Naplex 2014: Diabetes

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Type 1 DM

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Autoimmune destruction of the beta cells of the pancreas

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Type 2 DM

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Combination of insulin resistance and relative insulin deficiency; progressively lower insulin secretion over time

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Risk factors for Type 2 DM

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1st degree relative w/ DMNative American, African American, Asian, Hispanic, Pacific IslanderOverweightPhysical inactivityHTNHDL < 35 and/or TG > 250Hx of CVFPolycystic ovarian syndrome

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Microvascular complications

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RetinopathyNephropathyPeripheral neuropathyAutonomic neuropathy (ED, gastroparesis, loss of bladder control)

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Macrovascular complications

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Coronary artery disease (HTN, MI, HF)Cerebrovascular disease (TIA/stroke)Peripheral artery disease

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DM lifestyle modifications

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Weight lossWaist circumference < 35 in (female), < 40 in (male)DietMonitor carb intakeLimit saturated fat intake < 7% of total caloriesMinimize trans fat intakeExercise 30 min x 5 daysSmoking cessation

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Vaccinations required for diabetics

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InfluenzaHep BPneumovaxTdaP

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Metformin

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GlucophageBiguanideIR 500 mg QD-BID or 850 mg QDER 500-1000 mg QD w/ dinner1st line therapy for DMBLACK BOX --- lactic acidosis

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Janumet

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Sitagliptin + Metformin

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Metformin Contraindications

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SCr > 1.4 (female) or > 1.5 (male)CrCl < 60 mL/minMetabolic acidosisTemporary d/c w/ iodinated contrast media (resume after 48 hrs if renal function is normal)STOP in any case of hypoxiaHepatic impairment

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Metformin Adverse Effects

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D/N/V/flatulenceWeight neutral

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Metformin Interactions

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Alcohol, iodinated contrast dye - increase risk of lactic acidosisDecreases Vitamin B12 absorption

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Glipizide

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GlucotrolSulfonylureaIR 5-10 mg BIDXL 5-10 mg QD, max 20 mg QD

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Glimepiride

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AmarylSulfonylurea1-2 mg QD, max 8 mg QD

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Glyburide

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DiaBeta2.5-5 mg QD, max 20 mg/dContraindicated in CrCl < 50 ml/min

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Metformin MOA

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Decreases hepatic glucose productionDecreases intestinal absorption of glucoseImproves insulin sensitivity

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Sulfonylurea Info

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Stimulate insulin secretion from the pancreatic beta cellsSE - hypoglycemia, weight gainCYP 2C9 substratesTake w/ food

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Sulfonylurea Contraindications

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Use w/ meglitinidesSulfa allergyGlyburide --- CrCl < 50 mL/min

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Meglitinide Info

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Stimulate insulin secretion from the pancreatic beta cellsSE - hypoglycemia, mild weight gain, upper respiratory tract infxnRepaglinide, nateglinide

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Pioglitazone

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Actos15-30 mg QD, max 45 mg QDContra in active bladder cancer

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Thiazolidinedione MOA

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Peroxisome proliferator-activated receptor gamma agonistsIncreases uptake and utilization of glucose by the peripheral tissues

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TZD Warnings and Side Effects

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BLACK BOX --- NYHA Class III/IV heart failureDon't use pioglitazone in active bladder cancerCYP 2C8 substratesSE - peripheral edema, weight gain, UTRIsCHF, increased fracture risk, increased LFTs

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Alpha Glucosidase Inhibitors

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Cause reversible inhibition of membrane-bound intestinal alpha-glucosidases which hydrolyze oligosaccharides and disaccharides to glucoseDelays glucose absorptionEx. Acarbose, Miglitol

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Alpha-Glucosidase Inhibitor Warnings and Side Effects

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Contra in inflammatory bowel disease, colonic ulceration, partial or complete intestinal obstructionSE - GI effects, weight neutralTake w/ full glass of water w/ 1st bite of foodTreat hypoglycemia w/ glucose tablets or gel

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Sitagliptin

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JanuviaDPP-4 Inhibitor100 mg QDCrCl 30-49 --- 50 mg QDCrCl < 30 --- 25 mg QD

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DPP-4 Inhibitors

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Prevent the enzyme DPP-4 from breaking down incretin hormones, GLP-1, and GIPIncrease insulin release from the pancreatic beta cellsDecrease glucagon secretion from pancreatic alpha cellsEx. Sitagliptin, saxagliptin, linagliptin (no renal dose adjustment), alogliptin

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DPP-4 Inhibitor Adverse Effects and Interactions

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Nasopharyngitis, Upper RTIs, UTIs, peripheral edema, rash, hypoglycemiaWeight neutralSaxagliptin --- CYP 3A4 substrateLinagliptin --- CYP 3A4 and P-glycoprotein substrate

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Canagliflozin

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InvokanaSGLT2 Inhibitor100 mg Qbreakfast (max 300 mg Qbreakfast)CrCl 45-60 - 100 mg maxContra in CrCl < 45 mL/min

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SGLT2 Inhibitors

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Reduces reabsoprtion of filtered glucose and lowers renal threshold for glucose --- increases urinary glucose excretionUGT substrateEx. Canagliflozin

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SGLT2 Inhibitor Side Effects and Misc.

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SE - female genital mycotic infxns, UTIs, hyperkalemia, increased urination, hypoglycemiaContra - CrCl < 30 mL/min, ESRD, or on dialysisIncreases AUC of digoxin

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Exenatide

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Byetta, Bydureon (ER)GLP-1 agonistIR --- 5 mcg SC BID x 1 month, then 10 mcg SC BIDER --- 2 mg SC q7 days

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GLP-1 Agonists MOA

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Analogs of glucagon-like peptide-1Increases insulin secretionDecreases glucagon secretionSlows gastric emptying and improves satietyEx. Exenatide, liraglutide

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GLP-1 Agonists Misc.

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BLACK BOX --- possible thyroid cancerContra - family hx of medullatry thyroid carcinoma, Multiple Endocrine Neoplasia syndrome type 2, CrCl < 30 mL/min, severe GI diseaseSE - nausea, V/D/C, weight loss, hypoglycemiaPancreatitis, caution in moderate renal impairment

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Liraglutide

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VictozaGLP-1 Agonist0.6 mg SQ QD x 1 wk, then 1.2 mg SQ QD

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Pramlintide

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SymlinAnalog of amylinSlows gastric emptying and increases satietySE --- hypoglycemia, nausea, anorexiaBLACK BOX - coadmin w/ insulin

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Bromocriptine

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CyclosetDopamine agonistWorks in the CNS to decrease insulin resistanceTake w/ food

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Rapid acting Insulin

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Aspart (Novolog), Glulisine (Apidra), Lispro (Humalog)Last for a mealDosed for amount of carbs in a meal or in fixed regimenClear

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Regular insulin

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Humulin R, Novolin RInject 30 min before mealOnset of action - 30 minutes, lasts 6-10 hoursClear

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NPH insulin (Intermediate insulin)

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Humulin N, Novolin NOnset is 1-2 hours, peak of 4-8 hours, duration of 24 hrsCloudy

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Long-acting insulin

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Detemir (Levemir), Glargine (Lantus)Onset 1-2 hrs, duration ~24 hrsDO NOT PEAKDon 't mix w/ other insulins

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Diabetes drugs that cause hypoglycemia

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InsulinSulfonylureas and meglitinidesGLP-1 agonist, DPP-4 inhibitor, TZDs, InvokanaPramlintide (Symlin)

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Symptoms of hypoglycemia

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Dizziness, HAAnxiety, shakinessSweating, excessive hungerConfusion, clumsy or jerky movementsTremors, palpitations, blurred vision

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Diabetic ketoacidosis (DKA)

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Occurs when there is not enough insulin and the body breaks down fat to make energyMay be initial presentation of Type 1 DM or the result of patient stopping insulin therapy

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DKA Symptoms

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HyperglycemiaPolyuria, polyphagia, polydipsiaBlurred visionMetabolic acidosis (fruity breath, dyspnea)Dehydration

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DKA Lab Values

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Glucose > 300Ketones (+) in urine and bloodpH < 7.2Bicarb < 15WBC 15-40

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DKA Treatment

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IV fluids, electrolytesInsulin