Diabetes Mellitus: Diabetes Mellitus Brooke Y. Patterson, PharmD, BCPS
NU 7080 Advanced Pharmacology
Research College of Nursing
Epidemiology: Epidemiology 7% of the United States population has either Type 1 or Type 2 diabetes
14.6 million have diabetes
1/3 do not know that they have it
Diabetes prevalence increasing in all patient groups
Minority
Children
Pathophysiology: Pathophysiology Type 1
Beta-cell destruction
Absolute lack of insulin
Type 2
Progressive insulin secretory defect
Insulin resistance
Relative lack of insulin
Gestational
Glucose intolerance during pregnancy
Clinical Presentation: Clinical Presentation Obesity or unexplained weight loss
Polyuria
Polydipsia
Blurry vision
Fatigue
Neuropathy of hands or feet
Asymptomatic
Diagnosis of Non-Pregnant Adults: Diagnosis of Non-Pregnant Adults Random plasma glucose ≥200 mg/dL with symptoms
OR
Fasting plasma glucose ≥126 mg/dL
Fasting = no caloric intake X 8 hours
OR
2-hour-post glucose ≥200 mg/dL after an oral glucose tolerance test (OGTT)
ALL tests should be confirmed by repeat testing on a different day
Therapeutic Goals: Therapeutic Goals Glycemic control
Individualized
Less intense goals for certain patient populations
HgbA1C, preprandial, and post-prandial goals
ADA recommendations
www.diabetes.org
ADA Guidelines for Glycemic Control: ADA Guidelines for Glycemic Control *Some clinicians may prefer HgbA1C <6.5% (AACE)
Therapeutic Goals: Therapeutic Goals Blood Pressure
<130/80 mmHg
Treat with ACE inhibitor or Angiotensin Receptor Blocker (ARB)
Lipids
LDL <100 mg/dL
TGs <150 mg/dL
HDL >40 mg/dL
General Approach To Type 2 DM Treatment: General Approach To Type 2 DM Treatment
General Approach To Type 2 DM Treatment: General Approach To Type 2 DM Treatment
Sulfonylureas (SFU): Sulfonylureas (SFU) Stimulate insulin secretion
Improve insulin sensitivity at the receptor
Decrease hepatic glucose output
HgbA1C decreases 1-2% on average
Sulfonylureas: Sulfonylureas
Sulfonylureas: Sulfonylureas Hepatic Impairment
Give reduced dose
Renal impairment
Active metabolite and parent drug stay active
Decrease dose in renal impairment
Side Effects
Hypoglycemia
Photosensitivity
Rash
Weight gain
GI discomfort
Biguanides: Biguanides Metformin
Decreases hepatic glucose output
Increases peripheral glucose uptake and utilization
Decreases HgbA1C by 1-2%
Additive effect when combined with SFU
Metformin: Metformin Advantages
No hypoglycemia
Weight loss
Decreases TGs
Improve glycemic control in >90% patients
Better CV outcomes (UKPDS)
Adverse Effects
Anorexia
Nausea
Flatulence and GI discomfort
Lactic acidosis (rare)
Biguanides: Biguanides Metformin
Decreases hepatic glucose output
Increases peripheral glucose uptake and utilization
Decreases HgbA1C by 1-2%
Additive effect when combined with SFU
Metformin: Metformin Advantages
No hypoglycemia
Weight loss
Decreases TGs
Improve glycemic control in >90% patients
Better CV outcomes (UKPDS)
Adverse Effects
Anorexia
Nausea
Flatulence and GI discomfort
Lactic acidosis (rare)
Metformin: Metformin Contraindicated in renal impairment
Males SrCr ≥1.5 mg/dL
Females SrCr ≥1.4 mg/dL
Hepatic impairment
Hypoxic states
CHF
EtOH abuse
Patients >80 yo
Metformin: Metformin Initial dose 500mg PO BID
Titrate dose up gradually to avoid GI effects
1500-2000mg/day
Drug interactions
Alcohol
Iodinated contrast dye
Cimetidine
Thiazolidinediones: Thiazolidinediones PPAR agonist to promote glucose uptake into target cells
Decreases insulin resistance
Increases insulin sensitivity
No effect on insulin secretion
Decreases HgbA1C 0.6-1.3%
Addictive effect when used with metformin
Adverse Effects
Hepatotoxicity (monitor LFTs often)
Edema (contraindicated in CHF)
Resumption of ovulation
Thiazolidinediones: Thiazolidinediones Rosiglitazone (Avandia®)
4-8mg PO QD or divided BID
Pioglitazone (Actos®)
15-45mg PO QD
Delayed onset of activity; may take several weeks to see maximal effect
Repaglinide (Prandin®): Repaglinide (Prandin®) Meglitinide
Monotherapy or in combination with metformin
Stimulate insulin secretion
Decrease HgbA1C by 0.5-1.0%
Take immediately before meals
0.5mg-1 mg PO before meals 2-3X/day
Hypoglycemia, weight gain
Nateglinide (Starlix®): Nateglinide (Starlix®) Stimulates rapid release of insulin from pancrease
Reduces HgbA1C by 0.6-0.8%
120mg PO TID with meals
Rarely used
Alpha-Glucosidase Inhibitors: Alpha-Glucosidase Inhibitors Potent competitive inhibitors of brush border alpha-glucosidases necessary in breakdown of complex carbohydrates
Decreases HgbA1C minimally
Adjunct therapy
Acarbose (Precose®) and Miglitol (Glyset®)
Adverse Effects
Abdominal pain
Flatulence
Diarrhea
Treatment of hypoglycemia: glucose tablets ONLY
Rarely used
Exenatide (Byetta®): Exenatide (Byetta®) Stimulation of the glucagons-like-peptide-1 (GLP-1) receptor
Production of insulin in response to high glucose levels
Inhibition of release of glucagons after meals
Slows rate of gastric emptying
Adjunctive therapy for type 2 DM no adequately controlled with metformin, SFUs, or combination.
5 mcg SQ BID within 60 minutes of morning and evening meals
Prefilled syringe pens
May increase dose to 10 mcg SQ BID
Decrease SFU dose
Exenatide (Byetta®): Exenatide (Byetta®) Adverse Effects
Hypoglycemia (when combined with SFU)
Nausea
Diarrhea
NOT a substitute for insulin in Type 1
Decreases HgbA1C 0.5-1.0% in combination therapy
Weight loss (?)
Pramlinitide (Symlin®): Pramlinitide (Symlin®) Synthetic analog of human neuroendocrine hormone amylin
Modulates gastric emptying
Decreases post-prandial glucagons release
Increased satiety
Type 1 and Type 2 DM
Type 1: adjunctive therapy to meal time insulin
Type 2: adjunctive therapy to meal time insulin with or without metformin/SFU
Pramlinitide (Symlin®): Pramlinitide (Symlin®) Type 1
15 mcg SQ prior to major meals
Titrate by 15 mcg increments up to 60 mcg
Decrease rapid acting insulin by 50%
Type 2
Initiate at 60 mcg prior to major meals
May increase to 120 mcg in 3-7 days
Decrease preprandial or short acting insulin by 50%
Pramlinitide (Symlin®): Pramlinitide (Symlin®) Adverse Effects
Severe hypoglycemia (Black Box Warning)
Nausea
Insulin: Insulin Total daily dose of insulin is based on actual body weight
Type 1: Initial dose 0.5-0.8 units/kg/day
Type 2: Variable; usually start with long acting HS insulin at low dose.
Insulin adjustment in Type 1 DM requires expertise
CDE
Endocrinologists
Titrate slowly!
Insulin: Insulin
Adjusting Insulin: Adjusting Insulin
Case: Case PR is a 35 yo AAM with a history of Type I DM and HTN. His current regimen is lisinopril 20 mg, regular insulin 10 units before meals and NPH insulin 30 minutes at breakfast. He brings his blood glucose log with him to the visit. The log shows fairly good glycemic control with pre-dinner blood glucose consistently in the 200-250 range.
Prevention of DM Complications: Prevention of DM Complications ASA therapy
Prevention of CV risk
ASA 81 mg QD
Hypertension
ACE inhibitors
Hyperlipidemia
Statin therapy
Vaccinations
Influenza annually
Pneumococcal vaccine
Slide33: Part of the secret of success in life is to eat what you like and let the food fight it out inside.
-Mark Twain