INSULINFLAME LECTURE: 8RISH 11.1.18

LEARNING OBJECTIVESu To understand Insulin use in diabetes u To describe indications, mechanism of action, and

side effects of InsulinuPrerequisites: None uSee also – for closely related topics

uFLAMEs on Type 2 DM / Medications for treatment of DM

INDICATIONS FOR INSULIN u Type 1 Diabetesu Type 2 Diabetes

u If lifestyle changes and oral therapy are not adequate for glycemic control u Can add to oral therapy if A1c remains >8.5% u Initial therapy if presenting A1c >9.0%

u If insulin monotherapy, usually use basal insulin

u All patient with end stage renal disease

u Gestational diabetesu Acute hyperkalemia

MECHANISM OF ACTIONu Lowers blood glucose levels by promoting absorption from blood and

into storage u Storage in liver, skeletal muscle, and adipose tissue

u Carbohydrates: u Increases: uptake of glucose into cell, increase glycogenesis and glycolysisu Decreases: glycogenolysis and gluconeogenesis

u Lipids: u Increases: lipid synthesisu Decreases: lipolysis and ketogenesis

u Proteins: u Increase: protein synthesis and uptake of amino acids u Decreases: proteolysis

u Other: u Increase: K uptake, cell growth, secretion of gastric acid

PHARMACOKINETICSu Rapid-acting insulin: Lispro/Aspart= “meal-time insulin”

u Onset: 15-30 minu Peak: 30 min-1.5 hru Duration: 3-5 hr

u Short-acting insulin: Regular insulinu Onset: 30 min-1hru Peak: 2-4 hru Duration: 5-8 hr

u Intermediate-acting insulin: NPH insulin (usually BID administration) u Onset: 1-2 hru Peak: 4-12 hru Duration 14-24 hr

PHARMACOKINETICS (CONT)u Long-acting insulin: Glargine/Detemir (once a day or BID)

u Detemir: u Onset: 3-4 hr

u Peak 6-8 hr

u Duration: 6-23 hr

u Glargineu Onset: 1.5 hr

u Peak: None

u Duration: 24 hr

u Mixed insulin = mix of regular and NPH (ex: 70/30) (BID or TID)u Onset: 15-60 min u Duration: 14-24 hr

DOSING

u 0.3-0.6 U/kg/dayu 50% basalu 50% bolus

u 1/3 breakfast

u 1/3 lunch

u 1/3 dinner

u Ex: Patient weighs 120 kg à 120 x 0.6= 72 Uu 36 U basal

u 36 U bolusu 12 U at each breakfast, lunch, and dinner

u If initiating basal only: usually 0.2 U/kg w/ of minimum 10 U

MORE TO KNOW ABOUT DOSING

u Insulin Sensitivity: how much 1U of insulin is expected to decrease the blood glucose level u When blood glucose above pre-defined goal, short-acting

insulin is added to the normal bolus dose or given separately between meals

u Calculation: 1800/total daily insulin requirement u On average, 1U will lower serum glucose by 25 mg/dL

u Correcting for carbohydrates: # of units of insulin needed to cover for # of grams of carbohydrates ingestedu Calculation: 500/total daily insulinu On average, about 1 unit/10 g carb

MORE TO KNOW ABOUT DOSING

uSliding Scale: checking blood glucose level and dosing insulin based on the value

BLOOD SUGAR (mg/dL)

INSULIN DOSE (Units of rapid

or short-acting)<150 0150-200 2201-250 4251-300 6301-350 8351-400 10401-450 12>450 14

DOSE TITRATIONu Fasting glucose values used to titrate basal

u Usually titrate 2-4U every 3-7 days until at goal u Pre-prandial and post-prandial values used to titrate

bolus/meal-timeu Increase/decrease by approx 10% based on home readings

u Can do this every 3-7 days until at goal u Titrate based on the following goals

u Fasting: 90-130 u Postprandial: <180 u A1c: <7.0

u Should have patient follow up at least every 3 months for insulin review/management

SIDE EFFECTSu Hypoglycemia

u More common in premixed and bolus

u Weight gainu More common with large bolus (“meal-time”) regimens

u Lidodystrophy at injection siteu Pain and erythema of injection siteu Hypokalemiau Allergic reaction (rare)u Edema (rare)

RESOURCESu Am Fam Physician. 2011 Jul 15;84(2):183-190.u Am Fam Physician. 2009 Jan 1;79(1):29-36.u Am Fam Physician. 2010 May 1;81(9):1130-1135u Am Fam Physician. 2018 Jan 1;97(1):29-37.