin (basal, bolus, correction regimen, continuous infusion or pump)
Guidelines for DMII pharm therapy in adults (ADA)
- first line: metformin unless C/I’d
- +/- insulin if symptomatic and/or markedly elevated A1c or glucose
- Add second PO drug, GLP-1 agonist, or insulin if goal A1c not achieved w/max tolerated dose after 3 mths
Guidelines for DMI pharm therapy in kids (ADA)
Insulin (basal, bolus, correction regimen, continuous infusion or pump)
Guidelines for DMII pharm therapy in kids (ADA)
10-18yo w/random BG ≥ 250mg/dL, HbA1c >9%, or w/ketoacidosis: same as DMI
10-18yo w/o above features: Glucophage (metformin)
Always w/lifestyle modifications
Sulfonylureas: indication
DMII
Need some β cell function
Sulfonylureas: MOA/PK
- Binds to ATP dependent K+ channel in β cell.
- Closes channel which depolarizes cell
- Altered resting membrane potential opens Ca++ channel.
- Ca++ influx leads to insulin secretion
- Net effect: stimulate insulin release through β cells
Sulfonylureas: ADRs
- Weight gain (increased glc)
- Hypoglycemia
- Rare CV deaths (may be increased w/glimepiride)
Sulfonylureas: Relative Efficacy
reduced A1c 1-2%
Sulfonylureas: special considerations
- increased glycogen, fat, protein formation
- may → β cell burnout
- avoid in sulfa allergy
Sulfonylureas: drug names
Diabinese (chlorpropamide)
Diabeta (glyburide)
Glucotrol (glipizide)
Amaryl (glimepiride)
Diabinese (chlorpropamide): Dose, peak, duration
- 250-750 mg/day
- Peak: 3-6h
- Duration: 24h
(sulfonylurea)
Diabinese (chlorpropamide): important considerations
- reduce dose in renal impairment
- CYP2C9 substrate
- active metabolite – can accumulate
- high risk d/t unpredictable PKs, longer acting
- rarely used
(sulfonylurea)
Diabeta (glyburide): Dose, peak, duration
- 2.5 – 20mg/day micronized: 1.25 – 12mg/day
- Peak: 2-4h
- Duration: ≤ 24h
(sulfonylurea)
Diabeta (glyburide): important considerations
- Caution in renal impairment
- CYP2C9 substrate
- risk d/t longer acting
(sulfonylurea)
Diabeta (glyburide): GDM
not as good as insulin or metformin in GDM (insulin recommended (sulfonylurea)
Glucotrol (glipizide): Dose, peak, duration
- 5-20 mg/day
- Peak: 1-3h
- Duration: 12-24h
(sulfonylurea)
Glucotrol (glipizide): important considerations
- CYP2C9 substrate
- recommended
(sulfonylurea)
Amaryl (glimepiride): Dose, peak, duration
- -5 mg/day
- Peak: 2-3h
- Duration: 24h
(sulfonylurea)
Amaryl (glimepiride) important considerations
- CYP2C9 substrate
- recommended
(sulfonylurea)
Which sulfonylurea is safe in elderly?
Amaryl (glimepiride)
no active renal metabolite = safe in elderly
Which sulfonylureas are recommended?
Amaryl (glimepiride)
Glucotrol (glipizide):
Meglinitides: typical dosing
Typically 2-3x/day
Meglinitides: agents
Prandin (repaglinide)
Starlix (nateglinide)
Meglinitides: MOA
Stimulate insulin release through β cells
Quick peak, short duration compared to sulfonylureas
Meglinitides: ADRs
Weight gain
hypoglycemia
Meglinitides: hypoglycemia risk
Important counseling: Skip a meal, skip a dose to avoid hypoglycemia
Meglinitides: relative efficacy
Reduces A1c A1c 1-1.5%
Meglinitides: important considerations
increase glycogen, fat, protein formation
Most effective for postprandial hyperglycemia
Prandin (repaglinide): dose, peak, duration
- 0.5-4mg ac
- Peak: 1h
- Duration: 4-6h
(Meglinitide)
Prandin (repaglinide): metabolism
CYP3A4 substrate
(Meglinitide)
Starlix (nateglinide): dose, peak, duration
- 60-120mg ac
- Peak: 1h
- Duration: 4h
*no dose titration required!
(Meglinitide)
Starlix (nateglinide): metabolism
CYP2C9 & CYP3A4 substrate
(Meglinitide)
Meglinitides - hepatic or renal impairment
no adjustment
Biguanides: agents
Glucophage (metformin)
Glucophage (metformin): Dose
1000-3000mg QD divided into 2 doses or as ER formulation
Glucophage (metformin): renal / hepatic impairment
AVOID in renal impairment (men SCr >1.5mg/dL, women SCr >1.4mg/dL) (Biguanide)
Glucophage (metformin): MOA/PK
- Reduce A1c 1-1.5%
- hepatic gluconeogenesis
- Increase insulin sensitivity – often insulin resistance is the problem & not lack of insulin (Biguanide)
Glucophage (metformin) ADRs
GI distress, vit B12 deficiency, lactic acidosis (Biguanide)
Glucophage (metformin) hypoglycemia
No! except in combo w/other agents (Biguanide)
Glucophage (metformin) relative efficacy
Reduce A1c 1-2%
(Biguanide)
Glucophage (metformin): how to minimize GI effects
Minimize GI SEs via slow titration -start low, go slow!
(Biguanide)
Glucophage (metformin): when to avoid
Avoid in renal impairment, dehydration, CHF, or recent contrast dye administration
(Biguanide)
Glucophage (metformin): weight
weight neutral
(Biguanide)
Glucophage (metformin): GDM
GDM: did better than insulin for weight gain, but earlier births, etc. Insulin still rec’d.
(Biguanide)
THIAZOLIDINEDIONES: Agents
Actos (pioglitazone)
Avandia (rosiglitazone)
Actos (pioglitazone): dose
15-45mg PO QD
(thiazolidinediones)